SH2B2_MOUSE
ID SH2B2_MOUSE Reviewed; 621 AA.
AC Q9JID9; O88936; Q6PG00;
DT 15-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=SH2B adapter protein 2;
DE AltName: Full=Adapter protein with pleckstrin homology and Src homology 2 domains;
DE AltName: Full=SH2 and PH domain-containing adapter protein APS;
GN Name=Sh2b2; Synonyms=Aps;
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 {ECO:0000312|EMBL:AAF37891.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND PHOSPHORYLATION AT
RP TYR-47 AND TYR-618.
RC TISSUE=Splenocyte {ECO:0000312|EMBL:AAF37891.1};
RX PubMed=10872802; DOI=10.1006/bbrc.2000.2736;
RA Iseki M., Takaki S., Takatsu K.;
RT "Molecular cloning of the mouse APS as a member of the Lnk family adaptor
RT proteins.";
RL Biochem. Biophys. Res. Commun. 272:45-54(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Adipose tissue;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 [4] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 370-525.
RA Belhadri A., Goren H.J.;
RT "Insulin receptor cytoplasmic domain contains five functional SH2 motifs:
RT mapping SH2 motifs for p85alpha, c-Src, c-Abl, Grb-10, ras-Gap, and mouse
RT APS.";
RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN [5] {ECO:0000305}
RP INTERACTION WITH EPOR AND KIT.
RX PubMed=12444928; DOI=10.1042/bj20020716;
RA Wollberg P., Lennartsson J., Gottfridsson E., Yoshimura A., Ronnstrand L.;
RT "The adapter protein APS associates with the multifunctional docking sites
RT Tyr-568 and Tyr-936 in c-Kit.";
RL Biochem. J. 370:1033-1038(2003).
RN [6]
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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-597, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-130 AND SER-303, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, and 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 [9] {ECO:0000305}
RP STRUCTURE BY NMR OF 178-299.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the pleckstrin homology domain of mouse APS.";
RL Submitted (MAY-2004) to the PDB data bank.
CC -!- FUNCTION: Adapter protein for several members of the tyrosine kinase
CC receptor family. Involved in multiple signaling pathways. May be
CC involved in coupling from immunoreceptor to Ras signaling. Acts as a
CC negative regulator of cytokine signaling in collaboration with CBL.
CC Binds to EPOR and suppresses EPO-induced STAT5 activation, possibly
CC through a masking effect on STAT5 docking sites in EPOR. Suppresses
CC PDGF-induced mitogenesis. May induce cytoskeletal reorganization via
CC interaction with VAV3 (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homodimer. Interacts with KIT/c-KIT, SHC1, EPOR, PDGFR, VAV1
CC and VAV3. Interacts (via N-terminal region) with SHC1. Interacts (via
CC the phosphorylated C-terminus) with GRB2. Interacts (via its SH2
CC domain) with EPOR, INSR and KIT. Interacts with GRB2 after B-cell
CC antigen receptor stimulation. Interacts (via PH domain) with VAV3.
CC Interacts with NTRK1, NTRK2 and NTRK3 (phosphorylated); after
CC stimulation of the receptor by its extracellular ligand and subsequent
CC autophosphorylation of the receptor. Binds INSR, GRB2, ASB6 and CAP.
CC Insulin stimulation leads to dissociation of CAP. Binds CBS only when
CC SH2B2/APS has become phosphorylated. INSR binding does not depend on
CC the phosphorylation of SH2B2/APS (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q9JID9; Q61851: Fgfr3; NbExp=3; IntAct=EBI-8100899, EBI-6287052;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane
CC {ECO:0000250}. Note=Cytoplasmic before PDGF stimulation. After PDGF
CC stimulation, localized at the cell membrane and peripheral region (By
CC similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Strongly expressed in brain; also expressed in
CC spleen, kidney and skeletal muscle, and at low levels in small
CC intestine and bone marrow. Strongly expressed in B-cell lines, but not
CC T-cell lines. Also expressed in myeloid and fibroblast cell lines.
CC {ECO:0000269|PubMed:10872802}.
CC -!- PTM: Tyrosine phosphorylated by JAK2, KIT and other kinases activated
CC by B-cell receptor in response to stimulation with cytokines, IL3, IL5,
CC PDGF, IGF1, IGF2, CSF2/GM-CSF and cross-linking of the B-cell receptor
CC complex. {ECO:0000269|PubMed:10872802}.
