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Conserved domains on  [gi|153792029|ref|NP_001093101|]
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SH2 domain-containing protein 5 [Mus musculus]

Protein Classification

PTB and SH2 domain-containing protein( domain architecture ID 10192152)

PTB (phosphotyrosine-binding) and SH2 (Src homology 2) domain-containing protein, similar to SH2 domain-containing protein 5 (SH2D5) that may be involved in synaptic plasticity regulation through the control of Rac-GTP levels

Gene Symbol:  SH2D5
PubMed:  10610414|8987385|15567406|15680235

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PTB_tensin-related cd13157
Tensin-related Phosphotyrosine-binding (PTB) domain; Tensin plays critical roles in renal ...
 23-150 1.00e-58

Tensin-related Phosphotyrosine-binding (PTB) domain; Tensin plays critical roles in renal function, muscle regeneration, and cell migration. It binds to actin filaments and interacts with the cytoplasmic tails of beta-integrin via its PTB domain, allowing tensin to link actin filaments to integrin receptors. Tensin functions as a platform for assembly and disassembly of signaling complexes at focal adhesions by recruiting tyrosine-phosphorylated signaling molecules, and also by providing interaction sites for other proteins. In addition to its PTB domain, it contains a C-terminal SH2 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.


:

Pssm-ID: 269979  Cd Length: 129  Bit Score: 188.36  E-value: 1.00e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153792029  23 CIAKLAQYVGSFPVDDLDTQESVGLVQQQLWALQDC-SRRRAVILKFSLQGLKIYSGEGEVLLMAHALKRILYATWYPAA 101
Cdd:cd13157    1 TVSRNAQYIGSFPVSGLDVADRADSVRKQLESLKESgSRGRPVILSVSLSGIKICSEDGKVVLMAHALRRVSYSTCRPAH 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 153792029 102 CQFAFIARNPRSPSSKLFCHLFVGSQPGEVHILYLLLCRSFQLAYLLQH 150
Cdd:cd13157   81 AQFAFVARNPGGPTNRQYCHVFVTRSPREAQELNLLLCRAFQLAYLKQH 129
SH2 cd00173
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...
 302-378 1.47e-07

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: 48.61  E-value: 1.47e-07
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 153792029 302 WAFAGLSRSCALSLLRRDVHGAFLLWPEPGTSDQWSLSVRTQCGVVPH-QVFRNHLGRFCLEHLPAEFPSLEALVESH 378
Cdd:cd00173    2 WFHGSISREEAERLLRGKPDGTFLVRESSSEPGDYVLSVRSGDGKVKHyLIERNEGGYYLLGGSGRTFPSLPELVEHY 79
 
Name Accession Description Interval E-value
PTB_tensin-related cd13157
Tensin-related Phosphotyrosine-binding (PTB) domain; Tensin plays critical roles in renal ...
 23-150 1.00e-58

Tensin-related Phosphotyrosine-binding (PTB) domain; Tensin plays critical roles in renal function, muscle regeneration, and cell migration. It binds to actin filaments and interacts with the cytoplasmic tails of beta-integrin via its PTB domain, allowing tensin to link actin filaments to integrin receptors. Tensin functions as a platform for assembly and disassembly of signaling complexes at focal adhesions by recruiting tyrosine-phosphorylated signaling molecules, and also by providing interaction sites for other proteins. In addition to its PTB domain, it contains a C-terminal SH2 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.


Pssm-ID: 269979  Cd Length: 129  Bit Score: 188.36  E-value: 1.00e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153792029  23 CIAKLAQYVGSFPVDDLDTQESVGLVQQQLWALQDC-SRRRAVILKFSLQGLKIYSGEGEVLLMAHALKRILYATWYPAA 101
Cdd:cd13157    1 TVSRNAQYIGSFPVSGLDVADRADSVRKQLESLKESgSRGRPVILSVSLSGIKICSEDGKVVLMAHALRRVSYSTCRPAH 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 153792029 102 CQFAFIARNPRSPSSKLFCHLFVGSQPGEVHILYLLLCRSFQLAYLLQH 150
Cdd:cd13157   81 AQFAFVARNPGGPTNRQYCHVFVTRSPREAQELNLLLCRAFQLAYLKQH 129
PTB smart00462
Phosphotyrosine-binding domain, phosphotyrosine-interaction (PI) domain; PTB/PI domain ...
 28-148 1.08e-10

