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Conserved domains on  [gi|187953453|gb|AAI37134|]
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Tensin 3 [Homo sapiens]

Protein Classification

phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN( domain architecture ID 12998495)

phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN acts as a dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PTP_tensin-3 cd14561
protein tyrosine phosphatase-like domain of tensin-3; Tensin-3 (TNS3) is also called ...
 8-166 2.59e-116

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: 361.19  E-value: 2.59e-116
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453    8 DLTYITERIIAVSFPAGCSEESYLHNLQEVTRMLKSKHGDNYLVLNLSEKRYDLTKLNPKIMDVGWPELHAPPLDKMCTI 87
Cdd:cd14561     1 DLTYITERIIAVSFPADCSEETYLHNLQDVTRMLKSKHGDNYLVLNLSEKRYELTKLNPKIMDVGWPDLHAPPLDKMCTI 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 187953453   88 CKAQESWLNSNLQHVVVIHCRGGKGRIGVVISSYMHFTNVSASADQALDRFAMKKFYDDKVSALMQPSQKRYVQFLSGL 166
Cdd:cd14561    81 CKAMESWLNSDPLHVVVIHCRGGKGRIGVVISSYMHFTNVSASADQALDRFAMKKFYDDKVSALMQPSQKRYVQFLSGL 159
PTB_tensin cd01213
Tensin Phosphotyrosine-binding (PTB) domain; Tensin is a a focal adhesion protein, which ...
 1308-1439 2.75e-84

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: 271.42  E-value: 2.75e-84
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453 1308 GAACNVWYLNSVEMESLTGHQAIQKALSITLVQEPPPVSTVVHFKVSAQGITLTDNQRKLFFRRHYPVNSVIFCALDPQD 1387
Cdd:cd01213     1 GAACNVLYLGSVDTESLTGPQAVRKAVSETLERDPLPTPTVVHFKVSEQGITLTDNQRKLFFRRHYPLNTVSFCGMDPEN 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 187953453 1388 RKWIK----DGPSSKVFGFVARKQGSATDNVCHLFAEHDPEQPASAIVNFVSKVMI 1439
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. ...
 1168-1284 2.24e-66

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: 219.22  E-value: 2.24e-66
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453 1168 TSKFWYKADISREQAIAMLKDKEPGSFIVRDSHSFRGAYGLAMKVATPPPSVLQLNKKaGDLANELVRHFLIECTPKGVR 1247
Cdd:cd09927     1 TSKYWYKPNISRDQAIALLKDKPPGTFLVRDSTTYKGAYGLAVKVATPPPGVNPFEAK-GDPESELVRHFLIEPSPKGVK 79

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 187953453 1248 LKGCSNEPYFGSLTALVCQHSITPLALPCKLLIPERD 1284
Cdd:cd09927    80 LKGCPNEPVFGSLSALVYQHSITPLALPCKLRIPDRD 116
PTEN_C2 pfam10409
C2 domain of PTEN tumour-suppressor protein; This is the C2 domain-like domain, in greek key ...
 173-299 3.75e-47

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: 165.14  E-value: 3.75e-47
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453   173 MNASPLFLHFVILHGTPNFDTGGVCRPFLKLYQAMQPV-YTSGIYNVGPENPSRICIVIEPAQL-LKGDVMVKCYHKKYR 250
Cdd:pfam10409    1 PPPKPLTLHSIILHGIPNFKSGGGCRPYIRIYQNKKKVfSTSGKYKKLKEYQQDDCVILFPKGIpVQGDVLVEFYHKGSD 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 187953453   251 SATRDVIFRLQFHTGAVQGYGLVFGKEDLDNASKD---DRFPDYGKVELVFS 299
Cdd:pfam10409   81 LLSEEKMFRFWFNTSFIEDNTLTLPKNELDKADKDkkdKRFPKDFKVELLFS 132
PHA03247 super family cl33720
large tegument protein UL36; Provisional
 624-1058 4.92e-05

large tegument protein UL36; Provisional


The actual alignment was detected with superfamily member PHA03247:

Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 48.40  E-value: 4.92e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453  624 QAQPRVPLTPtRGTSSRVAVQRGVGSGPHPPDTQQPSPSKAfkPRFPGDQVVNGAGPELSTGPSPGSPTLDIDQSIEQLN 703
Cdd:PHA03247 2595 SARPRAPVDD-RGDPRGPAPPSPLPPDTHAPDPPPPSPSPA--ANEPDPHPPPTVPPPERPRDDPAPGRVSRPRRARRLG 2671

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453  704 RLILELDPTFEPIPthmnalgsqangSVSPDSVgGGLRASSRLPDTGEGPSRATGRQGSSAEQPLGGRlrklslgqydnD 783
Cdd:PHA03247 2672 RAAQASSPPQRPRR------------RAARPTV-GSLTSLADPPPPPPTPEPAPHALVSATPLPPGPA-----------A 2727

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453  784 AGGQLPfskcawgkagvdyAPNLPPFPsPADVKETMTPGYPQDldiIDGRILSSKESMCSTPAFPVSPETPYV-KTALRH 862
Cdd:PHA03247 2728 ARQASP-------------ALPAAPAP-PAVPAGPATPGGPAR---PARPPTTAGPPAPAPPAAPAAGPPRRLtRPAVAS 2790

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453  863 PPFSPPEPPLSSPASQHKGGREPRSCPETLTHAvgmSESPIGPKSTMLRADASSTPSFQQAFASSC-TISSNGPGQRRES 941
Cdd:PHA03247 2791 LSESRESLPSPWDPADPPAAVLAPAAALPPAAS---PAGPLPPPTSAQPTAPPPPPGPPPPSLPLGgSVAPGGDVRRRPP 2867

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453  942 SSSAERQwVESSPKPMVSLLgsGRPTGSPLSAEFSgtrkdSPVLSCFPPSELQAPFHSHELSLAEPPDSLAP-------P 1014
Cdd:PHA03247 2868 SRSPAAK-PAAPARPPVRRL--ARPAVSRSTESFA-----LPPDQPERPPQPQAPPPPQPQPQPPPPPQPQPpppppprP 2939

                         410       420       430       440       450
                  ....*....|....*....|....*....|....*....|....*....|..
gi 187953453 1015 SSQAFLGFGTAPVG--SGLPPEEDLGALLANSHGA------SPTPSIPLTAT 1058
Cdd:PHA03247 2940 QPPLAPTTDPAGAGepSGAVPQPWLGALVPGRVAVprfrvpQPAPSREAPAS 2991
 
Name Accession Description Interval E-value
PTP_tensin-3 cd14561
protein tyrosine phosphatase-like domain of tensin-3; Tensin-3 (TNS3) is also called ...
 8-166 2.59e-116

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: 361.19  E-value: 2.59e-116
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453    8 DLTYITERIIAVSFPAGCSEESYLHNLQEVTRMLKSKHGDNYLVLNLSEKRYDLTKLNPKIMDVGWPELHAPPLDKMCTI 87
Cdd:cd14561     1 DLTYITERIIAVSFPADCSEETYLHNLQDVTRMLKSKHGDNYLVLNLSEKRYELTKLNPKIMDVGWPDLHAPPLDKMCTI 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 187953453   88 CKAQESWLNSNLQHVVVIHCRGGKGRIGVVISSYMHFTNVSASADQALDRFAMKKFYDDKVSALMQPSQKRYVQFLSGL 166
Cdd:cd14561    81 CKAMESWLNSDPLHVVVIHCRGGKGRIGVVISSYMHFTNVSASADQALDRFAMKKFYDDKVSALMQPSQKRYVQFLSGL 159
PTB_tensin cd01213
Tensin Phosphotyrosine-binding (PTB) domain; Tensin is a a focal adhesion protein, which ...
 1308-1439 2.75e-84

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: 271.42  E-value: 2.75e-84
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453 1308 GAACNVWYLNSVEMESLTGHQAIQKALSITLVQEPPPVSTVVHFKVSAQGITLTDNQRKLFFRRHYPVNSVIFCALDPQD 1387
Cdd:cd01213     1 GAACNVLYLGSVDTESLTGPQAVRKAVSETLERDPLPTPTVVHFKVSEQGITLTDNQRKLFFRRHYPLNTVSFCGMDPEN 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 187953453 1388 RKWIK----DGPSSKVFGFVARKQGSATDNVCHLFAEHDPEQPASAIVNFVSKVMI 1439
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. ...
 1168-1284 2.24e-66

