NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|568960994|ref|XP_006510994|]
View 

protein unc-13 homolog C isoform X1 [Mus musculus]

Protein Classification

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

 Name Accession Description Interval E-value
MUN pfam06292
MUN domain; This entry corresponds to the MUN domain found in Munc13 proteins. These ...
 1536-2034 0e+00

MUN domain; This entry corresponds to the MUN domain found in Munc13 proteins. These constitute a family of three highly homologous molecules (Munc13-1, Munc13-2 and Munc13-3) with homology to Caenorhabditis elegans unc-13p. Munc13 proteins contain a phorbol ester-binding C1 domain and two C2 domains, which are Ca2+/phospholipid binding domains. Sequence analyses have uncovered two regions called Munc13 homology domains 1 (MHD1) and 2 (MHD2) that are arranged between two flanking C2 domains. MHD1 and MHD2 domains are present in a wide variety of proteins from Arabidopsis thaliana, C. elegans, Drosophila melanogaster, mouse, rat and human, some of which may function in a Munc13-like manner to regulate membrane trafficking. Structural studies have defined MHD1 and MHD2 to be part of the larger MUN domain which forms an elongated structure composed of any pairs of alpha helices.


:

Pssm-ID: 461870  Cd Length: 473  Bit Score: 739.60  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994  1536 AVVKDCVRACLDSTYKYIFDNCHELYSQLIDPsKKQDVPREDQ--GPTTKNLDFWPQLITLMVTIIDEDKTAYTPVLNQF 1613
Cdd:pfam06292    1 QVVKDCLKAAALSNYQRLFENAYELSREFKIE-DKESIPEESQglGPSEKRLDFWIKLIELCVSVLQQDKEHYAPVLNQF 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994  1614 PQELNMGKISAEIMWSLFALDMKYALEEHEKQRLCKSTDYMNLHFKVKWFYNEYVRELPAFKD--AVPEYSLWFEPFVMQ 1691
Cdd:pfam06292   80 PWELDLGAEHAEIFWSLFAVDMDAALEEHEQHRLCKPDSWMNLHFKVKWLLNDYLRDDPTLKNgkFHPHYPDWFEPFVMR 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994  1692 WLDENEDVSMEFLHGALGRDKKDGFQQTSDHALFSCSVVDVFAQLNQSFEIIKKLECPNPEALSHLMRRFAKTINKVLVQ 1771
Cdd:pfam06292  160 YLDLNESSIAQSLHGGFERDKKDGFQQSSEHALFSSSVVDLFWKLNQLQDFIKKLEWPDPEFAAHLEKRFKLMASDMLLA 239

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994  1772 YAAIVSNDFSSYCDKETVPCILMNNIQQLRVQLEKMFESMGGKekkegerfsyELDPEASTILKELQIKLNGVLDALSIT 1851
Cdd:pfam06292  240 YAKRTRKAFDSKLKKPRTACTMMNNIQQARVQLEKMFLCMGGD----------ELDGEAHQYLTELQVLLEGVLDEMSSI 309

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994  1852 YGESFQLTIEECIKQMGAELNQMRANgnstaNKNSAAMDAEIVLRPLMDFLDKTLSLSAKICEKTVLKRVLKELWKLVLN 1931
Cdd:pfam06292  310 FADSFEPVLESVLSKLSRLLQQIKGS-----NRNNAAYDEGTLLSPLMDFLDGNLSLFARICEKTVLKRVLKELWKIVMN 384

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994  1932 KIEKQIVLPPLTDQTGPQMifiaakdlgqlsklKEHMIREDAKGLTPRQCAIVEVVLATIKQYFHAGGNGLKKNFLEKSP 2011
Cdd:pfam06292  385 TLEKTVVLPPLSDQSGSQL--------------KLLMSLEGAKNLTPKQCAILDAALETIFQYFHAGGNGLKKTWLEKSP 450

                          490       500
                   ....*....|....*....|...
gi 568960994  2012 DLHSLRYALSLYTQTTDALIKKF 2034
Cdd:pfam06292  451 ELQLLRYALSLYTQTTDKLIKDF 473
C2B_Munc13 cd04027
C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...
 1216-1342 4.56e-82

C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


:

Pssm-ID: 175993 [Multi-domain]  Cd Length: 127  Bit Score: 265.20  E-value: 4.56e-82
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1216 AKITITVVSAQGLQAKDKTGSSDPYVTVQVGKNKRRTKTIFGNLNPVWDEKFFFECHNSTDRIKVRVWDEDDDIKSRVKQ 1295
Cdd:cd04027     1 AKISITVVCAQGLIAKDKTGTSDPYVTVQVGKTKKRTKTIPQNLNPVWNEKFHFECHNSSDRIKVRVWDEDDDIKSRLKQ 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 568960994 1296 HFKKESDDFLGQTIVEVRTLSGEMDVWYNLEKRTDKSAVSGAIRLKI 1342
Cdd:cd04027    81 KFTRESDDFLGQTIIEVRTLSGEMDVWYNLEKRTDKSAVSGAIRLHI 127
C2C_Munc13 cd08395
C2 domain third repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...
 2068-2187 7.03e-71

C2 domain third repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins.C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


:

Pssm-ID: 176041 [Multi-domain]  Cd Length: 120  Bit Score: 233.06  E-value: 7.03e-71
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 2068 KVTVKVIAINDLNWQTTAMFRPFVEVCMLGPSLGDKKRKQGTKTKSNTWSPKYNETFQFILGNENRPGAYELHLSVKDYC 2147
Cdd:cd08395     1 KVTVKVVAANDLKWQTTGMFRPFVEVNLIGPHLSDKKRKFATKSKNNNWSPKYNETFQFILGNEDDPESYELHICVKDYC 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 568960994 2148 FAREDRIIGMTVIQLQNIAEKGSYGAWYPLLKNLSMDETG 2187
Cdd:cd08395    81 FARDDRLVGVTVLQLRDIAQAGSCACWLPLGRRIHMDETG 120
C1_Munc13-2-like cd20859
protein kinase C conserved region 1 (C1 domain) found in Munc13-2, Munc13-3 and similar ...
 1075-1156 2.57e-52

protein kinase C conserved region 1 (C1 domain) found in Munc13-2, Munc13-3 and similar proteins; Munc13-2, also called protein unc-13 homolog B (Unc13B), plays a role in vesicle maturation during exocytosis as a target of the diacylglycerol second messenger pathway. It is involved in neurotransmitter release by acting in synaptic vesicle priming prior to vesicle fusion and participates in the activity-dependent refilling of readily releasable vesicle pool (RRP). Munc13-2 is essential for normal release probability at hippocampal mossy fiber synapses. Munc13-3 is almost exclusively expressed in the cerebellum. It acts as a tumor suppressor and plays a critical role in the formation of release sites with calcium channel nanodomains. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


:

Pssm-ID: 410409  Cd Length: 82  Bit Score: 178.33  E-value: 2.57e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1075 HVFRKTLQALIYPISSTTPHNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADCLQRAAEKSSKH 1154
Cdd:cd20859     1 HVYKKTLQALIYPISCTTPHNFEVWTATTPTYCYECEGLLWGIARQGMRCSECGVKCHEKCQDLLNADCLQRAAEKSSKH 80


                  ..
gi 568960994 1155 GA 1156
Cdd:cd20859    81 GA 82
 
Name Accession Description Interval E-value
MUN pfam06292
MUN domain; This entry corresponds to the MUN domain found in Munc13 proteins. These ...
 1536-2034 0e+00

MUN domain; This entry corresponds to the MUN domain found in Munc13 proteins. These constitute a family of three highly homologous molecules (Munc13-1, Munc13-2 and Munc13-3) with homology to Caenorhabditis elegans unc-13p. Munc13 proteins contain a phorbol ester-binding C1 domain and two C2 domains, which are Ca2+/phospholipid binding domains. Sequence analyses have uncovered two regions called Munc13 homology domains 1 (MHD1) and 2 (MHD2) that are arranged between two flanking C2 domains. MHD1 and MHD2 domains are present in a wide variety of proteins from Arabidopsis thaliana, C. elegans, Drosophila melanogaster, mouse, rat and human, some of which may function in a Munc13-like manner to regulate membrane trafficking. Structural studies have defined MHD1 and MHD2 to be part of the larger MUN domain which forms an elongated structure composed of any pairs of alpha helices.


Pssm-ID: 461870  Cd Length: 473  Bit Score: 739.60  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994  1536 AVVKDCVRACLDSTYKYIFDNCHELYSQLIDPsKKQDVPREDQ--GPTTKNLDFWPQLITLMVTIIDEDKTAYTPVLNQF 1613
Cdd:pfam06292    1 QVVKDCLKAAALSNYQRLFENAYELSREFKIE-DKESIPEESQglGPSEKRLDFWIKLIELCVSVLQQDKEHYAPVLNQF 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994  1614 PQELNMGKISAEIMWSLFALDMKYALEEHEKQRLCKSTDYMNLHFKVKWFYNEYVRELPAFKD--AVPEYSLWFEPFVMQ 1691
Cdd:pfam06292   80 PWELDLGAEHAEIFWSLFAVDMDAALEEHEQHRLCKPDSWMNLHFKVKWLLNDYLRDDPTLKNgkFHPHYPDWFEPFVMR 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994  1692 WLDENEDVSMEFLHGALGRDKKDGFQQTSDHALFSCSVVDVFAQLNQSFEIIKKLECPNPEALSHLMRRFAKTINKVLVQ 1771
Cdd:pfam06292  160 YLDLNESSIAQSLHGGFERDKKDGFQQSSEHALFSSSVVDLFWKLNQLQDFIKKLEWPDPEFAAHLEKRFKLMASDMLLA 239

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994  1772 YAAIVSNDFSSYCDKETVPCILMNNIQQLRVQLEKMFESMGGKekkegerfsyELDPEASTILKELQIKLNGVLDALSIT 1851
Cdd:pfam06292  240 YAKRTRKAFDSKLKKPRTACTMMNNIQQARVQLEKMFLCMGGD----------ELDGEAHQYLTELQVLLEGVLDEMSSI 309

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994  1852 YGESFQLTIEECIKQMGAELNQMRANgnstaNKNSAAMDAEIVLRPLMDFLDKTLSLSAKICEKTVLKRVLKELWKLVLN 1931
Cdd:pfam06292  310 FADSFEPVLESVLSKLSRLLQQIKGS-----NRNNAAYDEGTLLSPLMDFLDGNLSLFARICEKTVLKRVLKELWKIVMN 384

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994  1932 KIEKQIVLPPLTDQTGPQMifiaakdlgqlsklKEHMIREDAKGLTPRQCAIVEVVLATIKQYFHAGGNGLKKNFLEKSP 2011
Cdd:pfam06292  385 TLEKTVVLPPLSDQSGSQL--------------KLLMSLEGAKNLTPKQCAILDAALETIFQYFHAGGNGLKKTWLEKSP 450

                          490       500
                   ....*....|....*....|...
gi 568960994  2012 DLHSLRYALSLYTQTTDALIKKF 2034
Cdd:pfam06292  451 ELQLLRYALSLYTQTTDKLIKDF 473
C2B_Munc13 cd04027
C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...
 1216-1342 4.56e-82

C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 175993 [Multi-domain]  Cd Length: 127  Bit Score: 265.20  E-value: 4.56e-82
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1216 AKITITVVSAQGLQAKDKTGSSDPYVTVQVGKNKRRTKTIFGNLNPVWDEKFFFECHNSTDRIKVRVWDEDDDIKSRVKQ 1295
Cdd:cd04027     1 AKISITVVCAQGLIAKDKTGTSDPYVTVQVGKTKKRTKTIPQNLNPVWNEKFHFECHNSSDRIKVRVWDEDDDIKSRLKQ 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 568960994 1296 HFKKESDDFLGQTIVEVRTLSGEMDVWYNLEKRTDKSAVSGAIRLKI 1342
Cdd:cd04027    81 KFTRESDDFLGQTIIEVRTLSGEMDVWYNLEKRTDKSAVSGAIRLHI 127
C2C_Munc13 cd08395
C2 domain third repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...
 2068-2187 7.03e-71

C2 domain third repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins.C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 176041 [Multi-domain]  Cd Length: 120  Bit Score: 233.06  E-value: 7.03e-71
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 2068 KVTVKVIAINDLNWQTTAMFRPFVEVCMLGPSLGDKKRKQGTKTKSNTWSPKYNETFQFILGNENRPGAYELHLSVKDYC 2147
Cdd:cd08395     1 KVTVKVVAANDLKWQTTGMFRPFVEVNLIGPHLSDKKRKFATKSKNNNWSPKYNETFQFILGNEDDPESYELHICVKDYC 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 568960994 2148 FAREDRIIGMTVIQLQNIAEKGSYGAWYPLLKNLSMDETG 2187
Cdd:cd08395    81 FARDDRLVGVTVLQLRDIAQAGSCACWLPLGRRIHMDETG 120
C1_Munc13-2-like cd20859
protein kinase C conserved region 1 (C1 domain) found in Munc13-2, Munc13-3 and similar ...
 1075-1156 2.57e-52

protein kinase C conserved region 1 (C1 domain) found in Munc13-2, Munc13-3 and similar proteins; Munc13-2, also called protein unc-13 homolog B (Unc13B), plays a role in vesicle maturation during exocytosis as a target of the diacylglycerol second messenger pathway. It is involved in neurotransmitter release by acting in synaptic vesicle priming prior to vesicle fusion and participates in the activity-dependent refilling of readily releasable vesicle pool (RRP). Munc13-2 is essential for normal release probability at hippocampal mossy fiber synapses. Munc13-3 is almost exclusively expressed in the cerebellum. It acts as a tumor suppressor and plays a critical role in the formation of release sites with calcium channel nanodomains. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410409  Cd Length: 82  Bit Score: 178.33  E-value: 2.57e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1075 HVFRKTLQALIYPISSTTPHNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADCLQRAAEKSSKH 1154
Cdd:cd20859     1 HVYKKTLQALIYPISCTTPHNFEVWTATTPTYCYECEGLLWGIARQGMRCSECGVKCHEKCQDLLNADCLQRAAEKSSKH 80


                  ..
gi 568960994 1155 GA 1156
Cdd:cd20859    81 GA 82
C2 pfam00168
C2 domain;
1217-1325 1.97e-26

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 105.48  E-value: 1.97e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994  1217 KITITVVSAQGLQAKDKTGSSDPYVTVQV--GKNKRRTKTIFGNLNPVWDEKFFFECHNSTDR-IKVRVWDEDddiksrv 1293
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDGNGTSDPYVKVYLldGKQKKKTKVVKNTLNPVWNETFTFSVPDPENAvLEIEVYDYD------- 74

                           90       100       110
                   ....*....|....*....|....*....|....
gi 568960994  1294 kqhfKKESDDFLGQTIVEVRTL--SGEMDVWYNL 1325
Cdd:pfam00168   75 ----RFGRDDFIGEVRIPLSELdsGEGLDGWYPL 104
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 1217-1322 1.16e-23

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 97.17  E-value: 1.16e-23
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994   1217 KITITVVSAQGLQAKDKTGSSDPYVTVQVG---KNKRRTKTIFGNLNPVWDEKFFFEC-HNSTDRIKVRVWDEDddiksr 1292
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDgdpKEKKKTKVVKNTLNPVWNETFEFEVpPPELAELEIEVYDKD------ 74

                            90       100       110
                    ....*....|....*....|....*....|..
gi 568960994   1293 vkqhfKKESDDFLGQTIVEVRTL--SGEMDVW 1322
Cdd:smart00239   75 -----RFGRDDFIGQVTIPLSDLllGGRHEKL 101
C2 pfam00168
C2 domain;
2067-2177 1.08e-18

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 83.14  E-value: 1.08e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994  2067 HKVTVKVIAINDL-NWQTTAMFRPFVEVCMLgpslgDKKRKQGTKTKSNTWSPKYNETFQFILGNENRpgaYELHLSVKD 2145
Cdd:pfam00168    1 GRLTVTVIEAKNLpPKDGNGTSDPYVKVYLL-----DGKQKKKTKVVKNTLNPVWNETFTFSVPDPEN---AVLEIEVYD 72

                           90       100       110
                   ....*....|....*....|....*....|..
gi 568960994  2146 YCFAREDRIIGMTVIQLQNIAEKGSYGAWYPL 2177
Cdd:pfam00168   73 YDRFGRDDFIGEVRIPLSELDSGEGLDGWYPL 104
C1 smart00109
Protein kinase C conserved region 1 (C1) domains (Cysteine-rich domains); Some bind phorbol ...
 1094-1143 7.90e-18

Protein kinase C conserved region 1 (C1) domains (Cysteine-rich domains); Some bind phorbol esters and diacylglycerol. Some bind RasGTP. Zinc-binding domains.


Pssm-ID: 197519  Cd Length: 50  Bit Score: 79.05  E-value: 7.90e-18
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|
gi 568960994   1094 HNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADC 1143
Cdd:smart00109    1 HKHVFRTFTKPTFCCVCRKSIWGSFKQGLRCSECKVKCHKKCADKVPKAC 50
C1_1 pfam00130
Phorbol esters/diacylglycerol binding domain (C1 domain); This domain is also known as the ...
 1094-1143 4.33e-15

Phorbol esters/diacylglycerol binding domain (C1 domain); This domain is also known as the Protein kinase C conserved region 1 (C1) domain.


Pssm-ID: 395079  Cd Length: 53  Bit Score: 71.32  E-value: 4.33e-15
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 568960994  1094 HNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADC 1143
Cdd:pfam00130    1 HHFVHRNFKQPTFCDHCGEFLWGLGKQGLKCSWCKLNVHKRCHEKVPPEC 50
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 2068-2174 4.12e-14

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 70.21  E-value: 4.12e-14
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994   2068 KVTVKVIAINDLNW-QTTAMFRPFVEVCMLGpslgDKKRKQGTKTKSNTWSPKYNETFQFILgneNRPGAYELHLSVKDY 2146
Cdd:smart00239    1 TLTVKIISARNLPPkDKGGKSDPYVKVSLDG----DPKEKKKTKVVKNTLNPVWNETFEFEV---PPPELAELEIEVYDK 73

                            90       100
                    ....*....|....*....|....*...
gi 568960994   2147 CFAREDRIIGMTVIQLQNIAEKGSYGAW 2174
Cdd:smart00239   74 DRFGRDDFIGQVTIPLSDLLLGGRHEKL 101
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
1215-1343 4.86e-09

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 62.08  E-value: 4.86e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1215 SAKITITVVSAQGLQAKDKTGSSDPYVTVQV-GKNKRRTKTIFGNLNPVWDEKFFFECHN-STDRIKVRVWDEDDDiksr 1292
Cdd:COG5038  1039 SGYLTIMLRSGENLPSSDENGYSDPFVKLFLnEKSVYKTKVVKKTLNPVWNEEFTIEVLNrVKDVLTINVNDWDSG---- 1114

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568960994 1293 vkqhfkkESDDFLGQTIVEVRTLSGEMDVWYNLeKRTDKSA--VSGAIRLKIN 1343
Cdd:COG5038  1115 -------EKNDLLGTAEIDLSKLEPGGTTNSNI-PLDGKTFivLDGTLHPGFN 1159
 
Name Accession Description Interval E-value
MUN pfam06292
MUN domain; This entry corresponds to the MUN domain found in Munc13 proteins. These ...
 1536-2034 0e+00

MUN domain; This entry corresponds to the MUN domain found in Munc13 proteins. These constitute a family of three highly homologous molecules (Munc13-1, Munc13-2 and Munc13-3) with homology to Caenorhabditis elegans unc-13p. Munc13 proteins contain a phorbol ester-binding C1 domain and two C2 domains, which are Ca2+/phospholipid binding domains. Sequence analyses have uncovered two regions called Munc13 homology domains 1 (MHD1) and 2 (MHD2) that are arranged between two flanking C2 domains. MHD1 and MHD2 domains are present in a wide variety of proteins from Arabidopsis thaliana, C. elegans, Drosophila melanogaster, mouse, rat and human, some of which may function in a Munc13-like manner to regulate membrane trafficking. Structural studies have defined MHD1 and MHD2 to be part of the larger MUN domain which forms an elongated structure composed of any pairs of alpha helices.


Pssm-ID: 461870  Cd Length: 473  Bit Score: 739.60  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994  1536 AVVKDCVRACLDSTYKYIFDNCHELYSQLIDPsKKQDVPREDQ--GPTTKNLDFWPQLITLMVTIIDEDKTAYTPVLNQF 1613
Cdd:pfam06292    1 QVVKDCLKAAALSNYQRLFENAYELSREFKIE-DKESIPEESQglGPSEKRLDFWIKLIELCVSVLQQDKEHYAPVLNQF 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994  1614 PQELNMGKISAEIMWSLFALDMKYALEEHEKQRLCKSTDYMNLHFKVKWFYNEYVRELPAFKD--AVPEYSLWFEPFVMQ 1691
Cdd:pfam06292   80 PWELDLGAEHAEIFWSLFAVDMDAALEEHEQHRLCKPDSWMNLHFKVKWLLNDYLRDDPTLKNgkFHPHYPDWFEPFVMR 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994  1692 WLDENEDVSMEFLHGALGRDKKDGFQQTSDHALFSCSVVDVFAQLNQSFEIIKKLECPNPEALSHLMRRFAKTINKVLVQ 1771
Cdd:pfam06292  160 YLDLNESSIAQSLHGGFERDKKDGFQQSSEHALFSSSVVDLFWKLNQLQDFIKKLEWPDPEFAAHLEKRFKLMASDMLLA 239

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994  1772 YAAIVSNDFSSYCDKETVPCILMNNIQQLRVQLEKMFESMGGKekkegerfsyELDPEASTILKELQIKLNGVLDALSIT 1851
Cdd:pfam06292  240 YAKRTRKAFDSKLKKPRTACTMMNNIQQARVQLEKMFLCMGGD----------ELDGEAHQYLTELQVLLEGVLDEMSSI 309

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994  1852 YGESFQLTIEECIKQMGAELNQMRANgnstaNKNSAAMDAEIVLRPLMDFLDKTLSLSAKICEKTVLKRVLKELWKLVLN 1931
Cdd:pfam06292  310 FADSFEPVLESVLSKLSRLLQQIKGS-----NRNNAAYDEGTLLSPLMDFLDGNLSLFARICEKTVLKRVLKELWKIVMN 384

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994  1932 KIEKQIVLPPLTDQTGPQMifiaakdlgqlsklKEHMIREDAKGLTPRQCAIVEVVLATIKQYFHAGGNGLKKNFLEKSP 2011
Cdd:pfam06292  385 TLEKTVVLPPLSDQSGSQL--------------KLLMSLEGAKNLTPKQCAILDAALETIFQYFHAGGNGLKKTWLEKSP 450

                          490       500
                   ....*....|....*....|...
gi 568960994  2012 DLHSLRYALSLYTQTTDALIKKF 2034
Cdd:pfam06292  451 ELQLLRYALSLYTQTTDKLIKDF 473
C2B_Munc13 cd04027
C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...
 1216-1342 4.56e-82

C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 175993 [Multi-domain]  Cd Length: 127  Bit Score: 265.20  E-value: 4.56e-82
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1216 AKITITVVSAQGLQAKDKTGSSDPYVTVQVGKNKRRTKTIFGNLNPVWDEKFFFECHNSTDRIKVRVWDEDDDIKSRVKQ 1295
Cdd:cd04027     1 AKISITVVCAQGLIAKDKTGTSDPYVTVQVGKTKKRTKTIPQNLNPVWNEKFHFECHNSSDRIKVRVWDEDDDIKSRLKQ 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 568960994 1296 HFKKESDDFLGQTIVEVRTLSGEMDVWYNLEKRTDKSAVSGAIRLKI 1342
Cdd:cd04027    81 KFTRESDDFLGQTIIEVRTLSGEMDVWYNLEKRTDKSAVSGAIRLHI 127
C2C_Munc13 cd08395
C2 domain third repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...
 2068-2187 7.03e-71

