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Conserved domains on  [gi|74220133|dbj|BAE31254|]
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unnamed protein product, partial [Mus musculus]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
SMP_SF super family cl45903
synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain superfamily; The SMP ...
 127-302 1.22e-123

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain superfamily; The SMP domain is a lipid transport domain found in phospholipid transfer proteins such as synaptotagmin family proteins, tricalbin (TCB) family proteins, maintenance of mitochondrial morphology protein 1 (MMM1), mitochondrial distribution and morphology protein 12 (MDM12), mitochondrial distribution and morphology protein 34 (MDM34), PDZ domain-containing protein 8 (PDZD8), testis-expressed protein 2 (TEX2), meiotically up-regulated gene 190 protein (Mug190), C2 domain-containing protein 2 (C2CD2) and C2 domain-containing protein 2-like (C2CD2L). The SMP domain belongs to a superfamily of lipid/hydrophobic ligand-binding domains called TULIP (tubular lipid-binding proteins). It adopts a TULIP fold with two alpha helices and a highly curved antiparallel beta sheet forming a cornucopia-like structure.


The actual alignment was detected with superfamily member cd21679:

Pssm-ID: 459248  Cd Length: 176  Bit Score: 362.96  E-value: 1.22e-123
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 127 EKAEWLNKIVAQVWPFLGQYMEKLLAETVAPAVRGANPHLQTFTFTRVELGEKPLRIIGVKVHPSQRKDQILLDLNVSYV 206
Cdd:cd21679   1 EKAEWLNKILAQAWPFVGQYLEKLLVESIAPAIRASNNHLQTFSFTKVDLGEKPLKVVGVKAHTEFDKRQIILDLHISYV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 207 GDVQIDVEVKKYFCKAGVKGMQLHGVLRVILEPLTGDLPIVGAVSMFFIKRPTLDINWTGMTNLLDIPGLSSLSDTMIMD 286
Cdd:cd21679  81 GDVEINVEVKKYFCKAGVKGIQLHGMLRVILEPLIGDVPLVGAVTMFFIRRPVLDINWTGMTNLLDIPGLSSMSDTMIMD 160

                       170
                ....*....|....*.
gi 74220133 287 SIAAFLVLPNRLLVPL 302
Cdd:cd21679 161 TIASFLVLPNRLTVPL 176
C2A_C2C_Synaptotagmin_like cd08391
C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a ...
 319-438 2.67e-47

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: 162.08  E-value: 2.67e-47
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 319 GIIRIHLLAARGLSSKDKYVKGLIEGKSDPYALVRVGTQTFCSRVIDEELNPHWGETYEVIVHEVPGQEIEVEVFDKDPD 398
Cdd:cd08391   1 GVLRIHVIEAQDLVAKDKFVGGLVKGKSDPYVIVRVGAQTFKSKVIKENLNPKWNEVYEAVVDEVPGQELEIELFDEDPD 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 74220133 399 KDDFLGRMKLDVGKVLQAGVLDNWYPLQG-GQGQVHLRLEW 438
Cdd:cd08391  81 KDDFLGRLSIDLGSVEKKGFIDEWLPLEDvKSGRLHLKLEW 121
C2B_Synaptotagmin-like cd04050
C2 domain second repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
 469-573 1.52e-46

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: 159.27  E-value: 1.52e-46
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 469 ILVVYLDRAQDLPLKKGNKEPNPMVQLSVQDVTRESKATYSTNSPVWEEAFRFFLQDPRSQELDVQVKDDSRALTLGALT 548
Cdd:cd04050   1 LLFVYLDSAKNLPLAKSTKEPSPYVELTVGKTTQKSKVKERTNNPVWEEGFTFLVRNPENQELEIEVKDDKTGKSLGSLT 80

                        90       100
                ....*....|....*....|....*
gi 74220133 549 LPLARLLTASELTLDQWFQLSSSGP 573
Cdd:cd04050  81 LPLSELLKEPDLTLDQPFPLDNSGP 105
 
Name Accession Description Interval E-value
SMP_ESyt1 cd21679
synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in extended ...
 127-302 1.22e-123

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in extended synaptotagmin-1 (E-Syt1) and similar proteins; Extended synaptotagmin-1 (E-Syt1), also called membrane-bound C2 domain-containing protein (MBC2), binds glycerophospholipids in a barrel-like domain and may play a role in cellular lipid transport. It also binds calcium via the C2 domains and translocates to sites of contact between the endoplasmic reticulum and the cell membrane in response to increased cytosolic calcium levels. E-Syt1 tethers the endoplasmic reticulum to the cell membrane and promotes the formation of appositions between the endoplasmic reticulum and the cell membrane. E-Syt1 consists of an N-terminal endoplasmic reticulum (ER)-membrane anchor, a central SMP-domain, and five C-terminal cytoplasmic C2-domains. The ER-membrane anchor and C2 domains are required for tethering, and the SMP domain may be implicated in lipid transport. This model corresponds to the SMP domain.


Pssm-ID: 439235  Cd Length: 176  Bit Score: 362.96  E-value: 1.22e-123
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 127 EKAEWLNKIVAQVWPFLGQYMEKLLAETVAPAVRGANPHLQTFTFTRVELGEKPLRIIGVKVHPSQRKDQILLDLNVSYV 206
Cdd:cd21679   1 EKAEWLNKILAQAWPFVGQYLEKLLVESIAPAIRASNNHLQTFSFTKVDLGEKPLKVVGVKAHTEFDKRQIILDLHISYV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 207 GDVQIDVEVKKYFCKAGVKGMQLHGVLRVILEPLTGDLPIVGAVSMFFIKRPTLDINWTGMTNLLDIPGLSSLSDTMIMD 286
Cdd:cd21679  81 GDVEINVEVKKYFCKAGVKGIQLHGMLRVILEPLIGDVPLVGAVTMFFIRRPVLDINWTGMTNLLDIPGLSSMSDTMIMD 160

                       170
                ....*....|....*.
gi 74220133 287 SIAAFLVLPNRLLVPL 302
Cdd:cd21679 161 TIASFLVLPNRLTVPL 176
SMP_LBD pfam17047
Synaptotagmin-like mitochondrial-lipid-binding domain; SMP is a proposed lipid-binding module, ...
 125-303 3.83e-80

Synaptotagmin-like mitochondrial-lipid-binding domain; SMP is a proposed lipid-binding module, ie a synaptotagmin-like mitochondrial-lipid-binding domain found in eukaryotes. The SMP domain has a beta-barrel structure like protein modules in the tubular-lipid-binding (TULIP) superfamily. It dimerizes to form an approximately 90-Angstrom-long cylinder traversed by a channel lined entirely with hydrophobic residues. The following two C2 domains then form arched structures flexibly linked to the SMP domain. The SMP domain is a lipid-binding domain that links the ER with other lipid bilayer-membranes within the cell.


Pssm-ID: 465339  Cd Length: 180  Bit Score: 251.11  E-value: 3.83e-80
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133   125 DVEKAEWLNKIVAQVWPFLGQYMEKLLAETVAPAVRGANPHLQTFTFTRVELGEKPLRIIGVKVHPSQ-RKDQILLDLNV 203
Cdd:pfam17047   1 DTERAEWLNKTVKHMWPFICQFIEKLFRETIEPAVRGANTHLSTFSFTKVDVGQQPLRINGVKVYTENvDKRQIILDLQI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133   204 SYVGDVQIDVEVKKYFCKAGVKGMQLHGVLRVILEPLTGDLPIVGAVSMFFIKRPTLDINWTGMTNLLDIPGLSSLSDTM 283
Cdd:pfam17047  81 SFVGNCEIDLEIKRYFCRAGVKSIQIHGTMRVILEPLIGDMPLVGALSIFFLRKPLLEINWTGLTNLLDVPGLNGLSDTI 160

                         170       180
                  ....*....|....*....|
gi 74220133   284 IMDSIAAFLVLPNRLLVPLV 303
Cdd:pfam17047 161 ILDIISNYLVLPNRITVPLV 180
C2A_C2C_Synaptotagmin_like cd08391
C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a ...
 319-438 2.67e-47

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: 162.08  E-value: 2.67e-47
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 319 GIIRIHLLAARGLSSKDKYVKGLIEGKSDPYALVRVGTQTFCSRVIDEELNPHWGETYEVIVHEVPGQEIEVEVFDKDPD 398
Cdd:cd08391   1 GVLRIHVIEAQDLVAKDKFVGGLVKGKSDPYVIVRVGAQTFKSKVIKENLNPKWNEVYEAVVDEVPGQELEIELFDEDPD 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 74220133 399 KDDFLGRMKLDVGKVLQAGVLDNWYPLQG-GQGQVHLRLEW 438
Cdd:cd08391  81 KDDFLGRLSIDLGSVEKKGFIDEWLPLEDvKSGRLHLKLEW 121
C2B_Synaptotagmin-like cd04050
C2 domain second repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
 469-573 1.52e-46

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: 159.27  E-value: 1.52e-46
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 469 ILVVYLDRAQDLPLKKGNKEPNPMVQLSVQDVTRESKATYSTNSPVWEEAFRFFLQDPRSQELDVQVKDDSRALTLGALT 548
Cdd:cd04050   1 LLFVYLDSAKNLPLAKSTKEPSPYVELTVGKTTQKSKVKERTNNPVWEEGFTFLVRNPENQELEIEVKDDKTGKSLGSLT 80

