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Conserved domains on  [gi|206597474|ref|NP_082458|]
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SH2 domain-containing protein 4A [Mus musculus]

Protein Classification

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
SH2_SH2D4A cd10350
Src homology 2 domain found in the SH2 domain containing protein 4A (SH2D4A); SH2D4A contains ...
307-409 2.44e-72

Src homology 2 domain found in the SH2 domain containing protein 4A (SH2D4A); SH2D4A contains a single 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: 198213  Cd Length: 103  Bit Score: 222.11  E-value: 2.44e-72
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474 307 KNSDTIAPWFHGILTLKKANELLSTGVPGSFLIRVSEKIKGYALSYLSEEGCKHFLIDASANSYSFLGVDQLQHATLADL 386
Cdd:cd10350    1 KSSDTIAPWFHGILTLKKANELLLSTMPGSFLIRVSEKIKGYALSYLSEEGCKHFLIDASADSYSFLGVDQLQHATLADL 80
                         90       100
                 ....*....|....*....|...
gi 206597474 387 VEYHKEEPITSLGKELLLYPCGQ 409
Cdd:cd10350   81 VEYHKEEPITSLGKELLLYPCGQ 103
PTZ00121 super family cl31754
MAEBL; Provisional
32-242 1.07e-03

MAEBL; Provisional


The actual alignment was detected with superfamily member PTZ00121:

Pssm-ID: 173412 [Multi-domain]  Cd Length: 2084  Bit Score: 41.67  E-value: 1.07e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474   32 REEQIRRWKEREAAMERKESLPVK----SRPKKENGKSVHWKLGADKQVWVWVMGEHHLDKPYDVLCDEILAEREHLRAA 107
Cdd:PTZ00121 1207 KAEEERKAEEARKAEDAKKAEAVKkaeeAKKDAEEAKKAEEERNNEEIRKFEEARMAHFARRQAAIKAEEARKADELKKA 1286
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474  108 ----KDSELRKTQSLELANSLKIKSQNCDLQAMKKTEPQNVTRKA------------ASEEASGQGPRAIPTRKDDKAQT 171
Cdd:PTZ00121 1287 eekkKADEAKKAEEKKKADEAKKKAEEAKKADEAKKKAEEAKKKAdaakkkaeeakkAAEAAKAEAEAAADEAEAAEEKA 1366
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 206597474  172 KPVKEKDHEEMKQTEDEKTKQIYKSWKEDSEWQASLRKSKAADEKRRSLAKQAREDYKRLSQRGRSGDGLQ 242
Cdd:PTZ00121 1367 EAAEKKKEEAKKKADAAKKKAEEKKKADEAKKKAEEDKKKADELKKAAAAKKKADEAKKKAEEKKKADEAK 1437
 
Name Accession Description Interval E-value
SH2_SH2D4A cd10350
Src homology 2 domain found in the SH2 domain containing protein 4A (SH2D4A); SH2D4A contains ...
307-409 2.44e-72

Src homology 2 domain found in the SH2 domain containing protein 4A (SH2D4A); SH2D4A contains a single 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: 198213  Cd Length: 103  Bit Score: 222.11  E-value: 2.44e-72
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474 307 KNSDTIAPWFHGILTLKKANELLSTGVPGSFLIRVSEKIKGYALSYLSEEGCKHFLIDASANSYSFLGVDQLQHATLADL 386
Cdd:cd10350    1 KSSDTIAPWFHGILTLKKANELLLSTMPGSFLIRVSEKIKGYALSYLSEEGCKHFLIDASADSYSFLGVDQLQHATLADL 80
                         90       100
                 ....*....|....*....|...
gi 206597474 387 VEYHKEEPITSLGKELLLYPCGQ 409
Cdd:cd10350   81 VEYHKEEPITSLGKELLLYPCGQ 103
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
314-395 1.03e-17

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: 77.27  E-value: 1.03e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474   314 PWFHGILTLKKANELLSTGVPGSFLIRVSEKIKG-YALSYLSEEGCKHFLI-DASANSYSFlgVDQLQHATLADLVEYHK 391
Cdd:smart00252   2 PWYHGFISREEAEKLLKNEGDGDFLVRDSESSPGdYVLSVRVKGKVKHYRIrRNEDGKFYL--EGGRKFPSLVELVEHYQ 79

                   ....
gi 206597474   392 EEPI 395
Cdd:smart00252  80 KNSL 83
SH2 pfam00017
SH2 domain;
315-390 3.81e-14

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 67.24  E-value: 3.81e-14
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 206597474  315 WFHGILTLKKANELL-STGVPGSFLIRVSEKIKG-YALSYLSEEGCKHFLIDASANSYSFLGvDQLQHATLADLVEYH 390
Cdd:pfam00017   1 WYHGKISRQEAERLLlNGKPDGTFLVRESESTPGgYTLSVRDDGKVKHYKIQSTDNGGYYIS-GGVKFSSLAELVEHY 77
PTZ00121 PTZ00121
MAEBL; Provisional
32-242 1.07e-03

MAEBL; Provisional


Pssm-ID: 173412 [Multi-domain]  Cd Length: 2084  Bit Score: 41.67  E-value: 1.07e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474   32 REEQIRRWKEREAAMERKESLPVK----SRPKKENGKSVHWKLGADKQVWVWVMGEHHLDKPYDVLCDEILAEREHLRAA 107
Cdd:PTZ00121 1207 KAEEERKAEEARKAEDAKKAEAVKkaeeAKKDAEEAKKAEEERNNEEIRKFEEARMAHFARRQAAIKAEEARKADELKKA 1286
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474  108 ----KDSELRKTQSLELANSLKIKSQNCDLQAMKKTEPQNVTRKA------------ASEEASGQGPRAIPTRKDDKAQT 171
Cdd:PTZ00121 1287 eekkKADEAKKAEEKKKADEAKKKAEEAKKADEAKKKAEEAKKKAdaakkkaeeakkAAEAAKAEAEAAADEAEAAEEKA 1366
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 206597474  172 KPVKEKDHEEMKQTEDEKTKQIYKSWKEDSEWQASLRKSKAADEKRRSLAKQAREDYKRLSQRGRSGDGLQ 242
Cdd:PTZ00121 1367 EAAEKKKEEAKKKADAAKKKAEEKKKADEAKKKAEEDKKKADELKKAAAAKKKADEAKKKAEEKKKADEAK 1437
 
Name Accession Description Interval E-value
SH2_SH2D4A cd10350
Src homology 2 domain found in the SH2 domain containing protein 4A (SH2D4A); SH2D4A contains ...
307-409 2.44e-72

Src homology 2 domain found in the SH2 domain containing protein 4A (SH2D4A); SH2D4A contains a single 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: 198213  Cd Length: 103  Bit Score: 222.11  E-value: 2.44e-72
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474 307 KNSDTIAPWFHGILTLKKANELLSTGVPGSFLIRVSEKIKGYALSYLSEEGCKHFLIDASANSYSFLGVDQLQHATLADL 386
Cdd:cd10350    1 KSSDTIAPWFHGILTLKKANELLLSTMPGSFLIRVSEKIKGYALSYLSEEGCKHFLIDASADSYSFLGVDQLQHATLADL 80
                         90       100
                 ....*....|....*....|...
gi 206597474 387 VEYHKEEPITSLGKELLLYPCGQ 409
Cdd:cd10350   81 VEYHKEEPITSLGKELLLYPCGQ 103
SH2_SH2D4B cd10351
Src homology 2 domain found in the SH2 domain containing protein 4B (SH2D4B); SH2D4B contains ...
307-409 7.33e-47

Src homology 2 domain found in the SH2 domain containing protein 4B (SH2D4B); SH2D4B contains a single 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: 198214  Cd Length: 103  Bit Score: 156.20  E-value: 7.33e-47
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474 307 KNSDTIAPWFHGILTLKKANELLSTGVPGSFLIRVSEKIKGYALSYLSEEGCKHFLIDASANSYSFLGVDQLQHATLADL 386
Cdd:cd10351    1 RNTKTIAPWFHGIISREEAEALLMNATEGSFLVRVSEKIWGYTLSYRLQSGFKHFLVDASGDFYSFLGVDPNRHATLTDL 80
                         90       100
                 ....*....|....*....|...
gi 206597474 387 VEYHKEEPITSLGKELLLYPCGQ 409
Cdd:cd10351   81 IDFHKEEIITTSGGELLQEPCGQ 103
SH2_HSH2_like cd09946
Src homology 2 domain found in hematopoietic SH2 (HSH2) protein; HSH2 is thought to function ...
310-409 1.14e-21

