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Conserved domains on  [gi|2327432701|ref|NP_001400719|]
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tensin-1 isoform e [Mus musculus]

Protein Classification

SH2_Tensin_like and PTB_tensin domain-containing protein( domain architecture ID 13212388)

protein containing domains PTP_DSP_cys, PTEN_C2, SH2_Tensin_like, and PTB_tensin

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PTP_DSP_cys super family cl28904
cys-based protein tyrosine phosphatase and dual-specificity phosphatase superfamily; This ...
35-193 2.75e-114

cys-based protein tyrosine phosphatase and dual-specificity phosphatase superfamily; This superfamily is composed of cys-based phosphatases, which includes classical protein tyrosine phosphatases (PTPs) as well as dual-specificity phosphatases (DUSPs or DSPs). They are characterized by a CxxxxxR conserved catalytic loop (where C is the catalytic cysteine, x is any amino acid, and R is an arginine). PTPs are part of the tyrosine phosphorylation/dephosphorylation regulatory mechanism, and are important in the response of the cells to physiologic and pathologic changes in their environment. DUSPs show more substrate diversity (including RNA and lipids) and include pTyr, pSer, and pThr phosphatases.


The actual alignment was detected with superfamily member cd14560:

Pssm-ID: 475123 [Multi-domain]  Cd Length: 159  Bit Score: 357.75  E-value: 2.75e-114
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701   35 DLVYVTERIIAVSFPSTANEENFRSNLREVAQMLKSKHGGNYLLFNLSEQRPDITKLHAKVLEFGWPDLHTPALEKICSV 114
Cdd:cd14560      1 DLVYITERIISVSFPSTAEEPSFRSNLKEVAQMLKSKHGDNYLLFNLSERRHDISKLHPKVLDFGWPDLHAPALEKICSI 80
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2327432701  115 CKAMDTWLNADPHNVVVLHNKGNRGRIGVVIAAYLHYSNISASADQALDRFAMKRFYEDKIVPIGQPSQRRYVHYFSGL 193
Cdd:cd14560     81 CKAMDTWLNADPHNVVVIHNKGNRGRTGVVIAAYMHYSNISASADQALDRFAMKRFYEDKVVPVGQPSQKRYVHYFSGL 159
PTB_tensin cd01213
Tensin Phosphotyrosine-binding (PTB) domain; Tensin is a a focal adhesion protein, which ...
1578-1711 1.48e-86

Tensin Phosphotyrosine-binding (PTB) domain; Tensin is a a focal adhesion protein, which contains a C-terminal SH2 domain followed by a PTB domain. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.


:

Pssm-ID: 269924  Cd Length: 136  Bit Score: 277.97  E-value: 1.48e-86
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1578 GAACNVLFVNSVDMESLTGPQAISKATSETLAADPTPAATIVHFKVSAQGITLTDNQRKLFFRRHYPLNTVTFCDLDPQE 1657
Cdd:cd01213      1 GAACNVLYLGSVDTESLTGPQAVRKAVSETLERDPLPTPTVVHFKVSEQGITLTDNQRKLFFRRHYPLNTVSFCGMDPEN 80
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2327432701 1658 RKWMKTE--GGAPAKLFGFVARKQGSTTDNACHLFAELDPNQPASAIVNFVSKVML 1711
Cdd:cd01213     81 RKWQKYDlrGSKPSRIFGFVARKQGSSTENVCHLFAELDPEQPASAIVNFVNKVLL 136
SH2_Tensin_like cd09927
Src homology 2 domain found in Tensin-like proteins; SH2 domain found in Tensin-like proteins. ...
1441-1556 2.97e-68

Src homology 2 domain found in Tensin-like proteins; SH2 domain found in Tensin-like proteins. The Tensins are a family of intracellular proteins that interact with receptor tyrosine kinases (RTKs), integrins, and actin. They are thought act as signaling bridges between the extracellular space and the cytoskeleton. There are four homologues: Tensin1, Tensin2 (TENC1, C1-TEN), Tensin3 and Tensin4 (cten), all of which contain a C-terminal tandem SH2-PTB domain pairing, as well as actin-binding regions that may localize them to focal adhesions. The isoforms of Tensin2 and Tensin3 contain N-terminal C1 domains, which are atypical and not expected to bind to phorbol esters. Tensins 1-3 contain a phosphatase (PTPase) and C2 domain pairing which resembles PTEN (phosphatase and tensin homologue deleted on chromosome 10) protein. PTEN is a lipid phosphatase that dephosphorylates phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) to yield phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). As PtdIns(3,4,5)P3 is the product of phosphatidylinositol 3-kinase (PI3K) activity, PTEN is therefore a key negative regulator of the PI3K pathway. Because of their PTEN-like domains, the Tensins may also possess phosphoinositide-binding or phosphatase capabilities. However, only Tensin2 and Tensin3 have the potential to be phosphatases since only their PTPase domains contain a cysteine residue that is essential for catalytic activity. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


:

Pssm-ID: 198181 [Multi-domain]  Cd Length: 116  Bit Score: 225.00  E-value: 2.97e-68
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1441 TSKYWYKPEISREQAIALLKDQEPGAFIIRDSHSFRGAYGLAMKVSSPPPTITQQGKKGDMTHELVRHFLIETGPRGVKL 1520
Cdd:cd09927      1 TSKYWYKPNISRDQAIALLKDKPPGTFLVRDSTTYKGAYGLAVKVATPPPGVNPFEAKGDPESELVRHFLIEPSPKGVKL 80
                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 2327432701 1521 KGCPNEPNFGSLSALVYQHSVIPLALPCKLVIPSRD 1556
Cdd:cd09927     81 KGCPNEPVFGSLSALVYQHSITPLALPCKLRIPDRD 116
PTEN_C2 pfam10409
C2 domain of PTEN tumour-suppressor protein; This is the C2 domain-like domain, in greek key ...
200-326 6.93e-50

C2 domain of PTEN tumour-suppressor protein; This is the C2 domain-like domain, in greek key form, of the PTEN protein, phosphatidyl-inositol triphosphate phosphatase, and it is the C-terminus. This domain may well include a CBR3 loop which means it plays a central role in membrane binding. This domain associates across an extensive interface with the N-terminal phosphatase domain DSPc (pfam00782) suggesting that the C2 domain productively positions the catalytic part of the protein onto the membrane.


:

Pssm-ID: 463081  Cd Length: 133  Bit Score: 173.23  E-value: 6.93e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  200 MNNKPLFLHHVIMHGIPNFESKGGCRPFLRIYQAMQPV-YTSGIYNIPGDSQASICITIEP-GLLLKGDILLKCYHKKFR 277
Cdd:pfam10409    1 PPPKPLTLHSIILHGIPNFKSGGGCRPYIRIYQNKKKVfSTSGKYKKLKEYQQDDCVILFPkGIPVQGDVLVEFYHKGSD 80
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2327432701  278 SPARDVIFRVQFHTCAIHDLGVVFGKEDLDEAFKD---DRFPDYGKVEFVFS 326
Cdd:pfam10409   81 LLSEEKMFRFWFNTSFIEDNTLTLPKNELDKADKDkkdKRFPKDFKVELLFS 132
PHA03247 super family cl33720
large tegument protein UL36; Provisional
758-1444 1.30e-11

large tegument protein UL36; Provisional


The actual alignment was detected with superfamily member PHA03247:

Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 70.35  E-value: 1.30e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  758 SPLSSQPLLGSSRQSHPLTQ--------SRSGYIPSGHSLGTPELVSSGRPYSPYDYQLHPAGSNQSFHPKSPASSTFLP 829
Cdd:PHA03247  2462 APFSLSLLLGELFPGAPVYRrpaearfpFAAGAAPDPGGGGPPDPDAPPAPSRLAPAILPDEPVGEPVHPRMLTWIRGLE 2541
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  830 SPHS--SAGPQEP-PASLPGLIAQPQLPPKETTSDPSrtpeeEPlnleglvahrvaGVQARERQPAEPPGPLRRRAASDG 906
Cdd:PHA03247  2542 ELASddAGDPPPPlPPAAPPAAPDRSVPPPRPAPRPS-----EP------------AVTSRARRPDAPPQSARPRAPVDD 2604
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  907 QYENQSPEATSPRSPGVRSPvqcvSPElaltialNPGGRPKephlhsykeAFEEMEGTSPSSPPHSVARSPPGLAKTPLS 986
Cdd:PHA03247  2605 RGDPRGPAPPSPLPPDTHAP----DPP-------PPSPSPA---------ANEPDPHPPPTVPPPERPRDDPAPGRVSRP 2664
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  987 ALGLKPHNPADILLHPTG-EPRSYVESVAR-TAVAGPRAQDVEPksfsAPAAHAYGHETPLRNGTPGGSfvspsplstss 1064
Cdd:PHA03247  2665 RRARRLGRAAQASSPPQRpRRRAARPTVGSlTSLADPPPPPPTP----EPAPHALVSATPLPPGPAAAR----------- 2729
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1065 pilsadstsvGSFPSVVSSDQGPRTPFQPMLDSSIRSGSlGQPSPAALSYQSSSPVPVGGSSYNSPDYSLQPFSSSPESQ 1144
Cdd:PHA03247  2730 ----------QASPALPAAPAPPAVPAGPATPGGPARPA-RPPTTAGPPAPAPPAAPAAGPPRRLTRPAVASLSESRESL 2798
                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1145 GQPQYSAASVHMVPGsPQARHRTVGTNTPPSPgfgrravNPTMAAPGSPSLshrqvmgPSGPgfhgnVVSGHPASAATTP 1224
Cdd:PHA03247  2799 PSPWDPADPPAAVLA-PAAALPPAASPAGPLP-------PPTSAQPTAPPP-------PPGP-----PPPSLPLGGSVAP 2858
                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1225 GSPSLGRHPVGShqvpglhssvvtTPGSPSLGRHPGAhqgnlaSSLHSNAVISPGSPSlgrhlggsgSVVPGSPSLDRHA 1304
Cdd:PHA03247  2859 GGDVRRRPPSRS------------PAAKPAAPARPPV------RRLARPAVSRSTESF---------ALPPDQPERPPQP 2911
                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1305 AyggysTPEDRRPTLSRQSSASGYQAPSTPSFPVSPAYYPGLSSPATSPSPDSAAFRQGSPTPALPEKRRMSVGDRAGSL 1384
Cdd:PHA03247  2912 Q-----APPPPQPQPQPPPPPQPQPPPPPPPRPQPPLAPTTDPAGAGEPSGAVPQPWLGALVPGRVAVPRFRVPQPAPSR 2986
                          650       660       670       680       690       700
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2327432701 1385 PNYATINGKVSSSPVAnGMASGSSTVSFsHTLPDFSKYSM------PDNSPETRAKVKFVQDTSKY 1444
Cdd:PHA03247  2987 EAPASSTPPLTGHSLS-RVSSWASSLAL-HEETDPPPVSLkqtlwpPDDTEDSDADSLFDSDSERS 3050
PHA03307 super family cl33723
transcriptional regulator ICP4; Provisional
535-927 1.07e-03

transcriptional regulator ICP4; Provisional


The actual alignment was detected with superfamily member PHA03307:

Pssm-ID: 223039 [Multi-domain]  Cd Length: 1352  Bit Score: 44.01  E-value: 1.07e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  535 GSMGTLSSLDGVTNTSESGYPETLSPLTNGLDKPystepvlNGGGYPYEAANRVIPVHSSHSAPIRPSYSAQEGLAGYQR 614
Cdd:PHA03307    38 GSQGQLVSDSAELAAVTVVAGAAACDRFEPPTGP-------PPGPGTEAPANESRSTPTWSLSTLAPASPAREGSPTPPG 110
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  615 EGPHPAWSQQVTSAHCGCDPsGLFRSQSFPDVEPQLPQAPTR---GGSSREAVQRGL-NSWQQQQPHPPPRQQERSPLQS 690
Cdd:PHA03307   111 PSSPDPPPPTPPPASPPPSP-APDLSEMLRPVGSPGPPPAASppaAGASPAAVASDAaSSRQAALPLSSPEETARAPSSP 189
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  691 LARSKPSPQLSAETPVAALPEFPRAASQQEIEQSIETlnmlMLDLEPASAAAPLHKSQSVPGAWPGAS-----PLSSQPL 765
Cdd:PHA03307   190 PAEPPPSTPPAAASPRPPRRSSPISASASSPAPAPGR----SAADDAGASSSDSSSSESSGCGWGPENecplpRPAPITL 265
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  766 LGSSRQSHPLTQSRSGYIPSGHSLGTPEL---VSSGRPYSPYDYQLHPAGSNQSFHPKSPASSTfLPSPHSSAGPQEPPA 842
Cdd:PHA03307   266 PTRIWEASGWNGPSSRPGPASSSSSPRERspsPSPSSPGSGPAPSSPRASSSSSSSRESSSSST-SSSSESSRGAAVSPG 344
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  843 SLPGLIAQPQLPPkeTTSDPSRTPEEEPLNleglvahrvAGVQARERQPAEPPGPlRRRAASDGQYENQSpeaTSPRSPG 922
Cdd:PHA03307   345 PSPSRSPSPSRPP--PPADPSSPRKRPRPS---------RAPSSPAASAGRPTRR-RARAAVAGRARRRD---ATGRFPA 409

                   ....*
gi 2327432701  923 VRSPV 927
Cdd:PHA03307   410 GRPRP 414
 
Name Accession Description Interval E-value
PTP_tensin-1 cd14560
protein tyrosine phosphatase-like domain of tensin-1; Tensin-1 (TNS1) is part of the tensin ...
35-193 2.75e-114

protein tyrosine phosphatase-like domain of tensin-1; Tensin-1 (TNS1) is part of the tensin family of intracellular proteins (tensin-1, -2, -3 and -4), which act as links between the extracellular matrix and the cytoskeleton, and thereby mediate signaling for cell shape and motility. It plays an essential role in TGF-beta-induced myofibroblast differentiation and myofibroblast-mediated formation of extracellular fibronectin and collagen matrix. It also positively regulates RhoA activity through its interaction with DLC1, a RhoGAP-containing tumor suppressor; the tensin-1-DLC1-RhoA signaling axis is critical in regulating cellular functions that lead to angiogenesis. Tensin-1 contains an N-terminal region with a protein tyrosine phosphatase (PTP)-like domain followed by a protein kinase 2 (C2) domain, and a C-terminal region with SH2 and pTyr binding (PTB) domains.


Pssm-ID: 350408 [Multi-domain]  Cd Length: 159  Bit Score: 357.75  E-value: 2.75e-114
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701   35 DLVYVTERIIAVSFPSTANEENFRSNLREVAQMLKSKHGGNYLLFNLSEQRPDITKLHAKVLEFGWPDLHTPALEKICSV 114
Cdd:cd14560      1 DLVYITERIISVSFPSTAEEPSFRSNLKEVAQMLKSKHGDNYLLFNLSERRHDISKLHPKVLDFGWPDLHAPALEKICSI 80
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2327432701  115 CKAMDTWLNADPHNVVVLHNKGNRGRIGVVIAAYLHYSNISASADQALDRFAMKRFYEDKIVPIGQPSQRRYVHYFSGL 193
Cdd:cd14560     81 CKAMDTWLNADPHNVVVIHNKGNRGRTGVVIAAYMHYSNISASADQALDRFAMKRFYEDKVVPVGQPSQKRYVHYFSGL 159
PTB_tensin cd01213
Tensin Phosphotyrosine-binding (PTB) domain; Tensin is a a focal adhesion protein, which ...
1578-1711 1.48e-86

Tensin Phosphotyrosine-binding (PTB) domain; Tensin is a a focal adhesion protein, which contains a C-terminal SH2 domain followed by a PTB domain. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.


