SH2B1_MOUSE
ID SH2B1_MOUSE Reviewed; 756 AA.
AC Q91ZM2; O54867; Q05DJ7; Q792R7; Q91ZM3; Q91ZV5; Q9WVM5;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 18-MAR-2008, sequence version 2.
DT 03-AUG-2022, entry version 147.
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;
DE AltName: Full=SH2-B PH domain-containing signaling mediator 1;
GN Name=Sh2b1; Synonyms=Sh2bpsm1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, AND
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6), ALTERNATIVE SPLICING (ISOFORMS 1; 2
RP AND 3), TISSUE SPECIFICITY, AND 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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4), FUNCTION, AND
RP PHOSPHORYLATION.
RC TISSUE=Brain;
RX PubMed=11502739; DOI=10.1074/jbc.m104191200;
RA Yousaf N., Deng Y., Kang Y., Riedel H.;
RT "Four PSM/SH2-B alternative splice variants and their differential roles in
RT mitogenesis.";
RL J. Biol. Chem. 276:40940-40948(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC STRAIN=NOD;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 4 AND 5).
RC STRAIN=C57BL/6J, and FVB/N; TISSUE=Mammary tumor;
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 518-631, AND INTERACTION WITH INSR AND IGF1R.
RX PubMed=9452421; DOI=10.1074/jbc.273.6.3136;
RA Wang J., Riedel H.;
RT "Insulin-like growth factor-I receptor and insulin receptor association
RT with a Src homology-2 domain-containing putative adapter.";
RL J. Biol. Chem. 273:3136-3139(1998).
RN [7]
RP FUNCTION IN GH SIGNALING, AND INTERACTION WITH JAK2.
RC TISSUE=Kidney;
RX PubMed=9343427; DOI=10.1128/mcb.17.11.6633;
RA Rui L., Mathews L.S., Hotta K., Gustafson T.A., Carter-Su C.;
RT "Identification of SH2-Bbeta as a substrate of the tyrosine kinase JAK2
RT involved in growth hormone signaling.";
RL Mol. Cell. Biol. 17:6633-6644(1997).
RN [8]
RP FUNCTION IN LEPTIN SIGNALING, AND INTERACTION WITH JAK2; ISR1 AND ISR2.
RX PubMed=15316008; DOI=10.1074/jbc.m408495200;
RA Duan C., Li M., Rui L.;
RT "SH2-B promotes insulin receptor substrate 1 (IRS1)- and IRS2-mediated
RT activation of the phosphatidylinositol 3-kinase pathway in response to
RT leptin.";
RL J. Biol. Chem. 279:43684-43691(2004).
RN [9]
RP FUNCTION IN LEPTIN SIGNALING.
RX PubMed=16098827; DOI=10.1016/j.cmet.2005.07.004;
RA Ren D., Li M., Duan C., Rui L.;
RT "Identification of SH2-B as a key regulator of leptin sensitivity, energy
RT balance, and body weight in mice.";
RL Cell Metab. 2:95-104(2005).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-88; SER-96; SER-417 AND
RP SER-420, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, Liver, Pancreas, Spleen, and
RC Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [12]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-270, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Embryo;
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).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 519-627 IN COMPLEX WITH JAK2.
RX PubMed=16824542; DOI=10.1016/j.jmb.2006.05.070;
RA Hu J., Hubbard S.R.;
RT "Structural basis for phosphotyrosine recognition by the Src homology-2
RT domains of the adapter proteins SH2-B and APS.";
RL J. Mol. Biol. 361:69-79(2006).
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 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 (By similarity).
CC Isoforms seem to be differentially involved in IGF-I and PDGF-induced
CC mitogenesis, according the order: isoform 3 > isoform 4 > isoform 1 >
CC isoform 2. {ECO:0000250, ECO:0000269|PubMed:11502739,
CC ECO:0000269|PubMed:15316008, ECO:0000269|PubMed:16098827,
CC ECO:0000269|PubMed:9343427}.