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: 59.25  E-value: 1.08e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153792029    28 AQYVGSFPVDDLDtqeSVGLVQ---QQLWALQDCSRR--RAVILKFSLQGLKIYSGEGEVLLMAHALKRILYATWYPA-A 101
Cdd:smart00462   8 VKYLGSVEVPEAR---GLQVVQeaiRKLRAAQGSEKKepQKVILSISSRGVKLIDEDTKAVLHEHPLRRISFCAVGPDdL 84

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 153792029   102 CQFAFIARNPrsPSSKLFCHLFVgSQPGEVHILyLLLCRSFQLAYLL 148
Cdd:smart00462  85 DVFGYIARDP--GSSRFACHVFR-CEKAAEDIA-LAIGQAFQLAYEL 127
SH2 cd00173
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...
 302-378 1.47e-07

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: 48.61  E-value: 1.47e-07
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 153792029 302 WAFAGLSRSCALSLLRRDVHGAFLLWPEPGTSDQWSLSVRTQCGVVPH-QVFRNHLGRFCLEHLPAEFPSLEALVESH 378
Cdd:cd00173    2 WFHGSISREEAERLLRGKPDGTFLVRESSSEPGDYVLSVRSGDGKVKHyLIERNEGGYYLLGGSGRTFPSLPELVEHY 79
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
 302-378 8.72e-05

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: 41.06  E-value: 8.72e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 153792029   302 WAFAGLSRSCALSLLRRDVHGAFLLWPEPGTSDQWSLSVRTQCGVVpH-QVFRNHLGRFCLEHLPAeFPSLEALVESH 378
Cdd:smart00252   3 WYHGFISREEAEKLLKNEGDGDFLVRDSESSPGDYVLSVRVKGKVK-HyRIRRNEDGKFYLEGGRK-FPSLVELVEHY 78
PID pfam00640
Phosphotyrosine interaction domain (PTB/PID);
64-130 1.85e-04

Phosphotyrosine interaction domain (PTB/PID);


Pssm-ID: 395515  Cd Length: 133  Bit Score: 41.19  E-value: 1.85e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 153792029   64 VILKFSLQGLKIYSGEGEVLLMAHALKRILYATWYPA--ACQFAFIARNPrsPSSKLFCHLFVGSQPGE 130
Cdd:pfam00640  54 VDLFISTDGLKLLNPDTQELIHDHPLVSISFCADGDPdlMRYFAYIARDK--ATNKFACHVFESEDGAQ 120
 
Name Accession Description Interval E-value
PTB_tensin-related cd13157
Tensin-related Phosphotyrosine-binding (PTB) domain; Tensin plays critical roles in renal ...
 23-150 1.00e-58

Tensin-related Phosphotyrosine-binding (PTB) domain; Tensin plays critical roles in renal function, muscle regeneration, and cell migration. It binds to actin filaments and interacts with the cytoplasmic tails of beta-integrin via its PTB domain, allowing tensin to link actin filaments to integrin receptors. Tensin functions as a platform for assembly and disassembly of signaling complexes at focal adhesions by recruiting tyrosine-phosphorylated signaling molecules, and also by providing interaction sites for other proteins. In addition to its PTB domain, it contains a C-terminal SH2 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.