Pssm-ID: 269924  Cd Length: 136  Bit Score: 277.97  E-value: 1.48e-86
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1578 GAACNVLFVNSVDMESLTGPQAISKATSETLAADPTPAATIVHFKVSAQGITLTDNQRKLFFRRHYPLNTVTFCDLDPQE 1657
Cdd:cd01213      1 GAACNVLYLGSVDTESLTGPQAVRKAVSETLERDPLPTPTVVHFKVSEQGITLTDNQRKLFFRRHYPLNTVSFCGMDPEN 80
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2327432701 1658 RKWMKTE--GGAPAKLFGFVARKQGSTTDNACHLFAELDPNQPASAIVNFVSKVML 1711
Cdd:cd01213     81 RKWQKYDlrGSKPSRIFGFVARKQGSSTENVCHLFAELDPEQPASAIVNFVNKVLL 136
SH2_Tensin_like cd09927
Src homology 2 domain found in Tensin-like proteins; SH2 domain found in Tensin-like proteins. ...
1441-1556 2.97e-68

Src homology 2 domain found in Tensin-like proteins; SH2 domain found in Tensin-like proteins. The Tensins are a family of intracellular proteins that interact with receptor tyrosine kinases (RTKs), integrins, and actin. They are thought act as signaling bridges between the extracellular space and the cytoskeleton. There are four homologues: Tensin1, Tensin2 (TENC1, C1-TEN), Tensin3 and Tensin4 (cten), all of which contain a C-terminal tandem SH2-PTB domain pairing, as well as actin-binding regions that may localize them to focal adhesions. The isoforms of Tensin2 and Tensin3 contain N-terminal C1 domains, which are atypical and not expected to bind to phorbol esters. Tensins 1-3 contain a phosphatase (PTPase) and C2 domain pairing which resembles PTEN (phosphatase and tensin homologue deleted on chromosome 10) protein. PTEN is a lipid phosphatase that dephosphorylates phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) to yield phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). As PtdIns(3,4,5)P3 is the product of phosphatidylinositol 3-kinase (PI3K) activity, PTEN is therefore a key negative regulator of the PI3K pathway. Because of their PTEN-like domains, the Tensins may also possess phosphoinositide-binding or phosphatase capabilities. However, only Tensin2 and Tensin3 have the potential to be phosphatases since only their PTPase domains contain a cysteine residue that is essential for catalytic activity. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198181 [Multi-domain]  Cd Length: 116  Bit Score: 225.00  E-value: 2.97e-68
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1441 TSKYWYKPEISREQAIALLKDQEPGAFIIRDSHSFRGAYGLAMKVSSPPPTITQQGKKGDMTHELVRHFLIETGPRGVKL 1520
Cdd:cd09927      1 TSKYWYKPNISRDQAIALLKDKPPGTFLVRDSTTYKGAYGLAVKVATPPPGVNPFEAKGDPESELVRHFLIEPSPKGVKL 80
                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 2327432701 1521 KGCPNEPNFGSLSALVYQHSVIPLALPCKLVIPSRD 1556
Cdd:cd09927     81 KGCPNEPVFGSLSALVYQHSITPLALPCKLRIPDRD 116
PTEN_C2 pfam10409
C2 domain of PTEN tumour-suppressor protein; This is the C2 domain-like domain, in greek key ...
200-326 6.93e-50

C2 domain of PTEN tumour-suppressor protein; This is the C2 domain-like domain, in greek key form, of the PTEN protein, phosphatidyl-inositol triphosphate phosphatase, and it is the C-terminus. This domain may well include a CBR3 loop which means it plays a central role in membrane binding. This domain associates across an extensive interface with the N-terminal phosphatase domain DSPc (pfam00782) suggesting that the C2 domain productively positions the catalytic part of the protein onto the membrane.


Pssm-ID: 463081  Cd Length: 133  Bit Score: 173.23  E-value: 6.93e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  200 MNNKPLFLHHVIMHGIPNFESKGGCRPFLRIYQAMQPV-YTSGIYNIPGDSQASICITIEP-GLLLKGDILLKCYHKKFR 277
Cdd:pfam10409    1 PPPKPLTLHSIILHGIPNFKSGGGCRPYIRIYQNKKKVfSTSGKYKKLKEYQQDDCVILFPkGIPVQGDVLVEFYHKGSD 80
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2327432701  278 SPARDVIFRVQFHTCAIHDLGVVFGKEDLDEAFKD---DRFPDYGKVEFVFS 326
Cdd:pfam10409   81 LLSEEKMFRFWFNTSFIEDNTLTLPKNELDKADKDkkdKRFPKDFKVELLFS 132
PTB pfam08416
Phosphotyrosine-binding domain; The phosphotyrosine-binding domain (PTB, also ...
1580-1716 1.84e-37

Phosphotyrosine-binding domain; The phosphotyrosine-binding domain (PTB, also phosphotyrosine-interaction or PI domain) in the protein tensin tends to be found at the C-terminus. Tensin is a multi-domain protein that binds to actin filaments and functions as a focal-adhesion molecule (focal adhesions are regions of plasma membrane through which cells attach to the extracellular matrix). Human tensin has actin-binding sites, an SH2 (pfam00017) domain and a region similar to the tumour suppressor PTEN. The PTB domain interacts with the cytoplasmic tails of beta integrin by binding to an NPXY motif.


Pssm-ID: 429984  Cd Length: 131  Bit Score: 137.48  E-value: 1.84e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1580 ACNVLFVNSVDMESLTGPQAISKAT--SETLAADPTPAATIVHFKVSAQGITLTDNQRKLFFrRHYPLNTVTFCDLDPQE 1657
Cdd:pfam08416    1 QYRVEHLTTFELDSLTGLQAVEDAIrkLQLLDAQGRVWTQEMLLQVSDQGITLTDNETKEEL-ESYPLDSISHCQAVLND 79
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2327432701 1658 RKWmkteggapAKLFGFVARKQGSTTDNAcHLFA--ELDPNQPASAIVNFVSKVMLSAGQK 1716
Cdd:pfam08416   80 GRY--------NSILALVCQEPGQSKPDV-HLFQcdELGAELIAEDIESALSDVRLGKPKK 131
PTB smart00462
Phosphotyrosine-binding domain, phosphotyrosine-interaction (PI) domain; PTB/PI domain ...
1577-1717 3.30e-22

Phosphotyrosine-binding domain, phosphotyrosine-interaction (PI) domain; PTB/PI domain structure similar to those of pleckstrin homology (PH) and IRS-1-like PTB domains.


Pssm-ID: 214675  Cd Length: 134  Bit Score: 93.92  E-value: 3.30e-22
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  1577 QGAACNVLFVNSVDMESLTGPQAISKATSETLAADP--TPAATIVHFKVSAQGITLTDNQRKlFFRRHYPLNTVTFCDLD 1654
Cdd:smart00462    2 SGVSFRVKYLGSVEVPEARGLQVVQEAIRKLRAAQGseKKEPQKVILSISSRGVKLIDEDTK-AVLHEHPLRRISFCAVG 80
                            90       100       110       120       130       140
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2327432701  1655 PQErkwmkteggapAKLFGFVARKQGStTDNACHLFAELDP--NQPASAIVNFVSKVMLSAGQKR 1717
Cdd:smart00462   81 PDD-----------LDVFGYIARDPGS-SRFACHVFRCEKAaeDIALAIGQAFQLAYELKLKARS 133
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
1445-1543 2.29e-12

Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides via 2 surface pockets. Specificity is provided via interaction with residues that are distinct from the phosphotyrosine. Only a single occurrence of a SH2 domain has been found in S. cerevisiae.


Pssm-ID: 214585 [Multi-domain]  Cd Length: 84  Bit Score: 64.17  E-value: 2.29e-12
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  1445 WYKPEISREQAIALLKDQEPGAFIIRDSHSFRGAYGLAMKVssppptitqqgkkgdmtHELVRHFLIE-TGPRGVKLKGc 1523
Cdd:smart00252    3 WYHGFISREEAEKLLKNEGDGDFLVRDSESSPGDYVLSVRV-----------------KGKVKHYRIRrNEDGKFYLEG- 64
                            90       100
                    ....*....|....*....|..
gi 2327432701  1524 pnEPNFGSLSALV--YQHSVIP 1543
Cdd:smart00252   65 --GRKFPSLVELVehYQKNSLG 84
PHA03247 PHA03247
large tegument protein UL36; Provisional
758-1444 1.30e-11

large tegument protein UL36; Provisional


Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 70.35  E-value: 1.30e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  758 SPLSSQPLLGSSRQSHPLTQ--------SRSGYIPSGHSLGTPELVSSGRPYSPYDYQLHPAGSNQSFHPKSPASSTFLP 829
Cdd:PHA03247  2462 APFSLSLLLGELFPGAPVYRrpaearfpFAAGAAPDPGGGGPPDPDAPPAPSRLAPAILPDEPVGEPVHPRMLTWIRGLE 2541
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  830 SPHS--SAGPQEP-PASLPGLIAQPQLPPKETTSDPSrtpeeEPlnleglvahrvaGVQARERQPAEPPGPLRRRAASDG 906
Cdd:PHA03247  2542 ELASddAGDPPPPlPPAAPPAAPDRSVPPPRPAPRPS-----EP------------AVTSRARRPDAPPQSARPRAPVDD 2604
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  907 QYENQSPEATSPRSPGVRSPvqcvSPElaltialNPGGRPKephlhsykeAFEEMEGTSPSSPPHSVARSPPGLAKTPLS 986
Cdd:PHA03247  2605 RGDPRGPAPPSPLPPDTHAP----DPP-------PPSPSPA---------ANEPDPHPPPTVPPPERPRDDPAPGRVSRP 2664
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  987 ALGLKPHNPADILLHPTG-EPRSYVESVAR-TAVAGPRAQDVEPksfsAPAAHAYGHETPLRNGTPGGSfvspsplstss 1064
Cdd:PHA03247  2665 RRARRLGRAAQASSPPQRpRRRAARPTVGSlTSLADPPPPPPTP----EPAPHALVSATPLPPGPAAAR----------- 2729
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1065 pilsadstsvGSFPSVVSSDQGPRTPFQPMLDSSIRSGSlGQPSPAALSYQSSSPVPVGGSSYNSPDYSLQPFSSSPESQ 1144
Cdd:PHA03247  2730 ----------QASPALPAAPAPPAVPAGPATPGGPARPA-RPPTTAGPPAPAPPAAPAAGPPRRLTRPAVASLSESRESL 2798
                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1145 GQPQYSAASVHMVPGsPQARHRTVGTNTPPSPgfgrravNPTMAAPGSPSLshrqvmgPSGPgfhgnVVSGHPASAATTP 1224
Cdd:PHA03247  2799 PSPWDPADPPAAVLA-PAAALPPAASPAGPLP-------PPTSAQPTAPPP-------PPGP-----PPPSLPLGGSVAP 2858
                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1225 GSPSLGRHPVGShqvpglhssvvtTPGSPSLGRHPGAhqgnlaSSLHSNAVISPGSPSlgrhlggsgSVVPGSPSLDRHA 1304
Cdd:PHA03247  2859 GGDVRRRPPSRS------------PAAKPAAPARPPV------RRLARPAVSRSTESF---------ALPPDQPERPPQP 2911
                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1305 AyggysTPEDRRPTLSRQSSASGYQAPSTPSFPVSPAYYPGLSSPATSPSPDSAAFRQGSPTPALPEKRRMSVGDRAGSL 1384
Cdd:PHA03247  2912 Q-----APPPPQPQPQPPPPPQPQPPPPPPPRPQPPLAPTTDPAGAGEPSGAVPQPWLGALVPGRVAVPRFRVPQPAPSR 2986
                          650       660       670       680       690       700
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2327432701 1385 PNYATINGKVSSSPVAnGMASGSSTVSFsHTLPDFSKYSM------PDNSPETRAKVKFVQDTSKY 1444
Cdd:PHA03247  2987 EAPASSTPPLTGHSLS-RVSSWASSLAL-HEETDPPPVSLkqtlwpPDDTEDSDADSLFDSDSERS 3050
PTPc_motif smart00404
Protein tyrosine phosphatase, catalytic domain motif;
98-213 1.13e-09

Protein tyrosine phosphatase, catalytic domain motif;


Pssm-ID: 214649 [Multi-domain]  Cd Length: 105  Bit Score: 57.37  E-value: 1.13e-09
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701    98 FGWPDLHTPAL-EKICSVCKAMDTWLNA-DPHNVVVLHNKGNRGRIGVVIAAYLHYSNISASAdqaldrfamkrfyedki 175
Cdd:smart00404    8 TGWPDHGVPESpDSILELLRAVKKNLNQsESSGPVVVHCSAGVGRTGTFVAIDILLQQLEAEA----------------- 70
                            90       100       110
                    ....*....|....*....|....*....|....*...
gi 2327432701   176 vpiGQPSQRRYVHYFSGLLSGSIKMNNKPLFLHHVIMH 213
Cdd:smart00404   71 ---GEVDIFDTVKELRSQRPGMVQTEEQYLFLYRALLE 105
SH2 pfam00017
SH2 domain;
1445-1539 1.94e-08

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 52.60  E-value: 1.94e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1445 WYKPEISREQAIALLK-DQEPGAFIIRDSHSFRGAYGLAMKVssppptitqQGKkgdmthelVRHFLI-ETGPRGVKLKG 1522
Cdd:pfam00017    1 WYHGKISRQEAERLLLnGKPDGTFLVRESESTPGGYTLSVRD---------DGK--------VKHYKIqSTDNGGYYISG 63
                           90
                   ....*....|....*..
gi 2327432701 1523 cpnEPNFGSLSALVYQH 1539
Cdd:pfam00017   64 ---GVKFSSLAELVEHY 77
CDC14 COG2453
Protein-tyrosine phosphatase [Signal transduction mechanisms];
94-190 9.34e-06

Protein-tyrosine phosphatase [Signal transduction mechanisms];


Pssm-ID: 441989 [Multi-domain]  Cd Length: 140  Bit Score: 46.89  E-value: 9.34e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701   94 KVLEFGWPDLHTPALEKICSVCKAMDTWLNADpHNVVVlHNKGNRGRIGVVIAAYLHYSNIsaSADQALDRFAMKRfyeD 173
Cdd:COG2453     49 EYLHLPIPDFGAPDDEQLQEAVDFIDEALREG-KKVLV-HCRGGIGRTGTVAAAYLVLLGL--SAEEALARVRAAR---P 121
                           90
                   ....*....|....*..
gi 2327432701  174 KIVPigQPSQRRYVHYF 190
Cdd:COG2453    122 GAVE--TPAQRAFLERF 136
Herpes_BLLF1 pfam05109
Herpes virus major outer envelope glycoprotein (BLLF1); This family consists of the BLLF1 ...
1109-1432 4.13e-05

Herpes virus major outer envelope glycoprotein (BLLF1); This family consists of the BLLF1 viral late glycoprotein, also termed gp350/220. It is the most abundantly expressed glycoprotein in the viral envelope of the Herpesviruses and is the major antigen responsible for stimulating the production of neutralising antibodies in vivo.