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: 219.22  E-value: 2.24e-66
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453 1168 TSKFWYKADISREQAIAMLKDKEPGSFIVRDSHSFRGAYGLAMKVATPPPSVLQLNKKaGDLANELVRHFLIECTPKGVR 1247
Cdd:cd09927     1 TSKYWYKPNISRDQAIALLKDKPPGTFLVRDSTTYKGAYGLAVKVATPPPGVNPFEAK-GDPESELVRHFLIEPSPKGVK 79

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 187953453 1248 LKGCSNEPYFGSLTALVCQHSITPLALPCKLLIPERD 1284
Cdd:cd09927    80 LKGCPNEPVFGSLSALVYQHSITPLALPCKLRIPDRD 116
PTB pfam08416
Phosphotyrosine-binding domain; The phosphotyrosine-binding domain (PTB, also ...
 1310-1444 3.90e-48

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: 167.91  E-value: 3.90e-48
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453  1310 ACNVWYLNSVEMESLTGHQAIQKAL--SITLVQEPPPVSTVVHFKVSAQGITLTDNQRKLFFrRHYPVNSVIFCALDPQD 1387
Cdd:pfam08416    1 QYRVEHLTTFELDSLTGLQAVEDAIrkLQLLDAQGRVWTQEMLLQVSDQGITLTDNETKEEL-ESYPLDSISHCQAVLND 79

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 187953453  1388 RKWIkdgpssKVFGFVARKQGSATDNVcHLFA--EHDPEQPASAIVNFVSKVMIGSPKK 1444
Cdd:pfam08416   80 GRYN------SILALVCQEPGQSKPDV-HLFQcdELGAELIAEDIESALSDVRLGKPKK 131
PTEN_C2 pfam10409
C2 domain of PTEN tumour-suppressor protein; This is the C2 domain-like domain, in greek key ...
 173-299 3.75e-47

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: 165.14  E-value: 3.75e-47
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453   173 MNASPLFLHFVILHGTPNFDTGGVCRPFLKLYQAMQPV-YTSGIYNVGPENPSRICIVIEPAQL-LKGDVMVKCYHKKYR 250
Cdd:pfam10409    1 PPPKPLTLHSIILHGIPNFKSGGGCRPYIRIYQNKKKVfSTSGKYKKLKEYQQDDCVILFPKGIpVQGDVLVEFYHKGSD 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 187953453   251 SATRDVIFRLQFHTGAVQGYGLVFGKEDLDNASKD---DRFPDYGKVELVFS 299
Cdd:pfam10409   81 LLSEEKMFRFWFNTSFIEDNTLTLPKNELDKADKDkkdKRFPKDFKVELLFS 132
PTB smart00462
Phosphotyrosine-binding domain, phosphotyrosine-interaction (PI) domain; PTB/PI domain ...
 1307-1433 1.12e-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: 95.07  E-value: 1.12e-22
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453   1307 QGAACNVWYLNSVEMESLTGHQAIQKALSITLVQEPPPVSTV--VHFKVSAQGITLTDNQRKlFFRRHYPVNSVIFCALD 1384
Cdd:smart00462    2 SGVSFRVKYLGSVEVPEARGLQVVQEAIRKLRAAQGSEKKEPqkVILSISSRGVKLIDEDTK-AVLHEHPLRRISFCAVG 80

                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|.
gi 187953453   1385 PQDrkwikdgpsSKVFGFVARKQGSaTDNVCHLF--AEHDPEQPASAIVNF 1433
Cdd:smart00462   81 PDD---------LDVFGYIARDPGS-SRFACHVFrcEKAAEDIALAIGQAF 121
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
 1172-1272 1.02e-14

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: 70.72  E-value: 1.02e-14
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453   1172 WYKADISREQAIAMLKDKEPGSFIVRDSHSFRGAYGLAMKVatpppsvlqlnkkagdlaNELVRHFLIECTPKGVRlkGC 1251
Cdd:smart00252    3 WYHGFISREEAEKLLKNEGDGDFLVRDSESSPGDYVLSVRV------------------KGKVKHYRIRRNEDGKF--YL 62

                            90       100
                    ....*....|....*....|.
gi 187953453   1252 SNEPYFGSLTALVCQHSITPL 1272
Cdd:smart00252   63 EGGRKFPSLVELVEHYQKNSL 83
SH2 pfam00017
SH2 domain;
1172-1264 7.27e-10

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 56.46  E-value: 7.27e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453  1172 WYKADISREQAIAMLK-DKEPGSFIVRDSHSFRGAYGLamkvatpppSVlqlnkkagdLANELVRHFLIECTPKGVRLkg 1250
Cdd:pfam00017    1 WYHGKISRQEAERLLLnGKPDGTFLVRESESTPGGYTL---------SV---------RDDGKVKHYKIQSTDNGGYY-- 60

                           90
                   ....*....|....
gi 187953453  1251 CSNEPYFGSLTALV 1264
Cdd:pfam00017   61 ISGGVKFSSLAELV 74
PTPc_motif smart00404
Protein tyrosine phosphatase, catalytic domain motif;
72-186 3.75e-08

Protein tyrosine phosphatase, catalytic domain motif;


Pssm-ID: 214649 [Multi-domain]  Cd Length: 105  Bit Score: 52.75  E-value: 3.75e-08
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453     72 GWPELHAPPL-DKMCTICKAQESWLN-SNLQHVVVIHCRGGKGRIGVVISSYMHFTNVSASADqaldrfamkkfyddkvs 149
Cdd:smart00404    9 GWPDHGVPESpDSILELLRAVKKNLNqSESSGPVVVHCSAGVGRTGTFVAIDILLQQLEAEAG----------------- 71

                            90       100       110
                    ....*....|....*....|....*....|....*..
gi 187953453    150 almQPSQKRYVQFLSGLLSGSVKMNASPLFLHFVILH 186
Cdd:smart00404   72 ---EVDIFDTVKELRSQRPGMVQTEEQYLFLYRALLE 105
CDC14 COG2453
Protein-tyrosine phosphatase [Signal transduction mechanisms];
73-137 1.81e-05

Protein-tyrosine phosphatase [Signal transduction mechanisms];


Pssm-ID: 441989 [Multi-domain]  Cd Length: 140  Bit Score: 46.12  E-value: 1.81e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 187953453   73 WPELHAPPLDKMCTICKaqesWLNSNLQ--HVVVIHCRGGKGRIGVVISSYMHFTNVsaSADQALDR 137
Cdd:COG2453    55 IPDFGAPDDEQLQEAVD----FIDEALRegKKVLVHCRGGIGRTGTVAAAYLVLLGL--SAEEALAR 115
PHA03247 PHA03247
large tegument protein UL36; Provisional
 624-1058 4.92e-05

large tegument protein UL36; Provisional


Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 48.40  E-value: 4.92e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453  624 QAQPRVPLTPtRGTSSRVAVQRGVGSGPHPPDTQQPSPSKAfkPRFPGDQVVNGAGPELSTGPSPGSPTLDIDQSIEQLN 703
Cdd:PHA03247 2595 SARPRAPVDD-RGDPRGPAPPSPLPPDTHAPDPPPPSPSPA--ANEPDPHPPPTVPPPERPRDDPAPGRVSRPRRARRLG 2671

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453  704 RLILELDPTFEPIPthmnalgsqangSVSPDSVgGGLRASSRLPDTGEGPSRATGRQGSSAEQPLGGRlrklslgqydnD 783
Cdd:PHA03247 2672 RAAQASSPPQRPRR------------RAARPTV-GSLTSLADPPPPPPTPEPAPHALVSATPLPPGPA-----------A 2727

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453  784 AGGQLPfskcawgkagvdyAPNLPPFPsPADVKETMTPGYPQDldiIDGRILSSKESMCSTPAFPVSPETPYV-KTALRH 862
Cdd:PHA03247 2728 ARQASP-------------ALPAAPAP-PAVPAGPATPGGPAR---PARPPTTAGPPAPAPPAAPAAGPPRRLtRPAVAS 2790

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453  863 PPFSPPEPPLSSPASQHKGGREPRSCPETLTHAvgmSESPIGPKSTMLRADASSTPSFQQAFASSC-TISSNGPGQRRES 941
Cdd:PHA03247 2791 LSESRESLPSPWDPADPPAAVLAPAAALPPAAS---PAGPLPPPTSAQPTAPPPPPGPPPPSLPLGgSVAPGGDVRRRPP 2867

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453  942 SSSAERQwVESSPKPMVSLLgsGRPTGSPLSAEFSgtrkdSPVLSCFPPSELQAPFHSHELSLAEPPDSLAP-------P 1014
Cdd:PHA03247 2868 SRSPAAK-PAAPARPPVRRL--ARPAVSRSTESFA-----LPPDQPERPPQPQAPPPPQPQPQPPPPPQPQPpppppprP 2939

