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Conserved domains on  [gi|15292417|gb|AAK93477|]
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LP07668p [Drosophila melanogaster]

Protein Classification

SH2 domain-containing protein( domain architecture ID 10074561)

SH2 (Src homology 2) domain-containing protein may act as an intracellular signal-transducing protein

CATH:  3.30.505.10
Gene Ontology:  GO:0007165|GO:0035591|GO:0005515
SCOP:  4001650

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
SH2 cd00173
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...
248-325 1.21e-16

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


:

Pssm-ID: 198173 [Multi-domain]  Cd Length: 79  Bit Score: 74.03  E-value: 1.21e-16
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 15292417 248 PWYQPRITAKAALEHLQQATPGSFLLRRSTPRHFELVLRL-ERNNKVKTYPVQSTRNQMYRLKGAKKQFTSLKALITHH 325
Cdd:cd00173   1 PWFHGSISREEAERLLRGKPDGTFLVRESSSEPGDYVLSVrSGDGKVKHYLIERNEGGYYLLGGSGRTFPSLPELVEHY 79
 
Name Accession Description Interval E-value
SH2 cd00173
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...
248-325 1.21e-16

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


Pssm-ID: 198173 [Multi-domain]  Cd Length: 79  Bit Score: 74.03  E-value: 1.21e-16
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 15292417 248 PWYQPRITAKAALEHLQQATPGSFLLRRSTPRHFELVLRL-ERNNKVKTYPVQSTRNQMYRLKGAKKQFTSLKALITHH 325
Cdd:cd00173   1 PWFHGSISREEAERLLRGKPDGTFLVRESSSEPGDYVLSVrSGDGKVKHYLIERNEGGYYLLGGSGRTFPSLPELVEHY 79
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
247-329 3.54e-14

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


Pssm-ID: 214585 [Multi-domain]  Cd Length: 84  Bit Score: 67.25  E-value: 3.54e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15292417    247 CPWYQPRITAKAALEHLQQATPGSFLLRRS--TPRHFELVLRleRNNKVKTYPVQSTRNQMYRLKGaKKQFTSLKALITH 324
Cdd:smart00252   1 QPWYHGFISREEAEKLLKNEGDGDFLVRDSesSPGDYVLSVR--VKGKVKHYRIRRNEDGKFYLEG-GRKFPSLVELVEH 77

                   ....*
gi 15292417    325 HSVMA 329
Cdd:smart00252  78 YQKNS 82
SH2 pfam00017
SH2 domain;
249-325 5.07e-09

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 52.60  E-value: 5.07e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15292417   249 WYQPRITAKAALEHLQQA-TPGSFLLR--RSTPRHFELVLRleRNNKVKTYPVQSTRNQMYRLKGAKKqFTSLKALITHH 325
Cdd:pfam00017   1 WYHGKISRQEAERLLLNGkPDGTFLVResESTPGGYTLSVR--DDGKVKHYKIQSTDNGGYYISGGVK-FSSLAELVEHY 77
 
Name Accession Description Interval E-value
SH2 cd00173
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...
248-325 1.21e-16

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


Pssm-ID: 198173 [Multi-domain]  Cd Length: 79  Bit Score: 74.03  E-value: 1.21e-16
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 15292417 248 PWYQPRITAKAALEHLQQATPGSFLLRRSTPRHFELVLRL-ERNNKVKTYPVQSTRNQMYRLKGAKKQFTSLKALITHH 325
Cdd:cd00173   1 PWFHGSISREEAERLLRGKPDGTFLVRESSSEPGDYVLSVrSGDGKVKHYLIERNEGGYYLLGGSGRTFPSLPELVEHY 79
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
247-329 3.54e-14

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


Pssm-ID: 214585 [Multi-domain]  Cd Length: 84  Bit Score: 67.25  E-value: 3.54e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15292417    247 CPWYQPRITAKAALEHLQQATPGSFLLRRS--TPRHFELVLRleRNNKVKTYPVQSTRNQMYRLKGaKKQFTSLKALITH 324
Cdd:smart00252   1 QPWYHGFISREEAEKLLKNEGDGDFLVRDSesSPGDYVLSVR--VKGKVKHYRIRRNEDGKFYLEG-GRKFPSLVELVEH 77