                        90       100
                ....*....|....*....|....*
gi 74220133 549 LPLARLLTASELTLDQWFQLSSSGP 573
Cdd:cd04050  81 LPLSELLKEPDLTLDQPFPLDNSGP 105
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
125-589 8.48e-29

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


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 122.95  E-value: 8.48e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133  125 DVEKAEWLNKIVAQVWPFLGQYMEKLLAETVAPAVRGANPH------LQTFTftrveLGEKPLRIIGVKVHPSQRKDQIL 198
Cdd:COG5038  219 DYESVEWLNTFLQKFWPIIEPSISQQVVDQVNQQLAEAIPSfidalaLDEFT-----LGSKPPRIDGIRSYPSTESDTVV 293

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133  199 LDLNVSY----VGDV-------------QIDVEVKKYFCKAG----VKGMQLHGVLRVILEpLTGDLPIVGAVSMFFIKR 257
Cdd:COG5038  294 MDVDFSFtphdISDVtatsarasvnpkiSLVVKKGKSFGSFTlpilVEDLFFKGRVRVRVE-LMSKYPFIKTVSFQLLEV 372

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133  258 PTLDINWTGM------TNLLDIPGLSSLSDTMIMDSIAAFLVLPNRLLVplvpDLQDVAQLRSPLPRGIIRIHLLAARGL 331
Cdd:COG5038  373 PEFDFILVPLggdffgVDIFAIPGLSRFIQEIINSTLGPMLLPPNSLTI----DISQIMAGDSGTAIGVVEVKIKSAEGL 448

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133  332 SSKDkyvkGLIEGKSDPYalVRVGTQTF---CSRVIDEELNPHWGETYEVIVHEVpGQEIEVEV-FDKDPDKDDFLGRMK 407
Cdd:COG5038  449 KKSD----STINGTVDPY--ITVTFSDRvigKTRVKKNTLNPVWNETFYILLNSF-TDPLNLSLyDFNSFKSDKVVGSTQ 521

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133  408 LDVGKVLQAGVLDN--WYPLQGGQ--GQVHLRLEWLSLLPDAEKLDqvlqwnrGITSRPEPPSAAILVVYLDRAQDLplk 483
Cdd:COG5038  522 LDLALLHQNPVKKNelYEFLRNTKnvGRLTYDLRFFPVIEDKKELK-------GSVEPLEDSNTGILKVTLREVKAL--- 591

                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133  484 kgnKEPNPMVQLSVQDVTRESKATYS------TNSPVWEEAFRFFLQDPRSQELDVQVKDDSRALTLGALTLPLARLLTA 557
Cdd:COG5038  592 ---DELSSKKDNKSAELYTNAKEVYStgklkfTNHPSWNLQYNVLVTDRKNSSIKVVTFDVQSGKVIATEGSTLPDLIDR 668

                        490       500       510
                 ....*....|....*....|....*....|..
gi 74220133  558 SELTLdQWFQLSSsgPNSRLYMKLVMRILYLD 589
Cdd:COG5038  669 TLDTF-LVFPLRN--PKGRIFITNYWKPIYNA 697
C2 pfam00168
C2 domain;
319-425 1.82e-16

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 75.43  E-value: 1.82e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133   319 GIIRIHLLAARGLSSKDKYvkglieGKSDPYALVRV--GTQTFCSRVIDEELNPHWGETYEVIVHEVPGQEIEVEVF-DK 395
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKDGN------GTSDPYVKVYLldGKQKKKTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYdYD 74

                          90       100       110
                  ....*....|....*....|....*....|
gi 74220133   396 DPDKDDFLGRMKLDVGKVLQAGVLDNWYPL 425
Cdd:pfam00168  75 RFGRDDFIGEVRIPLSELDSGEGLDGWYPL 104
C2 pfam00168
C2 domain;
469-568 2.66e-15

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 71.97  E-value: 2.66e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133   469 ILVVYLDRAQDLPLKKGNKEPNPMVQLSVQD--VTRESKATYSTNSPVWEEAFRFFLQDPRSQELDVQVKDDSRAL---T 543
Cdd:pfam00168   2 RLTVTVIEAKNLPPKDGNGTSDPYVKVYLLDgkQKKKTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRFGrddF 81

                          90       100
                  ....*....|....*....|....*
gi 74220133   544 LGALTLPLARLLtaSELTLDQWFQL 568
Cdd:pfam00168  82 IGEVRIPLSELD--SGEGLDGWYPL 104
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 469-556 5.42e-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: 68.28  E-value: 5.42e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133    469 ILVVYLDRAQDLPLKKGNKEPNPMVQLSVQDVTRESKAT---YSTNSPVWEEAFRFFLQDPRSQELDVQVKDD---SRAL 542
Cdd:smart00239   1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGDPKEKKKTkvvKNTLNPVWNETFEFEVPPPELAELEIEVYDKdrfGRDD 80

                           90
                   ....*....|....
gi 74220133    543 TLGALTLPLARLLT 556
Cdd:smart00239  81 FIGQVTIPLSDLLL 94
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 320-422 4.28e-12

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: 62.89  E-value: 4.28e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133    320 IIRIHLLAARGLSSKDKYvkglieGKSDPYALVRVGTQ---TFCSRVIDEELNPHWGETYEVIVHEVPGQEIEVEVF-DK 395
Cdd:smart00239   1 TLTVKIISARNLPPKDKG------GKSDPYVKVSLDGDpkeKKKTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYdKD 74

                           90       100
                   ....*....|....*....|....*..
gi 74220133    396 DPDKDDFLGRMKLDVGKVLQAGVLDNW 422
Cdd:smart00239  75 RFGRDDFIGQVTIPLSDLLLGGRHEKL 101
 
Name Accession Description Interval E-value
SMP_ESyt1 cd21679
synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in extended ...
 127-302 1.22e-123

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in extended synaptotagmin-1 (E-Syt1) and similar proteins; Extended synaptotagmin-1 (E-Syt1), also called membrane-bound C2 domain-containing protein (MBC2), binds glycerophospholipids in a barrel-like domain and may play a role in cellular lipid transport. It also binds calcium via the C2 domains and translocates to sites of contact between the endoplasmic reticulum and the cell membrane in response to increased cytosolic calcium levels. E-Syt1 tethers the endoplasmic reticulum to the cell membrane and promotes the formation of appositions between the endoplasmic reticulum and the cell membrane. E-Syt1 consists of an N-terminal endoplasmic reticulum (ER)-membrane anchor, a central SMP-domain, and five C-terminal cytoplasmic C2-domains. The ER-membrane anchor and C2 domains are required for tethering, and the SMP domain may be implicated in lipid transport. This model corresponds to the SMP domain.


Pssm-ID: 439235  Cd Length: 176  Bit Score: 362.96  E-value: 1.22e-123
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 127 EKAEWLNKIVAQVWPFLGQYMEKLLAETVAPAVRGANPHLQTFTFTRVELGEKPLRIIGVKVHPSQRKDQILLDLNVSYV 206
Cdd:cd21679   1 EKAEWLNKILAQAWPFVGQYLEKLLVESIAPAIRASNNHLQTFSFTKVDLGEKPLKVVGVKAHTEFDKRQIILDLHISYV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 207 GDVQIDVEVKKYFCKAGVKGMQLHGVLRVILEPLTGDLPIVGAVSMFFIKRPTLDINWTGMTNLLDIPGLSSLSDTMIMD 286
Cdd:cd21679  81 GDVEINVEVKKYFCKAGVKGIQLHGMLRVILEPLIGDVPLVGAVTMFFIRRPVLDINWTGMTNLLDIPGLSSMSDTMIMD 160

                       170
                ....*....|....*.
gi 74220133 287 SIAAFLVLPNRLLVPL 302
Cdd:cd21679 161 TIASFLVLPNRLTVPL 176
SMP_ESyt2 cd21680
synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in extended ...
 125-302 3.84e-93

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in extended synaptotagmin-2 (E-Syt2) and similar proteins; Extended synaptotagmin-2 (E-Syt2), also called Chr2Syt, tethers the endoplasmic reticulum to the cell membrane and promotes the formation of appositions between the endoplasmic reticulum and the cell membrane. It binds glycerophospholipids in a barrel-like domain and may play a role in cellular lipid transport. E-Syt2 plays a role in fibroblast growth factor (FGF) signaling via its role in the rapid internalization of FGFreceptor 1 (FGFR1) that has been activated by FGF1 binding; this occurs most likely via the AP-2 complex. E-Syt2 consists of an N-terminal endoplasmic reticulum (ER)-membrane anchor, a central SMP-domain, and three C-terminal cytoplasmic C2-domains. The ER-membrane anchor and C2 domains are required for tethering, and the SMP domain may be implicated in lipid transport. This model corresponds to SMP domain.


