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Conserved domains on  [gi|130502162|ref|NP_075055|]
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RAS protein activator like-3 isoform 1 [Homo sapiens]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
RasGAP_DAB2IP cd05136
Ras-GTPase Activating Domain of DAB2IP and similar proteins; The DAB2IP family of Ras ...
 426-743 6.23e-174

Ras-GTPase Activating Domain of DAB2IP and similar proteins; The DAB2IP family of Ras GTPase-activating proteins includes DAB2IP, nGAP, and Syn GAP. Disabled 2 interactive protein, (DAB2IP; also known as ASK-interacting protein 1 (AIP1)), is a member of the GTPase-activating proteins, down-regulates Ras-mediated signal pathways, and mediates TNF-induced activation of ASK1-JNK signaling pathways. The mechanism by which TNF signaling is coupled to DAB2IP is not known.


:

Pssm-ID: 213338  Cd Length: 324  Bit Score: 509.82  E-value: 6.23e-174
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  426 VLPSERYKELAEFLTFHYARLCGALEPALPAQAKEELAAAMVRVLRATGRAQALVTDLGTAELARCGgREALLFRENTLA 505
Cdd:cd05136     7 ILPLEVYKEFLEYLTNNYLDLCEVLEPVLSVKAKEELATALVHILQSTGKAKEFLTDLVMAEVDRLD-DEHLIFRGNTLA 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  506 TKAIDEYMKLVAQDYLQETLGQVVRRLCASTEDCEVDPSKCPAS-ELPEHQARLRNSCEEVFETIIHSYDWFPAELGIVF 584
Cdd:cd05136    86 TKAMEAYLKLVGQKYLQETLGEFIRALYESEEDCEVDPSKCPPSaSLSRNQANLRRSVELAWCKILSSHCVFPRELREVF 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  585 SSWREACKERGSEVLGPRLVCASLFLRLLCPAILAPSLFGLAPDHPAPGPARTLTLIAKVIQNLANRAPFGEKEAYMGFM 664
Cdd:cd05136   166 SSWRERLEERGREDIADRLISASLFLRFLCPAILSPSLFNLTQEYPSERAARNLTLIAKVIQNLANFTRFGGKEEYMEFM 245

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 130502162  665 NSFLEEHGPAMQCFLDQVAMVDVDAAPSGYQGSGDLALQLAVLHAQLCTIFAELDQTTRDTLEPLPTILRAIEEGQPVL 743
Cdd:cd05136   246 NDFVEQEWPNMKQFLQEISSPSPSSNSSDFDGYIDLGRELSLLHSLLVEIISKLNQTTLDKLGPLPRILNDITEALRNP 324
PH_RASAL3 cd13374
RAS protein activator like-3 Pleckstrin homology (PH) domain; RASAL3 is thought to be a Ras ...
 180-321 2.09e-88

RAS protein activator like-3 Pleckstrin homology (PH) domain; RASAL3 is thought to be a Ras GTPase-activating protein. It is involved in positive regulation of Ras GTPase activity and of small GTPase mediated signal transduction as well as negative regulation of Ras protein signal transduction. It contains a PH domain, a C2 domain, and a Ras-GAP domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


:

Pssm-ID: 270177  Cd Length: 146  Bit Score: 279.21  E-value: 2.09e-88
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  180 DPDRMPGKTEPETAGPNQVHNVRGLLKRLKEKKKARLE----PRDGPPSALGSRESLATLSELDLGAERDVRIWPLHPSL 255
Cdd:cd13374     1 DPDREPGKTEPEAAGPNQGHNVRGLLKRLKEKKKAKAEstgtGRDGPPSALGSRESLATISELDLGAERDVRVWPLHPSL 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 130502162  256 LGEPHCFQVTWTGGSRCFSCRSAAERDRWIEDLRRQFQPTQDNVEREETWLSVWVHEAKGLPRAAA 321
Cdd:cd13374    81 LGEPHCFQVTWPGGSRCFSCRSAAERDRWIEDLRRSFQPHQDNVEREETWLSVWVHEAKGLPRAAA 146
C2 super family cl14603
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 294-406 1.58e-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.


The actual alignment was detected with superfamily member cd04013:

Pssm-ID: 472691 [Multi-domain]  Cd Length: 146  Bit Score: 71.57  E-value: 1.58e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  294 PTQDNVEREETWLSVWVHEAKGLPraaagaPGVR--AELWLDGALLARTAPRAGPGQLFWAERFHFEALPPARR------ 365
Cdd:cd04013     1 PNRDNSRRTENSLKLWIIEAKGLP------PKKRyyCELCLDKTLYARTTSKLKTDTLFWGEHFEFSNLPPVSVitvnly 74

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 130502162  366 LSLRLRGLGPGSAVLGRVALALEELDApRAPaagLERWFPL 406
Cdd:cd04013    75 RESDKKKKKDKSQLIGTVNIPVTDVSS-RQF---VEKWYPV 111
COG4372 COG4372
Uncharacterized protein, contains DUF3084 domain [Function unknown];
890-986 5.82e-05

Uncharacterized protein, contains DUF3084 domain [Function unknown];


:

Pssm-ID: 443500 [Multi-domain]  Cd Length: 370  Bit Score: 46.43  E-value: 5.82e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  890 KLAELQCEVAALREEQKVLSRLVESLSTQIRALTEQQEQLRGQLQDLDSRLRAGSSEFDSEHNLTSNEGHSLKNLEHRLN 969
Cdd:COG4372    39 ELDKLQEELEQLREELEQAREELEQLEEELEQARSELEQLEEELEELNEQLQAAQAELAQAQEELESLQEEAEELQEELE 118

                          90
                  ....*....|....*..
gi 130502162  970 EMERTQAQLRDAVQSLQ 986
Cdd:COG4372   119 ELQKERQDLEQQRKQLE 135
 
Name Accession Description Interval E-value
RasGAP_DAB2IP cd05136
Ras-GTPase Activating Domain of DAB2IP and similar proteins; The DAB2IP family of Ras ...
 426-743 6.23e-174

Ras-GTPase Activating Domain of DAB2IP and similar proteins; The DAB2IP family of Ras GTPase-activating proteins includes DAB2IP, nGAP, and Syn GAP. Disabled 2 interactive protein, (DAB2IP; also known as ASK-interacting protein 1 (AIP1)), is a member of the GTPase-activating proteins, down-regulates Ras-mediated signal pathways, and mediates TNF-induced activation of ASK1-JNK signaling pathways. The mechanism by which TNF signaling is coupled to DAB2IP is not known.


Pssm-ID: 213338  Cd Length: 324  Bit Score: 509.82  E-value: 6.23e-174
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  426 VLPSERYKELAEFLTFHYARLCGALEPALPAQAKEELAAAMVRVLRATGRAQALVTDLGTAELARCGgREALLFRENTLA 505
Cdd:cd05136     7 ILPLEVYKEFLEYLTNNYLDLCEVLEPVLSVKAKEELATALVHILQSTGKAKEFLTDLVMAEVDRLD-DEHLIFRGNTLA 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  506 TKAIDEYMKLVAQDYLQETLGQVVRRLCASTEDCEVDPSKCPAS-ELPEHQARLRNSCEEVFETIIHSYDWFPAELGIVF 584
Cdd:cd05136    86 TKAMEAYLKLVGQKYLQETLGEFIRALYESEEDCEVDPSKCPPSaSLSRNQANLRRSVELAWCKILSSHCVFPRELREVF 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  585 SSWREACKERGSEVLGPRLVCASLFLRLLCPAILAPSLFGLAPDHPAPGPARTLTLIAKVIQNLANRAPFGEKEAYMGFM 664
Cdd:cd05136   166 SSWRERLEERGREDIADRLISASLFLRFLCPAILSPSLFNLTQEYPSERAARNLTLIAKVIQNLANFTRFGGKEEYMEFM 245

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 130502162  665 NSFLEEHGPAMQCFLDQVAMVDVDAAPSGYQGSGDLALQLAVLHAQLCTIFAELDQTTRDTLEPLPTILRAIEEGQPVL 743
Cdd:cd05136   246 NDFVEQEWPNMKQFLQEISSPSPSSNSSDFDGYIDLGRELSLLHSLLVEIISKLNQTTLDKLGPLPRILNDITEALRNP 324
PH_RASAL3 cd13374
RAS protein activator like-3 Pleckstrin homology (PH) domain; RASAL3 is thought to be a Ras ...
 180-321 2.09e-88

RAS protein activator like-3 Pleckstrin homology (PH) domain; RASAL3 is thought to be a Ras GTPase-activating protein. It is involved in positive regulation of Ras GTPase activity and of small GTPase mediated signal transduction as well as negative regulation of Ras protein signal transduction. It contains a PH domain, a C2 domain, and a Ras-GAP domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270177  Cd Length: 146  Bit Score: 279.21  E-value: 2.09e-88
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  180 DPDRMPGKTEPETAGPNQVHNVRGLLKRLKEKKKARLE----PRDGPPSALGSRESLATLSELDLGAERDVRIWPLHPSL 255
Cdd:cd13374     1 DPDREPGKTEPEAAGPNQGHNVRGLLKRLKEKKKAKAEstgtGRDGPPSALGSRESLATISELDLGAERDVRVWPLHPSL 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 130502162  256 LGEPHCFQVTWTGGSRCFSCRSAAERDRWIEDLRRQFQPTQDNVEREETWLSVWVHEAKGLPRAAA 321
Cdd:cd13374    81 LGEPHCFQVTWPGGSRCFSCRSAAERDRWIEDLRRSFQPHQDNVEREETWLSVWVHEAKGLPRAAA 146
RasGAP smart00323
GTPase-activator protein for Ras-like GTPases; All alpha-helical domain that accelerates the ...
 426-708 3.63e-78

GTPase-activator protein for Ras-like GTPases; All alpha-helical domain that accelerates the GTPase activity of Ras, thereby "switching" it into an "off" position. Improved domain limits from structure.


Pssm-ID: 214617  Cd Length: 344  Bit Score: 259.16  E-value: 3.63e-78
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162    426 VLPSERYKELAEFLTFHY-ARLCGALEPALPAQAKEELAAAMVRVLRATGRAQALVTDLGTAELARCGgREALLFRENTL 504
Cdd:smart00323   20 ILPSEYYEELLELLLFSLdLSLASALSEVCSGLDKDELATKLVRLFLRRGRGHPFLRALIDPEVERTD-DPNTIFRGNSL 98

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162    505 ATKAIDEYMKLVAQDYLQETLGQVVRRLCASTEDCEVDPSKCPASELPEHQARLRNSCEEVFETIIHSYDWFPAELGIVF 584
Cdd:smart00323   99 ATKSMEVYMKLVGNQYLHTTLKPVLKKIVESKKSCEVDPAKLEGEDLETNLENLLQYVERLFDAIINSSDRLPYGLRDIC 178

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162    585 SSWREACKERGSEVLGP-RLVCASLFLRLLCPAILAPSLFGLAPDHPAPGPARTLTLIAKVIQNLANRAPFGEKEAYMGF 663
Cdd:smart00323  179 KQLRQAAEKRFPDADVIyKAVSSFVFLRFFCPAIVSPKLFNLVDEHPDPTTRRTLTLIAKVLQNLANLSEFGSKEPWMEP 258

                           250       260       270       280
                    ....*....|....*....|....*....|....*....|....*
gi 130502162    664 MNSFLEEHGPAMQCFLDQVAMVDVDAAPSGYQGSGDLALQLAVLH 708
Cdd:smart00323  259 LNDFLLSHKDRVKDFLDELSSVPEILVDKVSDSTTISGRELSLLH 303
RasGAP pfam00616
GTPase-activator protein for Ras-like GTPase; All alpha-helical domain that accelerates the ...
 498-650 8.62e-25

GTPase-activator protein for Ras-like GTPase; All alpha-helical domain that accelerates the GTPase activity of Ras, thereby "switching" it into an "off" position.