                   ....*
gi 15292417    325 HSVMA 329
Cdd:smart00252  78 YQKNS 82
SH2_Tensin_like cd09927
Src homology 2 domain found in Tensin-like proteins; SH2 domain found in Tensin-like proteins. ...
249-339 2.12e-09

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


Pssm-ID: 198181 [Multi-domain]  Cd Length: 116  Bit Score: 54.74  E-value: 2.12e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15292417 249 WYQPRITAKAALEHLQQATPGSFLLRRST--PRHFELVLRLERN--NKVKTYPVQSTRNQMYR------------LKGAK 312
Cdd:cd09927   5 WYKPNISRDQAIALLKDKPPGTFLVRDSTtyKGAYGLAVKVATPppGVNPFEAKGDPESELVRhfliepspkgvkLKGCP 84
                        90       100
                ....*....|....*....|....*....
gi 15292417 313 KQ--FTSLKALITHHSVMAEQLPLVLDMP 339
Cdd:cd09927  85 NEpvFGSLSALVYQHSITPLALPCKLRIP 113
SH2_N-SH2_Zap70_Syk_like cd09938
N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
248-347 3.44e-09

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: 53.94  E-value: 3.44e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15292417 248 PWYQPRITAKAALEHLQQAT--PGSFLLRRSTPRHFELVLRLERNNKVKTYPVQSTRNQMYRLKGAkKQFTSLKALITHH 325
Cdd:cd09938   2 PFFYGSITREEAEEYLKLAGmsDGLFLLRQSLRSLGGYVLSVCHGRKFHHYTIERQLNGTYAIAGG-KAHCGPAELCEYH 80
                        90       100
                ....*....|....*....|...
gi 15292417 326 SVMAEQLPLVLDMPRERHV-VKP 347
Cdd:cd09938  81 STDLDGLVCLLRKPCNRPPgVEP 103
SH2 pfam00017
SH2 domain;
249-325 5.07e-09

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 52.60  E-value: 5.07e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15292417   249 WYQPRITAKAALEHLQQA-TPGSFLLR--RSTPRHFELVLRleRNNKVKTYPVQSTRNQMYRLKGAKKqFTSLKALITHH 325
Cdd:pfam00017   1 WYHGKISRQEAERLLLNGkPDGTFLVResESTPGGYTLSVR--DDGKVKHYKIQSTDNGGYYISGGVK-FSSLAELVEHY 77
SH2_Fps_family cd10361
Src homology 2 (SH2) domain found in feline sarcoma, Fujinami poultry sarcoma, and fes-related ...
247-334 4.28e-08

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: 50.22  E-value: 4.28e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15292417 247 CPWYQ---PRITAKAALEHlqqatPGSFLLRRSTPRHF---ELVLRLERNNKVKTYPVQSTRNQMYRLKGakKQFTSLKA 320
Cdd:cd10361   6 EPYYHgllPREDAEELLKN-----DGDFLVRKTEPKGGgkrKLVLSVRWDGKIRHFVINRDDGGKYYIEG--KSFKSISE 78
                        90
                ....*....|....
gi 15292417 321 LITHHsvMAEQLPL 334
Cdd:cd10361  79 LINYY--QKTKEPI 90
SH2_Cterm_shark_like cd10348
C-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
249-332 4.52e-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: 47.42  E-value: 4.52e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15292417 249 WYQPRITAKAALEHLQQA--TPGSFLLRRSTPRHFELVLRLERNNKVKTYPVQSTRNQMYRLKGAkKQFTSLKALITHHS 326
Cdd:cd10348   2 WLHGALDRNEAVEILKQKadADGSFLVRYSRRRPGGYVLTLVYENHVYHFEIQNRDDKWFYIDDG-PYFESLEHLIEHYT 80

                ....*.
gi 15292417 327 VMAEQL 332
Cdd:cd10348  81 QFADGL 86
SH2_ABL cd09935
Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ...
248-339 9.86e-07

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: 46.61  E-value: 9.86e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15292417 248 PWYQPRITAKAALEHLQQATPGSFLLRRS--TPRHFELVLRLErnNKVKTYPVQSTRNQMYRLKGAKKqFTSLKALITHH 325
Cdd:cd09935   4 SWYHGPISRNAAEYLLSSGINGSFLVRESesSPGQYSISLRYD--GRVYHYRISEDSDGKVYVTQEHR-FNTLAELVHHH 80
                        90
                ....*....|....
gi 15292417 326 SVMAEQLPLVLDMP 339
Cdd:cd09935  81 SKNADGLITTLRYP 94
SH2_RIN_family cd10339
Src homology 2 (SH2) domain found in Ras and Rab interactor (RIN)-family; The RIN (AKA Ras ...
244-334 5.75e-06

