GenomeNet

Database: UniProt
Entry: SH2B1_HUMAN
LinkDB: SH2B1_HUMAN
Original site: SH2B1_HUMAN 
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   28-MAR-2018, entry version 140.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; 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
RP   IGF1R, PHOSPHORYLATION, TISSUE SPECIFICITY, MUTAGENESIS OF PHE-29;
RP   ALA-34; ALA-38; PHE-41; ALA-42; TYR-48; PHE-68; PHE-72 AND ARG-555,
RP   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.,
RA   Hansen L., 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
RP   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.
RT   The complete sequences of 150 new cDNA clones from brain which code
RT   for large 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.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   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.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., 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
RP   SEQUENCE [LARGE SCALE MRNA] OF 144-756 (ISOFORM 3), AND VARIANT
RP   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.,
RA   Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA   Ottenwaelder B., Poustka A., 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.,
RA   Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A.,
RA   Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.,
RA   Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L.,
RA   Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A.,
RA   Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D.,
RA   Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J.,
RA   Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA   Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I.,
RA   Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W.,
RA   Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A.,
RA   Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S.,
RA   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.,
RA   Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A.,
RA   Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L.,
RA   Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N.,
RA   Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M.,
RA   Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L.,
RA   Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D.,
RA   Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P.,
RA   Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M.,
RA   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
RT   project: 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
RT   partner of 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
RT   SH2-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.,
RA   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
RT   protein 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
RT   activation 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-
RT   induced 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
RT   signaling.";
RL   Oncogene 26:6546-6559(2007).
RN   [16]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-96, AND IDENTIFICATION
RP   BY 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.,
RA   Yates J.R. III;
RT   "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT   efficient phosphoproteomic analysis.";
RL   J. Proteome Res. 7:1346-1351(2008).
RN   [17]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-96, AND IDENTIFICATION
RP   BY 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.,
RA   Wang L., Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human
RT   liver phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [20]
RP   METHYLATION [LARGE SCALE ANALYSIS] AT ARG-270, AND IDENTIFICATION BY
RP   MASS 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.,
RA   Aguiar M., Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C.,
RA   Vemulapalli V., 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
CC       kinase receptor family. Involved in multiple signaling pathways
CC       mediated by Janus kinase (JAK) and receptor tyrosine kinases,
CC       including the receptors of insulin (INS), insulin-like growth
CC       factor I (IGF1), nerve growth factor (NGF), brain-derived
CC       neurotrophic factor (BDNF), glial cell line-derived neurotrophic
CC       factor (GDNF), platelet-derived growth factor (PDGF) and
CC       fibroblast growth factors (FGFs). In growth hormone (GH)
CC       signaling, autophosphorylated ('Tyr-813') JAK2 recruits SH2B1,
CC       which in turn is phosphorylated by JAK2 on tyrosine residues.
CC       These phosphotyrosines form potential binding sites for other
CC       signaling proteins. GH also promotes serine/threonine
CC       phosphorylation of SH2B1 and these phosphorylated residues may
CC       serve to recruit other proteins to the GHR-JAK2-SH2B1 complexes,
CC       such as RAC1. In leptin (LEP) signaling, binds to and potentiates
CC       the activation of JAK2 by globally enhancing downstream pathways.
CC       In response to leptin, binds simultaneously to both, JAK2 and IRS1
CC       or IRS2, thus mediating formation of a complex of JAK2, SH2B1 and
CC       IRS1 or IRS2. Mediates tyrosine phosphorylation of IRS1 and IRS2,
CC       resulting in activation of the PI 3-kinase pathway. Acts as
CC       positive regulator of NGF-mediated activation of the Akt/Forkhead
CC       pathway; prolongs NGF-induced phosphorylation of AKT1 on 'Ser-473'
CC       and AKT1 enzymatic activity. Enhances the kinase activity of the
CC       cytokine receptor-associated tyrosine kinase JAK2 and of other
CC       receptor tyrosine kinases, such as FGFR3 and NTRK1. For JAK2, the
CC       mechanism seems to involve dimerization of both, SH2B1 and JAK2.
CC       Enhances RET phosphorylation and kinase activity. Isoforms seem to
CC       be differentially involved in IGF-I and PDGF-induced mitogenesis
CC       (By 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
CC       with SH2B2. Isoform 1 interacts via its SH2 domain with JAK2.