Pssm-ID: 439236  Cd Length: 179  Bit Score: 284.86  E-value: 3.84e-93
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 125 DVEKAEWLNKIVAQVWPFLGQYMEKLLAETVAPAVRGANPHLQTFTFTRVELGEKPLRIIGVKVHPSQ-RKDQILLDLNV 203
Cdd:cd21680   1 DTERAEWLNKTVKHMWPFICQFIEKLFRETIEPAVRGANAHLSTFSFTKIDLGDQPLRINGVKVYTENvDKRQIILDLQI 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 204 SYVGDVQIDVEVKKYFCKAGVKGMQLHGVLRVILEPLTGDLPIVGAVSMFFIKRPTLDINWTGMTNLLDIPGLSSLSDTM 283
Cdd:cd21680  81 SFVGNCEIDLEIKRYFCRAGVKSIQIHGTMRVILEPLIGDMPLVGALSIFFLRKPLLEINWTGLTNLLDIPGLNGLSDTI 160

                       170
                ....*....|....*....
gi 74220133 284 IMDSIAAFLVLPNRLLVPL 302
Cdd:cd21680 161 ILDIISNYLVLPNRITVPL 179
SMP_LBD pfam17047
Synaptotagmin-like mitochondrial-lipid-binding domain; SMP is a proposed lipid-binding module, ...
 125-303 3.83e-80

Synaptotagmin-like mitochondrial-lipid-binding domain; SMP is a proposed lipid-binding module, ie a synaptotagmin-like mitochondrial-lipid-binding domain found in eukaryotes. The SMP domain has a beta-barrel structure like protein modules in the tubular-lipid-binding (TULIP) superfamily. It dimerizes to form an approximately 90-Angstrom-long cylinder traversed by a channel lined entirely with hydrophobic residues. The following two C2 domains then form arched structures flexibly linked to the SMP domain. The SMP domain is a lipid-binding domain that links the ER with other lipid bilayer-membranes within the cell.


Pssm-ID: 465339  Cd Length: 180  Bit Score: 251.11  E-value: 3.83e-80
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133   125 DVEKAEWLNKIVAQVWPFLGQYMEKLLAETVAPAVRGANPHLQTFTFTRVELGEKPLRIIGVKVHPSQ-RKDQILLDLNV 203
Cdd:pfam17047   1 DTERAEWLNKTVKHMWPFICQFIEKLFRETIEPAVRGANTHLSTFSFTKVDVGQQPLRINGVKVYTENvDKRQIILDLQI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133   204 SYVGDVQIDVEVKKYFCKAGVKGMQLHGVLRVILEPLTGDLPIVGAVSMFFIKRPTLDINWTGMTNLLDIPGLSSLSDTM 283
Cdd:pfam17047  81 SFVGNCEIDLEIKRYFCRAGVKSIQIHGTMRVILEPLIGDMPLVGALSIFFLRKPLLEINWTGLTNLLDVPGLNGLSDTI 160

                         170       180
                  ....*....|....*....|
gi 74220133   284 IMDSIAAFLVLPNRLLVPLV 303
Cdd:pfam17047 161 ILDIISNYLVLPNRITVPLV 180
SMP_ESyt3 cd21681
synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in extended ...
 127-302 3.89e-79

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in extended synaptotagmin-3 (E-Syt3) and similar proteins; Extended synaptotagmin-3 (E-Syt3), also called Chr3Syt, binds glycerophospholipids in a barrel-like domain and may play a role in cellular lipid transport. It tethers the endoplasmic reticulum to the cell membrane and promotes the formation of appositions between the endoplasmic reticulum and the cell membrane. E-Syt3 consists of an N-terminal endoplasmic reticulum (ER)-membrane anchor, a central SMP-domain, and three C-terminal cytoplasmic C2-domains. The ER-membrane anchor and C2 domains are required for tethering, and the SMP domain may be implicated in lipid transport. This model corresponds to the SMP domain.


Pssm-ID: 439237  Cd Length: 177  Bit Score: 248.20  E-value: 3.89e-79
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 127 EKAEWLNKIVAQVWPFLGQYMEKLLAETVAPAVRGANPHLQTFTFTRVELGEKPLRIIGVKVHPSQ-RKDQILLDLNVSY 205
Cdd:cd21681   1 ERVEWLNKIVSQAWPYIGMIMEKKFKEKLEPKIREKSVHLKTFTFTKLHFGEKCPRINGVKVYTKEvDRRQVILDLQICY 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 206 VGDVQIDVEVKKyfCKAGVKGMQLHGVLRVILEPLTGDLPIVGAVSMFFIKRPTLDINWTGMTNLLDIPGLSSLSDTMIM 285
Cdd:cd21681  81 IGDCEINVEIKK--CKAGVKGVQLHGTLRVILEPLLVDKPFVGAVTLFFIQKPHLEINWTGLTNLLDIPGINDMSDSLIE 158

                       170
                ....*....|....*..
gi 74220133 286 DSIAAFLVLPNRLLVPL 302
Cdd:cd21681 159 DLIASHLVLPNRFTVPL 175
SMP_ESyt cd21670
synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain of the extended ...
 127-302 1.44e-75

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain of the extended synaptotagmin (E-Syt) family; The extended synaptotagmin (E-Syt) family includes a group of Ca2+-regulated intrinsic membrane proteins, such as E-Syt1, E-Syt2 and E-Syt3. They are composed of an N-terminal endoplasmic reticulum (ER)-membrane anchor, a central SMP-domain, and five (E-Syt1) or three C-terminal cytoplasmic C2-domains (E-Syt2 and E-Syt3). The ER-membrane anchor and C2 domains are required for tethering, while the SMP domain is a lipid-binding domain that links the ER with other lipid bilayer-membranes within the cell. This model corresponds to the SMP domain, which has a beta-barrel structure like protein modules in the tubular-lipid-binding (TULIP) superfamily. It dimerizes to form an approximately 90-Angstrom-long cylinder traversed by a channel lined entirely with hydrophobic residues. The following two C2 domains then form arched structures flexibly linked to the SMP domain.


Pssm-ID: 439226  Cd Length: 177  Bit Score: 239.00  E-value: 1.44e-75
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 127 EKAEWLNKIVAQVWPFLGQYMEKLLAETVAPAVR-GANPHLQTFTFTRVELGEKPLRIIGVKVHPS-QRKDQILLDLNVS 204
Cdd:cd21670   1 ERAEWLNKIIKQLWPYINEYVEKLLKEKIEPSIRaLLPGPLKSFRFEKIDLGDKPPRIGGVKVYTDnVDRDEIILDLDIS 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 205 YVGDVQIDVEVKKYFcKAGVKGMQLHGVLRVILEPLTGDLPIVGAVSMFFIKRPTLDINWTGMTNLLDIPGLSSLSDTMI 284
Cdd:cd21670  81 YDGDADIEVSVGTGI-KAGIKDIQLRGTLRIVLKPLLSELPLVGGVQIFFLNPPEIDFDLTGLANLLDIPGLSNLLRKII 159

                       170
                ....*....|....*...
gi 74220133 285 MDSIAAFLVLPNRLLVPL 302
Cdd:cd21670 160 VDQIASFLVLPNRITIPL 177
C2A_C2C_Synaptotagmin_like cd08391
C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a ...
 319-438 2.67e-47

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: 162.08  E-value: 2.67e-47
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 319 GIIRIHLLAARGLSSKDKYVKGLIEGKSDPYALVRVGTQTFCSRVIDEELNPHWGETYEVIVHEVPGQEIEVEVFDKDPD 398
Cdd:cd08391   1 GVLRIHVIEAQDLVAKDKFVGGLVKGKSDPYVIVRVGAQTFKSKVIKENLNPKWNEVYEAVVDEVPGQELEIELFDEDPD 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 74220133 399 KDDFLGRMKLDVGKVLQAGVLDNWYPLQG-GQGQVHLRLEW 438
Cdd:cd08391  81 KDDFLGRLSIDLGSVEKKGFIDEWLPLEDvKSGRLHLKLEW 121
C2B_Synaptotagmin-like cd04050
C2 domain second repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
 469-573 1.52e-46

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: 159.27  E-value: 1.52e-46
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 469 ILVVYLDRAQDLPLKKGNKEPNPMVQLSVQDVTRESKATYSTNSPVWEEAFRFFLQDPRSQELDVQVKDDSRALTLGALT 548
Cdd:cd04050   1 LLFVYLDSAKNLPLAKSTKEPSPYVELTVGKTTQKSKVKERTNNPVWEEGFTFLVRNPENQELEIEVKDDKTGKSLGSLT 80

                        90       100
                ....*....|....*....|....*
gi 74220133 549 LPLARLLTASELTLDQWFQLSSSGP 573
Cdd:cd04050  81 LPLSELLKEPDLTLDQPFPLDNSGP 105
SMP_SYT cd21677
synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in the synaptotagmin ...
 118-302 2.56e-42

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in the synaptotagmin family, mostly plants; The synaptotagmin family includes Arabidopsis thaliana synaptotagmins (AtSYT1-5) and similar proteins. AtSYT1, also called NTMC2T1.1, or synaptotagmin A (SYTA), plays an important role in maintaining plasma membrane integrity during freezing and osmotic stresses. It may function in membrane resealing during calcium-dependent freezing tolerance. It regulates endocytosis and endosome recycling at the plasma membrane and cell-to-cell trafficking of cabbage leaf curl virus (CaLCuV) and tobacco mosaic virus (TMV) movement proteins via plasmodesmata. AtSYT2, also called NTMC2T1.2, or synaptotagmin B (SYTB), may play an important role in regulating an unconventional protein trafficking from the cytosol to the extracellular matrix. AtSYT3 (also called NTMC2T1.3, or synaptotagmin C, or SYTC), AtSYT4 (also called NTMC2T2.2, or synaptotagmin D, or SYTD) and AtSYT5 (also called NTMC2T2.1, or synaptotagmin E, or SYTE) may also be involved in membrane trafficking. This model corresponds to the SMP domain of SYT family proteins, which may be implicated in lipid transport.