C2 domain third repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins.C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 176041 [Multi-domain]  Cd Length: 120  Bit Score: 233.06  E-value: 7.03e-71
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 2068 KVTVKVIAINDLNWQTTAMFRPFVEVCMLGPSLGDKKRKQGTKTKSNTWSPKYNETFQFILGNENRPGAYELHLSVKDYC 2147
Cdd:cd08395     1 KVTVKVVAANDLKWQTTGMFRPFVEVNLIGPHLSDKKRKFATKSKNNNWSPKYNETFQFILGNEDDPESYELHICVKDYC 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 568960994 2148 FAREDRIIGMTVIQLQNIAEKGSYGAWYPLLKNLSMDETG 2187
Cdd:cd08395    81 FARDDRLVGVTVLQLRDIAQAGSCACWLPLGRRIHMDETG 120
C1_Munc13-2-like cd20859
protein kinase C conserved region 1 (C1 domain) found in Munc13-2, Munc13-3 and similar ...
 1075-1156 2.57e-52

protein kinase C conserved region 1 (C1 domain) found in Munc13-2, Munc13-3 and similar proteins; Munc13-2, also called protein unc-13 homolog B (Unc13B), plays a role in vesicle maturation during exocytosis as a target of the diacylglycerol second messenger pathway. It is involved in neurotransmitter release by acting in synaptic vesicle priming prior to vesicle fusion and participates in the activity-dependent refilling of readily releasable vesicle pool (RRP). Munc13-2 is essential for normal release probability at hippocampal mossy fiber synapses. Munc13-3 is almost exclusively expressed in the cerebellum. It acts as a tumor suppressor and plays a critical role in the formation of release sites with calcium channel nanodomains. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410409  Cd Length: 82  Bit Score: 178.33  E-value: 2.57e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1075 HVFRKTLQALIYPISSTTPHNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADCLQRAAEKSSKH 1154
Cdd:cd20859     1 HVYKKTLQALIYPISCTTPHNFEVWTATTPTYCYECEGLLWGIARQGMRCSECGVKCHEKCQDLLNADCLQRAAEKSSKH 80


                  ..
gi 568960994 1155 GA 1156
Cdd:cd20859    81 GA 82
C1_Munc13-1 cd20858
protein kinase C conserved region 1 (C1 domain) found in Munc13-1 and similar proteins; ...
 1087-1146 2.94e-40

protein kinase C conserved region 1 (C1 domain) found in Munc13-1 and similar proteins; Munc13-1, also called protein unc-13 homolog A (Unc13A), is a diacylglycerol (DAG) receptor that plays a role in vesicle maturation during exocytosis as a target of the diacylglycerol second messenger pathway. It is involved in neurotransmitter release by acting in synaptic vesicle priming prior to vesicle fusion and participates in the activity-dependent refilling of readily releasable vesicle pool (RRP). Loss of MUNC13-1 function causes microcephaly, cortical hyperexcitability, and fatal myasthenia. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410408  Cd Length: 60  Bit Score: 143.30  E-value: 2.94e-40
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1087 PISSTTPHNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADCLQR 1146
Cdd:cd20858     1 PISCTTPHNFEVWTATTPTYCYECEGLLWGIARQGMRCTECGVKCHEKCQDLLNADCLQR 60
C1_Munc13 cd20807
protein kinase C conserved region 1 (C1 domain) found in the Munc13 family; The Munc13 gene ...
 1094-1146 9.73e-37

protein kinase C conserved region 1 (C1 domain) found in the Munc13 family; The Munc13 gene family encodes a family of neuron-specific, synaptic molecules that bind to syntaxin, an essential mediator of neurotransmitter release. Munc13-1 is a component of presynaptic active zones in which it acts as an essential synaptic vesicle priming protein. Munc13-2 is essential for normal release probability at hippocampal mossy fiber synapses. Munc13-3 is almost exclusively expressed in the cerebellum. It acts as a tumor suppressor and plays a critical role in the formation of release sites with calcium channel nanodomains. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410357  Cd Length: 53  Bit Score: 132.99  E-value: 9.73e-37
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568960994 1094 HNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADCLQR 1146
Cdd:cd20807     1 HNFEVWTATTPTYCYECEGLLWGIARQGVRCTECGVKCHEKCKDLLNADCLQR 53
C2 pfam00168
C2 domain;
1217-1325 1.97e-26

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 105.48  E-value: 1.97e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994  1217 KITITVVSAQGLQAKDKTGSSDPYVTVQV--GKNKRRTKTIFGNLNPVWDEKFFFECHNSTDR-IKVRVWDEDddiksrv 1293
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDGNGTSDPYVKVYLldGKQKKKTKVVKNTLNPVWNETFTFSVPDPENAvLEIEVYDYD------- 74

                           90       100       110
                   ....*....|....*....|....*....|....
gi 568960994  1294 kqhfKKESDDFLGQTIVEVRTL--SGEMDVWYNL 1325
Cdd:pfam00168   75 ----RFGRDDFIGEVRIPLSELdsGEGLDGWYPL 104
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 1218-1325 2.45e-25

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175973 [Multi-domain]  Cd Length: 102  Bit Score: 102.15  E-value: 2.45e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1218 ITITVVSAQGLQAKDKTGSSDPYVTVQVG-KNKRRTKTIFGNLNPVWDEKFFFECHN-STDRIKVRVWDEDddiksrvkq 1295
Cdd:cd00030     1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGgKQKFKTKVVKNTLNPVWNETFEFPVLDpESDTLTVEVWDKD--------- 71

                          90       100       110
                  ....*....|....*....|....*....|...
gi 568960994 1296 hfKKESDDFLGQTIVEVRTL---SGEMDVWYNL 1325
Cdd:cd00030    72 --RFSKDDFLGEVEIPLSELldsGKEGELWLPL 102
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 1217-1322 1.16e-23

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 97.17  E-value: 1.16e-23
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994   1217 KITITVVSAQGLQAKDKTGSSDPYVTVQVG---KNKRRTKTIFGNLNPVWDEKFFFEC-HNSTDRIKVRVWDEDddiksr 1292
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDgdpKEKKKTKVVKNTLNPVWNETFEFEVpPPELAELEIEVYDKD------ 74

                            90       100       110
                    ....*....|....*....|....*....|..
gi 568960994   1293 vkqhfKKESDDFLGQTIVEVRTL--SGEMDVW 1322
Cdd:smart00239   75 -----RFGRDDFIGQVTIPLSDLllGGRHEKL 101
C2A_C2C_Synaptotagmin_like cd08391
C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a ...
 1220-1326 1.71e-20

C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains either the first or third repeat in Synaptotagmin-like proteins with a type-I topology.


Pssm-ID: 176037 [Multi-domain]  Cd Length: 121  Bit Score: 88.89  E-value: 1.71e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1220 ITVVSAQGLQAKDK------TGSSDPYVTVQVGKNKRRTKTIFGNLNPVWDEKF---FFECHNSTdrIKVRVWDEDDDik 1290
Cdd:cd08391     5 IHVIEAQDLVAKDKfvgglvKGKSDPYVIVRVGAQTFKSKVIKENLNPKWNEVYeavVDEVPGQE--LEIELFDEDPD-- 80

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 568960994 1291 srvkqhfkkeSDDFLGQTIVEVRTL--SGEMDVWYNLE 1326
Cdd:cd08391    81 ----------KDDFLGRLSIDLGSVekKGFIDEWLPLE 108
C2A_MCTP_PRT_plant cd04022
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 1217-1342 3.09e-20

C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 175989 [Multi-domain]  Cd Length: 127  Bit Score: 88.55  E-value: 3.09e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1217 KITITVVSAQGLQAKDKTGSSDPYVTVQVGKNKRRTKTIFGNLNPVWDEKFFFECH----NSTDRIKVRVWDEDDDIKSR 1292
Cdd:cd04022     1 KLVVEVVDAQDLMPKDGQGSSSAYVELDFDGQKKRTRTKPKDLNPVWNEKLVFNVSdpsrLSNLVLEVYVYNDRRSGRRR 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568960994 1293 vkqhfkkesdDFLGQTIVEVRTLSGEMD---VWYNLEKRTDKSAVSGAIRLKI 1342
Cdd:cd04022    81 ----------SFLGRVRISGTSFVPPSEavvQRYPLEKRGLFSRVRGEIGLKV 123
C2 pfam00168
C2 domain;
2067-2177 1.08e-18

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 83.14  E-value: 1.08e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994  2067 HKVTVKVIAINDL-NWQTTAMFRPFVEVCMLgpslgDKKRKQGTKTKSNTWSPKYNETFQFILGNENRpgaYELHLSVKD 2145
Cdd:pfam00168    1 GRLTVTVIEAKNLpPKDGNGTSDPYVKVYLL-----DGKQKKKTKVVKNTLNPVWNETFTFSVPDPEN---AVLEIEVYD 72

                           90       100       110
                   ....*....|....*....|....*....|..
gi 568960994  2146 YCFAREDRIIGMTVIQLQNIAEKGSYGAWYPL 2177
Cdd:pfam00168   73 YDRFGRDDFIGEVRIPLSELDSGEGLDGWYPL 104
C1_Sbf-like cd20827
protein kinase C conserved region 1 (C1 domain) found in the myotubularin-related protein Sbf ...
 1093-1143 1.89e-18

protein kinase C conserved region 1 (C1 domain) found in the myotubularin-related protein Sbf and similar proteins; This group includes Drosophila melanogaster SET domain binding factor (Sbf), the single homolog of human MTMR5/MTMR13, and similar proteins, that show high sequence similarity to vertebrate myotubularin-related proteins (MTMRs) which may function as guanine nucleotide exchange factors (GEFs). Sbf is a pseudophosphatase that coordinates both phosphatidylinositol 3-phosphate (PI(3)P) turnover and Rab21 GTPase activation in an endosomal pathway that controls macrophage remodeling. It also functions as a GEF that promotes Rab21 GTPase activation associated with PI(3)P endosomes. Vertebrate MTMR5 and MTMR13 contain an N-terminal DENN domain, a PH-GRAM domain, an inactive PTP domain, a SET interaction domain, a coiled-coil domain, and a C-terminal PH domain. Members of this family contain these domains and have an additional C1 domain. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410377  Cd Length: 53  Bit Score: 80.92  E-value: 1.89e-18
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568960994 1093 PHNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADC 1143
Cdd:cd20827     1 PHRFEKHNFTTPTYCDYCSSLLWGLVKTGMRCADCGYSCHEKCLEHVPKNC 51
C1 smart00109
Protein kinase C conserved region 1 (C1) domains (Cysteine-rich domains); Some bind phorbol ...
 1094-1143 7.90e-18

Protein kinase C conserved region 1 (C1) domains (Cysteine-rich domains); Some bind phorbol esters and diacylglycerol. Some bind RasGTP. Zinc-binding domains.


Pssm-ID: 197519  Cd Length: 50  Bit Score: 79.05  E-value: 7.90e-18
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|
gi 568960994   1094 HNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADC 1143
Cdd:smart00109    1 HKHVFRTFTKPTFCCVCRKSIWGSFKQGLRCSECKVKCHKKCADKVPKAC 50
C1_RASGRP cd20808
protein kinase C conserved region 1 (C1 domain) found in the RAS guanyl-releasing protein ...
 1093-1143 1.08e-17

protein kinase C conserved region 1 (C1 domain) found in the RAS guanyl-releasing protein (RASGRP) family; The RASGRP family includes RASGRP1-4. They function as cation-, usually calcium-, and diacylglycerol (DAG)-regulated nucleotide exchange factor activating Ras through the exchange of bound GDP for GTP. RASGRP1, also called calcium and DAG-regulated guanine nucleotide exchange factor II (CalDAG-GEFII) or Ras guanyl-releasing protein, activates the Erk/MAP kinase cascade and regulates T-cell/B-cell development, homeostasis and differentiation by coupling T-lymphocyte/B-lymphocyte antigen receptors to Ras. RASGRP1 also regulates NK cell cytotoxicity and ITAM-dependent cytokine production by activation of Ras-mediated ERK and JNK pathways. RASGRP2, also called calcium and DAG-regulated guanine nucleotide exchange factor I (CalDAG-GEFI), Cdc25-like protein (CDC25L), or F25B3.3 kinase-like protein, specifically activates Rap and may also activate other GTPases such as RRAS, RRAS2, NRAS, KRAS but not HRAS. RASGRP2 is involved in aggregation of platelets and adhesion of T-lymphocytes and neutrophils probably through inside-out integrin activation, as well as in the muscarinic acetylcholine receptor M1/CHRM1 signaling pathway. RASGRP3, also called calcium and DAG-regulated guanine nucleotide exchange factor III (CalDAG-GEFIII), or guanine nucleotide exchange factor for Rap1, is a guanine nucleotide-exchange factor activating H-Ras, R-Ras and Ras-associated protein-1/2. It functions as an important mediator of signaling downstream from receptor coupled phosphoinositide turnover in B and T cells. RASGRP4 may function in mast cell differentiation. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410358  Cd Length: 52  Bit Score: 78.53  E-value: 1.08e-17
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568960994 1093 PHNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADC 1143
Cdd:cd20808     1 KHNFQETTYFKPTFCDHCTGLLWGLIKQGYKCKDCGINCHKHCKDLVVVEC 51
C2C_MCTP_PRT cd08377
C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 1219-1344 2.81e-17

C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. The cds in this family contain multiple C2 domains as well as a C-terminal PRT domain. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 176023 [Multi-domain]  Cd Length: 119  Bit Score: 79.65  E-value: 2.81e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1219 TITVVSAQGLQAKDKTGSSDPYVTVQVGKNKRRTKTIFGNLNPVWDEKFFFECHNSTDRIKVRVWDEDddiksrvkqhfK 1298
Cdd:cd08377     4 QVKVIRASGLAAADIGGKSDPFCVLELVNARLQTHTIYKTLNPEWNKIFTFPIKDIHDVLEVTVYDED-----------K 72

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 568960994 1299 KESDDFLGQTIVEVRTL-SGEMDvWYNLEKRTDKSAVSGAIRLKINV 1344
Cdd:cd08377    73 DKKPEFLGKVAIPLLSIkNGERK-WYALKDKKLRTRAKGSILLEMDV 118
C2D_Tricalbin-like cd04040
C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 1218-1341 5.41e-17

C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fifth C2 repeat, C2E, and has a type-II topology.


Pssm-ID: 176005 [Multi-domain]  Cd Length: 115  Bit Score: 78.76  E-value: 5.41e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1218 ITITVVSAQGLQAKDKTGSSDPYVTVQV-GKNKRRTKTIFGNLNPVWDEKFFFECHN-STDRIKVRVWDEDddiksRVkq 1295
Cdd:cd04040     1 LTVDVISAENLPSADRNGKSDPFVKFYLnGEKVFKTKTIKKTLNPVWNESFEVPVPSrVRAVLKVEVYDWD-----RG-- 73

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 568960994 1296 hfkkESDDFLGQTIVEVRTLSGEMDVWYNLEKRTDKSAVSGAIRLK 1341
Cdd:cd04040    74 ----GKDDLLGSAYIDLSDLEPEETTELTLPLDGQGGGKLGAVFLP 115
C1 cd00029
protein kinase C conserved region 1 (C1 domain) superfamily; The C1 domain is a cysteine-rich ...
 1094-1143 6.78e-17

protein kinase C conserved region 1 (C1 domain) superfamily; The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains. It contains the motif HX12CX2CXnCX2CX4HX2CX7C, where C and H are cysteine and histidine, respectively; X represents other residues; and n is either 13 or 14. C1 has a globular fold with two separate Zn(2+)-binding sites. It was originally discovered as lipid-binding modules in protein kinase C (PKC) isoforms. C1 domains that bind and respond to phorbol esters (PE) and diacylglycerol (DAG) are referred to as typical, and those that do not respond to PE and DAG are deemed atypical. A C1 domain may also be referred to as PKC or non-PKC C1, based on the parent protein's activity. Most C1 domain-containing non-PKC proteins act as lipid kinases and scaffolds, except PKD which acts as a protein kinase. PKC C1 domains play roles in membrane translocation and activation of the enzyme.


Pssm-ID: 410341  Cd Length: 50  Bit Score: 76.40  E-value: 6.78e-17
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568960994 1094 HNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADC 1143
Cdd:cd00029     1 HRFVPTTFSSPTFCDVCGKLIWGLFKQGLKCSDCGLVCHKKCLDKAPSPC 50
C1_MTMR-like cd20828
protein kinase C conserved region 1 (C1 domain) found in uncharacterized proteins similar to ...
 1091-1143 7.03e-17

protein kinase C conserved region 1 (C1 domain) found in uncharacterized proteins similar to myotubularin-related proteins; The family includes a group of uncharacterized proteins that show high sequence similarity to vertebrate myotubularin-related proteins (MTMRs), such as MTMR5 and MTMR13. MTMRs may function as guanine nucleotide exchange factors (GEFs). Vertebrate MTMR5 and MTMR13 contain an N-terminal DENN domain, a PH-GRAM domain, an inactive PTP domain, a SET interaction domain, a coiled-coil domain, and a C-terminal PH domain. Members of this family contain these domains and have an additional C1 domain. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410378  Cd Length: 57  Bit Score: 76.33  E-value: 7.03e-17
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568960994 1091 TTPHNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADC 1143
Cdd:cd20828     3 TQPHNFEPHSFVTPTNCDYCLQILWGIVKKGMKCSECGYNCHEKCQPQVPKQC 55
C1_RASGRP4 cd20863
protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 4 ...
 1093-1146 1.98e-16

protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 4 (RASGRP4) and similar proteins; RASGRP4 functions as a cation- and diacylglycerol (DAG)-regulated nucleotide exchange factor activating Ras through the exchange of bound GDP for GTP. It may function in mast cell differentiation. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410413  Cd Length: 57  Bit Score: 75.20  E-value: 1.98e-16
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568960994 1093 PHNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADCLQR 1146
Cdd:cd20863     3 LHNFHETTFKKPTFCDSCSGFLWGVTKQGYRCQDCGINCHKHCKDQVDVECKKR 56
C1_PKD_rpt2 cd20796
second protein kinase C conserved region 1 (C1 domain) found in the family of protein kinase D ...
 1093-1144 8.21e-16

second protein kinase C conserved region 1 (C1 domain) found in the family of protein kinase D (PKD); PKDs are important regulators of many intracellular signaling pathways such as ERK and JNK, and cellular processes including the organization of the trans-Golgi network, membrane trafficking, cell proliferation, migration, and apoptosis. They are activated in a PKC-dependent manner by many agents including diacylglycerol (DAG), PDGF, neuropeptides, oxidative stress, and tumor-promoting phorbol esters, among others. Mammals harbor three types of PKDs: PKD1 (or PKCmu), PKD2, and PKD3 (or PKCnu). PKDs contain N-terminal tandem cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. This model corresponds to the second C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410346  Cd Length: 54  Bit Score: 73.09  E-value: 8.21e-16
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568960994 1093 PHNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADCL 1144
Cdd:cd20796     1 PHTFVVHTYTKPTVCQHCKKLLKGLFRQGLQCKDCKFNCHKKCAEKVPKDCT 52
C2_Calpain cd04046
C2 domain present in Calpain proteins; A single C2 domain is found in calpains (EC 3.4.22.52, ...
 1218-1343 1.16e-15

C2 domain present in Calpain proteins; A single C2 domain is found in calpains (EC 3.4.22.52, EC 3.4.22.53), calcium-dependent, non-lysosomal cysteine proteases. Caplains are classified as belonging to Clan CA by MEROPS and include six families: C1, C2, C10, C12, C28, and C47. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176011 [Multi-domain]  Cd Length: 126  Bit Score: 75.39  E-value: 1.16e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1218 ITITVVSAQGLQAKDKTGSSDPYVTVQVGKNKRRTKTIFGNLNPVWDEKFFFECHNSTDRIKVRVWDEDddiksrvkqhf 1297
Cdd:cd04046     5 TQVHVHSAEGLSKQDSGGGADPYVIIKCEGESVRSPVQKDTLSPEFDTQAIFYRKKPRSPIKIQVWNSN----------- 73

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 568960994 1298 kKESDDFLGQTIVEVRTLSGEMDVWYNLEKRTDKSA--VSGAIRLKIN 1343
Cdd:cd04046    74 -LLCDEFLGQATLSADPNDSQTLRTLPLRKRGRDAAgeVPGTISVKVT 120
C2A_RIM1alpha cd04031
C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
 1219-1326 4.24e-15

C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are believed to organize specialized sites of the plasma membrane called active zones. They also play a role in controlling neurotransmitter release, plasticity processes, as well as memory and learning. RIM contains an N-terminal zinc finger domain, a PDZ domain, and two C-terminal C2 domains (C2A, C2B). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology and do not bind Ca2+.


Pssm-ID: 175997 [Multi-domain]  Cd Length: 125  Bit Score: 73.82  E-value: 4.24e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1219 TITVVSAQGLQAKDKTGSSDPYVTV-----QVGKNKRRTKTIFGNLNPVWDEKF-FFECHNSTDR---IKVRVWDEDDDi 1289
Cdd:cd04031    19 IVTVLQARDLPPRDDGSLRNPYVKVyllpdRSEKSKRRTKTVKKTLNPEWNQTFeYSNVRRETLKertLEVTVWDYDRD- 97

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 568960994 1290 ksrvkqhfkkESDDFLGQTIVEVRT--LSGEMdVWYNLE 1326
Cdd:cd04031    98 ----------GENDFLGEVVIDLADalLDDEP-HWYPLQ 125
C1_1 pfam00130
Phorbol esters/diacylglycerol binding domain (C1 domain); This domain is also known as the ...
 1094-1143 4.33e-15

Phorbol esters/diacylglycerol binding domain (C1 domain); This domain is also known as the Protein kinase C conserved region 1 (C1) domain.


Pssm-ID: 395079  Cd Length: 53  Bit Score: 71.32  E-value: 4.33e-15
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 568960994  1094 HNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADC 1143
Cdd:pfam00130    1 HHFVHRNFKQPTFCDHCGEFLWGLGKQGLKCSWCKLNVHKRCHEKVPPEC 50
C2A_Synaptotagmin-like cd04024
C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
 1220-1341 7.01e-15

C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 175990 [Multi-domain]  Cd Length: 128  Bit Score: 73.23  E-value: 7.01e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1220 ITVVSAQGLQAKD--KTGSSDPYVTVQVGKNKRRTKTIFGNLNPVWDEKFFFEcHNST--DRIKVRVWDEDDdiksrvkq 1295
Cdd:cd04024     5 VHVVEAKDLAAKDrsGKGKSDPYAILSVGAQRFKTQTIPNTLNPKWNYWCEFP-IFSAqnQLLKLILWDKDR-------- 75

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568960994 1296 hFKKesDDFLGQ-----TIVEVRTLSGEMDVWYNLE-KRTDK-SAVSGAIRLK 1341
Cdd:cd04024    76 -FAG--KDYLGEfdialEEVFADGKTGQSDKWITLKsTRPGKtSVVSGEIHLQ 125
C2_NEDD4_NEDD4L cd04033
C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated ...
 1220-1342 1.21e-14

C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42); Nedd4 and Nedd4-2 are two of the nine members of the Human Nedd4 family. All vertebrates appear to have both Nedd4 and Nedd4-2 genes. They are thought to participate in the regulation of epithelial Na+ channel (ENaC) activity. They also have identical specificity for ubiquitin conjugating enzymes (E2). Nedd4 and Nedd4-2 are composed of a C2 domain, 2-4 WW domains, and a ubiquitin ligase Hect domain. Their WW domains can bind PPxY (PY) or LPSY motifs, and in vitro studies suggest that WW3 and WW4 of both proteins bind PY motifs in the key substrates, with WW3 generally exhibiting higher affinity. Most Nedd4 family members, especially Nedd4-2, also have multiple splice variants, which might play different roles in regulating their substrates. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175999 [Multi-domain]  Cd Length: 133  Bit Score: 72.77  E-value: 1.21e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1220 ITVVSAQGLQAKDKTGSSDPYVTVQVGKNKR-------RTKTIFGNLNPVWDEKFFFECHNSTDRIKVRVWDEDddiksR 1292
Cdd:cd04033     4 VKVLAGIDLAKKDIFGASDPYVKISLYDPDGngeidsvQTKTIKKTLNPKWNEEFFFRVNPREHRLLFEVFDEN-----R 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1293 VKQhfkkesDDFLGQtiVEVRTLSGE----------MDVWYNLEKRTDKSAVSGAIRLKI 1342
Cdd:cd04033    79 LTR------DDFLGQ--VEVPLNNLPtetpgnerryTFKDYLLRPRSSKSRVKGHLRLYM 130
C1_RASGRP1 cd20860
protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 1 ...
 1093-1146 1.26e-14

protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 1 (RASGRP1) and similar proteins; RASGRP1, also called calcium and DAG-regulated guanine nucleotide exchange factor II (CalDAG-GEFII) or Ras guanyl-releasing protein, functions as a calcium- and diacylglycerol (DAG)-regulated nucleotide exchange factor specifically activating Ras through the exchange of bound GDP for GTP. It activates the Erk/MAP kinase cascade and regulates T-cell/B-cell development, homeostasis and differentiation by coupling T-lymphocyte/B-lymphocyte antigen receptors to Ras. RASGRP1 also regulates NK cell cytotoxicity and ITAM-dependent cytokine production by activation of Ras-mediated ERK and JNK pathways. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410410  Cd Length: 55  Bit Score: 69.96  E-value: 1.26e-14
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568960994 1093 PHNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADCLQR 1146
Cdd:cd20860     2 PHNFQETTYLKPTFCDNCAGFLWGVIKQGYRCKDCGMNCHKQCKDLVVFECKKR 55
C2B_MCTP_PRT cd08376
C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 1218-1327 1.37e-14

C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. MCTP is composed of a variable N-terminal sequence, three C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176022 [Multi-domain]  Cd Length: 116  Bit Score: 71.90  E-value: 1.37e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1218 ITITVVSAQGLQAKDKTGSSDPYVTVQVGKNKRRTKTIFGNLNPVWDEKFFFECHNSTDRI-KVRVWDEDddiksrvkqh 1296
Cdd:cd08376     2 VTIVLVEGKNLPPMDDNGLSDPYVKFRLGNEKYKSKVCSKTLNPQWLEQFDLHLFDDQSQIlEIEVWDKD---------- 71

                          90       100       110
                  ....*....|....*....|....*....|...
gi 568960994 1297 fKKESDDFLGQTIVEVRTLSGEM--DVWYNLEK 1327
Cdd:cd08376    72 -TGKKDEFIGRCEIDLSALPREQthSLELELED 103
C2A_MCTP_PRT cd04042
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 1217-1315 1.41e-14

C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. MCTP is composed of a variable N-terminal sequence, three C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 176007 [Multi-domain]  Cd Length: 121  Bit Score: 71.92  E-value: 1.41e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1217 KITITVVSAQGLQAKDKTGSSDPYVTVQV-GKNKRRTKTIFGNLNPVWDEKFFFECHNSTDRIKVRVWDEDddiksrvkq 1295
Cdd:cd04042     1 QLDIHLKEGRNLAARDRGGTSDPYVKFKYgGKTVYKSKTIYKNLNPVWDEKFTLPIEDVTQPLYIKVFDYD--------- 71

                          90       100
                  ....*....|....*....|
gi 568960994 1296 hfKKESDDFLGQTIVEVRTL 1315
Cdd:cd04042    72 --RGLTDDFMGSAFVDLSTL 89
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 1217-1315 1.66e-14

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) to d-myo-inositol-1,4,5-trisphosphate (1,4,5-IP3) and sn-1,2-diacylglycerol (DAG). 1,4,5-IP3 and DAG are second messengers in eukaryotic signal transduction cascades. PLC is composed of a N-terminal PH domain followed by a series of EF hands, a catalytic TIM barrel and a C-terminal C2 domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-II topology.