CC       Isoform 2 interacts via its SH2 domain and its N-terminus with
CC       JAK2; the SH2 domain is required for the major interaction with
CC       JAK2 phosphorylated on tyrosine residues; the N-terminus provides
CC       a low-affinity binding to JAK2 independent of JAK2
CC       phosphorylation. Isoform 3 interacts via its SH2 domain with JAK2.
CC       Isoform 1 interacts via its SH2 domain with INSR; the interaction
CC       requires receptor activation. Isoform 3 interacts via its SH2
CC       domain with INSR; the interaction requires receptor activation and
CC       requires INSR phosphorylation at 'Tyr-1185'. Isoform 1 interacts
CC       with IGF1R; the interaction requires receptor activation. Isoform
CC       2 interacts with PRKAR1A/RET (PTC2) fusion protein; the
CC       interaction requires RET 'Tyr-905' and Tyr-981'. Isoform 2
CC       interacts via its SH2 domain with FGFR3; the interaction requires
CC       FGFR3 'Tyr-724' and 'Tyr-760'. Isoform 2 interacts with RET; the
CC       interaction requires RET kinase activity and RET 'Tyr-981'.
CC       Isoform 2 interacts with RAC1. Isoform 2 interacts with PDGFRA
CC       and/or PDGFRB; the interaction requires receptor activation.
CC       Interacts with ISR1 and ISR2. Isoform 3 is probably part of a
CC       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)
CC       with NTRK1 (phosphorylated) (By similarity). {ECO:0000250}.
CC   -!- INTERACTION:
CC       P00533:EGFR; NbExp=2; IntAct=EBI-310491, EBI-297353;
CC       P06213:INSR; NbExp=6; IntAct=EBI-310491, EBI-475899;
CC       P42227:Stat3 (xeno); NbExp=5; IntAct=EBI-310491, EBI-602878;
CC       P52631:Stat3 (xeno); NbExp=2; IntAct=EBI-310491, EBI-10764775;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Membrane
CC       {ECO:0000305}. Nucleus {ECO:0000250}. Note=Shuttles between the
CC       nucleus and the 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
CC       skeletal muscle and ovary. {ECO:0000269|PubMed:15767667}.
CC   -!- PTM: Phosphorylated on tyrosine residues in response to receptor
CC       kinase stimulation. Phosphorylated by RET.
CC       {ECO:0000269|PubMed:11751854, ECO:0000269|PubMed:15767667,
CC       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=Translation N-terminally extended.; Evidence={ECO:0000305};
CC       Sequence=BAA92537.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};
CC       Sequence=BAB55148.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
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. [Q9NRF2-1]
DR   RefSeq; XP_016878604.1; XM_017023115.1. [Q9NRF2-1]
DR   RefSeq; XP_016878605.1; XM_017023116.1. [Q9NRF2-1]
DR   UniGene; Hs.15744; -.
DR   PDB; 5W3R; X-ray; 1.39 A; A=519-628.
DR   PDBsum; 5W3R; -.
DR   ProteinModelPortal; Q9NRF2; -.
DR   SMR; Q9NRF2; -.
DR   BioGrid; 117455; 18.
DR   IntAct; Q9NRF2; 15.
DR   MINT; Q9NRF2; -.
DR   STRING; 9606.ENSP00000321221; -.
DR   iPTMnet; Q9NRF2; -.
DR   PhosphoSitePlus; Q9NRF2; -.
DR   BioMuta; SH2B1; -.
DR   DMDM; 313104186; -.
DR   MaxQB; Q9NRF2; -.
DR   PaxDb; Q9NRF2; -.
DR   PeptideAtlas; Q9NRF2; -.
DR   PRIDE; Q9NRF2; -.
DR   Ensembl; ENST00000322610; ENSP00000321221; ENSG00000178188. [Q9NRF2-1]
DR   Ensembl; ENST00000337120; ENSP00000337163; ENSG00000178188. [Q9NRF2-2]
DR   Ensembl; ENST00000359285; ENSP00000352232; ENSG00000178188. [Q9NRF2-3]
DR   Ensembl; ENST00000395532; ENSP00000378903; ENSG00000178188. [Q9NRF2-2]
DR   Ensembl; ENST00000618521; ENSP00000481709; ENSG00000178188. [Q9NRF2-1]
DR   GeneID; 25970; -.
DR   KEGG; hsa:25970; -.
DR   UCSC; uc002dri.4; human. [Q9NRF2-1]
DR   CTD; 25970; -.
DR   DisGeNET; 25970; -.
DR   EuPathDB; HostDB:ENSG00000178188.14; -.
DR   GeneCards; SH2B1; -.