Pssm-ID: 439233  Cd Length: 189  Bit Score: 151.16  E-value: 2.56e-42
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 118 PAWVSFPDVEKAEWLNKIVAQVWPFLGQYMEKLLAETVAPAV-RGANPHLQTFTFTRVELGEKPLRIIGVKVHPSqRKDQ 196
Cdd:cd21677   1 PSWVKFPDYERVDWLNKLLEKLWPYLDKAASKLVKESVEPLLeQYKPSFISSIKFKKLTLGTVPPRIEGVKVVES-DEDE 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 197 ILLDLNVSYVGDVQIDVEVKKYFC---KAGVKGMQLHGVLRVILEPLTGDLPIVGAVSMFFIKRPTLDINWTGMT-NLLD 272
Cdd:cd21677  80 VILDVDFRWAGDPDIVLAVKLLPGlslPVQVKDLQLSGTVRITLKPLVDELPCFGAVSVSLVEKPVVDFDLKLLGgDDMA 159

                       170       180       190
                ....*....|....*....|....*....|
gi 74220133 273 IPGLSSLSDTMIMDSIAAFLVLPNRLLVPL 302
Cdd:cd21677 160 LPGLKSWLDSFIRDALLDMLVWPKRIVIPI 189
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
125-589 8.48e-29

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


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 122.95  E-value: 8.48e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133  125 DVEKAEWLNKIVAQVWPFLGQYMEKLLAETVAPAVRGANPH------LQTFTftrveLGEKPLRIIGVKVHPSQRKDQIL 198
Cdd:COG5038  219 DYESVEWLNTFLQKFWPIIEPSISQQVVDQVNQQLAEAIPSfidalaLDEFT-----LGSKPPRIDGIRSYPSTESDTVV 293

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133  199 LDLNVSY----VGDV-------------QIDVEVKKYFCKAG----VKGMQLHGVLRVILEpLTGDLPIVGAVSMFFIKR 257
Cdd:COG5038  294 MDVDFSFtphdISDVtatsarasvnpkiSLVVKKGKSFGSFTlpilVEDLFFKGRVRVRVE-LMSKYPFIKTVSFQLLEV 372

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133  258 PTLDINWTGM------TNLLDIPGLSSLSDTMIMDSIAAFLVLPNRLLVplvpDLQDVAQLRSPLPRGIIRIHLLAARGL 331
Cdd:COG5038  373 PEFDFILVPLggdffgVDIFAIPGLSRFIQEIINSTLGPMLLPPNSLTI----DISQIMAGDSGTAIGVVEVKIKSAEGL 448

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133  332 SSKDkyvkGLIEGKSDPYalVRVGTQTF---CSRVIDEELNPHWGETYEVIVHEVpGQEIEVEV-FDKDPDKDDFLGRMK 407
Cdd:COG5038  449 KKSD----STINGTVDPY--ITVTFSDRvigKTRVKKNTLNPVWNETFYILLNSF-TDPLNLSLyDFNSFKSDKVVGSTQ 521

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133  408 LDVGKVLQAGVLDN--WYPLQGGQ--GQVHLRLEWLSLLPDAEKLDqvlqwnrGITSRPEPPSAAILVVYLDRAQDLplk 483
Cdd:COG5038  522 LDLALLHQNPVKKNelYEFLRNTKnvGRLTYDLRFFPVIEDKKELK-------GSVEPLEDSNTGILKVTLREVKAL--- 591

                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133  484 kgnKEPNPMVQLSVQDVTRESKATYS------TNSPVWEEAFRFFLQDPRSQELDVQVKDDSRALTLGALTLPLARLLTA 557
Cdd:COG5038  592 ---DELSSKKDNKSAELYTNAKEVYStgklkfTNHPSWNLQYNVLVTDRKNSSIKVVTFDVQSGKVIATEGSTLPDLIDR 668

                        490       500       510
                 ....*....|....*....|....*....|..
gi 74220133  558 SELTLdQWFQLSSsgPNSRLYMKLVMRILYLD 589
Cdd:COG5038  669 TLDTF-LVFPLRN--PKGRIFITNYWKPIYNA 697
SMP_SF cd21669
synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain superfamily; The SMP ...
 143-301 5.55e-24

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain superfamily; The SMP domain is a lipid transport domain found in phospholipid transfer proteins such as synaptotagmin family proteins, tricalbin (TCB) family proteins, maintenance of mitochondrial morphology protein 1 (MMM1), mitochondrial distribution and morphology protein 12 (MDM12), mitochondrial distribution and morphology protein 34 (MDM34), PDZ domain-containing protein 8 (PDZD8), testis-expressed protein 2 (TEX2), meiotically up-regulated gene 190 protein (Mug190), C2 domain-containing protein 2 (C2CD2) and C2 domain-containing protein 2-like (C2CD2L). The SMP domain belongs to a superfamily of lipid/hydrophobic ligand-binding domains called TULIP (tubular lipid-binding proteins). It adopts a TULIP fold with two alpha helices and a highly curved antiparallel beta sheet forming a cornucopia-like structure.


Pssm-ID: 439225  Cd Length: 165  Bit Score: 98.93  E-value: 5.55e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 143 LGQYMEKLLAETVAPAVRgaNPHLQTFTFTRVELGEKPLRIIGVKVHPS-QRKDQILLDLNVSYVGDVQIDVEVK----- 216
Cdd:cd21669   1 LEQLIRESLQELLEEVKK--PSFIESLELTEFTLGSNPPRIKSVRVLDSpSSDLQLVLDLDLEYAGDFSVVLSAKlgggg 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 217 -KYFCKAGVKGMQLHGVLRVILEPLTgDLPIVGAVSMFFIKRPTLDINWT--GMTNLLDIPGLSSLSDTMIMDSIAAFLV 293
Cdd:cd21669  79 lGLPVPVSVSDLSLEGRLRVRLTLLP-EFPYVGALSISFVEPPDIDFSIRplGGVDLMELPGLSSWLEKLLTDALVELLV 157


                ....*...
gi 74220133 294 LPNRLLVP 301
Cdd:cd21669 158 EPNRIVID 165
SMP_TCB cd21678
synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in the tricalbin ...
 127-302 4.98e-21

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in the tricalbin (TCB) family; The tricalbin (TCB) family includes Saccharomyces cerevisiae TCB1-3 and similar proteins. They may play a role in membrane trafficking. This model corresponds to the SMP domain of TCB family proteins, which may be implicated in lipid transport.


Pssm-ID: 439234  Cd Length: 203  Bit Score: 91.47  E-value: 4.98e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 127 EKAEWLNKIVAQVWPFLGQYMEKLLAETVAPAVRGANP------HLQTFTftrveLGEKPLRIIGVKVHPSQRKDQILLD 200
Cdd:cd21678   1 ESVEWLNYFLQKFWLIYEPVLSETIVTNVNPVLAENCPsfldslRLTEFT-----LGTKAPRIEGVRTYPKTEDDVVVMD 75

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 201 LNVSYV----GD-------------VQIDVEVKKYFCKAG----VKGMQLHGVLRVILEpLTGDLPIVGAVSMFFIKRPT 259
Cdd:cd21678  76 WEFSFTpndtSDltakqiknkvnpkIVLTARVGKGVVGIDlpilVEDLSFSGKLRVRLK-LMPDFPHIKTVEVSFLEPPE 154

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*...
gi 74220133 260 LDinWT-----GMTNLLDIPGLSSLSDTMIMDSIAAFLVLPNRLLVPL 302
Cdd:cd21678 155 ID--FVlkplgGGFDIMDIPGLSTFIRSIIHSILGPMMYAPNSFTLDL 200
C2A_Synaptotagmin-like cd04024
C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
 319-438 1.11e-17

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: 79.39  E-value: 1.11e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 319 GIIRIHLLAARGLSSKDKYVKGliegKSDPYALVRVGTQTFCSRVIDEELNPHWGETYEVIVHEVPGQEIEVEV-FDKDP 397
Cdd:cd04024   1 GVLRVHVVEAKDLAAKDRSGKG----KSDPYAILSVGAQRFKTQTIPNTLNPKWNYWCEFPIFSAQNQLLKLILwDKDRF 76

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|..
gi 74220133 398 DKDDFLGRMKLDVGKVLQAGVL---DNWYPLQGGQ--------GQVHLRLEW 438
Cdd:cd04024  77 AGKDYLGEFDIALEEVFADGKTgqsDKWITLKSTRpgktsvvsGEIHLQFSW 128
C2 pfam00168
C2 domain;
319-425 1.82e-16

