SH2 domain-containing adapter protein B

 SHB_MOUSE               Reviewed;         503 AA.
 Q6PD21; A2AKW3; Q3ULM3;
 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
 25-JUL-2006, sequence version 2.
 02-DEC-2020, entry version 120.
 RecName: Full=SH2 domain-containing adapter protein B;
 Name=Shb;
 Mus musculus (Mouse).
 Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
 Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
 Murinae; Mus; Mus.
 NCBI_TaxID=10090;
 [1]
 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
 STRAIN=C57BL/6J; TISSUE=Embryo;
 PubMed=16141072; DOI=10.1126/science.1112014;
 Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
 Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
 Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
 Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
 Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
 Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
 Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
 Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
 Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
 Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
 Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
 Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
 Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
 Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
 Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
 Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
 Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
 Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
 Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
 Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
 Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
 Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
 Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
 Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
 Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
 van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
 Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
 Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
 Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
 Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
 Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
 Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
 Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
 Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
 "The transcriptional landscape of the mammalian genome.";
 Science 309:1559-1563(2005).
 [2]
 NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
 STRAIN=C57BL/6J;
 PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
 Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
 Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
 Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
 Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
 Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
 Eichler E.E., Ponting C.P.;
 "Lineage-specific biology revealed by a finished genome assembly of the
 mouse.";
 PLoS Biol. 7:E1000112-E1000112(2009).
 [3]
 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
 STRAIN=C57BL/6J; TISSUE=Fetal brain;
 PubMed=15489334; DOI=10.1101/gr.2596504;
 The MGC Project Team;
 "The status, quality, and expansion of the NIH full-length cDNA project:
 the Mammalian Gene Collection (MGC).";
 Genome Res. 14:2121-2127(2004).
 [4]
 TISSUE SPECIFICITY.
 PubMed=8302579;
 Welsh M., Mares J., Karlsson T., Lavergne C., Breant B., Claesson-Welsh L.;
 "Shb is a ubiquitously expressed Src homology 2 protein.";
 Oncogene 9:19-27(1994).
 [5]
 INDUCTION BY OKADAIC ACID AND GENISTEIN.
 PubMed=8777141; DOI=10.1016/0898-6568(95)02019-5;
 Lavergne C., Mares J., Karlsson T., Breant B., Welsh M.;
 "Control of SHB gene expression by protein phosphorylation.";
 Cell. Signal. 8:55-58(1996).
 [6]
 INTERACTION WITH PTPN11.
 PubMed=12181353; DOI=10.1091/mbc.e02-02-0103;
 Cross M.J., Lu L., Magnusson P., Nyqvist D., Holmqvist K., Welsh M.,
 Claesson-Welsh L.;
 "The Shb adaptor protein binds to tyrosine 766 in the FGFR-1 and regulates
 the Ras/MEK/MAPK pathway via FRS2 phosphorylation in endothelial cells.";
 Mol. Biol. Cell 13:2881-2893(2002).
 [7]
 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
 TISSUE=Liver;
 PubMed=17242355; DOI=10.1073/pnas.0609836104;
 Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
 "Large-scale phosphorylation analysis of mouse liver.";
 Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
 [8]
 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-382, AND IDENTIFICATION BY
 MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
 PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
 Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
 Thibault P.;
 "The phagosomal proteome in interferon-gamma-activated macrophages.";
 Immunity 30:143-154(2009).
 [9]
 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-382, AND IDENTIFICATION BY
 MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
 TISSUE=Brain, Heart, Kidney, Lung, and Pancreas;
 PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
 Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
 Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
 "A tissue-specific atlas of mouse protein phosphorylation and expression.";
 Cell 143:1174-1189(2010).
 -!- FUNCTION: Adapter protein which regulates several signal transduction
     cascades by linking activated receptors to downstream signaling
     components. May play a role in angiogenesis by regulating FGFR1, VEGFR2
     and PDGFR signaling. May also play a role in T-cell antigen
     receptor/TCR signaling, interleukin-2 signaling, apoptosis and neuronal
     cells differentiation by mediating basic-FGF and NGF-induced signaling
     cascades. May also regulate IRS1 and IRS2 signaling in insulin-
     producing cells (By similarity). {ECO:0000250}.
 -!- SUBUNIT: Interacts with phosphorylated 'Tyr-720' of the ligand-
     activated receptor PDGFRA via its SH2 domain. Interacts with the
     ligand-activated receptors PDGFRB, FGFR1, KDR/VEGFR2, IL2RB and IL2RG.