Pssm-ID: 269979  Cd Length: 129  Bit Score: 188.36  E-value: 1.00e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153792029  23 CIAKLAQYVGSFPVDDLDTQESVGLVQQQLWALQDC-SRRRAVILKFSLQGLKIYSGEGEVLLMAHALKRILYATWYPAA 101
Cdd:cd13157    1 TVSRNAQYIGSFPVSGLDVADRADSVRKQLESLKESgSRGRPVILSVSLSGIKICSEDGKVVLMAHALRRVSYSTCRPAH 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 153792029 102 CQFAFIARNPRSPSSKLFCHLFVGSQPGEVHILYLLLCRSFQLAYLLQH 150
Cdd:cd13157   81 AQFAFVARNPGGPTNRQYCHVFVTRSPREAQELNLLLCRAFQLAYLKQH 129
PTB cd00934
Phosphotyrosine-binding (PTB) PH-like fold; PTB domains have a common PH-like fold and are ...
 28-142 9.85e-12

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: 61.76  E-value: 9.85e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153792029  28 AQYVGSFPVDDLDTQESVGLVQQQLWALQDCSRRRA--VILKFSLQGLKIYSGEGEVLLMAHALKRILYATWYP-AACQF 104
Cdd:cd00934    5 VKYLGSVEVGSSRGVDVVEEALKALAAALKSSKRKPgpVLLEVSSKGVKLLDLDTKELLLRHPLHRISYCGRDPdNPNVF 84

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 153792029 105 AFIARNPrsPSSKLFCHLFVGSQPGEVHILYLLLCRSF 142
Cdd:cd00934   85 AFIAGEE--GGSGFRCHVFQCEDEEEAEEILQAIGQAF 120
PTB smart00462
Phosphotyrosine-binding domain, phosphotyrosine-interaction (PI) domain; PTB/PI domain ...
 28-148 1.08e-10

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: 59.25  E-value: 1.08e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153792029    28 AQYVGSFPVDDLDtqeSVGLVQ---QQLWALQDCSRR--RAVILKFSLQGLKIYSGEGEVLLMAHALKRILYATWYPA-A 101
Cdd:smart00462   8 VKYLGSVEVPEAR---GLQVVQeaiRKLRAAQGSEKKepQKVILSISSRGVKLIDEDTKAVLHEHPLRRISFCAVGPDdL 84

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 153792029   102 CQFAFIARNPrsPSSKLFCHLFVgSQPGEVHILyLLLCRSFQLAYLL 148
Cdd:smart00462  85 DVFGYIARDP--GSSRFACHVFR-CEKAAEDIA-LAIGQAFQLAYEL 127
SH2 cd00173
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...
 302-378 1.47e-07

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: 48.61  E-value: 1.47e-07
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 153792029 302 WAFAGLSRSCALSLLRRDVHGAFLLWPEPGTSDQWSLSVRTQCGVVPH-QVFRNHLGRFCLEHLPAEFPSLEALVESH 378
Cdd:cd00173    2 WFHGSISREEAERLLRGKPDGTFLVRESSSEPGDYVLSVRSGDGKVKHyLIERNEGGYYLLGGSGRTFPSLPELVEHY 79
SH2_Grb2_like cd09941
Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar ...
 298-378 2.33e-06

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: 45.72  E-value: 2.33e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153792029 298 TENIWAFAGLSRSCALSLLRRDVH-GAFLL---WPEPGtsdQWSLSVRTQCGVVPHQVFRNHLGRFCLEHLpaEFPSLEA 373
Cdd:cd09941    1 KPHPWFHGKISRAEAEEILMNQRPdGAFLIresESSPG---DFSLSVKFGNDVQHFKVLRDGAGKYFLWVV--KFNSLNE 75


                 ....*
gi 153792029 374 LVESH 378
Cdd:cd09941   76 LVDYH 80
SH2_Srm cd10360
Src homology 2 (SH2) domain found in Src-related kinase lacking C-terminal regulatory tyrosine ...
 302-375 8.16e-06

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: 43.79  E-value: 8.16e-06
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 153792029 302 WAFAGLSRSCALSLLRR--DVHGAFLLWPEPGTSDQWSLSVRTQCGVVPHQVFRNHLGRFCLE--HLpaeFPSLEALV 375
Cdd:cd10360    2 WYFSGISRTQAQQLLLSppNEPGAFLIRPSESSLGGYSLSVRAQAKVCHYRICMAPSGSLYLQkgRL---FPGLEELL 76
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
 302-378 8.72e-05