Pssm-ID: 282904 [Multi-domain]  Cd Length: 886  Bit Score: 48.37  E-value: 4.13e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1109 PAALSYQSSSPVPVGGSSYNSP-DYSLQPFSSSPESQGQPQYSAASVHMVPgSPQARHRTVGTNTPP----SPGFGRRAV 1183
Cdd:pfam05109  466 PTVSTADVTSPTPAGTTSGASPvTPSPSPRDNGTESKAPDMTSPTSAVTTP-TPNATSPTPAVTTPTpnatSPTLGKTSP 544
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1184 NPTMAAPGSPSLSHR-QVMGPSGPGFHGNVVSGHPASAATTPG----SPSLGRHP----VGSHQVPGLHSSVVTTPGSPS 1254
Cdd:pfam05109  545 TSAVTTPTPNATSPTpAVTTPTPNATIPTLGKTSPTSAVTTPTpnatSPTVGETSpqanTTNHTLGGTSSTPVVTSPPKN 624
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1255 LGRHPGAHQGNLASSLHSNAVISPGSPSLGRHLGGSGSVVPGSPSLDRHAAYGGYSTpedrrpTLSRQSSASGYQAPSTp 1334
Cdd:pfam05109  625 ATSAVTTGQHNITSSSTSSMSLRPSSISETLSPSTSDNSTSHMPLLTSAHPTGGENI------TQVTPASTSTHHVSTS- 697
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1335 sfpvSPAYYPGLSSPATSPSPDSAAFRQG--SPTPALPEKRRMSVGDRAG---SLPNYATINGKVSSSPVANGMASGSST 1409
Cdd:pfam05109  698 ----SPAPRPGTTSQASGPGNSSTSTKPGevNVTKGTPPKNATSPQAPSGqktAVPTVTSTGGKANSTTGGKHTTGHGAR 773
                          330       340
                   ....*....|....*....|...
gi 2327432701 1410 VSFSHTlpdfSKYSMPDNSPETR 1432
Cdd:pfam05109  774 TSTEPT----TDYGGDSTTPRTR 792
PHA03307 PHA03307
transcriptional regulator ICP4; Provisional
535-927 1.07e-03

transcriptional regulator ICP4; Provisional


Pssm-ID: 223039 [Multi-domain]  Cd Length: 1352  Bit Score: 44.01  E-value: 1.07e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  535 GSMGTLSSLDGVTNTSESGYPETLSPLTNGLDKPystepvlNGGGYPYEAANRVIPVHSSHSAPIRPSYSAQEGLAGYQR 614
Cdd:PHA03307    38 GSQGQLVSDSAELAAVTVVAGAAACDRFEPPTGP-------PPGPGTEAPANESRSTPTWSLSTLAPASPAREGSPTPPG 110
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  615 EGPHPAWSQQVTSAHCGCDPsGLFRSQSFPDVEPQLPQAPTR---GGSSREAVQRGL-NSWQQQQPHPPPRQQERSPLQS 690
Cdd:PHA03307   111 PSSPDPPPPTPPPASPPPSP-APDLSEMLRPVGSPGPPPAASppaAGASPAAVASDAaSSRQAALPLSSPEETARAPSSP 189
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  691 LARSKPSPQLSAETPVAALPEFPRAASQQEIEQSIETlnmlMLDLEPASAAAPLHKSQSVPGAWPGAS-----PLSSQPL 765
Cdd:PHA03307   190 PAEPPPSTPPAAASPRPPRRSSPISASASSPAPAPGR----SAADDAGASSSDSSSSESSGCGWGPENecplpRPAPITL 265
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  766 LGSSRQSHPLTQSRSGYIPSGHSLGTPEL---VSSGRPYSPYDYQLHPAGSNQSFHPKSPASSTfLPSPHSSAGPQEPPA 842
Cdd:PHA03307   266 PTRIWEASGWNGPSSRPGPASSSSSPRERspsPSPSSPGSGPAPSSPRASSSSSSSRESSSSST-SSSSESSRGAAVSPG 344
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  843 SLPGLIAQPQLPPkeTTSDPSRTPEEEPLNleglvahrvAGVQARERQPAEPPGPlRRRAASDGQYENQSpeaTSPRSPG 922
Cdd:PHA03307   345 PSPSRSPSPSRPP--PPADPSSPRKRPRPS---------RAPSSPAASAGRPTRR-RARAAVAGRARRRD---ATGRFPA 409

                   ....*
gi 2327432701  923 VRSPV 927
Cdd:PHA03307   410 GRPRP 414
Chi1 COG3469
Chitinase [Carbohydrate transport and metabolism];
1144-1372 1.62e-03

Chitinase [Carbohydrate transport and metabolism];


Pssm-ID: 442692 [Multi-domain]  Cd Length: 534  Bit Score: 43.20  E-value: 1.62e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1144 QGQPQYSAASVHMVPGSPQARHRTVGTNTPPSPGFGrraVNPTMAAPGSPSLSHRQVMGPSGPGFHGNVVSGHPASAATT 1223
Cdd:COG3469     12 AGGASATAVTLLGAAATAASVTLTAATATTVVSTTG---SVVVAASGSAGSGTGTTAASSTAATSSTTSTTATATAAAAA 88
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1224 PGSPSLGRHPVGSHQVPGLHSSVVTTPGSPslgrhpgahQGNLASSLHSNAVISPGSPSLGRHLGGSGSVVPGSPSLDrh 1303
Cdd:COG3469     89 ATSTSATLVATSTASGANTGTSTVTTTSTG---------AGSVTSTTSSTAGSTTTSGASATSSAGSTTTTTTVSGTE-- 157
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2327432701 1304 AAYGGYSTPedrrptlsrqsSASGYQAPSTPSFPVSPAYYPGLSSPATSPSPDSAAFRQGSPTPALPEK 1372
Cdd:COG3469    158 TATGGTTTT-----------STTTTTTSASTTPSATTTATATTASGATTPSATTTATTTGPPTPGLPKH 215
 
Name Accession Description Interval E-value
PTP_tensin-1 cd14560
protein tyrosine phosphatase-like domain of tensin-1; Tensin-1 (TNS1) is part of the tensin ...
35-193 2.75e-114

protein tyrosine phosphatase-like domain of tensin-1; Tensin-1 (TNS1) is part of the tensin family of intracellular proteins (tensin-1, -2, -3 and -4), which act as links between the extracellular matrix and the cytoskeleton, and thereby mediate signaling for cell shape and motility. It plays an essential role in TGF-beta-induced myofibroblast differentiation and myofibroblast-mediated formation of extracellular fibronectin and collagen matrix. It also positively regulates RhoA activity through its interaction with DLC1, a RhoGAP-containing tumor suppressor; the tensin-1-DLC1-RhoA signaling axis is critical in regulating cellular functions that lead to angiogenesis. Tensin-1 contains an N-terminal region with a protein tyrosine phosphatase (PTP)-like domain followed by a protein kinase 2 (C2) domain, and a C-terminal region with SH2 and pTyr binding (PTB) domains.


Pssm-ID: 350408 [Multi-domain]  Cd Length: 159  Bit Score: 357.75  E-value: 2.75e-114
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701   35 DLVYVTERIIAVSFPSTANEENFRSNLREVAQMLKSKHGGNYLLFNLSEQRPDITKLHAKVLEFGWPDLHTPALEKICSV 114
Cdd:cd14560      1 DLVYITERIISVSFPSTAEEPSFRSNLKEVAQMLKSKHGDNYLLFNLSERRHDISKLHPKVLDFGWPDLHAPALEKICSI 80
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2327432701  115 CKAMDTWLNADPHNVVVLHNKGNRGRIGVVIAAYLHYSNISASADQALDRFAMKRFYEDKIVPIGQPSQRRYVHYFSGL 193
Cdd:cd14560     81 CKAMDTWLNADPHNVVVIHNKGNRGRTGVVIAAYMHYSNISASADQALDRFAMKRFYEDKVVPVGQPSQKRYVHYFSGL 159
PTP_tensin cd14508
protein tyrosine phosphatase-like domain of tensins; The tensin family of intracellular ...
35-193 2.19e-94

protein tyrosine phosphatase-like domain of tensins; The tensin family of intracellular proteins (tensin-1, -2, -3 and -4) act as links between the extracellular matrix and the cytoskeleton, and thereby mediate signaling for cell shape and motility. Dysregulation of tensin expression has been implicated in human cancer. Tensin-1, -2, and -3 contain an N-terminal region with a protein tyrosine phosphatase (PTP)-like domain followed by a protein kinase 2 (C2) domain, and a C-terminal region with SH2 and pTyr binding (PTB) domains. In addition, tensin-2 contains a zinc finger N-terminal to its PTP domain. Tensin-4 is not included in this model as it does not contain a PTP-like domain.


Pssm-ID: 350358 [Multi-domain]  Cd Length: 159  Bit Score: 301.62  E-value: 2.19e-94
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701   35 DLVYVTERIIAVSFPSTANEENFRSNLREVAQMLKSKHGGNYLLFNLSEQRPDITKLHAKVLEFGWPDLHTPALEKICSV 114
Cdd:cd14508      1 DLTYITERIIALSFPSTCSEQTYRHNLREAAHLLQSKHGDNYMVFNLSERRHDLRSLNPKVLDFGWPELHAPPLEKLCSI 80
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2327432701  115 CKAMDTWLNADPHNVVVLHNKGNRGRIGVVIAAYLHYSNISASADQALDRFAMKRFYEDKIVPIGQPSQRRYVHYFSGL 193
Cdd:cd14508     81 CKNMDSWLNADPQNVVVLHCKGGKGRLGVVVSAYMHYSKISATADQALDRFAMKRFYDDKVGPLGQPSQKRYVGYFSGL 159
PTB_tensin cd01213
Tensin Phosphotyrosine-binding (PTB) domain; Tensin is a a focal adhesion protein, which ...
1578-1711 1.48e-86

Tensin Phosphotyrosine-binding (PTB) domain; Tensin is a a focal adhesion protein, which contains a C-terminal SH2 domain followed by a PTB domain. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.


Pssm-ID: 269924  Cd Length: 136  Bit Score: 277.97  E-value: 1.48e-86
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1578 GAACNVLFVNSVDMESLTGPQAISKATSETLAADPTPAATIVHFKVSAQGITLTDNQRKLFFRRHYPLNTVTFCDLDPQE 1657
Cdd:cd01213      1 GAACNVLYLGSVDTESLTGPQAVRKAVSETLERDPLPTPTVVHFKVSEQGITLTDNQRKLFFRRHYPLNTVSFCGMDPEN 80
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2327432701 1658 RKWMKTE--GGAPAKLFGFVARKQGSTTDNACHLFAELDPNQPASAIVNFVSKVML 1711
Cdd:cd01213     81 RKWQKYDlrGSKPSRIFGFVARKQGSSTENVCHLFAELDPEQPASAIVNFVNKVLL 136
PTP_tensin-3 cd14561
protein tyrosine phosphatase-like domain of tensin-3; Tensin-3 (TNS3) is also called ...
35-193 3.88e-81

protein tyrosine phosphatase-like domain of tensin-3; Tensin-3 (TNS3) is also called tensin-like SH2 domain-containing protein 1 (TENS1) or tumor endothelial marker (TEM6). It is part of the tensin family of intracellular proteins (tensin-1, -2, -3 and -4), which act as links between the extracellular matrix and the cytoskeleton, and thereby mediate signaling for cell shape and motility. Tensin-3 contributes to cell migration, anchorage-independent growth, tumorigenesis, and metastasis of cancer cells. It cooperates with Dock5, an exchange factor for the small GTPase Rac, for osteoclast activity to ensure the correct organization of podosomes. Tensin-3 contains an N-terminal region with a protein tyrosine phosphatase (PTP)-like domain followed by a protein kinase 2 (C2) domain, and a C-terminal region with SH2 and pTyr binding (PTB) domains.


Pssm-ID: 350409 [Multi-domain]  Cd Length: 159  Bit Score: 263.73  E-value: 3.88e-81
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701   35 DLVYVTERIIAVSFPSTANEENFRSNLREVAQMLKSKHGGNYLLFNLSEQRPDITKLHAKVLEFGWPDLHTPALEKICSV 114
Cdd:cd14561      1 DLTYITERIIAVSFPADCSEETYLHNLQDVTRMLKSKHGDNYLVLNLSEKRYELTKLNPKIMDVGWPDLHAPPLDKMCTI 80
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2327432701  115 CKAMDTWLNADPHNVVVLHNKGNRGRIGVVIAAYLHYSNISASADQALDRFAMKRFYEDKIVPIGQPSQRRYVHYFSGL 193
Cdd:cd14561     81 CKAMESWLNSDPLHVVVIHCRGGKGRIGVVISSYMHFTNVSASADQALDRFAMKKFYDDKVSALMQPSQKRYVQFLSGL 159
PTP_tensin-2 cd14562
protein tyrosine phosphatase-like domain of tensin-2; Tensin-2 (TNS2) is also called ...
35-193 3.74e-80

protein tyrosine phosphatase-like domain of tensin-2; Tensin-2 (TNS2) is also called tensin-like C1 domain-containing phosphatase (TENC1) or C1 domain-containing phosphatase and tensin homolog (C1-TEN). It is part of the tensin family of intracellular proteins (tensin-1, -2, -3 and -4), which act as links between the extracellular matrix and the cytoskeleton, and thereby mediate signaling for cell shape and motility. Tensin-2 is an essential component for the maintenance of glomerular basement membrane (GBM) structures. It also modulates cell contractility and remodeling of collagen fibers through the DLC1, a RhoGAP that binds to tensins in focal adhesions. Tensin-2 may have phosphatase activity; it reduces AKT1 phosphorylation. It contains an N-terminal region with a zinc finger, a protein tyrosine phosphatase (PTP)-like domain and a protein kinase 2 (C2) domain, and a C-terminal region with SH2 and pTyr binding (PTB) domains.


Pssm-ID: 350410 [Multi-domain]  Cd Length: 159  Bit Score: 261.04  E-value: 3.74e-80
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701   35 DLVYVTERIIAVSFPSTANEENFRSNLREVAQMLKSKHGGNYLLFNLSEQRPDITKLHAKVLEFGWPDLHTPALEKICSV 114
Cdd:cd14562      1 DLTYITERIISVFFPPALEEQRYRGNLREVAQMLKSKHEDKYLLFNLSEKRHDITRLNPKVQDFGWPDLHAPPLDKICSI 80
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2327432701  115 CKAMDTWLNADPHNVVVLHNKGNRGRIGVVIAAYLHYSNISASADQALDRFAMKRFYEDKIVPIGQPSQRRYVHYFSGL 193
Cdd:cd14562     81 CKAMETWLNADPQHVVVLHCKGNKGKTGVIVAAYMHYSKISAGADQALSTLAMRKFCEDKVATSLQPSQRRYISYFGGL 159
SH2_Tensin_like cd09927
Src homology 2 domain found in Tensin-like proteins; SH2 domain found in Tensin-like proteins. ...
1441-1556 2.97e-68

Src homology 2 domain found in Tensin-like proteins; SH2 domain found in Tensin-like proteins. The Tensins are a family of intracellular proteins that interact with receptor tyrosine kinases (RTKs), integrins, and actin. They are thought act as signaling bridges between the extracellular space and the cytoskeleton. There are four homologues: Tensin1, Tensin2 (TENC1, C1-TEN), Tensin3 and Tensin4 (cten), all of which contain a C-terminal tandem SH2-PTB domain pairing, as well as actin-binding regions that may localize them to focal adhesions. The isoforms of Tensin2 and Tensin3 contain N-terminal C1 domains, which are atypical and not expected to bind to phorbol esters. Tensins 1-3 contain a phosphatase (PTPase) and C2 domain pairing which resembles PTEN (phosphatase and tensin homologue deleted on chromosome 10) protein. PTEN is a lipid phosphatase that dephosphorylates phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) to yield phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). As PtdIns(3,4,5)P3 is the product of phosphatidylinositol 3-kinase (PI3K) activity, PTEN is therefore a key negative regulator of the PI3K pathway. Because of their PTEN-like domains, the Tensins may also possess phosphoinositide-binding or phosphatase capabilities. However, only Tensin2 and Tensin3 have the potential to be phosphatases since only their PTPase domains contain a cysteine residue that is essential for catalytic activity. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198181 [Multi-domain]  Cd Length: 116  Bit Score: 225.00  E-value: 2.97e-68
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1441 TSKYWYKPEISREQAIALLKDQEPGAFIIRDSHSFRGAYGLAMKVSSPPPTITQQGKKGDMTHELVRHFLIETGPRGVKL 1520
Cdd:cd09927      1 TSKYWYKPNISRDQAIALLKDKPPGTFLVRDSTTYKGAYGLAVKVATPPPGVNPFEAKGDPESELVRHFLIEPSPKGVKL 80
                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 2327432701 1521 KGCPNEPNFGSLSALVYQHSVIPLALPCKLVIPSRD 1556
Cdd:cd09927     81 KGCPNEPVFGSLSALVYQHSITPLALPCKLRIPDRD 116
PTP_PTEN-like cd14497
protein tyrosine phosphatase-like domain of phosphatase and tensin homolog and similar ...
35-193 1.59e-64

protein tyrosine phosphatase-like domain of phosphatase and tensin homolog and similar proteins; Phosphatase and tensin homolog (PTEN) is a tumor suppressor that acts as a dual-specificity protein phosphatase and as a lipid phosphatase. It dephosphorylates phosphoinositide trisphosphate. In addition to PTEN, this family includes tensins, voltage-sensitive phosphatases (VSPs), and auxilins. They all contain a protein tyrosine phosphatase-like domain although not all are active phosphatases. Tensins are intracellular proteins that act as links between the extracellular matrix and the cytoskeleton, and thereby mediate signaling for cell shape and motility, and they may or may not have phosphatase activity. VSPs are phosphoinositide phosphatases with substrates that include phosphatidylinositol-4,5-diphosphate and phosphatidylinositol-3,4,5-trisphosphate. Auxilins are J domain-containing proteins that facilitate Hsc70-mediated dissociation of clathrin from clathrin-coated vesicles, and they do not exhibit phosphatase activity.