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: 89.18  E-value: 1.14e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474 310 DTIAPWFHGILTLKKANELLSTGVPGSFLIRVSEKIKGYALSYLSEEGCKHFLIDASA-NSYSFLGvDQLQHATLADLVE 388
Cdd:cd09946    4 DGVPEWFHGAISREAAENMLESQPLGSFLIRVSHSHVGYTLSYKAQSSCRHFMVKLLDdGTFMIPG-EKVAHTSLHALVT 82
                         90       100
                 ....*....|....*....|.
gi 206597474 389 YHKEEPITSLGkELLLYPCGQ 409
Cdd:cd09946   83 FHQQKPIEPRR-ELLTQACRQ 102
SH2 cd00173
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...
314-390 5.04e-21

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: 86.36  E-value: 5.04e-21
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 206597474 314 PWFHGILTLKKANELLSTGVPGSFLIRVSEKIKG-YALSYLSEEG-CKHFLIDASANSYSFLGVDQLQHATLADLVEYH 390
Cdd:cd00173    1 PWFHGSISREEAERLLRGKPDGTFLVRESSSEPGdYVLSVRSGDGkVKHYLIERNEGGYYLLGGSGRTFPSLPELVEHY 79
SH2_SH2D7 cd10417
Src homology 2 domain found in the SH2 domain containing protein 7 (SH2D7); SH2D7 contains a ...
314-407 2.46e-20

Src homology 2 domain found in the SH2 domain containing protein 7 (SH2D7); SH2D7 contains a single 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: 199832  Cd Length: 102  Bit Score: 85.33  E-value: 2.46e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474 314 PWFHGILTLKKANELLSTGVPGSFLIRVSEKIKGYALSYLSEEGCKHFLIDASANSYSFLGVDQLQHATLADLVEYHKEE 393
Cdd:cd10417    8 PWFHGFITRKQTEQLLRDKALGSFLIRLSDRATGYILSYRGSDRCRHFVINQLRNRRYLISGDTSSHSTLAELVRHYQEV 87
                         90
                 ....*....|....
gi 206597474 394 PITSLGkELLLYPC 407
Cdd:cd10417   88 QLEPFG-ETLTAAC 100
SH2_SH2D2A_SH2D7 cd10349
Src homology 2 domain found in the SH2 domain containing protein 2A and 7 (SH2D2A and SH2D7); ...
314-390 7.77e-18

Src homology 2 domain found in the SH2 domain containing protein 2A and 7 (SH2D2A and SH2D7); SH2D2A and SH7 both contain a single 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: 199830  Cd Length: 77  Bit Score: 77.56  E-value: 7.77e-18
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 206597474 314 PWFHGILTLKKANELLSTGVPGSFLIRVSEKIKGYALSYLSEEGCKHFLIDASANSYSFLGVDQLQHATLADLVEYH 390
Cdd:cd10349    1 AWFHGFITRREAERLLEPKPQGCYLVRFSESAVTFVLSYRSRTCCRHFLLAQLRDGRHVVLGEDSAHARLQDLLLHY 77
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
314-395 1.03e-17

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: 77.27  E-value: 1.03e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474   314 PWFHGILTLKKANELLSTGVPGSFLIRVSEKIKG-YALSYLSEEGCKHFLI-DASANSYSFlgVDQLQHATLADLVEYHK 391
Cdd:smart00252   2 PWYHGFISREEAEKLLKNEGDGDFLVRDSESSPGdYVLSVRVKGKVKHYRIrRNEDGKFYL--EGGRKFPSLVELVEHYQ 79

                   ....
gi 206597474   392 EEPI 395
Cdd:smart00252  80 KNSL 83
SH2 pfam00017
SH2 domain;
315-390 3.81e-14

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 67.24  E-value: 3.81e-14
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 206597474  315 WFHGILTLKKANELL-STGVPGSFLIRVSEKIKG-YALSYLSEEGCKHFLIDASANSYSFLGvDQLQHATLADLVEYH 390
Cdd:pfam00017   1 WYHGKISRQEAERLLlNGKPDGTFLVRESESTPGgYTLSVRDDGKVKHYKIQSTDNGGYYIS-GGVKFSSLAELVEHY 77
SH2_SH2D2A cd10416
Src homology 2 domain found in the SH2 domain containing protein 2A (SH2D2A); SH2D2A contains ...
313-406 8.03e-13

Src homology 2 domain found in the SH2 domain containing protein 2A (SH2D2A); SH2D2A contains a single 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: 198279  Cd Length: 102  Bit Score: 64.29  E-value: 8.03e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474 313 AP-WFHGILTLKKANELLSTGVPGSFLIRVSEKIKGYALSYLSEEGCKHFLIDASANS-YSFLGVDQlQHATLADLVEYH 390
Cdd:cd10416    6 APaWFHGFITRREAERLLEPKPQGCYLVRFSESAVTFVLTYRSRTCCRHFLLAQLRDGrHVVLGEDS-AHARLQDLLLHY 84
                         90
                 ....*....|....*.
gi 206597474 391 KEEPITSLGkELLLYP 406
Cdd:cd10416   85 TAHPLSPYG-ETLTEP 99
SH2_C-SH2_SHP_like cd09931
C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
315-395 7.45e-12

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: 61.53  E-value: 7.45e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474 315 WFHGILTLKKANELL-STGVPGSFLIRVSEKIKG-YALSYLSEEG-CKHFLIDASANSYSFLGVDQLQhaTLADLVEYHK 391
Cdd:cd09931    2 WFHGHLSGKEAEKLLlEKGKPGSFLVRESQSKPGdFVLSVRTDDDkVTHIMIRCQGGKYDVGGGEEFD--SLTDLVEHYK 79

                 ....
gi 206597474 392 EEPI 395
Cdd:cd09931   80 KNPM 83
SH2_Cterm_RasGAP cd10354
C-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP ...
314-390 1.86e-09

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: 53.97  E-value: 1.86e-09
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 206597474 314 PWFHGILTLKKA-NELLSTGVPGSFLIRVSEKIKG-YALSYLSEEGCKHFLIDASANSYSFLGvdQLQHATLADLVEYH 390
Cdd:cd10354    1 IWFHGKISREEAyNMLVKVGGPGSFLVRESDNTPGdYSLSFRVNEGIKHFKIIPTGNNQFMMG--GRYFSSLDDVIDRY 77
SH2_Fps_family cd10361
Src homology 2 (SH2) domain found in feline sarcoma, Fujinami poultry sarcoma, and fes-related ...
314-395 8.83e-09

Src homology 2 (SH2) domain found in feline sarcoma, Fujinami poultry sarcoma, and fes-related (Fes/Fps/Fer) proteins; The Fps family consists of members Fps/Fes and Fer/Flk/Tyk3. They are cytoplasmic protein-tyrosine kinases implicated in signaling downstream from cytokines, growth factors and immune receptors. Fes/Fps/Fer contains three coiled-coil regions, an SH2 (Src-homology-2) and a TK (tyrosine kinase catalytic) domain signature. Members here include: Fps/Fes, Fer, Kin-31, and 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: 198224  Cd Length: 90  Bit Score: 52.53  E-value: 8.83e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474 314 PWFHGILTLKKANELLSTgvPGSFLIRVSEKIKG----YALSYLSEEGCKHFLIDASANSYsfLGVDQLQHATLADLVEY 389
Cdd:cd10361    7 PYYHGLLPREDAEELLKN--DGDFLVRKTEPKGGgkrkLVLSVRWDGKIRHFVINRDDGGK--YYIEGKSFKSISELINY 82

                 ....*...
gi 206597474 390 HKE--EPI 395
Cdd:cd10361   83 YQKtkEPI 90
SH2_DAPP1_BAM32_like cd10355
Src homology 2 domain found in dual adaptor for phosphotyrosine and 3-phosphoinositides ( ...
315-395 1.06e-08

Src homology 2 domain found in dual adaptor for phosphotyrosine and 3-phosphoinositides ( DAPP1)/B lymphocyte adaptor molecule of 32 kDa (Bam32)-like proteins; DAPP1/Bam32 contains a putative myristoylation site at its N-terminus, followed by a SH2 domain, and a pleckstrin homology (PH) domain at its C-terminus. DAPP1 could potentially be recruited to the cell membrane by any of these domains. Its putative myristoylation site could facilitate the interaction of DAPP1 with the lipid bilayer. Its SH2 domain may also interact with phosphotyrosine residues on membrane-associated proteins such as activated tyrosine kinase receptors. And finally its PH domain exhibits a high-affinity interaction with the PtdIns(3,4,5)P(3) PtdIns(3,4)P(2) second messengers produced at the cell membrane following the activation of PI 3-kinases. DAPP1 is thought to interact with both tyrosine phosphorylated proteins and 3-phosphoinositides and therefore may play a role in regulating the location and/or activity of such proteins(s) in response to agonists that elevate PtdIns(3,4,5)P(3) and PtdIns(3,4)P(2). This protein is likely to play an important role in triggering signal transduction pathways that lie downstream from receptor tyrosine kinases and PI 3-kinase. It is likely that DAPP1 functions as an adaptor to recruit other proteins to the plasma membrane in response to extracellular signals. 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: 198218  Cd Length: 92  Bit Score: 52.10  E-value: 1.06e-08
                         10        20        30        40        50        60        70        80
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gi 206597474 315 WFHGILTLKKANE-LLSTGVPGSFLIRVS-EKIKGYALSYLSEEGCKHFLIDASANSYSFlGVDQLqhATLADLVEYHKE 392
Cdd:cd10355    8 WYHGNLTRHAAEAlLLSNGVDGSYLLRNSnEGTGLFSLSVRAKDSVKHFHVEYTGYSFKF-GFNEF--SSLQDFVKHFAN 84