Src homology 2 (SH2) domain found in Ras and Rab interactor (RIN)-family; The RIN (AKA Ras interaction/interference) family is composed of RIN1, RIN2 and RIN3. These proteins have multifunctional domains including SH2 and proline-rich (PR) domains in the N-terminal region, and RIN-family homology (RH), VPS9 and Ras-association (RA) domains in the C-terminal region. RIN proteins function as Rab5-GEFs, and RIN3 specifically functions as a Rab31-GEF. 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: 198202  Cd Length: 101  Bit Score: 44.45  E-value: 5.75e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15292417 244 LLACP-WYQPRITAKAALEHLQQATPGSFLLRRSTPRHFE-LVLRL---ERNNKVKTYPVQSTRNQMYrLKGAKKQFTSL 318
Cdd:cd10339   6 LLTRPvWLQLQLNAAEAAHMLQTEPPGTFLVRKSNTRQCQvLCMRLpeaSGPAFVSEHYIKESPGGVS-LEGSELMFPDL 84
                        90
                ....*....|....*.
gi 15292417 319 KALITHHSVMAEQLPL 334
Cdd:cd10339  85 FRLIAFYCHSRDILPF 100
SH2_Cterm_RasGAP cd10354
C-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP ...
248-325 3.10e-05

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


Pssm-ID: 198217  Cd Length: 77  Bit Score: 41.64  E-value: 3.10e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15292417 248 PWYQPRITAKAALEHL-QQATPGSFLLRRS--TPRHFELVLRLerNNKVKTYPVQSTRNQMYRLKGakKQFTSLKALITH 324
Cdd:cd10354   1 IWFHGKISREEAYNMLvKVGGPGSFLVRESdnTPGDYSLSFRV--NEGIKHFKIIPTGNNQFMMGG--RYFSSLDDVIDR 76

                .
gi 15292417 325 H 325
Cdd:cd10354  77 Y 77
SH2_RIN1 cd10393
Src homology 2 (SH2) domain found in Ras and Rab interactor 1 (RIN1)-like proteins; RIN1, a ...
249-334 1.38e-04

Src homology 2 (SH2) domain found in Ras and Rab interactor 1 (RIN1)-like proteins; RIN1, a member of the RIN (AKA Ras interaction/interference) family, have multifunctional domains including SH2 and proline-rich (PR) domains in the N-terminal region, and RIN-family homology (RH), VPS9 and Ras-association (RA) domains in the C-terminal region. RIN proteins function as Rab5-GEFs. Previous studies showed that RIN1 interacts with EGF receptors via its SH2 domain and regulates trafficking and degradation of EGF receptors via its interaction with STAM, indicating a vital role for RIN1 in regulating endosomal trafficking of receptor tyrosine kinases (RTKs). RIN1 was first identified as a Ras-binding protein that suppresses the activated RAS2 allele in S. cerevisiae. RIN1 binds to the activated Ras through its carboxyl-terminal domain and this Ras-binding domain also binds to 14-3-3 proteins as Raf-1 does. The SH2 domain of RIN1 are thought to interact with the phosphotyrosine-containing proteins, but the physiological partners for this domain are unknown. The proline-rich domain in RIN1 is similar to the consensus SH3 binding regions. 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: 198256  Cd Length: 101  Bit Score: 40.61  E-value: 1.38e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15292417 249 WYQPRITAKAALEHLQQATPGSFLLRRSTPRHFE-LVLRLERNNK---VKTYPVQSTRNQMYrLKGAKKQFTSLKALITH 324
Cdd:cd10393  12 WLQLRANAAAALHVLRTEPPGTFLVRKSNTRQCQaLCVRLPEASGpsfVSSHYIQESPGGVS-LEGSELTFPDLVQLICA 90
                        90
                ....*....|
gi 15292417 325 HSVMAEQLPL 334
Cdd:cd10393  91 YCHTRDILLL 100
SH2_Src_Src42 cd10370
Src homology 2 (SH2) domain found in the Src oncogene at 42A (Src42); Src42 is a member of the ...
248-339 1.39e-04