Pssm-ID: 350347 [Multi-domain]  Cd Length: 160  Bit Score: 216.29  E-value: 1.59e-64
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701   35 DLVYVTERIIAVSFPSTAN-EENFRSNLREVAQMLKSKHGGNYLLFNLSEQRPDI-TKLHAKVLEFGWPDLHTPALEKIC 112
Cdd:cd14497      1 DLSYITPRIIAMSFPATGYpESLYRNSIDDVANFLNTHHPDHYMIFNLSEEEYDDdSKFEGRVLHYGFPDHHPPPLGLLL 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  113 SVCKAMDTWLNADPHNVVVLHNKGNRGRIGVVIAAYLHYSNISASADQALDRFAMKRFYEdKIVPIGQPSQRRYVHYFSG 192
Cdd:cd14497     81 EIVDDIDSWLSEDPNNVAVVHCKAGKGRTGTVICAYLLYYGQYSTADEALEYFAKKRFKE-GLPGVTIPSQLRYLQYFER 159

                   .
gi 2327432701  193 L 193
Cdd:cd14497    160 L 160
PTEN_C2 pfam10409
C2 domain of PTEN tumour-suppressor protein; This is the C2 domain-like domain, in greek key ...
200-326 6.93e-50

C2 domain of PTEN tumour-suppressor protein; This is the C2 domain-like domain, in greek key form, of the PTEN protein, phosphatidyl-inositol triphosphate phosphatase, and it is the C-terminus. This domain may well include a CBR3 loop which means it plays a central role in membrane binding. This domain associates across an extensive interface with the N-terminal phosphatase domain DSPc (pfam00782) suggesting that the C2 domain productively positions the catalytic part of the protein onto the membrane.


Pssm-ID: 463081  Cd Length: 133  Bit Score: 173.23  E-value: 6.93e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  200 MNNKPLFLHHVIMHGIPNFESKGGCRPFLRIYQAMQPV-YTSGIYNIPGDSQASICITIEP-GLLLKGDILLKCYHKKFR 277
Cdd:pfam10409    1 PPPKPLTLHSIILHGIPNFKSGGGCRPYIRIYQNKKKVfSTSGKYKKLKEYQQDDCVILFPkGIPVQGDVLVEFYHKGSD 80
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2327432701  278 SPARDVIFRVQFHTCAIHDLGVVFGKEDLDEAFKD---DRFPDYGKVEFVFS 326
Cdd:pfam10409   81 LLSEEKMFRFWFNTSFIEDNTLTLPKNELDKADKDkkdKRFPKDFKVELLFS 132
PTP_PTEN cd14509
protein tyrosine phosphatase-like catalytic domain of phosphatase and tensin homolog; ...
35-193 3.57e-48

protein tyrosine phosphatase-like catalytic domain of phosphatase and tensin homolog; Phosphatase and tensin homolog (PTEN), also phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN or mutated in multiple advanced cancers 1 (MMAC1), is a tumor suppressor that acts as a dual-specificity protein phosphatase and as a lipid phosphatase. It is a critical endogenous inhibitor of phosphoinositide signaling. It dephosphorylates phosphoinositide trisphosphate, and therefore, has the function of negatively regulating Akt. The PTEN/PI3K/AKT pathway regulates the signaling of multiple biological processes such as apoptosis, metabolism, cell proliferation, and cell growth. PTEN contains an N-terminal PIP-binding domain, a protein tyrosine phosphatase (PTP)-like catalytic domain, a regulatory C2 domain responsible for its cellular location, a C-tail containing phosphorylation sites, and a C-terminal PDZ domain.


Pssm-ID: 350359 [Multi-domain]  Cd Length: 158  Bit Score: 169.31  E-value: 3.57e-48
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701   35 DLVYVTERIIAVSFPSTANEENFRSNLREVAQMLKSKHGGNYLLFNL-SEQRPDITKLHAKVLEFGWPDLHTPALEKICS 113
Cdd:cd14509      1 DLTYITPNIIAMGFPAEGVEGVYRNPIDDVQRFLETKHKGHYKVYNLcSERSYDPSKFNGRVAEYPFDDHNPPPLELIKP 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  114 VCKAMDTWLNADPHNVVVLHNKGNRGRIGVVIAAYLHYSNISASADQALDRFAMKRFYEDKIVPIgqPSQRRYVHYFSGL 193
Cdd:cd14509     81 FCEDVDEWLKEDEKNVAAVHCKAGKGRTGVMICCYLLYLGKFPSAKEALDFYGAKRTKNKKGVTI--PSQRRYVYYYSRL 158
PTP_VSP_TPTE cd14510
protein tyrosine phosphatase-like catalytic domain of voltage-sensitive phosphatase ...
26-193 6.46e-41

protein tyrosine phosphatase-like catalytic domain of voltage-sensitive phosphatase/transmembrane phosphatase with tensin homology; Voltage-sensitive phosphatase (VSP) proteins comprise a family of phosphoinositide phosphatases with substrates that include phosphatidylinositol-4,5-diphosphate and phosphatidylinositol-3,4,5-trisphosphate. This family is conserved in deuterostomes; VSP was first identified as a sperm flagellar plasma membrane protein in Ciona intestinalis. Gene duplication events in primates resulted in the presence of paralogs, transmembrane phosphatase with tensin homology (TPTE) and TPTE2, that retain protein domain architecture but, in the case of TPTE, have lost catalytic activity. TPTE, also called cancer/testis antigen 44 (CT44), may play a role in the signal transduction pathways of the endocrine or spermatogenic function of the testis. TPTE2, also called TPTE and PTEN homologous inositol lipid phosphatase (TPIP), occurs in several differentially spliced forms; TPIP alpha displays phosphoinositide 3-phosphatase activity and is localized on the endoplasmic reticulum, while TPIP beta is cytosolic and lacks detectable phosphatase activity. VSP/TPTE proteins contain an N-terminal voltage sensor consisting of four transmembrane segments, a protein tyrosine phosphatase (PTP)-like phosphoinositide phosphatase catalytic domain, followed by a regulatory C2 domain.


Pssm-ID: 350360 [Multi-domain]  Cd Length: 177  Bit Score: 149.05  E-value: 6.46e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701   26 RAMEDSCELDLVYVTERIIAVSFPSTANEENFRSNLREVAQMLKSKHGGNYLLFNL-SEQRPDITKLHAKVLEFGWPDLH 104
Cdd:cd14510      6 RYQKDGFDLDLTYVTDRVIAMSFPSSGKQAFYRNPIEEVVRFLDTKHPDHYKVYNLcSERGYDPKYFHNRVERVPIDDHN 85
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  105 TPALEKICSVCKAMDTWLNADPHNVVVLHNKGNRGRIGVVIAAYLHYSNISASADQALDRFAMKRfyEDKIVP-----IG 179
Cdd:cd14510     86 VPTLDEMLSFTAEVREWMAADPKNVVAIHCKGGKGRTGTMVCAWLIYSGQFESAKEALEYFGERR--TDKSVSskfqgVE 163
                          170
                   ....*....|....
gi 2327432701  180 QPSQRRYVHYFSGL 193
Cdd:cd14510    164 TPSQSRYVGYFEKL 177
PTP_auxilin-like cd14511
protein tyrosine phosphatase-like domain of auxilin and similar proteins; This subfamily ...
33-193 2.01e-39

protein tyrosine phosphatase-like domain of auxilin and similar proteins; This subfamily contains proteins similar to auxilin, characterized by also containing a J domain. It includes auxilin, also called auxilin-1, and cyclin-G-associated kinase (GAK), also called auxilin-2. Auxilin-1 and -2 facilitate Hsc70-mediated dissociation of clathrin from clathrin-coated vesicles. GAK is expressed ubiquitously and is enriched in the Golgi, while auxilin-1 which is nerve-specific. Both proteins contain a protein tyrosine phosphatase (PTP)-like domain similar to the PTP-like domain of PTEN (a phosphoinositide 3-phosphatase), and a C-terminal region with clathrin-binding and J domains. In addition, GAK contains an N-terminal protein kinase domain that phosphorylates the mu subunits of adaptor protein (AP) 1 and AP2.


Pssm-ID: 350361 [Multi-domain]  Cd Length: 164  Bit Score: 144.42  E-value: 2.01e-39
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701   33 ELDLVYVTERIIAVSFPSTANEENFRSN-LREVAQMLKSKHGGNYLLFNLSEQRPDITKLHAKVLEFGWPDLHTPALEKI 111
Cdd:cd14511      8 DLDISYITSRIIVMPFPAEGIESTYRKNnIEDVRAFLDSRHPQKYSVYNLSPRSYPTLRLPSRVVECSWPYRRAPSLHAL 87
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  112 CSVCKAMDTWLNADPHNVVVLHNKGNRGRIGVVIAAYLHYSNISASADQALDRFAMKRfyedkiVPIG-QPSQRRYVHYF 190
Cdd:cd14511     88 YALCRDIYQWLNKDPKNVIVIHCTDGKAASATVVCALLVYCGLFKTPEDALQMFAVKR------CPPGlSPSELRYLYYF 161

                   ...
gi 2327432701  191 SGL 193
Cdd:cd14511    162 SDI 164
PTB pfam08416
Phosphotyrosine-binding domain; The phosphotyrosine-binding domain (PTB, also ...
1580-1716 1.84e-37

Phosphotyrosine-binding domain; The phosphotyrosine-binding domain (PTB, also phosphotyrosine-interaction or PI domain) in the protein tensin tends to be found at the C-terminus. Tensin is a multi-domain protein that binds to actin filaments and functions as a focal-adhesion molecule (focal adhesions are regions of plasma membrane through which cells attach to the extracellular matrix). Human tensin has actin-binding sites, an SH2 (pfam00017) domain and a region similar to the tumour suppressor PTEN. The PTB domain interacts with the cytoplasmic tails of beta integrin by binding to an NPXY motif.


Pssm-ID: 429984  Cd Length: 131  Bit Score: 137.48  E-value: 1.84e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1580 ACNVLFVNSVDMESLTGPQAISKAT--SETLAADPTPAATIVHFKVSAQGITLTDNQRKLFFrRHYPLNTVTFCDLDPQE 1657
Cdd:pfam08416    1 QYRVEHLTTFELDSLTGLQAVEDAIrkLQLLDAQGRVWTQEMLLQVSDQGITLTDNETKEEL-ESYPLDSISHCQAVLND 79
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2327432701 1658 RKWmkteggapAKLFGFVARKQGSTTDNAcHLFA--ELDPNQPASAIVNFVSKVMLSAGQK 1716
Cdd:pfam08416   80 GRY--------NSILALVCQEPGQSKPDV-HLFQcdELGAELIAEDIESALSDVRLGKPKK 131
PTP_GAK cd14564
protein tyrosine phosphatase-like domain of cyclin-G-associated kinase; cyclin-G-associated ...
33-189 1.16e-30

protein tyrosine phosphatase-like domain of cyclin-G-associated kinase; cyclin-G-associated kinase (GAK), also called auxilin-2, contains an N-terminal protein kinase domain that phosphorylates the mu subunits of adaptor protein (AP) 1 and AP2. In addition, it contains an auxilin-1-like domain structure consisting of a protein tyrosine phosphatase (PTP)-like domain similar to the PTP-like domain of PTEN (a phosphoinositide 3-phosphatase), and a C-terminal region with clathrin-binding and J domains. Like auxilin-1, GAK facilitates Hsc70-mediated dissociation of clathrin from clathrin-coated vesicles. GAK is expressed ubiquitously and is enriched in the Golgi, unlike auxilin-1 which is nerve-specific. GAK also plays regulatory roles outside of clathrin-mediated membrane traffic including the maintenance of centrosome integrity and chromosome congression, neural patterning, survival of neurons, and immune responses through interaction with the interleukin 12 receptor.


Pssm-ID: 350412 [Multi-domain]  Cd Length: 163  Bit Score: 119.24  E-value: 1.16e-30
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701   33 ELDLVYVTERIIAVSFPSTANEENFRSNLREVAQMLKSKHGGNYLLFNLSEQRPDITKLHAKVLEFGWPDLHTPALEKIC 112
Cdd:cd14564      8 DLDISYITSRIAVMSFPAEGVESAIKNNIEDVRLFLDSRHPGHYAVYNLSQRTYRPSRFHNRVSECGWPARRAPNLQNLY 87
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2327432701  113 SVCKAMDTWLNADPHNVVVLHNKGNRGRIGVVIAAYLHYSNISASADQALDRFAMKRfyedkiVPIG-QPSQRRYVHY 189
Cdd:cd14564     88 SICKNMHLWLKQDQKNICIVHCLDGRAASAVVVCSFLCFCRLFTTAEAAVYMFSMKR------CPPGiWPSHKRYIEY 159
PTP_auxilin_N cd14563
N-terminal protein tyrosine phosphatase-like domain of auxilin; Auxilin, also called auxilin-1 ...
33-193 1.08e-25

N-terminal protein tyrosine phosphatase-like domain of auxilin; Auxilin, also called auxilin-1 or DnaJ homolog subfamily C member 6 (DNAJC6), is a J-domain containing protein that recruits the ATP-dependent chaperone Hsc70 to newly budded clathrin-coated vesicles and promotes uncoating of clathrin-coated vesicles, driving the clathrin assembly#disassembly cycle. Mutations in the DNAJC6 gene, encoding auxilin, are associated with early-onset Parkinson's disease. Auxilin contains an N-terminal protein tyrosine phosphatase (PTP)-like domain similar to the PTP-like domain of PTEN, a phosphoinositide 3-phosphatase, and a C-terminal region with clathrin-binding and J domains.


Pssm-ID: 350411 [Multi-domain]  Cd Length: 163  Bit Score: 104.96  E-value: 1.08e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701   33 ELDLVYVTERIIAVSFPSTANEENFRSNLREVAQMLKSKHGGNYLLFNLSEQRPDITKLHAKVLEFGWPDLHTPALEKIC 112
Cdd:cd14563      8 ELDISYITSRIIVMSYPAEGVELGFRNHIEDVRSFLDSRHLDHYTVFNLSQKSYRSAKFHNRVSECSWPVRQAPSLHNLF 87
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  113 SVCKAMDTWLNADPHNVVVLHNKGNRGRIGVVIAAYLHYSNISASADQALDRFAMKRfyeDKIVPigQPSQRRYVHYFSG 192
Cdd:cd14563     88 AVCKNMHNWLQQNPKNVCVIHCMDGRAASAVLVSAMFCFCHLFSNPVPAMQLLNAKR---PGIGL--WPSHRRYIGYICD 162

                   .
gi 2327432701  193 L 193
Cdd:cd14563    163 L 163
PTB smart00462
Phosphotyrosine-binding domain, phosphotyrosine-interaction (PI) domain; PTB/PI domain ...
1577-1717 3.30e-22

Phosphotyrosine-binding domain, phosphotyrosine-interaction (PI) domain; PTB/PI domain structure similar to those of pleckstrin homology (PH) and IRS-1-like PTB domains.


Pssm-ID: 214675  Cd Length: 134  Bit Score: 93.92  E-value: 3.30e-22
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  1577 QGAACNVLFVNSVDMESLTGPQAISKATSETLAADP--TPAATIVHFKVSAQGITLTDNQRKlFFRRHYPLNTVTFCDLD 1654
Cdd:smart00462    2 SGVSFRVKYLGSVEVPEARGLQVVQEAIRKLRAAQGseKKEPQKVILSISSRGVKLIDEDTK-AVLHEHPLRRISFCAVG 80
                            90       100       110       120       130       140
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2327432701  1655 PQErkwmkteggapAKLFGFVARKQGStTDNACHLFAELDP--NQPASAIVNFVSKVMLSAGQKR 1717
Cdd:smart00462   81 PDD-----------LDVFGYIARDPGS-SRFACHVFRCEKAaeDIALAIGQAFQLAYELKLKARS 133
SH2 cd00173
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...
1445-1539 1.66e-15

Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they bind pTyr-containing polypeptide ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. They are present in a wide array of proteins including: adaptor proteins (Nck1, Crk, Grb2), scaffolds (Slp76, Shc, Dapp1), kinases (Src, Syk, Fps, Tec), phosphatases (Shp-1, Shp-2), transcription factors (STAT1), Ras signaling molecules (Ras-Gap), ubiquitination factors (c-Cbl), cytoskeleton regulators (Tensin), signal regulators (SAP), and phospholipid second messengers (PLCgamma), amongst others.