                 ...
gi 206597474 393 EPI 395
Cdd:cd10355   85 QPL 87
SH2_ABL cd09935
Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ...
314-406 1.64e-08

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: 51.62  E-value: 1.64e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474 314 PWFHGILTLKKANELLSTGVPGSFLIRVSEKIKG-YALSYLSEEGCKHFLIDASANSYSFLGVDQlQHATLADLVEYHKE 392
Cdd:cd09935    4 SWYHGPISRNAAEYLLSSGINGSFLVRESESSPGqYSISLRYDGRVYHYRISEDSDGKVYVTQEH-RFNTLAELVHHHSK 82
                         90
                 ....*....|....*..
gi 206597474 393 EP---ITslgkeLLLYP 406
Cdd:cd09935   83 NAdglIT-----TLRYP 94
SH2_Nck_family cd09943
Src homology 2 (SH2) domain found in the Nck family; Nck proteins are adaptors that modulate ...
314-405 3.50e-08

Src homology 2 (SH2) domain found in the Nck family; Nck proteins are adaptors that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. There are two members known in this family: Nck1 (Nckalpha) and Nck2 (Nckbeta and Growth factor receptor-bound protein 4 (Grb4)). They are characterized by having 3 SH3 domains and a C-terminal SH2 domain. Nck1 and Nck2 have overlapping functions as determined by gene knockouts. Both bind receptor tyrosine kinases and other tyrosine-phosphorylated proteins through their SH2 domains. In addition they also bind distinct targets. Neuronal signaling proteins: EphrinB1, EphrinB2, and Disabled-1 (Dab-1) all bind to Nck-2 exclusively. And in the case of PDGFR, Tyr(P)751 binds to Nck1 while Tyr(P)1009 binds to Nck2. Nck1 and Nck2 have a role in the infection process of enteropathogenic Escherichia coli (EPEC). Their SH3 domains are involved in recruiting and activating the N-WASP/Arp2/3 complex inducing actin polymerization resulting in the production of pedestals, dynamic bacteria-presenting protrusions of the plasma membrane. A similar thing occurs in the vaccinia virus where motile plasma membrane projections are formed beneath the virus. Recently it has been shown that the SH2 domains of both Nck1 and Nck2 bind the G-protein coupled receptor kinase-interacting protein 1 (GIT1) in a phosphorylation-dependent manner. 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: 198196  Cd Length: 93  Bit Score: 50.98  E-value: 3.50e-08
                         10        20        30        40        50        60        70        80
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gi 206597474 314 PWFHGILTLKKANELLST-GVPGSFLIRVSEKIKG-YALSYLSEEGCKHFLIDASANSYSflgVDQLQHATLADLVEYHK 391
Cdd:cd09943    2 PWYYGRITRHQAETLLNEhGHEGDFLIRDSESNPGdYSVSLKAPGRNKHFKVQVVDNVYC---IGQRKFHTMDELVEHYK 78
                         90
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gi 206597474 392 EEPITSLGKELLLY 405
Cdd:cd09943   79 KAPIFTSEQGEKLY 92
SH2_N-SH2_SHP_like cd10340
N-terminal Src homology 2 (N-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
315-394 1.05e-07

N-terminal Src homology 2 (N-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): [IVL]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: 198203  Cd Length: 99  Bit Score: 49.71  E-value: 1.05e-07
                         10        20        30        40        50        60        70        80
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gi 206597474 315 WFHGILTLKKANELLST-GVPGSFLIRVSEKIKG-YALSYLSEEGCKHFLIDASANSYSFLGVDQLqhATLADLVEYHKE 392
Cdd:cd10340    2 WFHPVISGIEAENLLKTrGVDGSFLARPSKSNPGdFTLSVRRGDEVTHIKIQNTGDYYDLYGGEKF--ATLSELVQYYME 79

                 ..
gi 206597474 393 EP 394
Cdd:cd10340   80 QH 81
SH2_SHD cd10390
Src homology 2 domain found in SH2 domain-containing adapter proteins D (SHD); The expression ...
314-406 1.22e-07

Src homology 2 domain found in SH2 domain-containing adapter proteins D (SHD); The expression of SHD is restricted to the brain. SHD may be a physiological substrate of c-Abl and may function as an adapter protein in the central nervous system. It is also thought to be involved in apoptotic regulation. SHD contains five YXXP motifs, a substrate sequence preferred by Abl tyrosine kinases, in addition to a poly-proline rich region and a 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: 198253  Cd Length: 98  Bit Score: 49.31  E-value: 1.22e-07
                         10        20        30        40        50        60        70        80
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gi 206597474 314 PWFHGILTLKKANELLSTGVPGSFLIRVSE-KIKGYALSYLSEEGCKHFLIDASANSYSFLGVDQLQHATLADLVEYHKE 392
Cdd:cd10390    2 PWFHGPLSRADAENLLSLCKEGSYLVRLSEtRPQDCSLSLRSSQGFLHLKFARTRENQVVLGQHSGPFPSVPELVLHYSS 81
                         90
                 ....*....|....*.
gi 206597474 393 EPITSLGKE--LLLYP 406
Cdd:cd10390   82 RPLPVQGAEhlALLYP 97
SH2_Nterm_RasGAP cd10353
N-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP ...
312-390 1.87e-07

N-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 the 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 N-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: 198216  Cd Length: 103  Bit Score: 49.06  E-value: 1.87e-07
                         10        20        30        40        50        60        70        80
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gi 206597474 312 IAP----WFHGILTLKKANE-LLSTGVPGSFLIRVSEKIKG-YALSYLSEEGCKHFLIDASANSYSFLGvdqLQHATLAD 385
Cdd:cd10353   14 TAPptnqWYHGRLDRTIAEErLRQAGKLGSYLIRESDRRPGsFVLSFLSRTGVNHFRIIAMCGDYYIGG---RRFSSLSD 90

                 ....*
gi 206597474 386 LVEYH 390
Cdd:cd10353   91 LIGYY 95
SH2_SHIP cd10343
Src homology 2 (SH2) domain found in SH2-containing inositol-5'-phosphatase (SHIP) and ...
313-406 2.38e-07

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: 48.59  E-value: 2.38e-07
                         10        20        30        40        50        60        70        80
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gi 206597474 313 APWFHGILTLKKANELLS-TGVPGSFLIRVSEKIKG-YALSYLSEEgCKH-----------FLIDASAnsysflGVDQLQ 379
Cdd:cd10343    3 PPWYHGNITRSKAEELLSkAGKDGSFLVRDSESVSGaYALCVLYQN-CVHtyrilpnaedkLSVQASE------GVPVRF 75
                         90       100       110
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gi 206597474 380 HATLADLVEYHKEEP---ITSlgkelLLYP 406
Cdd:cd10343   76 FTTLPELIEFYQKENmglVTH-----LLYP 100
SH2_C-SH2_PLC_gamma_like cd09932
C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
314-394 2.52e-07

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: 48.80  E-value: 2.52e-07
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gi 206597474 314 PWFHGILTLKKANELLSTgVP--GSFLIRVSEK-IKGYALSYLSEEGCKHFLIDASANSYsflGVDQLQHATLADLVEYH 390
Cdd:cd09932    5 EWFHANLTREQAEEMLMR-VPrdGAFLVRPSETdPNSFAISFRAEGKIKHCRIKQEGRLF---VIGTSQFESLVELVSYY 80

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gi 206597474 391 KEEP 394
Cdd:cd09932   81 EKHP 84
SH2_Cterm_shark_like cd10348
C-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
315-373 3.69e-07

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: 47.80  E-value: 3.69e-07
                         10        20        30        40        50        60
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gi 206597474 315 WFHGILTLKKANELLST--GVPGSFLIRVSEKIKG-YALSYLSEEGCKHFLIDASANSYSFL 373
Cdd:cd10348    2 WLHGALDRNEAVEILKQkaDADGSFLVRYSRRRPGgYVLTLVYENHVYHFEIQNRDDKWFYI 63
SH2_N-SH2_Zap70_Syk_like cd09938
N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
314-407 5.07e-07