     Interacts with EPS8 and V-SRC. Interacts with GRB2 and GRAP. Interacts
     with CD3Z. Interacts with tyrosine-phosphorylated LAT upon T-cell
     antigen receptor activation. Interacts with PLCG1. Interacts with
     ZAP70, LCP2/SLP-76, VAV1 and GRAP2. Interacts with JAK1 and JAK3.
     Interacts with PTK2/FAK1. Interacts with CRK/CrKII. Interacts with IRS2
     (By similarity). Interacts with PTPN11. {ECO:0000250,
     ECO:0000269|PubMed:12181353}.
 -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane
     {ECO:0000250}; Peripheral membrane protein {ECO:0000250}; Cytoplasmic
     side {ECO:0000250}. Note=Associates with membrane lipid rafts upon TCR
     stimulation. {ECO:0000250}.
 -!- ALTERNATIVE PRODUCTS:
     Event=Alternative splicing; Named isoforms=2;
     Name=1;
       IsoId=Q6PD21-1; Sequence=Displayed;
     Name=2;
       IsoId=Q6PD21-2; Sequence=VSP_019848, VSP_019849, VSP_019850;
 -!- TISSUE SPECIFICITY: Expressed in heart, liver, brain and kidney (at
     protein level). {ECO:0000269|PubMed:8302579}.
 -!- INDUCTION: Up-regulated by okadaic acid and genistein.
     {ECO:0000269|PubMed:8777141}.
 -!- DOMAIN: The SH2 domain preferentially binds phosphopeptides with the
     consensus sequence Y-[TVI]-X-L and mediates interaction with PDGFRA,
     PDGFRB, FGRFR1, IL2RB, IL2RG, CD3Z and CRK/CrKII. {ECO:0000250}.
 -!- PTM: Phosphorylated upon PDGFRA, PDGFRB, TCR, IL2 receptor, FGFR1 or
     VEGFR2 activation. {ECO:0000250}.
 -!- SEQUENCE CAUTION:
     Sequence=AAH58986.1; Type=Erroneous initiation; Evidence={ECO:0000305};
 ---------------------------------------------------------------------------
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 EMBL; AK145414; BAE26425.1; -; mRNA.
 EMBL; AL772376; -; NOT_ANNOTATED_CDS; Genomic_DNA.
 EMBL; BC058986; AAH58986.1; ALT_INIT; mRNA.
 CCDS; CCDS51173.1; -. [Q6PD21-1]
 RefSeq; NP_001028478.1; NM_001033306.1. [Q6PD21-1]
 BioGRID; 230937; 2.
 IntAct; Q6PD21; 2.
 MINT; Q6PD21; -.
 STRING; 10090.ENSMUSP00000060433; -.
 iPTMnet; Q6PD21; -.
 PhosphoSitePlus; Q6PD21; -.
 PaxDb; Q6PD21; -.
 PRIDE; Q6PD21; -.
 Ensembl; ENSMUST00000061986; ENSMUSP00000060433; ENSMUSG00000044813. [Q6PD21-1]
 GeneID; 230126; -.
 KEGG; mmu:230126; -.
 UCSC; uc008sst.2; mouse. [Q6PD21-1]
 UCSC; uc008ssu.1; mouse. [Q6PD21-2]
 CTD; 6461; -.
 MGI; MGI:98294; Shb.
 eggNOG; ENOG502RT81; Eukaryota.
 GeneTree; ENSGT00940000161591; -.
 HOGENOM; CLU_029444_0_0_1; -.
 InParanoid; Q6PD21; -.
 OMA; PAAASCF; -.
 OrthoDB; 1120795at2759; -.
 PhylomeDB; Q6PD21; -.
 TreeFam; TF325799; -.
 Reactome; R-MMU-4420097; VEGFA-VEGFR2 Pathway.
 BioGRID-ORCS; 230126; 3 hits in 19 CRISPR screens.
 ChiTaRS; Shb; mouse.
 PRO; PR:Q6PD21; -.
 Proteomes; UP000000589; Chromosome 4.
 RNAct; Q6PD21; protein.
 Bgee; ENSMUSG00000044813; Expressed in decidua and 230 other tissues.
 ExpressionAtlas; Q6PD21; baseline and differential.
 Genevisible; Q6PD21; MM.
 GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; ISO:MGI.
 GO; GO:0005829; C:cytosol; ISO:MGI.
 GO; GO:0005654; C:nucleoplasm; ISO:MGI.
 GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
 GO; GO:0001784; F:phosphotyrosine residue binding; ISO:MGI.
 GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
 GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
 GO; GO:0042100; P:B cell proliferation; IDA:MGI.