Pssm-ID: 459871  Cd Length: 207  Bit Score: 103.13  E-value: 8.62e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162   498 LFRENTLATKAIDEYMKL-VAQDYLQETLGQVVRRLCASTE-DCEVDPSK------------------------CPASEL 551
Cdd:pfam00616   19 LLRGNSLVSKLLETYNRRpRGQEYLKKVLGPLVRKIIEDEDlDLESDPRKiyeslinqeelktgrsdlprdvspEEAIED 98

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162   552 PE-------HQARLRNSCEEVFETIIHSYDWFPAELGIV----FSSWREACKERGSEVLgpRLVCAS-LFLRLLCPAILA 619
Cdd:pfam00616   99 PEvrqifedNLQKLRELADEFLDAIYSSLNQLPYGIRYIckqlYELLEEKFPDASEEEI--LNAIGGfLFLRFFCPAIVN 176

                          170       180       190
                   ....*....|....*....|....*....|.
gi 130502162   620 PSLFGLAPDHPAPGPARTLTLIAKVIQNLAN 650
Cdd:pfam00616  177 PDLFGLVDHQISPKQRRNLTLIAKVLQNLAN 207
C2_SynGAP_like cd04013
C2 domain present in Ras GTPase activating protein (GAP) family; SynGAP, GAP1, RasGAP, and ...
 294-406 1.58e-14

C2 domain present in Ras GTPase activating protein (GAP) family; SynGAP, GAP1, RasGAP, and neurofibromin are all members of the Ras-specific GAP (GTPase-activating protein) family. SynGAP regulates the MAP kinase signaling pathway and is critical for cognition and synapse function. Mutations in this gene causes mental retardation in humans. SynGAP contains a PH-like domain, a C2 domain, and a Ras-GAP domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175980 [Multi-domain]  Cd Length: 146  Bit Score: 71.57  E-value: 1.58e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  294 PTQDNVEREETWLSVWVHEAKGLPraaagaPGVR--AELWLDGALLARTAPRAGPGQLFWAERFHFEALPPARR------ 365
Cdd:cd04013     1 PNRDNSRRTENSLKLWIIEAKGLP------PKKRyyCELCLDKTLYARTTSKLKTDTLFWGEHFEFSNLPPVSVitvnly 74

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 130502162  366 LSLRLRGLGPGSAVLGRVALALEELDApRAPaagLERWFPL 406
Cdd:cd04013    75 RESDKKKKKDKSQLIGTVNIPVTDVSS-RQF---VEKWYPV 111
COG4372 COG4372
Uncharacterized protein, contains DUF3084 domain [Function unknown];
890-986 5.82e-05

Uncharacterized protein, contains DUF3084 domain [Function unknown];


Pssm-ID: 443500 [Multi-domain]  Cd Length: 370  Bit Score: 46.43  E-value: 5.82e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  890 KLAELQCEVAALREEQKVLSRLVESLSTQIRALTEQQEQLRGQLQDLDSRLRAGSSEFDSEHNLTSNEGHSLKNLEHRLN 969
Cdd:COG4372    39 ELDKLQEELEQLREELEQAREELEQLEEELEQARSELEQLEEELEELNEQLQAAQAELAQAQEELESLQEEAEELQEELE 118

                          90
                  ....*....|....*..
gi 130502162  970 EMERTQAQLRDAVQSLQ 986
Cdd:COG4372   119 ELQKERQDLEQQRKQLE 135
SMC_prok_B TIGR02168
chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...
 869-986 5.68e-04

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274008 [Multi-domain]  Cd Length: 1179  Bit Score: 43.89  E-value: 5.68e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162   869 QRQMDQPQDRNQALGThrpvnKLAELQCEVAALREE-QKVLSRL-------------VESLSTQIRALTEQQEQLRGQLQ 934
Cdd:TIGR02168  788 EAQIEQLKEELKALRE-----ALDELRAELTLLNEEaANLRERLeslerriaaterrLEDLEEQIEELSEDIESLAAEIE 862

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 130502162   935 DLDSRLRAGSSEFDSEHNL--TSNEG-----HSLKNLEHRLNEMERTQAQLRDAVQSLQ 986
Cdd:TIGR02168  863 ELEELIEELESELEALLNEraSLEEAlallrSELEELSEELRELESKRSELRRELEELR 921
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 252-290 6.35e-04

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 40.22  E-value: 6.35e-04
                            10        20        30        40
                    ....*....|....*....|....*....|....*....|
gi 130502162    252 HPSLLGEPHCFQV-TWTGGSRCFSCRSAAERDRWIEDLRR 290
Cdd:smart00233   60 DPDSSKKPHCFEIkTSDRKTLLLQAESEEEREKWVEALRK 99
SUN2_cc1 cd21438
coiled-coil domain 1 of SUN domain-containing protein 2 and similar proteins; SUN ...
 871-927 1.78e-03

coiled-coil domain 1 of SUN domain-containing protein 2 and similar proteins; SUN domain-containing protein 2 (SUN2), also called protein unc-84 homolog B, Rab5-interacting protein (Rab5IP), or Sad1/unc-84 protein-like 2, is a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex which is involved in the connection between the nuclear lamina and the cytoskeleton. Besides the core SUN domain, SUN2 contains two coiled-coil domains (CC1 and CC2), which act as the intrinsic dynamic regulators for controlling the activity of the SUN domain. This model corresponds to CC1 that functions as an activation segment to release CC2-mediated inhibition of the SUN domain.


Pssm-ID: 410604 [Multi-domain]  Cd Length: 55  Bit Score: 37.29  E-value: 1.78e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 130502162  871 QMDQPQDRNQALGthRPVNKLAELQCEVAALREEQKVLSRLVESLSTQIRALTEQQE 927
Cdd:cd21438     1 QEDLQENFQKELG--RLEAQLAGLRQELAALRSDQKALSQQVESFPGQIKAVRDDVE 55
UPF0242 pfam06785
Uncharacterized protein family (UPF0242) N-terminus; This region includes an N-terminal ...
 877-980 3.93e-03

Uncharacterized protein family (UPF0242) N-terminus; This region includes an N-terminal transmembrane region and a C-terminal coiled-coil.


Pssm-ID: 429117 [Multi-domain]  Cd Length: 194  Bit Score: 39.80  E-value: 3.93e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162   877 DRNQALGTHRPVNKLAELQCEVAALREEQKVLSRLVESLSTQIRALTEQQEQLRGQLQDLDSRLRAGSSEFDSE------ 950
Cdd:pfam06785   71 EEKEAKLTELDAEGFKILEETLEELQSEEERLEEELSQKEEELRRLTEENQQLQIQLQQISQDFAEFRLESEEQlaekql 150

                           90       100       110
                   ....*....|....*....|....*....|..
gi 130502162   951 -HNLTSNEGHSLKN-LEHRLNEMERTQAQLRD 980
Cdd:pfam06785  151 lINEYQQTIEEQRSvLEKRQDQIENLESKVRD 182
 
Name Accession Description Interval E-value
RasGAP_DAB2IP cd05136
Ras-GTPase Activating Domain of DAB2IP and similar proteins; The DAB2IP family of Ras ...
 426-743 6.23e-174

Ras-GTPase Activating Domain of DAB2IP and similar proteins; The DAB2IP family of Ras GTPase-activating proteins includes DAB2IP, nGAP, and Syn GAP. Disabled 2 interactive protein, (DAB2IP; also known as ASK-interacting protein 1 (AIP1)), is a member of the GTPase-activating proteins, down-regulates Ras-mediated signal pathways, and mediates TNF-induced activation of ASK1-JNK signaling pathways. The mechanism by which TNF signaling is coupled to DAB2IP is not known.


Pssm-ID: 213338  Cd Length: 324  Bit Score: 509.82  E-value: 6.23e-174
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  426 VLPSERYKELAEFLTFHYARLCGALEPALPAQAKEELAAAMVRVLRATGRAQALVTDLGTAELARCGgREALLFRENTLA 505
Cdd:cd05136     7 ILPLEVYKEFLEYLTNNYLDLCEVLEPVLSVKAKEELATALVHILQSTGKAKEFLTDLVMAEVDRLD-DEHLIFRGNTLA 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  506 TKAIDEYMKLVAQDYLQETLGQVVRRLCASTEDCEVDPSKCPAS-ELPEHQARLRNSCEEVFETIIHSYDWFPAELGIVF 584
Cdd:cd05136    86 TKAMEAYLKLVGQKYLQETLGEFIRALYESEEDCEVDPSKCPPSaSLSRNQANLRRSVELAWCKILSSHCVFPRELREVF 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  585 SSWREACKERGSEVLGPRLVCASLFLRLLCPAILAPSLFGLAPDHPAPGPARTLTLIAKVIQNLANRAPFGEKEAYMGFM 664
Cdd:cd05136   166 SSWRERLEERGREDIADRLISASLFLRFLCPAILSPSLFNLTQEYPSERAARNLTLIAKVIQNLANFTRFGGKEEYMEFM 245

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 130502162  665 NSFLEEHGPAMQCFLDQVAMVDVDAAPSGYQGSGDLALQLAVLHAQLCTIFAELDQTTRDTLEPLPTILRAIEEGQPVL 743
Cdd:cd05136   246 NDFVEQEWPNMKQFLQEISSPSPSSNSSDFDGYIDLGRELSLLHSLLVEIISKLNQTTLDKLGPLPRILNDITEALRNP 324
PH_RASAL3 cd13374
RAS protein activator like-3 Pleckstrin homology (PH) domain; RASAL3 is thought to be a Ras ...
 180-321 2.09e-88

RAS protein activator like-3 Pleckstrin homology (PH) domain; RASAL3 is thought to be a Ras GTPase-activating protein. It is involved in positive regulation of Ras GTPase activity and of small GTPase mediated signal transduction as well as negative regulation of Ras protein signal transduction. It contains a PH domain, a C2 domain, and a Ras-GAP domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270177  Cd Length: 146  Bit Score: 279.21  E-value: 2.09e-88
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  180 DPDRMPGKTEPETAGPNQVHNVRGLLKRLKEKKKARLE----PRDGPPSALGSRESLATLSELDLGAERDVRIWPLHPSL 255
Cdd:cd13374     1 DPDREPGKTEPEAAGPNQGHNVRGLLKRLKEKKKAKAEstgtGRDGPPSALGSRESLATISELDLGAERDVRVWPLHPSL 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 130502162  256 LGEPHCFQVTWTGGSRCFSCRSAAERDRWIEDLRRQFQPTQDNVEREETWLSVWVHEAKGLPRAAA 321
Cdd:cd13374    81 LGEPHCFQVTWPGGSRCFSCRSAAERDRWIEDLRRSFQPHQDNVEREETWLSVWVHEAKGLPRAAA 146
RasGAP smart00323
GTPase-activator protein for Ras-like GTPases; All alpha-helical domain that accelerates the ...
 426-708 3.63e-78

GTPase-activator protein for Ras-like GTPases; All alpha-helical domain that accelerates the GTPase activity of Ras, thereby "switching" it into an "off" position. Improved domain limits from structure.