N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70) and Spleen tyrosine kinase (Syk) proteins; ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the N-terminus SH2 domains of both Syk and Zap70. 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: 198191  Cd Length: 104  Bit Score: 47.77  E-value: 5.07e-07
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gi 206597474 314 PWFHGILTLKKANELLSTG--VPGSFLIRVS-EKIKGYALSYLSEEGCKHFLIDASAN-SYSFLGvdQLQHATLADLVEY 389
Cdd:cd09938    2 PFFYGSITREEAEEYLKLAgmSDGLFLLRQSlRSLGGYVLSVCHGRKFHHYTIERQLNgTYAIAG--GKAHCGPAELCEY 79
                         90       100
                 ....*....|....*....|.
gi 206597474 390 HKEEP---ITslgkeLLLYPC 407
Cdd:cd09938   80 HSTDLdglVC-----LLRKPC 95
SH2_SHB_SHD_SHE_SHF_like cd09945
Src homology 2 domain found in SH2 domain-containing adapter proteins B, D, E, and F (SHB, SHD, ...
314-406 2.54e-06

Src homology 2 domain found in SH2 domain-containing adapter proteins B, D, E, and F (SHB, SHD, SHE, SHF); SHB, SHD, SHE, and SHF are SH2 domain-containing proteins that play various roles throughout the cell. SHB functions in generating signaling compounds in response to tyrosine kinase activation. SHB contains proline-rich motifs, a phosphotyrosine binding (PTB) domain, tyrosine phosphorylation sites, and a SH2 domain. SHB mediates certain aspects of platelet-derived growth factor (PDGF) receptor-, fibroblast growth factor (FGF) receptor-, neural growth factor (NGF) receptor TRKA-, T cell receptor-, interleukin-2 (IL-2) receptor- and focal adhesion kinase- (FAK) signaling. SRC-like FYN-Related Kinase FRK/RAK (also named BSK/IYK or GTK) and SHB regulate apoptosis, proliferation and differentiation. SHB promotes apoptosis and is also required for proper mitogenicity, spreading and tubular morphogenesis in endothelial cells. SHB also plays a role in preventing early cavitation of embryoid bodies and reduces differentiation to cells expressing albumin, amylase, insulin and glucagon. SHB is a multifunctional protein that has difference responses in different cells under various conditions. SHE is expressed in heart, lung, brain, and skeletal muscle, while expression of SHD is restricted to the brain. SHF is mainly expressed in skeletal muscle, brain, liver, prostate, testis, ovary, small intestine, and colon. SHD may be a physiological substrate of c-Abl and may function as an adapter protein in the central nervous system. It is also thought to be involved in apoptotic regulation. SHD contains five YXXP motifs, a substrate sequence preferred by Abl tyrosine kinases, in addition to a poly-proline rich region and a C-terminal SH2 domain. SHE contains two pTry protein binding domains, protein interaction domain (PID) and a SH2 domain, followed by a glycine-proline rich region, all of which are N-terminal to the phosphotyrosine binding (PTB) domain. SHF contains four putative tyrosine phosphorylation sites and an 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: 198198  Cd Length: 98  Bit Score: 45.50  E-value: 2.54e-06
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gi 206597474 314 PWFHGILTLKKANELLSTGVPGSFLIRVSEKIKG-YALSYLSEEGCKHFLIDASANSYSFLGVDQLQHATLADLVEYHKE 392
Cdd:cd09945    2 GWYHGAITRIEAESLLRPCKEGSYLVRNSESTKQdYSLSLKSAKGFMHMRIQRNETGQYILGQFSRPFETIPEMIRHYCL 81
                         90
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gi 206597474 393 EPITSLGKE--LLLYP 406
Cdd:cd09945   82 NKLPVRGAEhmCLLEP 97
SH2_N-SH2_PLC_gamma_like cd10341
N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
314-397 6.04e-06

N-terminal Src homology 2 (N-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: 199829  Cd Length: 99  Bit Score: 44.65  E-value: 6.04e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474 314 PWFHGILTLKK--ANELLS---TGVPGSFLIRVSEKIKG-YALSYLSEEGCKHFLIDAS--ANSYSFLGVDQLQHATLAD 385
Cdd:cd10341    5 PWFHGKLGDGRdeAEKLLLeycEGGDGTFLVRESETFVGdYTLSFWRNGKVQHCRIRSRqeNGEKKYYLTDNLVFDSLYE 84
                         90
                 ....*....|..
gi 206597474 386 LVEYHKEEPITS 397
Cdd:cd10341   85 LIDYYRQNPLRC 96
SH2_cSH2_p85_like cd09930
C-terminal Src homology 2 (cSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
315-398 7.20e-06

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: 44.71  E-value: 7.20e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474 315 WFHGILTLKKANELLSTGVPGSFLIRVSEKIKGYALSYLSEEGCKHFLIDASANSYSFLGVDQLqHATLADLVEYHKEep 394
Cdd:cd09930    8 WLVGDINRTQAEELLRGKPDGTFLIRESSTQGCYACSVVCNGEVKHCVIYKTETGYGFAEPYNL-YESLKELVLHYAH-- 84

                 ....
gi 206597474 395 iTSL 398
Cdd:cd09930   85 -NSL 87
SH2_SH2B2 cd10411
Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B2 (APS), ...
314-395 8.65e-06

Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B2 (APS), like other members of the SH2B adapter protein family, contains a pleckstrin homology domain, at least one dimerization domain, and a C-terminal SH2 domain which binds to phosphorylated tyrosines in a variety of tyrosine kinases. SH2B1 and SH2B2 function in signaling pathways found downstream of growth hormone receptor and receptor tyrosine kinases, including the insulin, insulin-like growth factor-I (IGF-I), platelet-derived growth factor (PDGF), nerve growth factor, hepatocyte growth factor, and fibroblast growth factor receptors. SH2B2beta, a new isoform of SH2B2, is an endogenous inhibitor of SH2B1 and/or SH2B2 (SH2B2alpha), negatively regulating insulin signaling and/or JAK2-mediated cellular responses. 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: 198274  Cd Length: 97  Bit Score: 44.22  E-value: 8.65e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474 314 PWFHGILTLKKANELLSTGVP---GSFLIRVSEKIKG-YALSYLSEEGCKHFLIdaSANSYSFLGVDQLQHATLADLVEY 389
Cdd:cd10411    9 PWFHGTLSRVKAAQLVLAGGPrshGLFVIRQSETRPGeYVLTFNFQGKAKHLRL--SLNGHGQCHVQHLWFQSVFDMLRH 86

                 ....*.
gi 206597474 390 HKEEPI 395
Cdd:cd10411   87 FHTHPI 92
SH2_Nck1 cd10408
Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin ...
314-404 2.34e-05

Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. There are two members known in this family: Nck1 (Nckalpha) and Nck2 (Nckbeta and Growth factor receptor-bound protein 4 (Grb4)). They are characterized by having 3 SH3 domains and a C-terminal SH2 domain. Nck1 and Nck2 have overlapping functions as determined by gene knockouts. Both bind receptor tyrosine kinases and other tyrosine-phosphorylated proteins through their SH2 domains. In addition they also bind distinct targets. Neuronal signaling proteins: EphrinB1, EphrinB2, and Disabled-1 (Dab-1) all bind to Nck-2 exclusively. And in the case of PDGFR, Tyr(P)751 binds to Nck1 while Tyr(P)1009 binds to Nck2. Nck1 and Nck2 have a role in the infection process of enteropathogenic Escherichia coli (EPEC). Their SH3 domains are involved in recruiting and activating the N-WASP/Arp2/3 complex inducing actin polymerization resulting in the production of pedestals, dynamic bacteria-presenting protrusions of the plasma membrane. A similar thing occurs in the vaccinia virus where motile plasma membrane projections are formed beneath the virus. Recently it has been shown that the SH2 domains of both Nck1 and Nck2 bind the G-protein coupled receptor kinase-interacting protein 1 (GIT1) in a phosphorylation-dependent manner. 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: 198271  Cd Length: 97  Bit Score: 43.10  E-value: 2.34e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474 314 PWFHGILTLKKANELLST-GVPGSFLIRVSEKIKG-YALSYLSEEGCKHFLIDASANSYSflgVDQLQHATLADLVEYHK 391
Cdd:cd10408    2 PWYYGKVTRHQAEMALNErGNEGDFLIRDSESSPNdFSVSLKAQGKNKHFKVQLKECVYC---IGQRKFSSMEELVEHYK 78
                         90
                 ....*....|....*
gi 206597474 392 EEPI--TSLGKELLL 404
Cdd:cd10408   79 KAPIftSEQGEKLYL 93
SH2_SHC cd09925
Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC); SHC is involved in a wide ...
314-404 3.55e-05

Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC); SHC is involved in a wide variety of pathways including regulating proliferation, angiogenesis, invasion and metastasis, and bone metabolism. An adapter protein, SHC has been implicated in Ras activation following the stimulation of a number of different receptors, including growth factors [insulin, epidermal growth factor (EGF), nerve growth factor, and platelet derived growth factor (PDGF)], cytokines [interleukins 2, 3, and 5], erythropoietin, and granulocyte/macrophage colony-stimulating factor, and antigens [T-cell and B-cell receptors]. SHC has been shown to bind to tyrosine-phosphorylated receptors, and receptor stimulation leads to tyrosine phosphorylation of SHC. Upon phosphorylation, SHC interacts with another adapter protein, Grb2, which binds to the Ras GTP/GDP exchange factor mSOS which leads to Ras activation. SHC is composed of an N-terminal domain that interacts with proteins containing phosphorylated tyrosines, a (glycine/proline)-rich collagen-homology domain that contains the phosphorylated binding site, and a C-terminal SH2 domain. SH2 has been shown to interact with the tyrosine-phosphorylated receptors of EGF and PDGF and with the tyrosine-phosphorylated C chain of the T-cell receptor, providing one of the mechanisms of T-cell-mediated Ras activation. 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: 198179  Cd Length: 104  Bit Score: 42.72  E-value: 3.55e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474 314 PWFHGILTLKKANELLSTGvpGSFLIRVSEKIKG-YALSYLSEEGCKHF-LIDASANsysflgVDQLQHA--TLADLVEY 389
Cdd:cd09925    8 PWYHGKMSRRDAESLLQTD--GDFLVRESTTTPGqYVLTGMQNGQPKHLlLVDPEGV------VRTKDRVfeSISHLINY 79
                         90
                 ....*....|....*..
gi 206597474 390 HKEE--PITSLGKELLL 404
Cdd:cd09925   80 HVTNglPIISEGSELHL 96
SH2_SH2B_family cd10346
Src homology 2 (SH2) domain found in SH2B adapter protein family; The SH2B adapter protein ...
314-395 7.14e-05

Src homology 2 (SH2) domain found in SH2B adapter protein family; The SH2B adapter protein family has 3 members: SH2B1 (SH2-B, PSM), SH2B2 (APS), and SH2B3 (Lnk). SH2B family members contain a pleckstrin homology domain, at least one dimerization domain, and a C-terminal SH2 domain which binds to phosphorylated tyrosines in a variety of tyrosine kinases. SH2B1 and SH2B2 function in signaling pathways found downstream of growth hormone receptor and receptor tyrosine kinases, including the insulin, insulin-like growth factor-I (IGF-I), platelet-derived growth factor (PDGF), nerve growth factor, hepatocyte growth factor, and fibroblast growth factor receptors. SH2B2beta, a new isoform of SH2B2, is an endogenous inhibitor of SH2B1 and/or SH2B2 (SH2B2alpha), negatively regulating insulin signaling and/or JAK2-mediated cellular responses. SH2B3 negatively regulates lymphopoiesis and early hematopoiesis. The lnk-deficiency results in enhanced production of B cells, and expansion as well as enhanced function of hematopoietic stem cells (HSCs), demonstrating negative regulatory functions of Sh2b3/Lnk in cytokine signaling. Sh2b3/Lnk also functions in responses controlled by cell adhesion and in crosstalk between integrin- and cytokine-mediated 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: 198209  Cd Length: 97  Bit Score: 41.64  E-value: 7.14e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474 314 PWFHGILTLKKANELLSTGVPGS---FLIRVSEKIKG-YALSYLSEEGCKHFLIdaSANSYSFLGVDQLQHATLADLVEY 389
Cdd:cd10346    9 PWFHGTLSRSDAAQLVLHSGADGhgvFLVRQSETRRGeFVLTFNFQGRAKHLRL--TLNEKGQCRVQHLWFPSIFDMLEH 86

                 ....*.
gi 206597474 390 HKEEPI 395
Cdd:cd10346   87 FRQNPI 92
SH2_csk_like cd09937
Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal ...
314-393 7.62e-05

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: 7.62e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474 314 PWFHGILTLKKANELLSTGVPGSFLIRVSEKIKG-YALSYLSEEGCKHFLIDASANSysfLGVDQLQH-ATLADLVEYHK 391
Cdd:cd09937    4 PWFHGKISREEAERLLQPPEDGLFLVRESTNYPGdYTLCVSFEGKVEHYRVIYRNGK---LTIDEEEYfENLIQLVEHYT 80

                 ..
gi 206597474 392 EE 393
Cdd:cd09937   81 KD 82
SH2_SHF cd10392
Src homology 2 domain found in SH2 domain-containing adapter protein F (SHF); SHF is thought ...
315-406 7.80e-05

Src homology 2 domain found in SH2 domain-containing adapter protein F (SHF); SHF is thought to play a role in PDGF-receptor signaling and regulation of apoptosis. SHF is mainly expressed in skeletal muscle, brain, liver, prostate, testis, ovary, small intestine, and colon. SHF contains four putative tyrosine phosphorylation sites and an 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: 198255  Cd Length: 98  Bit Score: 41.59  E-value: 7.80e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474 315 WFHGILTLKKANELLSTGVPGSFLIRVSEKIKG-YALSYLSEEGCKHFLIDASANSYSFLGVDQLQHATLADLVEYHKEE 393
Cdd:cd10392    3 WYHGAISRTDAENLLRLCKEASYLVRNSETSKNdFSLSLKSSQGFMHMKLSRTKEHKYVLGQNSPPFSSVPEIIHHYASR 82
                         90
                 ....*....|....*
gi 206597474 394 PITSLGKE--LLLYP 406
Cdd:cd10392   83 KLPIKGAEhmSLLYP 97
SH2_Nck2 cd10409
Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin ...
315-395 1.35e-04

Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. There are two members known in this family: Nck1 (Nckalpha) and Nck2 (Nckbeta and Growth factor receptor-bound protein 4 (Grb4)). They are characterized by having 3 SH3 domains and a C-terminal SH2 domain. Nck1 and Nck2 have overlapping functions as determined by gene knockouts. Both bind receptor tyrosine kinases and other tyrosine-phosphorylated proteins through their SH2 domains. In addition they also bind distinct targets. Neuronal signaling proteins: EphrinB1, EphrinB2, and Disabled-1 (Dab-1) all bind to Nck-2 exclusively. And in the case of PDGFR, Tyr(P)751 binds to Nck1 while Tyr(P)1009 binds to Nck2. Nck1 and Nck2 have a role in the infection process of enteropathogenic Escherichia coli (EPEC). Their SH3 domains are involved in recruiting and activating the N-WASP/Arp2/3 complex inducing actin polymerization resulting in the production of pedestals, dynamic bacteria-presenting protrusions of the plasma membrane. A similar thing occurs in the vaccinia virus where motile plasma membrane projections are formed beneath the virus. Recently it has been shown that the SH2 domains of both Nck1 and Nck2 bind the G-protein coupled receptor kinase-interacting protein 1 (GIT1) in a phosphorylation-dependent manner. 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: 198272  Cd Length: 98  Bit Score: 40.79  E-value: 1.35e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474 315 WFHGILTLKKANELLST-GVPGSFLIRVSEKIKG-YALSYLSEEGCKHFLIDASANSYSflgVDQLQHATLADLVEYHKE 392
Cdd:cd10409    3 WYYGNVTRHQAECALNErGVEGDFLIRDSESSPSdFSVSLKAVGKNKHFKVQLVDNVYC---IGQRRFNSMDELVEHYKK 79

                 ...
gi 206597474 393 EPI 395
Cdd:cd10409   80 API 82
SH2_Grb2_like cd09941
Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar ...
314-404 1.38e-04

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


Pssm-ID: 199828  Cd Length: 95  Bit Score: 40.72  E-value: 1.38e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474 314 PWFHGILTLKKANELLSTGVP-GSFLIRVSE-KIKGYALSYLSEEGCKHFLIDASANSYSFLGVDQLqhATLADLVEYHK 391
Cdd:cd09941    4 PWFHGKISRAEAEEILMNQRPdGAFLIRESEsSPGDFSLSVKFGNDVQHFKVLRDGAGKYFLWVVKF--NSLNELVDYHR 81
                         90
                 ....*....|...
gi 206597474 392 EEPItSLGKELLL 404
Cdd:cd09941   82 TTSV-SRNQQIFL 93
SH2_Grb7_family cd09944
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) ...
314-363 1.46e-04

