Concanavalin A-like lectin/glucanases superfamily; This domain belongs to the Concanavalin A-like lectin/glucanases superfamily.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 334182641   20 VDVEVENKAFETFSLCFWVYLLDSTTYPSAIIrqinlfcelgekvhSDMSVSAPFLVLDENKKMMLLpltllhreapdpV 99
Cdd:pfam13385   7 VTLPDALLPTSDFTVSAWVKPDSLPGWARAII--------------SSSGGGGYSLGLDGDGRLRFA------------V 60

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 334182641  100 NTSSwTEVPNVSTTAKFPLQKWVHVGCEVSRNYMRLYICGELVGEQVLTSLMTNGTNSDcarkislFSVGGDGYSVQGF 178
Cdd:pfam13385  61 NGGN-GGWDTVTSGASVPLGQWTHVAVTYDGGTLRLYVNGVLVGSSTLTGGPPPGTGGP-------LYIGRSPGGDDYF 131

Concanavalin A-like lectin/glucanases superfamily; This domain belongs to the Concanavalin A-like lectin/glucanases superfamily.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 334182641   20 VDVEVENKAFETFSLCFWVYLLDSTTYPSAIIrqinlfcelgekvhSDMSVSAPFLVLDENKKMMLLpltllhreapdpV 99
Cdd:pfam13385   7 VTLPDALLPTSDFTVSAWVKPDSLPGWARAII--------------SSSGGGGYSLGLDGDGRLRFA------------V 60

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 334182641  100 NTSSwTEVPNVSTTAKFPLQKWVHVGCEVSRNYMRLYICGELVGEQVLTSLMTNGTNSDcarkislFSVGGDGYSVQGF 178
Cdd:pfam13385  61 NGGN-GGWDTVTSGASVPLGQWTHVAVTYDGGTLRLYVNGVLVGSSTLTGGPPPGTGGP-------LYIGRSPGGDDYF 131

SH2 domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 334182641  557 WIEGFVTKEEAERSLQNQVP-GTFILRFptSRSWPhpdaGSVVVTyVGHDLVIHH 610
Cdd:pfam00017   1 WYHGKISRQEAERLLLNGKPdGTFLVRE--SESTP----GGYTLS-VRDDGKVKH 48

Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) family; STAT proteins mediate the signaling of cytokines and a number of growth factors from the receptors of these extracellular signaling molecules to the cell nucleus. STATs are specifically phosphorylated by receptor-associated Janus kinases, receptor tyrosine kinases, or cytoplasmic tyrosine kinases. The phosphorylated STAT molecules dimerize by reciprocal binding of their SH2 domains to the phosphotyrosine residues. These dimeric STATs translocate into the nucleus, bind to specific DNA sequences, and regulate the transcription of their target genes. However there are a number of unphosphorylated STATs that travel between the cytoplasm and nucleus and some STATs that exist as dimers in unstimulated cells that can exert biological functions independent of being activated by a receptor. There are seven mammalian STAT family members which have been identified: STAT1, STAT2, STAT3, STAT4, STAT5 (STAT5A and STAT5B), and STAT6. There are 6 conserved domains in STAT: N-terminal domain (NTD), coiled-coil domain (CCD), DNA-binding domain (DBD), alpha-helical linker domain (LD), SH2 domain, and transactivation domain (TAD). NTD is involved in dimerization of unphosphorylated STATs monomers and for the tetramerization between STAT1, STAT3, STAT4 and STAT5 on promoters with two or more tandem STAT binding sites. It also plays a role in promoting interactions with transcriptional co-activators such as CREB binding protein (CBP)/p300, as well as being important for nuclear import and deactivation of STATs involving tyrosine de-phosphorylation. The CCD interacts with other proteins, such as IFN regulatory protein 9 (IRF-9/p48) with STAT1 and c-JUN with STAT3 and is also thought to participate in the negative regulation of these proteins. Distinct genes are bound to STATs via their DBD domain. This domain is also involved in nuclear translocation of activated STAT1 and STAT3 phosphorylated dimers upon cytokine stimulation. LD links the DNA-binding and SH2 domains and is important for the transcriptional activation of STAT1 in response to IFN-gamma. It also plays a role in protein-protein interactions and has also been implicated in the constitutive nucleocytoplasmic shuttling of unphosphorylated STATs in resting cells. The SH2 domain is necessary for receptor association and tyrosine phosphodimer formation. Residues within this domain may be particularly important for some cellular functions mediated by the STATs as well as residues adjacent to this domain. The TAD interacts with several proteins, namely minichromosome maintenance complex component 5 (MCM5), breast cancer 1 (BRCA1) and CBP/p300. TAD also contains a modulatory phosphorylation site that regulates STAT activity and is necessary for maximal transcription of a number of target genes. The conserved tyrosine residue present in the C-terminus is crucial for dimerization via interaction with the SH2 domain upon the interaction of the ligand with the receptor. STAT activation by tyrosine phosphorylation also determines nuclear import and retention, DNA binding to specific DNA elements in the promoters of responsive genes, and transcriptional activation of STAT dimers. In addition to the SH2 domain there is a coiled-coil domain, a DNA binding domain, and a transactivation domain in the STAT 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 334182641 533 WLFPVASAVSRGLiNGMWRSAspkWIEGFVTKEEAERSLQNQVPGTFILRFPTSrswphpDAGSVVVTYVGHDLVIHHRL 612
Cdd:cd09919    1 WFFAIMLLTKRHL-LKLWQDG---LIMGFISKEEAEDLLKKKPPGTFLLRFSDS------ELGGITIAWVNEDPDGQSQV 70