Pssm-ID: 198173 [Multi-domain]  Cd Length: 79  Bit Score: 72.87  E-value: 1.66e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1445 WYKPEISREQAIALLKDQEPGAFIIRDSHSFRGAYGLAMKvssppptiTQQGKkgdmthelVRHFLIETGPRGVKLKGCP 1524
Cdd:cd00173      2 WFHGSISREEAERLLRGKPDGTFLVRESSSEPGDYVLSVR--------SGDGK--------VKHYLIERNEGGYYLLGGS 65
                           90
                   ....*....|....*
gi 2327432701 1525 NEPnFGSLSALVYQH 1539
Cdd:cd00173     66 GRT-FPSLPELVEHY 79
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
1445-1543 2.29e-12

Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides via 2 surface pockets. Specificity is provided via interaction with residues that are distinct from the phosphotyrosine. Only a single occurrence of a SH2 domain has been found in S. cerevisiae.


Pssm-ID: 214585 [Multi-domain]  Cd Length: 84  Bit Score: 64.17  E-value: 2.29e-12
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  1445 WYKPEISREQAIALLKDQEPGAFIIRDSHSFRGAYGLAMKVssppptitqqgkkgdmtHELVRHFLIE-TGPRGVKLKGc 1523
Cdd:smart00252    3 WYHGFISREEAEKLLKNEGDGDFLVRDSESSPGDYVLSVRV-----------------KGKVKHYRIRrNEDGKFYLEG- 64
                            90       100
                    ....*....|....*....|..
gi 2327432701  1524 pnEPNFGSLSALV--YQHSVIP 1543
Cdd:smart00252   65 --GRKFPSLVELVehYQKNSLG 84
PHA03247 PHA03247
large tegument protein UL36; Provisional
758-1444 1.30e-11

large tegument protein UL36; Provisional


Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 70.35  E-value: 1.30e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  758 SPLSSQPLLGSSRQSHPLTQ--------SRSGYIPSGHSLGTPELVSSGRPYSPYDYQLHPAGSNQSFHPKSPASSTFLP 829
Cdd:PHA03247  2462 APFSLSLLLGELFPGAPVYRrpaearfpFAAGAAPDPGGGGPPDPDAPPAPSRLAPAILPDEPVGEPVHPRMLTWIRGLE 2541
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  830 SPHS--SAGPQEP-PASLPGLIAQPQLPPKETTSDPSrtpeeEPlnleglvahrvaGVQARERQPAEPPGPLRRRAASDG 906
Cdd:PHA03247  2542 ELASddAGDPPPPlPPAAPPAAPDRSVPPPRPAPRPS-----EP------------AVTSRARRPDAPPQSARPRAPVDD 2604
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  907 QYENQSPEATSPRSPGVRSPvqcvSPElaltialNPGGRPKephlhsykeAFEEMEGTSPSSPPHSVARSPPGLAKTPLS 986
Cdd:PHA03247  2605 RGDPRGPAPPSPLPPDTHAP----DPP-------PPSPSPA---------ANEPDPHPPPTVPPPERPRDDPAPGRVSRP 2664
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  987 ALGLKPHNPADILLHPTG-EPRSYVESVAR-TAVAGPRAQDVEPksfsAPAAHAYGHETPLRNGTPGGSfvspsplstss 1064
Cdd:PHA03247  2665 RRARRLGRAAQASSPPQRpRRRAARPTVGSlTSLADPPPPPPTP----EPAPHALVSATPLPPGPAAAR----------- 2729
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1065 pilsadstsvGSFPSVVSSDQGPRTPFQPMLDSSIRSGSlGQPSPAALSYQSSSPVPVGGSSYNSPDYSLQPFSSSPESQ 1144
Cdd:PHA03247  2730 ----------QASPALPAAPAPPAVPAGPATPGGPARPA-RPPTTAGPPAPAPPAAPAAGPPRRLTRPAVASLSESRESL 2798
                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1145 GQPQYSAASVHMVPGsPQARHRTVGTNTPPSPgfgrravNPTMAAPGSPSLshrqvmgPSGPgfhgnVVSGHPASAATTP 1224
Cdd:PHA03247  2799 PSPWDPADPPAAVLA-PAAALPPAASPAGPLP-------PPTSAQPTAPPP-------PPGP-----PPPSLPLGGSVAP 2858
                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1225 GSPSLGRHPVGShqvpglhssvvtTPGSPSLGRHPGAhqgnlaSSLHSNAVISPGSPSlgrhlggsgSVVPGSPSLDRHA 1304
Cdd:PHA03247  2859 GGDVRRRPPSRS------------PAAKPAAPARPPV------RRLARPAVSRSTESF---------ALPPDQPERPPQP 2911
                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1305 AyggysTPEDRRPTLSRQSSASGYQAPSTPSFPVSPAYYPGLSSPATSPSPDSAAFRQGSPTPALPEKRRMSVGDRAGSL 1384
Cdd:PHA03247  2912 Q-----APPPPQPQPQPPPPPQPQPPPPPPPRPQPPLAPTTDPAGAGEPSGAVPQPWLGALVPGRVAVPRFRVPQPAPSR 2986
                          650       660       670       680       690       700
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2327432701 1385 PNYATINGKVSSSPVAnGMASGSSTVSFsHTLPDFSKYSM------PDNSPETRAKVKFVQDTSKY 1444
Cdd:PHA03247  2987 EAPASSTPPLTGHSLS-RVSSWASSLAL-HEETDPPPVSLkqtlwpPDDTEDSDADSLFDSDSERS 3050
PTB cd00934
Phosphotyrosine-binding (PTB) PH-like fold; PTB domains have a common PH-like fold and are ...
1581-1710 2.18e-10

Phosphotyrosine-binding (PTB) PH-like fold; PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to bind peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains.


Pssm-ID: 269911  Cd Length: 120  Bit Score: 59.83  E-value: 2.18e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1581 CNVLFVNSVDMESLTGPQAISKATSETLAAD--PTPAATIVHFKVSAQGITLTDNQRKLFFRRHyPLNTVTFCDLDPQER 1658
Cdd:cd00934      3 FQVKYLGSVEVGSSRGVDVVEEALKALAAALksSKRKPGPVLLEVSSKGVKLLDLDTKELLLRH-PLHRISYCGRDPDNP 81
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2327432701 1659 kwmkteggapaKLFGFVARKQGStTDNACHLFAELDPnQPASAIVNFVSKVM 1710
Cdd:cd00934     82 -----------NVFAFIAGEEGG-SGFRCHVFQCEDE-EEAEEILQAIGQAF 120
PTPc_motif smart00404
Protein tyrosine phosphatase, catalytic domain motif;
98-213 1.13e-09

Protein tyrosine phosphatase, catalytic domain motif;


Pssm-ID: 214649 [Multi-domain]  Cd Length: 105  Bit Score: 57.37  E-value: 1.13e-09
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701    98 FGWPDLHTPAL-EKICSVCKAMDTWLNA-DPHNVVVLHNKGNRGRIGVVIAAYLHYSNISASAdqaldrfamkrfyedki 175
Cdd:smart00404    8 TGWPDHGVPESpDSILELLRAVKKNLNQsESSGPVVVHCSAGVGRTGTFVAIDILLQQLEAEA----------------- 70
                            90       100       110
                    ....*....|....*....|....*....|....*...
gi 2327432701   176 vpiGQPSQRRYVHYFSGLLSGSIKMNNKPLFLHHVIMH 213
Cdd:smart00404   71 ---GEVDIFDTVKELRSQRPGMVQTEEQYLFLYRALLE 105
PTPc_DSPc smart00012
Protein tyrosine phosphatase, catalytic domain, undefined specificity; Protein tyrosine ...
98-213 1.13e-09

Protein tyrosine phosphatase, catalytic domain, undefined specificity; Protein tyrosine phosphatases. Homologues detected by this profile and not by those of "PTPc" or "DSPc" are predicted to be protein phosphatases with a similar fold to DSPs and PTPs, yet with unpredicted specificities.


Pssm-ID: 214469 [Multi-domain]  Cd Length: 105  Bit Score: 57.37  E-value: 1.13e-09
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701    98 FGWPDLHTPAL-EKICSVCKAMDTWLNA-DPHNVVVLHNKGNRGRIGVVIAAYLHYSNISASAdqaldrfamkrfyedki 175
Cdd:smart00012    8 TGWPDHGVPESpDSILELLRAVKKNLNQsESSGPVVVHCSAGVGRTGTFVAIDILLQQLEAEA----------------- 70
                            90       100       110
                    ....*....|....*....|....*....|....*...
gi 2327432701   176 vpiGQPSQRRYVHYFSGLLSGSIKMNNKPLFLHHVIMH 213
Cdd:smart00012   71 ---GEVDIFDTVKELRSQRPGMVQTEEQYLFLYRALLE 105
PHA03247 PHA03247
large tegument protein UL36; Provisional
581-1037 2.40e-09

large tegument protein UL36; Provisional


Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 62.65  E-value: 2.40e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  581 PYEAANRVIPVHSSHSAPIRPSYSAQEGlagyqregpHPAWSQQVTSAHCGCDPSGLFRSQSFPDVEPQLPQAPTRGGSS 660
Cdd:PHA03247  2560 PPAAPDRSVPPPRPAPRPSEPAVTSRAR---------RPDAPPQSARPRAPVDDRGDPRGPAPPSPLPPDTHAPDPPPPS 2630
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  661 REAVQRGLNSWQQQQPHPPPRQQERSPLQSLARSKPSPQLSAETPVAALPEFPRAASQQEIEQSIETLnmlmldlepASA 740
Cdd:PHA03247  2631 PSPAANEPDPHPPPTVPPPERPRDDPAPGRVSRPRRARRLGRAAQASSPPQRPRRRAARPTVGSLTSL---------ADP 2701
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  741 AAPLHKSQSVPGAWPGASPLSSQPllGSSRQSHPLTQSRSGYIPSGHSLGTPelVSSGRPYSPYDyqlhPAGSNQSFHPK 820
Cdd:PHA03247  2702 PPPPPTPEPAPHALVSATPLPPGP--AAARQASPALPAAPAPPAVPAGPATP--GGPARPARPPT----TAGPPAPAPPA 2773
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  821 SPA-----------------SSTFLPSPH---------SSAGPQEPPASLPGLIAQPQLPPKETTSDPSRTPEEEPLNLE 874
Cdd:PHA03247  2774 APAagpprrltrpavaslseSRESLPSPWdpadppaavLAPAAALPPAASPAGPLPPPTSAQPTAPPPPPGPPPPSLPLG 2853
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  875 GLVAhrvagvqarerqpaePPGPLRRRAASdgqyENQSPEATSPRSPGVRSPVQCVSPELALTIALNPGGRPKEPHLHSY 954
Cdd:PHA03247  2854 GSVA---------------PGGDVRRRPPS----RSPAAKPAAPARPPVRRLARPAVSRSTESFALPPDQPERPPQPQAP 2914
                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  955 KEAFEEME---GTSPSSPPHSVARSPPGLAKTPLSALGLKPHNPADILLHPTGEPRSYveSVARTAVAGPRAQDVEPKSF 1031
Cdd:PHA03247  2915 PPPQPQPQpppPPQPQPPPPPPPRPQPPLAPTTDPAGAGEPSGAVPQPWLGALVPGRV--AVPRFRVPQPAPSREAPASS 2992

                   ....*.
gi 2327432701 1032 SAPAAH 1037
Cdd:PHA03247  2993 TPPLTG 2998
SH2 pfam00017
SH2 domain;
1445-1539 1.94e-08

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 52.60  E-value: 1.94e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1445 WYKPEISREQAIALLK-DQEPGAFIIRDSHSFRGAYGLAMKVssppptitqQGKkgdmthelVRHFLI-ETGPRGVKLKG 1522
Cdd:pfam00017    1 WYHGKISRQEAERLLLnGKPDGTFLVRESESTPGGYTLSVRD---------DGK--------VKHYKIqSTDNGGYYISG 63
                           90
                   ....*....|....*..
gi 2327432701 1523 cpnEPNFGSLSALVYQH 1539
Cdd:pfam00017   64 ---GVKFSSLAELVEHY 77
PTP_PTPDC1 cd14506
protein tyrosine phosphatase domain of PTP domain-containing protein 1; protein tyrosine ...
95-169 8.96e-08

protein tyrosine phosphatase domain of PTP domain-containing protein 1; protein tyrosine phosphatase domain-containing protein 1 (PTPDC1) is an uncharacterized non-receptor class protein-tyrosine phosphatase (PTP). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. Small interfering RNA (siRNA) knockdown of the ptpdc1 gene is associated with elongated cilia.


Pssm-ID: 350356 [Multi-domain]  Cd Length: 206  Bit Score: 54.28  E-value: 8.96e-08
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2327432701   95 VLEFGWPDLHTPALEKICSVCKAMDTWLNaDPHNVVVlHNKGNRGRIGVVIAAYLHYSNiSASADQALDRFAMKR 169
Cdd:cd14506     79 FYNFGWKDYGVPSLTTILDIVKVMAFALQ-EGGKVAV-HCHAGLGRTGVLIACYLVYAL-RMSADQAIRLVRSKR 150
PHA03307 PHA03307
transcriptional regulator ICP4; Provisional
945-1374 3.29e-06

transcriptional regulator ICP4; Provisional


Pssm-ID: 223039 [Multi-domain]  Cd Length: 1352  Bit Score: 52.10  E-value: 3.29e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  945 RPKEPHLHSYKEAFEEMEG------TSPSSPPHSVARSPPGLAKTPLSALGLKPHNpADILLHPTGEPRSYVESVARTAV 1018
Cdd:PHA03307     1 SDNAPDLYDLIEAAAEGGEffprppATPGDAADDLLSGSQGQLVSDSAELAAVTVV-AGAAACDRFEPPTGPPPGPGTEA 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1019 AGPRAQDVEPKSFSAPAAhayGHETPLRNGTPGGSfvspsplstsspilsadsTSVGSFPSVVSSDQGPRTPFQPMLDSS 1098
Cdd:PHA03307    80 PANESRSTPTWSLSTLAP---ASPAREGSPTPPGP------------------SSPDPPPPTPPPASPPPSPAPDLSEML 138
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1099 IRSGSLGQPSPAALSYQSSSPVPVGGSSYNSPDYSLqpFSSSPESQGQPqysaasvhmvPGSPQArhrTVGTNTPPSPGF 1178
Cdd:PHA03307   139 RPVGSPGPPPAASPPAAGASPAAVASDAASSRQAAL--PLSSPEETARA----------PSSPPA---EPPPSTPPAAAS 203
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1179 GRRAVNPTMAAPGSPSlshrqvmgpSGPGFHGNVVSGHPASAATTPGSPSLGRHPVGSHQVPGLHSSVVTTPGSPSLGrH 1258
Cdd:PHA03307   204 PRPPRRSSPISASASS---------PAPAPGRSAADDAGASSSDSSSSESSGCGWGPENECPLPRPAPITLPTRIWEA-S 273
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1259 PGAHQGNLASSLHSNAVISPGSPSLGRHLGGSGSVVPGSPSLDRHAAYGGYSTPEDRRPTLSRQSSASGYQAPSTPSFPV 1338
Cdd:PHA03307   274 GWNGPSSRPGPASSSSSPRERSPSPSPSSPGSGPAPSSPRASSSSSSSRESSSSSTSSSSESSRGAAVSPGPSPSRSPSP 353
                          410       420       430
                   ....*....|....*....|....*....|....*.
gi 2327432701 1339 SPAYYPGLSSPATSPSPDSAAFRQGSPTPALPEKRR 1374
Cdd:PHA03307   354 SRPPPPADPSSPRKRPRPSRAPSSPAASAGRPTRRR 389
CDC14 COG2453
Protein-tyrosine phosphatase [Signal transduction mechanisms];
94-190 9.34e-06

Protein-tyrosine phosphatase [Signal transduction mechanisms];


Pssm-ID: 441989 [Multi-domain]  Cd Length: 140  Bit Score: 46.89  E-value: 9.34e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701   94 KVLEFGWPDLHTPALEKICSVCKAMDTWLNADpHNVVVlHNKGNRGRIGVVIAAYLHYSNIsaSADQALDRFAMKRfyeD 173
Cdd:COG2453     49 EYLHLPIPDFGAPDDEQLQEAVDFIDEALREG-KKVLV-HCRGGIGRTGTVAAAYLVLLGL--SAEEALARVRAAR---P 121
                           90
                   ....*....|....*..
gi 2327432701  174 KIVPigQPSQRRYVHYF 190
Cdd:COG2453    122 GAVE--TPAQRAFLERF 136
PTZ00395 PTZ00395
Sec24-related protein; Provisional
855-1260 1.36e-05