Pssm-ID: 214617  Cd Length: 344  Bit Score: 259.16  E-value: 3.63e-78
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162    426 VLPSERYKELAEFLTFHY-ARLCGALEPALPAQAKEELAAAMVRVLRATGRAQALVTDLGTAELARCGgREALLFRENTL 504
Cdd:smart00323   20 ILPSEYYEELLELLLFSLdLSLASALSEVCSGLDKDELATKLVRLFLRRGRGHPFLRALIDPEVERTD-DPNTIFRGNSL 98

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162    505 ATKAIDEYMKLVAQDYLQETLGQVVRRLCASTEDCEVDPSKCPASELPEHQARLRNSCEEVFETIIHSYDWFPAELGIVF 584
Cdd:smart00323   99 ATKSMEVYMKLVGNQYLHTTLKPVLKKIVESKKSCEVDPAKLEGEDLETNLENLLQYVERLFDAIINSSDRLPYGLRDIC 178

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162    585 SSWREACKERGSEVLGP-RLVCASLFLRLLCPAILAPSLFGLAPDHPAPGPARTLTLIAKVIQNLANRAPFGEKEAYMGF 663
Cdd:smart00323  179 KQLRQAAEKRFPDADVIyKAVSSFVFLRFFCPAIVSPKLFNLVDEHPDPTTRRTLTLIAKVLQNLANLSEFGSKEPWMEP 258

                           250       260       270       280
                    ....*....|....*....|....*....|....*....|....*
gi 130502162    664 MNSFLEEHGPAMQCFLDQVAMVDVDAAPSGYQGSGDLALQLAVLH 708
Cdd:smart00323  259 LNDFLLSHKDRVKDFLDELSSVPEILVDKVSDSTTISGRELSLLH 303
RasGAP cd04519
Ras GTPase Activating Domain; RasGAP functions as an enhancer of the hydrolysis of GTP that is ...
 430-684 5.63e-69

Ras GTPase Activating Domain; RasGAP functions as an enhancer of the hydrolysis of GTP that is bound to Ras-GTPases. Proteins having a RasGAP domain include p120GAP, IQGAP, Rab5-activating protein 6, and Neurofibromin, among others. Although the Rho (Ras homolog) GTPases are most closely related to members of the Ras family, RhoGAP and RasGAP exhibit no similarity at their amino acid sequence level. RasGTPases function as molecular switches in a large number of signaling pathways. They are in the on state when bound to GTP, and in the off state when bound to GDP. The RasGAP domain speeds up the hydrolysis of GTP in Ras-like proteins acting as a negative regulator.


Pssm-ID: 213328  Cd Length: 256  Bit Score: 230.84  E-value: 5.63e-69
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  430 ERYKELAEFLTFHYARLCGALEPALPAQAKEELAAAMVRVLRATGRAQALVTDLGTAELARCGgREALLFRENTLATKAI 509
Cdd:cd04519     1 EEYRLLSLLLTESPLALLRELSQVLPVKDKEEVATALLRIFESRGLALEFLRYLVRSEVKNTK-NPNTLFRGNSLATKLL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  510 DEYMKLVAQDYLQETLGQVVRRLCASTEDCEVDPSKCPASELPEHQARLRNSCEEVFETIIHSYDWFPAELGIVFSSWRE 589
Cdd:cd04519    80 DQYMKLVGQEYLKETLSPLIREILESKESCEIDTKLPVGEDLEENLENLLELVNKLVDRILSSLDRLPPELRYVFKILRE 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  590 ACKER--GSEVLGPRLVCASLFLRLLCPAILAPSLFGLAPDHPAPGPARTLTLIAKVIQNLANRAPFGEKEAYMGFMNSF 667
Cdd:cd04519   160 FLAERfpEEPDEAYQAVSGFLFLRFICPAIVSPELFGLVPDEPSEQARRNLTLISKVLQSLANGVEFGDKEPFMKPLNDF 239

                         250
                  ....*....|....*..
gi 130502162  668 LEEHGPAMQCFLDQVAM 684
Cdd:cd04519   240 IKSNKPKLKQFLDELSS 256
RasGAP_CLA2_BUD2 cd05137
Ras-GTPase Activating Domain of CLA2/BUD2; CLA2/BUD2 functions as a GTPase-activating protein ...
 426-730 1.16e-62

Ras-GTPase Activating Domain of CLA2/BUD2; CLA2/BUD2 functions as a GTPase-activating protein (GAP) for BUD1/RSR1 and is necessary for proper bud-site selection in yeast. BUD2 has sequence similarity to the catalytic domain of RasGAPs, and stimulates the hydrolysis of BUD1-GTP to BUD1-GDP. Elimination of Bud2p activity by mutation causes a random budding pattern with no growth defect. Overproduction of Bud2p also alters the budding pattern.


Pssm-ID: 213339 [Multi-domain]  Cd Length: 356  Bit Score: 216.66  E-value: 1.16e-62
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  426 VLPSERYKELAEFLTFHYARLCGALEPALPAQAKEELAAAMVRVLRATGRA----QALVTD---------LGTAELARCG 492
Cdd:cd05137     9 VLPSKNYKPLEELLHNFDLGLTLQIAELVPGDKLERLSEILLDIFQASGREdewfMALVEDeidgidkstSKNKDMGKSS 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  493 GREA-LLFRENTLATKAIDEYMKLVAQDYLQETLGQVVRRLCASTEDCEVDPSKCPASE-------LPEHQARLRNSCEE 564
Cdd:cd05137    89 NNEAnLLFRGNSLLTKSLEKYMRRIGKEYLEKSIGDVIRKICEENKDCEVDPSRVKESDsiekeedLEENWENLISLTEE 168

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  565 VFETIIHSYDWFPAELGIVFSSWREACKER-GSEVLGPRLVCAS--LFLRLLCPAILAPSLFGLAPDHPAPGPARTLTLI 641
Cdd:cd05137   169 IWNSIYITSNDCPPELRKILKHIRAKVEDRyGDFLRTVTLNSVSgfLFLRFFCPAILNPKLFGLLKDHPRPRAQRTLTLI 248

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  642 AKVIQNLANRAPFGEKEAYMGFMNSFLEEHGPAMQCFLDQVAMVDVDAAPSGYQGSGDLALqlavlhaqlcTIFAELDQT 721
Cdd:cd05137   249 AKVLQNLANLTTFGQKEPWMEPMNEFLTTHREELKDYIDKITGIKLDFTPKILPLSYSTPI----------RILGRLPPL 318


                  ....*....
gi 130502162  722 TRDTLEPLP 730
Cdd:cd05137   319 SREGLPTLP 327
RasGAP_GAP1_like cd05128
Ras-GTPase Activating Domain of GAP1 and similar proteins; The GAP1 family of Ras ...
 432-685 1.91e-52

Ras-GTPase Activating Domain of GAP1 and similar proteins; The GAP1 family of Ras GTPase-activating proteins includes GAP1(m) (or RASA2), GAP1_IP4BP (or RASA3), Ca2+ -promoted Ras inactivator (CAPRI, or RASAL4), and Ras GTPase activating-like proteins (RASAL) or RASAL1. The members are characterized by a conserved domain structure comprising N-terminal tandem C2 domains, a highly conserved central RasGAP domain, and a C-terminal pleckstrin homology domain that is associated with a Bruton's tyrosine kinase motif. While this domain structure is conserved, a small change in the function of each individual domain and the interaction between domains has a marked effect on the regulation of each protein.


Pssm-ID: 213330  Cd Length: 269  Bit Score: 184.76  E-value: 1.91e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  432 YKELAEFLT------FHYARLCGALEpALPAQAKEELAAAMVRVLRATGRAQALVTDLGTAELARCGgREALLFRENTLA 505
Cdd:cd05128     3 YEPLLNLLLesldvpPFTASAVYLLE-ELVKVDKDDVARPLVRIFLHHGQIVPLLRALASREISKTQ-DPNTLFRGNSLA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  506 TKAIDEYMKLVAQDYLQETLGQVVRRLCASTEDCEVDPSKCPASELPE-HQARLRNSCEEVFETIIHSYDWFPAELGIVF 584
Cdd:cd05128    81 SKCMDEFMKLVGMQYLHETLKPVIDEIFSEKKSCEIDPSKLKDGEVLEtNLANLRGYVERVFKAITSSARRCPTLMCEIF 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  585 SSWREACKERGSEVLGPRLVCAS--LFLRLLCPAILAPSLFGLAPDHPAPGPARTLTLIAKVIQNLAN----RAPFGEKE 658
Cdd:cd05128   161 SDLRESAAQRFPDNEDVPYTAVSgfIFLRFFAPAILNPKLFGLREEHPDPQTARTLTLISKTIQTLGNlgssSSGLGVKE 240

                         250       260
                  ....*....|....*....|....*....
gi 130502162  659 AYM-GFMNSFL-EEHGPAMQCFLDQVAMV 685
Cdd:cd05128   241 AYMsPLYERFTdEQHVDAVKKFLDRISSV 269
RasGAP_p120GAP cd05391
Ras-GTPase Activating Domain of p120; p120GAP is a negative regulator of Ras that stimulates ...
 426-740 2.96e-45

Ras-GTPase Activating Domain of p120; p120GAP is a negative regulator of Ras that stimulates hydrolysis of bound GTP to GDP. Once the Ras regulator p120GAP, a member of the GAP protein family, is recruited to the membrane, it is transiently immobilized to interact with Ras-GTP. The down-regulation of Ras by p120GAP is a critical step in the regulation of many cellular processes, which is disrupted in approximately 30% of human cancers. p120GAP contains SH2, SH3, PH, calcium- and lipid-binding domains, suggesting its involvement in a complex network of cellular interactions in vivo.