                         90       100
                 ....*....|....*....|....*.
gi 334182641 613 LTINHicdsserYTdAKQLQDMLLAE 638
Cdd:cd09919   71 IHLQP-------YT-KKDLDIRSLAD 88

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 334182641 553 ASPKWIEGFVTKEEAERSLQNQVPGTFILRFPTSrswphpdAGSVVVTYVGHDLVIHHRLLTI---NHIC---DSSEryt 626
Cdd:cd10416    5 AAPAWFHGFITRREAERLLEPKPQGCYLVRFSES-------AVTFVLTYRSRTCCRHFLLAQLrdgRHVVlgeDSAH--- 74

                         90       100
                 ....*....|....*....|....
gi 334182641 627 daKQLQDMLL--AEPELSRLGRII 648
Cdd:cd10416   75 --ARLQDLLLhyTAHPLSPYGETL 96

Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) 3 proteins; STAT3 encoded by this gene is a member of the STAT protein family. STAT3 mediates the expression of a variety of genes in response to cell stimuli, and plays a key role in many cellular processes such as cell growth and apoptosis. The small GTPase Rac1 regulates the activity of STAT3 and PIAS3 inhibits it. Three alternatively spliced transcript variants encoding distinct isoforms have been described. STAT 3 activation is required for self-renewal of embryonic stem cells (ESCs) and is essential for the differentiation of the TH17 helper T cells. Mutations in the STAT3 gene result in Hyperimmunoglobulin E syndrome and human cancers. STAT3 has been shown to interact with Androgen receptor, C-jun, ELP2, EP300, Epidermal growth factor receptor, Glucocorticoid receptor, HIF1A, Janus kinase 1, KHDRBS1, Mammalian target of rapamycin, MyoD, NDUFA13, NFKB1, Nuclear receptor coactivator 1, Promyelocytic leukemia protein, RAC1, RELA, RET proto-oncogene, RPA2, Src, STAT1, and TRIP10. STAT proteins mediate the signaling of cytokines and a number of growth factors from the receptors of these extracellular signaling molecules to the cell nucleus. STATs are specifically phosphorylated by receptor-associated Janus kinases, receptor tyrosine kinases, or cytoplasmic tyrosine kinases. The phosphorylated STAT molecules dimerize by reciprocal binding of their SH2 domains to the phosphotyrosine residues. These dimeric STATs translocate into the nucleus, bind to specific DNA sequences, and regulate the transcription of their target genes. However there are a number of unphosphorylated STATs that travel between the cytoplasm and nucleus and some STATs that exist as dimers in unstimulated cells that can exert biological functions independent of being activated. There are seven mammalian STAT family members which have been identified: STAT1, STAT2, STAT3, STAT4, STAT5 (STAT5A and STAT5B), and STAT6. There are 6 conserved domains in STAT: N-terminal domain (NTD), coiled-coil domain (CCD), DNA-binding domain (DBD), alpha-helical linker domain (LD), SH2 domain, and transactivation domain (TAD). NTD is involved in dimerization of unphosphorylated