Sec24-related protein; Provisional


Pssm-ID: 185594 [Multi-domain]  Cd Length: 1560  Bit Score: 50.46  E-value: 1.36e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  855 PKETTSDPSRTPEEEPLNleGLVAHRVAGvQARERQPAEPPgPLRRRAASDGQYENQSPEATSPRSPGVRSPVQCVS--- 931
Cdd:PTZ00395   116 ACEQSNQQSNIPIGDPVN--HLRGHPNFG-EPRERAEDAAP-HAQHNHSGKTNGDNPPTGGQYHQSGGTSRNHQMMDsnk 191
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  932 --PELALTIALNPGGR----------PKEPHLHS-------YK-EAFEEMEGTSPSSPP------------HSVARSPPG 979
Cdd:PTZ00395   192 ncPADALFNETNPSGEhkrnsidgdiPSDIYIDSqpnegdvQKtNPWQGKQGNSATSPPanennavtlscsNDQQRGASS 271
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  980 LAKTPLS---ALGLKPHNPADILLHPTGEPRSYVESVARTAVAGP--RAQDVEPKSFSAPAAHAYGHETPLRNGTPGGSF 1054
Cdd:PTZ00395   272 AAESGYAhhrGSNIASHTPNDNIMHAANNPLNNTNDAQRNAIQGDlvRGAPNDKNSFDRGNEKTYQIYGGFHDGSPNAAS 351
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1055 VSPSPLstsspilSADSTSVGSFPSVVSSDQ------GPRT--PFQPMLDSSIRSGSLGQpSPAALSYQSSSPVPVGGSS 1126
Cdd:PTZ00395   352 AGAPFN-------GLGNQADGGHINQVHPDArgawagGPHSnaSYNCAAYSNAAQSNAAQ-SNAGFSNAGYSNPGNSNPG 423
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1127 YNSPDYSLQPFSSSPESQ---GQPQYSAASVHMVPGSPQARHRTVGTNTPPSPGFGRRAVNPTmaapgspSLSHRQVMGP 1203
Cdd:PTZ00395   424 YNNAPNSNTPYNNPPNSNtpySNPPNSNPPYSNLPYSNTPYSNAPLSNAPPSSAKDHHSAYHA-------AYQHRAANQP 496
                          410       420       430       440       450
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2327432701 1204 SGPGFHGNVVSGHP--ASAATTPGSPSLGRhPVGSHQVPGLHSSVVTTPGSPSLGRHPG 1260
Cdd:PTZ00395   497 AANLPTANQPAANNfhGAAGNSVGNPFASR-PFGSAPYGGNAATTADPNGIAKREDHPE 554
Herpes_BLLF1 pfam05109
Herpes virus major outer envelope glycoprotein (BLLF1); This family consists of the BLLF1 ...
1109-1432 4.13e-05

Herpes virus major outer envelope glycoprotein (BLLF1); This family consists of the BLLF1 viral late glycoprotein, also termed gp350/220. It is the most abundantly expressed glycoprotein in the viral envelope of the Herpesviruses and is the major antigen responsible for stimulating the production of neutralising antibodies in vivo.


Pssm-ID: 282904 [Multi-domain]  Cd Length: 886  Bit Score: 48.37  E-value: 4.13e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1109 PAALSYQSSSPVPVGGSSYNSP-DYSLQPFSSSPESQGQPQYSAASVHMVPgSPQARHRTVGTNTPP----SPGFGRRAV 1183
Cdd:pfam05109  466 PTVSTADVTSPTPAGTTSGASPvTPSPSPRDNGTESKAPDMTSPTSAVTTP-TPNATSPTPAVTTPTpnatSPTLGKTSP 544
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1184 NPTMAAPGSPSLSHR-QVMGPSGPGFHGNVVSGHPASAATTPG----SPSLGRHP----VGSHQVPGLHSSVVTTPGSPS 1254
Cdd:pfam05109  545 TSAVTTPTPNATSPTpAVTTPTPNATIPTLGKTSPTSAVTTPTpnatSPTVGETSpqanTTNHTLGGTSSTPVVTSPPKN 624
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1255 LGRHPGAHQGNLASSLHSNAVISPGSPSLGRHLGGSGSVVPGSPSLDRHAAYGGYSTpedrrpTLSRQSSASGYQAPSTp 1334
Cdd:pfam05109  625 ATSAVTTGQHNITSSSTSSMSLRPSSISETLSPSTSDNSTSHMPLLTSAHPTGGENI------TQVTPASTSTHHVSTS- 697
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1335 sfpvSPAYYPGLSSPATSPSPDSAAFRQG--SPTPALPEKRRMSVGDRAG---SLPNYATINGKVSSSPVANGMASGSST 1409
Cdd:pfam05109  698 ----SPAPRPGTTSQASGPGNSSTSTKPGevNVTKGTPPKNATSPQAPSGqktAVPTVTSTGGKANSTTGGKHTTGHGAR 773
                          330       340
                   ....*....|....*....|...
gi 2327432701 1410 VSFSHTlpdfSKYSMPDNSPETR 1432
Cdd:pfam05109  774 TSTEPT----TDYGGDSTTPRTR 792
PHA03307 PHA03307
transcriptional regulator ICP4; Provisional
819-1227 7.27e-05

transcriptional regulator ICP4; Provisional


Pssm-ID: 223039 [Multi-domain]  Cd Length: 1352  Bit Score: 47.86  E-value: 7.27e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  819 PKSPASSTFLPSPHSSAGPQEPPASLPGLIAQPQLPPKETTSDPSRTPEEEPLNLEGLVAHRVAGVQARERQPAEPPGPL 898
Cdd:PHA03307    68 PTGPPPGPGTEAPANESRSTPTWSLSTLAPASPAREGSPTPPGPSSPDPPPPTPPPASPPPSPAPDLSEMLRPVGSPGPP 147
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  899 RRRAASDGQyENQSPEATSPRSPGVRSPVQCVSPELAltialnpggrpkephlhsykeafeemegTSPSSPPHSVARSPP 978
Cdd:PHA03307   148 PAASPPAAG-ASPAAVASDAASSRQAALPLSSPEETA----------------------------RAPSSPPAEPPPSTP 198
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  979 GLAKTPlsalglKPHNPADILLHPTGEPRSyveSVARTAVAGPRAqdvepKSFSAPAAHAYGHETPLRNGTPGGSFVSPS 1058
Cdd:PHA03307   199 PAAASP------RPPRRSSPISASASSPAP---APGRSAADDAGA-----SSSDSSSSESSGCGWGPENECPLPRPAPIT 264
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1059 PLSTSSPILSADSTSVGSFPSvvSSDQGPRTPFQPMLDSSIRSGSLGQPSPAALSYQSSSPVPVGGSSYNSPDYSLQPFS 1138
Cdd:PHA03307   265 LPTRIWEASGWNGPSSRPGPA--SSSSSPRERSPSPSPSSPGSGPAPSSPRASSSSSSSRESSSSSTSSSSESSRGAAVS 342
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1139 SSPESQGQPQYSAASVHMVPGSPQARHR--TVGTNTPPSPGFGRRavnptmaAPGSPSLSHRQVMGPSGPGFHGNVVSGH 1216
Cdd:PHA03307   343 PGPSPSRSPSPSRPPPPADPSSPRKRPRpsRAPSSPAASAGRPTR-------RRARAAVAGRARRRDATGRFPAGRPRPS 415
                          410
                   ....*....|.
gi 2327432701 1217 PASAATTPGSP 1227
Cdd:PHA03307   416 PLDAGAASGAF 426
SH2_Srm cd10360
Src homology 2 (SH2) domain found in Src-related kinase lacking C-terminal regulatory tyrosine ...
1445-1484 1.84e-04

Src homology 2 (SH2) domain found in Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristoylation sites (srm); Srm is a nonreceptor protein kinase that has two SH2 domains, a SH3 domain, and a kinase domain with a tyrosine residue for autophosphorylation. However it lacks an N-terminal glycine for myristoylation and a C-terminal tyrosine which suppresses kinase activity when phosphorylated. Srm is most similar to members of the Tec family who other members include: Tec, Btk/Emb, and Itk/Tsk/Emt. However Srm differs in its N-terminal unique domain it being much smaller than in the Tec family and is closer to Src. Srm is thought to be a new family of nonreceptor tyrosine kinases that may be redundant in function. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198223  Cd Length: 79  Bit Score: 41.48  E-value: 1.84e-04
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 2327432701 1445 WYKPEISREQAIALL--KDQEPGAFIIRDSHSFRGAYGLAMK 1484
Cdd:cd10360      2 WYFSGISRTQAQQLLlsPPNEPGAFLIRPSESSLGGYSLSVR 43
SH2_Tec_family cd09934
Src homology 2 (SH2) domain found in Tec-like proteins; The Tec protein tyrosine kinase is the ...
1443-1553 2.69e-04

Src homology 2 (SH2) domain found in Tec-like proteins; The Tec protein tyrosine kinase is the founding member of a family that includes Btk, Itk, Bmx, and Txk. The members have a PH domain, a zinc-binding motif, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. Btk is involved in B-cell receptor signaling with mutations in Btk responsible for X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (xid) in mice. Itk is involved in T-cell receptor signaling. Tec is expressed in both T and B cells, and is thought to function in activated and effector T lymphocytes to induce the expression of genes regulated by NFAT transcription factors. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198188  Cd Length: 104  Bit Score: 42.00  E-value: 2.69e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1443 KY-WYKPEISREQAIALLKDQ-EPGAFIIRDShSFRGAYGLA--MKVSSPPptitqqgkkgdmtheLVRHFLIETGPRG- 1517
Cdd:cd09934      5 KYeWYVGDMSRQRAESLLKQEdKEGCFVVRNS-STKGLYTVSlfTKVPGSP---------------HVKHYHIKQNARSe 68
                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 2327432701 1518 --VKLKGCpnepnFGSLSALVYQHSVIPLALPCKLVIP 1553
Cdd:cd09934     69 fyLAEKHC-----FETIPELINYHQHNSGGLATRLKYP 101
SH2_Grb2_like cd09941
Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar ...
1445-1542 3.02e-04

Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar proteins; The adaptor proteins here include homologs Grb2 in humans, Sex muscle abnormal protein 5 (Sem-5) in Caenorhabditis elegans, and Downstream of receptor kinase (drk) in Drosophila melanogaster. They are composed of one SH2 and two SH3 domains. Grb2/Sem-5/drk regulates the Ras pathway by linking the tyrosine kinases to the Ras guanine nucleotide releasing protein Sos, which converts Ras to the active GTP-bound state. The SH2 domain of Grb2/Sem-5/drk binds class II phosphotyrosyl peptides while its SH3 domain binds to Sos and Sos-derived, proline-rich peptides. Besides it function in Ras signaling, Grb2 is also thought to play a role in apoptosis. Unlike most SH2 structures in which the peptide binds in an extended conformation (such that the +3 peptide residue occupies a hydrophobic pocket in the protein, conferring a modest degree of selectivity), Grb2 forms several hydrogen bonds via main chain atoms with the side chain of +2 Asn. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199828  Cd Length: 95  Bit Score: 41.49  E-value: 3.02e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1445 WYKPEISREQAIALLKDQEP-GAFIIRDSHSFRGAYGLAMKVssppptitqqgkkgdmtHELVRHFLIETGPRG------ 1517
Cdd:cd09941      5 WFHGKISRAEAEEILMNQRPdGAFLIRESESSPGDFSLSVKF-----------------GNDVQHFKVLRDGAGkyflwv 67
                           90       100
                   ....*....|....*....|....*..
gi 2327432701 1518 VKlkgcpnepnFGSLSALV--YQHSVI 1542
Cdd:cd09941     68 VK---------FNSLNELVdyHRTTSV 85
SH2_ABL cd09935
Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ...
1445-1553 4.82e-04

Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ABL-family proteins are highly conserved tyrosine kinases. Each ABL protein contains an SH3-SH2-TK (Src homology 3-Src homology 2-tyrosine kinase) domain cassette, which confers autoregulated kinase activity and is common among nonreceptor tyrosine kinases. Several types of posttranslational modifications control ABL catalytic activity, subcellular localization, and stability, with consequences for both cytoplasmic and nuclear ABL functions. Binding partners provide additional regulation of ABL catalytic activity, substrate specificity, and downstream signaling. By combining this cassette with actin-binding and -bundling domain, ABL proteins are capable of connecting phosphoregulation with actin-filament reorganization. Vertebrate paralogs, ABL1 and ABL2, have evolved to perform specialized functions. ABL1 includes nuclear localization signals and a DNA binding domain which is used to mediate DNA damage-repair functions, while ABL2 has additional binding capacity for actin and for microtubules to enhance its cytoskeletal remodeling functions. SH2 is involved in several autoinhibitory mechanism that constrain the enzymatic activity of the ABL-family kinases. In one mechanism SH2 and SH3 cradle the kinase domain while a cap sequence stabilizes the inactive conformation resulting in a locked inactive state. Another involves phosphatidylinositol 4,5-bisphosphate (PIP2) which binds the SH2 domain through residues normally required for phosphotyrosine binding in the linker segment between the SH2 and kinase domains. The SH2 domain contributes to ABL catalytic activity and target site specificity. It is thought that the ABL catalytic site and SH2 pocket have coevolved to recognize the same sequences. Recent work now supports a hierarchical processivity model in which the substrate target site most compatible with ABL kinase domain preferences is phosphorylated with greatest efficiency. If this site is compatible with the ABL SH2 domain specificity, it will then reposition and dock in the SH2 pocket. This mechanism also explains how ABL kinases phosphorylates poor targets on the same substrate if they are properly positioned and how relatively poor substrate proteins might be recruited to ABL through a complex with strong substrates that can also dock with the SH2 pocket. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198189  Cd Length: 94  Bit Score: 40.83  E-value: 4.82e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1445 WYKPEISREQAIALLKDQEPGAFIIRDSHSFRGAYGLAMKVssppptitqqgkkgdmtHELVRHFLIETGPRGvKLKGCP 1524
Cdd:cd09935      5 WYHGPISRNAAEYLLSSGINGSFLVRESESSPGQYSISLRY-----------------DGRVYHYRISEDSDG-KVYVTQ 66
                           90       100
                   ....*....|....*....|....*....
gi 2327432701 1525 NEPnFGSLSALVYQHSVIPLALPCKLVIP 1553
Cdd:cd09935     67 EHR-FNTLAELVHHHSKNADGLITTLRYP 94
PTP_DSP_cys cd14494
cys-based protein tyrosine phosphatase and dual-specificity phosphatase superfamily; This ...
73-189 4.93e-04

cys-based protein tyrosine phosphatase and dual-specificity phosphatase superfamily; This superfamily is composed of cys-based phosphatases, which includes classical protein tyrosine phosphatases (PTPs) as well as dual-specificity phosphatases (DUSPs or DSPs). They are characterized by a CxxxxxR conserved catalytic loop (where C is the catalytic cysteine, x is any amino acid, and R is an arginine). PTPs are part of the tyrosine phosphorylation/dephosphorylation regulatory mechanism, and are important in the response of the cells to physiologic and pathologic changes in their environment. DUSPs show more substrate diversity (including RNA and lipids) and include pTyr, pSer, and pThr phosphatases.