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-1175'. Isoform 1 interacts
CC with IGF1R; the interaction requires receptor activation. Isoform 2
CC interacts via its SH2 domain with FGFR3; the interaction requires FGFR3
CC 'Tyr-719' and 'Tyr-755'. Isoform 2 interacts with RET; the interaction
CC requires RET kinase activity and RET 'Tyr-982'. Isoform 2 interacts
CC with RAC1. Isoform 2 interacts with PDGFRA and/or PDGFRB; the
CC interaction requires receptor activation. Interacts with ISR1 and ISR2.
CC Isoform 3 is probably part of a complex consisting of INSR, ISR1 and
CC SH2B1. Probably part of a ternary complex consisting of SH2B1, JAK2 and
CC ISR1 or ISR2. May interact with FCER1G (By similarity). Interacts (via
CC SH2 domain) with NTRK1 (phosphorylated) (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q91ZM2; Q62120: Jak2; NbExp=3; IntAct=EBI-7178606, EBI-646604;
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=6;
CC Name=1; Synonyms=Alpha;
CC IsoId=Q91ZM2-1; Sequence=Displayed;
CC Name=2; Synonyms=Beta;
CC IsoId=Q91ZM2-2; Sequence=VSP_032032;
CC Name=3; Synonyms=Gamma;
CC IsoId=Q91ZM2-3; Sequence=VSP_032033;
CC Name=4; Synonyms=Delta;
CC IsoId=Q91ZM2-4; Sequence=VSP_032034;
CC Name=5;
CC IsoId=Q91ZM2-5; Sequence=VSP_032029, VSP_032031;
CC Name=6; Synonyms=Sh2bpsm1 gamma;
CC IsoId=Q91ZM2-6; Sequence=VSP_032030, VSP_032033;
CC -!- TISSUE SPECIFICITY: Widely expressed with highest levels in liver,
CC brain and heart. Isoform 3 is widely expressed.
CC {ECO:0000269|PubMed:10594240, ECO:0000269|PubMed:9498552}.
CC -!- PTM: Phosphorylated on tyrosine residues in response to IGF-I and PDGF
CC stimulation. {ECO:0000269|PubMed:11502739}.
CC -!- SIMILARITY: Belongs to the SH2B adapter family. {ECO:0000305}.
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DR EMBL; AF020526; AAC33414.1; -; mRNA.
DR EMBL; AF380422; AAL07566.1; -; mRNA.
DR EMBL; AF074329; AAD41655.1; -; mRNA.
DR EMBL; AF421138; AAL16069.1; -; mRNA.
DR EMBL; AF421139; AAL16070.1; -; mRNA.
DR EMBL; AK168439; BAE40344.1; -; mRNA.
DR EMBL; AK170444; BAE41802.1; -; mRNA.
DR EMBL; BC011422; AAH11422.1; -; mRNA.
DR EMBL; BC051978; AAH51978.1; -; mRNA.
DR EMBL; AF036355; AAC39955.2; -; mRNA.
DR CCDS; CCDS40126.1; -. [Q91ZM2-3]
DR CCDS; CCDS85410.1; -. [Q91ZM2-4]
DR CCDS; CCDS85411.1; -. [Q91ZM2-1]
DR CCDS; CCDS85412.1; -. [Q91ZM2-2]
DR PIR; JC5886; JC5886.