 GO; GO:0001568; P:blood vessel development; IMP:MGI.
 GO; GO:0048514; P:blood vessel morphogenesis; IMP:MGI.
 GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
 GO; GO:0071425; P:hematopoietic stem cell proliferation; IMP:MGI.
 GO; GO:0030097; P:hemopoiesis; IMP:MGI.
 GO; GO:1900194; P:negative regulation of oocyte maturation; IMP:MGI.
 GO; GO:0006469; P:negative regulation of protein kinase activity; IMP:MGI.
 GO; GO:0045931; P:positive regulation of mitotic cell cycle; IMP:MGI.
 GO; GO:0045624; P:positive regulation of T-helper cell differentiation; IMP:MGI.
 GO; GO:0050852; P:T cell receptor signaling pathway; IMP:MGI.
 CDD; cd10389; SH2_SHB; 1.
 Gene3D; 3.30.505.10; -; 1.
 InterPro; IPR000980; SH2.
 InterPro; IPR036860; SH2_dom_sf.
 InterPro; IPR035040; SHB.
 InterPro; IPR035045; SHB_SH2.
 PANTHER; PTHR15127:SF31; PTHR15127:SF31; 1.
 Pfam; PF00017; SH2; 1.
 PRINTS; PR00401; SH2DOMAIN.
 SMART; SM00252; SH2; 1.
 SUPFAM; SSF55550; SSF55550; 1.
 PROSITE; PS50001; SH2; 1.
 1: Evidence at protein level;
 Alternative splicing; Angiogenesis; Apoptosis; Cell membrane; Cytoplasm;
 Developmental protein; Differentiation; Isopeptide bond; Membrane;
 Phosphoprotein; Reference proteome; SH2 domain; Ubl conjugation.
 CHAIN           1..503
                 /note="SH2 domain-containing adapter protein B"
                 /id="PRO_0000246325"
 DOMAIN          404..498
                 /note="SH2"
                 /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
 MOD_RES         101
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:Q15464"
 MOD_RES         301
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:Q15464"
 MOD_RES         311
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:Q15464"
 MOD_RES         382
                 /note="Phosphoserine"
                 /evidence="ECO:0000244|PubMed:19144319,
                 ECO:0000244|PubMed:21183079"
 CROSSLNK        186
                 /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
                 G-Cter in SUMO2)"
                 /evidence="ECO:0000250|UniProtKB:Q15464"
 VAR_SEQ         1..262
                 /note="Missing (in isoform 2)"
                 /evidence="ECO:0000303|PubMed:16141072"
                 /id="VSP_019848"
 VAR_SEQ         443..479
                 /note="KSNQGFMHMKLAKTKEKYVLGQNSPPFDSVPEVIHYY -> NYADPEAVCAM
                 PILPRTARPSVRPSVHPSVRKICARR (in isoform 2)"
                 /evidence="ECO:0000303|PubMed:16141072"
                 /id="VSP_019849"
 VAR_SEQ         480..503
                 /note="Missing (in isoform 2)"
                 /evidence="ECO:0000303|PubMed:16141072"
                 /id="VSP_019850"
 SEQUENCE   503 AA;  54708 MW;  9A668DFC429F41E3 CRC64;
 MAKWLNKYFS LGNSKTKSPP QPPRPDYREQ RRRGERREQP PQAVPQACSA SSASCGSAAA
 CFSASSGSLP DDSGSTSDLI RAYRAQKERD FEDPYNGPGS SLRKLRAMCR LDYCGGGGGG
 DPGGGQRAFT AAAGAAGCCC AAAGAGAAAS SSSSSGSPHL YRSSSERRPT TPAEVRYISP
 KHRLIKVESA SAAGDPPGGV CSGGRTWSPT TCGGKKLLNK CSAEETGAGQ KDKVTIADDY
 SDPFDAKSDL KSKAGKGESA GYMEPYEAQR IMTEFQRQES VRSQHKGIQL YDTPYEPEGQ
 SVDSDSESTV SLRLRESKLP QDDDRPADEY DQPWEWNRVT IPALAAQFNG NEKRQSSPSP
 SRDRRRQLRA PGGGFKPIKH GSPEFCGILG ERVDPTIPLE KQIWYHGAIS RSDAENLLRL
 CKECSYLVRN SQTSKHDYSL SLKSNQGFMH MKLAKTKEKY VLGQNSPPFD SVPEVIHYYT
 TRKLPIKGAE HLSLLYPVAV RTL

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