Pssm-ID: 350344 [Multi-domain]  Cd Length: 113  Bit Score: 41.57  E-value: 4.93e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701   73 GGNYLLFNLSEQRPDitKLHAKVLEFGWPDLHTPALEKICSVCKAMDTWLNADPhnVVVLHNKGNRGRIGVVIAAYL-HY 151
Cdd:cd14494      6 PLRLIAGALPLSPLE--ADSRFLKQLGVTTIVDLTLAMVDRFLEVLDQAEKPGE--PVLVHCKAGVGRTGTLVACYLvLL 81
                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 2327432701  152 SNIsaSADQALDRfaMKRFYEDKIVPIgqPSQRRYVHY 189
Cdd:cd14494     82 GGM--SAEEAVRI--VRLIRPGGIPQT--IEQLDFLIK 113
SH2_Nterm_shark_like cd10347
N-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
1445-1483 6.54e-04

N-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) proteins; These non-receptor protein-tyrosine kinases contain two SH2 domains, five ankyrin (ANK)-like repeats, and a potential tyrosine phosphorylation site in the carboxyl-terminal tail which resembles the phosphorylation site in members of the src family. Like, mammalian non-receptor protein-tyrosine kinases, ZAP-70 and syk proteins, they do not have SH3 domains. However, the presence of ANK makes these unique among protein-tyrosine kinases. Both tyrosine kinases and ANK repeats have been shown to transduce developmental signals, and SH2 domains are known to participate intimately in tyrosine kinase signaling. These tyrosine kinases are believed to be involved in epithelial cell polarity. The members of this family include the shark (SH2 domains, ANK, and kinase domain) gene in Drosophila and yellow fever mosquitos, as well as the hydra protein HTK16. Drosophila Shark is proposed to transduce intracellularly the Crumbs, a protein necessary for proper organization of ectodermal epithelia, intercellular signal. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198210  Cd Length: 81  Bit Score: 40.05  E-value: 6.54e-04
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 2327432701 1445 WYKPEISREQAIALLKDQEP--GAFIIRDSHSFRGAYGLAM 1483
Cdd:cd10347      3 WYHGKISREVAEALLLREGGrdGLFLVRESTSAPGDYVLSL 43
SH2_BLNK_SLP-76 cd09929
Src homology 2 (SH2) domain found in B-cell linker (BLNK) protein and SH2 domain-containing ...
1442-1561 6.59e-04

Src homology 2 (SH2) domain found in B-cell linker (BLNK) protein and SH2 domain-containing leukocyte protein of 76 kDa (SLP-76); BLNK (also known as SLP-65 or BASH) is an important adaptor protein expressed in B-lineage cells. BLNK consists of a N-terminal sterile alpha motif (SAM) domain and a C-terminal SH2 domain. BLNK is a cytoplasmic protein, but a part of it is bound to the plasma membrane through an N-terminal leucine zipper motif and transiently bound to a cytoplasmic domain of Iga through its C-terminal SH2 domain upon B cell antigen receptor (BCR)-stimulation. A non-ITAM phosphotyrosine in Iga is necessary for the binding with the BLNK SH2 domain and/or for normal BLNK function in signaling and B cell activation. Upon phosphorylation BLNK binds Btk and PLCgamma2 through their SH2 domains and mediates PLCgamma2 activation by Btk. BLNK also binds other signaling molecules such as Vav, Grb2, Syk, and HPK1. BLNK has been shown to be necessary for BCR-mediated Ca2+ mobilization, for the activation of mitogen-activated protein kinases such as ERK, JNK, and p38 in a chicken B cell line DT40, and for activation of transcription factors such as NF-AT and NF-kappaB in human or mouse B cells. BLNK is involved in B cell development, B cell survival, activation, proliferation, and T-independent immune responses. BLNK is structurally homologous to SLP-76. SLP-76 and (linker for activation of T cells) LAT are adaptor/linker proteins in T cell antigen receptor activation and T cell development. BLNK interacts with many downstream signaling proteins that interact directly with both SLP-76 and LAT. New data suggest functional complementation of SLP-76 and LAT in T cell antigen receptor function with BLNK in BCR function. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198183  Cd Length: 121  Bit Score: 41.15  E-value: 6.59e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1442 SKYWYKPEISREQA-IALLKDQEPGAFIIRDS--HSFRGAYGLAM----KVSSPPptITQQGKKgdmthelvRHFLIETG 1514
Cdd:cd09929     10 PKEWYAGNIDRKEAeEALRRSNKDGTFLVRDSsgKDSSQPYTLMVlyndKVYNIQ--IRFLENT--------RQYALGTG 79
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 2327432701 1515 PRGvklkgcpnEPNFGSLSALVYQHSVIPLALpcklvIPSRDPTDES 1561
Cdd:cd09929     80 LRG--------EETFSSVAEIIEHHQKTPLLL-----IDGKDNTKDS 113
PLN02217 PLN02217
probable pectinesterase/pectinesterase inhibitor
1203-1326 8.01e-04

probable pectinesterase/pectinesterase inhibitor


Pssm-ID: 215130 [Multi-domain]  Cd Length: 670  Bit Score: 44.31  E-value: 8.01e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1203 PSGPGfhgnVVSGHPASAATTPGSPSLGRHPVGSHQVPglhSSVVTTPGSPslgrhPGAHQGNLASSlhSNAVISPGSPS 1282
Cdd:PLN02217   556 PYIPG----LFAGNPGSTNSTPTGSAASSNTTFSSDSP---STVVAPSTSP-----PAGHLGSPPAT--PSKIVSPSTSP 621
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 2327432701 1283 LGRHLgGSGSVVPGSPSLDRHAAYGGYSTPEDRRPTLSRQSSAS 1326
Cdd:PLN02217   622 PASHL-GSPSTTPSSPESSIKVASTETASPESSIKVASTESSVS 664
PHA03307 PHA03307
transcriptional regulator ICP4; Provisional
535-927 1.07e-03

transcriptional regulator ICP4; Provisional


Pssm-ID: 223039 [Multi-domain]  Cd Length: 1352  Bit Score: 44.01  E-value: 1.07e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  535 GSMGTLSSLDGVTNTSESGYPETLSPLTNGLDKPystepvlNGGGYPYEAANRVIPVHSSHSAPIRPSYSAQEGLAGYQR 614
Cdd:PHA03307    38 GSQGQLVSDSAELAAVTVVAGAAACDRFEPPTGP-------PPGPGTEAPANESRSTPTWSLSTLAPASPAREGSPTPPG 110
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  615 EGPHPAWSQQVTSAHCGCDPsGLFRSQSFPDVEPQLPQAPTR---GGSSREAVQRGL-NSWQQQQPHPPPRQQERSPLQS 690
Cdd:PHA03307   111 PSSPDPPPPTPPPASPPPSP-APDLSEMLRPVGSPGPPPAASppaAGASPAAVASDAaSSRQAALPLSSPEETARAPSSP 189
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  691 LARSKPSPQLSAETPVAALPEFPRAASQQEIEQSIETlnmlMLDLEPASAAAPLHKSQSVPGAWPGAS-----PLSSQPL 765
Cdd:PHA03307   190 PAEPPPSTPPAAASPRPPRRSSPISASASSPAPAPGR----SAADDAGASSSDSSSSESSGCGWGPENecplpRPAPITL 265
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  766 LGSSRQSHPLTQSRSGYIPSGHSLGTPEL---VSSGRPYSPYDYQLHPAGSNQSFHPKSPASSTfLPSPHSSAGPQEPPA 842
Cdd:PHA03307   266 PTRIWEASGWNGPSSRPGPASSSSSPRERspsPSPSSPGSGPAPSSPRASSSSSSSRESSSSST-SSSSESSRGAAVSPG 344
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  843 SLPGLIAQPQLPPkeTTSDPSRTPEEEPLNleglvahrvAGVQARERQPAEPPGPlRRRAASDGQYENQSpeaTSPRSPG 922
Cdd:PHA03307   345 PSPSRSPSPSRPP--PPADPSSPRKRPRPS---------RAPSSPAASAGRPTRR-RARAAVAGRARRRD---ATGRFPA 409

                   ....*
gi 2327432701  923 VRSPV 927
Cdd:PHA03307   410 GRPRP 414
PTZ00449 PTZ00449
104 kDa microneme/rhoptry antigen; Provisional
747-1051 1.28e-03

104 kDa microneme/rhoptry antigen; Provisional


Pssm-ID: 185628 [Multi-domain]  Cd Length: 943  Bit Score: 43.52  E-value: 1.28e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  747 SQSVPGAWPGASPLSSQPLLGSSRQSHPLTQSRSGYIPSGHSLGTPELVSSGRPYSPYDYQLHPAGSNQSFHPKSPASST 826
Cdd:PTZ00449   516 ASGLPPKAPGDKEGEEGEHEDSKESDEPKEGGKPGETKEGEVGKKPGPAKEHKPSKIPTLSKKPEFPKDPKHPKDPEEPK 595
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  827 FLPSPHSSAGPQEPPA-SLPGLIAQPQLPPK-ETTSDPSRTPEEEplnleglvahrvagvqaRERQPAEPPGPlrrraas 904
Cdd:PTZ00449   596 KPKRPRSAQRPTRPKSpKLPELLDIPKSPKRpESPKSPKRPPPPQ-----------------RPSSPERPEGP------- 651
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  905 dgqyenQSPEAT-SPRSPGVrsPVQCVSPELALTIALNPGGRPKE-----PHLHSYKEAFEEMEGTSPSSPPHSVARSPP 978
Cdd:PTZ00449   652 ------KIIKSPkPPKSPKP--PFDPKFKEKFYDDYLDAAAKSKEtkttvVLDESFESILKETLPETPGTPFTTPRPLPP 723
                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2327432701  979 GLAKTPLSalglkPHNpadillhPTGEPRSyvesvartavagPRAQDVEpkSFSAPAAHA-YGHETPLRNGTPG 1051
Cdd:PTZ00449   724 KLPRDEEF-----PFE-------PIGDPDA------------EQPDDIE--FFTPPEEERtFFHETPADTPLPD 771
SH2_nSH2_p85_like cd09942
N-terminal Src homology 2 (nSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
1445-1484 1.37e-03

N-terminal Src homology 2 (nSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are essential for cell growth, migration, and survival. p110, the catalytic subunit, is composed of an adaptor-binding domain, a Ras-binding domain, a C2 domain, a helical domain, and a kinase domain. The regulatory unit is called p85 and is composed of an SH3 domain, a RhoGap domain, a N-terminal SH2 (nSH2) domain, an internal SH2 (iSH2) domain, and C-terminal (cSH2) domain. There are 2 inhibitory interactions between p110alpha and p85 of P13K: (1) p85 nSH2 domain with the C2, helical, and kinase domains of p110alpha and (2) p85 iSH2 domain with C2 domain of p110alpha. There are 3 inhibitory interactions between p110beta and p85 of P13K: (1) p85 nSH2 domain with the C2, helical, and kinase domains of p110beta, (2) p85 iSH2 domain with C2 domain of p110alpha, and (3) p85 cSH2 domain with the kinase domain of p110alpha. It is interesting to note that p110beta is oncogenic as a wild type protein while p110alpha lacks this ability. One explanation is the idea that the regulation of p110beta by p85 is unique because of the addition of inhibitory contacts from the cSH2 domain and the loss of contacts in the iSH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198195  Cd Length: 110  Bit Score: 40.00  E-value: 1.37e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 2327432701 1445 WYKPEISREQAIALLKDQEPGAFIIRDSHSFRGAYGLAMK 1484
Cdd:cd09942      9 WYWGDISREEVNEKMRDTPDGTFLVRDASTMKGDYTLTLR 48
Chi1 COG3469
Chitinase [Carbohydrate transport and metabolism];
1144-1372 1.62e-03

Chitinase [Carbohydrate transport and metabolism];


Pssm-ID: 442692 [Multi-domain]  Cd Length: 534  Bit Score: 43.20  E-value: 1.62e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1144 QGQPQYSAASVHMVPGSPQARHRTVGTNTPPSPGFGrraVNPTMAAPGSPSLSHRQVMGPSGPGFHGNVVSGHPASAATT 1223
Cdd:COG3469     12 AGGASATAVTLLGAAATAASVTLTAATATTVVSTTG---SVVVAASGSAGSGTGTTAASSTAATSSTTSTTATATAAAAA 88
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1224 PGSPSLGRHPVGSHQVPGLHSSVVTTPGSPslgrhpgahQGNLASSLHSNAVISPGSPSLGRHLGGSGSVVPGSPSLDrh 1303
Cdd:COG3469     89 ATSTSATLVATSTASGANTGTSTVTTTSTG---------AGSVTSTTSSTAGSTTTSGASATSSAGSTTTTTTVSGTE-- 157
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2327432701 1304 AAYGGYSTPedrrptlsrqsSASGYQAPSTPSFPVSPAYYPGLSSPATSPSPDSAAFRQGSPTPALPEK 1372
Cdd:COG3469    158 TATGGTTTT-----------STTTTTTSASTTPSATTTATATTASGATTPSATTTATTTGPPTPGLPKH 215
COG5099 COG5099
RNA-binding protein of the Puf family, translational repressor [Translation, ribosomal ...
1096-1462 1.74e-03

RNA-binding protein of the Puf family, translational repressor [Translation, ribosomal structure and biogenesis];


Pssm-ID: 227430 [Multi-domain]  Cd Length: 777  Bit Score: 43.20  E-value: 1.74e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1096 DSSIRSGSLGQPSPAALSYQSSSP--VPVGGSSYNSPDYSLQPFSSSPESQGQPQYSAASVHmvpGSPQARHRTVGTNTP 1173
Cdd:COG5099     73 SSSSRRKPSGSWSVAISSSTSGSQslLMELPSSSFNPSTSSRNKSNSALSSTQQGNANSSVT---LSSSTASSMFNSNKL 149
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1174 PSPGFGrraVNPTMAAPGSPSLSHrqvMGPSgPGFHGNVVSghPASAATTPGSPSLGRHPVGSHQVPgLHSSVVTTPGSP 1253
Cdd:COG5099    150 PLPNPN---HSNSATTNQSGSSFI---NTPA-SSSSQPLTN--LVVSSIKRFPYLTSLSPFFNYLID-PSSDSATASADT 219
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1254 SLgrhpgahQGNLASSLHSNAVISPGSPSLGRH---LGGSGSVVPGSPSLDRHAAYGGYSTPEDRRPT-------LSRQS 1323
Cdd:COG5099    220 SP-------SFNPPPNLSPNNLFSTSDLSPLPDtqsVENNIILNSSSSINELTSIYGSVPSIRNLRGLnsalvsfLNVSS 292
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1324 SASGYQAPSTPsfPVSPAYYPGLSSPATSPSPDSA-AFRQGSPTPA-LPEKRRMSVGDRagSLPNYATIN-GKVSSSPVA 1400
Cdd:COG5099    293 SSLAFSALNGK--EVSPTGSPSTRSFARVLPKSSPnNLLTEILTTGvNPPQSLPSLLNP--VFLSTSTGFsLTNLSGYLN 368
                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2327432701 1401 NGMASGSSTVSFSHTLPDFSKYSMPDNSPETRAKVKFVQDTskywYKPEISREQAIALLKDQ 1462
Cdd:COG5099    369 PNKNLKKNTLSSLSNLGYSSNVPSPSSSESTRNILGNISPN----FKTSSNLTNLNSLLKEK 426
SH2_CRK_like cd09926
Src homology 2 domain found in cancer-related signaling adaptor protein CRK; SH2 domain in the ...
1445-1487 2.02e-03

Src homology 2 domain found in cancer-related signaling adaptor protein CRK; SH2 domain in the CRK proteins. CRKI (SH2-SH3) and CRKII (SH2-SH3-SH3) are splicing isoforms of the oncoprotein CRK. CRKs regulate transcription and cytoskeletal reorganization for cell growth and motility by linking tyrosine kinases to small G proteins. The SH2 domain of CRK associates with tyrosine-phosphorylated receptors or components of focal adhesions, such as p130Cas and paxillin. CRK transmits signals to small G proteins through effectors that bind its SH3 domain, such as C3G, the guanine-nucleotide exchange factor (GEF) for Rap1 and R-Ras, and DOCK180, the GEF for Rac6. The binding of p130Cas to the CRK-C3G complex activates Rap1, leading to regulation of cell adhesion, and activates R-Ras, leading to JNK-mediated activation of cell proliferation, whereas the binding of CRK DOCK180 induces Rac1-mediated activation of cellular migration. The activity of the different splicing isoforms varies greatly with CRKI displaying substantial transforming activity, CRKII less so, and phosphorylated CRKII with no biological activity whatsoever. CRKII has a linker region with a phosphorylated Tyr and an additional C-terminal SH3 domain. The phosphorylated Tyr creates a binding site for its SH2 domain which disrupts the association between CRK and its SH2 target proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198180 [Multi-domain]  Cd Length: 106  Bit Score: 39.38  E-value: 2.02e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 2327432701 1445 WYKPEISREQAIALLKDQEPGAFIIRDSHSFRGAYGLAMKVSS 1487
Cdd:cd09926      9 WYFGPMSRQEAQELLQGQRHGVFLVRDSSTIPGDYVLSVSENS 51
PHA03378 PHA03378
EBNA-3B; Provisional
715-946 2.21e-03