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 75.43  E-value: 1.82e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133   319 GIIRIHLLAARGLSSKDKYvkglieGKSDPYALVRV--GTQTFCSRVIDEELNPHWGETYEVIVHEVPGQEIEVEVF-DK 395
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKDGN------GTSDPYVKVYLldGKQKKKTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYdYD 74

                          90       100       110
                  ....*....|....*....|....*....|
gi 74220133   396 DPDKDDFLGRMKLDVGKVLQAGVLDNWYPL 425
Cdd:pfam00168  75 RFGRDDFIGEVRIPLSELDSGEGLDGWYPL 104
C2 pfam00168
C2 domain;
469-568 2.66e-15

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 71.97  E-value: 2.66e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133   469 ILVVYLDRAQDLPLKKGNKEPNPMVQLSVQD--VTRESKATYSTNSPVWEEAFRFFLQDPRSQELDVQVKDDSRAL---T 543
Cdd:pfam00168   2 RLTVTVIEAKNLPPKDGNGTSDPYVKVYLLDgkQKKKTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRFGrddF 81

                          90       100
                  ....*....|....*....|....*
gi 74220133   544 LGALTLPLARLLtaSELTLDQWFQL 568
Cdd:pfam00168  82 IGEVRIPLSELD--SGEGLDGWYPL 104
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 470-568 3.28e-14

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: 68.63  E-value: 3.28e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 470 LVVYLDRAQDLPLKKGNKEPNPMVQLSVQDV-TRESKATYSTNSPVWEEAFRFFLQDPRSQELDVQVKDDSRALT---LG 545
Cdd:cd00030   1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGGKqKFKTKVVKNTLNPVWNETFEFPVLDPESDTLTVEVWDKDRFSKddfLG 80

                        90       100
                ....*....|....*....|...
gi 74220133 546 ALTLPLARLLTASELTlDQWFQL 568
Cdd:cd00030  81 EVEIPLSELLDSGKEG-ELWLPL 102
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 321-425 3.98e-14

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: 68.63  E-value: 3.98e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 321 IRIHLLAARGLSSKDKYvkglieGKSDPYALVRVG-TQTFCSRVIDEELNPHWGETYEVIVHEVPGQEIEVEVF-DKDPD 398
Cdd:cd00030   1 LRVTVIEARNLPAKDLN------GKSDPYVKVSLGgKQKFKTKVVKNTLNPVWNETFEFPVLDPESDTLTVEVWdKDRFS 74

                        90       100
                ....*....|....*....|....*...
gi 74220133 399 KDDFLGRMKLDVGKVLQAG-VLDNWYPL 425
Cdd:cd00030  75 KDDFLGEVEIPLSELLDSGkEGELWLPL 102
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 469-556 5.42e-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: 68.28  E-value: 5.42e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133    469 ILVVYLDRAQDLPLKKGNKEPNPMVQLSVQDVTRESKAT---YSTNSPVWEEAFRFFLQDPRSQELDVQVKDD---SRAL 542
Cdd:smart00239   1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGDPKEKKKTkvvKNTLNPVWNETFEFEVPPPELAELEIEVYDKdrfGRDD 80

                           90
                   ....*....|....
gi 74220133    543 TLGALTLPLARLLT 556
Cdd:smart00239  81 FIGQVTIPLSDLLL 94
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 320-422 4.28e-12

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: 62.89  E-value: 4.28e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133    320 IIRIHLLAARGLSSKDKYvkglieGKSDPYALVRVGTQ---TFCSRVIDEELNPHWGETYEVIVHEVPGQEIEVEVF-DK 395
Cdd:smart00239   1 TLTVKIISARNLPPKDKG------GKSDPYVKVSLDGDpkeKKKTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYdKD 74

                           90       100
                   ....*....|....*....|....*..
gi 74220133    396 DPDKDDFLGRMKLDVGKVLQAGVLDNW 422
Cdd:smart00239  75 RFGRDDFIGQVTIPLSDLLLGGRHEKL 101
C2C_Tricalbin-like cd04045
C2 domain third repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 319-392 9.30e-10

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: 56.44  E-value: 9.30e-10
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 74220133 319 GIIRIHLLAARGLSSKDKYvkglieGKSDPYALVRV-GTQTFCSRVIDEELNPHWGETYEVIVHEvPGQEIEVEV 392
Cdd:cd04045   1 GVLRLHIRKANDLKNLEGV------GKIDPYVRVLVnGIVKGRTVTISNTLNPVWDEVLYVPVTS-PNQKITLEV 68
C2B_RasA1_RasA4 cd04025
C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase ...
 321-426 2.96e-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: 55.18  E-value: 2.96e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 321 IRIHLLAARGLSSKDkyvkglIEGKSDPYALVRVGTQTFCSRVIDEELNPHWGETYEVIVHEVPGQEIEVEV-FDKDPDK 399
Cdd:cd04025   2 LRCHVLEARDLAPKD------RNGTSDPFVRVFYNGQTLETSVVKKSCYPRWNEVFEFELMEGADSPLSVEVwDWDLVSK 75

                        90       100
                ....*....|....*....|....*..
gi 74220133 400 DDFLGRMKLDVGKVLQAGVLDNWYPLQ 426
Cdd:cd04025  76 NDFLGKVVFSIQTLQQAKQEEGWFRLL 102
C2B_Tricalbin-like cd04052
C2 domain second repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 484-584 3.34e-09

C2 domain second 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 second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176017 [Multi-domain]  Cd Length: 111  Bit Score: 54.92  E-value: 3.34e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 484 KGNKEPNPMVQLSVQD--VTRESKATYsTNSPVWEEAFRFFLQDPRSQELDVQVKDDSRAL--TLGALTLPLARLLTASE 559
Cdd:cd04052   8 SKTGLLSPYAELYLNGklVYTTRVKKK-TNNPSWNASTEFLVTDRRKSRVTVVVKDDRDRHdpVLGSVSISLNDLIDATS 86

                        90       100
                ....*....|....*....|....*
gi 74220133 560 lTLDQWFQLsSSGPNSRLYMKLVMR 584
Cdd:cd04052  87 -VGQQWFPL-SGNGQGRIRISALWK 109
C2_fungal_Inn1p-like cd08681
C2 domain found in fungal Ingression 1 (Inn1) proteins; Saccharomyces cerevisiae Inn1 ...
 469-572 2.99e-08

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: 52.25  E-value: 2.99e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 469 ILVVYLDRAQDLPLKKGNKEPNPMVQLSVQDVTRESKATY-STNSPVWEEAFRFFL--QDPRSQELDVQVKDDSRALTLG 545
Cdd:cd08681   2 TLVVVVLKARNLPNKRKLDKQDPYCVLRIGGVTKKTKTDFrGGQHPEWDEELRFEIteDKKPILKVAVFDDDKRKPDLIG 81

                        90       100
                ....*....|....*....|....*..
gi 74220133 546 ALTLPLARLLTASEltLDQWFQLSSSG 572
Cdd:cd08681  82 DTEVDLSPALKEGE--FDDWYELTLKG 106
C2B_MCTP_PRT cd08376
C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 320-434 5.58e-07

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: 48.41  E-value: 5.58e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 320 IIRIHLLAARGLSSKDKyvkgliEGKSDPYALVRVGTQTFCSRVIDEELNPHWGETYEVIVHEVPGQEIEVEV-FDKDPD 398
Cdd:cd08376   1 VVTIVLVEGKNLPPMDD------NGLSDPYVKFRLGNEKYKSKVCSKTLNPQWLEQFDLHLFDDQSQILEIEVwDKDTGK 74

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 74220133 399 KDDFLGRMKLDVGKVL--QAGVLdnWYPLQGGQGQVHL 434
Cdd:cd08376  75 KDEFIGRCEIDLSALPreQTHSL--ELELEDGEGSLLL 110
C2_Calpain cd04046
C2 domain present in Calpain proteins; A single C2 domain is found in calpains (EC 3.4.22.52, ...
 317-392 6.85e-07

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: 48.43  E-value: 6.85e-07
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 74220133 317 PRGIIRIHLLAARGLSSKDKyvkgliEGKSDPYALVRVGTQTFCSRVIDEELNPHWgeTYEVIVH-EVPGQEIEVEV 392
Cdd:cd04046   1 PQVVTQVHVHSAEGLSKQDS------GGGADPYVIIKCEGESVRSPVQKDTLSPEF--DTQAIFYrKKPRSPIKIQV 69
C2A_Ferlin cd08373
C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 476-563 9.99e-07

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: 48.02  E-value: 9.99e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 476 RAQDLPLKKGnkEPNPMVQLSVQDVTRESKATYSTNSPVWEEAFRFFLQDP--RSQELDVQVKDDSRALT---LGALTLP 550
Cdd:cd08373   4 SLKNLPGLKG--KGDRIAKVTFRGVKKKTRVLENELNPVWNETFEWPLAGSpdPDESLEIVVKDYEKVGRnrlIGSATVS 81

                        90
                ....*....|...
gi 74220133 551 LARLLTASELTLD 563
Cdd:cd08373  82 LQDLVSEGLLEVT 94
C2A_MCTP_PRT_plant cd04022
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 470-589 1.43e-06