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


Pssm-ID: 198197 [Multi-domain]  Cd Length: 108  Bit Score: 40.87  E-value: 1.46e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 206597474 314 PWFHGILTLKKANELLST--GVPGSFLIRVSE-KIKGYALSYLSEEGCKHFLI 363
Cdd:cd09944    6 PWFHGGISRDEAARLIRQqgLVDGVFLVRESQsNPGAFVLSLKHGQKIKHYQI 58
SH2_Nterm_shark_like cd10347
N-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
315-390 1.47e-04

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


Pssm-ID: 198210  Cd Length: 81  Bit Score: 40.05  E-value: 1.47e-04
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 206597474 315 WFHGILTLKKANELLS--TGVPGSFLIRVSEKIKG-YALSYLSEEGCKHFLIDASANSYSFLGVDQLQHATLADLVEYH 390
Cdd:cd10347    3 WYHGKISREVAEALLLreGGRDGLFLVRESTSAPGdYVLSLLAQGEVLHYQIRRHGEDAFFSDDGPLIFHGLDTLIEHY 81
SH2_SHE cd10391
Src homology 2 domain found in SH2 domain-containing adapter protein E (SHE); SHE is expressed ...
314-406 2.09e-04

Src homology 2 domain found in SH2 domain-containing adapter protein E (SHE); SHE is expressed in heart, lung, brain, and skeletal muscle. SHE contains two pTry protein binding domains, protein interaction domain (PID) and a SH2 domain, followed by a glycine-proline rich region, all of which are N-terminal to the phosphotyrosine binding (PTB) 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: 198254  Cd Length: 98  Bit Score: 40.32  E-value: 2.09e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474 314 PWFHGILTLKKANELLSTGVPGSFLIRVSEKIKG-YALSYLSEEGCKHFLIDASANSYSFLGVDQLQHATLADLVEYHKE 392
Cdd:cd10391    2 PWYHGSISRAEAESRLQPCKEASYLVRNSESGNSkYSIALKTSQGCVHIIVAQTKDNKYTLNQTSAVFDSIPEVVHYYSN 81
                         90
                 ....*....|....*.
gi 206597474 393 EPITSLGKE--LLLYP 406
Cdd:cd10391   82 EKLPFKGAEhmTLLHP 97
SH2_SLAP cd10344
Src homology 2 domain found in Src-like adaptor proteins; SLAP belongs to the subfamily of ...
315-392 2.12e-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: 40.17  E-value: 2.12e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474 315 WFHGILTLKKANELLS--TGVPGSFLIRVSEKIKG-YALS-----YLSEEGCKHFLIDASANSYSFLGvDQLQHATLADL 386
Cdd:cd10344   12 WLFEGLSREKAEELLMlpGNQVGSFLIRESETRRGcYSLSvrhrgSQSRDSVKHYRIFRLDNGWFYIS-PRLTFQCLEDM 90

                 ....*.
gi 206597474 387 VEYHKE 392
Cdd:cd10344   91 VNHYSE 96
SH2_SH2B3 cd10412
Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B3 (Lnk), ...
314-395 3.72e-04

Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B3 (Lnk), like other members of the SH2B adapter protein family, contains a pleckstrin homology domain, at least one dimerization domain, and a C-terminal SH2 domain which binds to phosphorylated tyrosines in a variety of tyrosine kinases. SH2B3 negatively regulates lymphopoiesis and early hematopoiesis. The lnk-deficiency results in enhanced production of B cells, and expansion as well as enhanced function of hematopoietic stem cells (HSCs), demonstrating negative regulatory functions of Sh2b3/Lnk in cytokine signaling. Sh2b3/Lnk also functions in responses controlled by cell adhesion and in crosstalk between integrin- and cytokine-mediated 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: 198275  Cd Length: 97  Bit Score: 39.49  E-value: 3.72e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474 314 PWFHGILTLKKANELLSTGVP---GSFLIRVSEKIKG-YALSYLSEEGCKHFLIdaSANSYSFLGVDQLQHATLADLVEY 389
Cdd:cd10412    9 PWFHGPISRVKAAQLVQLQGPdahGVFLVRQSETRRGeYVLTFNFQGRAKHLRL--SLTERGQCRVQHLHFPSVVDMLHH 86

                 ....*.
gi 206597474 390 HKEEPI 395
Cdd:cd10412   87 FQRSPI 92
SH2_C-SH2_Zap70 cd10402
C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
314-394 4.49e-04

C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70); ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the C-terminus SH2 domains of Zap70. 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: 198265  Cd Length: 105  Bit Score: 39.52  E-value: 4.49e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474 314 PWFHGILTLKKANELLSTGVP--GSFLIRVSEKIKGYALSYLSEEGCKHFLIDA-SANSYSFlgVDQLQHATLADLVEYH 390
Cdd:cd10402   11 PWYHGSIARDEAERRLYSGAQpdGKFLLRERKESGTYALSLVYGKTVYHYRIDQdKSGKYSI--PEGTKFDTLWQLVEYL 88

                 ....
gi 206597474 391 KEEP 394
Cdd:cd10402   89 KLKP 92
SH2_Src_family cd09933
Src homology 2 (SH2) domain found in the Src family of non-receptor tyrosine kinases; The Src ...
314-393 5.26e-04

Src homology 2 (SH2) domain found in the Src family of non-receptor tyrosine kinases; The Src family kinases are nonreceptor tyrosine kinases that have been implicated in pathways regulating proliferation, angiogenesis, invasion and metastasis, and bone metabolism. It is thought that transforming ability of Src is linked to its ability to activate key signaling molecules in these pathways, rather than through direct activity. As such blocking Src activation has been a target for drug companies. Src family members can be divided into 3 groups based on their expression pattern: 1) Src, Fyn, and Yes; 2) Blk, Fgr, Hck, Lck, and Lyn; and 3) Frk-related kinases Frk/Rak and Iyk/Bsk Of these, cellular c-Src is the best studied and most frequently implicated in oncogenesis. The c-Src contains five distinct regions: a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Src exists in both active and inactive conformations. Negative regulation occurs through phosphorylation of Tyr, resulting in an intramolecular association between phosphorylated Tyr and the SH2 domain of SRC, which locks the protein in a closed conformation. Further stabilization of the inactive state occurs through interactions between the SH3 domain and a proline-rich stretch of residues within the kinase domain. Conversely, dephosphorylation of Tyr allows SRC to assume an open conformation. Full activity requires additional autophosphorylation of a Tyr residue within the catalytic domain. Loss of the negative-regulatory C-terminal segment has been shown to result in increased activity and transforming potential. Phosphorylation of the C-terminal Tyr residue by C-terminal Src kinase (Csk) and Csk homology kinase results in increased intramolecular interactions and consequent Src inactivation. Specific phosphatases, protein tyrosine phosphatase a (PTPa) and the SH-containing phosphatases SHP1/SHP2, have also been shown to take a part in Src activation. Src is also activated by direct binding of focal adhesion kinase (Fak) and Crk-associated substrate (Cas) to the SH2 domain. SRC activity can also be regulated by numerous receptor tyrosine kinases (RTKs), such as Her2, epidermal growth factor receptor (EGFR), fibroblast growth factor receptor, platelet-derived growth factor receptor (PDGFR), and vascular endothelial growth factor receptor (VEGFR). 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: 199827  Cd Length: 101  Bit Score: 39.10  E-value: 5.26e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474 314 PWFHGILTLKKA-NELLSTGVP-GSFLIRVSEKIKG-YALSYLSEE-----GCKHFLIDASANSYSFLgVDQLQHATLAD 385
Cdd:cd09933    4 EWFFGKIKRKDAeKLLLAPGNPrGTFLIRESETTPGaYSLSVRDGDdargdTVKHYRIRKLDNGGYYI-TTRATFPTLQE 82

                 ....*...
gi 206597474 386 LVEYHKEE 393
Cdd:cd09933   83 LVQHYSKD 90
SH2_SH2B1 cd10410
Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B1 (SH2-B, ...
314-395 6.20e-04

Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B1 (SH2-B, PSM), like other members of the SH2B adapter protein family, contains a pleckstrin homology domain, at least one dimerization domain, and a C-terminal SH2 domain which binds to phosphorylated tyrosines in a variety of tyrosine kinases. SH2B1 and SH2B2 function in signaling pathways found downstream of growth hormone receptor and receptor tyrosine kinases, including the insulin, insulin-like growth factor-I (IGF-I), platelet-derived growth factor (PDGF), nerve growth factor, hepatocyte growth factor, and fibroblast growth factor receptors. SH2B2beta, a new isoform of SH2B2, is an endogenous inhibitor of SH2B1 and/or SH2B2 (SH2B2alpha), negatively regulating insulin signaling and/or JAK2-mediated cellular responses. 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: 198273  Cd Length: 97  Bit Score: 38.84  E-value: 6.20e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474 314 PWFHGILTLKKANELL---STGVPGSFLIRVSEKIKG-YALSYLSEEGCKHFLIdaSANSYSFLGVDQLQHATLADLVEY 389
Cdd:cd10410    9 PWFHGMLSRLKAAQLVlegGTGSHGVFLVRQSETRRGeYVLTFNFQGKAKHLRL--SLNEEGQCRVQHLWFQSIFDMLEH 86