CC -!- SIMILARITY: Belongs to the SH2B adapter family. {ECO:0000305}.
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DR EMBL; AF234838; AAF37891.1; -; mRNA.
DR EMBL; AK140319; BAE24331.1; -; mRNA.
DR EMBL; AK140325; BAE24336.1; -; mRNA.
DR EMBL; AF086810; AAC36336.1; -; mRNA.
DR EMBL; BC057334; AAH57334.1; -; mRNA.
DR CCDS; CCDS39327.1; -.
DR PIR; JC7278; JC7278.
DR RefSeq; NP_001289867.1; NM_001302938.1.
DR RefSeq; NP_001289868.1; NM_001302939.1.
DR RefSeq; NP_061295.2; NM_018825.4.
DR RefSeq; XP_006504483.2; XM_006504420.3.
DR RefSeq; XP_006504485.1; XM_006504422.2.
DR PDB; 1V5M; NMR; -; A=177-299.
DR PDBsum; 1V5M; -.
DR AlphaFoldDB; Q9JID9; -.
DR BMRB; Q9JID9; -.
DR SMR; Q9JID9; -.
DR BioGRID; 204795; 9.
DR IntAct; Q9JID9; 1.
DR MINT; Q9JID9; -.
DR STRING; 10090.ENSMUSP00000005188; -.
DR iPTMnet; Q9JID9; -.
DR PhosphoSitePlus; Q9JID9; -.
DR jPOST; Q9JID9; -.
DR MaxQB; Q9JID9; -.
DR PaxDb; Q9JID9; -.
DR PeptideAtlas; Q9JID9; -.
DR PRIDE; Q9JID9; -.
DR ProteomicsDB; 261341; -.
DR Antibodypedia; 31045; 80 antibodies from 17 providers.
DR DNASU; 23921; -.
DR Ensembl; ENSMUST00000005188; ENSMUSP00000005188; ENSMUSG00000005057.
DR Ensembl; ENSMUST00000196397; ENSMUSP00000142398; ENSMUSG00000005057.
DR GeneID; 23921; -.
DR KEGG; mmu:23921; -.
DR UCSC; uc009aag.2; mouse.
DR CTD; 10603; -.
DR MGI; MGI:1345171; Sh2b2.
DR VEuPathDB; HostDB:ENSMUSG00000005057; -.
DR eggNOG; ENOG502QT43; Eukaryota.
DR GeneTree; ENSGT00950000183191; -.
DR InParanoid; Q9JID9; -.
DR OMA; KMEGERF; -.
DR OrthoDB; 556279at2759; -.
DR PhylomeDB; Q9JID9; -.
DR TreeFam; TF323184; -.
DR Reactome; R-MMU-1433559; Regulation of KIT signaling.
DR Reactome; R-MMU-983231; Factors involved in megakaryocyte development and platelet production.
DR BioGRID-ORCS; 23921; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Sh2b2; mouse.
DR EvolutionaryTrace; Q9JID9; -.
DR PRO; PR:Q9JID9; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q9JID9; protein.
DR Bgee; ENSMUSG00000005057; Expressed in brown adipose tissue and 164 other tissues.
DR ExpressionAtlas; Q9JID9; baseline and differential.
DR Genevisible; Q9JID9; MM.
DR GO; GO:0005884; C:actin filament; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0001726; C:ruffle; IDA:MGI.
DR GO; GO:0001725; C:stress fiber; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0042169; F:SH2 domain binding; ISO:MGI.
DR GO; GO:0035591; F:signaling adaptor activity; IDA:UniProtKB.
DR GO; GO:0005068; F:transmembrane receptor protein tyrosine kinase adaptor activity; IDA:MGI.
DR GO; GO:0030036; P:actin cytoskeleton organization; IMP:MGI.
DR GO; GO:0050851; P:antigen receptor-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0050853; P:B cell receptor signaling pathway; IDA:MGI.
DR GO; GO:0001922; P:B-1 B cell homeostasis; IMP:MGI.
DR GO; GO:0050873; P:brown fat cell differentiation; IDA:MGI.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IDA:MGI.
DR GO; GO:0051649; P:establishment of localization in cell; ISA:MGI.
DR GO; GO:0042593; P:glucose homeostasis; ISA:MGI.
