ID SH2B1_HUMAN Reviewed; 756 AA. AC Q9NRF2; A8K2R7; Q96FK3; Q96SX3; Q9NRF1; Q9NRF3; Q9P2P7; Q9Y3Y3; DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot. DT 30-NOV-2010, sequence version 3. DT 24-JAN-2024, entry version 175. DE RecName: Full=SH2B adapter protein 1; DE AltName: Full=Pro-rich, PH and SH2 domain-containing signaling mediator; DE Short=PSM; DE AltName: Full=SH2 domain-containing protein 1B; GN Name=SH2B1; Synonyms=KIAA1299, SH2B; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), FUNCTION IN JAK2 RP ACTIVATION, SELF-ASSOCIATION, INTERACTION WITH JAK2; SH2B2; INSR AND IGF1R, RP PHOSPHORYLATION, TISSUE SPECIFICITY, MUTAGENESIS OF PHE-29; ALA-34; ALA-38; RP PHE-41; ALA-42; TYR-48; PHE-68; PHE-72 AND ARG-555, AND VARIANT ALA-484. RX PubMed=15767667; DOI=10.1128/mcb.25.7.2607-2621.2005; RA Nishi M., Werner E.D., Oh B.C., Frantz J.D., Dhe-Paganon S., Hansen L., RA Lee J., Shoelson S.E.; RT "Kinase activation through dimerization by human SH2-B."; RL Mol. Cell. Biol. 25:2607-2621(2005). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT ALA-541. RC TISSUE=Brain; RX PubMed=10718198; DOI=10.1093/dnares/7.1.65; RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XVI. The RT complete sequences of 150 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 7:65-73(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Teratocarcinoma, and Tongue; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 144-756 (ISOFORM 3), AND VARIANT ALA-484. RC TISSUE=Mammary cancer; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15616553; DOI=10.1038/nature03187; RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M., RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., RA Myers R.M., Rubin E.M., Pennacchio L.A.; RT "The sequence and analysis of duplication-rich human chromosome 16."; RL Nature 432:988-994(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 60-756 (ISOFORM 2). RC TISSUE=Eye; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP INTERACTION WITH INSR. RX PubMed=9498552; DOI=10.1093/oxfordjournals.jbchem.a021868; RA Riedel H., Wang J., Hansen H., Yousaf N.; RT "PSM, an insulin-dependent, pro-rich, PH, SH2 domain containing partner of RT the insulin receptor."; RL J. Biochem. 122:1105-1113(1997). RN [8] RP FUNCTION, INTERACTION WITH INSR, AND PHOSPHORYLATION. RX PubMed=9742218; DOI=10.1042/bj3350103; RA Kotani K., Wilden P., Pillay T.S.; RT "SH2-Balpha is an insulin-receptor adapter protein and substrate that RT interacts with the activation loop of the insulin-receptor kinase."; RL Biochem. J. 335:103-109(1998). RN [9] RP FUNCTION IN PDGF SIGNALING, AND INTERACTION WITH PDGFRA/B. RX PubMed=9694882; DOI=10.1074/jbc.273.33.21239; RA Rui L., Carter-Su C.; RT "Platelet-derived growth factor (PDGF) stimulates the association of SH2- RT Bbeta with PDGF receptor and phosphorylation of SH2-Bbeta."; RL J. Biol. Chem. 273:21239-21245(1998). RN [10] RP INTERACTION WITH INSR AND ISR1. RX PubMed=10594240; DOI=10.1007/s003359901183; RA Nelms K., O'Neill T.J., Li S., Hubbard S.R., Gustafson T.A., Paul W.E.; RT "Alternative splicing, gene localization, and binding of SH2-B to the RT insulin receptor kinase domain."; RL Mamm. Genome 