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: 41.06  E-value: 8.72e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 153792029   302 WAFAGLSRSCALSLLRRDVHGAFLLWPEPGTSDQWSLSVRTQCGVVpH-QVFRNHLGRFCLEHLPAeFPSLEALVESH 378
Cdd:smart00252   3 WYHGFISREEAEKLLKNEGDGDFLVRDSESSPGDYVLSVRVKGKVK-HyRIRRNEDGKFYLEGGRK-FPSLVELVEHY 78
PTB_LDLRAP-mammal-like cd13159
Low Density Lipoprotein Receptor Adaptor Protein 1 (LDLRAP1) in mammals and similar proteins ...
 30-143 1.12e-04

Low Density Lipoprotein Receptor Adaptor Protein 1 (LDLRAP1) in mammals and similar proteins Phosphotyrosine-binding (PTB) PH-like fold; The null mutations in the LDL receptor adaptor protein 1 (LDLRAP1) gene, which serves as an adaptor for LDLR endocytosis in the liver, causes autosomal recessive hypercholesterolemia (ARH). LDLRAP1 contains a single 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 contains mammals, insects, and sponges.


Pssm-ID: 269981  Cd Length: 123  Bit Score: 41.55  E-value: 1.12e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153792029  30 YVGSFPVDDLDTQESVGLVQQQLWALQDCSRR--RAVILKFSLQGLKIYSGEGEVLLMAHALKRILYATWYPAACQ-FAF 106
Cdd:cd13159    9 YLGSTLVEKPKGEGATAEAVKTIIAMAKASGKklQKVTLTVSPKGIKVTDSATNETILEVSIYRISYCTADANHDKvFAF 88

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 153792029 107 IARNPRspSSKLFCHLFVGSQPGEVHILYLLLCRSFQ 143
Cdd:cd13159   89 IATNQD--NEKLECHAFLCAKRKMAQAVTLTVAQAFN 123
PID pfam00640
Phosphotyrosine interaction domain (PTB/PID);
64-130 1.85e-04

Phosphotyrosine interaction domain (PTB/PID);


Pssm-ID: 395515  Cd Length: 133  Bit Score: 41.19  E-value: 1.85e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 153792029   64 VILKFSLQGLKIYSGEGEVLLMAHALKRILYATWYPA--ACQFAFIARNPrsPSSKLFCHLFVGSQPGE 130
Cdd:pfam00640  54 VDLFISTDGLKLLNPDTQELIHDHPLVSISFCADGDPdlMRYFAYIARDK--ATNKFACHVFESEDGAQ 120
SH2_ABL cd09935
Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ...
 300-389 4.42e-04

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


Pssm-ID: 198189  Cd Length: 94  Bit Score: 39.29  E-value: 4.42e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153792029 300 NIWAFAGLSRSCALSLLRRDVHGAFLLWPEPGTSDQWSLSVRTQcGVVPHqvFRNHLGRFCLEHLPAE--FPSLEALVES 377
Cdd:cd09935    3 HSWYHGPISRNAAEYLLSSGINGSFLVRESESSPGQYSISLRYD-GRVYH--YRISEDSDGKVYVTQEhrFNTLAELVHH 79

                         90
                 ....*....|..
gi 153792029 378 HAGVERSLFCPL 389
Cdd:cd09935   80 HSKNADGLITTL 91
SH2_SLAP cd10344
Src homology 2 domain found in Src-like adaptor proteins; SLAP belongs to the subfamily of ...
 302-388 5.24e-03

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


Pssm-ID: 198207  Cd Length: 104  Bit Score: 36.32  E-value: 5.24e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153792029 302 WAFAGLSRSCALSLLR--RDVHGAFLLWPEPGTSDQWSLSVRTQCGVVPHQVfrNHLGRFCLEH-----LPA-EFPSLEA 373
Cdd:cd10344   12 WLFEGLSREKAEELLMlpGNQVGSFLIRESETRRGCYSLSVRHRGSQSRDSV--KHYRIFRLDNgwfyiSPRlTFQCLED 89

                         90
                 ....*....|....*
gi 153792029 374 LVESHAGVERSLFCP 388
Cdd:cd10344   90 MVNHYSESADGLCCV 104
 
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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