Pssm-ID: 175974 [Multi-domain]  Cd Length: 128  Bit Score: 72.19  E-value: 1.66e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1217 KITITVVSAQGL--QAKDKTGSSDPYVTVQV------GKNKRRTKTIFGN-LNPVWDEKFFFECHN-STDRIKVRVWDED 1286
Cdd:cd00275     3 TLTIKIISGQQLpkPKGDKGSIVDPYVEVEIhglpadDSAKFKTKVVKNNgFNPVWNETFEFDVTVpELAFLRFVVYDED 82

                          90       100
                  ....*....|....*....|....*....
gi 568960994 1287 ddiksrvkqhfkKESDDFLGQTIVEVRTL 1315
Cdd:cd00275    83 ------------SGDDDFLGQACLPLDSL 99
C2A_fungal cd04041
C2 domain first repeat; fungal group; C2 domains were first identified in Protein Kinase C ...
 1218-1294 3.49e-14

C2 domain first repeat; fungal group; C2 domains were first identified in Protein Kinase C (PKC). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176006 [Multi-domain]  Cd Length: 111  Bit Score: 70.75  E-value: 3.49e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1218 ITITVVSAQGLQAKD-KTGSSDPYVTVQ---VGKNKRRTKTIFGNLNPVWDEKFFF----ECHNSTDRIKVRVWDED--- 1286
Cdd:cd04041     3 LVVTIHRATDLPKADfGTGSSDPYVTASfakFGKPLYSTRIIRKDLNPVWEETWFVlvtpDEVKAGERLSCRLWDSDrft 82


                  ....*....
gi 568960994 1287 -DDIKSRVK 1294
Cdd:cd04041    83 aDDRLGRVE 91
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 2068-2174 4.12e-14

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 70.21  E-value: 4.12e-14
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994   2068 KVTVKVIAINDLNW-QTTAMFRPFVEVCMLGpslgDKKRKQGTKTKSNTWSPKYNETFQFILgneNRPGAYELHLSVKDY 2146
Cdd:smart00239    1 TLTVKIISARNLPPkDKGGKSDPYVKVSLDG----DPKEKKKTKVVKNTLNPVWNETFEFEV---PPPELAELEIEVYDK 73

                            90       100
                    ....*....|....*....|....*...
gi 568960994   2147 CFAREDRIIGMTVIQLQNIAEKGSYGAW 2174
Cdd:smart00239   74 DRFGRDDFIGQVTIPLSDLLLGGRHEKL 101
C1_RASGRP3 cd20862
protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 3 ...
 1094-1143 5.69e-14

protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 3 (RASGRP3) and similar proteins; RASGRP3, also called calcium and DAG-regulated guanine nucleotide exchange factor III (CalDAG-GEFIII), or guanine nucleotide exchange factor for Rap1, is a guanine nucleotide-exchange factor activating H-Ras, R-Ras and Ras-associated protein-1/2. It functions as an important mediator of signaling downstream from receptor coupled phosphoinositide turnover in B and T cells. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410412  Cd Length: 59  Bit Score: 68.14  E-value: 5.69e-14
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568960994 1094 HNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADC 1143
Cdd:cd20862     8 HNFQEMTYLKPTFCEHCAGFLWGIIKQGYKCKDCGVNCHKQCKDLLVLAC 57
C1_nPKC_theta-like_rpt2 cd20837
second protein kinase C conserved region 1 (C1 domain) found in novel protein kinase C (nPKC) ...
 1094-1143 7.03e-14

second protein kinase C conserved region 1 (C1 domain) found in novel protein kinase C (nPKC) theta, delta, and similar proteins; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. Members of this family contain two copies of C1 domain. This model corresponds to the second one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410387  Cd Length: 50  Bit Score: 67.85  E-value: 7.03e-14
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568960994 1094 HNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADC 1143
Cdd:cd20837     1 HRFKVYNYMSPTFCDHCGSLLWGLFRQGLKCEECGMNVHHKCQKKVANLC 50
C2_ArfGAP cd04038
C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating ...
 1217-1315 9.59e-14

C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating protein which regulates the ADP ribosylation factor Arf, a member of the Ras superfamily of GTP-binding proteins. The GTP-bound form of Arf is involved in Golgi morphology and is involved in recruiting coat proteins. ArfGAP is responsible for the GDP-bound form of Arf which is necessary for uncoating the membrane and allowing the Golgi to fuse with an acceptor compartment. These proteins contain an N-terminal ArfGAP domain containing the characteristic zinc finger motif (Cys-x2-Cys-x(16,17)-x2-Cys) and C-terminal C2 domain. C2 domains were first identified in Protein Kinase C (PKC). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176003 [Multi-domain]  Cd Length: 145  Bit Score: 70.43  E-value: 9.59e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1217 KITITVVSAQGLQAKDKTgSSDPYVTVQVGKNKRRTKTIFGNLNPVWDEKFFFECHNSTDRIKVRVWDEDddiksrvkqH 1296
Cdd:cd04038     3 LLKVRVVRGTNLAVRDFT-SSDPYVVLTLGNQKVKTRVIKKNLNPVWNEELTLSVPNPMAPLKLEVFDKD---------T 72

                          90
                  ....*....|....*....
gi 568960994 1297 FKKesDDFLGQTIVEVRTL 1315
Cdd:cd04038    73 FSK--DDSMGEAEIDLEPL 89
C1_cPKC_nPKC_rpt2 cd20793
second protein kinase C conserved region 1 (C1 domain) found in classical (or conventional) ...
 1094-1143 2.41e-13

second protein kinase C conserved region 1 (C1 domain) found in classical (or conventional) protein kinase C (cPKC), novel protein kinase C (nPKC), and similar proteins; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. nPKCs are calcium-independent, but require DAG and PS for activity, while atypical PKCs (aPKCs) only require PS. PKCs phosphorylate and modify the activities of a wide variety of cellular proteins including receptors, enzymes, cytoskeletal proteins, transcription factors, and other kinases. They play a central role in signal transduction pathways that regulate cell migration and polarity, proliferation, differentiation, and apoptosis. This family includes classical PKCs (cPKCs) and novel PKCs (nPKCs). There are four cPKC isoforms (named alpha, betaI, betaII, and gamma) and four nPKC isoforms (delta, epsilon, eta, and theta). Members of this family contain two copies of C1 domain. This model corresponds to the second one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410343  Cd Length: 50  Bit Score: 66.15  E-value: 2.41e-13
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568960994 1094 HNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADC 1143
Cdd:cd20793     1 HKFKVHTYYSPTFCDHCGSLLYGLVRQGLKCKDCGMNVHHRCKENVPHLC 50
C2_PKC_alpha_gamma cd04026
C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha ...
 1217-1286 2.62e-13

C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha and gamma. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1(alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.


Pssm-ID: 175992 [Multi-domain]  Cd Length: 131  Bit Score: 68.83  E-value: 2.62e-13
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568960994 1217 KITITVVSAQGLQAKDKTGSSDPYVTVQV-----GKNKRRTKTIFGNLNPVWDEKFFFECHNSTD--RIKVRVWDED 1286
Cdd:cd04026    14 KLTVEVREAKNLIPMDPNGLSDPYVKLKLipdpkNETKQKTKTIKKTLNPVWNETFTFDLKPADKdrRLSIEVWDWD 90
C2_Munc13_fungal cd04043
C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are ...
 1219-1351 3.69e-13

C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176008 [Multi-domain]  Cd Length: 126  Bit Score: 68.06  E-value: 3.69e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1219 TITVVSAQGLQAKDKTGSSDPYVTVQVGKNKRR---TKTIFGNLNPVWDEKFFFEC-HNSTDRIKVRVWDEDDDIKSRV- 1293
Cdd:cd04043     4 TIRIVRAENLKADSSNGLSDPYVTLVDTNGKRRiakTRTIYDTLNPRWDEEFELEVpAGEPLWISATVWDRSFVGKHDLc 83

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568960994 1294 -KQHF----KKESDDFLGQtivevrtlsgemDVWYNLEKRTdksavsgaiRLKINVEIKGEEK 1351
Cdd:cd04043    84 gRASLkldpKRFGDDGLPR------------EIWLDLDTQG---------RLLLRVSMEGERD 125
C2A_Munc13-like cd08676
C2 domain first repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
 1185-1325 4.43e-13

C2 domain first repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176058 [Multi-domain]  Cd Length: 153  Bit Score: 68.94  E-value: 4.43e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1185 IQEMFQISKEDFVQYTKAAKQSvldgtSKWSAKITITVVSAQGLQAKDKTGSSDPY--VTVQVGKNKR------------ 1250
Cdd:cd08676     2 AQQAFGVSPEEHEALLERVREA-----EPPIFVLKVTVIEAKGLLAKDVNGFSDPYcmLGIVPASRERnsekskkrkshr 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1251 ---------------RTKTIFGNLNPVWDEKFFFECHN-STDRIKVRVWDEDddiksrvkqhfkkesDDFLGQTIVEVRT 1314
Cdd:cd08676    77 kkavlkdtvpaksikVTEVKPQTLNPVWNETFRFEVEDvSNDQLHLDIWDHD---------------DDFLGCVNIPLKD 141

                         170
                  ....*....|..
gi 568960994 1315 LSGE-MDVWYNL 1325
Cdd:cd08676   142 LPSCgLDSWFKL 153
C1_RASGRP2 cd20861
protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 2 ...
 1094-1146 5.55e-13

protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 2 (RASGRP2) and similar proteins; RASGRP2, also called calcium and DAG-regulated guanine nucleotide exchange factor I (CalDAG-GEFI), Cdc25-like protein (CDC25L), or F25B3.3 kinase-like protein, functions as a calcium- and DAG-regulated nucleotide exchange factor specifically activating Rap through the exchange of bound GDP for GTP. It may also activate other GTPases such as RRAS, RRAS2, NRAS, KRAS but not HRAS. RASGRP2 is also involved in aggregation of platelets and adhesion of T-lymphocytes and neutrophils probably through inside-out integrin activation, as well as in the muscarinic acetylcholine receptor M1/CHRM1 signaling pathway. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410411  Cd Length: 56  Bit Score: 65.29  E-value: 5.55e-13
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568960994 1094 HNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADCLQR 1146
Cdd:cd20861     4 HNFAERTFLRPVACRHCKNLILGIYKQGLKCRACGVNCHKQCKDHLSIECRKR 56
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
 1217-1310 5.96e-13

C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. There are several classes of Synaptotagmins. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175975 [Multi-domain]  Cd Length: 134  Bit Score: 67.99  E-value: 5.96e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1217 KITITVVSAQGLQAKDKTGSSDPYVTV---QVGK--NKRRTKTIFGNLNPVWDEKFFFEChnSTDRIkvrvwdEDDDIKS 1291
Cdd:cd00276    15 RLTVVVLKARNLPPSDGKGLSDPYVKVsllQGGKklKKKKTSVKKGTLNPVFNEAFSFDV--PAEQL------EEVSLVI 86

                          90
                  ....*....|....*....
gi 568960994 1292 RVKQHFKKESDDFLGQTIV 1310
Cdd:cd00276    87 TVVDKDSVGRNEVIGQVVL 105
C1_CeDKF1-like_rpt2 cd20798
second protein kinase C conserved region 1 (C1 domain) found in Caenorhabditis elegans serine ...
 1093-1143 1.87e-12

second protein kinase C conserved region 1 (C1 domain) found in Caenorhabditis elegans serine/threonine-protein kinase DKF-1 and similar proteins; DKF-1 converts transient diacylglycerol (DAG) signals into prolonged physiological effects, independently of PKC. It plays a role in the regulation of growth and neuromuscular control of movement. It is involved in immune response to Staphylococcus aureus bacterium by activating transcription factor hlh-30 downstream of phospholipase plc-1. Members of this group contain two copies of the C1 domain. This model corresponds to the second one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410348  Cd Length: 54  Bit Score: 63.67  E-value: 1.87e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568960994 1093 PHNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADC 1143
Cdd:cd20798     1 PHTLAEHNYKKPTVCKVCDKLLVGLVRQGLKCRDCGVNVHKKCASLLPSNC 51
C2_Perforin cd04032
C2 domain of Perforin; Perforin contains a single copy of a C2 domain in its C-terminus and ...
 1216-1306 2.03e-12

C2 domain of Perforin; Perforin contains a single copy of a C2 domain in its C-terminus and plays a role in lymphocyte-mediated cytotoxicity. Mutations in perforin leads to familial hemophagocytic lymphohistiocytosis type 2. The function of perforin is calcium dependent and the C2 domain is thought to confer this binding to target cell membranes. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175998 [Multi-domain]  Cd Length: 127  Bit Score: 66.13  E-value: 2.03e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1216 AKITITVVSAQGLQAkDKTGSSDPYVTVQVGKNKRRTKTIFGNLNPVWDEKFFFECHN--STDRIKVRVWDEDDdiksrv 1293
Cdd:cd04032    28 ATLTVTVLRATGLWG-DYFTSTDGYVKVFFGGQEKRTEVIWNNNNPRWNATFDFGSVElsPGGKLRFEVWDRDN------ 100

                          90
                  ....*....|...
gi 568960994 1294 kqhfkKESDDFLG 1306
Cdd:cd04032   101 -----GWDDDLLG 108
C1_CHN cd20806
protein kinase C conserved region 1 (C1 domain) found in the chimaerin family; Chimaerins are ...
 1093-1143 2.14e-12

protein kinase C conserved region 1 (C1 domain) found in the chimaerin family; Chimaerins are a family of phorbolester- and diacylglycerol-responsive GTPase activating proteins (GAPs) specific for the Rho-like GTPase Rac. Alpha1-chimerin (formerly known as N-chimerin) and alpha2-chimerin are alternatively spliced products of a single gene, as are beta1- and beta2-chimerin. Alpha1- and beta1-chimerin have a relatively short N-terminal region that does not encode any recognizable domains, whereas alpha2- and beta2-chimerin both include a functional SH2 domain that can bind to phosphotyrosine motifs within receptors. All the isoforms contain a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410356  Cd Length: 53  Bit Score: 63.48  E-value: 2.14e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568960994 1093 PHNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADC 1143
Cdd:cd20806     1 PHNFKVHTFKGPHWCDYCGNFMWGLIAQGVKCEDCGFNAHKQCSKLVPHDC 51
C1_cPKC_nPKC_rpt1 cd20792
first protein kinase C conserved region 1 (C1 domain) found in classical (or conventional) ...
 1093-1143 2.77e-12

first protein kinase C conserved region 1 (C1 domain) found in classical (or conventional) protein kinase C (cPKC), novel protein kinase C (nPKC), and similar proteins; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domains. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. nPKCs are calcium-independent, but require DAG and PS for activity, while atypical PKCs (aPKCs) only require PS. PKCs phosphorylate and modify the activities of a wide variety of cellular proteins including receptors, enzymes, cytoskeletal proteins, transcription factors, and other kinases. They play a central role in signal transduction pathways that regulate cell migration and polarity, proliferation, differentiation, and apoptosis. This family includes classical PKCs (cPKCs) and novel PKCs (nPKCs). There are four cPKC isoforms (named alpha, betaI, betaII, and gamma) and four nPKC isoforms (delta, epsilon, eta, and theta). Members of this family contain two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410342  Cd Length: 53  Bit Score: 63.03  E-value: 2.77e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568960994 1093 PHNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADC 1143
Cdd:cd20792     1 GHKFVATFFKQPTFCSHCKDFIWGLGKQGYQCQVCRFVVHKRCHEYVVFKC 51
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 2069-2177 5.58e-12

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175973 [Multi-domain]  Cd Length: 102  Bit Score: 64.01  E-value: 5.58e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 2069 VTVKVIAINDL-NWQTTAMFRPFVEVcmlgpSLGDKKRKQgTKTKSNTWSPKYNETFQFILgneNRPGAYELHLSVKDYC 2147
Cdd:cd00030     1 LRVTVIEARNLpAKDLNGKSDPYVKV-----SLGGKQKFK-TKVVKNTLNPVWNETFEFPV---LDPESDTLTVEVWDKD 71

                          90       100       110
                  ....*....|....*....|....*....|.
gi 568960994 2148 FAREDRIIGMTVIQLQNIAEKGSYGA-WYPL 2177
Cdd:cd00030    72 RFSKDDFLGEVEIPLSELLDSGKEGElWLPL 102
C1_SpBZZ1-like cd20824
protein kinase C conserved region 1 (C1 domain) found in Schizosaccharomyces pombe protein ...
 1093-1143 1.01e-11

protein kinase C conserved region 1 (C1 domain) found in Schizosaccharomyces pombe protein BZZ1 and similar proteins; BZZ1 is a syndapin-like F-BAR protein that plays a role in endocytosis and trafficking to the vacuole. It functions with type I myosins to restore polarity of the actin cytoskeleton after NaCl stress. BZZ1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. Schizosaccharomyces pombe BZZ1 also harbors a C1 domain, but Saccharomyces cerevisiae BZZ1 doesn't have any. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410374  Cd Length: 53  Bit Score: 61.56  E-value: 1.01e-11
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568960994 1093 PHNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADC 1143
Cdd:cd20824     1 PHNFKPHSFSIPTKCDYCGEKIWGLSKKGLSCKDCGFNCHIKCELKVPPEC 51
C1_PKD2_rpt2 cd20843
second protein kinase C conserved region 1 (C1 domain) found in protein kinase D2 (PKD2) and ...
 1093-1160 1.63e-11

second protein kinase C conserved region 1 (C1 domain) found in protein kinase D2 (PKD2) and similar proteins; PKD2, also called PRKD2, HSPC187, or serine/threonine-protein kinase D2 (nPKC-D2), is a serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of cell proliferation via MAPK1/3 (ERK1/2) signaling, oxidative stress-induced NF-kappa-B activation, inhibition of HDAC7 transcriptional repression, signaling downstream of T-cell antigen receptor (TCR) and cytokine production, and plays a role in Golgi membrane trafficking, angiogenesis, secretory granule release and cell adhesion. PKD2 contains N-terminal tandem cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. This model corresponds to the second C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410393  Cd Length: 79  Bit Score: 61.91  E-value: 1.63e-11
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568960994 1093 PHNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADCLQRAAEKSSKHGAEDKT 1160
Cdd:cd20843    11 PHTFVIHSYTRPTVCQFCKKLLKGLFRQGLQCKDCKFNCHKRCATRVPNDCLGETLFNGDLVPMEAAS 78
C1_cPKC_rpt2 cd20836
second protein kinase C conserved region 1 (C1 domain) found in the classical (or conventional) ...
 1094-1136 2.00e-11

second protein kinase C conserved region 1 (C1 domain) found in the classical (or conventional) protein kinase C (cPKC) family; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. cPKCs are potent kinases for histones, myelin basic protein, and protamine. They depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. There are four cPKC isoforms, named alpha, betaI, betaII, and gamma. PKC-alpha is expressed in many tissues and is associated with cell proliferation, apoptosis, and cell motility. It plays a role in the signaling of the growth factors PDGF, VEGF, EGF, and FGF. Abnormal levels of PKC-alpha have been detected in many transformed cell lines and several human tumors. In addition, PKC-alpha is required for HER2 dependent breast cancer invasion. The PKC beta isoforms (I and II), generated by alternative splicing of a single gene, are preferentially activated by hyperglycemia-induced DAG (1,2-diacylglycerol) in retinal tissues. This is implicated in diabetic microangiopathy such as ischemia, neovascularization, and abnormal vasodilator function. PKC-beta also plays an important role in VEGF signaling. In addition, glucose regulates proliferation in retinal endothelial cells via PKC-betaI. PKC-beta is also being explored as a therapeutic target in cancer. It contributes to tumor formation and is involved in the tumor host mechanisms of inflammation and angiogenesis. PKC-gamma is mainly expressed in neuronal tissues. It plays a role in protection from ischemia. Members of this family contain two copies of C1 domain. This model corresponds to the second one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410386  Cd Length: 54  Bit Score: 60.81  E-value: 2.00e-11
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 568960994 1094 HNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQ 1136
Cdd:cd20836     1 HKFKVHTYSSPTFCDHCGSLLYGLIHQGMKCDTCDMNVHKRCV 43
C1_MRCK cd20809
protein kinase C conserved region 1 (C1 domain) found in the Myotonic dystrophy kinase-related ...
 1094-1137 2.08e-11

protein kinase C conserved region 1 (C1 domain) found in the Myotonic dystrophy kinase-related Cdc42-binding kinase (MRCK) family; MRCK is thought to be a coincidence detector of signaling by the small GTPase Cdc42 and phosphoinositides. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. MRCK has been shown to promote cytoskeletal reorganization, which affects many biological processes. Three isoforms of MRCK are known, named alpha, beta and gamma. MRCKgamma is expressed in heart and skeletal muscles, unlike MRCKalpha and MRCKbeta, which are expressed ubiquitously. MRCK consists of a serine/threonine kinase domain, a cysteine rich (C1) region, a PH domain and a p21 binding motif. This model corresponds to C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410359  Cd Length: 53  Bit Score: 60.75  E-value: 2.08e-11
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 568960994 1094 HNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQD 1137
Cdd:cd20809     1 HKFIVRTFSTPTKCNHCTSLMVGLVRQGLVCEVCGYACHVSCAD 44
C1_PKD3_rpt2 cd20844
second protein kinase C conserved region 1 (C1 domain) found in protein kinase D3 (PKD3) and ...
 1093-1144 2.63e-11

second protein kinase C conserved region 1 (C1 domain) found in protein kinase D3 (PKD3) and similar proteins; PKD3 is also called PRKD3, PRKCN, serine/threonine-protein kinase D3 (nPKC-D3), protein kinase C nu type (nPKC-nu), or protein kinase EPK2. It converts transient diacylglycerol (DAG) signals into prolonged physiological effects, downstream of PKC. It is involved in the regulation of the cell cycle by modulating microtubule nucleation and dynamics. PKD3 acts as a key mediator in several cancer development signaling pathways. PKD3 contains N-terminal tandem cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. This model corresponds to the second C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410394  Cd Length: 69  Bit Score: 61.18  E-value: 2.63e-11
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568960994 1093 PHNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADCL 1144
Cdd:cd20844     5 PHTFAVHSYTRPTICQYCKRLLKGLFRQGMQCKDCRFNCHKRCASKVPRDCL 56
C2B_Synaptotagmin-7 cd08405
C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 1218-1322 4.02e-11