DR RefSeq; NP_001074928.1; NM_001081459.2. [Q91ZM2-2]
DR RefSeq; NP_001276467.1; NM_001289538.1. [Q91ZM2-1]
DR RefSeq; NP_001276468.1; NM_001289539.1. [Q91ZM2-2]
DR RefSeq; NP_001276469.1; NM_001289540.1. [Q91ZM2-2]
DR RefSeq; NP_001276470.1; NM_001289541.1. [Q91ZM2-4]
DR RefSeq; NP_001276471.1; NM_001289542.1. [Q91ZM2-4]
DR RefSeq; NP_035493.2; NM_011363.3. [Q91ZM2-3]
DR RefSeq; XP_006507541.1; XM_006507478.3. [Q91ZM2-1]
DR RefSeq; XP_006507543.1; XM_006507480.3. [Q91ZM2-1]
DR RefSeq; XP_006507544.1; XM_006507481.3. [Q91ZM2-1]
DR RefSeq; XP_006507545.1; XM_006507482.1. [Q91ZM2-1]
DR RefSeq; XP_006507548.1; XM_006507485.3. [Q91ZM2-3]
DR RefSeq; XP_006507550.1; XM_006507487.3. [Q91ZM2-2]
DR PDB; 2HDV; X-ray; 2.00 A; A/B=519-627.
DR PDB; 2HDX; X-ray; 2.35 A; A/B/C/D/E/F=519-627.
DR PDBsum; 2HDV; -.
DR PDBsum; 2HDX; -.
DR AlphaFoldDB; Q91ZM2; -.
DR SMR; Q91ZM2; -.
DR BioGRID; 203201; 3.
DR IntAct; Q91ZM2; 4.
DR MINT; Q91ZM2; -.
DR STRING; 10090.ENSMUSP00000032978; -.
DR iPTMnet; Q91ZM2; -.
DR PhosphoSitePlus; Q91ZM2; -.
DR EPD; Q91ZM2; -.
DR jPOST; Q91ZM2; -.
DR MaxQB; Q91ZM2; -.
DR PaxDb; Q91ZM2; -.
DR PeptideAtlas; Q91ZM2; -.
DR PRIDE; Q91ZM2; -.
DR ProteomicsDB; 257132; -. [Q91ZM2-1]
DR ProteomicsDB; 257133; -. [Q91ZM2-2]
DR ProteomicsDB; 257134; -. [Q91ZM2-3]
DR ProteomicsDB; 257135; -. [Q91ZM2-4]
DR ProteomicsDB; 257136; -. [Q91ZM2-5]
DR ProteomicsDB; 257137; -. [Q91ZM2-6]
DR Antibodypedia; 26583; 289 antibodies from 31 providers.
DR Ensembl; ENSMUST00000032978; ENSMUSP00000032978; ENSMUSG00000030733. [Q91ZM2-3]
DR Ensembl; ENSMUST00000205340; ENSMUSP00000145953; ENSMUSG00000030733. [Q91ZM2-2]
DR Ensembl; ENSMUST00000205440; ENSMUSP00000145554; ENSMUSG00000030733. [Q91ZM2-2]
DR Ensembl; ENSMUST00000205497; ENSMUSP00000145842; ENSMUSG00000030733. [Q91ZM2-4]
DR Ensembl; ENSMUST00000205733; ENSMUSP00000145754; ENSMUSG00000030733. [Q91ZM2-1]
DR Ensembl; ENSMUST00000205889; ENSMUSP00000146282; ENSMUSG00000030733. [Q91ZM2-4]
DR Ensembl; ENSMUST00000206664; ENSMUSP00000146121; ENSMUSG00000030733. [Q91ZM2-5]
DR GeneID; 20399; -.
DR KEGG; mmu:20399; -.
DR UCSC; uc009jrh.2; mouse. [Q91ZM2-2]
DR UCSC; uc009jrj.2; mouse. [Q91ZM2-4]
DR UCSC; uc009jrk.2; mouse. [Q91ZM2-3]
DR UCSC; uc009jrm.2; mouse. [Q91ZM2-1]
DR CTD; 25970; -.
DR MGI; MGI:1201407; Sh2b1.
DR VEuPathDB; HostDB:ENSMUSG00000030733; -.
DR eggNOG; ENOG502QT43; Eukaryota.
DR GeneTree; ENSGT00950000183191; -.