10:1160-1167(1999). RN [11] RP INTERACTION WITH JAK1; JAK2 AND JAK3, AND PHOSPHORYLATION. RX PubMed=11751854; DOI=10.1074/jbc.m109165200; RA O'Brien K.B., O'Shea J.J., Carter-Su C.; RT "SH2-B family members differentially regulate JAK family tyrosine RT kinases."; RL J. Biol. Chem. 277:8673-8681(2002). RN [12] RP FUNCTION IN FGF SIGNALING, AND INTERACTION WITH FGFR3. RX PubMed=11827956; DOI=10.1074/jbc.m102777200; RA Kong M., Wang C.S., Donoghue D.J.; RT "Interaction of fibroblast growth factor receptor 3 and the adapter protein RT SH2-B. A role in STAT5 activation."; RL J. Biol. Chem. 277:15962-15970(2002). RN [13] RP FUNCTION IN NGF SIGNALING. RX PubMed=14565960; DOI=10.1074/jbc.m310040200; RA Wang X., Chen L., Maures T.J., Herrington J., Carter-Su C.; RT "SH2-B is a positive regulator of nerve growth factor-mediated activation RT of the Akt/Forkhead pathway in PC12 cells."; RL J. Biol. Chem. 279:133-141(2004). RN [14] RP FUNCTION IN GDNF SIGNALING, AND INTERACTION WITH RET. RX PubMed=16569669; DOI=10.1242/jcs.02845; RA Zhang Y., Zhu W., Wang Y.G., Liu X.J., Jiao L., Liu X., Zhang Z.H., RA Lu C.L., He C.; RT "Interaction of SH2-Bbeta with RET is involved in signaling of GDNF-induced RT neurite outgrowth."; RL J. Cell Sci. 119:1666-1676(2006). RN [15] RP FUNCTION IN RET SIGNALING, AND INTERACTION WITH PRKAR1A/RET. RX PubMed=17471236; DOI=10.1038/sj.onc.1210480; RA Donatello S., Fiorino A., Degl'Innocenti D., Alberti L., Miranda C., RA Gorla L., Bongarzone I., Rizzetti M.G., Pierotti M.A., Borrello M.G.; RT "SH2B1beta adaptor is a key enhancer of RET tyrosine kinase signaling."; RL Oncogene 26:6546-6559(2007). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-96, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18220336; DOI=10.1021/pr0705441; RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient RT phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-96, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [19] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [20] RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-270, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Colon carcinoma; RX PubMed=24129315; DOI=10.1074/mcp.o113.027870; RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M., RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V., RA Bedford M.T., Comb M.J.; RT "Immunoaffinity enrichment and mass spectrometry analysis of protein RT methylation."; RL Mol. Cell. Proteomics 13:372-387(2014). CC -!- FUNCTION: Adapter protein for several members of the tyrosine kinase CC receptor family. Involved in multiple signaling pathways mediated by CC Janus kinase (JAK) and receptor tyrosine kinases, including the CC receptors of insulin (INS), insulin-like growth factor I (IGF1), nerve CC growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial CC cell line-derived neurotrophic factor (GDNF), platelet-derived growth CC factor (PDGF) and fibroblast growth factors (FGFs). In growth hormone CC (GH) signaling, autophosphorylated ('Tyr-813') JAK2 recruits SH2B1, CC which in turn is phosphorylated by JAK2 on tyrosine residues. These CC phosphotyrosines form potential binding sites for other signaling CC proteins. GH also promotes