                 ....*.
gi 206597474 390 HKEEPI 395
Cdd:cd10410   87 FRVHPI 92
SH2_a2chimerin_b2chimerin cd10352
Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins ...
316-387 6.51e-04

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: 38.50  E-value: 6.51e-04
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 206597474 316 FHGILTLKKANELLSTGVPGSFLIRVSEKIKG-YALSYLSEEGCKHF-LIDASANSYSFLGvdQLQHATLADLV 387
Cdd:cd10352    9 YHGLISREEAEQLLSGASDGSYLIRESSRDDGyYTLSLRFNGKVKNYkLYYDGKNHYHYVG--EKRFDTIHDLV 80
SH2_Srm cd10360
Src homology 2 (SH2) domain found in Src-related kinase lacking C-terminal regulatory tyrosine ...
314-390 7.33e-04

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


Pssm-ID: 198223  Cd Length: 79  Bit Score: 38.01  E-value: 7.33e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474 314 PWFHGILTLKKANELLST--GVPGSFLIRVSE-KIKGYALSYLSEEGCKHFLIDASANSYSFLGVDQLqHATLADLVEYH 390
Cdd:cd10360    1 PWYFSGISRTQAQQLLLSppNEPGAFLIRPSEsSLGGYSLSVRAQAKVCHYRICMAPSGSLYLQKGRL-FPGLEELLAYY 79
SH2_Src_Fyn cd10368
Src homology 2 (SH2) domain found in Fyn; Fyn is a member of the Src non-receptor type ...
315-392 9.58e-04

Src homology 2 (SH2) domain found in Fyn; Fyn is a member of the Src non-receptor type tyrosine kinase family of proteins. Fyn is involved in the control of cell growth and is required in the following pathways: T and B cell receptor signaling, integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the Fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. FYN has been shown to interact with a number of proteins including: BCAR1, Cbl, Janus kinase, nephrin, Sky, tyrosine kinase, Wiskott-Aldrich syndrome protein, and Zap-70. Fyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. 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: 198231 [Multi-domain]  Cd Length: 101  Bit Score: 38.47  E-value: 9.58e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474 315 WFHGILTLKKAN-ELLSTGVP-GSFLIRVSEKIKG-YALSY-----LSEEGCKHFLIDASANSYSFLgVDQLQHATLADL 386
Cdd:cd10368    5 WYFGKLGRKDAErQLLSFGNPrGTFLIRESETTKGaYSLSIrdwddMKGDHVKHYKIRKLDNGGYYI-TTRAQFETLQQL 83

                 ....*.
gi 206597474 387 VEYHKE 392
Cdd:cd10368   84 VQHYSE 89
PTZ00121 PTZ00121
MAEBL; Provisional
32-242 1.07e-03

MAEBL; Provisional


Pssm-ID: 173412 [Multi-domain]  Cd Length: 2084  Bit Score: 41.67  E-value: 1.07e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474   32 REEQIRRWKEREAAMERKESLPVK----SRPKKENGKSVHWKLGADKQVWVWVMGEHHLDKPYDVLCDEILAEREHLRAA 107
Cdd:PTZ00121 1207 KAEEERKAEEARKAEDAKKAEAVKkaeeAKKDAEEAKKAEEERNNEEIRKFEEARMAHFARRQAAIKAEEARKADELKKA 1286
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474  108 ----KDSELRKTQSLELANSLKIKSQNCDLQAMKKTEPQNVTRKA------------ASEEASGQGPRAIPTRKDDKAQT 171
Cdd:PTZ00121 1287 eekkKADEAKKAEEKKKADEAKKKAEEAKKADEAKKKAEEAKKKAdaakkkaeeakkAAEAAKAEAEAAADEAEAAEEKA 1366
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 206597474  172 KPVKEKDHEEMKQTEDEKTKQIYKSWKEDSEWQASLRKSKAADEKRRSLAKQAREDYKRLSQRGRSGDGLQ 242
Cdd:PTZ00121 1367 EAAEKKKEEAKKKADAAKKKAEEKKKADEAKKKAEEDKKKADELKKAAAAKKKADEAKKKAEEKKKADEAK 1437
SH2_Src_Frk cd10369
Src homology 2 (SH2) domain found in the Fyn-related kinase (Frk); Frk is a member of the Src ...
314-390 1.47e-03

Src homology 2 (SH2) domain found in the Fyn-related kinase (Frk); Frk is a member of the Src non-receptor type tyrosine kinase family of proteins. The Frk subfamily is composed of Frk/Rak and Iyk/Bsk/Gst. It is expressed primarily epithelial cells. Frk is a nuclear protein and may function during G1 and S phase of the cell cycle and suppress growth. Unlike the other Src members it lacks a glycine at position 2 of SH4 which is important for addition of a myristic acid moiety that is involved in targeting Src PTKs to cellular membranes. FRK and SHB exert similar effects when overexpressed in rat phaeochromocytoma (PC12) and beta-cells, where both induce PC12 cell differentiation and beta-cell proliferation. Under conditions that cause beta-cell degeneration these proteins augment beta-cell apoptosis. The FRK-SHB responses involve FAK and insulin receptor substrates (IRS) -1 and -2. Frk has been demonstrated to interact with retinoblastoma protein. Frk regulates PTEN protein stability by phosphorylating PTEN, which in turn prevents PTEN degradation. Frk also plays a role in regulation of embryonal pancreatic beta cell formation. Frk has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its activation loop. The tryosine involved is at the same site as the tyrosine involved in the autophosphorylation of Src. 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: 199831  Cd Length: 96  Bit Score: 37.94  E-value: 1.47e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474 314 PWFHGILTLKKANE--LLSTGVPGSFLIRVSEKIKG-YALSYLSEEGCKHFLIDASANSYSFLGVDQLQHaTLADLVEYH 390
Cdd:cd10369    4 PWFFGAIKRADAEKqlLYSENQTGAFLIRESESQKGeFSLSVLDGGVVKHYRIRRLDEGGFFLTRRKTFS-TLNEFVNYY 82
SH2_Src_Fyn_isoform_a_like cd10418
Src homology 2 (SH2) domain found in Fyn isoform a like proteins; Fyn is a member of the Src ...
315-392 1.82e-03

Src homology 2 (SH2) domain found in Fyn isoform a like proteins; Fyn is a member of the Src non-receptor type tyrosine kinase family of proteins. This cd contains the SH2 domain found in Fyn isoform a type proteins. Fyn is involved in the control of cell growth and is required in the following pathways: T and B cell receptor signaling, integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the Fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. FYN has been shown to interact with a number of proteins including: BCAR1, Cbl, Janus kinase, nephrin, Sky, tyrosine kinase, Wiskott-Aldrich syndrome protein, and Zap-70. Fyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. 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: 198281  Cd Length: 101  Bit Score: 37.67  E-value: 1.82e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474 315 WFHGILTLKKAN-ELLSTGVP-GSFLIRVSEKIKG-YALS---YLSEEG--CKHFLIDASANSYSFLgVDQLQHATLADL 386
Cdd:cd10418    5 WYFGKLGRKDAErQLLSFGNPrGTFLIRESETTKGaYSLSirdWDDMKGdhVKHYKIRKLDNGGYYI-TTRAQFETLQQL 83

                 ....*.
gi 206597474 387 VEYHKE 392
Cdd:cd10418   84 VQHYSE 89
SH2_PTK6_Brk cd10358
Src homology 2 domain found in protein-tyrosine kinase-6 (PTK6) which is also known as breast ...
314-407 2.06e-03