Pssm-ID: 213340  Cd Length: 328  Bit Score: 166.12  E-value: 2.96e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  426 VLPSERYKELAEFL-------TFHYARLCGalepalpaQAKEELAAAMVRVLRATGRAQALVTDLGTAELARcGGREALL 498
Cdd:cd05391     4 IMPEEEYSELKELIlqkelhvVYALAHVCG--------QDRTLLASILLRIFRHEKLESLLLRTLNDREISM-EDEATTL 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  499 FRENTLATKAIDEYMKLVAQDYLQETLGQVVRRLCASTEDCEVDPSKC-PASELPEHQARLRNSCEEVFETIIHSYDWFP 577
Cdd:cd05391    75 FRATTLASTLMEQYMKATATPFVHHALKDTILKILESKQSCELNPSKLeKNEDVNTNLEHLLNILSELVEKIFMAAEILP 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  578 AELGIVFSSWREACKER--GSEVLGPRLVCASLFLRLLCPAILAPSLFGLAPDHPAPGPARTLTLIAKVIQNLANRAPFG 655
Cdd:cd05391   155 PTLRYIYGCLQKSVQQKwpTNTTVRTRVVSGFVFLRLICPAILNPRMFNIISETPSPTAARTLTLVAKSLQNLANLVEFG 234

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  656 EKEAYMGFMNSFLEEHGPAMQCFLDQVAMVDvDAAPSGYQGSGDLALQLAVLHaQLCTIFA-ELDQ--TTRDTLEPLPTI 732
Cdd:cd05391   235 AKEPYMEGVNPFIKKNKERMIMFLDELGNVP-ELPDTTEHSRTDLSRDLAALH-EICVAHSdELRTlsNERGALKKLLAV 312


                  ....*...
gi 130502162  733 LRAIEEGQ 740
Cdd:cd05391   313 TELLQQKQ 320
RasGAP_Neurofibromin_like cd05392
Ras-GTPase Activating Domain of proteins similar to neurofibromin; Neurofibromin-like proteins ...
 428-708 8.01e-44

Ras-GTPase Activating Domain of proteins similar to neurofibromin; Neurofibromin-like proteins include the Saccharomyces cerevisiae RasGAP proteins Ira1 and Ira2, the closest homolog of neurofibromin, which is responsible for the human autosomal dominant disease neurofibromatosis type I (NF1). The RasGAP Ira1/2 proteins are negative regulators of the Ras-cAMP signaling pathway and conserved from yeast to human. In yeast Ras proteins are activated by GEFs, and inhibited by two GAPs, Ira1 and Ira2. Ras proteins activate the cAMP/protein kinase A (PKA) pathway, which controls metabolism, stress resistance, growth, and meiosis. Recent studies showed that the kelch proteins Gpb1 and Gpb2 inhibit Ras activity via association with Ira1 and Ira2. Gpb1/2 bind to a conserved C-terminal domain of Ira1/2, and loss of Gpb1/2 results in a destabilization of Ira1 and Ira2, leading to elevated levels of Ras2-GTP and uninhibited cAMP-PKA signaling. Since the Gpb1/2 binding domain on Ira1/2 is conserved in the human neurofibromin protein, the studies suggest that an analogous signaling mechanism may contribute to the neoplastic development of NF1.


Pssm-ID: 213341  Cd Length: 317  Bit Score: 161.68  E-value: 8.01e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  428 PSERYKELAEFLTFHYaRLCGALEPALPAQAKEELAAAMVRVLRATGRAQALVTDLGTAELARCGgREALLFRENTLATK 507
Cdd:cd05392     2 KSEAYDELLELLIEDP-QLLLAIAEVCPSSEVDLLAQSLLNLFETRNRLLPLISWLIEDEISHTS-RAADLFRRNSVATR 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  508 AIDEYMKLVAQDYLQETLGQVVRRLCASTEDCEVDPSKCPASELPEHQARLRNSCEEVFETIIHSYDWFPAELGIVFSSW 587
Cdd:cd05392    80 LLTLYAKSVGNKYLRKVLRPLLTEIVDNKDYFEVEKIKPDDENLEENADLLMKYAQMLLDSITDSVDQLPPSFRYICNTI 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  588 REACKERGSEvLGPRLVCASLFLRLLCPAILAPSLFGLAPDHPAPGPARTLTLIAKVIQNLANRAPFGEKEAYMGFMNSF 667
Cdd:cd05392   160 YESVSKKFPD-AALIAVGGFLFLRFICPAIVSPESENLLDPPPTPEARRSLILIAKVLQNIANGVLFSLKEPYLESLNEF 238

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|.
gi 130502162  668 LEEHGPAMQCFLDQVAMVDVDAAPSGYQGSGDLALQLAVLH 708
Cdd:cd05392   239 LKKNSDRIQQFLSEVSTIPPTDPIFDESDEEPITADLRYLH 279
PH_RasSynGAP-like cd13262
Synaptic Ras-GTPase activating protein family Pleckstrin homology (PH) domain; The RasSynGAP ...
 184-302 6.30e-41

Synaptic Ras-GTPase activating protein family Pleckstrin homology (PH) domain; The RasSynGAP family is composed of members: DAB2IP, nGAP, and SynGAP. Neuronal growth-associated proteins (nGAPs) are growth cone markers found in multiple types of neurons. There are many nGAPs including Cap1 (Adenylate cyclase-associated protein 1), Capzb (Capping protein (actin filament) muscle Z-line, beta), Clptm1 (Cleft lip and palate associated transmembrane protein 1), Cotl1 (Coactosin-like 1), Crmp1 (Collapsin response mediator protein 1), Cyfip1 (Cytoplasmic FMR1 interacting protein 1), Fabp7 (Fatty acid binding protein 7, brain), Farp2 (FERM, RhoGEF and pleckstrin domain protein 2), Gap43 (Growth associated protein 43), Gnao1 (Guanine nucleotide binding protein (G protein), alpha activating activity polypeptide O), Gnai2 (Guanine nucleotide binding protein (G protein), alpha inhibiting 2), Pacs1 (Phosphofurin acidic cluster sorting protein 1), Rtn1 (Reticulon 1), Sept2 (Septin 2), Snap25 (Synaptosomal-associated protein 25), Strap (Serine/threonine kinase receptor associated protein), Stx7 (Syntaxin 7), and Tmod2 (Tropomodulin 2). SynGAP, a neuronal Ras-GAP, has been shown display both Ras-GAP activity and Ras-related protein (Rap)-GAP activity. Saccharomyces cerevisiae Bud2 and GAP1 members CAPRI (Ca2+-promoted Ras inactivator) and RASAL (Ras-GTPase-activating-like protein) also possess this dual activity. Human DOC-2/DAB2-interacting protein (DAB2IP) is encoded by a tumor suppressor gene and a newly recognized member of the Ras-GTPase-activating family. DAB2IP is a critical component of many signal transduction pathways mediated by Ras and tumor necrosis factors including apoptosis pathways, and it is involved in the formation of many types of tumors. DAB2IP participates in regulation of gene expression and pluripotency of cells. It has been reported that DAB2IP was expressed in different tumor tissues. Little information is available concerning the expression levels of DAB2IP in normal tissues and cells, however, and no studies of its expression patterns during the development of human embryos have been reported. DAB2IP was expressed primarily in cell cytoplasm throughout the fetal development. The expression levels varied among tissues and different gestational ages. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270082  Cd Length: 125  Bit Score: 146.42  E-value: 6.30e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  184 MPGKTEPETAGPNQVHNVRGLLKRLKEKKKAR----LEPRDGPPSALGSRESLATLSE--LDLGAERDVRIWPLHPSLLG 257
Cdd:cd13262     1 ASGFFSRRLKGPLKRTKSVTKLERKSSKRLPRtrlaRAPAGPRLRGSRSHESLLSSSSaaLDLSADEDVVIRPLHSSILG 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 130502162  258 EPHCFQVTWTGGSRCFSCRSAAERDRWIEDLRRQFQPTQDNVERE 302
Cdd:cd13262    81 RKHCFQVTTSEGTRCFSCRSAAERDRWIEDLRRAAQPNKDNCRRT 125
RasGAP_RASA3 cd05134
Ras-GTPase Activating Domain of RASA3; RASA3 (or GAP1_IP4BP) is a member of the GAP1 family ...
 459-683 1.36e-37

Ras-GTPase Activating Domain of RASA3; RASA3 (or GAP1_IP4BP) is a member of the GAP1 family and has been shown to specifically bind 1,3,4,5-tetrakisphosphate (IP4). Thus, RASA3 may function as an IP4 receptor. The members of GAP1 family are characterized by a conserved domain structure comprising N-terminal tandem C2 domains, a highly conserved central RasGAP domain, and a C-terminal pleckstrin-homology domain that is associated with a Bruton's tyrosine kinase motif. Purified RASA3 stimulates GAP activity on Ras with about a five-fold lower potency than p120RasGAP, but shows no GAP-stimulating activity at all against Rac or Rab3A.


Pssm-ID: 213336  Cd Length: 269  Bit Score: 142.09  E-value: 1.36e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  459 KEELAAAMVRVLRATGRAQALVTDLGTAELARCGGREALlFRENTLATKAIDEYMKLVAQDYLQETLGQVVRRLCASTED 538
Cdd:cd05134    35 KQEAAIPLVRLFLHYGKIVPFISAIASAEVNRTQDPNTI-FRGNSLTSKCIDETMKLAGMHYLQVTLKPIIDEICQEHKP 113

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  539 CEVDPSKCPASE-LPEHQARLRNSCEEVFETIIHSYDWFPAELGIVFSSWREACKERGSEVLGPRLVCAS--LFLRLLCP 615
Cdd:cd05134   114 CEIDPVKLKDGEnLENNRENLRQYVDRIFRVITKSGVSCPTVMCDIFFSLRESAAKRFQVDPDVRYTAVSsfIFLRFFAP 193

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 130502162  616 AILAPSLFGLAPDHPAPGPARTLTLIAKVIQNL-----ANRAPFgeKEAYMG-FMNSFLEE-HGPAMQCFLDQVA 683
Cdd:cd05134   194 AILSPNLFQLTPHHPDPQTSRTLTLISKTIQTLgslskSKSANF--KESYMAaFYDYFNEQkYADAVKNFLDLIS 266
PH_SynGAP cd13375
Synaptic Ras-GTPase activating protein Pleckstrin homology (PH) domain; SynGAP is a member of ...
 228-358 9.46e-29

Synaptic Ras-GTPase activating protein Pleckstrin homology (PH) domain; SynGAP is a member of the RasSynGAP family along with DOC-2/DAB2-interacting protein (DAB2IP) and neuronal growth-associated protein (nGAP/RASAL2). SynGAP, a neuronal Ras-GAP, has been shown display both Ras-GAP activity and Ras-related protein (Rap)-GAP activity. Saccharomyces cerevisiae Bud2 and GAP1 members CAPRI (Ca2+-promoted Ras inactivator) and RASAL (Ras-GTPase-activating-like protein) also possess this dual activity. Human DOC-2/DAB2-interacting protein (DAB2IP) is encoded by a tumor suppressor gene and a newly recognized member of the Ras-GTPase-activating family. Members here include mammals, amphibians, and bony fish. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270178  Cd Length: 189  Bit Score: 114.02  E-value: 9.46e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  228 SRESLATLSE----LDLGAERDVRIWPLHPSLLGEPHCFQVTWTGGSRCFSCRSAAERDRWIEDLRRQFQPTQDNVEREE 303
Cdd:cd13375    61 SHESLLSPSSaaeaLDLNLDEDSIIKPVHSSILGQEFCFEVTTASGTKCFACRSAAERDKWIENLQRAVKPNKDNSRRVD 140