                         410       420       430       440       450
                  ....*....|....*....|....*....|....*....|....*....|..
gi 187953453 1015 SSQAFLGFGTAPVG--SGLPPEEDLGALLANSHGA------SPTPSIPLTAT 1058
Cdd:PHA03247 2940 QPPLAPTTDPAGAGepSGAVPQPWLGALVPGRVAVprfrvpQPAPSREAPAS 2991
 
Name Accession Description Interval E-value
PTP_tensin-3 cd14561
protein tyrosine phosphatase-like domain of tensin-3; Tensin-3 (TNS3) is also called ...
 8-166 2.59e-116

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: 361.19  E-value: 2.59e-116
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453    8 DLTYITERIIAVSFPAGCSEESYLHNLQEVTRMLKSKHGDNYLVLNLSEKRYDLTKLNPKIMDVGWPELHAPPLDKMCTI 87
Cdd:cd14561     1 DLTYITERIIAVSFPADCSEETYLHNLQDVTRMLKSKHGDNYLVLNLSEKRYELTKLNPKIMDVGWPDLHAPPLDKMCTI 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 187953453   88 CKAQESWLNSNLQHVVVIHCRGGKGRIGVVISSYMHFTNVSASADQALDRFAMKKFYDDKVSALMQPSQKRYVQFLSGL 166
Cdd:cd14561    81 CKAMESWLNSDPLHVVVIHCRGGKGRIGVVISSYMHFTNVSASADQALDRFAMKKFYDDKVSALMQPSQKRYVQFLSGL 159
PTP_tensin cd14508
protein tyrosine phosphatase-like domain of tensins; The tensin family of intracellular ...
 8-166 2.10e-97

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: 308.93  E-value: 2.10e-97
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453    8 DLTYITERIIAVSFPAGCSEESYLHNLQEVTRMLKSKHGDNYLVLNLSEKRYDLTKLNPKIMDVGWPELHAPPLDKMCTI 87
Cdd:cd14508     1 DLTYITERIIALSFPSTCSEQTYRHNLREAAHLLQSKHGDNYMVFNLSERRHDLRSLNPKVLDFGWPELHAPPLEKLCSI 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 187953453   88 CKAQESWLNSNLQHVVVIHCRGGKGRIGVVISSYMHFTNVSASADQALDRFAMKKFYDDKVSALMQPSQKRYVQFLSGL 166
Cdd:cd14508    81 CKNMDSWLNADPQNVVVLHCKGGKGRLGVVVSAYMHYSKISATADQALDRFAMKRFYDDKVGPLGQPSQKRYVGYFSGL 159
PTP_tensin-1 cd14560
protein tyrosine phosphatase-like domain of tensin-1; Tensin-1 (TNS1) is part of the tensin ...
 8-166 4.14e-85

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: 274.55  E-value: 4.14e-85
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453    8 DLTYITERIIAVSFPAGCSEESYLHNLQEVTRMLKSKHGDNYLVLNLSEKRYDLTKLNPKIMDVGWPELHAPPLDKMCTI 87
Cdd:cd14560     1 DLVYITERIISVSFPSTAEEPSFRSNLKEVAQMLKSKHGDNYLLFNLSERRHDISKLHPKVLDFGWPDLHAPALEKICSI 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 187953453   88 CKAQESWLNSNLQHVVVIHCRGGKGRIGVVISSYMHFTNVSASADQALDRFAMKKFYDDKVSALMQPSQKRYVQFLSGL 166
Cdd:cd14560    81 CKAMDTWLNADPHNVVVIHNKGNRGRTGVVIAAYMHYSNISASADQALDRFAMKRFYEDKVVPVGQPSQKRYVHYFSGL 159
PTB_tensin cd01213
Tensin Phosphotyrosine-binding (PTB) domain; Tensin is a a focal adhesion protein, which ...
 1308-1439 2.75e-84

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: 271.42  E-value: 2.75e-84
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453 1308 GAACNVWYLNSVEMESLTGHQAIQKALSITLVQEPPPVSTVVHFKVSAQGITLTDNQRKLFFRRHYPVNSVIFCALDPQD 1387
Cdd:cd01213     1 GAACNVLYLGSVDTESLTGPQAVRKAVSETLERDPLPTPTVVHFKVSEQGITLTDNQRKLFFRRHYPLNTVSFCGMDPEN 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 187953453 1388 RKWIK----DGPSSKVFGFVARKQGSATDNVCHLFAEHDPEQPASAIVNFVSKVMI 1439
Cdd:cd01213    81 RKWQKydlrGSKPSRIFGFVARKQGSSTENVCHLFAELDPEQPASAIVNFVNKVLL 136
PTP_tensin-2 cd14562
protein tyrosine phosphatase-like domain of tensin-2; Tensin-2 (TNS2) is also called ...
 8-166 8.77e-81

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: 262.19  E-value: 8.77e-81
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453    8 DLTYITERIIAVSFPAGCSEESYLHNLQEVTRMLKSKHGDNYLVLNLSEKRYDLTKLNPKIMDVGWPELHAPPLDKMCTI 87
Cdd:cd14562     1 DLTYITERIISVFFPPALEEQRYRGNLREVAQMLKSKHEDKYLLFNLSEKRHDITRLNPKVQDFGWPDLHAPPLDKICSI 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 187953453   88 CKAQESWLNSNLQHVVVIHCRGGKGRIGVVISSYMHFTNVSASADQALDRFAMKKFYDDKVSALMQPSQKRYVQFLSGL 166
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. ...
 1168-1284 2.24e-66

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: 219.22  E-value: 2.24e-66
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453 1168 TSKFWYKADISREQAIAMLKDKEPGSFIVRDSHSFRGAYGLAMKVATPPPSVLQLNKKaGDLANELVRHFLIECTPKGVR 1247
Cdd:cd09927     1 TSKYWYKPNISRDQAIALLKDKPPGTFLVRDSTTYKGAYGLAVKVATPPPGVNPFEAK-GDPESELVRHFLIEPSPKGVK 79

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 187953453 1248 LKGCSNEPYFGSLTALVCQHSITPLALPCKLLIPERD 1284
Cdd:cd09927    80 LKGCPNEPVFGSLSALVYQHSITPLALPCKLRIPDRD 116
PTP_PTEN-like cd14497
protein tyrosine phosphatase-like domain of phosphatase and tensin homolog and similar ...
 8-166 4.15e-57

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: 194.72  E-value: 4.15e-57
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453    8 DLTYITERIIAVSFPA-GCSEESYLHNLQEVTRMLKSKHGDNYLVLNLSEKRYDL-TKLNPKIMDVGWPELHAPPLDKMC 85
Cdd:cd14497     1 DLSYITPRIIAMSFPAtGYPESLYRNSIDDVANFLNTHHPDHYMIFNLSEEEYDDdSKFEGRVLHYGFPDHHPPPLGLLL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453   86 TICKAQESWLNSNLQHVVVIHCRGGKGRIGVVISSYMHFTNVSASADQALDRFAMKKFyDDKVSALMQPSQKRYVQFLSG 165
Cdd:cd14497    81 EIVDDIDSWLSEDPNNVAVVHCKAGKGRTGTVICAYLLYYGQYSTADEALEYFAKKRF-KEGLPGVTIPSQLRYLQYFER 159


                  .
gi 187953453  166 L 166
Cdd:cd14497   160 L 160
PTB pfam08416
Phosphotyrosine-binding domain; The phosphotyrosine-binding domain (PTB, also ...
 1310-1444 3.90e-48

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: 167.91  E-value: 3.90e-48
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453  1310 ACNVWYLNSVEMESLTGHQAIQKAL--SITLVQEPPPVSTVVHFKVSAQGITLTDNQRKLFFrRHYPVNSVIFCALDPQD 1387
Cdd:pfam08416    1 QYRVEHLTTFELDSLTGLQAVEDAIrkLQLLDAQGRVWTQEMLLQVSDQGITLTDNETKEEL-ESYPLDSISHCQAVLND 79

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 187953453  1388 RKWIkdgpssKVFGFVARKQGSATDNVcHLFA--EHDPEQPASAIVNFVSKVMIGSPKK 1444
Cdd:pfam08416   80 GRYN------SILALVCQEPGQSKPDV-HLFQcdELGAELIAEDIESALSDVRLGKPKK 131
PTEN_C2 pfam10409
C2 domain of PTEN tumour-suppressor protein; This is the C2 domain-like domain, in greek key ...
 173-299 3.75e-47