Src homology 2 (SH2) domain found in the Src oncogene at 42A (Src42); Src42 is a member of the Src non-receptor type tyrosine kinase family of proteins. The integration of receptor tyrosine kinase-induced RAS and Src42 signals by Connector eNhancer of KSR (CNK) as a two-component input is essential for RAF activation in Drosophila. Src42 is present in a wide variety of organisms including: California sea hare, pea aphid, yellow fever mosquito, honey bee, Panamanian leafcutter ant, and sea urchin. Src42 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 C-terminal tail. 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: 198233  Cd Length: 96  Bit Score: 40.57  E-value: 1.39e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15292417 248 PWY---QPRITAKAALEHLQQATpGSFLLRRSTPRHFELVLRLERNNKVKTYPVQSTRNQMYRLkGAKKQFTSLKALITH 324
Cdd:cd10370   4 PWYfgkIKRIEAEKKLLLPENEH-GAFLIRDSESRHNDYSLSVRDGDTVKHYRIRQLDEGGFFI-ARRTTFRTLQELVEH 81
                        90
                ....*....|....*
gi 15292417 325 HSVMAEQLPLVLDMP 339
Cdd:cd10370  82 YSKDSDGLCVNLRKP 96
SH2_N-SH2_SHP_like cd10340
N-terminal Src homology 2 (N-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
249-332 2.90e-04

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: 39.69  E-value: 2.90e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15292417 249 WYQPRITAKAALEHLQQ-ATPGSFLLR--RSTPRHFELVLRleRNNKVKTYPVQSTrNQMYRLKGAKKqFTSLKALITHH 325
Cdd:cd10340   2 WFHPVISGIEAENLLKTrGVDGSFLARpsKSNPGDFTLSVR--RGDEVTHIKIQNT-GDYYDLYGGEK-FATLSELVQYY 77

                ....*..
gi 15292417 326 SVMAEQL 332
Cdd:cd10340  78 MEQHGQL 84
SH2_SH2D7 cd10417
Src homology 2 domain found in the SH2 domain containing protein 7 (SH2D7); SH2D7 contains a ...
248-326 7.98e-04

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: 38.34  E-value: 7.98e-04
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 15292417 248 PWYQPRITAKAALEHLQQATPGSFLLRRSTpRHFELVLRLERNNKVKTYPVQSTRNQMYRLKGAKKQFTSLKALITHHS 326
Cdd:cd10417   8 PWFHGFITRKQTEQLLRDKALGSFLIRLSD-RATGYILSYRGSDRCRHFVINQLRNRRYLISGDTSSHSTLAELVRHYQ 85
SH2_C-SH2_SHP_like cd09931
C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
249-326 1.05e-03

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: 38.03  E-value: 1.05e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15292417 249 WYQPRITAKAALEHLQ-QATPGSFLLR--RSTPRHFELVLRLErNNKVKTYPVqstRNQMYRLK-GAKKQFTSLKALITH 324
Cdd:cd09931   2 WFHGHLSGKEAEKLLLeKGKPGSFLVResQSKPGDFVLSVRTD-DDKVTHIMI---RCQGGKYDvGGGEEFDSLTDLVEH 77

                ..
gi 15292417 325 HS 326
Cdd:cd09931  78 YK 79
SH2_CRK_like cd09926
Src homology 2 domain found in cancer-related signaling adaptor protein CRK; SH2 domain in the ...
249-342 1.90e-03

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


Pssm-ID: 198180 [Multi-domain]  Cd Length: 106  Bit Score: 37.45  E-value: 1.90e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15292417 249 WYQPRITAKAALEHLQQATPGSFLLRRSTPRHFELVLRLERNNKVKTYPVQSTRNQMY---RLKGAKKQFTSLKALITHH 325
Cdd:cd09926   9 WYFGPMSRQEAQELLQGQRHGVFLVRDSSTIPGDYVLSVSENSRVSHYIINSLGQPAPnqsRYRIGDQEFDDLPALLEFY 88
                        90
                ....*....|....*...
gi 15292417 326 SVM-AEQLPLVLDMPRER 342
Cdd:cd09926  89 KLHyLDTTTLIEPASRGR 106
SH2_RIN3 cd10395
Src homology 2 (SH2) domain found in Ras and Rab interactor 3 (RIN3)-like proteins; RIN3, a ...
247-333 2.46e-03