C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176050 [Multi-domain]  Cd Length: 136  Bit Score: 62.82  E-value: 4.02e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1218 ITITVVSAQGLQAKDKTGSSDPYVTVQV---GK--NKRRTKTIFGNLNPVWDEKFFFEChnSTDRIK-----VRVWDEDd 1287
Cdd:cd08405    17 ITVNIIKARNLKAMDINGTSDPYVKVWLmykDKrvEKKKTVIKKRTLNPVFNESFIFNI--PLERLRettliITVMDKD- 93

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 568960994 1288 diksrvkqhfKKESDDFLGQTIVEVRTLSGEMDVW 1322
Cdd:cd08405    94 ----------RLSRNDLIGKIYLGWKSGGLELKHW 118
C1_DGKtheta_typeV_rpt1 cd20803
first protein kinase C conserved region 1 (C1 domain) found in type V diacylglycerol kinase, ...
 1093-1143 4.26e-11

first protein kinase C conserved region 1 (C1 domain) found in type V diacylglycerol kinase, DAG kinase theta, and similar proteins; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. DAG kinase theta, also called diglyceride kinase theta (DGK-theta), is the only isoform classified as type V; it contains a pleckstrin homology (PH)-like domain and an additional C1 domain, compared to other DGKs. It may regulate the activity of protein kinase C by controlling the balance between the two signaling lipids, diacylglycerol and phosphatidic acid. DAG kinase theta contains three copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410353  Cd Length: 56  Bit Score: 60.01  E-value: 4.26e-11
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568960994 1093 PHNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADC 1143
Cdd:cd20803     1 GHSFRKKTFHKPTYCHHCTDLLWGLLNQGYQCEVCNFVSHERCLKTVVTPC 51
C1_RASSF1 cd20885
protein kinase C conserved region 1 (C1 domain) found in Ras association domain-containing ...
 1094-1143 4.32e-11

protein kinase C conserved region 1 (C1 domain) found in Ras association domain-containing protein 1 (RASSF1) and similar proteins; RASSF1 is a member of a family of RAS effectors, of which there are currently 8 members (RASSF1-8), all containing a Ras-association (RA) domain of the Ral-GDS/AF6 type. RASSF1 has eight transcripts (A-H) arising from alternative splicing and differential promoter usage. RASSF1A and 1C are the most extensively studied RASSF1 with both localized to microtubules and involved in regulation of growth and migration. RASSF1 is a potential tumor suppressor that is required for death receptor-dependent apoptosis. It contains a C1 domain, which is descibed in this model. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410435  Cd Length: 54  Bit Score: 59.98  E-value: 4.32e-11
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568960994 1094 HNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADC 1143
Cdd:cd20885     4 HDFQPCSLTNPTWCDLCGDFIWGLYKQCLRCTHCKYTCHLRCRDLVTLDC 53
C2_fungal_Inn1p-like cd08681
C2 domain found in fungal Ingression 1 (Inn1) proteins; Saccharomyces cerevisiae Inn1 ...
 1222-1341 4.91e-11

C2 domain found in fungal Ingression 1 (Inn1) proteins; Saccharomyces cerevisiae Inn1 associates with the contractile actomyosin ring at the end of mitosis and is needed for cytokinesis. The C2 domain of Inn1, located at the N-terminus, is required for ingression of the plasma membrane. The C-terminus is relatively unstructured and contains eight PXXP motifs that are thought to mediate interaction of Inn1 with other proteins with SH3 domains in the cytokinesis proteins Hof1 (an F-BAR protein) and Cyk3 (whose overexpression can restore primary septum formation in Inn1Delta cells) as well as recruiting Inn1 to the bud-neck by binding to Cyk3. Inn1 and Cyk3 appear to cooperate in activating chitin synthase Chs2 for primary septum formation, which allows coordination of actomyosin ring contraction with ingression of the cleavage furrow. It is thought that the C2 domain of Inn1 helps to preserve the link between the actomyosin ring and the plasma membrane, contributing both to membrane ingression, as well as to stability of the contracting ring. Additionally, Inn1 might induce curvature of the plasma membrane adjacent to the contracting ring, thereby promoting ingression of the membrane. It has been shown that the C2 domain of human synaptotagmin induces curvature in target membranes and thereby contributes to fusion of these membranes with synaptic vesicles. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176063 [Multi-domain]  Cd Length: 118  Bit Score: 61.88  E-value: 4.91e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1222 VVSAQGLQAKDKTGSSDPYVTVQVGKNKRRTKTIF-GNLNPVWDEKFFFECHNSTDRI-KVRVWDEDddiksrvkqhfkK 1299
Cdd:cd08681     7 VLKARNLPNKRKLDKQDPYCVLRIGGVTKKTKTDFrGGQHPEWDEELRFEITEDKKPIlKVAVFDDD------------K 74

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 568960994 1300 ESDDFLGQTIVEVRT--LSGEMDVWYNLekrTDKSAVSGAIRLK 1341
Cdd:cd08681    75 RKPDLIGDTEVDLSPalKEGEFDDWYEL---TLKGRYAGEVYLE 115
C2C_Tricalbin-like cd04045
C2 domain third repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 1224-1348 5.45e-11

C2 domain third repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 176010 [Multi-domain]  Cd Length: 120  Bit Score: 61.84  E-value: 5.45e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1224 SAQGLQAKDKTGSSDPYVTVQV-GKNKRRTKTIFGNLNPVWDEKFFFECHNSTDRIKVRVWDEDDDIKSRvkqhfkkesd 1302
Cdd:cd04045     9 KANDLKNLEGVGKIDPYVRVLVnGIVKGRTVTISNTLNPVWDEVLYVPVTSPNQKITLEVMDYEKVGKDR---------- 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 568960994 1303 dFLGQTIVEVRTLSGEMDVWYNLEKRTDKSAVSgaiRLKINVEIKG 1348
Cdd:cd04045    79 -SLGSVEINVSDLIKKNEDGKYVEYDDEEERLK---RLLSLKGVKG 120
C1_PKD_rpt1 cd20795
first protein kinase C conserved region 1 (C1 domain) found in the protein kinase D (PKD) ...
 1093-1135 7.40e-11

first protein kinase C conserved region 1 (C1 domain) found in the protein kinase D (PKD) family; PKDs are important regulators of many intracellular signaling pathways such as ERK and JNK, and cellular processes including the organization of the trans-Golgi network, membrane trafficking, cell proliferation, migration, and apoptosis. They are activated in a PKC-dependent manner by many agents including diacylglycerol (DAG), PDGF, neuropeptides, oxidative stress, and tumor-promoting phorbol esters, among others. Mammals harbor three types of PKDs: PKD1 (or PKCmu), PKD2, and PKD3 (or PKCnu). PKDs contain N-terminal tandem cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. This model corresponds to the first C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410345  Cd Length: 56  Bit Score: 59.24  E-value: 7.40e-11
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 568960994 1093 PHNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKC 1135
Cdd:cd20795     3 PHSLFVHSYKSPTFCDFCGEMLFGLVRQGLKCEGCGLNFHKRC 45
C2B_RasA3 cd04010
C2 domain second repeat present in RAS p21 protein activator 3 (RasA3); RasA3 are members of ...
 1217-1343 8.04e-11

C2 domain second repeat present in RAS p21 protein activator 3 (RasA3); RasA3 are members of GTPase activating protein 1 (GAP1), a Ras-specific GAP, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. RasA3 contains an N-terminal C2 domain, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175977 [Multi-domain]  Cd Length: 148  Bit Score: 62.03  E-value: 8.04e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1217 KITITVVSAQGLQAKDktGSSDPYVTVQV-GKNKR----RTKTIFGNLNPVWDEKFFFECHNSTDRIKVRVWDEDDDIKS 1291
Cdd:cd04010     1 KLSVRVIECSDLALKN--GTCDPYASVTLiYSNKKqdtkRTKVKKKTNNPQFDEAFYFDVTIDSSPEKKQFEMPEEDAEK 78

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1292 RVKQH-FKKES----DDFLGQTIVEVRTLSGEMDV---WYNLEKRTDKSAVS----------GAIRLKIN 1343
Cdd:cd04010    79 LELRVdLWHASmgggDVFLGEVRIPLRGLDLQAGShqaWYFLQPREEKSTPPgtrsskdnslGSLRLKIN 148
C2_Rab11-FIP_classI cd08682
C2 domain found in Rab11-family interacting proteins (FIP) class I; Rab GTPases recruit ...
 1220-1347 9.29e-11

C2 domain found in Rab11-family interacting proteins (FIP) class I; Rab GTPases recruit various effector proteins to organelles and vesicles. Rab11-family interacting proteins (FIPs) are involved in mediating the role of Rab11. FIPs can be divided into three classes: class I FIPs (Rip11a, Rip11b, RCP, and FIP2) which contain a C2 domain after N-terminus of the protein, class II FIPs (FIP3 and FIP4) which contain two EF-hands and a proline rich region, and class III FIPs (FIP1) which exhibits no homology to known protein domains. All FIP proteins contain a highly conserved, 20-amino acid motif at the C-terminus of the protein, known as Rab11/25 binding domain (RBD). Class I FIPs are thought to bind to endocytic membranes via their C2 domain, which interacts directly with phospholipids. Class II FIPs do not have any membrane binding domains leaving much to speculate about the mechanism involving FIP3 and FIP4 interactions with endocytic membranes. The members in this CD are class I FIPs. The exact function of the Rab11 and FIP interaction is unknown, but there is speculation that it involves the role of forming a targeting complex that recruits a group of proteins involved in membrane transport to organelles. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176064 [Multi-domain]  Cd Length: 126  Bit Score: 61.31  E-value: 9.29e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1220 ITVVSAQGLQAKDKTGSSDPYVTVQVGKNKRRTKTIFGNLNPVWDEkfffEChnSTDRIKVRVWDEDDDIKSRVKQHFKK 1299
Cdd:cd08682     3 VTVLQARGLLCKGKSGTNDAYVIIQLGKEKYSTSVKEKTTSPVWKE----EC--SFELPGLLSGNGNRATLQLTVMHRNL 76

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568960994 1300 -ESDDFLGQTIVEVRTLSGEMDV----WYNLEKRTDKSAVSgaiRLKINVEIK 1347
Cdd:cd08682    77 lGLDKFLGQVSIPLNDLDEDKGRrrtrWFKLESKPGKDDKE---RGEIEVDIQ 126
C2A_Synaptotagmin-7 cd08386
C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 1218-1282 2.08e-10

C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176032 [Multi-domain]  Cd Length: 125  Bit Score: 60.42  E-value: 2.08e-10
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568960994 1218 ITITVVSAQGLQAKDKTGSSDPYVTV---QVGKNKRRTKTIFGNLNPVWDEKFFFECHnSTDRIKVRV 1282
Cdd:cd08386    18 LTLKILKAVELPAKDFSGTSDPFVKIyllPDKKHKLETKVKRKNLNPHWNETFLFEGF-PYEKLQQRV 84
C2A_Rabphilin_Doc2 cd04035
C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 1221-1318 3.10e-10

C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176000 [Multi-domain]  Cd Length: 123  Bit Score: 59.60  E-value: 3.10e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1221 TVVSAQGLQAKDKTGSSDPYVTVQV-----GKNKRRTKTIFGNLNPVWDEKFFFecHNSTDR------IKVRVWDEDddi 1289
Cdd:cd04035    20 TIIRAKGLKAMDANGLSDPYVKLNLlpgasKATKLRTKTVHKTRNPEFNETLTY--YGITEEdiqrktLRLLVLDED--- 94

                          90       100
                  ....*....|....*....|....*....
gi 568960994 1290 ksrvkqhfkKESDDFLGQTIVEVRTLSGE 1318
Cdd:cd04035    95 ---------RFGNDFLGETRIPLKKLKPN 114
C2C_KIAA1228 cd04030
C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins ...
 1217-1326 3.45e-10

C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins are uncharacterized human proteins. They were compiled by the Kazusa mammalian cDNA project which identified more than 2000 human genes. They are identified by 4 digit codes that precede the KIAA designation. Many KIAA genes are still functionally uncharacterized including KIAA1228. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175996 [Multi-domain]  Cd Length: 127  Bit Score: 59.59  E-value: 3.45e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1217 KITITVVSAQGLQAKDKTGSSDPYVTVQV--GKNK---RRTKTIFGNLNPVWDEKFFFEChnSTDRIKVRVWDEddDIKS 1291
Cdd:cd04030    17 KLIVTVHKCRNLPPCDSSDIPDPYVRLYLlpDKSKstrRKTSVKKDNLNPVFDETFEFPV--SLEELKRRTLDV--AVKN 92

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 568960994 1292 RVKqhFKKESDDFLGQTIVEV--RTLSGEMDVWYNLE 1326
Cdd:cd04030    93 SKS--FLSREKKLLGQVLIDLsdLDLSKGFTQWYDLT 127
C2_putative_Elicitor-responsive_gene cd04049
C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive ...
 1223-1312 4.61e-10

C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive proteins are triggered in response to specific elicitor molecules such as glycolproteins, peptides, carbohydrates and lipids. A host of defensive responses are also triggered resulting in localized cell death. Antimicrobial secondary metabolites, such as phytoalexins, or defense-related proteins, including pathogenesis-related (PR) proteins are also produced. There is a single C2 domain present here. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members have a type-II topology.


Pssm-ID: 176014 [Multi-domain]  Cd Length: 124  Bit Score: 59.27  E-value: 4.61e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1223 VSAQGLQAKDKTGSSDPYVTVQVGKNKRRTKTIFG-NLNPVWDEKFFFECHNSTdrikvrvWDEDDDIKSRVKQHFKKES 1301
Cdd:cd04049     8 ISAKGLQDTDFLGKIDPYVIIQCRTQERKSKVAKGdGRNPEWNEKFKFTVEYPG-------WGGDTKLILRIMDKDNFSD 80

                          90
                  ....*....|.
gi 568960994 1302 DDFLGQTIVEV 1312
Cdd:cd04049    81 DDFIGEATIHL 91
C1_alphaCHN cd20856
protein kinase C conserved region 1 (C1 domain) found in alpha-chimaerin and similar proteins; ...
 1094-1143 6.00e-10

protein kinase C conserved region 1 (C1 domain) found in alpha-chimaerin and similar proteins; Alpha-chimaerin, also called A-chimaerin, N-chimaerin (CHN), alpha-chimerin, N-chimerin (NC), or Rho GTPase-activating protein 2 (ARHGAP2), is a GTPase-activating protein (GAP) for p21-rac and a phorbol ester receptor. It is involved in the assembly of neuronal locomotor circuits as a direct effector of EPHA4 in axon guidance. Alpha-chimaerin contains a functional SH2 domain that can bind to phosphotyrosine motifs within receptors, a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410406  Cd Length: 57  Bit Score: 56.62  E-value: 6.00e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568960994 1094 HNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADC 1143
Cdd:cd20856     6 HNFKVHTFRGPHWCEYCANFMWGLIAQGVKCADCGLNVHKQCSKMVPNDC 55
C2B_RasGAP cd08675
C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
 1218-1336 9.37e-10

C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. The proteins here all contain two tandem C2 domains, a Ras-GAP domain, and a pleckstrin homology (PH)-like domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.


Pssm-ID: 176057 [Multi-domain]  Cd Length: 137  Bit Score: 58.92  E-value: 9.37e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1218 ITITVVSAQGLQAKdKTGSSDPYVTVQV---GKNK-RRTKTIFGNLNPVWDEKFFFECHNSTDRIKVRVWDEDDDIKSRV 1293
Cdd:cd08675     1 LSVRVLECRDLALK-SNGTCDPFARVTLnysSKTDtKRTKVKKKTNNPRFDEAFYFELTIGFSYEKKSFKVEEEDLEKSE 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 568960994 1294 KQH-FKKES----DDFLGQTIVEVRTL--SGEMDVWYNLEKRTDKSAVSG 1336
Cdd:cd08675    80 LRVeLWHASmvsgDDFLGEVRIPLQGLqqAGSHQAWYFLQPREAPGTRSS 129
C1_nPKC_epsilon-like_rpt2 cd20838
second protein kinase C conserved region 1 (C1 domain) found in novel protein kinase C (nPKC) ...
 1093-1136 1.03e-09

second protein kinase C conserved region 1 (C1 domain) found in novel protein kinase C (nPKC) epsilon, eta, and similar proteins; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. PKC-epsilon has been shown to behave as an oncoprotein. Its overexpression contributes to neoplastic transformation depending on the cell type. It contributes to oncogenesis by inducing disordered cell growth and inhibiting cell death. It also plays a role in tumor invasion and metastasis. PKC-epsilon has also been found to confer cardioprotection against ischemia and reperfusion-mediated damage. Other cellular functions include the regulation of gene expression, cell adhesion, and cell motility. PKC-eta is predominantly expressed in squamous epithelia, where it plays a crucial role in the signaling of cell-type specific differentiation. It is also expressed in pro-B cells and early-stage thymocytes, and acts as a key regulator in early B-cell development. PKC-eta increases glioblastoma multiforme (GBM) proliferation and resistance to radiation, and is being developed as a therapeutic target for the management of GBM. Members of this family contain two copies of C1 domain. This model corresponds to the second one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410388  Cd Length: 55  Bit Score: 56.13  E-value: 1.03e-09
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 568960994 1093 PHNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQ 1136
Cdd:cd20838     2 PHRFSVHNYKRPTFCDHCGSLLYGLYKQGLQCKVCKMNVHKRCQ 45
C2B_RasA1_RasA4 cd04025
C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase ...
 1221-1342 1.05e-09

C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase activating protein 1s ), Ras-specific GAP members, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. Both proteins contain two C2 domains, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175991 [Multi-domain]  Cd Length: 123  Bit Score: 58.27  E-value: 1.05e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1221 TVVSAQGLQAKDKTGSSDPYVTVQVGKNKRRTKTIFGNLNPVWDEKFFFECHNSTDR-IKVRVWDEddDIKSRvkqhfkk 1299
Cdd:cd04025     5 HVLEARDLAPKDRNGTSDPFVRVFYNGQTLETSVVKKSCYPRWNEVFEFELMEGADSpLSVEVWDW--DLVSK------- 75

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 568960994 1300 esDDFLGQTIVEVRTL--SGEMDVWYNLE----KRTDKSAVSGAIRLKI 1342
Cdd:cd04025    76 --NDFLGKVVFSIQTLqqAKQEEGWFRLLpdprAEEESGGNLGSLRLKV 122
C1_PKD1_rpt2 cd20842
second protein kinase C conserved region 1 (C1 domain) found in protein kinase D (PKD) and ...
 1093-1148 1.24e-09

second protein kinase C conserved region 1 (C1 domain) found in protein kinase D (PKD) and similar proteins; PKD is also called PKD1, PRKD1, protein kinase C mu type (nPKC-mu), PRKCM, serine/threonine-protein kinase D1, or nPKC-D1. It is a serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of MAPK8/JNK1 and Ras signaling, Golgi membrane integrity and trafficking, cell survival through NF-kappa-B activation, cell migration, cell differentiation by mediating HDAC7 nuclear export, cell proliferation via MAPK1/3 (ERK1/2) signaling, and plays a role in cardiac hypertrophy, VEGFA-induced angiogenesis, genotoxic-induced apoptosis and flagellin-stimulated inflammatory response. PKD contains N-terminal tandem cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. This model corresponds to the second C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410392  Cd Length: 94  Bit Score: 57.33  E-value: 1.24e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568960994 1093 PHNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADCLQRAA 1148
Cdd:cd20842    34 PHTFVIHSYTRPTVCQYCKKLLKGLFRQGLQCKDCKFNCHKRCAPKVPNNCLGEVA 89
C1_betaCHN cd20857
protein kinase C conserved region 1 (C1 domain) found in beta-chimaerin and similar proteins; ...
 1094-1143 1.27e-09

protein kinase C conserved region 1 (C1 domain) found in beta-chimaerin and similar proteins; Beta-chimaerin, also called beta-chimerin (BCH) or Rho GTPase-activating protein 3 (ARHGAP3), is a GTPase-activating protein (GAP) for p21-rac. Insufficient expression of beta-2 chimaerin is expected to lead to higher Rac activity and could therefore play a role in the progression from low-grade to high-grade tumors. Beta-chimaerin contains a functional SH2 domain that can bind to phosphotyrosine motifs within receptors, a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410407  Cd Length: 61  Bit Score: 55.82  E-value: 1.27e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568960994 1094 HNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADC 1143
Cdd:cd20857     6 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDC 55
C1_VAV cd20810
protein kinase C conserved region 1 (C1 domain) found in VAV proteins; VAV proteins function ...
 1092-1135 2.21e-09

protein kinase C conserved region 1 (C1 domain) found in VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and as scaffold proteins, and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410360  Cd Length: 52  Bit Score: 54.96  E-value: 2.21e-09
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 568960994 1092 TPHNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKC 1135
Cdd:cd20810     1 TGHSFELTTFKEPTTCSVCKKLLKGLFFQGYKCSVCGAAVHKEC 44
C2E_Ferlin cd04037
C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 1222-1310 2.40e-09

C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fifth C2 repeat, C2E, and has a type-II topology.


Pssm-ID: 176002 [Multi-domain]  Cd Length: 124  Bit Score: 57.17  E-value: 2.40e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1222 VVSAQGLQAKDKTGSSDPYVTVQVGKNK--RRTKTIFGNLNPVWDEKFFFEC---HNSTdrIKVRVWDEDddiksrvkqh 1296
Cdd:cd04037     6 VVRARNLQPKDPNGKSDPYLKIKLGKKKinDRDNYIPNTLNPVFGKMFELEAtlpGNSI--LKISVMDYD---------- 73

                          90
                  ....*....|....
gi 568960994 1297 fKKESDDFLGQTIV 1310
Cdd:cd04037    74 -LLGSDDLIGETVI 86
C2A_Synaptotagmin-1-5-6-9-10 cd08385
C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a ...
 1215-1327 3.17e-09

C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis as do synaptotagmins 5, 6, and 10. It is distinguished from the other synaptotagmins by having an N-glycosylated N-terminus. Synaptotagmins 5, 6, and 10, members of class 3 synaptotagmins, are located primarily in the brain and localized to the active zone and plasma membrane. They is distinguished from the other synaptotagmins by having disulfide bonds at its N-terminus. Synaptotagmin 6 also regulates the acrosome reaction, a unique Ca2+-regulated exocytosis, in sperm. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176031 [Multi-domain]  Cd Length: 124  Bit Score: 56.89  E-value: 3.17e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1215 SAKITITVVSAQGLQAKDKTGSSDPYVTVQVGKNKRR---TKTIFGNLNPVWDEKFFF-----ECHNSTdrIKVRVWDED 1286
Cdd:cd08385    15 SNQLTVGIIQAADLPAMDMGGTSDPYVKVYLLPDKKKkfeTKVHRKTLNPVFNETFTFkvpysELGNKT--LVFSVYDFD 92

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 568960994 1287 ddiksRVKQHfkkesdDFLGQTIVEVRT--LSGEMDVWYNLEK 1327
Cdd:cd08385    93 -----RFSKH------DLIGEVRVPLLTvdLGHVTEEWRDLES 124
C1_MRCKalpha cd20864
protein kinase C conserved region 1 (C1 domain) found in myotonic dystrophy kinase-related ...
 1094-1143 3.28e-09

protein kinase C conserved region 1 (C1 domain) found in myotonic dystrophy kinase-related Cdc42-binding kinase alpha (MRCK alpha) and similar proteins; MRCK alpha, also called Cdc42-binding protein kinase alpha, DMPK-like alpha, or myotonic dystrophy protein kinase-like alpha, is a serine/threonine-protein kinase expressed ubiquitously in many tissues. It plays a role in the regulation of peripheral actin reorganization and neurite outgrowth. It may also play a role in the transferrin iron uptake pathway. MRCK alpha is an important downstream effector of Cdc42 and plays a role in the regulation of cytoskeleton reorganization and cell migration. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410414  Cd Length: 60  Bit Score: 54.64  E-value: 3.28e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568960994 1094 HNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADC 1143
Cdd:cd20864     3 HQFVVKSFTTPTKCNQCTSLMVGLIRQGCTCEVCGFSCHVTCADKAPSVC 52
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
1215-1343 4.86e-09

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 62.08  E-value: 4.86e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1215 SAKITITVVSAQGLQAKDKTGSSDPYVTVQV-GKNKRRTKTIFGNLNPVWDEKFFFECHN-STDRIKVRVWDEDDDiksr 1292
Cdd:COG5038  1039 SGYLTIMLRSGENLPSSDENGYSDPFVKLFLnEKSVYKTKVVKKTLNPVWNEEFTIEVLNrVKDVLTINVNDWDSG---- 1114

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568960994 1293 vkqhfkkESDDFLGQTIVEVRTLSGEMDVWYNLeKRTDKSA--VSGAIRLKIN 1343
Cdd:COG5038  1115 -------EKNDLLGTAEIDLSKLEPGGTTNSNI-PLDGKTFivLDGTLHPGFN 1159
C2A_Tricalbin-like cd04044
C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 1220-1315 6.29e-09