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 130502162  304 TWLSVWVHEAKGLPraaagaPGVR--AELWLDGALLARTAPRAGPGQLFWAErfHFE 358
Cdd:cd13375   141 NVLKLWIIEARELP------PKKRyyCELCLDDMLYARTTSKPRTDTVFWGE--HFE 189
PH_DAB2IP cd13376
DOC-2/Disabled homolog 2-interacting protein Pleckstrin homology (PH) domain; DAB2IP (also ...
 228-358 1.07e-28

DOC-2/Disabled homolog 2-interacting protein Pleckstrin homology (PH) domain; DAB2IP (also called AIP1/ASK1-interacting protein-1 and DIP1/2) is a member of the RasSynGAP family along with Synaptic Ras-GTPase activating protein (SynGAP) and neuronal growth-associated protein (nGAP/RASAL2). DAB2IP is a critical component of many signal transduction pathways mediated by Ras and tumor necrosis factors including apoptosis pathways, and it is involved in the formation of many types of tumors. DAB2IP participates in regulation of gene expression and pluripotency of cells. Human DAB2IP is expressed in the adrenal gland, pancreas, endocardium, stomach, kidney, testis, small intestine, liver, trachea, skin, ovary, endometrium, lung, esophagus and bladder. No expression was observed in the cerebrum, parotid gland, thymus, thyroid gland and spleen. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270179  Cd Length: 182  Bit Score: 113.65  E-value: 1.07e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  228 SRESLATLSE----LDLGAERDVRIWPLHPSLLGEPHCFQVTWTGGSRCFSCRSAAERDRWIEDLRRQFQPTQDNVEREE 303
Cdd:cd13376    54 SHESLLSPSSaveaLDLSMEEEVVIKPVHSSILGQDYCFEVTTSSGSKCFSCRSAAERDKWMENLRRAVHPNKDNSRRVE 133

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 130502162  304 TWLSVWVHEAKGLPraaaGAPGVRAELWLDGALLARTAPRAGPGQLFWAErfHFE 358
Cdd:cd13376   134 NMLKLWIIEAKDLP----AKKKYLCELCLDDVLYARTTCKLKTDNVFWGE--HFE 182
RasGAP_RASA2 cd05394
Ras-GTPase Activating Domain of RASA2; RASA2 (or GAP1(m)) is a member of the GAP1 family of ...
 466-683 1.26e-27

Ras-GTPase Activating Domain of RASA2; RASA2 (or GAP1(m)) is a member of the GAP1 family of Ras GTPase-activating proteins that includes GAP1_IP4BP (or RASA3), CAPRI, and RASAL. In vitro, RASA2 has been shown to bind inositol 1,3,4,5-tetrakisphosphate (IP4), the water soluble inositol head group of the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate (PIP3). In vivo studies also demonstrated that RASA2 binds PIP3, and it is recruited to the plasma membrane following agonist stimulation of PI 3-kinase. Furthermore, the membrane translocation is a consequence of the ability of its pleckstrin homology (PH) domain to bind PIP3.


Pssm-ID: 213342  Cd Length: 272  Bit Score: 113.45  E-value: 1.26e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  466 MVRVLRATGRAQALVTDLgtAELARCGGREA-LLFRENTLATKAIDEYMKLVAQDYLQETLGQVVRRLCASTEDCEVDPS 544
Cdd:cd05394    42 LVRLLLHHNKLVPFVAAV--AALDLKDTQEAnTIFRGNSLATRCLDEMMKIVGKHYLKVTLKPVLDEICESPKPCEIDPI 119

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  545 KCPASELPE-HQARLRNSCEEVFETIIHSYDWFPAELGIVFSSWRE-ACKERGSEvlgPRL----VCASLFLRLLCPAIL 618
Cdd:cd05394   120 KLKEGDNVEnNKENLRYYVDKVFFSIVKSSMSCPTLMCDVFRSLRHlAVKRFPND---PHVqysaVSSFVFLRFFAVAVV 196

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 130502162  619 APSLFGLAPDHPAPGPARTLTLIAKVIQ------NLANRAPFGEKEAYM-GFMNSFLEE-HGPAMQCFLDQVA 683
Cdd:cd05394   197 SPHTFQLRPHHPDAQTSRTLTLISKTIQtlgswgSLSKSKLSSFKETFMcDFFKMFQEEkYIEKVKKFLDEIS 269
RasGAP_Neurofibromin cd05130
Ras-GTPase Activating Domain of neurofibromin; Neurofibromin is the product of the ...
 498-683 2.04e-26

Ras-GTPase Activating Domain of neurofibromin; Neurofibromin is the product of the neurofibromatosis type 1 gene (NF1) and shares a region of similarity with catalytic domain of the mammalian p120RasGAP protein and an extended similarity with the Saccharomyces cerevisiae RasGAP proteins Ira1 and Ira2. Neurofibromin has been shown to function as a GAP (GTPase-activating protein) which inhibits low molecular weight G proteins such as Ras by stimulating their intrinsic GTPase activity. NF1 is a common genetic disorder characterized by various symptoms ranging from predisposition for the development of tumors to learning disability or mental retardation. Loss of neurofibromin activity can be correlated to the increase in Ras-GTP concentration in neurofibromas of NF1 of patients, supporting the notion that unregulated Ras signaling may contribute to their development.


Pssm-ID: 213332 [Multi-domain]  Cd Length: 332  Bit Score: 111.26  E-value: 2.04e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  498 LFRENTLATKAIDEYMKLVAQDYLQETLGQVVRRLCASTE--DCEVDPSKCPASE-LPEHQARLRNSCEEVFETIIHSYD 574
Cdd:cd05130    77 LFRGNSLASKIMTFCFKVYGATYLQSLLEPLLRTMITSSEwvSYEVDPTRLEGNEnLEENQRNLLQLTEKFFHAIISSSD 156

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  575 WFPAELgivfsswREACKERgSEVLGPRL-------VCASLFLRLLCPAILAPSLFGLAPDHPAPGPARTLTLIAKVIQN 647
Cdd:cd05130   157 EFPPQL-------RSVCHCL-YQVVSHRFpnsglgaVGSAIFLRFINPAIVSPYEYGILDREPPPRVKRGLKLMSKILQN 228

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 130502162  648 LANRAPFgEKEAYMGFMNSFLEEHGPAMQCFLDQVA 683
Cdd:cd05130   229 IANHVLF-TKEAHMLPFNDFLRNHFEAGRRFFSSIA 263
RasGAP_RASAL cd05135
Ras-GTPase Activating Domain of RASAL1 and similar proteins; Ras GTPase activating-like ...
 450-688 2.75e-26

Ras-GTPase Activating Domain of RASAL1 and similar proteins; Ras GTPase activating-like protein (RASAL) or RASAL1 is a member of the GAP1 family, and a Ca2+ sensor responding in-phase to repetitive Ca2+ signals by associating with the plasma membrane and deactivating Ras. It contains a conserved domain structure comprising N-terminal tandem C2 domains, a highly conserved central RasGAP domain, and a C-terminal pleckstrin-homology domain that is associated with a Bruton's tyrosine kinase motif. RASAL, like Ca2+ -promoted Ras inactivator (CAPRI, or RASAL4), is a cytosolic protein that undergoes a rapid translocation to the plasma membrane in response to receptor-mediated elevation in the concentration of intracellular free Ca2+, a translocation that activates its ability to function as a RasGAP. However, unlike RASAL4, RASAL undergoes an oscillatory translocation to the plasma membrane that occurs in synchrony with repetitive Ca2+ spikes.


Pssm-ID: 213337  Cd Length: 287  Bit Score: 109.90  E-value: 2.75e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  450 LEPALPAQAKEELAAAMVRVLRATGRAQALVTDLGTAELARCGGREALlFRENTLATKAIDEYMKLVAQDYLQETLGQVV 529
Cdd:cd05135    31 LEEVTTGESRQDVATKLVKIFLGQGLVVPFLDYLNTREVGRTTDPNTL-FRSNSLASKSMEQFMKVVGMPYLHEVLKPVI 109

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  530 RRLCASTEDCEVDPSKCPASE---------LPEHQAR------LRNSCEEVFETIIHSYDWFPAELGIVFSSWREACKER 594
Cdd:cd05135   110 NRIFEEKKYVELDPCKIDLNRtrrisfkgsLSEAQVResslelLQGYLGSIIDAIVGSVDQCPPVMRVAFKQLHKRVEER 189

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  595 --GSEVLGPRLVCAS--LFLRLLCPAILAPSLFGLAPDHPAPGPARTLTLIAKVIQNLAN--RAPFGEKEAYMGFMNSFL 668
Cdd:cd05135   190 fpEAEHQDVKYLAISgfLFLRFFAPAILTPKLFQLREQHADPRTSRTLLLLAKAVQSIGNlgLQLGQGKEQWMAPLHPFI 269

                         250       260
                  ....*....|....*....|
gi 130502162  669 EEHGPAMQCFLDQvaMVDVD 688
Cdd:cd05135   270 LQSVARVKDFLDR--LIDID 287
RasGAP pfam00616
GTPase-activator protein for Ras-like GTPase; All alpha-helical domain that accelerates the ...
 498-650 8.62e-25

GTPase-activator protein for Ras-like GTPase; All alpha-helical domain that accelerates the GTPase activity of Ras, thereby "switching" it into an "off" position.


Pssm-ID: 459871  Cd Length: 207  Bit Score: 103.13  E-value: 8.62e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162   498 LFRENTLATKAIDEYMKL-VAQDYLQETLGQVVRRLCASTE-DCEVDPSK------------------------CPASEL 551
Cdd:pfam00616   19 LLRGNSLVSKLLETYNRRpRGQEYLKKVLGPLVRKIIEDEDlDLESDPRKiyeslinqeelktgrsdlprdvspEEAIED 98

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162   552 PE-------HQARLRNSCEEVFETIIHSYDWFPAELGIV----FSSWREACKERGSEVLgpRLVCAS-LFLRLLCPAILA 619
Cdd:pfam00616   99 PEvrqifedNLQKLRELADEFLDAIYSSLNQLPYGIRYIckqlYELLEEKFPDASEEEI--LNAIGGfLFLRFFCPAIVN 176

                          170       180       190
                   ....*....|....*....|....*....|.
gi 130502162   620 PSLFGLAPDHPAPGPARTLTLIAKVIQNLAN 650
Cdd:pfam00616  177 PDLFGLVDHQISPKQRRNLTLIAKVLQNLAN 207
RasGAP_GAPA cd05132
Ras-GTPase Activating Domain of GAPA; GAPA is an IQGAP-related protein and is predicted to ...
 498-686 1.92e-21

Ras-GTPase Activating Domain of GAPA; GAPA is an IQGAP-related protein and is predicted to bind to small GTPases, which are yet to be identified. IQGAP proteins are integral components of cytoskeletal regulation. Results from truncated GAPAs indicated that almost the entire region of GAPA homologous to IQGAP is required for cytokinesis in Dictyostelium. More members of the IQGAP family are emerging, and evidence suggests that there are both similarities and differences in their function.