DR   H-InvDB; HIX0017272; -.
DR   HGNC; HGNC:30417; SH2B1.
DR   HPA; HPA076175; -.
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   eggNOG; ENOG410IMWK; Eukaryota.
DR   eggNOG; ENOG41102PH; LUCA.
DR   GeneTree; ENSGT00530000063355; -.
DR   HOVERGEN; HBG006707; -.
DR   InParanoid; Q9NRF2; -.
DR   KO; K12459; -.
DR   OMA; GDRWTHR; -.
DR   OrthoDB; EOG091G04RI; -.
DR   PhylomeDB; Q9NRF2; -.
DR   TreeFam; TF323184; -.
DR   Reactome; R-HSA-1170546; Prolactin receptor signaling.
DR   Reactome; R-HSA-2586552; Signaling by Leptin.
DR   Reactome; R-HSA-982772; Growth hormone receptor signaling.
DR   Reactome; R-HSA-983231; Factors involved in megakaryocyte development and platelet production.
DR   SignaLink; Q9NRF2; -.
DR   SIGNOR; Q9NRF2; -.
DR   GeneWiki; SH2B1; -.
DR   GenomeRNAi; 25970; -.
DR   PRO; PR:Q9NRF2; -.
DR   Proteomes; UP000005640; Chromosome 16.
DR   Bgee; ENSG00000178188; -.
DR   CleanEx; HS_SH2B1; -.
DR   ExpressionAtlas; Q9NRF2; baseline and differential.
DR   Genevisible; Q9NRF2; HS.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0004871; F:signal transducer activity; IEA:InterPro.
DR   GO; GO:0035591; F:signaling adaptor activity; IEA:InterPro.
DR   GO; GO:0007596; P:blood coagulation; TAS:Reactome.
DR   GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
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:2000278; P:regulation of DNA biosynthetic process; IEA:Ensembl.
DR   CDD; cd10346; SH2_SH2B_family; 1.
DR   Gene3D; 2.30.29.30; -; 1.
DR   Gene3D; 3.30.505.10; -; 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; IPR030521; SH2B1.
DR   InterPro; IPR035057; SH2B1_SH2.
DR   PANTHER; PTHR10872; PTHR10872; 1.
DR   PANTHER; PTHR10872:SF3; PTHR10872:SF3; 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; SSF109805; SSF109805; 1.
DR   SUPFAM; SSF55550; SSF55550; 1.
DR   PROSITE; PS50001; SH2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Complete proteome; Cytoplasm;
KW   Membrane; Methylation; Nucleus; Phosphoprotein; Polymorphism;
KW   Reference proteome; SH2 domain.
FT   CHAIN         1    756       SH2B adapter protein 1.
FT                                /FTId=PRO_0000323593.
FT   DOMAIN      267    376       PH.
FT   DOMAIN      527    625       SH2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00191}.
FT   REGION        1    555       Interaction with JAK2 (low-affinity
FT                                binding; independent of JAK2
FT                                phosphorylation). {ECO:0000250}.
FT   REGION       24     85       Required for self-association.
FT   REGION       85    196       Interaction with RAC1. {ECO:0000250}.
FT   REGION      100    243       Required for NGF signaling.
FT                                {ECO:0000250}.
FT   REGION      224    233       Required for nuclear localization.
FT                                {ECO:0000250}.
FT   MOD_RES      88     88       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q91ZM2}.
FT   MOD_RES      96     96       Phosphoserine.
FT                                {ECO:0000244|PubMed:18220336,
FT                                ECO:0000244|PubMed:18669648}.
FT   MOD_RES     270    270       Omega-N-methylarginine.
FT                                {ECO:0000244|PubMed:24129315}.
FT   MOD_RES     417    417       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q91ZM2}.
FT   MOD_RES     420    420       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q91ZM2}.
FT   MOD_RES     439    439       Phosphotyrosine; by JAK1, JAK2 and PDGFR.
FT                                {ECO:0000250|UniProtKB:Q62985}.
FT   MOD_RES     494    494       Phosphotyrosine; by JAK1, JAK2.
FT                                {ECO:0000250|UniProtKB:Q62985}.
FT   VAR_SEQ     633    756       EPTTSHDPPQPPEPPSWTDPPQPGAEEASRAPEVAAAAAAA
FT                                AKERQEKEKAGGGGVPEELVPVVELVPVVELEEAIAPGSEA
FT                                QGAGSGGDAGVPPMVQLQQSPLGGDGEEGGHPRAINNQYSF
FT                                V -> GREQAGSHAGVCEGDGCHPDASCTLMPFGASDCVTD
FT                                HLP (in isoform 2).