C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 176009 [Multi-domain]  Cd Length: 124  Bit Score: 56.02  E-value: 6.29e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1220 ITVVSAQGLQAKDK-TGSSDPYVTVQVGKNKR--RTKTIFGNLNPVWDEKFFFECHNSTDRIKVRVWDEDDdiksrvkqh 1296
Cdd:cd04044     6 VTIKSARGLKGSDIiGGTVDPYVTFSISNRRElaRTKVKKDTSNPVWNETKYILVNSLTEPLNLTVYDFND--------- 76

                          90
                  ....*....|....*....
gi 568960994 1297 fkKESDDFLGQTIVEVRTL 1315
Cdd:cd04044    77 --KRKDKLIGTAEFDLSSL 93
C1_PIK3R-like_rpt2 cd20830
second protein kinase C conserved region 1 (C1 domain) found in uncharacterized ...
 1094-1135 6.60e-09

second protein kinase C conserved region 1 (C1 domain) found in uncharacterized phosphatidylinositol 3-kinase regulatory subunit-like proteins; The family includes a group of uncharacterized proteins that show high sequence similarity to vertebrate phosphatidylinositol 3-kinase regulatory subunits (PIK3Rs), which bind to activated (phosphorylated) protein-tyrosine kinases through its SH2 domain and regulate their kinase activity. Unlike typical PIK3Rs, members of this family have two C1 domains. This model corresponds to the second one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410380  Cd Length: 52  Bit Score: 53.79  E-value: 6.60e-09
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 568960994 1094 HNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKC 1135
Cdd:cd20830     1 HRFVEQSFSTLQWCDKCGKFLFGLVHQGLQCQDCGLVCHRTC 42
C2A_Synaptotagmin-8 cd08387
C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking ...
 1218-1322 7.88e-09

C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176033 [Multi-domain]  Cd Length: 124  Bit Score: 55.87  E-value: 7.88e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1218 ITITVVSAQGLQAKDKTGSSDPYVTVQV---GKNKRRTKTIFGNLNPVWDEKFFFECH-NSTDRIKVRVWDEDDDIKSRv 1293
Cdd:cd08387    18 LNVKLIQARNLQPRDFSGTADPYCKVRLlpdRSNTKQSKIHKKTLNPEFDESFVFEVPpQELPKRTLEVLLYDFDQFSR- 96

                          90       100       110
                  ....*....|....*....|....*....|...
gi 568960994 1294 kqhfkkesDDFLGqtIVEVR----TLSGEMDVW 1322
Cdd:cd08387    97 --------DECIG--VVELPlaevDLSEKLDLW 119
C2B_Ferlin cd04011
C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 1218-1284 8.99e-09

C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 175978 [Multi-domain]  Cd Length: 111  Bit Score: 55.27  E-value: 8.99e-09
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568960994 1218 ITITVVSAQGLQakdkTGSSDPYVTVQVGKNKRRTKTIFGNLNPVWDEKFFFECHNSTDR-----IKVRVWD 1284
Cdd:cd04011     6 VRVRVIEARQLV----GGNIDPVVKVEVGGQKKYTSVKKGTNCPFYNEYFFFNFHESPDElfdkiIKISVYD 73
C2A_Copine cd04048
C2 domain first repeat in Copine; There are 2 copies of the C2 domain present in copine, a ...
 1223-1333 9.34e-09

C2 domain first repeat in Copine; There are 2 copies of the C2 domain present in copine, a protein involved in membrane trafficking, protein-protein interactions, and perhaps even cell division and growth. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176013 [Multi-domain]  Cd Length: 120  Bit Score: 55.27  E-value: 9.34e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1223 VSAQGLQAKDKTGSSDPYVTVQVGKNKR-------RTKTIFGNLNPVWDEKF----FFEChnsTDRIKVRVWDEDDDIKs 1291
Cdd:cd04048     7 ISCRNLLDKDVLSKSDPFVVVYVKTGGSgqwveigRTEVIKNNLNPDFVTTFtvdyYFEE---VQKLRFEVYDVDSKSK- 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 568960994 1292 rvkqhfKKESDDFLGQTIVEVRTLSGEMDVWYNLEKRTDKSA 1333
Cdd:cd04048    83 ------DLSDHDFLGEAECTLGEIVSSPGQKLTLPLKGGKGK 118
C2A_Rasal1_RasA4 cd04054
C2 domain first repeat present in RasA1 and RasA4; Rasal1 and RasA4 are both members of GAP1 ...
 1220-1344 1.16e-08

C2 domain first repeat present in RasA1 and RasA4; Rasal1 and RasA4 are both members of GAP1 (GTPase activating protein 1). Rasal1 responds to repetitive Ca2+ signals by associating with the plasma membrane and deactivating Ras. RasA4 suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. Both of these proteins contains two C2 domains, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176018 [Multi-domain]  Cd Length: 121  Bit Score: 55.21  E-value: 1.16e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1220 ITVVSAQGLQAKDKTGSSDPYVTVQVGKNK-RRTKTIFGNLNPVWDEKFFFECHNSTDRIKVRVWDEDddiksrvkqhfK 1298
Cdd:cd04054     4 IRIVEGKNLPAKDITGSSDPYCIVKVDNEViIRTATVWKTLNPFWGEEYTVHLPPGFHTVSFYVLDED-----------T 72

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 568960994 1299 KESDDFLGQTIVEVRTLSGE---MDVWYNLEKRTDKSAVSGAIRLKINV 1344
Cdd:cd04054    73 LSRDDVIGKVSLTREVISAHprgIDGWMNLTEVDPDEEVQGEIHLELSV 121
C2_Smurf-like cd08382
C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 ...
 1217-1306 1.25e-08

C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 domain is found in Smurf proteins, C2-WW-HECT-domain E3s, which play an important role in the downregulation of the TGF-beta signaling pathway. Smurf proteins also regulate cell shape, motility, and polarity by degrading small guanosine triphosphatases (GTPases). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have type-II topology.


Pssm-ID: 176028 [Multi-domain]  Cd Length: 123  Bit Score: 55.01  E-value: 1.25e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1217 KITITVVSAQGLQAKDKTGSSDPYVTVQV-GKNKRRTKTIFGNLNPVWDEKFFFECHNStDRIKVRVWDEdddiksrvKQ 1295
Cdd:cd08382     1 KVRLTVLCADGLAKRDLFRLPDPFAVITVdGGQTHSTDVAKKTLDPKWNEHFDLTVGPS-SIITIQVFDQ--------KK 71

                          90
                  ....*....|.
gi 568960994 1296 hFKKESDDFLG 1306
Cdd:cd08382    72 -FKKKDQGFLG 81
C2A_RasGAP cd08383
C2 domain (first repeat) of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
 1220-1342 1.36e-08

C2 domain (first repeat) of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. The proteins here all contain either a single C2 domain or two tandem C2 domains, a Ras-GAP domain, and a pleckstrin homology (PH)-like domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.


Pssm-ID: 176029 [Multi-domain]  Cd Length: 117  Bit Score: 54.96  E-value: 1.36e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1220 ITVVSAQGLQAKdktGSSDPYVTVQVGKNK-RRTKTIFGnLNPVWDEKFFFE---CHNSTDRIKVRVWDED--DDIKSRV 1293
Cdd:cd08383     4 LRILEAKNLPSK---GTRDPYCTVSLDQVEvARTKTVEK-LNPFWGEEFVFDdppPDVTFFTLSFYNKDKRskDRDIVIG 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 568960994 1294 KQHFKKESddfLGQTIvevrtlsgemDVWYNLEKRTDKSAVSGAIRLKI 1342
Cdd:cd08383    80 KVALSKLD---LGQGK----------DEWFPLTPVDPDSEVQGSVRLRA 115
C1_Stac cd20817
protein kinase C conserved region 1 (C1 domain) found in the SH3 and cysteine-rich ...
 1094-1143 1.40e-08

protein kinase C conserved region 1 (C1 domain) found in the SH3 and cysteine-rich domain-containing protein (Stac) family; Stac proteins are putative adaptor proteins that are important for neuronal function. There are three mammalian members (Stac1, Stac2 and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. Stac proteins contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410367  Cd Length: 51  Bit Score: 52.72  E-value: 1.40e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568960994 1094 HNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLnADC 1143
Cdd:cd20817     1 HSFQEHTFKKPTFCDVCKELLVGLSKQGLRCKNCKMNVHHKCQEGV-PDC 49
C1_CeDKF1-like_rpt1 cd20797
first protein kinase C conserved region 1 (C1 domain) found in Caenorhabditis elegans serine ...
 1091-1135 1.67e-08

first protein kinase C conserved region 1 (C1 domain) found in Caenorhabditis elegans serine/threonine-protein kinase DKF-1 and similar proteins; DKF-1 converts transient diacylglycerol (DAG) signals into prolonged physiological effects, independently of PKC. It plays a role in the regulation of growth and neuromuscular control of movement. It is involved in immune response to Staphylococcus aureus bacterium by activating transcription factor hlh-30 downstream of phospholipase plc-1. Members of this group contain two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410347  Cd Length: 56  Bit Score: 52.47  E-value: 1.67e-08
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 568960994 1091 TTPHNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKC 1135
Cdd:cd20797     1 TRPHVVEVEQYMTPTFCDYCGEMLTGLMKQGVKCKNCRCNFHKRC 45
C2D_Ferlin cd04017
C2 domain fourth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 1225-1333 1.67e-08

C2 domain fourth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fourth C2 repeat, C2D, and has a type-II topology.


Pssm-ID: 175984 [Multi-domain]  Cd Length: 135  Bit Score: 55.24  E-value: 1.67e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1225 AQGLQAKDKTGSSDPYVTVQVGKNKRRTKTIFGNLNPVWDEKFFF---ECHNSTDRIK-------VRVWDEDDDIKsrvk 1294
Cdd:cd04017    10 ARDLLAADKSGLSDPFARVSFLNQSQETEVIKETLSPTWDQTLIFdevELYGSPEEIAqnpplvvVELFDQDSVGK---- 85

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 568960994 1295 qhfkkesDDFLGQTIV--EVRtLSGEMDV-----WYNLEKRTDKSA 1333
Cdd:cd04017    86 -------DEFLGRSVAkpLVK-LDLEEDFppklqWFPIYKGGQSAG 123
C1_RASSF1-like cd20820
protein kinase C conserved region 1 (C1 domain) found in the Ras association domain-containing ...
 1094-1143 1.71e-08

protein kinase C conserved region 1 (C1 domain) found in the Ras association domain-containing protein 1 (RASSF1)-like family; The RASSF1-like family includes RASSF1 and RASSF5. RASSF1 and RASSF5 are members of a family of RAS effectors, of which there are currently 8 members (RASSF1-8), all containing a Ras-association (RA) domain of the Ral-GDS/AF6 type. RASSF1 has eight transcripts (A-H) arising from alternative splicing and differential promoter usage. RASSF1A and 1C are the most extensively studied RASSF1; both are localized to microtubules and involved in the regulation of growth and migration. RASSF1 is a potential tumor suppressor that is required for death receptor-dependent apoptosis. RASSF5, also called new ras effector 1 (NORE1), or regulator for cell adhesion and polarization enriched in lymphoid tissues (RAPL), is expressed as three transcripts (A-C) via differential promoter usage and alternative splicing. RASSF5A is a pro-apoptotic Ras effector and functions as a Ras regulated tumor suppressor. RASSF5C is regulated by Ras related protein and modulates cellular adhesion. RASSF5 is a potential tumor suppressor that seems to be involved in lymphocyte adhesion by linking RAP1A activation upon T-cell receptor or chemokine stimulation to integrin activation. RASSF1 and RASSF5 contain a C1 domain, which is descibed in this model. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410370  Cd Length: 52  Bit Score: 52.44  E-value: 1.71e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568960994 1094 HNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADC 1143
Cdd:cd20820     2 HRFVPLELEQPTWCDLCGSVILGLFRKCLRCANCKMTCHPRCRSLVCLTC 51
C2B_Synaptotagmin-like cd04050
C2 domain second repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
 1224-1327 1.81e-08

C2 domain second repeat present in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176015 [Multi-domain]  Cd Length: 105  Bit Score: 54.11  E-value: 1.81e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1224 SAQGLQAKDKTGSSDPYVTVQVGKNKRRTKTIFGNLNPVWDEKFFFECHN-STDRIKVRVWDEDDDiKSrvkqhfkkesd 1302
Cdd:cd04050     8 SAKNLPLAKSTKEPSPYVELTVGKTTQKSKVKERTNNPVWEEGFTFLVRNpENQELEIEVKDDKTG-KS----------- 75

                          90       100
                  ....*....|....*....|....*....
gi 568960994 1303 dfLGQTIVEVRTLSGE----MDVWYNLEK 1327
Cdd:cd04050    76 --LGSLTLPLSELLKEpdltLDQPFPLDN 102
C1_nPKC_theta-like_rpt1 cd20834
first protein kinase C conserved region 1 (C1 domain) found in novel protein kinase C (nPKC) ...
 1103-1143 3.42e-08

first protein kinase C conserved region 1 (C1 domain) found in novel protein kinase C (nPKC) theta, delta, and similar proteins; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domains. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. Members of this family contain two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410384  Cd Length: 61  Bit Score: 51.94  E-value: 3.42e-08
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 568960994 1103 TPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADC 1143
Cdd:cd20834    17 QPTFCSVCKEFLWGFNKQGYQCRQCNAAVHKKCHDKILGKC 57
C1_ARHGEF-like cd20832
protein kinase C conserved region 1 (C1 domain) found in uncharacterized Rho guanine ...
 1094-1143 3.66e-08

protein kinase C conserved region 1 (C1 domain) found in uncharacterized Rho guanine nucleotide exchange factor (ARHGEF)-like proteins; The family includes a group of uncharacterized proteins that show high sequence similarity to vertebrate Rho guanine nucleotide exchange factors ARHGEF11 and ARHGEF12, which may play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). Unlike typical ARHGEF11 and ARHGEF12, members of this family contain a C1 domain. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410382  Cd Length: 53  Bit Score: 51.60  E-value: 3.66e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568960994 1094 HNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADC 1143
Cdd:cd20832     2 HQFVLQHYYQVTFCNHCSGLLWGIGYQGYQCSDCEFNIHKQCIEVIEESC 51
C2B_Synaptotagmin-1 cd08402
C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking ...
 1215-1322 3.79e-08

C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of the class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis. It, like synaptotagmin-2, has an N-glycosylated N-terminus. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176047 [Multi-domain]  Cd Length: 136  Bit Score: 54.33  E-value: 3.79e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1215 SAKITITVVSAQGLQAKDKTGSSDPYVTVQVGKNKRRTK----TIFGN-LNPVWDEKFFFEChnSTDRIK-----VRVWD 1284
Cdd:cd08402    14 AGKLTVVILEAKNLKKMDVGGLSDPYVKIHLMQNGKRLKkkktTIKKRtLNPYYNESFSFEV--PFEQIQkvhliVTVLD 91

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 568960994 1285 EDddiksrvkqhfKKESDDFLGQTIVEVRTLSGEMDVW 1322
Cdd:cd08402    92 YD-----------RIGKNDPIGKVVLGCNATGAELRHW 118
C1_PKD3_rpt1 cd20841
first protein kinase C conserved region 1 (C1 domain) found in protein kinase D3 (PKD3) and ...
 1093-1143 3.90e-08

first protein kinase C conserved region 1 (C1 domain) found in protein kinase D3 (PKD3) and similar proteins; PKD3 is also called PRKD3, PRKCN, serine/threonine-protein kinase D3 (nPKC-D3), protein kinase C nu type (nPKC-nu), or protein kinase EPK2. It converts transient diacylglycerol (DAG) signals into prolonged physiological effects, downstream of PKC. It is involved in the regulation of the cell cycle by modulating microtubule nucleation and dynamics. PKD3 acts as a key mediator in several cancer development signaling pathways. PKD3 contains N-terminal tandem cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. This model corresponds to the first C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410391  Cd Length: 75  Bit Score: 52.35  E-value: 3.90e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568960994 1093 PHNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADC 1143
Cdd:cd20841    10 PHTLYVHSYKAPTFCDYCGEMLWGLVRQGLKCEGCGLNYHKRCAFKIPNNC 60
C2_C21orf25-like cd08678
C2 domain found in the Human chromosome 21 open reading frame 25 (C21orf25) protein; The ...
 1220-1316 4.62e-08

C2 domain found in the Human chromosome 21 open reading frame 25 (C21orf25) protein; The members in this cd are named after the Human C21orf25 which contains a single C2 domain. Several other members contain a C1 domain downstream of the C2 domain. No other information on this protein is currently known. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176060 [Multi-domain]  Cd Length: 126  Bit Score: 53.53  E-value: 4.62e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1220 ITVVSAQGLQAKdkTGSSDPYVTVQ----VGKNKrrTKTIFGNLNPVWDEKFFFECHNSTDRIKVRVWDedddiksrvkq 1295
Cdd:cd08678     3 VKNIKANGLSEA--AGSSNPYCVLEmdepPQKYQ--SSTQKNTSNPFWDEHFLFELSPNSKELLFEVYD----------- 67

                          90       100
                  ....*....|....*....|.
gi 568960994 1296 HFKKESDDFLGQTIVEVRTLS 1316
Cdd:cd08678    68 NGKKSDSKFLGLAIVPFDELR 88
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
1218-1315 7.41e-08

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 58.23  E-value: 7.41e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1218 ITITVVSAQGLQAKDKT--GSSDPYVTVQV-GKNKRRTKTIFGNLNPVWDEKFFFECHNSTDRIKVRVWDEDDdiksrvk 1294
Cdd:COG5038   438 VEVKIKSAEGLKKSDSTinGTVDPYITVTFsDRVIGKTRVKKNTLNPVWNETFYILLNSFTDPLNLSLYDFNS------- 510

                          90       100
                  ....*....|....*....|.
gi 568960994 1295 qhfkKESDDFLGQTIVEVRTL 1315
Cdd:COG5038   511 ----FKSDKVVGSTQLDLALL 527
CRIK cd20814
protein kinase C conserved region 1 (C1 domain) found in citron Rho-interacting kinase (CRIK) ...
 1093-1143 9.00e-08

protein kinase C conserved region 1 (C1 domain) found in citron Rho-interacting kinase (CRIK) and similar proteins; CRIK, also called serine/threonine-protein kinase 21, is an effector of the small GTPase Rho. It plays an important function during cytokinesis and affects its contractile process. CRIK-deficient mice show severe ataxia and epilepsy as a result of abnormal cytokinesis and massive apoptosis in neuronal precursors. A Down syndrome critical region protein TTC3 interacts with CRIK and inhibits CRIK-dependent neuronal differentiation and neurite extension. CRIK contains a catalytic domain, a central coiled-coil domain, and a C-terminal region containing a Rho-binding domain (RBD), a zinc finger (C1 domain), and a pleckstrin homology (PH) domain, in addition to other motifs. This model corresponds to C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410364  Cd Length: 56  Bit Score: 50.71  E-value: 9.00e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568960994 1093 PHNFEVWTATTPTYCYEC-EGLLWGiaRQGMKCLECGVKCHEKCQDLLNADC 1143
Cdd:cd20814     4 PHRFTTGLNMRATKCAVClDGVPFG--RQASKCSECGIVCHPKCSSSLPNTC 53
C2B_RasGAP cd08675
C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
 2069-2178 9.99e-08

C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. The proteins here all contain two tandem C2 domains, a Ras-GAP domain, and a pleckstrin homology (PH)-like domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.


Pssm-ID: 176057 [Multi-domain]  Cd Length: 137  Bit Score: 53.15  E-value: 9.99e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 2069 VTVKVIAINDLNWQTTAMFRPFVEVCMLGPSLGDKKRkqgTKTKSNTWSPKYNETFQFILGNENRPGAYELHLSVKDYCF 2148
Cdd:cd08675     1 LSVRVLECRDLALKSNGTCDPFARVTLNYSSKTDTKR---TKVKKKTNNPRFDEAFYFELTIGFSYEKKSFKVEEEDLEK 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 568960994 2149 AR------------EDRIIGMTVIQLQNIAEKGSYGAWYPLL 2178
Cdd:cd08675    78 SElrvelwhasmvsGDDFLGEVRIPLQGLQQAGSHQAWYFLQ 119
C1_MRCKgamma cd20866
protein kinase C conserved region 1 (C1 domain) found in myotonic dystrophy kinase-related ...
 1094-1135 1.19e-07

protein kinase C conserved region 1 (C1 domain) found in myotonic dystrophy kinase-related Cdc42-binding kinase gamma (MRCK gamma) and similar proteins; MRCK gamma (MRCKG), also called Cdc42-binding protein kinase gamma, DMPK-like gamma, myotonic dystrophy protein kinase-like gamma, or myotonic dystrophy protein kinase-like alpha, is a serine/threonine-protein kinase expressed in heart and skeletal muscles. It may act as a downstream effector of Cdc42 in cytoskeletal reorganization and contributes to the actomyosin contractility required for cell invasion, through the regulation of MYPT1 and thus MLC2 phosphorylation. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410416  Cd Length: 52  Bit Score: 50.14  E-value: 1.19e-07
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 568960994 1094 HNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKC 1135
Cdd:cd20866     1 HTFKPKTFTSPTKCLRCTSLMVGLVRQGLACEACNYVCHVSC 42
C1_PKD1_rpt1 cd20839
first protein kinase C conserved region 1 (C1 domain) found in protein kinase D (PKD) and ...
 1093-1143 1.37e-07

first protein kinase C conserved region 1 (C1 domain) found in protein kinase D (PKD) and similar proteins; PKD is also called PKD1, PRKD1, protein kinase C mu type (nPKC-mu), PRKCM, serine/threonine-protein kinase D1, or nPKC-D1. It is a serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of MAPK8/JNK1 and Ras signaling, Golgi membrane integrity and trafficking, cell survival through NF-kappa-B activation, cell migration, cell differentiation by mediating HDAC7 nuclear export, cell proliferation via MAPK1/3 (ERK1/2) signaling, and plays a role in cardiac hypertrophy, VEGFA-induced angiogenesis, genotoxic-induced apoptosis and flagellin-stimulated inflammatory response. PKD contains N-terminal tandem cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. This model corresponds to the first C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410389  Cd Length: 72  Bit Score: 50.79  E-value: 1.37e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568960994 1093 PHNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADC 1143
Cdd:cd20839     7 PHALFVHSYRAPAFCDHCGEMLWGLVRQGLKCEGCGLNYHKRCAFKIPNNC 57
C2B_MCTP_PRT_plant cd08378
C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 1220-1337 2.04e-07

C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176024 [Multi-domain]  Cd Length: 121  Bit Score: 51.54  E-value: 2.04e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1220 ITVVSAQGLqakdKTGSSDPYVTVQVGKNKRRTKTIFGNLNPVWDEKFFFEcHNS--TDRIKVRVWDEDddiksrvkqhf 1297
Cdd:cd08378     4 VRVVKARGL----PANSNDPVVEVKLGNYKGSTKAIERTSNPEWNQVFAFS-KDRlqGSTLEVSVWDKD----------- 67

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568960994 1298 kKESDDFLGQTIVEVRtlsgemDV-------------WYNLEkrtDKSAVSGA 1337
Cdd:cd08378    68 -KAKDDFLGGVCFDLS------EVptrvppdsplapqWYRLE---DKKGGRVG 110
C2B_Rabphilin_Doc2 cd08384
C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 1220-1306 2.19e-07

C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176030 [Multi-domain]  Cd Length: 133  Bit Score: 51.96  E-value: 2.19e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1220 ITVVSAQGLQAKDKTGSSDPYVTVQ----VGKNKRRTKTI-FGNLNPVWDEKFFFEChNSTDRIK----VRVWDEDddik 1290
Cdd:cd08384    17 VGIIRCVNLAAMDANGYSDPFVKLYlkpdAGKKSKHKTQVkKKTLNPEFNEEFFYDI-KHSDLAKktleITVWDKD---- 91

                          90
                  ....*....|....*.
gi 568960994 1291 srvkqhfKKESDDFLG 1306
Cdd:cd08384    92 -------IGKSNDYIG 100
C2B_Munc13-like cd04009
C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
 1217-1270 2.51e-07

C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175976 [Multi-domain]  Cd Length: 133  Bit Score: 51.85  E-value: 2.51e-07
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568960994 1217 KITITVVSAQGLQAKDKTGSSDPYVTVQV-------GKNKRRTKTIFGNLNPVWDEKFFFE 1270
Cdd:cd04009    17 SLRVEILNARNLLPLDSNGSSDPFVKVELlprhlfpDVPTPKTQVKKKTLFPLFDESFEFN 77
C2_Intersectin cd08375
C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally ...
 1217-1313 2.54e-07

C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally in the intersectin protein. Intersectin functions as a scaffolding protein, providing a link between the actin cytoskeleton and the components of endocytosis and plays a role in signal transduction. In addition to C2, intersectin contains several additional domains including: Eps15 homology domains, SH3 domains, a RhoGEF domain, and a PH domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. The members here have topology I.