Src homology 2 domain found in protein-tyrosine kinase-6 (PTK6) which is also known as breast tumor kinase (Brk); Human protein-tyrosine kinase-6 (PTK6, also known as breast tumor kinase (Brk)) is a member of the non-receptor protein-tyrosine kinase family and is expressed in two-thirds of all breast tumors. PTK6 (9). PTK6 contains a SH3 domain, a SH2 domain, and catalytic domains. For the case of the non-receptor protein-tyrosine kinases, the SH2 domain is typically involved in negative regulation of kinase activity by binding to a phosphorylated tyrosine residue near to the C terminus. The C-terminal sequence of PTK6 (PTSpYENPT where pY is phosphotyrosine) is thought to be a self-ligand for the SH2 domain. The structure of the SH2 domain resembles other SH2 domains except for a centrally located four-stranded antiparallel beta-sheet (strands betaA, betaB, betaC, and betaD). There are also differences in the loop length which might be responsible for PTK6 ligand specificity. There are two possible means of regulation of PTK6: autoinhibitory with the phosphorylation of Tyr playing a role in its negative regulation and autophosphorylation at this site, though it has been shown that PTK6 might phosphorylate signal transduction-associated proteins Sam68 and signal transducing adaptor family member 2 (STAP/BKS) in vivo. 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: 198221  Cd Length: 100  Bit Score: 37.42  E-value: 2.06e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474 314 PWFHGILTLKKANELLST--GVPGSFLIRVSEKIKG-YALSYLSEEGCKHFLIDASANSYSFLGvDQLQHATLADLVEYH 390
Cdd:cd10358    3 PWFFGCISRSEAVRRLQAegNATGAFLIRVSEKPSAdYVLSVRDTQAVRHYKIWRRAGGRLHLN-EAVSFLSLPELVNYH 81
                         90
                 ....*....|....*..
gi 206597474 391 KEEPItSLGKELLLyPC 407
Cdd:cd10358   82 RAQSL-SHGLRLAA-PC 96
SH2_Vav2 cd10406
Src homology 2 (SH2) domain found in the Vav2 proteins; Proto-oncogene vav is a member of the ...
311-406 2.31e-03

Src homology 2 (SH2) domain found in the Vav2 proteins; Proto-oncogene vav is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. All vavs are activated by tyrosine phosphorylation leading to their activation. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, and Vav2 and Vav3 are more ubiquitously expressed. Vav2 is a GEF for RhoA, RhoB and RhoG and may activate Rac1 and Cdc42. Vav2 has been shown to interact with CD19 and Grb2. Alternatively spliced transcript variants encoding different isoforms have been found for Vav2. Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated 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: 198269  Cd Length: 103  Bit Score: 37.35  E-value: 2.31e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474 311 TIAPWFHGILTLKKANELLSTGVPGSFLIRV-SEKIKGYALSYLSEEGCKHFLIDASANSYSFLGVDQLQhaTLADLVEY 389
Cdd:cd10406    3 TAYPWFAGNMERQQTDNLLKSHASGTYLIRErPAEAERFAISIKFNDEVKHIKVVEKDNWIHITEAKKFE--SLLELVEY 80
                         90       100
                 ....*....|....*....|
gi 206597474 390 HKEEPITSLGKEL---LLYP 406
Cdd:cd10406   81 YQCHSLKESFKQLdttLKYP 100
SH2_BCAR3 cd10337
Src homology 2 (SH2) domain in the Breast Cancer Anti-estrogen Resistance protein 3; BCAR3 is ...
313-416 2.34e-03

Src homology 2 (SH2) domain in the Breast Cancer Anti-estrogen Resistance protein 3; BCAR3 is part of a growing family of guanine nucleotide exchange factors is responsible for activation of Ras-family GTPases, including Sos1 and 2, GRF1 and 2, CalDAG-GEF/GRP1-4, C3G, cAMP-GEF/Epac 1 and 2, PDZ-GEFs, MR-GEF, RalGDS family members, RalGPS, RasGEF, Smg GDS, and phospholipase C(epsilon). 12102558 21262352 BCAR3 binds to the carboxy-terminus of BCAR1/p130Cas, a focal adhesion adapter protein. Over expression of BCAR1 (p130Cas) and BCAR3 induces estrogen independent growth in normally estrogen-dependent cell lines. They have been linked to resistance to anti-estrogens in breast cancer, Rac activation, and cell motility, though the BCAR3/p130Cas complex is not required for this activity in BCAR3. Many BCAR3-mediated signaling events in epithelial and mesenchymal cells are independent of p130Cas association. Structurally these proteins contain a single SH2 domain upstream of their RasGEF domain, which is responsible for the ability of BCAR3 to enhance p130Cas over-expression-induced migration. 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: 198200 [Multi-domain]  Cd Length: 136  Bit Score: 38.08  E-value: 2.34e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474 313 APWFHGILTLKKANELLstGVPGSFLIRVSEKIKG-YALSYLSEEGCKHFLI------DASANSYSFLGVDQLQHATLAD 385
Cdd:cd10337    6 HAWYHGRIPRQVAESLV--QREGDFLVRDSLSSPGdYVLTCRWKGQPLHFKInrvvlrPSEAYTRVQYQFEDEQFDSIPA 83
                         90       100       110
                 ....*....|....*....|....*....|...
gi 206597474 386 LVEYH--KEEPITSLGKELLLYPCGQQDKLPDY 416
Cdd:cd10337   84 LVHFYvgNRRPISQASGAIISRPVNRTVPLRCL 116
SH2_C-SH2_Syk_like cd10401
C-terminal Src homology 2 (SH2) domain found in Spleen tyrosine kinase (Syk) proteins; ZAP-70 ...
314-394 2.81e-03

C-terminal Src homology 2 (SH2) domain found in Spleen tyrosine kinase (Syk) proteins; ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the C-terminus SH2 domains of Syk. 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: 198264  Cd Length: 99  Bit Score: 37.18  E-value: 2.81e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474 314 PWFHGILTLKKANELLSTG--VPGSFLIRVSEKIKGYALSYLSEEGCKHFLIDASANSYsfLGV-DQLQHATLADLVEYH 390
Cdd:cd10401    4 PWFHGKISREESEQILLIGskTNGKFLIRERDNNGSYALCLLHDGKVLHYRIDKDKTGK--LSIpDGKKFDTLWQLVEHY 81

                 ....
gi 206597474 391 KEEP 394
Cdd:cd10401   82 SYKP 85
SH2_Tec_Btk cd10397
Src homology 2 (SH2) domain found in Tec protein, Bruton's tyrosine kinase (Btk); A member of ...
308-391 4.01e-03

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: 36.74  E-value: 4.01e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474 308 NSDTIAPWFHGILTLKKANELLST-GVPGSFLIRVSEKIKGYALSYLSEEG------CKHFLIDASANSYSFLGVDQLqH 380
Cdd:cd10397    1 DSLEMYEWYSKNMTRSQAEQLLKQeGKEGGFIVRDSSKAGKYTVSVFAKSAgdpqgvIRHYVVCSTPQSQYYLAEKHL-F 79
                         90
                 ....*....|.
gi 206597474 381 ATLADLVEYHK 391
Cdd:cd10397   80 STIPELINYHQ 90
SH2_nSH2_p85_like cd09942
N-terminal Src homology 2 (nSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
313-406 4.56e-03

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


Pssm-ID: 198195  Cd Length: 110  Bit Score: 36.53  E-value: 4.56e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474 313 APWFHGILTLKKANELLSTGVPGSFLIRVSEKIKG-YALSyLSEEGC-KHFLIDASANSYSFlgVDQLQHATLADLVEYH 390
Cdd:cd09942    7 AEWYWGDISREEVNEKMRDTPDGTFLVRDASTMKGdYTLT-LRKGGNnKLIKIFHRDGKYGF--SDPLTFNSVVELINYY 83
                         90
                 ....*....|....*....
gi 206597474 391 KEEPITSLGKEL---LLYP 406
Cdd:cd09942   84 RNNSLAEYNRKLdvkLLYP 102
PTZ00121 PTZ00121
MAEBL; Provisional
95-242 5.81e-03

MAEBL; Provisional


Pssm-ID: 173412 [Multi-domain]  Cd Length: 2084  Bit Score: 39.35  E-value: 5.81e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474   95 DEILAEREHLRAAKDSELRKTQSLELANSLKIKSQncdlQAMKKTEPQNVTRKAASEEASGQGPRAIPTRKDDKAQTKPV 174
Cdd:PTZ00121 1305 DEAKKKAEEAKKADEAKKKAEEAKKKADAAKKKAE----EAKKAAEAAKAEAEAAADEAEAAEEKAEAAEKKKEEAKKKA 1380
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474  175 KE--KDHEEMKQTEDEKTKQIYKSWKEDSEWQASLRKSKAADEKRRSLAKQAREDYKRLSQRGRSGDGLQ 242
Cdd:PTZ00121 1381 DAakKKAEEKKKADEAKKKAEEDKKKADELKKAAAAKKKADEAKKKAEEKKKADEAKKKAEEAKKADEAK 1450
SH2_Vav_family cd09940
Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several ...
314-392 7.22e-03

Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, Vav2 and Vav3 are more ubiquitously expressed. The members here include insect and amphibian Vavs. 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: 198193  Cd Length: 102  Bit Score: 35.73  E-value: 7.22e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 206597474 314 PWFHGILTLKKANELLSTGVPGSFLIRVSEK-IKGYALSYLSEEGCKHFLIDASANSYSFLGVDQLqHATLADLVEYHKE 392
Cdd:cd09940    6 LWFVGEMERDTAENRLENRPDGTYLVRVRPQgETQYALSIKYNGDVKHMKIEQRSDGLYYLSESRH-FKSLVELVNYYER 84
 
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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