serine/threonine phosphorylation of SH2B1 CC and these phosphorylated residues may serve to recruit other proteins CC to the GHR-JAK2-SH2B1 complexes, such as RAC1. In leptin (LEP) CC signaling, binds to and potentiates the activation of JAK2 by globally CC enhancing downstream pathways. In response to leptin, binds CC simultaneously to both, JAK2 and IRS1 or IRS2, thus mediating formation CC of a complex of JAK2, SH2B1 and IRS1 or IRS2. Mediates tyrosine CC phosphorylation of IRS1 and IRS2, resulting in activation of the PI 3- CC kinase pathway. Acts as a positive regulator of NGF-mediated activation CC of the Akt/Forkhead pathway; prolongs NGF-induced phosphorylation of CC AKT1 on 'Ser-473' and AKT1 enzymatic activity. Enhances the kinase CC activity of the cytokine receptor-associated tyrosine kinase JAK2 and CC of other receptor tyrosine kinases, such as FGFR3 and NTRK1. For JAK2, CC the mechanism seems to involve dimerization of both, SH2B1 and JAK2. CC Enhances RET phosphorylation and kinase activity. Isoforms seem to be CC differentially involved in IGF-I and PDGF-induced mitogenesis (By CC similarity). {ECO:0000250, ECO:0000269|PubMed:11827956, CC ECO:0000269|PubMed:14565960, ECO:0000269|PubMed:15767667, CC ECO:0000269|PubMed:16569669, ECO:0000269|PubMed:17471236, CC ECO:0000269|PubMed:9694882, ECO:0000269|PubMed:9742218}. CC -!- SUBUNIT: Self-associates. Homopentamer (By similarity). Forms a CC heteromultimeric complex with SH2B2 (By similarity). Interacts with CC SH2B2. Isoform 1 interacts via its SH2 domain with JAK2. Isoform 2 CC interacts via its SH2 domain and its N-terminus with JAK2; the SH2 CC domain is required for the major interaction with JAK2 phosphorylated CC on tyrosine residues; the N-terminus provides a low-affinity binding to CC JAK2 independent of JAK2 phosphorylation. Isoform 3 interacts via its CC SH2 domain with JAK2. Isoform 1 interacts via its SH2 domain with INSR; CC the interaction requires receptor activation. Isoform 3 interacts via CC its SH2 domain with INSR; the interaction requires receptor activation CC and requires INSR phosphorylation at 'Tyr-1185'. Isoform 1 interacts CC with IGF1R; the interaction requires receptor activation. Isoform 2 CC interacts with PRKAR1A/RET (PTC2) fusion protein; the interaction CC requires RET 'Tyr-905' and Tyr-981'. Isoform 2 interacts via its SH2 CC domain with FGFR3; the interaction requires FGFR3 'Tyr-724' and 'Tyr- CC 760'. Isoform 2 interacts with RET; the interaction requires RET kinase CC activity and RET 'Tyr-981'. Isoform 2 interacts with RAC1. Isoform 2 CC interacts with PDGFRA and/or PDGFRB; the interaction requires receptor CC activation. Interacts with ISR1 and ISR2. Isoform 3 is probably part of CC a complex consisting of INSR, ISR1 and SH2B1. Probably part of a CC ternary complex consisting of SH2B1, JAK2 and ISR1 or ISR2. May CC interact with FCER1G (By similarity). Interacts (via SH2 domain) with CC NTRK1 (phosphorylated) (By similarity). {ECO:0000250}. CC -!