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: 47.72  E-value: 1.43e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 470 LVVYLDRAQDLPLKKGNKEPNPMVQLSVQDVTRESKATYSTNSPVWEEAFRFFLQDP---RSQELDVQVKDDSRALT--- 543
Cdd:cd04022   2 LVVEVVDAQDLMPKDGQGSSSAYVELDFDGQKKRTRTKPKDLNPVWNEKLVFNVSDPsrlSNLVLEVYVYNDRRSGRrrs 81

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 74220133 544 -LGALTLPLARLLTASELTLdQWFQLSSSGPNSRLYMKLVMRILYLD 589
Cdd:cd04022  82 fLGRVRISGTSFVPPSEAVV-QRYPLEKRGLFSRVRGEIGLKVYITD 127
C2B_Munc13 cd04027
C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...
 321-376 1.67e-06

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: 47.56  E-value: 1.67e-06
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 74220133 321 IRIHLLAARGLSSKDKyvkgliEGKSDPYALVRVGTQTFCSRVIDEELNPHWGETY 376
Cdd:cd04027   3 ISITVVCAQGLIAKDK------TGTSDPYVTVQVGKTKKRTKTIPQNLNPVWNEKF 52
C2A_fungal cd04041
C2 domain first repeat; fungal group; C2 domains were first identified in Protein Kinase C ...
 319-380 1.75e-06

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: 46.87  E-value: 1.75e-06
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 74220133 319 GIIRIHLLAARGLSSKDkyvkgLIEGKSDPY---ALVRVGTQTFCSRVIDEELNPHWGETYEVIV 380
Cdd:cd04041   1 GVLVVTIHRATDLPKAD-----FGTGSSDPYvtaSFAKFGKPLYSTRIIRKDLNPVWEETWFVLV 60
C2_Smurf-like cd08382
C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 ...
 321-381 2.11e-06

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: 47.30  E-value: 2.11e-06
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 74220133 321 IRIHLLAARGLSSKDKYvkglieGKSDPYALVRV-GTQTFCSRVIDEELNPHWGETYEVIVH 381
Cdd:cd08382   2 VRLTVLCADGLAKRDLF------RLPDPFAVITVdGGQTHSTDVAKKTLDPKWNEHFDLTVG 57
C2_fungal_Inn1p-like cd08681
C2 domain found in fungal Ingression 1 (Inn1) proteins; Saccharomyces cerevisiae Inn1 ...
 319-436 2.71e-06

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: 46.47  E-value: 2.71e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 319 GIIRIHLLAARGLSSKDKYvkglieGKSDPYALVRVGTQTFCSRVIDEE-LNPHWGETYEVIVHEVPGQEIEVEVFDKDP 397
Cdd:cd08681   1 GTLVVVVLKARNLPNKRKL------DKQDPYCVLRIGGVTKKTKTDFRGgQHPEWDEELRFEITEDKKPILKVAVFDDDK 74

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 74220133 398 DKDDFLGRMKLDVGKVLQAGVLDNWYPLQ-GGQ--GQVHLRL 436
Cdd:cd08681  75 RKPDLIGDTEVDLSPALKEGEFDDWYELTlKGRyaGEVYLEL 116
C2A_Munc13-like cd08676
C2 domain first repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
 509-568 5.58e-06

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: 46.60  E-value: 5.58e-06
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 74220133 509 STNSPVWEEAFRFFLQDPRSQELDVQV--KDDSralTLGALTLPLARLltaSELTLDQWFQL 568
Cdd:cd08676  98 QTLNPVWNETFRFEVEDVSNDQLHLDIwdHDDD---FLGCVNIPLKDL---PSCGLDSWFKL 153
SMP_Mug190 cd21676
synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in meiotically ...
 127-295 9.10e-06

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in meiotically up-regulated gene 190 protein (Mug190) and similar proteins; Meiotically up-regulated gene 190 protein (Mug190) has a role in meiosis. This model corresponds to the SMP domain of Mug190, which may be implicated in lipid transport.


Pssm-ID: 439232  Cd Length: 233  Bit Score: 47.21  E-value: 9.10e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 127 EKAEWLNKIVAQVWP------F--LGQYMEKLLAETVAPAVRGANphlqtftFTRVELGEKPLRIIGVKVHPSQRKDQ-- 196
Cdd:cd21676   1 ESVEWLNSLLAALWPlinpdlFtpVIDLLEDVMQASLPSFVHSVR-------VTDLGQGSQPLRILSMRILPDGEWDEsv 73

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 197 -------------------------ILLDLNVSY---VGDVQIDVEVKK-----YFcKAGVKGM------------QLHG 231
Cdd:cd21676  74 segghskeeeedaddeeeeeeggdyVNLEVAFAYrarPSGKSLSSKAKNahllaYF-GLGLKGLggvpipvwvevlGLVG 152

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 74220133 232 VLRVILEpLTGDLPIVGAVSMFFIKRPTLDINWT----GMTNLLDIPGLSSlsdtMIMDSIAAFL---VLP 295
Cdd:cd21676 153 TVRLRLQ-LTPDPPFVKTVTFSFMGLPKVDISARplskGAFNVMNLPLISS----FVNSSIDAVAaefVAP 218
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 477-554 1.14e-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: 45.22  E-value: 1.14e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 477 AQDLPLKKGNKE--PNPMVQLSVQDVTRESKATYSTN-------SPVWEEAFRFFLQDPrsqELDV---QVKDDSRALT- 543
Cdd:cd00275  11 GQQLPKPKGDKGsiVDPYVEVEIHGLPADDSAKFKTKvvknngfNPVWNETFEFDVTVP---ELAFlrfVVYDEDSGDDd 87

                        90
                ....*....|..
gi 74220133 544 -LGALTLPLARL 554
Cdd:cd00275  88 fLGQACLPLDSL 99
C2A_MCTP_PRT cd04042
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 322-392 1.18e-05

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: 44.96  E-value: 1.18e-05
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 74220133 322 RIHLLAARGLSSKDKyvkgliEGKSDPYALVRVGTQT-FCSRVIDEELNPHWGETYEVIVhEVPGQEIEVEV 392
Cdd:cd04042   3 DIHLKEGRNLAARDR------GGTSDPYVKFKYGGKTvYKSKTIYKNLNPVWDEKFTLPI-EDVTQPLYIKV 67
C2C_KIAA1228 cd04030
C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins ...
 470-569 1.82e-05

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: 44.57  E-value: 1.82e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 470 LVVYLDRAQDLPLKKGNKEPNPMVQLSV-----QDVTRESKATYSTNSPVWEEAFRFF--LQDPRSQELDVQVKDDSRAL 542
Cdd:cd04030  18 LIVTVHKCRNLPPCDSSDIPDPYVRLYLlpdksKSTRRKTSVKKDNLNPVFDETFEFPvsLEELKRRTLDVAVKNSKSFL 97

                        90       100       110
                ....*....|....*....|....*....|..
gi 74220133 543 -----TLGALTLPLARLLTASELTldQWFQLS 569
Cdd:cd04030  98 srekkLLGQVLIDLSDLDLSKGFT--QWYDLT 127
C2_ArfGAP cd04038
C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating ...
 318-392 2.18e-05

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: 44.62  E-value: 2.18e-05
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 74220133 318 RGIIRIHLLAARGLSSKDKyvkglieGKSDPYALVRVGTQTFCSRVIDEELNPHWGETYEVIVHEVPGQeIEVEV 392
Cdd:cd04038   1 LGLLKVRVVRGTNLAVRDF-------TSSDPYVVLTLGNQKVKTRVIKKNLNPVWNEELTLSVPNPMAP-LKLEV 67
C2_plant_PLD cd04015
C2 domain present in plant phospholipase D (PLD); PLD hydrolyzes terminal phosphodiester bonds ...
 318-431 2.48e-05

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: 44.99  E-value: 2.48e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 318 RGIIRIHLLAARGLSSKDKYVKGLIEGKSDPYALV-----RVGtQTfcsRVIDEELNPHWGETYEVIV-HEVPgqEIEVE 391
Cdd:cd04015  30 RRFFSKLVGCSEPTLKRPSSHRHVGKITSDPYATVdlagaRVA-RT---RVIENSENPVWNESFHIYCaHYAS--HVEFT 103

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 74220133 392 VFDKDPDKDDFLGRMKLDVGKVLQAGVLDNWYPLQGGQGQ 431
Cdd:cd04015 104 VKDNDVVGAQLIGRAYIPVEDLLSGEPVEGWLPILDSNGK 143
C2B_MCTP_PRT cd08376
C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 469-537 3.75e-05

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: 43.40  E-value: 3.75e-05
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 74220133 469 ILVVYLDRAQDLPLKKGNKEPNPMVQLSVQDVTRESKATYSTNSPVWEEAFRFFLQDPRSQELDVQVKD 537
Cdd:cd08376   1 VVTIVLVEGKNLPPMDDNGLSDPYVKFRLGNEKYKSKVCSKTLNPQWLEQFDLHLFDDQSQILEIEVWD 69
C2B_Synaptotagmin-like cd04050
C2 domain second repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
 347-428 3.81e-05