Src homology 2 (SH2) domain found in Ras and Rab interactor 3 (RIN3)-like proteins; RIN3, a member of the RIN (AKA Ras interaction/interference) family, have multifunctional domains including SH2 and proline-rich (PR) domains in the N-terminal region, and RIN-family homology (RH), VPS9 and Ras-association (RA) domains in the C-terminal region. RIN proteins function as Rab5-GEFs. RIN3 stimulated the formation of GTP-bound Rab31, a Rab5-subfamily GTPase, and formed enlarged vesicles and tubular structures, where it colocalized with Rab31. Transferrin appeared to be transported partly through the RIN3-positive vesicles to early endosomes. RIN3 interacts via its Pro-rich domain with amphiphysin II, which contains SH3 domain and participates in receptor-mediated endocytosis. RIN3, a Rab5 and Rab31 GEF, plays an important role in the transport pathway from plasma membrane to early endosomes. Mutations in the region between the SH2 and RH domain of RIN3 specifically abolished its GEF action on Rab31, but not Rab5. RIN3 was also found to partially translocate the cation-dependent mannose 6-phosphate receptor from the trans-Golgi network to peripheral vesicles and that this is dependent on its Rab31-GEF activity. These data indicate that RIN3 specifically acts as a GEF for Rab31. 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: 198258  Cd Length: 101  Bit Score: 37.06  E-value: 2.46e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15292417 247 CP-WYQPRITAKAALEHLQQATPGSFLLRR-STPRHFELVLRLERNN---KVKTYPVQSTRNQMYrLKGAKKQFTSLKAL 321
Cdd:cd10395   9 CPvWLQLGMNQAEAARILHKEVAGMFLVRRdSNSKQMVLCVHFPSNEssaEVLEYPIKEEKSILY-LEGSVLVFEDIFKL 87
                        90
                ....*....|..
gi 15292417 322 ITHHSVMAEQLP 333
Cdd:cd10395  88 IAFYCVSRDLLP 99
SH2_SOCS2 cd10383
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 ...
249-330 2.88e-03

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


Pssm-ID: 198246  Cd Length: 103  Bit Score: 36.78  E-value: 2.88e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15292417 249 WYQPRITAKAALEHLQQATPGSFLLRRSTPRHFELV-----------LRLE-RNNKVKTYPVQSTRNQMyrlkgakKQFT 316
Cdd:cd10383   9 WYWGSMTVNEAKEKLQDAPEGTFLVRDSSHSDYLLTisvktsagptnLRIEyQDGKFRLDSIICVKSKL-------KQFD 81
                        90
                ....*....|....
gi 15292417 317 SLKALITHHSVMAE 330
Cdd:cd10383  82 SVVHLIEYYVQMCK 95
SH2_Src_Lck cd10362
Src homology 2 (SH2) domain in lymphocyte cell kinase (Lck); Lck is a member of the Src ...
248-339 2.99e-03