- INTERACTION: CC Q9NRF2; P00533: EGFR; NbExp=4; IntAct=EBI-310491, EBI-297353; CC Q9NRF2; P06213: INSR; NbExp=6; IntAct=EBI-310491, EBI-475899; CC Q9NRF2; P42227: Stat3; Xeno; NbExp=5; IntAct=EBI-310491, EBI-602878; CC Q9NRF2-2; P62993: GRB2; NbExp=3; IntAct=EBI-10691662, EBI-401755; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Membrane {ECO:0000305}. CC Nucleus {ECO:0000250}. Note=Shuttles between the nucleus and the CC cytoplasm. {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=Alpha; CC IsoId=Q9NRF2-1; Sequence=Displayed; CC Name=2; Synonyms=Beta; CC IsoId=Q9NRF2-2; Sequence=VSP_032027; CC Name=3; Synonyms=Gamma; CC IsoId=Q9NRF2-3; Sequence=VSP_032028; CC -!- TISSUE SPECIFICITY: Widely expressed with highest levels in skeletal CC muscle and ovary. {ECO:0000269|PubMed:15767667}. CC -!- PTM: Phosphorylated on tyrosine residues in response to receptor kinase CC stimulation. Phosphorylated by RET. {ECO:0000269|PubMed:11751854, CC ECO:0000269|PubMed:15767667, ECO:0000269|PubMed:9742218}. CC -!- SIMILARITY: Belongs to the SH2B adapter family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH10704.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAA92537.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAB55148.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF227967; AAF73912.1; -; mRNA. DR EMBL; AF227968; AAF73913.1; -; mRNA. DR EMBL; AF227969; AAF73914.1; -; mRNA. DR EMBL; AB037720; BAA92537.1; ALT_INIT; mRNA. DR EMBL; AK027488; BAB55148.1; ALT_INIT; mRNA. DR EMBL; AK290332; BAF83021.1; -; mRNA. DR EMBL; AL049924; CAB43208.1; -; mRNA. DR EMBL; AL713760; CAD28530.1; -; mRNA. DR EMBL; AC133550; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC010704; AAH10704.1; ALT_INIT; mRNA. DR CCDS; CCDS32424.1; -. [Q9NRF2-2] DR CCDS; CCDS53996.1; -. [Q9NRF2-1] DR CCDS; CCDS53997.1; -. [Q9NRF2-3] DR PIR; T08662; T08662. DR RefSeq; NP_001139267.1; NM_001145795.1. [Q9NRF2-1] DR RefSeq; NP_001139268.1; NM_001145796.1. [Q9NRF2-2] DR RefSeq; NP_001139269.1; NM_001145797.1. [Q9NRF2-3] DR RefSeq; NP_001139284.1; NM_001145812.1. [Q9NRF2-2] DR RefSeq; NP_001295222.1; NM_001308293.1. [Q9NRF2-1] DR RefSeq; NP_001295223.1; NM_001308294.1. DR RefSeq; NP_056318.2; NM_015503.2. [Q9NRF2-2] DR RefSeq; XP_016878603.1; XM_017023114.1. DR RefSeq; XP_016878604.1; XM_017023115.1. DR RefSeq; XP_016878605.1; XM_017023116.1. DR PDB; 5W3R; X-ray; 1.39 A; A=519-628. DR PDBsum; 5W3R; -. DR AlphaFoldDB; Q9NRF2; -. DR SMR; Q9NRF2; -. DR BioGRID; 117455; 30. DR IntAct; Q9NRF2; 19. DR MINT; Q9NRF2; -. DR STRING; 9606.ENSP00000321221; -. DR iPTMnet; Q9NRF2; -. DR PhosphoSitePlus; Q9NRF2; -. DR BioMuta; SH2B1; -. DR DMDM; 313104186; -. DR EPD; Q9NRF2; -. DR jPOST; Q9NRF2; -. DR MassIVE; Q9NRF2; -. DR MaxQB; Q9NRF2; -. DR PaxDb; 9606-ENSP00000321221; -. DR PeptideAtlas; Q9NRF2; -. DR ProteomicsDB; 82346; -. [Q9NRF2-1] DR ProteomicsDB; 82347; -. [Q9NRF2-2] DR ProteomicsDB; 82348; -. [Q9NRF2-3] DR Pumba; Q9NRF2; -. DR Antibodypedia; 26583; 302 antibodies from 31 providers. DR DNASU; 25970; -. DR Ensembl; ENST00000322610.12; ENSP00000321221.7; ENSG00000178188.16. [Q9NRF2-1] DR Ensembl; ENST00000337120.9; ENSP00000337163.5; ENSG00000178188.16. [Q9NRF2-2] DR Ensembl; ENST00000359285.10; ENSP00000352232.5; ENSG00000178188.16. [Q9NRF2-3] DR Ensembl; ENST00000395532.8; ENSP00000378903.4; ENSG00000178188.16. [Q9NRF2-2] DR Ensembl; ENST00000618521.4; ENSP00000481709.1; ENSG00000178188.16. [Q9NRF2-1] DR