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: 42.94  E-value: 3.81e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 347 DPYALVRVGTQTFCSRVIDEELNPHWGETYEVIVHEVPGQEIEVEVfdKDPDKDDFLGRMKLDVGKVLQAG--VLDNWYP 424
Cdd:cd04050  22 SPYVELTVGKTTQKSKVKERTNNPVWEEGFTFLVRNPENQELEIEV--KDDKTGKSLGSLTLPLSELLKEPdlTLDQPFP 99


                ....
gi 74220133 425 LQGG 428
Cdd:cd04050 100 LDNS 103
C2B_Tricalbin-like cd04052
C2 domain second repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 329-438 4.28e-05

C2 domain second 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 second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176017 [Multi-domain]  Cd Length: 111  Bit Score: 42.97  E-value: 4.28e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 329 RGLSSKDKyvkglIEGKSDPYALVRVGTQ-TFCSRVIDEELNPHWGETYEVIVHEVPGQEIEVEVFDKDPDKDDFLGRMK 407
Cdd:cd04052   1 KGLDTSES-----KTGLLSPYAELYLNGKlVYTTRVKKKTNNPSWNASTEFLVTDRRKSRVTVVVKDDRDRHDPVLGSVS 75

                        90       100       110
                ....*....|....*....|....*....|...
gi 74220133 408 LDVGKVLQAG-VLDNWYPLQG-GQGQVHLRLEW 438
Cdd:cd04052  76 ISLNDLIDATsVGQQWFPLSGnGQGRIRISALW 108
C2D_Ferlin cd04017
C2 domain fourth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 322-385 5.42e-05

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: 43.30  E-value: 5.42e-05
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 74220133 322 RIHLLAARGLSSKDKyvkgliEGKSDPYALVRVGTQTFCSRVIDEELNPHWGET---YEVIVHEVPG 385
Cdd:cd04017   4 RAYIYQARDLLAADK------SGLSDPFARVSFLNQSQETEVIKETLSPTWDQTlifDEVELYGSPE 64
C2A_MCTP_PRT_plant cd04022
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 323-426 7.68e-05

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: 42.71  E-value: 7.68e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 323 IHLLAARGLSSKDKyvkgliEGKSDPYALVRVGTQTFCSRVIDEELNPHWGETYEVIVHEV---PGQEIEVEVFDKDPDK 399
Cdd:cd04022   4 VEVVDAQDLMPKDG------QGSSSAYVELDFDGQKKRTRTKPKDLNPVWNEKLVFNVSDPsrlSNLVLEVYVYNDRRSG 77

                        90       100       110
                ....*....|....*....|....*....|..
gi 74220133 400 DDF--LGRMKLDVGKVL---QAGVLdnWYPLQ 426
Cdd:cd04022  78 RRRsfLGRVRISGTSFVppsEAVVQ--RYPLE 107
C2B_RasGAP cd08675
C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
 321-426 8.14e-05

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: 42.74  E-value: 8.14e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 321 IRIHLLAARGLSSKdkyvkglIEGKSDPYALVRVG----TQTFCSRVIDEELNPHWGETYEVIVHE-------------- 382
Cdd:cd08675   1 LSVRVLECRDLALK-------SNGTCDPFARVTLNysskTDTKRTKVKKKTNNPRFDEAFYFELTIgfsyekksfkveee 73

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 74220133 383 -VPGQEIEVEVFDKDPDKDDF-LGRMKLDVGKVLQAGVLDNWYPLQ 426
Cdd:cd08675  74 dLEKSELRVELWHASMVSGDDfLGEVRIPLQGLQQAGSHQAWYFLQ 119
C2B_Ferlin cd04011
C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 472-547 8.93e-05

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: 42.18  E-value: 8.93e-05
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 74220133 472 VYLDRAQDLPlkkGNkEPNPMVQLSVQDVTRESKATYSTNSPVWEEAFRFFLQDPRSQELDVQVK---DDSRALTLGAL 547
Cdd:cd04011   8 VRVIEARQLV---GG-NIDPVVKVEVGGQKKYTSVKKGTNCPFYNEYFFFNFHESPDELFDKIIKisvYDSRSLRSDTL 82
C2_Munc13_fungal cd04043
C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are ...
 476-585 1.03e-04

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: 42.25  E-value: 1.03e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 476 RAQDLPLKKGNKEPNPMVQLSVQDVTRE---SKATYSTNSPVWEEAFRFFLQDPRSQELDVQVKDDSRA---LTLGALTL 549
Cdd:cd04043   9 RAENLKADSSNGLSDPYVTLVDTNGKRRiakTRTIYDTLNPRWDEEFELEVPAGEPLWISATVWDRSFVgkhDLCGRASL 88

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 74220133 550 PL-ARLLTASELTLDQWFQLSSSGpnsrlymKLVMRI 585
Cdd:cd04043  89 KLdPKRFGDDGLPREIWLDLDTQG-------RLLLRV 118
C2B_RasA1_RasA4 cd04025
C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase ...
 477-576 2.06e-04

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: 41.32  E-value: 2.06e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 477 AQDLPLKKGNKEPNPMVQLSVQDVTRESKATYSTNSPVWEEAFRFFLQDPRSQELDVQVKD-D--SRALTLGALTLPLAR 553
Cdd:cd04025   9 ARDLAPKDRNGTSDPFVRVFYNGQTLETSVVKKSCYPRWNEVFEFELMEGADSPLSVEVWDwDlvSKNDFLGKVVFSIQT 88

                        90       100
                ....*....|....*....|...
gi 74220133 554 LLTASELTldQWFQLSSSGPNSR 576
Cdd:cd04025  89 LQQAKQEE--GWFRLLPDPRAEE 109
C2B_RasGAP cd08675
C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
 470-569 3.99e-04

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: 40.82  E-value: 3.99e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 470 LVVYLDRAQDLPLKK-GNKEPNPMVQL--SVQDVTRESKATYSTNSPVWEEAFRFFLQDPRS---------------QEL 531
Cdd:cd08675   1 LSVRVLECRDLALKSnGTCDPFARVTLnySSKTDTKRTKVKKKTNNPRFDEAFYFELTIGFSyekksfkveeedlekSEL 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 74220133 532 DVQVKDDS---RALTLGALTLPLARLLTAseLTLDQWFQLS 569
Cdd:cd08675  81 RVELWHASmvsGDDFLGEVRIPLQGLQQA--GSHQAWYFLQ 119
C2C_MCTP_PRT cd08377
C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 319-377 4.30e-04

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: 40.36  E-value: 4.30e-04
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 74220133 319 GIIRIHLLAARGLSSKDkyvkglIEGKSDPYALVRVGTQTFCSRVIDEELNPHWGETYE 377
Cdd:cd08377   1 GFLQVKVIRASGLAAAD------IGGKSDPFCVLELVNARLQTHTIYKTLNPEWNKIFT 53
C2D_Tricalbin-like cd04040
C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 321-392 5.48e-04

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: 39.86  E-value: 5.48e-04
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 74220133 321 IRIHLLAARGLSSKDKyvkgliEGKSDPYALVRV-GTQTFCSRVIDEELNPHWGETYEVIVHEVPGQEIEVEV 392
Cdd:cd04040   1 LTVDVISAENLPSADR------NGKSDPFVKFYLnGEKVFKTKTIKKTLNPVWNESFEVPVPSRVRAVLKVEV 67
SMP_TEX2 cd21675
synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in testis-expressed ...
 166-297 7.50e-04

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in testis-expressed protein 2 (TEX2) and similar proteins; testis-expressed protein 2 (TEX2), also called transmembrane protein 96 (TMEM96), is a transmembrane protein with uncharacterized biological function. Diseases associated with TEX2 include Wernicke-Korsakoff Syndrome. This model corresponds to the SMP domain of TEX2, which may be implicated in lipid transport.


Pssm-ID: 439231  Cd Length: 186  Bit Score: 40.94  E-value: 7.50e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 166 LQTFTFTRVELGEKPLRIIGVKVHPSQRKDQILLDLNVSYVGDVQIDVEVKKYFCKAG-VKGMQLHGVLRVILEPLTGDL 244
Cdd:cd21675  40 LGEITVTDLDLGTSVPVISNPKLPSLDPDGGLWVDLDVSYRGGFSLTLETKLNLSKLKkEKVSNVPLVLAVEVKSLSGTL 119

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 74220133 245 pivgavsMFFIKRPTLDINWTGMTNL--LDI---PGLSSLSDTM----------IMDSIAAFLVLPNR 297
Cdd:cd21675 120 -------RLNIKPPPSNRLWYGFREMpkLELeiePVVGERQVTLphvtnwiekkLKEEIKESLVLPNM 180
C2_Ras_p21A1 cd08400
C2 domain present in RAS p21 protein activator 1 (RasA1); RasA1 is a GAP1 (GTPase activating ...
 470-589 8.35e-04

C2 domain present in RAS p21 protein activator 1 (RasA1); RasA1 is a GAP1 (GTPase activating protein 1), a Ras-specific GAP member, 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. RasA1 contains a C2 domain, a Ras-GAP domain, a pleckstrin homology (PH)-like domain, a SH3 domain, and 2 SH2 domains. 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: 176045 [Multi-domain]  Cd Length: 126  Bit Score: 39.66  E-value: 8.35e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 470 LVVYLDRAQDLPLKKgnkEPNPMVQLSVQDVTRESKATYSTNSPVWEEAFRF--FLQDPRSQELDVQVKDD-SRALTLGA 546
Cdd:cd08400   6 LQLNVLEAHKLPVKH---VPHPYCVISLNEVKVARTKVREGPNPVWSEEFVFddLPPDVNSFTISLSNKAKrSKDSEIAE 82