Src homology 2 (SH2) domain in lymphocyte cell kinase (Lck); Lck is a member of the Src non-receptor type tyrosine kinase family of proteins. It is expressed in the brain, T-cells, and NK cells. The unique domain of Lck mediates its interaction with two T-cell surface molecules, CD4 and CD8. It associates with their cytoplasmic tails on CD4 T helper cells and CD8 cytotoxic T cells to assist signaling from the T cell receptor (TCR) complex. When the T cell receptor is engaged by the specific antigen presented by MHC, Lck phosphorylase the intracellular chains of the CD3 and zeta-chains of the TCR complex, allowing ZAP-70 to bind them. Lck then phosphorylates and activates ZAP-70, which in turn phosphorylates Linker of Activated T cells (LAT), a transmembrane protein that serves as a docking site for proteins including: Shc-Grb2-SOS, PI3K, and phospholipase C (PLC). The tyrosine phosphorylation cascade culminates in the intracellular mobilization of a calcium ions and activation of important signaling cascades within the lymphocyte, including the Ras-MEK-ERK pathway, which goes on to activate certain transcription factors such as NFAT, NF-kappaB, and AP-1. These transcription factors regulate the production cytokines such as Interleukin-2 that promote long-term proliferation and differentiation of the activated lymphocytes. The N-terminal tail of Lck is myristoylated and palmitoylated and it tethers the protein to the plasma membrane of the cell. Lck also contains a SH3 domain, a SH2 domain, and a C-terminal tyrosine kinase domain. Lck has 2 phosphorylation sites, the first an autophosphorylation site that is linked to activation of the protein and the second which is phosphorylated by Csk, which inhibits it. Lck is also inhibited by SHP-1 dephosphorylation and by Cbl ubiquitin ligase, which is part of the ubiquitin-mediated pathway. 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: 198225  Cd Length: 101  Bit Score: 36.77  E-value: 2.99e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15292417 248 PWYQPRITAKAALEHL--QQATPGSFLLRRS--TPRHFELVLR-LERN--NKVKTYPVQSTRNQMYRLKgAKKQFTSLKA 320
Cdd:cd10362   4 PWFFKNLSRNDAERQLlaPGNTHGSFLIRESetTAGSFSLSVRdFDQNqgEVVKHYKIRNLDNGGFYIS-PRITFPGLHE 82
                        90
                ....*....|....*....
gi 15292417 321 LITHHSVMAEQLPLVLDMP 339
Cdd:cd10362  83 LVRHYTNASDGLCTRLSRP 101
SH2_csk_like cd09937
Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal ...
248-326 9.35e-03

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


Pssm-ID: 198190  Cd Length: 98  Bit Score: 35.34  E-value: 9.35e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15292417 248 PWYQPRITAKAALEHLQQATPGSFLLRRST--PRHFELVLRLERnnKVKTYPVQSTRNQM------YrlkgakkqFTSLK 319
Cdd:cd09937   4 PWFHGKISREEAERLLQPPEDGLFLVRESTnyPGDYTLCVSFEG--KVEHYRVIYRNGKLtideeeY--------FENLI 73

                ....*..
gi 15292417 320 ALITHHS 326
Cdd:cd09937  74 QLVEHYT 80
SH2_Jak_family cd09921
Src homology 2 (SH2) domain in the Janus kinase (Jak) family; The Janus kinases (Jak) are a ...
268-324 9.38e-03

Src homology 2 (SH2) domain in the Janus kinase (Jak) family; The Janus kinases (Jak) are a family of 4 non-receptor tyrosine kinases (Jak1, Jak2, Jak3, Tyk2) which respond to cytokine or growth factor receptor activation. To transduce cytokine signaling, a series of conformational changes occur in the receptor-Jak complex upon extracellular ligand binding. This results in trans-activation of the receptor-associated Jaks followed by phosphorylation of receptor tail tyrosine sites. The Signal Transducers and Activators of Transcription (STAT) are then recruited to the receptor tail, become phosphorylated and translocate to the nucleus to regulate transcription. Jaks have four domains: the pseudokinase domain, the catalytic tyrosine kinase domain, the FERM (band four-point-one, ezrin, radixin, and moesin) domain, and the SH2 (Src Homology-2) domain. The Jak kinases are regulated by several enzymatic and non-enzymatic mechanisms. First, the Jak kinase domain is regulated by phosphorylation of the activation loop which is associated with the catalytically competent kinase conformation and is distinct from the inactive kinase conformation. Second, the pseudokinase domain directly modulates Jak catalytic activity with the FERM domain maintaining an active state. Third, the suppressor of cytokine signaling (SOCS) family and tyrosine phosphatases directly regulate Jak activity. Dysregulation of Jak activity can manifest as either a reduction or an increase in kinase activity resulting in immunodeficiency, inflammatory diseases, hematological defects, autoimmune and myeloproliferative disorders, and susceptibility to infection. Altered Jak regulation occurs by many mechanisms, including: gene translocations, somatic or inherited point mutations, receptor mutations, and alterations in the activity of Jak regulators such as SOCS or phosphatases. 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: 198177  Cd Length: 97  Bit Score: 35.34  E-value: 9.38e-03
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 15292417 268 PGSFLLRRStPRHF-----ELVLRLERNNKVKTYPVQSTRNQMYRLKGAKKQFTSLKALITH 324
Cdd:cd09921  35 PGSYILRES-ETEYdtyyiDVCVKDGSRFQTKTFKIEKKEGGVFFLDGDSREYPSLRDLLNS 95
 
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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