DR GO; GO:0046323; P:glucose import; ISA:MGI.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IDA:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:UniProtKB.
DR GO; GO:0046325; P:negative regulation of glucose import; ISA:MGI.
DR GO; GO:0007399; P:nervous system development; ISO:MGI.
DR GO; GO:0050776; P:regulation of immune response; IMP:MGI.
DR GO; GO:0019222; P:regulation of metabolic process; IMP:MGI.
DR GO; GO:0046578; P:regulation of Ras protein signal transduction; ISO:MGI.
DR CDD; cd10411; SH2_SH2B2; 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; IPR030520; SH2B2.
DR InterPro; IPR035058; SH2B2_SH2.
DR PANTHER; PTHR10872; PTHR10872; 1.
DR PANTHER; PTHR10872:SF4; PTHR10872:SF4; 1.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF08916; Phe_ZIP; 1.
DR Pfam; PF00017; SH2; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00252; SH2; 1.
DR SUPFAM; SSF109805; SSF109805; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS50001; SH2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Cytoplasm; Membrane; Phosphoprotein;
KW Reference proteome; SH2 domain.
FT CHAIN 1..621
FT /note="SH2B adapter protein 2"
FT /id="PRO_0000064648"
FT DOMAIN 186..299
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145,
FT ECO:0000305"
FT DOMAIN 409..507
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191,
FT ECO:0000305"
FT REGION 143..166
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 507..528
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 549..611
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 549..572
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 47
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000305|PubMed:10872802"
FT MOD_RES 130
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 303
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 597
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319"
FT MOD_RES 618
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000305|PubMed:10872802"
FT CONFLICT 125
FT /note="S -> W (in Ref. 1; AAF37891)"
FT /evidence="ECO:0000305"
FT CONFLICT 442
FT /note="R -> K (in Ref. 4; AAC36336)"
FT /evidence="ECO:0000305"
FT STRAND 189..197
FT /evidence="ECO:0007829|PDB:1V5M"
FT STRAND 203..205
FT /evidence="ECO:0007829|PDB:1V5M"
FT STRAND 212..220
FT /evidence="ECO:0007829|PDB:1V5M"
FT STRAND 222..224
FT /evidence="ECO:0007829|PDB:1V5M"
FT STRAND 227..234
FT /evidence="ECO:0007829|PDB:1V5M"
FT STRAND 237..239
FT /evidence="ECO:0007829|PDB:1V5M"
FT TURN 246..248
FT /evidence="ECO:0007829|PDB:1V5M"
FT STRAND 258..260
FT /evidence="ECO:0007829|PDB:1V5M"
FT STRAND 276..280
FT /evidence="ECO:0007829|PDB:1V5M"
FT HELIX 284..299
FT /evidence="ECO:0007829|PDB:1V5M"
SQ SEQUENCE 621 AA; 66557 MW; DB20BD352F96D69E CRC64;
MNGATPSSAA APAPVPDWRQ FCELHAQVAA VDFAHKFCRF LRDNPTYDTP DAGTSFSRHF
AANFLAVFSE EVRRVLGSAA DTMEPEPAVT SVTSALKTAT YGHSRSSEDV SAHAATKARV
RKGFSLRNMS LCVVDGVRDL WHRRSSPEPD GGATPKAAEP ASEPRDKWTR RLRLARTLAA
KVELVDIQRE GALRFMVADD AASGPGGTAQ WQKCRLLLRR AVAGERFRLE FFVPPKASRP
KVSIPLSAII EVRTTMPLEM PEKDNTFVLK VENGAEYILE TIDSLQKHSW VADIQGCVDP
GDSEEDTGLS CARGGCLASR VASCSCELLT DADMPRPPET TTAVGAVVTA PHGRARDTVG
ESLAHVPLET FLQTLESSGG VSENNNPGDE GAELDTDAEA ELELSDYPWF HGTLSRVKAA
QLVLAGGPRS HGLFVIRQSE TRPGECVLTF NFQGKAKHLR LSLNGHGQCH VQHLWFQSVF
DMLRHFHTHP IPLESGGSAD ITLRSYVRAQ GPPPDPGPAP NTAAPVPACW TEPAGQHYFS
SLATATCPPA SPSNGAGASS SSGSSSSATS LPPRPAEGPL SAHSRSNSTE HLLDAASGAT
EEPTEATLGR ARAVENQYSF Y