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 74220133 547 LTLPLARLLTASEltLDQWFQLSSSGPNSRLYM-KLVMRILYLD 589
Cdd:cd08400  83 VTVQLSKLQNGQE--TDEWYPLSSASPLKGGEWgSLRIRARYSH 124
C2A_RIM1alpha cd04031
C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
 466-568 1.36e-03

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: 39.15  E-value: 1.36e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 466 SAAILVVYLDRAQDLPLKKGNKEPNPMVQL-----SVQDVTRESKATYSTNSPVWEEAFRFF---LQDPRSQELDVQVKD 537
Cdd:cd04031  14 VTSQLIVTVLQARDLPPRDDGSLRNPYVKVyllpdRSEKSKRRTKTVKKTLNPEWNQTFEYSnvrRETLKERTLEVTVWD 93

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 74220133 538 DSRALT---LGALTLPLARLLtaseltLD---QWFQL 568
Cdd:cd04031  94 YDRDGEndfLGEVVIDLADAL------LDdepHWYPL 124
C2A_Synaptotagmin-15-17 cd08390
C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a ...
 470-559 1.37e-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: 39.16  E-value: 1.37e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 470 LVVYLDRAQDLPLKKGNKEP-NPMVQLSV---QDVTRESKATYSTNSPVWEEAFRFFLQDPRSQE--LDVQVKD---DSR 540
Cdd:cd08390  16 LTVSLIKARNLPPRTKDVAHcDPFVKVCLlpdERRSLQSKVKRKTQNPNFDETFVFQVSFKELQRrtLRLSVYDvdrFSR 95

                        90
                ....*....|....*....
gi 74220133 541 ALTLGALTLPLARLLTASE 559
Cdd:cd08390  96 HCIIGHVLFPLKDLDLVKG 114
C2A_Synaptotagmin-8 cd08387
C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking ...
 319-389 1.96e-03

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: 38.54  E-value: 1.96e-03
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 74220133 319 GIIRIHLLAARGLSSKDkyvkglIEGKSDPYALVRV---GTQTFCSRVIDEELNPHWGETYeviVHEVPGQEIE 389
Cdd:cd08387  16 GILNVKLIQARNLQPRD------FSGTADPYCKVRLlpdRSNTKQSKIHKKTLNPEFDESF---VFEVPPQELP 80
C2A_RasGAP cd08383
C2 domain (first repeat) of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
 322-436 2.04e-03

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: 38.40  E-value: 2.04e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 322 RIHLLAARGLSSKdkyvkglieGKSDPYALVRVGTQTFCSRVIDEELNPHWGE--TYEVIVHEVPGQEIEVEVFDKDPDK 399
Cdd:cd08383   3 RLRILEAKNLPSK---------GTRDPYCTVSLDQVEVARTKTVEKLNPFWGEefVFDDPPPDVTFFTLSFYNKDKRSKD 73

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 74220133 400 DDfLGRMKLDVGKvLQAG-VLDNWYPLQ------GGQGQVHLRL 436
Cdd:cd08383  74 RD-IVIGKVALSK-LDLGqGKDEWFPLTpvdpdsEVQGSVRLRA 115
C2A_Ferlin cd08373
C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 336-377 2.45e-03

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: 38.39  E-value: 2.45e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 74220133 336 KYVKGLIeGKSDPYALVRVGTQTFCSRVIDEELNPHWGETYE 377
Cdd:cd08373   6 KNLPGLK-GKGDRIAKVTFRGVKKKTRVLENELNPVWNETFE 46
C2E_Ferlin cd04037
C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 320-378 2.67e-03

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: 38.30  E-value: 2.67e-03
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 74220133 320 IIRIHLLAARGLSSKDkyvkglIEGKSDPYALVRVGTQTFCSR--VIDEELNPHWGETYEV 378
Cdd:cd04037   1 LVRVYVVRARNLQPKD------PNGKSDPYLKIKLGKKKINDRdnYIPNTLNPVFGKMFEL 55
SMP_Mmm1 cd21671
synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in maintenance of ...
 127-306 2.81e-03

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in maintenance of mitochondrial morphology protein 1 (Mmm1) and similar proteins; Maintenance of mitochondrial morphology protein 1 (Mmm1), also called mitochondrial outer membrane protein Mmm1, or yeast mitochondrial escape protein 6 (YME6), is a mitochondrial outer membrane protein essential for establishing and maintaining the structure of mitochondria and maintenance of mtDNA nucleoids. It is a component of the ER-mitochondrion encounter structure/ mitochondrial distribution and morphology (ERMES/Mdm) complex, which serves as a molecular tether to connect the endoplasmic reticulum and mitochondria. Components of this complex are involved in the control of mitochondrial shape and protein biogenesis, and function in nonvesicular lipid trafficking between the ER and mitochondria. The Mdm12-Mmm1 subcomplex functions in the major beta-barrel assembly pathway that is responsible for biogenesis of all outer membrane beta-barrel proteins, and acts in a late step after the SAM complex. The Mdm10-Mdm12-Mmm1 subcomplex further acts in the TOM40-specific pathway after the action of the Mdm12-Mmm1 complex. This model corresponds to the SMP domain of Mmm1, which may be implicated in lipid transport.


Pssm-ID: 439227  Cd Length: 216  Bit Score: 39.43  E-value: 2.81e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 127 EKAEWLNKIVAQVwpfLGQYMEKLLAETVAPAV------RGANPH-LQTFTFTRVELGEKPLRIIGVKVHPSQRKDQILL 199
Cdd:cd21671  19 ESLDWLNVLLAQI---LAQYRSDAEGDDNLLRKleealnGERKPSfLDPIKVTDLDLGDDFPRFSNARIRPSDDSGGLRA 95

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 200 DLNVSYVGDVQIDVEV-------KKYF----CKAGVKGMQLHGVLRVILEPLTGDLPivgAVSMFFIKRPTLDINWTGM- 267
Cdd:cd21671  96 EIDIDYSDTISLGIDTslllnypKPRFaslpVSLSVSLVRFSGTLTIELPSPSSPGP---TLSFSLLPDFRLDLKVSSLi 172

                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 74220133 268 ---TNLLDIPGLSSLSDTMIMDSIAAFLVLPNRLLVPLvPDL 306
Cdd:cd21671 173 gsrAKLQDVPKLHSLIESRLRRWFADRCVEPNFWKIVL-PSL 213
C2B_RasA3 cd04010
C2 domain second repeat present in RAS p21 protein activator 3 (RasA3); RasA3 are members of ...
 470-569 3.63e-03

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: 38.53  E-value: 3.63e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 470 LVVYLDRAQDLPLKKGNKEPNPMVQL---SVQDVTRESKATYSTNSPVWEEAFRF---FLQDPRSQELDVQVKD-DSRAL 542
Cdd:cd04010   2 LSVRVIECSDLALKNGTCDPYASVTLiysNKKQDTKRTKVKKKTNNPQFDEAFYFdvtIDSSPEKKQFEMPEEDaEKLEL 81

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 74220133 543 T--------------LGALTLPLaRLLTASELTLDQWFQLS 569
Cdd:cd04010  82 RvdlwhasmgggdvfLGEVRIPL-RGLDLQAGSHQAWYFLQ 121
C2_putative_Elicitor-responsive_gene cd04049
C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive ...
 319-426 4.80e-03

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: 37.31  E-value: 4.80e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 319 GIIRIHLLAARGLSSKDkyvkglIEGKSDPYALVRVGTQTFCSRVI-DEELNPHWGETYEVIVhEVPGQEIEVEVFDK-- 395
Cdd:cd04049   1 GTLEVLLISAKGLQDTD------FLGKIDPYVIIQCRTQERKSKVAkGDGRNPEWNEKFKFTV-EYPGWGGDTKLILRim 73

                        90       100       110
                ....*....|....*....|....*....|....
gi 74220133 396 ---DPDKDDFLGRMKLDVGKVLQAGVLDNWYPLQ 426
Cdd:cd04049  74 dkdNFSDDDFIGEATIHLKGLFEEGVEPGTAELV 107
C2A_Synaptotagmin-like cd04024
C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
 469-573 5.21e-03

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: 37.40  E-value: 5.21e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74220133 469 ILVVYLDRAQDLPLK--KGNKEPNPMVQLSVQDVTRESKATYSTNSPVWEEAFRFFLQDPRSQELDVQVKDDSRAL---T 543
Cdd:cd04024   2 VLRVHVVEAKDLAAKdrSGKGKSDPYAILSVGAQRFKTQTIPNTLNPKWNYWCEFPIFSAQNQLLKLILWDKDRFAgkdY 81

                        90       100       110
                ....*....|....*....|....*....|.
gi 74220133 544 LGALTLPLARLLTASEL-TLDQWFQLSSSGP 573
Cdd:cd04024  82 LGEFDIALEEVFADGKTgQSDKWITLKSTRP 112
 
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.
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