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: 165.14  E-value: 3.75e-47
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453   173 MNASPLFLHFVILHGTPNFDTGGVCRPFLKLYQAMQPV-YTSGIYNVGPENPSRICIVIEPAQL-LKGDVMVKCYHKKYR 250
Cdd:pfam10409    1 PPPKPLTLHSIILHGIPNFKSGGGCRPYIRIYQNKKKVfSTSGKYKKLKEYQQDDCVILFPKGIpVQGDVLVEFYHKGSD 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 187953453   251 SATRDVIFRLQFHTGAVQGYGLVFGKEDLDNASKD---DRFPDYGKVELVFS 299
Cdd:pfam10409   81 LLSEEKMFRFWFNTSFIEDNTLTLPKNELDKADKDkkdKRFPKDFKVELLFS 132
PTP_PTEN cd14509
protein tyrosine phosphatase-like catalytic domain of phosphatase and tensin homolog; ...
 8-166 3.16e-42

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: 151.97  E-value: 3.16e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453    8 DLTYITERIIAVSFPAGCSEESYLHNLQEVTRMLKSKHGDNYLVLNL-SEKRYDLTKLNPKIMDVGWPELHAPPLDKMCT 86
Cdd:cd14509     1 DLTYITPNIIAMGFPAEGVEGVYRNPIDDVQRFLETKHKGHYKVYNLcSERSYDPSKFNGRVAEYPFDDHNPPPLELIKP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453   87 ICKAQESWLNSNLQHVVVIHCRGGKGRIGVVISSYMHFTNVSASADQALDRFAMKKFYDDKvsALMQPSQKRYVQFLSGL 166
Cdd:cd14509    81 FCEDVDEWLKEDEKNVAAVHCKAGKGRTGVMICCYLLYLGKFPSAKEALDFYGAKRTKNKK--GVTIPSQRRYVYYYSRL 158
PTP_VSP_TPTE cd14510
protein tyrosine phosphatase-like catalytic domain of voltage-sensitive phosphatase ...
 1-166 1.21e-39

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: 145.20  E-value: 1.21e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453    1 MEEGHGLDLTYITERIIAVSFPAGCSEESYLHNLQEVTRMLKSKHGDNYLVLNL-SEKRYDLTKLNPKIMDVGWPELHAP 79
Cdd:cd14510     8 QKDGFDLDLTYVTDRVIAMSFPSSGKQAFYRNPIEEVVRFLDTKHPDHYKVYNLcSERGYDPKYFHNRVERVPIDDHNVP 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453   80 PLDKMCTICKAQESWLNSNLQHVVVIHCRGGKGRIGVVISSYMHFTNVSASADQALDRFAMK---KFYDDKVSALMQPSQ 156
Cdd:cd14510    88 TLDEMLSFTAEVREWMAADPKNVVAIHCKGGKGRTGTMVCAWLIYSGQFESAKEALEYFGERrtdKSVSSKFQGVETPSQ 167

                         170
                  ....*....|
gi 187953453  157 KRYVQFLSGL 166
Cdd:cd14510   168 SRYVGYFEKL 177
PTP_auxilin-like cd14511
protein tyrosine phosphatase-like domain of auxilin and similar proteins; This subfamily ...
 7-166 2.37e-35

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: 132.48  E-value: 2.37e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453    7 LDLTYITERIIAVSFPAGCSEESYLHN-LQEVTRMLKSKHGDNYLVLNLSEKRYDLTKLNPKIMDVGWPELHAPPLDKMC 85
Cdd:cd14511     9 LDISYITSRIIVMPFPAEGIESTYRKNnIEDVRAFLDSRHPQKYSVYNLSPRSYPTLRLPSRVVECSWPYRRAPSLHALY 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453   86 TICKAQESWLNSNLQHVVVIHCRGGKGRIGVVISSYMHFTNVSASADQALDRFAMKKFYDDkvsalMQPSQKRYVQFLSG 165
Cdd:cd14511    89 ALCRDIYQWLNKDPKNVIVIHCTDGKAASATVVCALLVYCGLFKTPEDALQMFAVKRCPPG-----LSPSELRYLYYFSD 163


                  .
gi 187953453  166 L 166
Cdd:cd14511   164 I 164
PTP_GAK cd14564
protein tyrosine phosphatase-like domain of cyclin-G-associated kinase; cyclin-G-associated ...
 7-163 2.78e-29

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: 115.00  E-value: 2.78e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453    7 LDLTYITERIIAVSFPAGCSEESYLHNLQEVTRMLKSKHGDNYLVLNLSEKRYDLTKLNPKIMDVGWPELHAPPLDKMCT 86
Cdd:cd14564     9 LDISYITSRIAVMSFPAEGVESAIKNNIEDVRLFLDSRHPGHYAVYNLSQRTYRPSRFHNRVSECGWPARRAPNLQNLYS 88

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 187953453   87 ICKAQESWLNSNLQHVVVIHCRGGKGRIGVVISSYMHFTNVSASADQALDRFAMKkfyddKVSALMQPSQKRYVQFL 163
Cdd:cd14564    89 ICKNMHLWLKQDQKNICIVHCLDGRAASAVVVCSFLCFCRLFTTAEAAVYMFSMK-----RCPPGIWPSHKRYIEYM 160
PTP_auxilin_N cd14563
N-terminal protein tyrosine phosphatase-like domain of auxilin; Auxilin, also called auxilin-1 ...
 7-166 3.13e-26

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: 106.50  E-value: 3.13e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453    7 LDLTYITERIIAVSFPAGCSEESYLHNLQEVTRMLKSKHGDNYLVLNLSEKRYDLTKLNPKIMDVGWPELHAPPLDKMCT 86
Cdd:cd14563     9 LDISYITSRIIVMSYPAEGVELGFRNHIEDVRSFLDSRHLDHYTVFNLSQKSYRSAKFHNRVSECSWPVRQAPSLHNLFA 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453   87 ICKAQESWLNSNLQHVVVIHCRGGKGRIGVVISSYMHFTNVSASADQALDRFAMKkfyddKVSALMQPSQKRYVQFLSGL 166
Cdd:cd14563    89 VCKNMHNWLQQNPKNVCVIHCMDGRAASAVLVSAMFCFCHLFSNPVPAMQLLNAK-----RPGIGLWPSHRRYIGYICDL 163
PTB smart00462
Phosphotyrosine-binding domain, phosphotyrosine-interaction (PI) domain; PTB/PI domain ...
 1307-1433 1.12e-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: 95.07  E-value: 1.12e-22
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453   1307 QGAACNVWYLNSVEMESLTGHQAIQKALSITLVQEPPPVSTV--VHFKVSAQGITLTDNQRKlFFRRHYPVNSVIFCALD 1384
Cdd:smart00462    2 SGVSFRVKYLGSVEVPEARGLQVVQEAIRKLRAAQGSEKKEPqkVILSISSRGVKLIDEDTK-AVLHEHPLRRISFCAVG 80

                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|.
gi 187953453   1385 PQDrkwikdgpsSKVFGFVARKQGSaTDNVCHLF--AEHDPEQPASAIVNF 1433
Cdd:smart00462   81 PDD---------LDVFGYIARDPGS-SRFACHVFrcEKAAEDIALAIGQAF 121
SH2 cd00173
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...
 1172-1264 7.38e-16

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: 73.64  E-value: 7.38e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453 1172 WYKADISREQAIAMLKDKEPGSFIVRDSHSFRGAYGLAMKVatpppsvlqlnkkagdlANELVRHFLIECTPKGVRLKGC 1251
Cdd:cd00173     2 WFHGSISREEAERLLRGKPDGTFLVRESSSEPGDYVLSVRS-----------------GDGKVKHYLIERNEGGYYLLGG 64

                          90
                  ....*....|...
gi 187953453 1252 SNePYFGSLTALV 1264
Cdd:cd00173    65 SG-RTFPSLPELV 76
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
 1172-1272 1.02e-14

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: 70.72  E-value: 1.02e-14
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453   1172 WYKADISREQAIAMLKDKEPGSFIVRDSHSFRGAYGLAMKVatpppsvlqlnkkagdlaNELVRHFLIECTPKGVRlkGC 1251
Cdd:smart00252    3 WYHGFISREEAEKLLKNEGDGDFLVRDSESSPGDYVLSVRV------------------KGKVKHYRIRRNEDGKF--YL 62