EBNA-3B; Provisional


Pssm-ID: 223065 [Multi-domain]  Cd Length: 991  Bit Score: 42.75  E-value: 2.21e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  715 AASQQEIEQSIETLNMLMLDLEPASAAAPLHKSQSVPG----AWPGASPlsSQPLLGSSRQSH----------------- 773
Cdd:PHA03378   554 ASTEPVHDQLLPAPGLGPLQIQPLTSPTTSQLASSAPSyaqtPWPVPHP--SQTPEPPTTQSHipetsaprqwpmplrpi 631
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  774 PLTQSRSGYIPSGHSLG-TPELVSSGRPYSPYDYQLHPAGSNqsFHPKSPASSTFLPsPHSSAGPQEPPASLPGLIAQPQ 852
Cdd:PHA03378   632 PMRPLRMQPITFNVLVFpTPHQPPQVEITPYKPTWTQIGHIP--YQPSPTGANTMLP-IQWAPGTMQPPPRAPTPMRPPA 708
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  853 LPPKETTSDPSRTPEEEPLNLEGLVAHRVAGVQARERQPAEPPGPLRRRAASDGQYE--NQSPEATSPRSPGVRSPVQCV 930
Cdd:PHA03378   709 APPGRAQRPAAATGRARPPAAAPGRARPPAAAPGRARPPAAAPGRARPPAAAPGRARppAAAPGAPTPQPPPQAPPAPQQ 788
                          250
                   ....*....|....*.
gi 2327432701  931 SPELALTIALNPGGRP 946
Cdd:PHA03378   789 RPRGAPTPQPPPQAGP 804
SH2_C-SH2_PLC_gamma_like cd09932
C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
1442-1485 2.79e-03

C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLCgamma is composed of a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, 2 catalytic regions of PLC domains that flank 2 tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. Both N-SH2 and C-SH2 have a very similar binding affinity to pY. But in growth factor stimulated cells these domains bind to different target proteins. N-SH2 binds to pY containing sites in the C-terminal tails of tyrosine kinases and other receptors. Recently it has been shown that this interaction is mediated by phosphorylation-independent interactions between a secondary binding site found exclusively on the N-SH2 domain and a region of the FGFR1 tyrosine kinase domain. This secondary site on the SH2 cooperates with the canonical pY site to regulate selectivity in mediating a specific cellular process. C-SH2 binds to an intramolecular site on PLCgamma itself which allows it to hydrolyze phosphatidylinositol-4,5-bisphosphate into diacylglycerol and inositol triphosphate. These then activate protein kinase C and release calcium. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198186  Cd Length: 104  Bit Score: 39.17  E-value: 2.79e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 2327432701 1442 SKYWYKPEISREQAIALLKD-QEPGAFIIRDSHSFRGAYGLAMKV 1485
Cdd:cd09932      3 SKEWFHANLTREQAEEMLMRvPRDGAFLVRPSETDPNSFAISFRA 47
SH2_Grb7_family cd09944
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) ...
1442-1484 3.17e-03

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. There are 3 members of the Grb7 family of proteins: Grb7, Grb10, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb7 binds strongly to the erbB2 receptor, unlike Grb10 and Grb14 which bind weakly to it. Grb14 binds to Fibroblast Growth Factor Receptor (FGFR). Grb10 has been shown to interact with many different proteins, including the insulin and IGF1 receptors, platelet-derived growth factor (PDGF) receptor-beta, Ret, Kit, Raf1 and MEK1, and Nedd4. Grb7 family proteins are phosphorylated on serine/threonine as well as tyrosine residues. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198197 [Multi-domain]  Cd Length: 108  Bit Score: 38.94  E-value: 3.17e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 2327432701 1442 SKYWYKPEISREQAIALLKDQ--EPGAFIIRDSHSFRGAYGLAMK 1484
Cdd:cd09944      4 SQPWFHGGISRDEAARLIRQQglVDGVFLVRESQSNPGAFVLSLK 48
SH2_csk_like cd09937
Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal ...
1445-1483 3.34e-03

Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal Src kinase (CSK) and CSK-homologous kinase (CHK) are members of the CSK-family of protein tyrosine kinases. These proteins suppress activity of Src-family kinases (SFK) by selectively phosphorylating the conserved C-terminal tail regulatory tyrosine by a similar mechanism. CHK is also capable of inhibiting SFKs by a non-catalytic mechanism that involves binding of CHK to SFKs to form stable protein complexes. The unphosphorylated form of SFKs is inhibited by CSK and CHK by a two-step mechanism. The first step involves the formation of a complex of SFKs with CSK/CHK with the SFKs in the complex are inactive. The second step, involves the phosphorylation of the C-terminal tail tyrosine of SFKs, which then dissociates and adopt an inactive conformation. The structural basis of how the phosphorylated SFKs dissociate from CSK/CHK to adopt the inactive conformation is not known. The inactive conformation of SFKs is stabilized by two intramolecular inhibitory interactions: (a) the pYT:SH2 interaction in which the phosphorylated C-terminal tail tyrosine (YT) binds to the SH2 domain, and (b) the linker:SH3 interaction of which the SH2-kinase domain linker binds to the SH3 domain. SFKs are activated by multiple mechanisms including binding of the ligands to the SH2 and SH3 domains to displace the two inhibitory intramolecular interactions, autophosphorylation, and dephosphorylation of YT. By selective phosphorylation and the non-catalytic inhibitory mechanism CSK and CHK are able to inhibit the active forms of SFKs. CSK and CHK are regulated by phosphorylation and inter-domain interactions. They both contain SH3, SH2, and kinase domains separated by the SH3-SH2 connector and SH2 kinase linker, intervening segments separating the three domains. They lack a conserved tyrosine phosphorylation site in the kinase domain and the C-terminal tail regulatory tyrosine phosphorylation site. The CSK SH2 domain is crucial for stabilizing the kinase domain in the active conformation. A disulfide bond here regulates CSK kinase activity. The subcellular localization and activity of CSK are regulated by its SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198190  Cd Length: 98  Bit Score: 38.43  E-value: 3.34e-03
                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 2327432701 1445 WYKPEISREQAIALLKDQEPGAFIIRDSHSFRGAYGLAM 1483
Cdd:cd09937      5 WFHGKISREEAERLLQPPEDGLFLVRESTNYPGDYTLCV 43
SH2_cSH2_p85_like cd09930
C-terminal Src homology 2 (cSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
1445-1540 3.68e-03

C-terminal Src homology 2 (cSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are essential for cell growth, migration, and survival. p110, the catalytic subunit, is composed of an adaptor-binding domain, a Ras-binding domain, a C2 domain, a helical domain, and a kinase domain. The regulatory unit is called p85 and is composed of an SH3 domain, a RhoGap domain, a N-terminal SH2 (nSH2) domain, a inter SH2 (iSH2) domain, and C-terminal (cSH2) domain. There are 2 inhibitory interactions between p110alpha and p85 of P13K: 1) p85 nSH2 domain with the C2, helical, and kinase domains of p110alpha and 2) p85 iSH2 domain with C2 domain of p110alpha. There are 3 inhibitory interactions between p110beta and p85 of P13K: 1) p85 nSH2 domain with the C2, helical, and kinase domains of p110beta, 2) p85 iSH2 domain with C2 domain of p110alpha, and 3) p85 cSH2 domain with the kinase domain of p110alpha. It is interesting to note that p110beta is oncogenic as a wild type protein while p110alpha lacks this ability. One explanation is the idea that the regulation of p110beta by p85 is unique because of the addition of inhibitory contacts from the cSH2 domain and the loss of contacts in the iSH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198184  Cd Length: 104  Bit Score: 38.55  E-value: 3.68e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1445 WYKPEISREQAIALLKDQEPGAFIIRDShSFRGAYGLAMKVSSppptitqqgkkgdmtheLVRHFLIETGPRGVKLKgcp 1524
Cdd:cd09930      8 WLVGDINRTQAEELLRGKPDGTFLIRES-STQGCYACSVVCNG-----------------EVKHCVIYKTETGYGFA--- 66
                           90       100
                   ....*....|....*....|
gi 2327432701 1525 nEPN--FGSLSALV--YQHS 1540
Cdd:cd09930     67 -EPYnlYESLKELVlhYAHN 85
SH2_SOCS_family cd09923
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) family; SH2 ...
1445-1472 3.73e-03

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) family; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198178  Cd Length: 81  Bit Score: 37.95  E-value: 3.73e-03
                           10        20
                   ....*....|....*....|....*...
gi 2327432701 1445 WYKPEISREQAIALLKDQEPGAFIIRDS 1472
Cdd:cd09923      2 WYWGGITRYEAEELLAGKPEGTFLVRDS 29
Herpes_BLLF1 pfam05109
Herpes virus major outer envelope glycoprotein (BLLF1); This family consists of the BLLF1 ...
855-1361 3.76e-03

Herpes virus major outer envelope glycoprotein (BLLF1); This family consists of the BLLF1 viral late glycoprotein, also termed gp350/220. It is the most abundantly expressed glycoprotein in the viral envelope of the Herpesviruses and is the major antigen responsible for stimulating the production of neutralising antibodies in vivo.


Pssm-ID: 282904 [Multi-domain]  Cd Length: 886  Bit Score: 42.21  E-value: 3.76e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  855 PKETTSDPSrtpeeepLNLEGLVA-HRVAGVQARERQPAEPPGPlrrraASDGQYENqSPEATSPRSPGVRSPVQCVSPE 933
Cdd:pfam05109  425 PESTTTSPT-------LNTTGFAApNTTTGLPSSTHVPTNLTAP-----ASTGPTVS-TADVTSPTPAGTTSGASPVTPS 491
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701  934 LAltiALNPGGRPKEPHLHSYKEAFEEMEGTSPSSPPHSVARSP----PGLAKT-PLSALGLKPHN---PADILLHPTge 1005
Cdd:pfam05109  492 PS---PRDNGTESKAPDMTSPTSAVTTPTPNATSPTPAVTTPTPnatsPTLGKTsPTSAVTTPTPNatsPTPAVTTPT-- 566
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1006 PRSYVESVART----AVAGPRAQDVEPK-SFSAPAAHAYGHetplrngTPGGSFVSPSPLSTSSPILSADSTSVGSFPSV 1080
Cdd:pfam05109  567 PNATIPTLGKTsptsAVTTPTPNATSPTvGETSPQANTTNH-------TLGGTSSTPVVTSPPKNATSAVTTGQHNITSS 639
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1081 VSSDQgprtpfqpmldsSIRSGSLGQPSPAALSYQSSSPVPVGGSSYnspdyslqpfssspesqgqPQYSAASVHMVPGS 1160
Cdd:pfam05109  640 STSSM------------SLRPSSISETLSPSTSDNSTSHMPLLTSAH-------------------PTGGENITQVTPAS 688
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1161 PQARHrtVGTNTP-PSPGFGRRAvnptmAAPGSPSLSHRqvmgpsgPGfHGNVVSGHPASAATTPGSPSLGRHPVgshqv 1239
Cdd:pfam05109  689 TSTHH--VSTSSPaPRPGTTSQA-----SGPGNSSTSTK-------PG-EVNVTKGTPPKNATSPQAPSGQKTAV----- 748
                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2327432701 1240 pglhSSVVTTPGSPSlgrhpgahqgnlasslhsnavispgSPSLGRHLGGSGSVVPGSPSLDrhaaYGGYSTpedrrpTL 1319
Cdd:pfam05109  749 ----PTVTSTGGKAN-------------------------STTGGKHTTGHGARTSTEPTTD----YGGDST------TP 789
                          490       500       510       520
                   ....*....|....*....|....*....|....*....|....*.
gi 2327432701 1320 SRQSSASGYQAPSTPSfPVSPAYY----PGLSSPATSPSPDSAAFR 1361
Cdd:pfam05109  790 RTRYNATTYLPPSTSS-KLRPRWTftspPVTTAQATVPVPPTSQPR 834
SH2_SLAP cd10344
Src homology 2 domain found in Src-like adaptor proteins; SLAP belongs to the subfamily of ...
1445-1488 6.50e-03

Src homology 2 domain found in Src-like adaptor proteins; SLAP belongs to the subfamily of adapter proteins that negatively regulate cellular signaling initiated by tyrosine kinases. It has a myristylated N-terminus, SH3 and SH2 domains with high homology to Src family tyrosine kinases, and a unique C-terminal tail, which is important for c-Cbl binding. SLAP negatively regulates platelet-derived growth factor (PDGF)-induced mitogenesis in fibroblasts and regulates F-actin assembly for dorsal ruffles formation. c-Cbl mediated SLAP inhibition towards actin remodeling. Moreover, SLAP enhanced PDGF-induced c-Cbl phosphorylation by SFK. In contrast, SLAP mitogenic inhibition was not mediated by c-Cbl, but it rather involved a competitive mechanism with SFK for PDGF-receptor (PDGFR) association and mitogenic signaling. Accordingly, phosphorylation of the Src mitogenic substrates Stat3 and Shc were reduced by SLAP. Thus, we concluded that SLAP regulates PDGFR signaling by two independent mechanisms: a competitive mechanism for PDGF-induced Src mitogenic signaling and a non-competitive mechanism for dorsal ruffles formation mediated by c-Cbl. SLAP is a hematopoietic adaptor containing Src homology (SH)3 and SH2 motifs and a unique carboxy terminus. Unlike c-Src, SLAP lacks a tyrosine kinase domain. Unlike c-Src, SLAP does not impact resorptive function of mature osteoclasts but induces their early apoptosis. SLAP negatively regulates differentiation of osteoclasts and proliferation of their precursors. Conversely, SLAP decreases osteoclast death by inhibiting activation of caspase 3. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198207  Cd Length: 104  Bit Score: 37.86  E-value: 6.50e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 2327432701 1445 WYKPEISREQAIALLK--DQEPGAFIIRDSHSFRGAYGLAMKVSSP 1488
Cdd:cd10344     12 WLFEGLSREKAEELLMlpGNQVGSFLIRESETRRGCYSLSVRHRGS 57
SH2_Cterm_RasGAP cd10354
C-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP ...
1445-1517 7.57e-03

C-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP is part of the GAP1 family of GTPase-activating proteins. The protein is located in the cytoplasm and stimulates the GTPase activity of normal RAS p21, but not its oncogenic counterpart. Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in RAS inactivation, thereby allowing control of cellular proliferation and differentiation. Mutations leading to changes in the binding sites of either protein are associated with basal cell carcinomas. Alternative splicing results in two isoforms. The shorter isoform which lacks the N-terminal hydrophobic region, has the same activity, and is expressed in placental tissues. In general longer isoform contains 2 SH2 domains, a SH3 domain, a pleckstrin homology (PH) domain, and a calcium-dependent phospholipid-binding C2 domain. The C-terminus contains the catalytic domain of RasGap which catalyzes the activation of Ras by hydrolyzing GTP-bound active Ras into an inactive GDP-bound form of Ras. This model contains the C-terminal SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198217  Cd Length: 77  Bit Score: 37.02  E-value: 7.57e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2327432701 1445 WYKPEISREQAIALL-KDQEPGAFIIRDSHSFRGAYGLAMKVSsppptitqqgkkgdmthELVRHFLIETGPRG 1517
Cdd:cd10354      2 WFHGKISREEAYNMLvKVGGPGSFLVRESDNTPGDYSLSFRVN-----------------EGIKHFKIIPTGNN 58
SH2_a2chimerin_b2chimerin cd10352
Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins ...
1450-1484 9.62e-03

Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins are a family of phorbol ester- and diacylglycerol-responsive GTPase-activating proteins. Alpha1-chimerin (formerly known as n-chimerin) and alpha2-chimerin are alternatively spliced products of a single gene, as are beta1- and beta2-chimerin. alpha1- and beta1-chimerin have a relatively short N-terminal region that does not encode any recognizable domains, whereas alpha2- and beta2-chimerin both include a functional SH2 domain that can bind to phosphotyrosine motifs within receptors. All of the isoforms contain a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. Other C1 domain-containing diacylglycerol receptors including: PKC, Munc-13 proteins, phorbol ester binding scaffolding proteins involved in Ca2+-stimulated exocytosis, and RasGRPs, diacylglycerol-activated guanine-nucleotide exchange factors (GEFs) for Ras and Rap1. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198215  Cd Length: 91  Bit Score: 36.96  E-value: 9.62e-03
                           10        20        30
                   ....*....|....*....|....*....|....*
gi 2327432701 1450 ISREQAIALLKDQEPGAFIIRDSHSFRGAYGLAMK 1484
Cdd:cd10352     13 ISREEAEQLLSGASDGSYLIRESSRDDGYYTLSLR 47
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

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