Pssm-ID: 213334  Cd Length: 352  Bit Score: 97.04  E-value: 1.92e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  498 LFRENTLATKAIDEYMKLV-AQDYLQETLGQVVRRLcASTEDC--EVDPSK-------------CPASELPEH------- 554
Cdd:cd05132    47 LLRANTAVSRMMTTYTRRGpGQSYLKTVLADRINDL-ISLKDLnlEINPLKvyeqmindieldtGLPSNLPRGitpeeaa 125

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  555 ---------QARLRN---SCEEVFETIIHSYDWFPaeLGIvfsSW-----REACKERGSEVlgPRLVCASL-----FLRL 612
Cdd:cd05132   126 enpavqniiEPRLEMleeITNSFLEAIINSLDEVP--YGI---RWickqiRSLTRRKFPDA--SDETICSLiggffLLRF 198

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 130502162  613 LCPAILAPSLFGLAPDHPAPGPARTLTLIAKVIQNLANRAPFGeKEAYMGFMNSFLEEHGPAMQCFLDQVAMVD 686
Cdd:cd05132   199 INPAIVSPQAYMLVDGKPSDNTRRTLTLIAKLLQNLANKPSYS-KEPYMAPLQPFVEENKERLNKFLNDLCEVD 271
PH_nGAP cd13373
Neuronal growth-associated proteins Pleckstrin homology (PH) domain; nGAP (also called RASAL2 ...
 228-306 3.18e-21

Neuronal growth-associated proteins Pleckstrin homology (PH) domain; nGAP (also called RASAL2/RAS protein activator like-3) is a member of the RasSynGAP family along with DOC-2/DAB2-interacting protein (DAB2IP) and synaptic RasGAP (SynGAP). nGAPs are growth cone markers found in multiple types of neurons. There are many nGAPs including Cap1 (Adenylate cyclase-associated protein 1), Capzb (Capping protein (actin filament) muscle Z-line, beta), Clptm1 (Cleft lip and palate associated transmembrane protein 1), Cotl1 (Coactosin-like 1), Crmp1 (Collapsin response mediator protein 1), Cyfip1 (Cytoplasmic FMR1 interacting protein 1), Fabp7 (Fatty acid binding protein 7, brain), Farp2 (FERM, RhoGEF and pleckstrin domain protein 2), Gap43 (Growth associated protein 43), Gnao1 (Guanine nucleotide binding protein (G protein), alpha activating activity polypeptide O), Gnai2 (Guanine nucleotide binding protein (G protein), alpha inhibiting 2), Pacs1 (Phosphofurin acidic cluster sorting protein 1), Rtn1 (Reticulon 1), Sept2 (Septin 2), Snap25 (Synaptosomal-associated protein 25), Strap (Serine/threonine kinase receptor associated protein), Stx7 (Syntaxin 7), and Tmod2 (Tropomodulin 2). PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270176  Cd Length: 138  Bit Score: 90.56  E-value: 3.18e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  228 SRESL----ATLSELDLGAERDVRIWPLHPSLLGEPHCFQVTWTGGSRCFSCRSAAERDRWIEDLRRQFQPTQDNVEREE 303
Cdd:cd13373    54 SHESLlspgSAVEALDLGREEKVSVKPLHSSILGQDFCFEVTYSSGSKCFSCSSAAERDKWMENLRRTVQPNKDNCRRAE 133


                  ...
gi 130502162  304 TWL 306
Cdd:cd13373   134 NVL 136
RasGAP_RASA4 cd05395
Ras-GTPase Activating Domain of RASA4; Ras GTPase activating-like 4 protein (RASAL4), also ...
 428-661 3.20e-17

Ras-GTPase Activating Domain of RASA4; Ras GTPase activating-like 4 protein (RASAL4), also known as Ca2+ -promoted Ras inactivator (CAPRI), is a member of the GAP1 family. Members of the GAP1 family are characterized by a conserved domain structure comprising N-terminal tandem C2 domains, a highly conserved central RasGAP domain, and a C-terminal pleckstrin-homology domain that is associated with a Bruton's tyrosine kinase motif. RASAL4, like RASAL, is a cytosolic protein that undergoes a rapid translocation to the plasma membrane in response to a receptor-mediated elevation in the concentration of intracellular free Ca2+ ([Ca2+]i). However, unlike RASAL, RASAL4 does not sense oscillations in [Ca2+]i.


Pssm-ID: 213343 [Multi-domain]  Cd Length: 287  Bit Score: 83.38  E-value: 3.20e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  428 PSERYKELAEFLT--------FHYARLCGALEPALPAQAKEELAAAMVRVLRATGRAQALVTDLGTAELARCGgREALLF 499
Cdd:cd05395     1 PSSHYQPLVQLLCqevklghqAGPVQLISLIDETTTAECRQEVATNLVKLFLGQGLAKEFLDLLFQLELDKTT-EPNTLF 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  500 RENTLATKAIDEYMKLVAQDYLQETLGQVVRRLCASTEDCEVDPSK-------CPA-------SELPEHQAR-LRNSCEE 564
Cdd:cd05395    80 RSNSLASKSMESFLKVAGMQYLHSVLGPTINRVFEEKKYVELDPSKveikdvgCSGlhriqteSEVIEQSAQlLQSYLGE 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  565 VFETIIHSYDWFPAELGIVFSSWREACKERGSEVLGPRL----VCASLFLRLLCPAILAPSLFGLAPDHPAPGPARTLTL 640
Cdd:cd05395   160 LLSAISKSVKYCPAVIRATFRQLFKRVQERFPENQHQNVkfiaVTSFLCLRFFSPAIMSPKLFHLREKHADARTSRTLLL 239

                         250       260
                  ....*....|....*....|...
gi 130502162  641 IAKVIQNLANRAPFG--EKEAYM 661
Cdd:cd05395   240 LAKAVQNVGNMDTLAsrAKEAWM 262
C2_SynGAP_like cd04013
C2 domain present in Ras GTPase activating protein (GAP) family; SynGAP, GAP1, RasGAP, and ...
 294-406 1.58e-14

C2 domain present in Ras GTPase activating protein (GAP) family; SynGAP, GAP1, RasGAP, and neurofibromin are all members of the Ras-specific GAP (GTPase-activating protein) family. SynGAP regulates the MAP kinase signaling pathway and is critical for cognition and synapse function. Mutations in this gene causes mental retardation in humans. SynGAP contains a PH-like domain, a C2 domain, and a Ras-GAP domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175980 [Multi-domain]  Cd Length: 146  Bit Score: 71.57  E-value: 1.58e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  294 PTQDNVEREETWLSVWVHEAKGLPraaagaPGVR--AELWLDGALLARTAPRAGPGQLFWAERFHFEALPPARR------ 365
Cdd:cd04013     1 PNRDNSRRTENSLKLWIIEAKGLP------PKKRyyCELCLDKTLYARTTSKLKTDTLFWGEHFEFSNLPPVSVitvnly 74

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 130502162  366 LSLRLRGLGPGSAVLGRVALALEELDApRAPaagLERWFPL 406
Cdd:cd04013    75 RESDKKKKKDKSQLIGTVNIPVTDVSS-RQF---VEKWYPV 111
RasGAP_IQGAP_like cd05127
Ras-GTPase Activating Domain of IQ motif containing GTPase activating proteins; This family ...
 518-686 1.65e-10

Ras-GTPase Activating Domain of IQ motif containing GTPase activating proteins; This family represents IQ motif containing GTPase activating protein (IQGAP) which associated with the Ras GTP-binding protein. A primary function of IQGAP proteins is to modulate cytoskeletal architecture. There are three known IQGAP family members: IQGAP1, IQGAP2 and IQGAP3. Human IQGAP1 and IQGAP2 share 62% identity. IQGAPs are multi-domain molecules having a calponin-homology (CH) domain which binds F-actin, IQGAP-specific repeats, a single WW domain, four IQ motifs that mediate interactions with calmodulin, and a RasGAP related domain that binds active Rho family GTPases. IQGAP is an essential regulator of cytoskeletal function. IQGAP1 negatively regulates Ras family GTPases by stimulating their intrinsic GTPase activity, the protein actually lacks GAP activity. Both IQGAP1 and IQGAP2 specifically bind to Cdc42 and Rac1, but not to RhoA. Despite of their similarities to part of the sequence of RasGAP, neither IQGAP1 nor IQGAP2 interacts with Ras. IQGAP3, only present in mammals, regulates the organization of the cytoskeleton under the regulation of Rac1 and Cdc42 in neuronal cells. The depletion of IQGAP3 is shown to impair neurite or axon outgrowth in neuronal cells with disorganized cytoskeleton.


Pssm-ID: 213329 [Multi-domain]  Cd Length: 331  Bit Score: 63.76  E-value: 1.65e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  518 QDYLQETLGQVVRRLCASTE-DCEVDP------------------SKCP-------ASELPEHQAR-------LRNSCEE 564
Cdd:cd05127    53 QKYLRELLGPVVKEILDDDDlDLETDPvdiykawinqeesrtgepSKLPydvtreqALKDPEVRKRliehlekLRAITDK 132

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  565 VFETIIHSYDWFPAELGIVFSSWREACKER-----GSEVLgpRLVCASLFLRLLCPAILAPSLFGLAPDHPAPGPA---- 635
Cdd:cd05127   133 FLTAITESLDKMPYGMRYIAKVLKEALREKfpdapEEEIL--KIVGNLLYYRYMNPAIVAPEAFDIIDLSVGGQLSplqr 210

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 130502162  636 RTLTLIAKVIQNLANRAPFGEKEAYMGFMNSFLEEHGPAMQCFLDQVAMVD 686
Cdd:cd05127   211 RNLGSIAKVLQQAASGKLFGGENPYLSPLNPYISESHEKFKKFFLEACTVP 261
RasGAP_IQGAP2 cd05131
Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 2; IQGAP2 is a ...
 558-670 5.81e-05

Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 2; IQGAP2 is a member of the IQGAP family that contains a calponin-homology (CH) domain which binds F-actin, IQGAP-specific repeat, a single WW domain, four IQ motifs which mediate interactions with calmodulin, and a Ras-GTPase-activating protein (GAP)-related domain that binds Rho family GTPases. IQGAP2 and IQGAP3 play important roles in the regulation of the cytoskeleton for axon outgrowth in hippocampal neurons and are thought to stay in a common regulatory pathway. The results of RNA interference studies indicated that IQGAP3 partially compensates functions of IQGAP2, but has lesser ability than IQGAP2 to promote axon outgrowth in hippocampal neuron. Moreover, IQGAP2 is required for the cadherin-mediated cell-to-cell adhesion in Xenopus laevis embryos.