                            90       100
                    ....*....|....*....|.
gi 187953453   1252 SNEPYFGSLTALVCQHSITPL 1272
Cdd:smart00252   63 EGGRKFPSLVELVEHYQKNSL 83
PTB cd00934
Phosphotyrosine-binding (PTB) PH-like fold; PTB domains have a common PH-like fold and are ...
 1311-1438 7.02e-14

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: 69.46  E-value: 7.02e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453 1311 CNVWYLNSVEMESLTGHQAIQKALSITLVQ--EPPPVSTVVHFKVSAQGITLTDNQRKLFFRRHyPVNSVIFCALDPQDr 1388
Cdd:cd00934     3 FQVKYLGSVEVGSSRGVDVVEEALKALAAAlkSSKRKPGPVLLEVSSKGVKLLDLDTKELLLRH-PLHRISYCGRDPDN- 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 187953453 1389 kwikdgpsSKVFGFVARKQGSaTDNVCHLFAEHDPEQpASAIVNFVSKVM 1438
Cdd:cd00934    81 --------PNVFAFIAGEEGG-SGFRCHVFQCEDEEE-AEEILQAIGQAF 120
SH2 pfam00017
SH2 domain;
1172-1264 7.27e-10

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 56.46  E-value: 7.27e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453  1172 WYKADISREQAIAMLK-DKEPGSFIVRDSHSFRGAYGLamkvatpppSVlqlnkkagdLANELVRHFLIECTPKGVRLkg 1250
Cdd:pfam00017    1 WYHGKISRQEAERLLLnGKPDGTFLVRESESTPGGYTL---------SV---------RDDGKVKHYKIQSTDNGGYY-- 60

                           90
                   ....*....|....
gi 187953453  1251 CSNEPYFGSLTALV 1264
Cdd:pfam00017   61 ISGGVKFSSLAELV 74
PTPc_motif smart00404
Protein tyrosine phosphatase, catalytic domain motif;
72-186 3.75e-08

Protein tyrosine phosphatase, catalytic domain motif;


Pssm-ID: 214649 [Multi-domain]  Cd Length: 105  Bit Score: 52.75  E-value: 3.75e-08
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453     72 GWPELHAPPL-DKMCTICKAQESWLN-SNLQHVVVIHCRGGKGRIGVVISSYMHFTNVSASADqaldrfamkkfyddkvs 149
Cdd:smart00404    9 GWPDHGVPESpDSILELLRAVKKNLNqSESSGPVVVHCSAGVGRTGTFVAIDILLQQLEAEAG----------------- 71

                            90       100       110
                    ....*....|....*....|....*....|....*..
gi 187953453    150 almQPSQKRYVQFLSGLLSGSVKMNASPLFLHFVILH 186
Cdd:smart00404   72 ---EVDIFDTVKELRSQRPGMVQTEEQYLFLYRALLE 105
PTPc_DSPc smart00012
Protein tyrosine phosphatase, catalytic domain, undefined specificity; Protein tyrosine ...
 72-186 3.75e-08

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: 52.75  E-value: 3.75e-08
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453     72 GWPELHAPPL-DKMCTICKAQESWLN-SNLQHVVVIHCRGGKGRIGVVISSYMHFTNVSASADqaldrfamkkfyddkvs 149
Cdd:smart00012    9 GWPDHGVPESpDSILELLRAVKKNLNqSESSGPVVVHCSAGVGRTGTFVAIDILLQQLEAEAG----------------- 71

                            90       100       110
                    ....*....|....*....|....*....|....*..
gi 187953453    150 almQPSQKRYVQFLSGLLSGSVKMNASPLFLHFVILH 186
Cdd:smart00012   72 ---EVDIFDTVKELRSQRPGMVQTEEQYLFLYRALLE 105
SH2_nSH2_p85_like cd09942
N-terminal Src homology 2 (nSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
 1172-1281 1.87e-07

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: 50.79  E-value: 1.87e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453 1172 WYKADISREQAIAMLKDKEPGSFIVRDSHSFRGAYGLAMkvatpppsvlqlnKKAGdlANELVRHFLiectpKGVRLkGC 1251
Cdd:cd09942     9 WYWGDISREEVNEKMRDTPDGTFLVRDASTMKGDYTLTL-------------RKGG--NNKLIKIFH-----RDGKY-GF 67

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 187953453 1252 SNEPYFGSLTALVCQHSITPLA-----LPCKLLIP 1281
Cdd:cd09942    68 SDPLTFNSVVELINYYRNNSLAeynrkLDVKLLYP 102
PTP_PTPDC1 cd14506
protein tyrosine phosphatase domain of PTP domain-containing protein 1; protein tyrosine ...
 72-142 2.42e-07

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: 52.74  E-value: 2.42e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 187953453   72 GWPELHAPPLDKMCTICKAQESWLNsnLQHVVVIHCRGGKGRIGVVISSYMHFTNvSASADQALDRFAMKK 142
Cdd:cd14506    83 GWKDYGVPSLTTILDIVKVMAFALQ--EGGKVAVHCHAGLGRTGVLIACYLVYAL-RMSADQAIRLVRSKR 150
SH2_cSH2_p85_like cd09930
C-terminal Src homology 2 (cSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
 1172-1273 1.29e-05

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: 45.48  E-value: 1.29e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453 1172 WYKADISREQAIAMLKDKEPGSFIVRDShSFRGAYGLAMKVatpppsvlqlnkkagdlaNELVRHFLIECTPKGVRLKgc 1251
Cdd:cd09930     8 WLVGDINRTQAEELLRGKPDGTFLIRES-STQGCYACSVVC------------------NGEVKHCVIYKTETGYGFA-- 66

                          90       100
                  ....*....|....*....|....
gi 187953453 1252 snEPY--FGSLTALVCQHSITPLA 1273
Cdd:cd09930    67 --EPYnlYESLKELVLHYAHNSLE 88
CDC14 COG2453
Protein-tyrosine phosphatase [Signal transduction mechanisms];
73-137 1.81e-05

Protein-tyrosine phosphatase [Signal transduction mechanisms];


Pssm-ID: 441989 [Multi-domain]  Cd Length: 140  Bit Score: 46.12  E-value: 1.81e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 187953453   73 WPELHAPPLDKMCTICKaqesWLNSNLQ--HVVVIHCRGGKGRIGVVISSYMHFTNVsaSADQALDR 137
Cdd:COG2453    55 IPDFGAPDDEQLQEAVD----FIDEALRegKKVLVHCRGGIGRTGTVAAAYLVLLGL--SAEEALAR 115
PHA03247 PHA03247
large tegument protein UL36; Provisional
 624-1058 4.92e-05

large tegument protein UL36; Provisional


Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 48.40  E-value: 4.92e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453  624 QAQPRVPLTPtRGTSSRVAVQRGVGSGPHPPDTQQPSPSKAfkPRFPGDQVVNGAGPELSTGPSPGSPTLDIDQSIEQLN 703
Cdd:PHA03247 2595 SARPRAPVDD-RGDPRGPAPPSPLPPDTHAPDPPPPSPSPA--ANEPDPHPPPTVPPPERPRDDPAPGRVSRPRRARRLG 2671

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453  704 RLILELDPTFEPIPthmnalgsqangSVSPDSVgGGLRASSRLPDTGEGPSRATGRQGSSAEQPLGGRlrklslgqydnD 783
Cdd:PHA03247 2672 RAAQASSPPQRPRR------------RAARPTV-GSLTSLADPPPPPPTPEPAPHALVSATPLPPGPA-----------A 2727

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453  784 AGGQLPfskcawgkagvdyAPNLPPFPsPADVKETMTPGYPQDldiIDGRILSSKESMCSTPAFPVSPETPYV-KTALRH 862
Cdd:PHA03247 2728 ARQASP-------------ALPAAPAP-PAVPAGPATPGGPAR---PARPPTTAGPPAPAPPAAPAAGPPRRLtRPAVAS 2790

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453  863 PPFSPPEPPLSSPASQHKGGREPRSCPETLTHAvgmSESPIGPKSTMLRADASSTPSFQQAFASSC-TISSNGPGQRRES 941
Cdd:PHA03247 2791 LSESRESLPSPWDPADPPAAVLAPAAALPPAAS---PAGPLPPPTSAQPTAPPPPPGPPPPSLPLGgSVAPGGDVRRRPP 2867

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453  942 SSSAERQwVESSPKPMVSLLgsGRPTGSPLSAEFSgtrkdSPVLSCFPPSELQAPFHSHELSLAEPPDSLAP-------P 1014
Cdd:PHA03247 2868 SRSPAAK-PAAPARPPVRRL--ARPAVSRSTESFA-----LPPDQPERPPQPQAPPPPQPQPQPPPPPQPQPpppppprP 2939