Ensembl; ENST00000684370.1; ENSP00000507475.1; ENSG00000178188.16. [Q9NRF2-1] DR Ensembl; ENST00000707128.1; ENSP00000516756.1; ENSG00000178188.16. [Q9NRF2-2] DR GeneID; 25970; -. DR KEGG; hsa:25970; -. DR MANE-Select; ENST00000684370.1; ENSP00000507475.1; NM_001387430.1; NP_001374359.1. DR UCSC; uc002dri.4; human. [Q9NRF2-1] DR AGR; HGNC:30417; -. DR CTD; 25970; -. DR DisGeNET; 25970; -. DR GeneCards; SH2B1; -. DR HGNC; HGNC:30417; SH2B1. DR HPA; ENSG00000178188; Low tissue specificity. DR MalaCards; SH2B1; -. DR MIM; 608937; gene. DR neXtProt; NX_Q9NRF2; -. DR OpenTargets; ENSG00000178188; -. DR Orphanet; 261222; Distal 16p11.2 microdeletion syndrome. DR Orphanet; 261197; Proximal 16p11.2 microdeletion syndrome. DR Orphanet; 329249; Severe early-onset obesity-insulin resistance syndrome due to SH2B1 deficiency. DR PharmGKB; PA145148084; -. DR VEuPathDB; HostDB:ENSG00000178188; -. DR eggNOG; ENOG502QT43; Eukaryota. DR GeneTree; ENSGT00950000183191; -. DR HOGENOM; CLU_014885_4_0_1; -. DR InParanoid; Q9NRF2; -. DR OMA; AFSHRFV; -. DR OrthoDB; 2995825at2759; -. DR PhylomeDB; Q9NRF2; -. DR TreeFam; TF323184; -. DR PathwayCommons; Q9NRF2; -. DR Reactome; R-HSA-1170546; Prolactin receptor signaling. [Q9NRF2-2] DR Reactome; R-HSA-2586552; Signaling by Leptin. [Q9NRF2-2] DR Reactome; R-HSA-982772; Growth hormone receptor signaling. [Q9NRF2-2] DR Reactome; R-HSA-983231; Factors involved in megakaryocyte development and platelet production. DR SignaLink; Q9NRF2; -. DR SIGNOR; Q9NRF2; -. DR BioGRID-ORCS; 25970; 44 hits in 1160 CRISPR screens. DR ChiTaRS; SH2B1; human. DR GeneWiki; SH2B1; -. DR GenomeRNAi; 25970; -. DR Pharos; Q9NRF2; Tbio. DR PRO; PR:Q9NRF2; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; Q9NRF2; Protein. DR Bgee; ENSG00000178188; Expressed in right hemisphere of cerebellum and 177 other cell types or tissues. DR ExpressionAtlas; Q9NRF2; baseline and differential. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0005068; F:transmembrane receptor protein tyrosine kinase adaptor activity; IBA:GO_Central. DR GO; GO:0048870; P:cell motility; IEA:Ensembl. DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central. DR GO; GO:0030032; P:lamellipodium assembly; IEA:Ensembl. DR GO; GO:0045840; P:positive regulation of mitotic nuclear division; IEA:Ensembl. DR GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; IGI:MGI. DR GO; GO:2000278; P:regulation of DNA biosynthetic process; IEA:Ensembl. DR CDD; cd01231; PH_SH2B_family; 1. DR CDD; cd10346; SH2_SH2B_family; 1. DR Gene3D; 6.10.140.110; -; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR Gene3D; 3.30.505.10; SH2 domain; 1. DR InterPro; IPR011993; PH-like_dom_sf. DR InterPro; IPR001849; PH_domain. DR InterPro; IPR015012; Phe_ZIP. DR InterPro; IPR036290; Phe_ZIP_sf. DR InterPro; IPR000980; SH2. DR InterPro; IPR036860; SH2_dom_sf. DR InterPro; IPR030523; SH2B. DR InterPro; IPR035057; SH2B1_SH2. DR PANTHER; PTHR10872; SH2B ADAPTER PROTEIN; 1. DR PANTHER; PTHR10872:SF3; SH2B ADAPTER PROTEIN 1; 1. DR Pfam; PF00169; PH; 1. DR Pfam; PF08916; Phe_ZIP; 1. DR Pfam; PF00017; SH2; 1. DR PRINTS; PR00401; SH2DOMAIN. DR SMART; SM00233; PH; 1. DR