DR HOGENOM; CLU_014885_4_0_1; -.
DR InParanoid; Q91ZM2; -.
DR OMA; GILQWRS; -.
DR OrthoDB; 556279at2759; -.
DR PhylomeDB; Q91ZM2; -.
DR TreeFam; TF323184; -.
DR Reactome; R-MMU-1170546; Prolactin receptor signaling.
DR Reactome; R-MMU-982772; Growth hormone receptor signaling.
DR Reactome; R-MMU-983231; Factors involved in megakaryocyte development and platelet production.
DR BioGRID-ORCS; 20399; 5 hits in 72 CRISPR screens.
DR ChiTaRS; Sh2b1; mouse.
DR EvolutionaryTrace; Q91ZM2; -.
DR PRO; PR:Q91ZM2; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q91ZM2; protein.
DR Bgee; ENSMUSG00000030733; Expressed in retinal neural layer and 263 other tissues.
DR ExpressionAtlas; Q91ZM2; baseline and differential.
DR Genevisible; Q91ZM2; MM.
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:0001726; C:ruffle; TAS:MGI.
DR GO; GO:0005068; F:transmembrane receptor protein tyrosine kinase adaptor activity; IBA:GO_Central.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0030032; P:lamellipodium assembly; IDA:MGI.
DR GO; GO:0045840; P:positive regulation of mitotic nuclear division; IDA:UniProtKB.
DR GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; IEA:Ensembl.
DR GO; GO:2000278; P:regulation of DNA biosynthetic process; IMP:UniProtKB.
DR CDD; cd10346; SH2_SH2B_family; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR IDEAL; IID50098; -.
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; Cytoplasm; Membrane; Methylation;
KW Nucleus; Phosphoprotein; Reference proteome; SH2 domain.
FT CHAIN 1..756
FT /note="SH2B adapter protein 1"
FT /id="PRO_0000323594"
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 /evidence="ECO:0000250"
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..152
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 173..224
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..284
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 418..455
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 468..503
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 626..664
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 9..27
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 130..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 418..437
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 88
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 96
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
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:0007744|PubMed:21183079"
FT MOD_RES 420
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
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 437..443
FT /note="GAYGGLS -> AVDSEKT (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_032029"
FT VAR_SEQ 441..460
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:10594240"
FT /id="VSP_032030"
FT VAR_SEQ 444..756
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_032031"
FT VAR_SEQ 632..756