                         410       420       430       440       450
                  ....*....|....*....|....*....|....*....|....*....|..
gi 187953453 1015 SSQAFLGFGTAPVG--SGLPPEEDLGALLANSHGA------SPTPSIPLTAT 1058
Cdd:PHA03247 2940 QPPLAPTTDPAGAGepSGAVPQPWLGALVPGRVAVprfrvpQPAPSREAPAS 2991
SH2_Cterm_RasGAP cd10354
C-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP ...
 1172-1264 6.97e-05

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: 42.41  E-value: 6.97e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453 1172 WYKADISREQAIAML-KDKEPGSFIVRDSHSFRGAYGLAMKVatpppsvlqlnkkagdlaNELVRHFLIECTPKGVRLKG 1250
Cdd:cd10354     2 WFHGKISREEAYNMLvKVGGPGSFLVRESDNTPGDYSLSFRV------------------NEGIKHFKIIPTGNNQFMMG 63

                          90
                  ....*....|....
gi 187953453 1251 csnEPYFGSLTALV 1264
Cdd:cd10354    64 ---GRYFSSLDDVI 74
SH2_Tec_family cd09934
Src homology 2 (SH2) domain found in Tec-like proteins; The Tec protein tyrosine kinase is the ...
 1172-1281 8.69e-05

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: 43.16  E-value: 8.69e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453 1172 WYKADISREQAIAMLK--DKEpGSFIVRDShSFRGAYGLA--MKVATPPpsvlqlnkkagdlaneLVRHFLIECTPKG-- 1245
Cdd:cd09934     8 WYVGDMSRQRAESLLKqeDKE-GCFVVRNS-STKGLYTVSlfTKVPGSP----------------HVKHYHIKQNARSef 69

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 187953453 1246 -VRLKGCsnepyFGSLTALVCQHSITPLALPCKLLIP 1281
Cdd:cd09934    70 yLAEKHC-----FETIPELINYHQHNSGGLATRLKYP 101
SH2_Srm cd10360
Src homology 2 (SH2) domain found in Src-related kinase lacking C-terminal regulatory tyrosine ...
 1172-1214 8.93e-05

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: 42.25  E-value: 8.93e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 187953453 1172 WYKADISREQAIAML--KDKEPGSFIVRDSHSFRGAYGLAMKVAT 1214
Cdd:cd10360     2 WYFSGISRTQAQQLLlsPPNEPGAFLIRPSESSLGGYSLSVRAQA 46
SH2_C-SH2_SHP_like cd09931
C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
 1172-1272 1.00e-04

C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The SH2 domain phosphatases (SHP-1, SHP-2/Syp, Drosophila corkscrew (csw), and Caenorhabditis elegans Protein Tyrosine Phosphatase (Ptp-2)) are cytoplasmic signaling enzymes. They are both targeted and regulated by interactions of their SH2 domains with phosphotyrosine docking sites. These proteins contain two SH2 domains (N-SH2, C-SH2) followed by a tyrosine phosphatase (PTP) domain, and a C-terminal extension. Shp1 and Shp2 have two tyrosyl phosphorylation sites in their C-tails, which are phosphorylated differentially by receptor and nonreceptor PTKs. Csw retains the proximal tyrosine and Ptp-2 lacks both sites. Shp-binding proteins include receptors, scaffolding adapters, and inhibitory receptors. Some of these bind both Shp1 and Shp2 while others bind only one. Most proteins that bind a Shp SH2 domain contain one or more immuno-receptor tyrosine-based inhibitory motifs (ITIMs): [SIVL]xpYxx[IVL]. Shp1 N-SH2 domain blocks the catalytic domain and keeps the enzyme in the inactive conformation, and is thus believed to regulate the phosphatase activity of SHP-1. Its C-SH2 domain is thought to be involved in searching for phosphotyrosine activators. The SHP2 N-SH2 domain is a conformational switch; it either binds and inhibits the phosphatase, or it binds phosphoproteins and activates the enzyme. The C-SH2 domain contributes binding energy and specificity, but it does not have a direct role in activation. Csw SH2 domain function is essential, but either SH2 domain can fulfill this requirement. The role of the csw SH2 domains during Sevenless receptor tyrosine kinase (SEV) signaling is to bind Daughter of Sevenless rather than activated SEV. Ptp-2 acts in oocytes downstream of sheath/oocyte gap junctions to promote major sperm protein (MSP)-induced MAP Kinase (MPK-1) phosphorylation. Ptp-2 functions in the oocyte cytoplasm, not at the cell surface to inhibit multiple RasGAPs, resulting in sustained Ras activation. It is thought that MSP triggers PTP-2/Ras activation and ROS production to stimulate MPK-1 activity essential for oocyte maturation and that secreted MSP domains and Cu/Zn superoxide dismutases function antagonistically to control ROS and MAPK signaling. 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: 198185  Cd Length: 99  Bit Score: 42.65  E-value: 1.00e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453 1172 WYKADISREQAIAMLKDK-EPGSFIVRDSHSFRGAYGLamkvatpppSVLQLNKKagdlanelVRHFLIECtpKGVRLKG 1250
Cdd:cd09931     2 WFHGHLSGKEAEKLLLEKgKPGSFLVRESQSKPGDFVL---------SVRTDDDK--------VTHIMIRC--QGGKYDV 62

                          90       100
                  ....*....|....*....|..
gi 187953453 1251 CSNEPyFGSLTALVCQHSITPL 1272
Cdd:cd09931    63 GGGEE-FDSLTDLVEHYKKNPM 83
SH2_Tec_Btk cd10397
Src homology 2 (SH2) domain found in Tec protein, Bruton's tyrosine kinase (Btk); A member of ...
 1172-1245 1.44e-04

Src homology 2 (SH2) domain found in Tec protein, Bruton's tyrosine kinase (Btk); A member of the Tec protein tyrosine kinase Btk is expressed in bone marrow, spleen, all hematopoietic cells except T lymphocytes and plasma cells where it plays a crucial role in B cell maturation and mast cell activation. Btk has been shown to interact with GNAQ, PLCG2, protein kinase D1, B-cell linker, SH3BP5, caveolin 1, ARID3A, and GTF2I. Most of the Tec family members have a PH domain (Txk and the short (type 1) splice variant of Drosophila Btk29A are exceptions), a Tec homology (TH) domain, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. Btk is implicated in the primary immunodeficiency disease X-linked agammaglobulinemia (Bruton's agammaglobulinemia). The TH domain consists of a Zn2+-binding Btk motif and a proline-rich region. The Btk motif is found in Tec kinases, Ras GAP, and IGBP. It is crucial for the function of Tec PH domains and it's lack of presence in Txk is not surprising since it lacks a PH domain. The type 1 splice form of the Drosophila homolog also lacks both the PH domain and the Btk motif. The proline-rich regions are highly conserved for the most part with the exception of Bmx whose residues surrounding the PXXP motif are not conserved (TH-like) and Btk29A which is entirely unique with large numbers of glycine residues (TH-extended). Tec family members all lack a C-terminal tyrosine having an autoinhibitory function in its phosphorylated state. Two tyrosine phosphorylation (pY) sites have been identified in Btk: one located in the activation loop of the catalytic domain which regulates the transition between open (active) and closed (inactive) states and the other in its SH3 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: 198260 [Multi-domain]  Cd Length: 106  Bit Score: 42.51  E-value: 1.44e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 187953453 1172 WYKADISREQAIAMLK--DKEpGSFIVRDShSFRGAYglamkvatpppSVLQLNKKAGDLANeLVRHFLIECTPKG 1245
Cdd:cd10397     8 WYSKNMTRSQAEQLLKqeGKE-GGFIVRDS-SKAGKY-----------TVSVFAKSAGDPQG-VIRHYVVCSTPQS 69
PTP_DSP_cys cd14494
cys-based protein tyrosine phosphatase and dual-specificity phosphatase superfamily; This ...
 81-139 2.05e-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: 42.34  E-value: 2.05e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 187953453   81 LDKMCTICKAQESWLNSNlqHVVVIHCRGGKGRIGVVISSYM--HFTNvsaSADQALDRFA 139
Cdd:cd14494    39 LAMVDRFLEVLDQAEKPG--EPVLVHCKAGVGRTGTLVACYLvlLGGM---SAEEAVRIVR 94
SH2_csk_like cd09937
Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal ...
 1172-1267 2.60e-04