STATs monomers and for the tetramerization between STAT1, STAT3, STAT4 and STAT5 on promoters with two or more tandem STAT binding sites. It also plays a role in promoting interactions with transcriptional co-activators such as CREB binding protein (CBP)/p300, as well as being important for nuclear import and deactivation of STATs involving tyrosine de-phosphorylation. CCD interacts with other proteins, such as IFN regulatory protein 9 (IRF-9/p48) with STAT1 and c-JUN with STAT3 and is also thought to participate in the negative regulation of these proteins. Distinct genes are bound to STATs via their DBD domain. This domain is also involved in nuclear translocation of activated STAT1 and STAT3 phosphorylated dimers upon cytokine stimulation. LD links the DNA-binding and SH2 domains and is important for the transcriptional activation of STAT1 in response to IFN-gamma. It also plays a role in protein-protein interactions and has also been implicated in the constitutive nucleocytoplasmic shuttling of unphosphorylated STATs in resting cells. The SH2 domain is necessary for receptor association and tyrosine phosphodimer formation. Residues within this domain may be particularly important for some cellular functions mediated by the STATs as well as residues adjacent to this domain. The TAD interacts with several proteins, namely minichromosome maintenance complex component 5 (MCM5), breast cancer 1 (BRCA1) and CBP/p300. TAD also contains a modulatory phosphorylation site that regulates STAT activity and is necessary for maximal transcription of a number of target genes. The conserved tyrosine residue present in the C-terminus is crucial for dimerization via interaction with the SH2 domain upon the interaction of the ligand with the receptor. STAT activation by tyrosine phosphorylation also determines nuclear import and retention, DNA binding to specific DNA elements in the promoters of responsive genes, and transcriptional activation of STAT dimers. In addition to the SH2 domain there is a coiled-coil domain, a DNA binding domain, and a transactivation domain in the STAT 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 334182641 529 TMWCWLFPVASAVSRGLInGMWRSAspkWIEGFVTKEEAERSLQNQVPGTFILRFPTSRSwphpdAGSVVVTYVGHDLVI 608
Cdd:cd10374    7 SFWVWLDNIIDLVKKYIL-ALWNEG---YIMGFISKERERAILSTKPPGTFLLRFSESSK-----EGGVTFTWVEKDISG 77

                         90       100       110
                 ....*....|....*....|....*....|
gi 334182641 609 HHRLltinhicDSSERYTDaKQLQDMLLAE 638
Cdd:cd10374   78 KTQI-------QSVEPYTK-QQLNNMSFAE 99

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.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 334182641   560 GFVTKEEAERSLQNQVPGTFILRFptSRSwphpDAGSVVVTYVGHDLVIH 609
Cdd:smart00252   6 GFISREEAEKLLKNEGDGDFLVRD--SES----SPGDYVLSVRVKGKVKH 49

Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) 4proteins; STAT4 mediate signals from the IL-12 receptors. STAT4 is mainly phosphorylated by IL-12-mediated signaling pathway in T cells. STAT4 expression is restricted in myeloid cells, thymus and testis. L-12 is the major cytokine that can activate STAT4, resulting in its tyrosine phosphorylation. The IL-12 receptor has two chains, termed IL-12R 1 and IL-12R 2, and ligand binding results in heterodimer formation and activation of the receptor associated JAK kinases, Jak2 and Tyk2. Phosphorylated STAT4 homo-dimerizes via its SH2 domain, and translocates into nucleus where it can recognize traditional N3 STAT target sequences in IL-12 responsive genes. STAT4 can also be phosphorylated in response to IFN-gamma stimulation through activation of Jak1 and Tyk2 in human. IL-17 can also activate STAT4 in human monocytic leukemia cell lines and IL-2 can induce Jak2 and Stat4 activation in NK cells but not in T cells. T helper 1 (Th1) cells produce IL-2 and IFNgamma, whereas Th2 cells secrete IL-4, IL-5, IL-6 and IL-13. Th1 cells are responsible for cell-mediated/inflammatory immunity and can enhance defenses against infectious agents and cancer, while Th2 cells are essential for humoral immunity and the clearance of parasitic antigens. The most potent factors that can promote Th1 and Th2 differentiation are the cytokines IL-12 and IL-4 respectively Although STAT4 is expressed both in Th1 and Th2 cells, STAT4 can only be phosphorylated by IL-12 which suggests that STAT4 plays an important role in Th1 cell function or development. STAT4 activation leads to Th1 differentiation, including the target genes of STAT4 such as ERM, a transcription factor that belongs to the Ets family of transcription factors. The expression of ERM is specifically induced by IL-12 in wild-type Th1 cells, but not in STAT4-deficient T cells. STAT proteins mediate the signaling of cytokines and a number of growth factors from the receptors of these extracellular signaling molecules to the cell nucleus. STATs are specifically phosphorylated by receptor-associated Janus kinases, receptor tyrosine kinases, or cytoplasmic tyrosine kinases. The phosphorylated STAT molecules dimerize by reciprocal binding of their SH2 domains to the phosphotyrosine residues. These dimeric STATs translocate into the nucleus, bind to specific DNA sequences, and regulate the transcription of their target genes. However there are a number of unphosphorylated STATs that travel between the cytoplasm and nucleus and some STATs that exist as dimers in unstimulated cells that can exert biological functions independent of being activated. There are seven mammalian STAT family members which have been identified: STAT1, STAT2, STAT3, STAT4, STAT5 (STAT5A and STAT5B), and STAT6. There are 6 conserved domains in STAT: N-terminal domain (NTD), coiled-coil domain (CCD), DNA-binding domain (DBD), alpha-helical linker domain (LD), SH2 domain, and transactivation domain (TAD). NTD is involved in dimerization of unphosphorylated STATs monomers and for the tetramerization between STAT1, STAT3, STAT4 and STAT5 on promoters with two or more tandem STAT binding sites. It also plays a role in promoting interactions with transcriptional co-activators such as CREB binding protein (CBP)/p300, as well as being important for nuclear import and deactivation of STATs involving tyrosine de-phosphorylation. CCD interacts with other proteins, such as IFN regulatory protein 9 (IRF-9/p48) with STAT1 and c-JUN with STAT3 and is also thought to participate in the negative regulation of these proteins. Distinct genes are bound to STATs via their DBD domain. This domain is also involved in nuclear translocation of activated STAT1 and STAT3 phosphorylated dimers upon cytokine stimulation. LD links the DNA-binding and SH2 domains and is important for the transcriptional activation of STAT1 in response to IFN-gamma. It also plays a role in protein-protein interactions and has also been implicated in the constitutive nucleocytoplasmic shuttling of unphosphorylated STATs in resting cells. The SH2 domain is necessary for receptor association and tyrosine phosphodimer formation. Residues within this domain may be particularly important for some cellular functions mediated by the STATs as well as residues adjacent to this domain. The TAD interacts with several proteins, namely minichromosome maintenance complex component 5 (MCM5), breast cancer 1 (BRCA1) and CBP/p300. TAD also contains a modulatory phosphorylation site that regulates STAT activity and is necessary for maximal transcription of a number of target genes. The conserved tyrosine residue present in the C-terminus is crucial for dimerization via interaction with the SH2 domain upon the interaction of the ligand with the receptor. STAT activation by tyrosine phosphorylation also determines nuclear import and retention, DNA binding to specific DNA elements in the promoters of responsive genes, and transcriptional activation of STAT dimers. In addition to the SH2 domain there is a coiled-coil domain, a DNA binding domain, and a transactivation domain in the STAT 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 334182641 555 PKWIE----GFVTKEEAERSLQNQVPGTFILRFPTSRswphpdAGSVVVTYVGH 604
Cdd:cd10375   15 PLWIDgyimGFVSKEKERLLLKDKMPGTFLLRFSESH------LGGITFTWVDQ 62

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 334182641 553 ASPKWIEGFVTKEEAERSLQNQVPGTFILRFPTSrswphpdAGSVVVTYVGHDLVIH 609
Cdd:cd10417    5 ALPPWFHGFITRKQTEQLLRDKALGSFLIRLSDR-------ATGYILSYRGSDRCRH 54