Pssm-ID: 213333 [Multi-domain]  Cd Length: 359  Bit Score: 46.53  E-value: 5.81e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  558 LRNSCEEVFETIIHSYDWFPAELGIVFSSWREACKER-----GSEVLgpRLVCASLFLRLLCPAILAPSLFGLApDHPAP 632
Cdd:cd05131   136 LRSVTDKVLGSIFSSLDLIPYGMRYIAKVLKNSLHEKfpdatEDELL--KIVGNLLYYRYMNPAIVAPDGFDII-DMTAG 212

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 130502162  633 GPA-----RTLTLIAKVIQNLANRAPFGEKEAYMGFMNSFLEE 670
Cdd:cd05131   213 GQIhseqrRNLGSVAKVLQHAASNKLFEGENAHLSSMNSYLSQ 255
COG4372 COG4372
Uncharacterized protein, contains DUF3084 domain [Function unknown];
890-986 5.82e-05

Uncharacterized protein, contains DUF3084 domain [Function unknown];


Pssm-ID: 443500 [Multi-domain]  Cd Length: 370  Bit Score: 46.43  E-value: 5.82e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  890 KLAELQCEVAALREEQKVLSRLVESLSTQIRALTEQQEQLRGQLQDLDSRLRAGSSEFDSEHNLTSNEGHSLKNLEHRLN 969
Cdd:COG4372    39 ELDKLQEELEQLREELEQAREELEQLEEELEQARSELEQLEEELEELNEQLQAAQAELAQAQEELESLQEEAEELQEELE 118

                          90
                  ....*....|....*..
gi 130502162  970 EMERTQAQLRDAVQSLQ 986
Cdd:COG4372   119 ELQKERQDLEQQRKQLE 135
COG4372 COG4372
Uncharacterized protein, contains DUF3084 domain [Function unknown];
876-985 8.62e-05

Uncharacterized protein, contains DUF3084 domain [Function unknown];


Pssm-ID: 443500 [Multi-domain]  Cd Length: 370  Bit Score: 46.05  E-value: 8.62e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  876 QDRNQALgtHRPVNKLAELQCEVAALREEQKVLSRLVESLSTQIRALTEQQEQLRGQLQDLDSRLRAGSSEfdsehnlts 955
Cdd:COG4372    83 EELNEQL--QAAQAELAQAQEELESLQEEAEELQEELEELQKERQDLEQQRKQLEAQIAELQSEIAEREEE--------- 151

                          90       100       110
                  ....*....|....*....|....*....|
gi 130502162  956 neghsLKNLEHRLNEMERTQAQLRDAVQSL 985
Cdd:COG4372   152 -----LKELEEQLESLQEELAALEQELQAL 176
RasGAP_RAP6 cd05129
Ras-GTPase Activating Domain of Rab5-activating protein 6; Rab5-activating protein 6 (RAP6) is ...
 551-682 1.08e-04

Ras-GTPase Activating Domain of Rab5-activating protein 6; Rab5-activating protein 6 (RAP6) is an endosomal protein with a role in the regulation of receptor-mediated endocytosis. RAP6 contains a Vps9 domain, which is involved in the activation of Rab5, and a Ras GAP domain (RGD). Rab5 is a small GTPase required for the control of the endocytic route, and its activity is regulated by guanine nucleotide exchange factor, such as Rabex5, and GAPs, such as RN-tre. Human Rap6 protein is localized on the plasma membrane and on the endosome. RAP6 binds to Rab5 and Ras through the Vps9 and RGD domains, respectively.


Pssm-ID: 213331  Cd Length: 365  Bit Score: 45.80  E-value: 1.08e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  551 LPEHQA----RLRNSCEEVFETIIHSYDWFPAELG-IVFSSWREACKERGSEVLGPRLVCASL-FLRLLCPAILAPSLFG 624
Cdd:cd05129   164 LQQYRAeflsRLVALVNKFISSLRQSVYCFPQSLRwIVRQLRKILTRSGDDEEAEARALCTDLlFTNFICPAIVNPEQYG 243

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 130502162  625 LAPDHPAPGPAR-TLTLIAKVIQNLANRaPFGE-----KEAYMGFMNSFLEEhgpamqcFLDQV 682
Cdd:cd05129   244 IISDAPISEVARhNLMQVAQILQVLALT-EFESpdprlKELLSKFDKDCVSA-------FLDVV 299
RasGAP_IQGAP3 cd12207
Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 3; This family ...
 533-670 2.36e-04

Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 3; This family represents the IQ motif containing GTPase activating protein 3 (IQGAP3), which associates with Ras GTP-binding proteins. A primary function of IQGAP proteins is to modulate cytoskeletal architecture. There are three known IQGAP family members: IQGAP1, IQGAP2 and IQGAP3. Human IQGAP1 and IQGAP2 share 62% identity. IQGAPs are multi-domain molecules having a calponin-homology (CH) domain which binds F-actin, IQGAP-specific repeats, a single WW domain, four IQ motifs that mediate interactions with calmodulin, and a RasGAP related domain that binds active Rho family GTPases. IQGAP is an essential regulator of cytoskeletal function. IQGAP1 negatively regulates Ras family GTPases by stimulating their intrinsic GTPase activity, the protein actually lacks GAP activity. Both IQGAP1 and IQGAP2 specifically bind to Cdc42 and Rac1, but not to RhoA. Despite of their similarities to part of the sequence of RasGAP, neither IQGAP1 nor IQGAP2 interacts with Ras. IQGAP3, only present in mammals, regulates the organization of the cytoskeleton under the regulation of Rac1 and Cdc42 in neuronal cells. The depletion of IQGAP3 is shown to impair neurite or axon outgrowth in neuronal cells with disorganized cytoskeleton.


Pssm-ID: 213346 [Multi-domain]  Cd Length: 350  Bit Score: 44.43  E-value: 2.36e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  533 CASTEDCEVDPSKcpASELPEHQAR-------LRNSCEEVFETIIHSYDWFPAELGIVFSSWREACKER---GSEVLGPR 602
Cdd:cd12207   106 CRSSLPYEVSPEQ--ALSHPEVQRRldiairnLLAVTDKFLSAITSSVDKIPYGMRYVAKVLRDSLQEKfpgASEDEVYK 183

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 130502162  603 LVCASLFLRLLCPAILAPSLFGL----APDHPAPGPARTLTLIAKVIQNLANRAPFGEKEAYMGFMNSFLEE 670
Cdd:cd12207   184 VVGNLLYYRFMNPAVVAPDGFDIvdcsAGGALQPEQRRMLGSVAKVLQHAAANKHFQGDSEHLQALNQYLEE 255
COG4913 COG4913
Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];
889-982 2.78e-04

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];


Pssm-ID: 443941 [Multi-domain]  Cd Length: 1089  Bit Score: 44.91  E-value: 2.78e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  889 NKLAELQCEVAALREEQKVLSRLVESLSTQIRALTEQQEQLRGQLQDLDSRLRAGSSEFDSEHNL-----------TSNE 957
Cdd:COG4913   685 DDLAALEEQLEELEAELEELEEELDELKGEIGRLEKELEQAEEELDELQDRLEAAEDLARLELRAlleerfaaalgDAVE 764

                          90       100
                  ....*....|....*....|....*
gi 130502162  958 GHSLKNLEHRLNEMERTQAQLRDAV 982
Cdd:COG4913   765 RELRENLEERIDALRARLNRAEEEL 789
ZapB COG3074
Cell division protein ZapB, interacts with FtsZ [Cell cycle control, cell division, chromosome ...
 888-942 5.05e-04

Cell division protein ZapB, interacts with FtsZ [Cell cycle control, cell division, chromosome partitioning];


Pssm-ID: 442308 [Multi-domain]  Cd Length: 79  Bit Score: 39.57  E-value: 5.05e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 130502162  888 VNKLAELQCEVAALREEQKVLSRLVESLSTQIRALTEQQEQLRGQLQDLDSRLRA 942
Cdd:COG3074    17 VDTIELLQMEVEELKEKNEELEQENEELQSENEELQSENEQLKTENAEWQERIRS 71
SMC_prok_B TIGR02168
chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...
 869-986 5.68e-04

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274008 [Multi-domain]  Cd Length: 1179  Bit Score: 43.89  E-value: 5.68e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162   869 QRQMDQPQDRNQALGThrpvnKLAELQCEVAALREE-QKVLSRL-------------VESLSTQIRALTEQQEQLRGQLQ 934
Cdd:TIGR02168  788 EAQIEQLKEELKALRE-----ALDELRAELTLLNEEaANLRERLeslerriaaterrLEDLEEQIEELSEDIESLAAEIE 862

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 130502162   935 DLDSRLRAGSSEFDSEHNL--TSNEG-----HSLKNLEHRLNEMERTQAQLRDAVQSLQ 986
Cdd:TIGR02168  863 ELEELIEELESELEALLNEraSLEEAlallrSELEELSEELRELESKRSELRRELEELR 921
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 252-290 6.35e-04

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 40.22  E-value: 6.35e-04
                            10        20        30        40
                    ....*....|....*....|....*....|....*....|
gi 130502162    252 HPSLLGEPHCFQV-TWTGGSRCFSCRSAAERDRWIEDLRR 290
Cdd:smart00233   60 DPDSSKKPHCFEIkTSDRKTLLLQAESEEEREKWVEALRK 99
YhaN COG4717
Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];
862-997 6.54e-04

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];


Pssm-ID: 443752 [Multi-domain]  Cd Length: 641  Bit Score: 43.60  E-value: 6.54e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  862 RKPSVPWQRQMDQPQDRNQALGTHRpvnKLAELQCEVAALREEQKVLSRLVESLSTQIRALT---------EQQEQLRGQ 932
Cdd:COG4717    64 RKPELNLKELKELEEELKEAEEKEE---EYAELQEELEELEEELEELEAELEELREELEKLEkllqllplyQELEALEAE 140

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 130502162  933 LQDLDSRLRAGSSEFdsehnltsnegHSLKNLEHRLNEMERTQAQLRDAVQSL--QLSPRTRGSWSQ 997
Cdd:COG4717   141 LAELPERLEELEERL-----------EELRELEEELEELEAELAELQEELEELleQLSLATEEELQD 196
PH_RASA1 cd13260
RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 ...
 248-291 6.86e-04

RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 (also called RasGap1 or p120) is a member of the RasGAP family of GTPase-activating proteins. RASA1 contains N-terminal SH2-SH3-SH2 domains, followed by two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Splice variants lack the N-terminal domains. It is a cytosolic vertebrate protein that acts as a suppressor of RAS via its C-terminal GAP domain function, enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. Additionally, it is involved in mitogenic signal transmission towards downstream interacting partners through its N-terminal SH2-SH3-SH2 domains. RASA1 interacts with a number of proteins including: G3BP1, SOCS3, ANXA6, Huntingtin, KHDRBS1, Src, EPHB3, EPH receptor B2, Insulin-like growth factor 1 receptor, PTK2B, DOK1, PDGFRB, HCK, Caveolin 2, DNAJA3, HRAS, GNB2L1 and NCK1. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270080  Cd Length: 103  Bit Score: 40.02  E-value: 6.86e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 130502162  248 IWPLHPSLLGEPHCFQ--VTWTGGSRC--FSCRSAAERDRWIEDLRRQ 291
Cdd:cd13260    55 LYPVHDSLFGRPNCFQivVRALNESTItyLCADTAELAQEWMRALRAF 102
GumC COG3206
Exopolysaccharide export protein/domain GumC/Wzc1 [Cell wall/membrane/envelope biogenesis];
889-979 7.40e-04

Exopolysaccharide export protein/domain GumC/Wzc1 [Cell wall/membrane/envelope biogenesis];


Pssm-ID: 442439 [Multi-domain]  Cd Length: 687  Bit Score: 43.47  E-value: 7.40e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  889 NKLAELQCEVAALREEQKV--LSRLVESLSTQIRALTEQQEQLRGQLQDLDSRLRAGSSEFDSEHNLTSNEGHS--LKNL 964
Cdd:COG3206   189 KELEEAEAALEEFRQKNGLvdLSEEAKLLLQQLSELESQLAEARAELAEAEARLAALRAQLGSGPDALPELLQSpvIQQL 268

                          90
                  ....*....|....*
gi 130502162  965 EHRLNEMERTQAQLR 979
Cdd:COG3206   269 RAQLAELEAELAELS 283
COG4372 COG4372
Uncharacterized protein, contains DUF3084 domain [Function unknown];
889-986 8.12e-04

Uncharacterized protein, contains DUF3084 domain [Function unknown];


Pssm-ID: 443500 [Multi-domain]  Cd Length: 370  Bit Score: 42.97  E-value: 8.12e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  889 NKLAELQCEVAALREEQKVLSRLVESLSTQIRALTEQQEQLRGQLQDLD---SRLRAGSSEFDSEhnltsneghsLKNLE 965
Cdd:COG4372    80 EELEELNEQLQAAQAELAQAQEELESLQEEAEELQEELEELQKERQDLEqqrKQLEAQIAELQSE----------IAERE 149

                          90       100
                  ....*....|....*....|.
gi 130502162  966 HRLNEMERTQAQLRDAVQSLQ 986
Cdd:COG4372   150 EELKELEEQLESLQEELAALE 170
COG4913 COG4913
Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];
890-989 1.52e-03

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];


Pssm-ID: 443941 [Multi-domain]  Cd Length: 1089  Bit Score: 42.59  E-value: 1.52e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  890 KLAELQCEVAALREEQKVLSRLVESLSTQIRALTEQQEQLRGQLQDLDSRLRAgssEFDSEhnltsneghsLKNLEHRLN 969
Cdd:COG4913   289 RLELLEAELEELRAELARLEAELERLEARLDALREELDELEAQIRGNGGDRLE---QLERE----------IERLERELE 355

                          90       100
                  ....*....|....*....|
gi 130502162  970 EMERTQAQLRDAVQSLQLSP 989
Cdd:COG4913   356 ERERRRARLEALLAALGLPL 375
SUN2_cc1 cd21438
coiled-coil domain 1 of SUN domain-containing protein 2 and similar proteins; SUN ...
 871-927 1.78e-03

coiled-coil domain 1 of SUN domain-containing protein 2 and similar proteins; SUN domain-containing protein 2 (SUN2), also called protein unc-84 homolog B, Rab5-interacting protein (Rab5IP), or Sad1/unc-84 protein-like 2, is a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex which is involved in the connection between the nuclear lamina and the cytoskeleton. Besides the core SUN domain, SUN2 contains two coiled-coil domains (CC1 and CC2), which act as the intrinsic dynamic regulators for controlling the activity of the SUN domain. This model corresponds to CC1 that functions as an activation segment to release CC2-mediated inhibition of the SUN domain.


Pssm-ID: 410604 [Multi-domain]  Cd Length: 55  Bit Score: 37.29  E-value: 1.78e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 130502162  871 QMDQPQDRNQALGthRPVNKLAELQCEVAALREEQKVLSRLVESLSTQIRALTEQQE 927
Cdd:cd21438     1 QEDLQENFQKELG--RLEAQLAGLRQELAALRSDQKALSQQVESFPGQIKAVRDDVE 55
COG4913 COG4913
Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];
890-986 2.28e-03

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];


Pssm-ID: 443941 [Multi-domain]  Cd Length: 1089  Bit Score: 42.21  E-value: 2.28e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  890 KLAELQCEVAALREEQKVLSRLVESLSTQIRALTEQQEQLRG----------------QLQDLD---SRLRAGSSEFDS- 949
Cdd:COG4913   611 KLAALEAELAELEEELAEAEERLEALEAELDALQERREALQRlaeyswdeidvasaerEIAELEaelERLDASSDDLAAl 690

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 130502162  950 EHNLTSNEgHSLKNLEHRLNEMERTQAQLRDAVQSLQ 986
Cdd:COG4913   691 EEQLEELE-AELEELEEELDELKGEIGRLEKELEQAE 726
SMC_prok_B TIGR02168
chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...
 868-987 3.04e-03

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274008 [Multi-domain]  Cd Length: 1179  Bit Score: 41.58  E-value: 3.04e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162   868 WQRQMDQPQDRNQALGthrpvNKLAELQCEVAALREEQKVLSRLVESLSTQIRALTEQQEQLRGQLQDLDSRLRAGSSEf 947
Cdd:TIGR02168  328 LESKLDELAEELAELE-----EKLEELKEELESLEAELEELEAELEELESRLEELEEQLETLRSKVAQLELQIASLNNE- 401

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 130502162   948 dsehnLTSNEGHsLKNLEHRLNEMERTQAQLRDAVQSLQL 987
Cdd:TIGR02168  402 -----IERLEAR-LERLEDRRERLQQEIEELLKKLEEAEL 435
UPF0242 pfam06785
Uncharacterized protein family (UPF0242) N-terminus; This region includes an N-terminal ...
 877-980 3.93e-03

Uncharacterized protein family (UPF0242) N-terminus; This region includes an N-terminal transmembrane region and a C-terminal coiled-coil.


Pssm-ID: 429117 [Multi-domain]  Cd Length: 194  Bit Score: 39.80  E-value: 3.93e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162   877 DRNQALGTHRPVNKLAELQCEVAALREEQKVLSRLVESLSTQIRALTEQQEQLRGQLQDLDSRLRAGSSEFDSE------ 950
Cdd:pfam06785   71 EEKEAKLTELDAEGFKILEETLEELQSEEERLEEELSQKEEELRRLTEENQQLQIQLQQISQDFAEFRLESEEQlaekql 150

                           90       100       110
                   ....*....|....*....|....*....|..
gi 130502162   951 -HNLTSNEGHSLKN-LEHRLNEMERTQAQLRD 980
Cdd:pfam06785  151 lINEYQQTIEEQRSvLEKRQDQIENLESKVRD 182
Cast pfam10174
RIM-binding protein of the cytomatrix active zone; This is a family of proteins that form part ...
 892-986 4.18e-03

RIM-binding protein of the cytomatrix active zone; This is a family of proteins that form part of the CAZ (cytomatrix at the active zone) complex which is involved in determining the site of synaptic vesicle fusion. The C-terminus is a PDZ-binding motif that binds directly to RIM (a small G protein Rab-3A effector). The family also contains four coiled-coil domains.


Pssm-ID: 431111 [Multi-domain]  Cd Length: 766  Bit Score: 40.96  E-value: 4.18e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162   892 AELQCEVAALREEQKVLSRLVESLSTQIRALTEQQEQLRGQLQDLDSRLRAGSSEFDSEHNltsneghSLKNLEHRLNEM 971
Cdd:pfam10174  341 AILQTEVDALRLRLEEKESFLNKKTKQLQDLTEEKSTLAGEIRDLKDMLDVKERKINVLQK-------KIENLQEQLRDK 413

                           90
                   ....*....|....*
gi 130502162   972 ERTQAQLRDAVQSLQ 986
Cdd:pfam10174  414 DKQLAGLKERVKSLQ 428
Dynamitin pfam04912
Dynamitin; Dynamitin is a subunit of the microtubule-dependent motor complex and in implicated ...
 874-977 4.74e-03

Dynamitin; Dynamitin is a subunit of the microtubule-dependent motor complex and in implicated in cell adhesion by binding to macrophage-enriched myristoylated alanine-rice C kinase substrate (MacMARCKS).


Pssm-ID: 461477 [Multi-domain]  Cd Length: 390  Bit Score: 40.40  E-value: 4.74e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162   874 QPQDRNQALGTHR--PVNKLAELQCEVAALREE-QKVLSRLVESLSTQIRALTEQQEQLRGQLQDLDSRLRAGSsefDSE 950
Cdd:pfam04912   78 SGEYELAGEGEEKetPEQKLQRLQREVEELEEEvEKRKAAAKESEKADPVELAAQLASLQKQLDELKLEELLGP---DVA 154

                           90       100
                   ....*....|....*....|....*..
gi 130502162   951 HNLTSNEGHSLKNLEHRLNEMERTQAQ 977
Cdd:pfam04912  155 IGLTDPQGALSKRLLSQLEAFKQTSAP 181
EnvC COG4942
Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, ...
 871-985 6.48e-03

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, cell division, chromosome partitioning];


Pssm-ID: 443969 [Multi-domain]  Cd Length: 377  Bit Score: 40.13  E-value: 6.48e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162  871 QMDQPQDRNQALGTHRpvNKLAELQCEVAALREEQKVLSRLVESLSTQIRALTEQQEQLRGQLQDLDSRLRAgssefdse 950
Cdd:COG4942    18 QADAAAEAEAELEQLQ--QEIAELEKELAALKKEEKALLKQLAALERRIAALARRIRALEQELAALEAELAE-------- 87

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 130502162  951 hnltsneghslknLEHRLNEMERTQAQLRDAVQSL 985
Cdd:COG4942    88 -------------LEKEIAELRAELEAQKEELAEL 109
SMC_prok_B TIGR02168
chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...
 869-988 9.77e-03

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274008 [Multi-domain]  Cd Length: 1179  Bit Score: 40.04  E-value: 9.77e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 130502162   869 QRQMDQPQDRNQALgthrpVNKLAELQCEVAALREEQKVLSRLVESLSTQIRALTEQQEQLRGQLQDLDSRLRAGSSEFD 948
Cdd:TIGR02168  280 EEEIEELQKELYAL-----ANEISRLEQQKQILRERLANLERQLEELEAQLEELESKLDELAEELAELEEKLEELKEELE 354

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 130502162   949 SEHNLTSNEGHSLKNLEHRLNEMERTQAQLRDAVQSLQLS 988
Cdd:TIGR02168  355 SLEAELEELEAELEELESRLEELEEQLETLRSKVAQLELQ 394
 
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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