Pssm-ID: 176021 [Multi-domain]  Cd Length: 136  Bit Score: 51.62  E-value: 2.54e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1217 KITITVVSAQGLQAKDKTGSSDPYVTVQVGKNKRRTKTIFGNLNPVWDEKFFFECHN-STDRIKVRVWDEDddiksrvkq 1295
Cdd:cd08375    16 RLMVVIVEGRDLKPCNSNGKSDPYCEVSMGSQEHKTKVVSDTLNPKWNSSMQFFVKDlEQDVLCITVFDRD--------- 86

                          90
                  ....*....|....*...
gi 568960994 1296 HFkkESDDFLGQTivEVR 1313
Cdd:cd08375    87 FF--SPDDFLGRT--EIR 100
C2B_Munc13-like cd04009
C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
 2089-2165 2.90e-07

C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175976 [Multi-domain]  Cd Length: 133  Bit Score: 51.47  E-value: 2.90e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568960994 2089 PFVEVCMLGPSLGDKKRKQGTKTKSNTWSPKYNETFQFILGNENR--PGAYeLHLSVKDYCFAREDRIIGMTVIQLQNI 2165
Cdd:cd04009    39 PFVKVELLPRHLFPDVPTPKTQVKKKTLFPLFDESFEFNVPPEQCsvEGAL-LLFTVKDYDLLGSNDFEGEAFLPLNDI 116
C2C_MCTP_PRT_plant cd04019
C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 1220-1345 5.77e-07

C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175986 [Multi-domain]  Cd Length: 150  Bit Score: 51.13  E-value: 5.77e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1220 ITVVSAQGLQAKDKTGSSDPYVTVQVGKNKRRTKT-IFGNLNPVWDEKFFFechnstdrikvrVWDE--DDDIKSRVKQH 1296
Cdd:cd04019     4 VTVIEAQDLVPSDKNRVPEVFVKAQLGNQVLRTRPsQTRNGNPSWNEELMF------------VAAEpfEDHLILSVEDR 71

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568960994 1297 FKKESDDFLGQTIVEVRTLSGEMDV------WYNLEK------RTDKSAVSGAIRLKINVE 1345
Cdd:cd04019    72 VGPNKDEPLGRAVIPLNDIERRVDDrpvpsrWFSLERpggameQKKKRKFASRIHLRLCLD 132
C2_cPLA2 cd04036
C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is ...
 1219-1289 7.17e-07

C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is present in cPLA2 which releases arachidonic acid from membranes initiating the biosynthesis of potent inflammatory mediators such as prostaglandins, leukotrienes, and platelet-activating factor. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members of this cd have a type-II topology.


Pssm-ID: 176001 [Multi-domain]  Cd Length: 119  Bit Score: 49.95  E-value: 7.17e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568960994 1219 TITVVSAQGLQAKDKTGSSDPYVTVQV---GKNKRRTKTIFGNLNPVWDEKFFFECHNSTDRI-KVRVWDED---DDI 1289
Cdd:cd04036     3 TVRVLRATNITKGDLLSTPDCYVELWLptaSDEKKRTKTIKNSINPVWNETFEFRIQSQVKNVlELTVMDEDyvmDDH 80
C1_ScPKC1-like_rpt2 cd20823
second protein kinase C conserved region 1 (C1 domain) found in Saccharomyces cerevisiae ...
 1093-1138 1.30e-06

second protein kinase C conserved region 1 (C1 domain) found in Saccharomyces cerevisiae protein kinase C-like 1 (ScPKC1) and similar proteins; ScPKC1 is required for cell growth and for the G2 to M transition of the cell division cycle. It mediates a protein kinase cascade, activating BCK1 which itself activates MKK1/MKK2. The family also includes Schizosaccharomyces pombe PKC1 and PKC2, which are involved in the control of cell shape and act as targets of the inhibitor staurosporine. Members of this family contain two copies of C1 domain. This model corresponds to the second one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410373  Cd Length: 59  Bit Score: 47.30  E-value: 1.30e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 568960994 1093 PHNFEVWTATTPTYCYECeGLLWGIARQGM-KCLECGVKCHEKCQDL 1138
Cdd:cd20823     4 PHRFEPFTNLGANWCCHC-GQMLPLGRKQIrKCTECGKTAHAQCAHL 49
C1_aPKC_iota cd21094
protein kinase C conserved region 1 (C1 domain) found in the atypical protein kinase C (aPKC) ...
 1092-1143 1.34e-06

protein kinase C conserved region 1 (C1 domain) found in the atypical protein kinase C (aPKC) iota type; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. They contain a C2-like region, instead of a calcium-binding (C2) region found in classical PKCs, in their regulatory domain. There are two aPKC isoforms, zeta and iota. aPKCs are involved in many cellular functions including proliferation, migration, apoptosis, polarity maintenance and cytoskeletal regulation. They also play a critical role in the regulation of glucose metabolism and in the pathogenesis of type 2 diabetes. PKC-iota is directly implicated in carcinogenesis. It is critical to oncogenic signaling mediated by Ras and Bcr-Abl. The PKC-iota gene is the target of tumor-specific gene amplification in many human cancers, and has been identified as a human oncogene. In addition to its role in transformed growth, PKC-iota also promotes invasion, chemoresistance, and tumor cell survival. Expression profiling of PKC-iota is a prognostic marker of poor clinical outcome in several human cancers. PKC-iota also plays a role in establishing cell polarity, and has critical embryonic functions. Members of this family contain C1 domain found in aPKC isoform iota. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410447  Cd Length: 55  Bit Score: 47.30  E-value: 1.34e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568960994 1092 TPHNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADC 1143
Cdd:cd21094     1 NGHTFQAKRFNRRAHCAICTDRIWGLGRQGYKCINCKLLVHKKCHKLVTIEC 52
C2_NEDL1-like cd08691
C2 domain present in NEDL1 (NEDD4-like ubiquitin protein ligase-1); NEDL1 (AKA HECW1(HECT, C2 ...
 1218-1342 1.41e-06

C2 domain present in NEDL1 (NEDD4-like ubiquitin protein ligase-1); NEDL1 (AKA HECW1(HECT, C2 and WW domain containing E3 ubiquitin protein ligase 1)) is a newly identified HECT-type E3 ubiquitin protein ligase highly expressed in favorable neuroblastomas. In vertebrates it is found primarily in neuronal tissues, including the spinal cord. NEDL1 is thought to normally function in the quality control of cellular proteins by eliminating misfolded proteins. This is thought to be accomplished via a mechanism analogous to that of ER-associated degradation by forming tight complexes and aggregating misfolded proteins that have escaped ubiquitin-mediated degradation. NEDL1, is composed of a C2 domain, two WW domains, and a ubiquitin ligase Hect domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176073 [Multi-domain]  Cd Length: 137  Bit Score: 49.71  E-value: 1.41e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1218 ITITVVSAQGLQaKDKTGSSDPYV--TVQVGKN-----------KRRTKTIFGNLNPVWD-EKFFFECHnSTDRIKVRVW 1283
Cdd:cd08691     3 FSLSGLQARNLK-KGMFFNPDPYVkiSIQPGKRhifpalphhgqECRTSIVENTINPVWHrEQFVFVGL-PTDVLEIEVK 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568960994 1284 DEDDdiKSRVKqhFKKesddFLGQTIVEV-----RTLSGEMDVWYNLEKRTDKSAVSGAIRLKI 1342
Cdd:cd08691    81 DKFA--KSRPI--IRR----FLGKLSIPVqrlleRHAIGDQELSYTLGRRTPTDHVSGQLTFRF 136
C1_PKD2_rpt1 cd20840
first protein kinase C conserved region 1 (C1 domain) found in protein kinase D2 (PKD2) and ...
 1093-1143 1.60e-06

first protein kinase C conserved region 1 (C1 domain) found in protein kinase D2 (PKD2) and similar proteins; PKD2, also called PRKD2, HSPC187, or serine/threonine-protein kinase D2 (nPKC-D2), is a serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of cell proliferation via MAPK1/3 (ERK1/2) signaling, oxidative stress-induced NF-kappa-B activation, inhibition of HDAC7 transcriptional repression, signaling downstream of T-cell antigen receptor (TCR) and cytokine production, and plays a role in Golgi membrane trafficking, angiogenesis, secretory granule release and cell adhesion. PKD2 contains N-terminal tandem cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. This model corresponds to the first C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410390  Cd Length: 73  Bit Score: 47.74  E-value: 1.60e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568960994 1093 PHNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADC 1143
Cdd:cd20840    10 PHALNVHSYRAPAFCDHCGEMLFGLVRQGLKCDGCGLNYHKRCAFSIPNNC 60
C2_plant_PLD cd04015
C2 domain present in plant phospholipase D (PLD); PLD hydrolyzes terminal phosphodiester bonds ...
 1233-1286 1.62e-06

C2 domain present in plant phospholipase D (PLD); PLD hydrolyzes terminal phosphodiester bonds in diester glycerophospholipids resulting in the degradation of phospholipids. In vitro PLD transfers phosphatidic acid to primary alcohols. In plants PLD plays a role in germination, seedling growth, phosphatidylinositol metabolism, and changes in phospholipid composition. There is a single Ca(2+)/phospholipid-binding C2 domain in PLD. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175982 [Multi-domain]  Cd Length: 158  Bit Score: 50.00  E-value: 1.62e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568960994 1233 KTGSSDPYVTVQVGKNK-RRTKTIFGNLNPVWDEKFFFECHNSTDRIKVRVWDED 1286
Cdd:cd04015    54 GKITSDPYATVDLAGARvARTRVIENSENPVWNESFHIYCAHYASHVEFTVKDND 108
C2B_Synaptotagmin-3-5-6-9-10 cd08403
C2 domain second repeat present in Synaptotagmins 3, 5, 6, 9, and 10; Synaptotagmin is a ...
 1215-1270 1.97e-06

C2 domain second repeat present in Synaptotagmins 3, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 3, a member of class 3 synaptotagmins, is located in the brain and localized to the active zone and plasma membrane. It functions as a Ca2+ sensor for fast exocytosis. It, along with synaptotagmins 5,6, and 10, has disulfide bonds at its N-terminus. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176048 [Multi-domain]  Cd Length: 134  Bit Score: 49.04  E-value: 1.97e-06
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568960994 1215 SAKITITVVSAQGLQAKDKTGSSDPYVTVQV---GK--NKRRTKTIFGNLNPVWDEKFFFE 1270
Cdd:cd08403    13 AGRLTLTIIKARNLKAMDITGFSDPYVKVSLmceGRrlKKKKTSVKKNTLNPTYNEALVFD 73
C2A_Ferlin cd08373
C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 1221-1325 1.98e-06

C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 176019 [Multi-domain]  Cd Length: 127  Bit Score: 48.79  E-value: 1.98e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1221 TVVSAQGLQAKdkTGSSDPYVTVQVGKNKRRTKTIFGNLNPVWDEKFFFECHNSTDRikvrvwdeDDDIKSRVKQHFKKE 1300
Cdd:cd08373     1 LVVSLKNLPGL--KGKGDRIAKVTFRGVKKKTRVLENELNPVWNETFEWPLAGSPDP--------DESLEIVVKDYEKVG 70

                          90       100
                  ....*....|....*....|....*..
gi 568960994 1301 SDDFLGQTIVEVRTL--SGEMDVWYNL 1325
Cdd:cd08373    71 RNRLIGSATVSLQDLvsEGLLEVTEPL 97
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
 2068-2160 2.35e-06

C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. There are several classes of Synaptotagmins. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175975 [Multi-domain]  Cd Length: 134  Bit Score: 49.12  E-value: 2.35e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 2068 KVTVKVIAINDLNWQT-TAMFRPFVEVCMLGPSLGDKKRKqgTKTKSNTWSPKYNETFQFILGNENRPGAyELHLSVKDY 2146
Cdd:cd00276    15 RLTVVVLKARNLPPSDgKGLSDPYVKVSLLQGGKKLKKKK--TSVKKGTLNPVFNEAFSFDVPAEQLEEV-SLVITVVDK 91

                          90
                  ....*....|....
gi 568960994 2147 CFAREDRIIGMTVI 2160
Cdd:cd00276    92 DSVGRNEVIGQVVL 105
C1_aPKC_zeta cd21095
protein kinase C conserved region 1 (C1 domain) found in the atypical protein kinase C (aPKC) ...
 1094-1145 2.54e-06

protein kinase C conserved region 1 (C1 domain) found in the atypical protein kinase C (aPKC) zeta type; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. They contain a C2-like region, instead of a calcium-binding (C2) region found in classical PKCs, in their regulatory domain. There are two aPKC isoforms, zeta and iota. aPKCs are involved in many cellular functions including proliferation, migration, apoptosis, polarity maintenance and cytoskeletal regulation. They also play a critical role in the regulation of glucose metabolism and in the pathogenesis of type 2 diabetes. PKC-zeta plays a critical role in activating the glucose transport response. It is activated by glucose, insulin, and exercise through diverse pathways. PKC-zeta also plays a central role in maintaining cell polarity in yeast and mammalian cells. In addition, it affects actin remodeling in muscle cells. Members of this family contain C1 domain found in aPKC isoform zeta. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410448  Cd Length: 55  Bit Score: 46.52  E-value: 2.54e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568960994 1094 HNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADCLQ 1145
Cdd:cd21095     3 HLFQAKRFNRRAYCGQCSERIWGLGRQGYKCINCKLLVHKRCHKLVPLTCKR 54
C1_Raf cd20811
protein kinase C conserved region 1 (C1 domain) found in the Raf (Rapidly Accelerated ...
 1094-1143 2.93e-06

protein kinase C conserved region 1 (C1 domain) found in the Raf (Rapidly Accelerated Fibrosarcoma) kinase family; Raf kinases are serine/threonine kinases (STKs) that catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. They act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. Aberrant expression or activation of components in this pathway are associated with tumor initiation, progression, and metastasis. Raf proteins contain a Ras binding domain, a zinc finger cysteine-rich domain (C1), and a catalytic kinase domain. Vertebrates have three Raf isoforms (A-, B-, and C-Raf) with different expression profiles, modes of regulation, and abilities to function in the ERK cascade, depending on cellular context and stimuli. They have essential and non-overlapping roles during embryo- and organogenesis. Knockout of each isoform results in a lethal phenotype or abnormality in most mouse strains. This model describes the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410361  Cd Length: 49  Bit Score: 46.13  E-value: 2.93e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568960994 1094 HNFEVWTATTPTYCYECEGLLWgiarQGMKCLECGVKCHEKCQDLLNADC 1143
Cdd:cd20811     3 HNFVRKTFFTLAFCDVCRKLLF----QGFRCQTCGFKFHQRCSDQVPALC 48
C2A_Synaptotagmin-7 cd08386
C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 2089-2165 3.11e-06

C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176032 [Multi-domain]  Cd Length: 125  Bit Score: 48.48  E-value: 3.11e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 2089 PFVEVCMLgPslgDKKRKQGTKTKSNTWSPKYNETFQFilgnENRPgaYE------LHLSVKDY-CFAREDRiIGMTVIQ 2161
Cdd:cd08386    39 PFVKIYLL-P---DKKHKLETKVKRKNLNPHWNETFLF----EGFP--YEklqqrvLYLQVLDYdRFSRNDP-IGEVSLP 107


                  ....
gi 568960994 2162 LQNI 2165
Cdd:cd08386   108 LNKV 111
C2_SRC2_like cd04051
C2 domain present in Soybean genes Regulated by Cold 2 (SRC2)-like proteins; SRC2 production ...
 1217-1272 3.92e-06

C2 domain present in Soybean genes Regulated by Cold 2 (SRC2)-like proteins; SRC2 production is a response to pathogen infiltration. The initial response of increased Ca2+ concentrations are coupled to downstream signal transduction pathways via calcium binding proteins. SRC2 contains a single C2 domain which localizes to the plasma membrane and is involved in Ca2+ dependent protein binding. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176016 [Multi-domain]  Cd Length: 125  Bit Score: 48.00  E-value: 3.92e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 568960994 1217 KITITVVSAQGLQAKDKTGSSDPYVTVQV-GKNKRRTKTIF-GNLNPVWDEKFFFECH 1272
Cdd:cd04051     1 TLEITIISAEDLKNVNLFGKMKVYAVVWIdPSHKQSTPVDRdGGTNPTWNETLRFPLD 58
C1_MRCKbeta cd20865
protein kinase C conserved region 1 (C1 domain) found in myotonic dystrophy kinase-related ...
 1094-1137 4.15e-06

protein kinase C conserved region 1 (C1 domain) found in myotonic dystrophy kinase-related Cdc42-binding kinase beta (MRCK beta) and similar proteins; MRCK beta, also called Cdc42-binding protein kinase beta (Cdc42BP-beta), DMPK-like beta, or myotonic dystrophy protein kinase-like beta, is a serine/threonine-protein kinase expressed ubiquitously in many tissues. MRCK beta is an important downstream effector of Cdc42 and plays a role in the regulation of cytoskeleton reorganization and cell migration. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410415  Cd Length: 53  Bit Score: 45.74  E-value: 4.15e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 568960994 1094 HNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQD 1137
Cdd:cd20865     1 HQLSIKSFSSPTQCSHCTSLMVGLVRQGYACEVCSFACHVSCKD 44
C2B_Rabphilin_Doc2 cd08384
C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 2089-2180 4.98e-06

C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176030 [Multi-domain]  Cd Length: 133  Bit Score: 48.11  E-value: 4.98e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 2089 PFVEVCmLGPSLGdKKRKQGTKTKSNTWSPKYNETFQFILgNENRPGAYELHLSVKDYCFAREDRIIGMtvIQLqNIAEK 2168
Cdd:cd08384    36 PFVKLY-LKPDAG-KKSKHKTQVKKKTLNPEFNEEFFYDI-KHSDLAKKTLEITVWDKDIGKSNDYIGG--LQL-GINAK 109

                          90
                  ....*....|...
gi 568960994 2169 GSYGA-WYPLLKN 2180
Cdd:cd08384   110 GERLRhWLDCLKN 122
C2A_RIM1alpha cd04031
C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
 2065-2177 6.28e-06

C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are believed to organize specialized sites of the plasma membrane called active zones. They also play a role in controlling neurotransmitter release, plasticity processes, as well as memory and learning. RIM contains an N-terminal zinc finger domain, a PDZ domain, and two C-terminal C2 domains (C2A, C2B). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology and do not bind Ca2+.


Pssm-ID: 175997 [Multi-domain]  Cd Length: 125  Bit Score: 47.63  E-value: 6.28e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 2065 GDHKVTVKVIAINDLNWQTTAMFR-PFVEVCML-GPSLGDKKRkqgTKTKSNTWSPKYNETFQFilGNENRPGAYE--LH 2140
Cdd:cd04031    14 VTSQLIVTVLQARDLPPRDDGSLRnPYVKVYLLpDRSEKSKRR---TKTVKKTLNPEWNQTFEY--SNVRRETLKErtLE 88

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 568960994 2141 LSVKDYCFAREDRIIGMTVIQLQNIAEKGSyGAWYPL 2177
Cdd:cd04031    89 VTVWDYDRDGENDFLGEVVIDLADALLDDE-PHWYPL 124
C2_KIAA0528-like cd08688
C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the ...
 1218-1293 8.09e-06

C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the Human KIAA0528 cDNA clone. All members here contain a single C2 repeat. No other information on this protein is currently known. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176070 [Multi-domain]  Cd Length: 110  Bit Score: 46.92  E-value: 8.09e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1218 ITITVVSAQGLQAKDKT-GSSDPYVTVQVGKNKRRTKTIFGNLNPVW-DEKFFFECHNS--TDR-IKVRVWDED----DD 1288
Cdd:cd08688     1 LKVRVVAARDLPVMDRSsDLTDAFVEVKFGSTTYKTDVVKKSLNPVWnSEWFRFEVDDEelQDEpLQIRVMDHDtysaND 80


                  ....*
gi 568960994 1289 IKSRV 1293
Cdd:cd08688    81 AIGKV 85
C1_aPKC cd20794
protein kinase C conserved region 1 (C1 domain) found in the atypical protein kinase C (aPKC) ...
 1094-1146 8.86e-06

protein kinase C conserved region 1 (C1 domain) found in the atypical protein kinase C (aPKC) family; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. They contain a C2-like region, instead of a calcium-binding (C2) region found in classical PKCs, in their regulatory domain. There are two aPKC isoforms, zeta and iota. aPKCs are involved in many cellular functions including proliferation, migration, apoptosis, polarity maintenance and cytoskeletal regulation. They also play a critical role in the regulation of glucose metabolism and in the pathogenesis of type 2 diabetes. PKC-zeta plays a critical role in activating the glucose transport response. It is activated by glucose, insulin, and exercise through diverse pathways. PKC-zeta also plays a central role in maintaining cell polarity in yeast and mammalian cells. In addition, it affects actin remodeling in muscle cells. PKC-iota is directly implicated in carcinogenesis. It is critical to oncogenic signaling mediated by Ras and Bcr-Abl. The PKC-iota gene is the target of tumor-specific gene amplification in many human cancers, and has been identified as a human oncogene. In addition to its role in transformed growth, PKC-iota also promotes invasion, chemoresistance, and tumor cell survival. Expression profiling of PKC-iota is a prognostic marker of poor clinical outcome in several human cancers. PKC-iota also plays a role in establishing cell polarity, and has critical embryonic functions. Members of this family contain one C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410344  Cd Length: 55  Bit Score: 44.95  E-value: 8.86e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568960994 1094 HNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADCLQR 1146
Cdd:cd20794     3 HLFQAKRFNRRAVCAYCSDRIWGLGRQGYKCINCKLLVHKKCHKLVKVACGQQ 55
C1_PDZD8 cd20825
protein kinase C conserved region 1 (C1 domain) found in PDZ domain-containing protein 8 ...
 1093-1137 8.96e-06

protein kinase C conserved region 1 (C1 domain) found in PDZ domain-containing protein 8 (PDZD8) and similar proteins; PDZD8, also called Sarcoma antigen NY-SAR-84/NY-SAR-104, is a molecular tethering protein that connects endoplasmic reticulum (ER) and mitochondrial membranes. PDZD8-dependent ER-mitochondria membrane tethering is essential for ER-mitochondria Ca2+ transfer. In neurons, it is involved in the regulation of dendritic Ca2+ dynamics by regulating mitochondrial Ca2+ uptake. PDZD8 also plays an indirect role in the regulation of cell morphology and cytoskeletal organization. It contains a PDZ domain and a C1 domain. This model describes the C1 domain, a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410375  Cd Length: 55  Bit Score: 44.96  E-value: 8.96e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 568960994 1093 PHNFEVWTATTPTYCYECEGLLWgiARQGMKCLECGVKCHEKCQD 1137
Cdd:cd20825     3 KHDFVLTQFQNATYCDFCKKKIW--LKEAFQCRLCGMICHKKCLD 45
C2D_MCTP_PRT_plant cd08379
C2 domain fourth repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 1224-1284 1.23e-05

C2 domain fourth repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fourth C2 repeat, C2D, and has a type-II topology.