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: 41.51  E-value: 2.60e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453 1172 WYKADISREQAIAMLKDKEPGSFIVRDSHSFRGAYGLAMKvatpppsvlqLNKKagdlanelVRHFLIECTpkGVRLKgC 1251
Cdd:cd09937     5 WFHGKISREEAERLLQPPEDGLFLVRESTNYPGDYTLCVS----------FEGK--------VEHYRVIYR--NGKLT-I 63

                          90
                  ....*....|....*.
gi 187953453 1252 SNEPYFGSLTALVcQH 1267
Cdd:cd09937    64 DEEEYFENLIQLV-EH 78
SH2_Nterm_shark_like cd10347
N-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
 1172-1241 2.74e-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: 40.82  E-value: 2.74e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 187953453 1172 WYKADISREQAIAML--KDKEPGSFIVRDSHSFRGAYGLAMkvatpppsvlqlnkkagdLANELVRHFLIEC 1241
Cdd:cd10347     3 WYHGKISREVAEALLlrEGGRDGLFLVRESTSAPGDYVLSL------------------LAQGEVLHYQIRR 56
SH2_SOCS7 cd10388
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 ...
 1172-1201 3.86e-04

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; 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: 198251  Cd Length: 101  Bit Score: 41.19  E-value: 3.86e-04
                          10        20        30
                  ....*....|....*....|....*....|
gi 187953453 1172 WYKADISREQAIAMLKDKEPGSFIVRDSHS 1201
Cdd:cd10388    12 WYWGPMSWEDAEKVLSNKPDGSFLVRDSSD 41
SH2_SHIP cd10343
Src homology 2 (SH2) domain found in SH2-containing inositol-5'-phosphatase (SHIP) and ...
 1172-1208 4.71e-04

Src homology 2 (SH2) domain found in SH2-containing inositol-5'-phosphatase (SHIP) and SLAM-associated protein (SAP); The SH2-containing inositol-5'-phosphatase, SHIP (also called SHIP1/SHIP1a), is a hematopoietic-restricted phosphatidylinositide phosphatase that translocates to the plasma membrane after extracellular stimulation and hydrolyzes the phosphatidylinositol-3-kinase (PI3K)-generated second messenger PI-3,4,5-P3 (PIP3) to PI-3,4-P2. As a result, SHIP dampens down PIP3 mediated signaling and represses the proliferation, differentiation, survival, activation, and migration of hematopoietic cells. PIP3 recruits lipid-binding pleckstrin homology(PH) domain-containing proteins to the inner wall of the plasma membrane and activates them. PH domain-containing downstream effectors include the survival/proliferation enhancing serine/threonine kinase, Akt (protein kinase B), the tyrosine kinase, Btk, the regulator of protein translation, S6K, and the Rac and cdc42 guanine nucleotide exchange factor, Vav. SHIP is believed to act as a tumor suppressor during leukemogenesis and lymphomagenesis, and may play a role in activating the immune system to combat cancer. SHIP contains an N-terminal SH2 domain, a centrally located phosphatase domain that specifically hydrolyzes the 5'-phosphate from PIP3, PI-4,5-P2 and inositol-1,3,4,5- tetrakisphosphate (IP4), a C2 domain, that is an allosteric activating site when bound by SHIP's enzymatic product, PI-3,4-P2; 2 NPXY motifs that bind proteins with a phosphotyrosine binding (Shc, Dok 1, Dok 2) or an SH2 (p85a, SHIP2) domain; and a proline-rich domain consisting of four PxxP motifs that bind a subset of SH3-containing proteins including Grb2, Src, Lyn, Hck, Abl, PLCg1, and PIAS1. The SH2 domain of SHIP binds to the tyrosine phosphorylated forms of Shc, SHP-2, Doks, Gabs, CD150, platelet-endothelial cell adhesion molecule, Cas, c-Cbl, immunoreceptor tyrosine-based inhibitory motifs (ITIMs), and immunoreceptor tyrosine-based activation motifs (ITAMs). The X-linked lymphoproliferative syndrome (XLP) gene encodes SAP (also called SH2D1A/DSHP) a protein that consists of a 5 residue N-terminus, a single SH2 domain, and a short 25 residue C-terminal tail. XLP is characterized by an extreme sensitivity to Epstein-Barr virus. Both T and natural killer (NK) cell dysfunctions have been seen in XLP patients. SAP binds the cytoplasmic tail of Signaling lymphocytic activation molecule (SLAM), 2B4, Ly-9, and CD84. SAP is believed to function as a signaling inhibitor, by blocking or regulating binding of other signaling proteins. SAP and the SAP-like protein EAT-2 recognize the sequence motif TIpYXX(V/I), which is found in the cytoplasmic domains of a restricted number of T, B, and NK cell surface receptors and are proposed to be natural inhibitors or regulators of the physiological role of a small family of receptors on the surface of these cells. 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: 198206  Cd Length: 103  Bit Score: 40.89  E-value: 4.71e-04
                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 187953453 1172 WYKADISREQAIAML-KDKEPGSFIVRDSHSFRGAYGL 1208
Cdd:cd10343     5 WYHGNITRSKAEELLsKAGKDGSFLVRDSESVSGAYAL 42
SH2_SOCS_family cd09923
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) family; SH2 ...
 1172-1199 5.10e-04

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: 40.26  E-value: 5.10e-04
                          10        20
                  ....*....|....*....|....*...
gi 187953453 1172 WYKADISREQAIAMLKDKEPGSFIVRDS 1199
Cdd:cd09923     2 WYWGGITRYEAEELLAGKPEGTFLVRDS 29
SH2_SLAP cd10344
Src homology 2 domain found in Src-like adaptor proteins; SLAP belongs to the subfamily of ...
 1172-1245 5.88e-04

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: 40.55  E-value: 5.88e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 187953453 1172 WYKADISREQA--IAMLKDKEPGSFIVRDSHSFRGAYGLAMkvatpppsvlqlnKKAGDLANELVRHFLIECTPKG 1245
Cdd:cd10344    12 WLFEGLSREKAeeLLMLPGNQVGSFLIRESETRRGCYSLSV-------------RHRGSQSRDSVKHYRIFRLDNG 74
CDKN3-like cd14505
cyclin-dependent kinase inhibitor 3 and similar proteins; This family is composed of ...
 24-137 6.03e-04

cyclin-dependent kinase inhibitor 3 and similar proteins; This family is composed of eukaryotic cyclin-dependent kinase inhibitor 3 (CDKN3) and related archaeal and bacterial proteins. CDKN3 is also known as kinase-associated phosphatase (KAP), CDK2-associated dual-specificity phosphatase, cyclin-dependent kinase interactor 1 (CDI1), or cyclin-dependent kinase-interacting protein 2 (CIP2). It has been characterized as dual-specificity phosphatase, which function as a protein-serine/threonine phosphatase (EC 3.1.3.16) and protein-tyrosine-phosphatase (EC 3.1.3.48). It dephosphorylates CDK2 at a threonine residue in a cyclin-dependent manner, resulting in the inhibition of G1/S cell cycle progression. It also interacts with CDK1 and controls progression through mitosis by dephosphorylating CDC2. CDKN3 may also function as a tumor suppressor; its loss of function was found in a variety of cancers including glioblastoma and hepatocellular carcinoma. However, it has also been found over-expressed in many cancers such as breast, cervical, lung and prostate cancers, and may also have an oncogenic function.


Pssm-ID: 350355 [Multi-domain]  Cd Length: 163  Bit Score: 41.87  E-value: 6.03e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453   24 GCSEESYLHNLQEVTRMLKSKHGDnyLVLNLSEkRYDLTKLN----PKI-----MDVGW---PELHAPP-LDKMCTICKa 90
Cdd:cd14505    22 GCKFKDHRRDLQADLEELKDQGVD--DVVTLCT-DGELEELGvpdlLEQyqqagITWHHlpiPDGGVPSdIAQWQELLE- 97

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 187953453   91 qesWLNSNLQHV--VVIHCRGGKGRIGVVISSYMHFTNVSASADQALDR 137
Cdd:cd14505    98 ---ELLSALENGkkVLIHCKGGLGRTGLIAACLLLELGDTLDPEQAIAA 143
SH2_Cterm_shark_like cd10348
C-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
 1172-1267 6.20e-04

C-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 its 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: 198211  Cd Length: 86  Bit Score: 40.10  E-value: 6.20e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453 1172 WYKADISREQAIAMLKDKE--PGSFIVRDSHSFRGAYGLAMkvatpppsvlqlnkkagdLANELVRHFLIECtpKGVRLK 1249
Cdd:cd10348     2 WLHGALDRNEAVEILKQKAdaDGSFLVRYSRRRPGGYVLTL------------------VYENHVYHFEIQN--RDDKWF 61