SMART; SM00252; SH2; 1. DR SUPFAM; SSF50729; PH domain-like; 1. DR SUPFAM; SSF109805; Phenylalanine zipper; 1. DR SUPFAM; SSF55550; SH2 domain; 1. DR PROSITE; PS50001; SH2; 1. DR Genevisible; Q9NRF2; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; Membrane; Methylation; KW Nucleus; Phosphoprotein; Reference proteome; SH2 domain. FT CHAIN 1..756 FT /note="SH2B adapter protein 1" FT /id="PRO_0000323593" FT DOMAIN 267..376 FT /note="PH" FT DOMAIN 527..625 FT /note="SH2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191" FT REGION 1..555 FT /note="Interaction with JAK2 (low-affinity binding; FT independent of JAK2 phosphorylation)" FT /evidence="ECO:0000250" FT REGION 1..27 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 24..85 FT /note="Required for self-association" FT REGION 85..196 FT /note="Interaction with RAC1" FT /evidence="ECO:0000250" FT REGION 100..243 FT /note="Required for NGF signaling" FT /evidence="ECO:0000250" FT REGION 123..154 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 169..222 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 224..233 FT /note="Required for nuclear localization" FT /evidence="ECO:0000250" FT REGION 263..286 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 420..455 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 468..491 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 626..688 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 709..756 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 10..27 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 129..148 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 181..208 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 420..437 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 637..653 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 88 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q91ZM2" FT MOD_RES 96 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18220336, FT ECO:0007744|PubMed:18669648" FT MOD_RES 270 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0007744|PubMed:24129315" FT MOD_RES 417 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q91ZM2" FT MOD_RES 420 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q91ZM2" FT MOD_RES 439 FT /note="Phosphotyrosine; by JAK1, JAK2 and PDGFR" FT /evidence="ECO:0000250|UniProtKB:Q62985" FT MOD_RES 494 FT /note="Phosphotyrosine; by JAK1, JAK2" FT /evidence="ECO:0000250|UniProtKB:Q62985" FT VAR_SEQ 633..756 FT /note="EPTTSHDPPQPPEPPSWTDPPQPGAEEASRAPEVAAAAAAAAKERQEKEKAG FT GGGVPEELVPVVELVPVVELEEAIAPGSEAQGAGSGGDAGVPPMVQLQQSPLGGDGEEG FT GHPRAINNQYSFV -> GREQAGSHAGVCEGDGCHPDASCTLMPFGASDCVTDHLP FT (in isoform 2)" FT /evidence="ECO:0000303|PubMed:10718198, FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:15767667, ECO:0000303|PubMed:17974005" FT /id="VSP_032027" FT VAR_SEQ 633..756 FT /note="EPTTSHDPPQPPEPPSWTDPPQPGAEEASRAPEVAAAAAAAAKERQEKEKAG FT GGGVPEELVPVVELVPVVELEEAIAPGSEAQGAGSGGDAGVPPMVQLQQSPLGGDGEEG FT GHPRAINNQYSFV -> GEQSRSAGEEVPVHPRSEAGSRLGAMRGCAREMDATPMPPAP FT SCPSERVTV (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15767667, FT ECO:0000303|PubMed:17974005" FT /id="VSP_032028" FT VARIANT 484 FT /note="T -> A (in