Pssm-ID: 176025 [Multi-domain]  Cd Length: 126  Bit Score: 46.63  E-value: 1.23e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568960994 1224 SAQG---LQAKDKTGSSDPYVTVQVGKNKRRTKTIFGNLNPVWDEKFFFECHNSTDRIKVRVWD 1284
Cdd:cd08379     8 GAQGldvLRAKDGRGSTDAYCVAKYGPKWVRTRTVEDSSNPRWNEQYTWPVYDPCTVLTVGVFD 71
C2B_Synaptotagmin-4 cd08404
C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking ...
 1217-1270 1.26e-05

C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176049 [Multi-domain]  Cd Length: 136  Bit Score: 47.04  E-value: 1.26e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 568960994 1217 KITITVVSAQGLQAKDKTGSSDPYVTVQVGKN-----KRRTKTIFGNLNPVWDEKFFFE 1270
Cdd:cd08404    16 RLTVVVLKARHLPKMDVSGLADPYVKVNLYYGkkrisKKKTHVKKCTLNPVFNESFVFD 74
C1_cPKC_rpt1 cd20833
first protein kinase C conserved region 1 (C1 domain) found in the classical (or conventional) ...
 1104-1143 1.44e-05

first protein kinase C conserved region 1 (C1 domain) found in the classical (or conventional) protein kinase C (cPKC) family; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domains. cPKCs are potent kinases for histones, myelin basic protein, and protamine. They depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. There are four cPKC isoforms, named alpha, betaI, betaII, and gamma. PKC-alpha is expressed in many tissues and is associated with cell proliferation, apoptosis, and cell motility. It plays a role in the signaling of the growth factors PDGF, VEGF, EGF, and FGF. Abnormal levels of PKC-alpha have been detected in many transformed cell lines and several human tumors. In addition, PKC-alpha is required for HER2 dependent breast cancer invasion. The PKC beta isoforms (I and II), generated by alternative splicing of a single gene, are preferentially activated by hyperglycemia-induced DAG (1,2-diacylglycerol) in retinal tissues. This is implicated in diabetic microangiopathy such as ischemia, neovascularization, and abnormal vasodilator function. PKC-beta also plays an important role in VEGF signaling. In addition, glucose regulates proliferation in retinal endothelial cells via PKC-betaI. PKC-beta is also being explored as a therapeutic target in cancer. It contributes to tumor formation and is involved in the tumor host mechanisms of inflammation and angiogenesis. PKC-gamma is mainly expressed in neuronal tissues. It plays a role in protection from ischemia. Members of this family contain two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410383  Cd Length: 58  Bit Score: 44.32  E-value: 1.44e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 568960994 1104 PTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADC 1143
Cdd:cd20833    13 PTFCSHCTDFIWGFGKQGFQCQVCSFVVHKRCHEFVTFSC 52
C1_Myosin-IX cd20818
protein kinase C conserved region 1 (C1 domain) found in the unconventional myosin-IX family; ...
 1094-1143 1.51e-05

protein kinase C conserved region 1 (C1 domain) found in the unconventional myosin-IX family; Myosins IX (Myo9) is a class of unique motor proteins with a common structure of an N-terminal extension preceding a myosin head homologous to the Ras-association (RA) domain, a head (motor) domain, a neck with IQ motifs that bind light chains, and a C-terminal tail containing cysteine-rich zinc binding (C1) and Rho-GTPase activating protein (RhoGAP) domains. There are two genes for myosins IX in humans, IXa and IXb, that are different in their expression and localization. IXa is expressed abundantly in brain and testis, and IXb is expressed abundantly in tissues of the immune system. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410368  Cd Length: 56  Bit Score: 44.21  E-value: 1.51e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568960994 1094 HNFEVWTATTPTYCYECEGLLWGIARqGMKCLECGVKCHEKCQDLLNADC 1143
Cdd:cd20818     4 HKFATVQFNIPTYCEVCNSFIWLMEK-GLVCQVCKFTCHKKCYSKITAPC 52
C2B_RasA3 cd04010
C2 domain second repeat present in RAS p21 protein activator 3 (RasA3); RasA3 are members of ...
 2068-2177 1.82e-05

C2 domain second repeat present in RAS p21 protein activator 3 (RasA3); RasA3 are members of GTPase activating protein 1 (GAP1), a Ras-specific GAP, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. RasA3 contains an N-terminal C2 domain, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175977 [Multi-domain]  Cd Length: 148  Bit Score: 46.62  E-value: 1.82e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 2068 KVTVKVIAINDLNwQTTAMFRPFVEVCMLGPSlgDKKRKQGTKTKSNTWSPKYNETFQFILGNENRPGAYELHLSVKDYC 2147
Cdd:cd04010     1 KLSVRVIECSDLA-LKNGTCDPYASVTLIYSN--KKQDTKRTKVKKKTNNPQFDEAFYFDVTIDSSPEKKQFEMPEEDAE 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 568960994 2148 FAR------------EDRIIGMTVIQLQNI-AEKGSYGAWYPL 2177
Cdd:cd04010    78 KLElrvdlwhasmggGDVFLGEVRIPLRGLdLQAGSHQAWYFL 120
C2B_SLP_1-2-3-4 cd04020
C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically ...
 1202-1306 2.13e-05

C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175987 [Multi-domain]  Cd Length: 162  Bit Score: 46.93  E-value: 2.13e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1202 AAKQSVLDGTSKwSAKITITVVSAQGLQAKDKTGSSDPYVTVQV-----GKNKRRTKTIFGNLNPVWDEKFFFECHNSTD 1276
Cdd:cd04020    14 ESEGALKSKKPS-TGELHVWVKEAKNLPALKSGGTSDSFVKCYLlpdksKKSKQKTPVVKKSVNPVWNHTFVYDGVSPED 92

                          90       100       110
                  ....*....|....*....|....*....|....
gi 568960994 1277 R----IKVRVWDEDddiksrvkqhfKKESDDFLG 1306
Cdd:cd04020    93 LsqacLELTVWDHD-----------KLSSNDFLG 115
C2A_Synaptotagmin-15-17 cd08390
C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a ...
 2050-2164 2.47e-05

C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. It is thought to be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues and is Ca2+ independent. Human synaptotagmin 15 has 2 alternatively spliced forms that encode proteins with different C-termini. The larger, SYT15a, contains a N-terminal TM region, a putative fatty-acylation site, and 2 tandem C terminal C2 domains. The smaller, SYT15b, lacks the C-terminal portion of the second C2 domain. Unlike most other synaptotagmins it is nearly absent in the brain and rather is found in the heart, lungs, skeletal muscle, and testis. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176036 [Multi-domain]  Cd Length: 123  Bit Score: 45.71  E-value: 2.47e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 2050 GQI--SVHVDVTTTpgtgdhKVTVKVIAINDLNWQTTAMFR--PFVEVCMLgPslgDKKRKQGTKTKSNTWSPKYNETFQ 2125
Cdd:cd08390     1 GRLwfSVQYDLEEE------QLTVSLIKARNLPPRTKDVAHcdPFVKVCLL-P---DERRSLQSKVKRKTQNPNFDETFV 70

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 568960994 2126 F-ILGNENRpgAYELHLSVKDYCFAREDRIIGMTVIQLQN 2164
Cdd:cd08390    71 FqVSFKELQ--RRTLRLSVYDVDRFSRHCIIGHVLFPLKD 108
C2_E3_ubiquitin_ligase cd04021
C2 domain present in E3 ubiquitin ligase; E3 ubiquitin ligase is part of the ubiquitylation ...
 1215-1311 3.67e-05

C2 domain present in E3 ubiquitin ligase; E3 ubiquitin ligase is part of the ubiquitylation mechanism responsible for controlling surface expression of membrane proteins. The sequential action of several enzymes are involved: ubiquitin-activating enzyme E1, ubiquitin-conjugating enzyme E2, and ubiquitin-protein ligase E3 which is responsible for substrate recognition and promoting the transfer of ubiquitin to the target protein. E3 ubiquitin ligase is composed of an N-terminal C2 domain, 4 WW domains, and a HECTc domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175988 [Multi-domain]  Cd Length: 125  Bit Score: 45.35  E-value: 3.67e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1215 SAKITITVVSAQgLQAKDKTGSSDPYVTVQV-GKNKRRTKTIFGNLNPVWDEKFFFECHNSTdRIKVRVWDedddiksrv 1293
Cdd:cd04021     1 KSQLQITVESAK-LKSNSKSFKPDPYVEVTVdGQPPKKTEVSKKTSNPKWNEHFTVLVTPQS-TLEFKVWS--------- 69

                          90
                  ....*....|....*...
gi 568960994 1294 kqHFKKESDDFLGQTIVE 1311
Cdd:cd04021    70 --HHTLKADVLLGEASLD 85
C1_VAV2 cd20868
protein kinase C conserved region 1 (C1 domain) found in VAV2 protein; VAV2 is widely ...
 1094-1135 5.09e-05

protein kinase C conserved region 1 (C1 domain) found in VAV2 protein; VAV2 is widely expressed and functions as a guanine nucleotide exchange factor (GEF) for RhoA, RhoB and RhoG and also activates Rac1 and Cdc42. It is implicated in many cellular and physiological functions including blood pressure control, eye development, neurite outgrowth and branching, EGFR endocytosis and degradation, and cell cluster morphology, among others. It has been reported to associate with Nek3. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410418  Cd Length: 58  Bit Score: 42.95  E-value: 5.09e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 568960994 1094 HNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKC 1135
Cdd:cd20868     6 HNFQMYTFDKTTNCKACKMLLRGTFYQGYYCSKCGAGAHKEC 47
C1_nPKC_epsilon-like_rpt1 cd20835
first protein kinase C conserved region 1 (C1 domain) found in novel protein kinase C (nPKC) ...
 1094-1143 5.94e-05

first protein kinase C conserved region 1 (C1 domain) found in novel protein kinase C (nPKC) epsilon, eta, and similar proteins; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domains. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. PKC-epsilon has been shown to behave as an oncoprotein. Its overexpression contributes to neoplastic transformation depending on the cell type. It contributes to oncogenesis by inducing disordered cell growth and inhibiting cell death. It also plays a role in tumor invasion and metastasis. PKC-epsilon has also been found to confer cardioprotection against ischemia and reperfusion-mediated damage. Other cellular functions include the regulation of gene expression, cell adhesion, and cell motility. PKC-eta is predominantly expressed in squamous epithelia, where it plays a crucial role in the signaling of cell-type specific differentiation. It is also expressed in pro-B cells and early-stage thymocytes, and acts as a key regulator in early B-cell development. PKC-eta increases glioblastoma multiforme (GBM) proliferation and resistance to radiation, and is being developed as a therapeutic target for the management of GBM. Members of this family contain two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410385  Cd Length: 64  Bit Score: 42.84  E-value: 5.94e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568960994 1094 HNFEVWTATTPTYCYECEGLLWGI-ARQGMKCLECGVKCHEKCQDLLNADC 1143
Cdd:cd20835    10 HKFMATYLRQPTYCSHCKDFIWGViGKQGYQCQVCTCVVHKRCHQLVVTKC 60
C1_MgcRacGAP cd20821
protein kinase C conserved region 1 (C1 domain) found in male germ cell RacGap (MgcRacGAP) and ...
 1093-1143 5.96e-05

protein kinase C conserved region 1 (C1 domain) found in male germ cell RacGap (MgcRacGAP) and similar proteins; MgcRacGAP, also called Rac GTPase-activating protein 1 (RACGAP1) or protein CYK4, plays an important dual role in cytokinesis: i) it is part of centralspindlin-complex, together with the mitotic kinesin MKLP1, which is critical for the structure of the central spindle by promoting microtuble bundling; and ii) after phosphorylation by aurora B, MgcRacGAP becomes an effective regulator of RhoA and plays an important role in the assembly of the contractile ring and the initiation of cytokinesis. MgcRacGAP-like proteins contain an N-terminal C1 domain, and a C-terminal RhoGAP domain. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410371  Cd Length: 55  Bit Score: 42.39  E-value: 5.96e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568960994 1093 PHNFEVWTATTPTYCYECEGLLwGIARQGMKCLECGVKCHEKCQDLLNADC 1143
Cdd:cd20821     2 PHRFVSKTVIKPETCVVCGKRI-KFGKKALKCKDCRVVCHPDCKDKLPLPC 51
C1_DGK_typeII_rpt1 cd20800
first protein kinase C conserved region 1 (C1 domain) found in type II diacylglycerol kinases; ...
 1094-1143 6.15e-05

first protein kinase C conserved region 1 (C1 domain) found in type II diacylglycerol kinases; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. Type II DAG kinases (DGKs) contain pleckstrin homology (PH) and sterile alpha motifs (SAM) domains, in addition to C1 and catalytic domains that are present in all DGKs. The SAM domain mediates oligomerization of type II DGKs. Three DGK isozymes (delta, eta and kappa) are classified as type II. DAG kinase delta, also called 130 kDa DAG kinase, or diglyceride kinase delta (DGK-delta), is a residential lipid kinase in the endoplasmic reticulum. It promotes lipogenesis and is involved in triglyceride biosynthesis. DAG kinase eta, also called diglyceride kinase eta (DGK-eta), plays a key role in promoting cell growth. The DAG kinase eta gene, DGKH, is a replicated risk gene of bipolar disorder (BPD). DAG kinase kappa is also called diglyceride kinase kappa (DGK-kappa) or 142 kDa DAG kinase. Members of this family contain two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410350  Cd Length: 60  Bit Score: 42.69  E-value: 6.15e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568960994 1094 HNfevWTATT---PTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADC 1143
Cdd:cd20800     5 HN---WYACSharPTYCNVCREALSGVTSHGLSCEVCKFKAHKRCAVKAPNNC 54
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 2068-2165 6.57e-05

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) to d-myo-inositol-1,4,5-trisphosphate (1,4,5-IP3) and sn-1,2-diacylglycerol (DAG). 1,4,5-IP3 and DAG are second messengers in eukaryotic signal transduction cascades. PLC is composed of a N-terminal PH domain followed by a series of EF hands, a catalytic TIM barrel and a C-terminal C2 domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-II topology.


Pssm-ID: 175974 [Multi-domain]  Cd Length: 128  Bit Score: 44.45  E-value: 6.57e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 2068 KVTVKVIA---INDLNWQTTAMFRPFVEVCMLGPSLGDKKRKQgTKTKSNTW-SPKYNETFQFILGNEnrpgayEL---H 2140
Cdd:cd00275     3 TLTIKIISgqqLPKPKGDKGSIVDPYVEVEIHGLPADDSAKFK-TKVVKNNGfNPVWNETFEFDVTVP------ELaflR 75

                          90       100
                  ....*....|....*....|....*
gi 568960994 2141 LSVKDYCFAReDRIIGMTVIQLQNI 2165
Cdd:cd00275    76 FVVYDEDSGD-DDFLGQACLPLDSL 99
C2_PSD cd04039
C2 domain present in Phosphatidylserine decarboxylase (PSD); PSD is involved in the ...
 1220-1315 6.72e-05

C2 domain present in Phosphatidylserine decarboxylase (PSD); PSD is involved in the biosynthesis of aminophospholipid by converting phosphatidylserine (PtdSer) to phosphatidylethanolamine (PtdEtn). There is a single C2 domain present and it is thought to confer PtdSer binding motif that is common to PKC and synaptotagmin. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176004 [Multi-domain]  Cd Length: 108  Bit Score: 44.17  E-value: 6.72e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1220 ITVVSAQGL-QAKDKTGSS---DPYVTVQVGKNKRRTKTIFGNLNPVWDEKFFFEC--HNSTDRIKVRVWDEDddiksrv 1293
Cdd:cd04039     5 MEIKSITDLpPLKNMTRTGfdmDPFVIISFGRRVFRTSWRRHTLNPVFNERLAFEVypHEKNFDIQFKVLDKD------- 77

                          90       100
                  ....*....|....*....|..
gi 568960994 1294 kqhfKKESDDFLGQTIVEVRTL 1315
Cdd:cd04039    78 ----KFSFNDYVATGSLSVQEL 95
C2A_Tricalbin-like cd04044
C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 2089-2180 8.15e-05

C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 176009 [Multi-domain]  Cd Length: 124  Bit Score: 44.08  E-value: 8.15e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 2089 PFVEVcmlgpSLGDKKRKQGTKTKSNTWSPKYNETFQFILGNENRPgayeLHLSVKDYCFAREDRIIGMTVIQLQNIAEK 2168
Cdd:cd04044    26 PYVTF-----SISNRRELARTKVKKDTSNPVWNETKYILVNSLTEP----LNLTVYDFNDKRKDKLIGTAEFDLSSLLQN 96

                          90
                  ....*....|...
gi 568960994 2169 GSY-GAWYPLLKN 2180
Cdd:cd04044    97 PEQeNLTKNLLRN 109
C1_PIK3R-like_rpt1 cd20829
first protein kinase C conserved region 1 (C1 domain) found in uncharacterized ...
 1094-1135 9.93e-05

first protein kinase C conserved region 1 (C1 domain) found in uncharacterized phosphatidylinositol 3-kinase regulatory subunit-like proteins; The family includes a group of uncharacterized proteins that show high sequence similarity to vertebrate phosphatidylinositol 3-kinase regulatory subunits (PIK3Rs), which bind to activated (phosphorylated) protein-tyrosine kinases through its SH2 domain and regulate their kinase activity. Unlike typical PIK3Rs, members of this family have two C1 domains. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410379  Cd Length: 53  Bit Score: 41.95  E-value: 9.93e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 568960994 1094 HNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKC 1135
Cdd:cd20829     1 HRLVDVYFVTPILCRHCKDYIWGKGKVGVRCEDCHACFHLVC 42
C2E_Ferlin cd04037
C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 2099-2164 1.42e-04

C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fifth C2 repeat, C2E, and has a type-II topology.


Pssm-ID: 176002 [Multi-domain]  Cd Length: 124  Bit Score: 43.69  E-value: 1.42e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568960994 2099 SLGDKKRKQGTKTKSNTWSPKYNETFQF--ILgnenrPGAYELHLSVKDYCFAREDRIIGMTVIQLQN 2164
Cdd:cd04037    28 KLGKKKINDRDNYIPNTLNPVFGKMFELeaTL-----PGNSILKISVMDYDLLGSDDLIGETVIDLED 90
C1_DGK_typeI_rpt1 cd20799
first protein kinase C conserved region 1 (C1 domain) found in type I diacylglycerol kinases; ...
 1104-1145 1.50e-04

first protein kinase C conserved region 1 (C1 domain) found in type I diacylglycerol kinases; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. Type I DAG kinases (DGKs) contain EF-hand structures that bind Ca(2+) and recoverin homology domains, in addition to C1 and catalytic domains that are present in all DGKs. Type I DGKs, regulated by calcium binding, include three DGK isozymes (alpha, beta and gamma). DAG kinase alpha, also called 80 kDa DAG kinase, or diglyceride kinase alpha (DGK-alpha), is active upon cell stimulation, initiating the resynthesis of phosphatidylinositols and attenuating protein kinase C activity. DAG kinase beta, also called 90 kDa DAG kinase, or diglyceride kinase beta (DGK-beta), exhibits high phosphorylation activity for long-chain diacylglycerols. DAG kinase gamma, also called diglyceride kinase gamma (DGK-gamma), reverses the normal flow of glycerolipid biosynthesis by phosphorylating diacylglycerol back to phosphatidic acid. Members of this family contain two copies of the C1 domain. This model corresponds to the first one. DGK-alpha contains atypical C1 domains, while DGK-beta and DGK-gamma contain typical C1 domains that bind DAG and phorbol esters. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410349  Cd Length: 62  Bit Score: 41.59  E-value: 1.50e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 568960994 1104 PTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADCLQ 1145
Cdd:cd20799    16 PAYCNVCENMLVGLRKQGLCCTFCKYTVHERCVSRAPASCIR 57
C2A_Ferlin cd08373
C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 2088-2203 1.50e-04

C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 176019 [Multi-domain]  Cd Length: 127  Bit Score: 43.40  E-value: 1.50e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 2088 RPFVEVCMLGpslgDKKRkqgTKTKSNTWSPKYNETFQFILGNENRPGAYeLHLSVKDYCFAREDRIIGMTVIQLQNIAE 2167
Cdd:cd08373    16 DRIAKVTFRG----VKKK---TRVLENELNPVWNETFEWPLAGSPDPDES-LEIVVKDYEKVGRNRLIGSATVSLQDLVS 87

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 568960994 2168 KGSYGAWYPLLkNLSMDETGLTI-LRILSQRTSDDVA 2203
Cdd:cd08373    88 EGLLEVTEPLL-DSNGRPTGATIsLEVSYQPPDGAVG 123
C1_VAV3 cd20869
protein kinase C conserved region 1 (C1 domain) found in VAV3 protein; VAV3 is ubiquitously ...
 1094-1135 1.99e-04

protein kinase C conserved region 1 (C1 domain) found in VAV3 protein; VAV3 is ubiquitously expressed and functions as a phosphorylation-dependent guanine nucleotide exchange factor (GEF) for RhoA, RhoG, and Rac1. Its function has been implicated in the hematopoietic, bone, cerebellar, and cardiovascular systems. VAV3 is essential in axon guidance in neurons that control blood pressure and respiration. It is overexpressed in prostate cancer cells and plays a role in regulating androgen receptor transcriptional activity. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410419  Cd Length: 59  Bit Score: 41.35  E-value: 1.99e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 568960994 1094 HNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKC 1135
Cdd:cd20869     9 HDFKMHTFERVTSCKVCQMLLRGTFYQGYLCSKCGAGAHKEC 50
C2A_Synaptotagmin-14_16 cd08389
C2A domain first repeat present in Synaptotagmins 14 and 16; Synaptotagmin 14 and 16 are ...
 1217-1326 2.18e-04

C2A domain first repeat present in Synaptotagmins 14 and 16; Synaptotagmin 14 and 16 are membrane-trafficking proteins in specific tissues outside the brain. Both of these contain C-terminal tandem C2 repeats, but only Synaptotagmin 14 has an N-terminal transmembrane domain and a putative fatty-acylation site. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium and this is indeed the case here. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176035 [Multi-domain]  Cd Length: 124  Bit Score: 43.00  E-value: 2.18e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1217 KITITVVSAQGLQAKDKTGSSdpyvTVQV-------GKNKRRTKTIFGNlNPVWDEKFFFECHNSTD--RIKVRVwdedd 1287
Cdd:cd08389    17 KLTVTVIRAQDIPTKDRGGAS----SWQVhlvllpsKKQRAKTKVQRGP-NPVFNETFTFSRVEPEElnNMALRF----- 86

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 568960994 1288 diksRVKQHFKKESDDFLGQTIVEVRTLS--GEMDVWYNLE 1326
Cdd:cd08389    87 ----RLYGVERMRKERLIGEKVVPLSQLNleGETTVWLTLE 123
C1_RASSF5 cd20886
protein kinase C conserved region 1 (C1 domain) found in Ras association domain-containing ...
 1093-1143 2.84e-04

protein kinase C conserved region 1 (C1 domain) found in Ras association domain-containing protein 5 (RASSF5) and similar proteins; RASSF5, also called new ras effector 1 (NORE1), or regulator for cell adhesion and polarization enriched in lymphoid tissues (RAPL), is a member of a family of RAS effectors, of which there are currently 8 members (RASSF1-8), all containing a Ras-association (RA) domain of the Ral-GDS/AF6 type. It is expressed as three transcripts (A-C) via differential promoter usage and alternative splicing. RASSF5A is a pro-apoptotic Ras effector and functions as a Ras regulated tumor suppressor. RASSF5C is regulated by Ras related protein and modulates cellular adhesion. RASSF5 is a potential tumor suppressor that seems to be involved in lymphocyte adhesion by linking RAP1A activation upon T-cell receptor or chemokine stimulation to integrin activation. It contains a C1 domain, which is descibed in this model. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410436  Cd Length: 50  Bit Score: 40.44  E-value: 2.84e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568960994 1093 PHNFEVwTATTPTYCYECEGLlwgIARQGMKCLECGVKCHEKCQDLLNADC 1143
Cdd:cd20886     3 GHRFEP-GALGPGWCDLCGRY---ILSQALRCTNCKYTCHSECRDLVQLDC 49
C1_TNS2-like cd20826
protein kinase C conserved region 1 (C1 domain) found in tensin-2 like (TNS2-like) proteins; ...
 1093-1144 3.41e-04

protein kinase C conserved region 1 (C1 domain) found in tensin-2 like (TNS2-like) proteins; The TNS2-like group includes TNS2, and variants of TNS1 and TNS3. Tensin-2 (TNS2), also called C1 domain-containing phosphatase and tensin (C1-TEN), or tensin-like C1 domain-containing phosphatase (TENC1), is an essential component for the maintenance of glomerular basement membrane (GBM) structures. It regulates cell motility and proliferation. It may have phosphatase activity. TNS2 reduces AKT1 phosphorylation, lowers AKT1 kinase activity and interferes with AKT1 signaling. Tensin-1 (TNS1) plays a role in fibrillar adhesion formation. It may be involved in cell migration, cartilage development and in linking signal transduction pathways to the cytoskeleton. Tensin-3 (TNS3), also called tensin-like SH2 domain-containing protein 1 (TENS1), or tumor endothelial marker 6 (TEM6), may play a role in actin remodeling. It is involved in the dissociation of the integrin-tensin-actin complex. Typical TNS1 and TNS3 do not contain C1 domains, but some isoforms/variants do. Members of this family contain an N-terminal region with a zinc finger (C1 domain), a protein tyrosine phosphatase (PTP)-like domain and a protein kinase 2 (C2) domain, and a C-terminal region with SH2 and pTyr binding (PTB) domains. This model corresponds to C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410376  Cd Length: 52  Bit Score: 40.45  E-value: 3.41e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 568960994 1093 PHNFEVWTATTPTYCYECEGLLWGiarQGMKCLECGVKCHEKCQDLLNADCL 1144
Cdd:cd20826     2 SHSFKEKSFRKPRTCDVCKQIIWN---EGSSCRVCKYACHRKCEPKVTAACS 50
C1_Myosin-IXa cd20883
protein kinase C conserved region 1 (C1 domain) found in unconventional myosin-IXa and similar ...
 1094-1143 4.10e-04

protein kinase C conserved region 1 (C1 domain) found in unconventional myosin-IXa and similar proteins; Myosin-IXa, also called unconventional myosin-9a (Myo9a), is a single-headed, actin-dependent motor protein of the unconventional myosin IX class. It is expressed in several tissues and is enriched in the brain and testes. Myosin-IXa contains a Ras-associating (RA) domain, a motor domain, a protein kinase C conserved region 1 (C1), and a Rho GTPase activating domain (RhoGAP). Myosin-IXa binds the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) GluA2 subunit, and plays a key role in controlling the molecular structure and function of hippocampal synapses. Moreover, Myosin-IXa functions in epithelial cell morphology and differentiation, such that its knockout mice develop hydrocephalus and kidney dysfunction. Myosin-IXa regulates collective epithelial cell migration by targeting RhoGAP activity to cell-cell junctions. Myosin-IXa negatively regulates Rho GTPase signaling, and functions as a regulator of kidney tubule function. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410433  Cd Length: 58  Bit Score: 40.34  E-value: 4.10e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568960994 1094 HNFEVWTATTPTYCYECEGLLWGIARQGMkCLECGVKCHEKCQDLLNADC 1143
Cdd:cd20883     6 HIFKSTQYSIPTYCEYCSSLIWMMDRAYV-CKLCRYACHKKCCLKTTTKC 54
C2A_Synaptotagmin-4-11 cd08388
C2A domain first repeat present in Synaptotagmins 4 and 11; Synaptotagmin is a ...
 1220-1269 4.92e-04