FT /note="ERSTSRDPAQPSEPPPWTDPPHPGAEEASGAPEVAAATAAAAKERQEKEKAG
FT SGGVQEELVPVAELVPMVELEEAIAPGTEAQGGAGSSGDLEVSLMVQLQQLPLGGNGEE
FT GGHPRAINNQYSFV -> GREQAGSHAGVCEGDRCYPDASSTLLPFGASDCVTEHLP
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11502739,
FT ECO:0000303|PubMed:16141072, ECO:0000303|PubMed:9498552"
FT /id="VSP_032032"
FT VAR_SEQ 632..756
FT /note="ERSTSRDPAQPSEPPPWTDPPHPGAEEASGAPEVAAATAAAAKERQEKEKAG
FT SGGVQEELVPVAELVPMVELEEAIAPGTEAQGGAGSSGDLEVSLMVQLQQLPLGGNGEE
FT GGHPRAINNQYSFV -> GEQSRSAGEEVPVHPRSEAGSRLGAMQGCARATDATPMPPP
FT PSCPSERVTV (in isoform 3 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:10594240,
FT ECO:0000303|PubMed:11502739, ECO:0000303|PubMed:16141072"
FT /id="VSP_032033"
FT VAR_SEQ 632..756
FT /note="ERSTSRDPAQPSEPPPWTDPPHPGAEEASGAPEVAAATAAAAKERQEKEKAG
FT SGGVQEELVPVAELVPMVELEEAIAPGTEAQGGAGSSGDLEVSLMVQLQQLPLGGNGEE
FT GGHPRAINNQYSFV -> GEQSRSAGEEVPVHPRSENGAPPVTQPSPLNPLHGQIPHIL
FT GQKRRRGRQKLRQPQPQQPKRGKRKRKRAVEGSRKSWSPWLSWSPWLNWKRP (in
FT isoform 4)"
FT /evidence="ECO:0000303|PubMed:11502739,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_032034"
FT CONFLICT 172
FT /note="W -> C (in Ref. 2; AAD41655)"
FT /evidence="ECO:0000305"
FT CONFLICT 399
FT /note="F -> L (in Ref. 5; AAH11422)"
FT /evidence="ECO:0000305"
FT CONFLICT 564
FT /note="Y -> C (in Ref. 2; AAD41655)"
FT /evidence="ECO:0000305"
FT HELIX 522..524
FT /evidence="ECO:0007829|PDB:2HDV"
FT STRAND 528..531
FT /evidence="ECO:0007829|PDB:2HDV"
FT HELIX 534..542
FT /evidence="ECO:0007829|PDB:2HDV"
FT HELIX 545..548
FT /evidence="ECO:0007829|PDB:2HDV"
FT STRAND 551..556
FT /evidence="ECO:0007829|PDB:2HDV"
FT STRAND 558..560
FT /evidence="ECO:0007829|PDB:2HDX"
FT STRAND 563..570
FT /evidence="ECO:0007829|PDB:2HDV"
FT STRAND 573..581
FT /evidence="ECO:0007829|PDB:2HDV"
FT STRAND 587..589
FT /evidence="ECO:0007829|PDB:2HDV"
FT STRAND 592..596
FT /evidence="ECO:0007829|PDB:2HDV"
FT HELIX 597..604
FT /evidence="ECO:0007829|PDB:2HDV"
FT TURN 612..616
FT /evidence="ECO:0007829|PDB:2HDX"
SQ SEQUENCE 756 AA; 79625 MW; 388BDC44267E6DE8 CRC64;
MNGAPSPEDG VFPSPPALPP PPPPSWQEFC ESHARAAALD LARRFRLYLA SHPQYAEPGA
EAAFSGRFAE LFLQHFEAEV ARASGSLSPP VLAPLSPGVE IPPSHDLSLE SCRVGGPLAV
LGPSRSSEDL AGPLPSSVPS STTSSKPKLK KRFSLRSVGR SVRGSVRGIL QWRGAVDSPS
QAGPLETTSG PPVLGGNSNS NSSGGAGTVG RALANDGTSP GERWTHRFER LRLSRGGGTL
KDGAGMIQRE ELLSFMGAEE AAPDPAGVGR GGGAAGLTSG GGGQPQWQKC RLLLRSEGEG
GGGSRLEFFV PPKASRPRLS IPCSTITDVR TATALEMPDR ENTFVVKVEG PSEYILETSD
ALHVKAWVSD IQECLSPGPC PAISPRPMTL PLAPGTSFFT KDNTDSLELP CLNHSESLPS
QDLLLGPSES NDRLSQGAYG GLSDRPSASF SPSSASIAAS HFDSMELLPP ELPPRIPIEE
GPPAGTVHPL STPYPPLDTP EAATGSFLFQ GESEGGEGDQ PLSGYPWFHG MLSRLKAAQL
VLEGGTGSHG VFLVRQSETR RGEYVLTFNF QGKAKHLRLS LNEEGQCRVQ HLWFQSIFDM
LEHFRVHPIP LESGGSSDVV LVSYVPSQRQ QERSTSRDPA QPSEPPPWTD PPHPGAEEAS
GAPEVAAATA AAAKERQEKE KAGSGGVQEE LVPVAELVPM VELEEAIAPG TEAQGGAGSS
GDLEVSLMVQ LQQLPLGGNG EEGGHPRAIN NQYSFV