dbSNP:rs7498665)" FT /evidence="ECO:0000269|PubMed:15767667, FT ECO:0000269|PubMed:17974005" FT /id="VAR_039550" FT VARIANT 541 FT /note="V -> A (in dbSNP:rs17850682)" FT /evidence="ECO:0000269|PubMed:10718198" FT /id="VAR_039551" FT MUTAGEN 29 FT /note="F->R: Abolishes self-association and interaction FT with INSR and IGF1R." FT /evidence="ECO:0000269|PubMed:15767667" FT MUTAGEN 34 FT /note="A->D: Abolishes self-association and interaction FT with INSR and IGF1R." FT /evidence="ECO:0000269|PubMed:15767667" FT MUTAGEN 38 FT /note="A->D: Abolishes self-association and interaction FT with INSR and IGF1R." FT /evidence="ECO:0000269|PubMed:15767667" FT MUTAGEN 41 FT /note="F->A: Abolishes self-association and interaction FT with INSR and IGF1R." FT /evidence="ECO:0000269|PubMed:15767667" FT MUTAGEN 42 FT /note="A->D: Abolishes self-association and interaction FT with INSR and IGF1R." FT /evidence="ECO:0000269|PubMed:15767667" FT MUTAGEN 48 FT /note="Y->A: Abolishes self-association and interaction FT with INSR and IGF1R." FT /evidence="ECO:0000269|PubMed:15767667" FT MUTAGEN 68 FT /note="F->A: Abolishes self-association and interaction FT with INSR and IGF1R." FT /evidence="ECO:0000269|PubMed:15767667" FT MUTAGEN 72 FT /note="F->A: Abolishes self-association and interaction FT with INSR and IGF1R." FT /evidence="ECO:0000269|PubMed:15767667" FT MUTAGEN 555 FT /note="R->A: Abolishes self-association and interaction FT with INSR and IGF1R." FT /evidence="ECO:0000269|PubMed:15767667" FT CONFLICT 197 FT /note="N -> D (in Ref. 3; BAF83021)" FT /evidence="ECO:0000305" FT CONFLICT 519 FT /note="D -> G (in Ref. 3; BAF83021)" FT /evidence="ECO:0000305" FT HELIX 522..524 FT /evidence="ECO:0007829|PDB:5W3R" FT STRAND 528..531 FT /evidence="ECO:0007829|PDB:5W3R" FT HELIX 534..542 FT /evidence="ECO:0007829|PDB:5W3R" FT HELIX 545..548 FT /evidence="ECO:0007829|PDB:5W3R" FT STRAND 551..556 FT /evidence="ECO:0007829|PDB:5W3R" FT STRAND 558..560 FT /evidence="ECO:0007829|PDB:5W3R" FT STRAND 564..570 FT /evidence="ECO:0007829|PDB:5W3R" FT STRAND 573..581 FT /evidence="ECO:0007829|PDB:5W3R" FT STRAND 587..589 FT /evidence="ECO:0007829|PDB:5W3R" FT STRAND 592..596 FT /evidence="ECO:0007829|PDB:5W3R" FT HELIX 597..606 FT /evidence="ECO:0007829|PDB:5W3R" FT STRAND 614..616 FT /evidence="ECO:0007829|PDB:5W3R" SQ SEQUENCE 756 AA; 79366 MW; CF680B57114CB1D3 CRC64; MNGAPSPEDG ASPSSPPLPP PPPPSWREFC ESHARAAALD FARRFRLYLA SHPQYAGPGA EAAFSRRFAE LFLQHFEAEV ARASGSLSPP ILAPLSPGAE ISPHDLSLES CRVGGPLAVL GPSRSSEDLA GPLPSSVSSS STTSSKPKLK KRFSLRSVGR SVRGSVRGIL QWRGTVDPPS SAGPLETSSG PPVLGGNSNS NSSGGAGTVG RGLVSDGTSP GERWTHRFER LRLSRGGGAL KDGAGMVQRE ELLSFMGAEE AAPDPAGVGR GGGVAGPPSG GGGQPQWQKC RLLLRSEGEG GGGSRLEFFV PPKASRPRLS IPCSSITDVR TTTALEMPDR ENTFVVKVEG PSEYIMETVD AQHVKAWVSD IQECLSPGPC PATSPRPMTL PLAPGTSFLT RENTDSLELS CLNHSESLPS QDLLLGPSES NDRLSQGAYG GLSDRPSASI SPSSASIAAS HFDSMELLPP ELPPRIPIEE GPPTGTVHPL SAPYPPLDTP ETATGSFLFQ GEPEGGEGDQ PLSGYPWFHG MLSRLKAAQL VLTGGTGSHG VFLVRQSETR RGEYVLTFNF QGKAKHLRLS LNEEGQCRVQ HLWFQSIFDM LEHFRVHPIP LESGGSSDVV LVSYVPSSQR QQEPTTSHDP PQPPEPPSWT DPPQPGAEEA SRAPEVAAAA AAAAKERQEK EKAGGGGVPE ELVPVVELVP VVELEEAIAP GSEAQGAGSG GDAGVPPMVQ LQQSPLGGDG EEGGHPRAIN NQYSFV //