                          90
                  ....*....|....*...
gi 187953453 1250 GCSNEPYFGSLTALVcQH 1267
Cdd:cd10348    62 YIDDGPYFESLEHLI-EH 78
SH2_ABL cd09935
Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ...
 1172-1281 1.42e-03

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: 39.29  E-value: 1.42e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453 1172 WYKADISREQAIAMLKDKEPGSFIVRDSHSFRGAYGLAMKvatpppsvlqlnkkagdlANELVRHFLIECTPKGVRLkgC 1251
Cdd:cd09935     5 WYHGPISRNAAEYLLSSGINGSFLVRESESSPGQYSISLR------------------YDGRVYHYRISEDSDGKVY--V 64

                          90       100       110
                  ....*....|....*....|....*....|
gi 187953453 1252 SNEPYFGSLTALVCQHSITPLALPCKLLIP 1281
Cdd:cd09935    65 TQEHRFNTLAELVHHHSKNADGLITTLRYP 94
PHA03247 PHA03247
large tegument protein UL36; Provisional
 647-1061 2.24e-03

large tegument protein UL36; Provisional


Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 42.62  E-value: 2.24e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453  647 VGSGPHPPDtqqpSPSKAFKPRFPGDQVVNGAGPELSTGPSPGSPTLDidqsieqlnrlilelDPTFEPIPTHMNALGSQ 726
Cdd:PHA03247 2582 VTSRARRPD----APPQSARPRAPVDDRGDPRGPAPPSPLPPDTHAPD---------------PPPPSPSPAANEPDPHP 2642

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453  727 ANGSVSP-----DSVGGGLRASSRlpdtgegpSRATGRQGSSAEQPLGGRLRKLSlgqydnDAGGQLpfskcawgkagVD 801
Cdd:PHA03247 2643 PPTVPPPerprdDPAPGRVSRPRR--------ARRLGRAAQASSPPQRPRRRAAR------PTVGSL-----------TS 2697

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453  802 YAPNLPPFPSPADVKETMTPGYPQDLDIIDGRilSSKESMCSTPAFPVSPETPYVKTALRHPPFSPPEPPLSSPASQHKG 881
Cdd:PHA03247 2698 LADPPPPPPTPEPAPHALVSATPLPPGPAAAR--QASPALPAAPAPPAVPAGPATPGGPARPARPPTTAGPPAPAPPAAP 2775

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453  882 GREPrscPETLTHAVGMSESPIGPKSTMLRADASSTPSFQQAFASSCTISSNGPGQRRESSSSAERQWVESSPKPMVSLL 961
Cdd:PHA03247 2776 AAGP---PRRLTRPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPAASPAGPLPPPTSAQPTAPPPPPGPPPPSLPL 2852

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453  962 GSGRPTGSPLSAEF-SGTRKDSPVLSCFPP-SELQAPFHSHEL-SLAEPPDSLAPPSSQAflgFGTAPVGSGLPPEEDLG 1038
Cdd:PHA03247 2853 GGSVAPGGDVRRRPpSRSPAAKPAAPARPPvRRLARPAVSRSTeSFALPPDQPERPPQPQ---APPPPQPQPQPPPPPQP 2929

                         410       420
                  ....*....|....*....|...
gi 187953453 1039 ALLANSHGASPTPSIPLTATGAA 1061
Cdd:PHA03247 2930 QPPPPPPPRPQPPLAPTTDPAGA 2952
PTB_TK_HMTK cd13161
Tyrosine-specific kinase/HM-motif TK (TM/HMTK) Phosphotyrosine-binding (PTB) PH-like fold; TK ...
 1315-1418 2.67e-03

Tyrosine-specific kinase/HM-motif TK (TM/HMTK) Phosphotyrosine-binding (PTB) PH-like fold; TK kinases catalyzes the transfer of the terminal phosphate of ATP to a specific tyrosine residue on its target protein. TK kinases play significant roles in development and cell division. Tyrosine-protein kinases can be divided into two subfamilies: receptor tyrosine kinases, which have an intracellular tyrosine kinase domain, a transmembrane domain and an extracellular ligand-binding domain; and non-receptor (cytoplasmic) tyrosine kinases, which are soluble, cytoplasmic kinases. In HMTK the conserved His-Arg-Asp sequence within the catalytic loop is replaced by a His-Met sequence. TM/HMTK have are 2-3 N-terminal PTB domains. PTB domains in TKs are thought to function analogously to the membrane targeting (PH, myristoylation) and pTyr binding (SH2) domains of Src subgroup kinases. 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: 269983  Cd Length: 120  Bit Score: 39.15  E-value: 2.67e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453 1315 YLNSVEMESLTGHQAIQKALS--ITLVQEPPPVSTVvhfkVSAQGITL--TDNQRKLFFrrhYPVNSVIFCALDPQDRkw 1390
Cdd:cd13161     8 YLGSVPVKEPKGNDVVMAAVKrlKDLKLKPKPVVLV----VSSEGIRVveRLTGEVLTN---VPIKDISFVTVDPKDK-- 78

                          90       100
                  ....*....|....*....|....*...
gi 187953453 1391 ikdgpssKVFGFVARkQGSATDNVCHLF 1418
Cdd:cd13161    79 -------KLFAFISH-DPRLGRITCHVF 98
SH2_HSH2_like cd09946
Src homology 2 domain found in hematopoietic SH2 (HSH2) protein; HSH2 is thought to function ...
 1172-1272 2.73e-03

Src homology 2 domain found in hematopoietic SH2 (HSH2) protein; HSH2 is thought to function as an adapter protein involved in tyrosine kinase signaling. It may also be involved in regulating cytokine signaling and cytoskeletal reorganization in hematopoietic cells. HSH2 contains several putative protein-binding motifs, SH3-binding proline-rich regions, and phosphotyrosine sites, but lacks enzymatic motifs. HSH2 was found to interact with cytokine-regulated tyrosine kinase c-FES and an activated Cdc42-associated tyrosine kinase ACK1. HSH2 binds c-FES through both its C-terminal region and its N-terminal region including the SH2 domain and binds ACK1 via its N-terminal proline-rich region. Both kinases bound and tyrosine-phosphorylated HSH2 in mammalian cells. 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: 198199  Cd Length: 102  Bit Score: 38.72  E-value: 2.73e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187953453 1172 WYKADISREQAIAMLKDKEPGSFIVRDSHSFRGaYGLAMKvatpppsvlqlnkkagdlANELVRHFLIECTPKGVRLKGC 1251
Cdd:cd09946     9 WFHGAISREAAENMLESQPLGSFLIRVSHSHVG-YTLSYK------------------AQSSCRHFMVKLLDDGTFMIPG 69

                          90       100
                  ....*....|....*....|.
gi 187953453 1252 SNEPYfGSLTALVCQHSITPL 1272
Cdd:cd09946    70 EKVAH-TSLHALVTFHQQKPI 89
SH2_a2chimerin_b2chimerin cd10352
Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins ...
 1173-1211 3.19e-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: 38.11  E-value: 3.19e-03
                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 187953453 1173 YKADISREQAIAMLKDKEPGSFIVRDSHSFRGAYGLAMK 1211
Cdd:cd10352     9 YHGLISREEAEQLLSGASDGSYLIRESSRDDGYYTLSLR 47
SH2_CRK_like cd09926
Src homology 2 domain found in cancer-related signaling adaptor protein CRK; SH2 domain in the ...
 1172-1208 4.09e-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: 38.22  E-value: 4.09e-03
                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 187953453 1172 WYKADISREQAIAMLKDKEPGSFIVRDSHSFRGAYGL 1208
Cdd:cd09926     9 WYFGPMSRQEAQELLQGQRHGVFLVRDSSTIPGDYVL 45
SH2_Grb2_like cd09941
Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar ...
 1172-1211 6.26e-03

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: 37.63  E-value: 6.26e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 187953453 1172 WYKADISREQAIAML-KDKEPGSFIVRDSHSFRGAYGLAMK 1211
Cdd:cd09941     5 WFHGKISRAEAEEILmNQRPDGAFLIRESESSPGDFSLSVK 45
SH2_C-SH2_PLC_gamma_like cd09932
C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
 1169-1212 8.19e-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: 37.24  E-value: 8.19e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 187953453 1169 SKFWYKADISREQAIAMLKD-KEPGSFIVRDSHSFRGAYGLAMKV 1212
Cdd:cd09932     3 SKEWFHANLTREQAEEMLMRvPRDGAFLVRPSETDPNSFAISFRA 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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