FT                                {ECO:0000303|PubMed:10718198,
FT                                ECO:0000303|PubMed:14702039,
FT                                ECO:0000303|PubMed:15489334,
FT                                ECO:0000303|PubMed:15767667,
FT                                ECO:0000303|PubMed:17974005}.
FT                                /FTId=VSP_032027.
FT   VAR_SEQ     633    756       EPTTSHDPPQPPEPPSWTDPPQPGAEEASRAPEVAAAAAAA
FT                                AKERQEKEKAGGGGVPEELVPVVELVPVVELEEAIAPGSEA
FT                                QGAGSGGDAGVPPMVQLQQSPLGGDGEEGGHPRAINNQYSF
FT                                V -> GEQSRSAGEEVPVHPRSEAGSRLGAMRGCAREMDAT
FT                                PMPPAPSCPSERVTV (in isoform 3).
FT                                {ECO:0000303|PubMed:15767667,
FT                                ECO:0000303|PubMed:17974005}.
FT                                /FTId=VSP_032028.
FT   VARIANT     484    484       T -> A (in dbSNP:rs7498665).
FT                                {ECO:0000269|PubMed:15767667,
FT                                ECO:0000269|PubMed:17974005}.
FT                                /FTId=VAR_039550.
FT   VARIANT     541    541       V -> A (in dbSNP:rs17850682).
FT                                {ECO:0000269|PubMed:10718198}.
FT                                /FTId=VAR_039551.
FT   MUTAGEN      29     29       F->R: Abolishes self-association and
FT                                interaction with INSR and IGF1R.
FT                                {ECO:0000269|PubMed:15767667}.
FT   MUTAGEN      34     34       A->D: Abolishes self-association and
FT                                interaction with INSR and IGF1R.
FT                                {ECO:0000269|PubMed:15767667}.
FT   MUTAGEN      38     38       A->D: Abolishes self-association and
FT                                interaction with INSR and IGF1R.
FT                                {ECO:0000269|PubMed:15767667}.
FT   MUTAGEN      41     41       F->A: Abolishes self-association and
FT                                interaction with INSR and IGF1R.
FT                                {ECO:0000269|PubMed:15767667}.
FT   MUTAGEN      42     42       A->D: Abolishes self-association and
FT                                interaction with INSR and IGF1R.
FT                                {ECO:0000269|PubMed:15767667}.
FT   MUTAGEN      48     48       Y->A: Abolishes self-association and
FT                                interaction with INSR and IGF1R.
FT                                {ECO:0000269|PubMed:15767667}.
FT   MUTAGEN      68     68       F->A: Abolishes self-association and
FT                                interaction with INSR and IGF1R.
FT                                {ECO:0000269|PubMed:15767667}.
FT   MUTAGEN      72     72       F->A: Abolishes self-association and
FT                                interaction with INSR and IGF1R.
FT                                {ECO:0000269|PubMed:15767667}.
FT   MUTAGEN     555    555       R->A: Abolishes self-association and
FT                                interaction with INSR and IGF1R.
FT                                {ECO:0000269|PubMed:15767667}.
FT   CONFLICT    197    197       N -> D (in Ref. 3; BAF83021).
FT                                {ECO:0000305}.
FT   CONFLICT    519    519       D -> G (in Ref. 3; BAF83021).
FT                                {ECO:0000305}.
FT   HELIX       522    524       {ECO:0000244|PDB:5W3R}.
FT   STRAND      528    531       {ECO:0000244|PDB:5W3R}.
FT   HELIX       534    542       {ECO:0000244|PDB:5W3R}.
FT   HELIX       545    548       {ECO:0000244|PDB:5W3R}.
FT   STRAND      551    556       {ECO:0000244|PDB:5W3R}.
FT   STRAND      558    560       {ECO:0000244|PDB:5W3R}.
FT   STRAND      564    570       {ECO:0000244|PDB:5W3R}.
FT   STRAND      573    581       {ECO:0000244|PDB:5W3R}.
FT   STRAND      587    589       {ECO:0000244|PDB:5W3R}.
FT   STRAND      592    596       {ECO:0000244|PDB:5W3R}.
FT   HELIX       597    606       {ECO:0000244|PDB:5W3R}.
FT   STRAND      614    616       {ECO:0000244|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
//
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