C2A domain first repeat present in Synaptotagmins 4 and 11; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmins 4 and 11, class 4 synaptotagmins, are located in the brain. Their functions are unknown. They are distinguished from the other synaptotagmins by having and Asp to Ser substitution in their C2A domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176034 [Multi-domain]  Cd Length: 128  Bit Score: 41.95  E-value: 4.92e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568960994 1220 ITVVSAQGLQAKD-KTGSSDPYVTVQV---GKNKRRTKTIFGNLNPVWDEKFFF 1269
Cdd:cd08388    20 VNIIECRDLPAMDeQSGTSDPYVKLQLlpeKEHKVKTRVLRKTRNPVYDETFTF 73
C2C_Ferlin cd04018
C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 2089-2172 5.11e-04

C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175985 [Multi-domain]  Cd Length: 151  Bit Score: 42.62  E-value: 5.11e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 2089 PFVEVCMLGpslgdkkRKQGTKTKSNTWSPKYNETFQFilgNENRPGAYE-LHLSVKDYCFAREDRIIGMTVIQLQNIAE 2167
Cdd:cd04018    37 PYVEVSFAG-------QKVKTSVKKNSYNPEWNEQIVF---PEMFPPLCErIKIQIRDWDRVGNDDVIGTHFIDLSKISN 106


                  ....*
gi 568960994 2168 KGSYG 2172
Cdd:cd04018   107 SGDEG 111
C2C_KIAA1228 cd04030
C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins ...
 2100-2177 5.14e-04

C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins are uncharacterized human proteins. They were compiled by the Kazusa mammalian cDNA project which identified more than 2000 human genes. They are identified by 4 digit codes that precede the KIAA designation. Many KIAA genes are still functionally uncharacterized including KIAA1228. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175996 [Multi-domain]  Cd Length: 127  Bit Score: 41.87  E-value: 5.14e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 2100 LGDKKR--KQGTKTKSNTWSPKYNETFQFILGNENRPGAyELHLSVKD--YCFAREDRIIGMTVIQLQNIAEKGSYGAWY 2175
Cdd:cd04030    46 LPDKSKstRRKTSVKKDNLNPVFDETFEFPVSLEELKRR-TLDVAVKNskSFLSREKKLLGQVLIDLSDLDLSKGFTQWY 124


                  ..
gi 568960994 2176 PL 2177
Cdd:cd04030   125 DL 126
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
1179-1312 5.18e-04

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 45.52  E-value: 5.18e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1179 PEVFEVIQEMFQISKEDFVQYTKAAKQSVLDGTSKWS------------------AKITITVVSAQGLQAKDKTGSSDPY 1240
Cdd:COG5038   656 ATEGSTLPDLIDRTLDTFLVFPLRNPKGRIFITNYWKpiynaggsssktvydtpiGAIRVSVRKANDLRNEIPGGKSDPY 735

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1241 VTVQVGkNKRRTKTIFG--NLNPVWDEKFFFECHNSTDRIKVRVWDEDDDIKSR--------VKQHFKKESDDFLGQTIV 1310
Cdd:COG5038   736 ATVLVN-NLVKYRTIYGssTLNPIWNEILYVPVTSKNQRLTLECMDYEESGDDRnlgevninVSNVSKKDEDSALMETID 814


                  ..
gi 568960994 1311 EV 1312
Cdd:COG5038   815 GA 816
C2C_Ferlin cd04018
C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 1231-1320 5.51e-04

C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175985 [Multi-domain]  Cd Length: 151  Bit Score: 42.62  E-value: 5.51e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1231 KDKTGSSDPYVTVQVGKNKRRTKTIFGNLNPVWDEKFFFE------ChnstDRIKVRVWDEDddiksrvkqhfKKESDDF 1304
Cdd:cd04018    29 GEKKELVDPYVEVSFAGQKVKTSVKKNSYNPEWNEQIVFPemfpplC----ERIKIQIRDWD-----------RVGNDDV 93

                          90
                  ....*....|....*.
gi 568960994 1305 LGQTIVEVRTLSGEMD 1320
Cdd:cd04018    94 IGTHFIDLSKISNSGD 109
C2A_Munc13-like cd08676
C2 domain first repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
 2097-2177 6.96e-04

C2 domain first repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176058 [Multi-domain]  Cd Length: 153  Bit Score: 42.36  E-value: 6.96e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 2097 GPSLGD---KKRKQGTKTKSNTWSPKYNETFQFILGNENRPgayELHLSVKDycfaREDRIIGMTVIQLQNIAEKGsYGA 2173
Cdd:cd08676    78 KAVLKDtvpAKSIKVTEVKPQTLNPVWNETFRFEVEDVSND---QLHLDIWD----HDDDFLGCVNIPLKDLPSCG-LDS 149


                  ....
gi 568960994 2174 WYPL 2177
Cdd:cd08676   150 WFKL 153
C2A_Synaptotagmin-15-17 cd08390
C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a ...
 1215-1327 1.04e-03

C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. It is thought to be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues and is Ca2+ independent. Human synaptotagmin 15 has 2 alternatively spliced forms that encode proteins with different C-termini. The larger, SYT15a, contains a N-terminal TM region, a putative fatty-acylation site, and 2 tandem C terminal C2 domains. The smaller, SYT15b, lacks the C-terminal portion of the second C2 domain. Unlike most other synaptotagmins it is nearly absent in the brain and rather is found in the heart, lungs, skeletal muscle, and testis. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176036 [Multi-domain]  Cd Length: 123  Bit Score: 41.09  E-value: 1.04e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1215 SAKITITVVSAQGLQAKDKT-GSSDPYVTVQV---GKNKRRTKTIFGNLNPVWDEKFFFEChnSTDRIKVR-----VWDE 1285
Cdd:cd08390    13 EEQLTVSLIKARNLPPRTKDvAHCDPFVKVCLlpdERRSLQSKVKRKTQNPNFDETFVFQV--SFKELQRRtlrlsVYDV 90

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 568960994 1286 DddiksRVKQHfkkesdDFLGQTIVEVR--TLSGEMDVWYNLEK 1327
Cdd:cd08390    91 D-----RFSRH------CIIGHVLFPLKdlDLVKGGVVWRDLEP 123
C2A_MCTP_PRT_plant cd04022
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 2068-2179 1.11e-03

C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 175989 [Multi-domain]  Cd Length: 127  Bit Score: 41.17  E-value: 1.11e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 2068 KVTVKVIAINDL---NWQTTAmfRPFVEVCMLGpslgdkkRKQGTKTKSNTWSPKYNETFQFILGNENRPGAYELHLSV- 2143
Cdd:cd04022     1 KLVVEVVDAQDLmpkDGQGSS--SAYVELDFDG-------QKKRTRTKPKDLNPVWNEKLVFNVSDPSRLSNLVLEVYVy 71

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 568960994 2144 KDYCFAREDRIIGMTVIQLQNIAEKG-SYGAWYPLLK 2179
Cdd:cd04022    72 NDRRSGRRRSFLGRVRISGTSFVPPSeAVVQRYPLEK 108
C2A_C2C_Synaptotagmin_like cd08391
C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a ...
 2089-2177 1.20e-03

C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains either the first or third repeat in Synaptotagmin-like proteins with a type-I topology.


Pssm-ID: 176037 [Multi-domain]  Cd Length: 121  Bit Score: 40.74  E-value: 1.20e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 2089 PFVEVcmlgpSLGDKKRKqgTKTKSNTWSPKYNETFQFILGNEnrPGAyELHLSVKDYCFAREDrIIGMTVIQLQNIAEK 2168
Cdd:cd08391    30 PYVIV-----RVGAQTFK--SKVIKENLNPKWNEVYEAVVDEV--PGQ-ELEIELFDEDPDKDD-FLGRLSIDLGSVEKK 98


                  ....*....
gi 568960994 2169 GSYGAWYPL 2177
Cdd:cd08391    99 GFIDEWLPL 107
C2A_Synaptotagmin-1-5-6-9-10 cd08385
C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a ...
 2089-2162 1.35e-03

C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis as do synaptotagmins 5, 6, and 10. It is distinguished from the other synaptotagmins by having an N-glycosylated N-terminus. Synaptotagmins 5, 6, and 10, members of class 3 synaptotagmins, are located primarily in the brain and localized to the active zone and plasma membrane. They is distinguished from the other synaptotagmins by having disulfide bonds at its N-terminus. Synaptotagmin 6 also regulates the acrosome reaction, a unique Ca2+-regulated exocytosis, in sperm. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176031 [Multi-domain]  Cd Length: 124  Bit Score: 40.71  E-value: 1.35e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568960994 2089 PFVEVcMLGPslgDKKRKQGTKTKSNTWSPKYNETFQF-ILGNE--NRpgayELHLSVKDYC-FAREDrIIGMTVIQL 2162
Cdd:cd08385    39 PYVKV-YLLP---DKKKKFETKVHRKTLNPVFNETFTFkVPYSElgNK----TLVFSVYDFDrFSKHD-LIGEVRVPL 107
C1_DEF8 cd20819
protein kinase C conserved region 1 (C1 domain) found in differentially expressed in FDCP 8 ...
 1094-1135 1.43e-03

protein kinase C conserved region 1 (C1 domain) found in differentially expressed in FDCP 8 (DEF-8) and similar proteins; DEF-8 positively regulates lysosome peripheral distribution and ruffled border formation in osteoclasts. It is involved in bone resorption. DEF-8 contains a protein kinase C conserved region 1 (C1) domain followed by a putative zinc-RING and/or ribbon. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410369  Cd Length: 62  Bit Score: 38.80  E-value: 1.43e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 568960994 1094 HNFEVWTATTPT--YCYECEGLLWGIARQGMKCLECGVKCHEKC 1135
Cdd:cd20819     6 HHFVLQKSKSSSkqYCDKCCGIIWGLLQTWYRCTDCGYRCHSKC 49
C2B_Synaptotagmin-17 cd08410
C2 domain second repeat present in Synaptotagmin 17; Synaptotagmin is a membrane-trafficking ...
 1215-1310 1.80e-03

C2 domain second repeat present in Synaptotagmin 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176055 [Multi-domain]  Cd Length: 135  Bit Score: 40.64  E-value: 1.80e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1215 SAKITITVVSAQGLQAKDKTGSSDPYVTVQ------VGKNKrRTKTIFGNLNPVWDEKFFFECHNSTdrikvrvwDEDDD 1288
Cdd:cd08410    13 AGRLNVDIIRAKQLLQTDMSQGSDPFVKIQlvhglkLIKTK-KTSCMRGTIDPFYNESFSFKVPQEE--------LENVS 83

                          90       100
                  ....*....|....*....|..
gi 568960994 1289 IKSRVKQHFKKESDDFLGQTIV 1310
Cdd:cd08410    84 LVFTVYGHNVKSSNDFIGRIVI 105
C2_PKC_epsilon cd04014
C2 domain in Protein Kinase C (PKC) epsilon; A single C2 domain is found in PKC epsilon. The ...
 1215-1348 1.90e-03

C2 domain in Protein Kinase C (PKC) epsilon; A single C2 domain is found in PKC epsilon. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1 (alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-II topology.


Pssm-ID: 175981 [Multi-domain]  Cd Length: 132  Bit Score: 40.33  E-value: 1.90e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 1215 SAKITITVVSAQGLQAKD--------KTGSS--DPYVTVQV-----GKNKRRTKTifgnLNPVWDEKFFFECHNstdrik 1279
Cdd:cd04014     3 TGTLKIKICEAVDLKPTDwstrhavpKKGSQllDPYVSIDVddthiGKTSTKPKT----NSPVWNEEFTTEVHN------ 72

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568960994 1280 vrvwdeDDDIKSRVKQHFKKESDDFLGQTIVEVRTL----SGEMDVWYNLEKrtdksavsgAIRLKINVEIKG 1348
Cdd:cd04014    73 ------GRNLELTVFHDAAIGPDDFVANCTISFEDLiqrgSGSFDLWVDLEP---------QGKLHVKIELKG 130
C1_VAV1 cd20867
protein kinase C conserved region 1 (C1 domain) found in VAV1 protein; VAV1 is expressed ...
 1094-1135 2.15e-03

protein kinase C conserved region 1 (C1 domain) found in VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410417  Cd Length: 57  Bit Score: 38.39  E-value: 2.15e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 568960994 1094 HNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKC 1135
Cdd:cd20867     7 HDFQMFSFEETTSCKACQMLLRGTFYQGYRCHRCRAPAHKEC 48
C1_DGKepsilon_typeIII_rpt1 cd20801
first protein kinase C conserved region 1 (C1 domain) found in type III diacylglycerol kinase, ...
 1094-1135 2.98e-03

first protein kinase C conserved region 1 (C1 domain) found in type III diacylglycerol kinase, DAG kinase epsilon, and similar proteins; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. DAG kinase epsilon, also called diglyceride kinase epsilon (DGK-epsilon), is the only isoform classified as type III; it possesses a hydrophobic domain in addition to C1 and catalytic domains that are present in all DGKs, and shows selectivity for acyl chains. It is highly selective for arachidonate-containing species of DAG. It may terminate signals transmitted through arachidonoyl-DAG or may contribute to the synthesis of phospholipids with defined fatty acid composition. DAG kinase epsilon contains two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410351  Cd Length: 54  Bit Score: 37.68  E-value: 2.98e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 568960994 1094 HNfevWTATT----PTYCYECEGLLWgiarQGMKCLECGVKCHEKC 1135
Cdd:cd20801     4 HH---WVSTDlfskPTYCSVCETLIL----SGAFCDCCGLCVDEGC 42
C1_GMIP-like cd20816
protein kinase C conserved region 1 (C1 domain) found in the GEM-interacting protein (GMIP) ...
 1073-1146 3.40e-03

protein kinase C conserved region 1 (C1 domain) found in the GEM-interacting protein (GMIP)-like family; The GMIP-like family includes GMIP, Rho GTPase-activating protein 29 (ARHGAP29) and Rho GTPase-activating protein 45 (ARHGAP45). GMIP is a RhoA-specific GTPase-activating protein that acts as a key factor in saltatory neuronal migration. It associates with the Rab27a effector JFC1 and modulates vesicular transport and exocytosis. ARHGAP29, also called PTPL1-associated RhoGAP protein 1 (PARG1) or Rho-type GTPase-activating protein 29, is a GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. It has strong activity toward RHOA, and weaker activity toward RAC1 and CDC42. ARHGAP29 may act as a specific effector of RAP2A to regulate Rho. In concert with RASIP1, ARHGAP29 suppresses RhoA signaling and dampens ROCK and MYH9 activities in endothelial cells and plays an essential role in blood vessel tubulogenesis. ARHGAP45, also called minor histocompatibility antigen HA-1 (mHag HA-1), is a Rac-GAP (GTPase-Activating Protein) in endothelial cells. It acts as a novel regulator of endothelial integrity. ARHGAP45 contains a GTPase activator for the Rho-type GTPases (RhoGAP) domain that would be able to negatively regulate the actin cytoskeleton as well as cell spreading. However, it also contains N-terminally a BAR-domin which can play an autoinhibitory effect on this RhoGAP activity. Members of this family contain a zinc-binding C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410366  Cd Length: 51  Bit Score: 37.62  E-value: 3.40e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568960994 1073 KMHVFRKTlqaliypissttphnfevwtaTTPTYCYECEGLlwgIARQGMKCLECGVKCHEKCQDLLNADCLQR 1146
Cdd:cd20816     1 QTHRFRRL---------------------RTPSKCRECDSY---VYFNGAECEECGLACHKKCLETLAIQCGHK 50
C1_Stac2 cd20881
protein kinase C conserved region 1 (C1 domain) found in SH3 and cysteine-rich ...
 1094-1135 3.71e-03

protein kinase C conserved region 1 (C1 domain) found in SH3 and cysteine-rich domain-containing protein 2 (Stac2) and similar proteins; Stac2, also called 24b2/Stac2, or Src homology 3 and cysteine-rich domain-containing protein 2, plays a redundant role in promoting the expression of calcium channel CACNA1S at the cell membrane, and thereby contributes to increased channel activity. It slows down the inactivation rate of the calcium channel CACNA1C. Stac2 contains a cysteine-rich C1 domain and one SH3 domain at the C-terminus. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410431  Cd Length: 59  Bit Score: 37.51  E-value: 3.71e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 568960994 1094 HNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKC 1135
Cdd:cd20881     6 HSFQEHVFKKPSPCELCHQMIVGNSKQGLRCKMCKVSVHLWC 47
C1_DGKbeta_rpt1 cd20845
first protein kinase C conserved region 1 (C1 domain) found in diacylglycerol kinase beta (DAG ...
 1104-1144 3.95e-03

first protein kinase C conserved region 1 (C1 domain) found in diacylglycerol kinase beta (DAG kinase beta) and similar proteins; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. DAG kinase beta, also called 90 kDa diacylglycerol kinase, or diglyceride kinase beta (DGK-beta), exhibits high phosphorylation activity for long-chain diacylglycerols. It is classified as a type I DAG kinase (DGK), containing EF-hand structures that bind Ca(2+) and a recoverin homology domain, in addition to C1 and catalytic domains that are present in all DGKs. As a type I DGK, it is regulated by calcium binding. DAG kinase beta contains two copies of the C1 domain. This model corresponds to the first one. DGK-beta contains typical C1 domains that bind DAG and phorbol esters. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410395  Cd Length: 66  Bit Score: 37.91  E-value: 3.95e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 568960994 1104 PTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADCL 1144
Cdd:cd20845    18 PAYCNLCLNMLVGLGKQGLCCSFCKYTVHERCVQRAPASCI 58
C1_DGKgamma_rpt1 cd20846
first protein kinase C conserved region 1 (C1 domain) found in diacylglycerol kinase gamma ...
 1104-1135 4.01e-03

first protein kinase C conserved region 1 (C1 domain) found in diacylglycerol kinase gamma (DAG kinase gamma) and similar proteins; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. DAG kinase gamma, also called diglyceride kinase gamma (DGK-gamma), reverses the normal flow of glycerolipid biosynthesis by phosphorylating diacylglycerol back to phosphatidic acid. It is classified as a type I DAG kinase (DGK), containing EF-hand structures that bind Ca(2+) and a recoverin homology domain, in addition to C1 and catalytic domains that are present in all DGKs. As a type I DGK, it is regulated by calcium binding. DGK-gamma contains two copies of the C1 domain. This model corresponds to the first one. DGK-gamma contains typical C1 domains that bind DAG and phorbol esters. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410396  Cd Length: 73  Bit Score: 37.99  E-value: 4.01e-03
                          10        20        30
                  ....*....|....*....|....*....|..
gi 568960994 1104 PTYCYECEGLLWGIARQGMKCLECGVKCHEKC 1135
Cdd:cd20846    27 PAYCNFCHTMLLGVRKQGLCCSFCKYTVHERC 58
C2_E3_ubiquitin_ligase cd04021
C2 domain present in E3 ubiquitin ligase; E3 ubiquitin ligase is part of the ubiquitylation ...
 2089-2168 6.49e-03

C2 domain present in E3 ubiquitin ligase; E3 ubiquitin ligase is part of the ubiquitylation mechanism responsible for controlling surface expression of membrane proteins. The sequential action of several enzymes are involved: ubiquitin-activating enzyme E1, ubiquitin-conjugating enzyme E2, and ubiquitin-protein ligase E3 which is responsible for substrate recognition and promoting the transfer of ubiquitin to the target protein. E3 ubiquitin ligase is composed of an N-terminal C2 domain, 4 WW domains, and a HECTc domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175988 [Multi-domain]  Cd Length: 125  Bit Score: 38.80  E-value: 6.49e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 2089 PFVEVCmlgpSLGDKKRKqgTKTKSNTWSPKYNETFQfILGNENRpgayELHLSVKDYCFAREDRIIGMTVIQLQNIAEK 2168
Cdd:cd04021    24 PYVEVT----VDGQPPKK--TEVSKKTSNPKWNEHFT-VLVTPQS----TLEFKVWSHHTLKADVLLGEASLDLSDILKN 92
C2A_Rabphilin_Doc2 cd04035
C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 2089-2164 6.66e-03

C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176000 [Multi-domain]  Cd Length: 123  Bit Score: 38.80  E-value: 6.66e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568960994 2089 PFVEVCMLGPSlgDKKRKQGTKTKSNTWSPKYNETFQFILGNENRPGAYELHLSVKDycfarEDRI----IGMTVIQLQN 2164
Cdd:cd04035    38 PYVKLNLLPGA--SKATKLRTKTVHKTRNPEFNETLTYYGITEEDIQRKTLRLLVLD-----EDRFgndfLGETRIPLKK 110
C1_DGKdelta_rpt1 cd20847
first protein kinase C conserved region 1 (C1 domain) found in diacylglycerol kinase delta ...
 1094-1143 6.75e-03

first protein kinase C conserved region 1 (C1 domain) found in diacylglycerol kinase delta (DAG kinase delta) and similar proteins; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. DAG kinase delta, also called 130 kDa diacylglycerol kinase, or diglyceride kinase delta (DGK-delta), is a residential lipid kinase in the endoplasmic reticulum. It promotes lipogenesis and is involved in triglyceride biosynthesis. It is classified as a type II DAG kinase (DGK), containing pleckstrin homology (PH) and sterile alpha motifs (SAM) domains, in addition to C1 and catalytic domains that are present in all DGKs. The SAM domain mediates oligomerization of type II DGKs. DAG kinase delta contains two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410397  Cd Length: 85  Bit Score: 37.77  E-value: 6.75e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568960994 1094 HNFEVWTATTPTYCYECEGLLWGIARQGMKCLECGVKCHEKCQDLLNADC 1143
Cdd:cd20847    25 HNWYACSHARPTYCNVCREALSGVTSHGLSCEVCKFKAHKRCAVRATNNC 74
C2B_Synaptotagmin-like cd04050
C2 domain second repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
 2088-2145 7.72e-03

C2 domain second repeat present in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176015 [Multi-domain]  Cd Length: 105  Bit Score: 37.93  E-value: 7.72e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 568960994 2088 RPFVEVcmlgpSLGDKKRKqgTKTKSNTWSPKYNETFQFILGNenrPGAYELHLSVKD 2145
Cdd:cd04050    22 SPYVEL-----TVGKTTQK--SKVKERTNNPVWEEGFTFLVRN---PENQELEIEVKD 69
C1_Stac1 cd20880
protein kinase C conserved region 1 (C1 domain) found in SH3 and cysteine-rich ...
 1094-1137 8.77e-03

protein kinase C conserved region 1 (C1 domain) found in SH3 and cysteine-rich domain-containing protein (Stac1) and similar proteins; Stac1, also called Src homology 3 and cysteine-rich domain-containing protein, promotes expression of the ion channel CACNA1H at the cell membrane, and thereby contributes to the regulation of channel activity. It plays a minor and redundant role in promoting the expression of calcium channel CACNA1S at the cell membrane, and thereby contributes to increased channel activity. It slows down the inactivation rate of the calcium channel CACNA1C. Stac1 contains a cysteine-rich C1 domain and two SH3 domains at the C-terminus. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410430  Cd Length: 57  Bit Score: 36.46  E-value: 8.77e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 568960994 1094 HNFEVWTATTPTYCYECEGLLWGI-ARQGMKCLECGVKCHEKCQD 1137
Cdd:cd20880     3 HSFQEYIFKKPTFCDVCNHMIVGTnAKHGLRCKACKMSIHHKCTD 47
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH