STA5B_HUMAN
ID STA5B_HUMAN Reviewed; 787 AA.
AC P51692; Q8WWS8;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 16-JAN-2004, sequence version 2.
DT 03-AUG-2022, entry version 215.
DE RecName: Full=Signal transducer and activator of transcription 5B;
GN Name=STAT5B;
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], AND FUNCTION.
RX PubMed=8732682; DOI=10.1210/mend.10.5.8732682;
RA Silva C.M., Lu H., Day R.N.;
RT "Characterization and cloning of STAT5 from IM-9 cells and its activation
RT by growth hormone.";
RL Mol. Endocrinol. 10:508-518(1996).
RN [2]
RP SEQUENCE REVISION TO 628; 717 AND 720.
RA Silva C.M., Lu H.;
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8631883; DOI=10.1074/jbc.271.18.10738;
RA Lin J.-X., Mietz J., Modi W.S., John S., Leonard W.J.;
RT "Cloning of human Stat5B. Reconstitution of interleukin-2-induced Stat5A
RT and Stat5B DNA binding activity in COS-7 cells.";
RL J. Biol. Chem. 271:10738-10744(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=12039059; DOI=10.1016/s0378-1119(02)00421-3;
RA Ambrosio R., Fimiani G., Monfregola J., Sanzari E., De Felice N.,
RA Salerno M.C., Pignata C., D'Urso M., Ursini M.V.;
RT "The structure of human STAT5A and B genes reveals two regions of nearly
RT identical sequence and an alternative tissue specific STAT5B promoter.";
RL Gene 285:311-318(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lymph;
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 PHOSPHORYLATION BY INSR, INTERACTION WITH INSR, AND MUTAGENESIS OF THR-684.
RX PubMed=9428692; DOI=10.1111/j.1432-1033.1997.0411a.x;
RA Sawka-Verhelle D., Filloux C., Tartare-Deckert S., Mothe I.,
RA Van Obberghen E.;
RT "Identification of Stat 5B as a substrate of the insulin receptor.";
RL Eur. J. Biochem. 250:411-417(1997).
RN [7]
RP INTERACTION WITH NMI.
RX PubMed=9989503; DOI=10.1016/s0092-8674(00)80965-4;
RA Zhu M.-H., John S., Berg M., Leonard W.J.;
RT "Functional association of Nmi with Stat5 and Stat1 in IL-2- and IFNgamma-
RT mediated signaling.";
RL Cell 96:121-130(1999).
RN [8]
RP PHOSPHORYLATION AT TYR-699, AND MUTAGENESIS OF TYR-699.
RX PubMed=12411494; DOI=10.1093/emboj/cdf562;
RA Klejman A., Schreiner S.J., Nieborowska-Skorska M., Slupianek A.,
RA Wilson M., Smithgall T.E., Skorski T.;
RT "The Src family kinase Hck couples BCR/ABL to STAT5 activation in myeloid
RT leukemia cells.";
RL EMBO J. 21:5766-5774(2002).
RN [9]
RP CAUTION.
RX PubMed=11773439; DOI=10.1210/mend.16.1.0761;
RA Aoki N., Matsuda T.;
RT "A nuclear protein tyrosine phosphatase TC-PTP is a potential negative
RT regulator of the PRL-mediated signaling pathway: dephosphorylation and
RT deactivation of signal transducer and activator of transcription 5a and 5b
RT by TC-PTP in nucleus.";
RL Mol. Endocrinol. 16:58-69(2002).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-193, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-193, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [12]
RP IDENTIFICATION 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 [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-128, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-193, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-90; SER-128 AND SER-193, AND
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 [17]
RP RETRACTION NOTICE OF PUBMED:23186163, AND CAUTION.
RX PubMed=24319783; DOI=10.1210/me.2013-1264;
RA Aoki N., Matsuda T.;
RT "Retraction.";
RL Mol. Endocrinol. 27:1982-1982(2013).
RN [18]
RP INTERACTION WITH NCOA1.
RX PubMed=12954634; DOI=10.1074/jbc.m303644200;
RA Litterst C.M., Kliem S., Marilley D., Pfitzner E.;
RT "NCoA-1/SRC-1 is an essential coactivator of STAT5 that binds to the FDL
RT motif in the alpha-helical region of the STAT5 transactivation domain.";
RL J. Biol. Chem. 278:45340-45351(2003).
RN [19]
RP PHOSPHORYLATION IN RESPONSE TO FLT3 SIGNALING.
RX PubMed=14504097; DOI=10.1182/blood-2003-02-0418;
RA Taketani T., Taki T., Sugita K., Furuichi Y., Ishii E., Hanada R.,
RA Tsuchida M., Sugita K., Ida K., Hayashi Y.;
RT "FLT3 mutations in the activation loop of tyrosine kinase domain are
RT frequently found in infant ALL with MLL rearrangements and pediatric ALL
RT with hyperdiploidy.";
RL Blood 103:1085-1088(2004).
RN [20]
RP REVIEW ON ROLE IN KIT SIGNALING.
RX PubMed=15526160; DOI=10.1007/s00018-004-4189-6;
RA Ronnstrand L.;
RT "Signal transduction via the stem cell factor receptor/c-Kit.";
RL Cell. Mol. Life Sci. 61:2535-2548(2004).
RN [21]
RP PHOSPHORYLATION BY JAK2.
RX PubMed=15121872; DOI=10.1128/mcb.24.10.4557-4570.2004;
RA Kurzer J.H., Argetsinger L.S., Zhou Y.J., Kouadio J.L., O'Shea J.J.,
RA Carter-Su C.;
RT "Tyrosine 813 is a site of JAK2 autophosphorylation critical for activation
RT of JAK2 by SH2-B beta.";
RL Mol. Cell. Biol. 24:4557-4570(2004).
RN [22]
RP INTERACTION WITH SOCS7.
RX PubMed=15677474; DOI=10.1074/jbc.m411596200;
RA Martens N., Uzan G., Wery M., Hooghe R., Hooghe-Peters E.L., Gertler A.;
RT "Suppressor of cytokine signaling 7 inhibits prolactin, growth hormone, and
RT leptin signaling by interacting with STAT5 or STAT3 and attenuating their
RT nuclear translocation.";
RL J. Biol. Chem. 280:13817-13823(2005).
RN [23]
RP INVOLVEMENT IN GHISID1.
RX PubMed=15827093; DOI=10.1210/jc.2005-0515;
RA Hwa V., Little B., Adiyaman P., Kofoed E.M., Pratt K.L., Ocal G.,
RA Berberoglu M., Rosenfeld R.G.;
RT "Severe growth hormone insensitivity resulting from total absence of signal
RT transducer and activator of transcription 5b.";
RL J. Clin. Endocrinol. Metab. 90:4260-4266(2005).
RN [24]
RP PHOSPHORYLATION AT TYR-699 BY PTK6.
RX PubMed=17997837; DOI=10.1186/bcr1794;
RA Weaver A.M., Silva C.M.;
RT "Signal transducer and activator of transcription 5b: a new target of
RT breast tumor kinase/protein tyrosine kinase 6.";
RL Breast Cancer Res. 9:R79-R79(2007).
RN [25]
RP FUNCTION.
RX PubMed=20702587; DOI=10.1091/mbc.e10-01-0040;
RA Vignudelli T., Selmi T., Martello A., Parenti S., Grande A., Gemelli C.,
RA Zanocco-Marani T., Ferrari S.;
RT "ZFP36L1 negatively regulates erythroid differentiation of CD34+
RT hematopoietic stem cells by interfering with the Stat5b pathway.";
RL Mol. Biol. Cell 21:3340-3351(2010).
RN [26]
RP INTERACTION WITH CPEB3.
RX PubMed=20639532; DOI=10.1093/nar/gkq634;
RA Peng S.C., Lai Y.T., Huang H.Y., Huang H.D., Huang Y.S.;
RT "A novel role of CPEB3 in regulating EGFR gene transcription via
RT association with Stat5b in neurons.";
RL Nucleic Acids Res. 38:7446-7457(2010).
RN [27]
RP PHOSPHORYLATION IN RESPONSE TO KIT SIGNALING.
RX PubMed=21135090; DOI=10.1074/jbc.m110.182642;
RA Chaix A., Lopez S., Voisset E., Gros L., Dubreuil P., De Sepulveda P.;
RT "Mechanisms of STAT protein activation by oncogenic KIT mutants in
RT neoplastic mast cells.";
RL J. Biol. Chem. 286:5956-5966(2011).
RN [28]
RP INVOLVEMENT IN GHISID2, VARIANTS GHISID2 PRO-177; ARG-474 AND VAL-478,
RP CHARACTERIZATION OF VARIANTS GHISID2 PRO-177; ARG-474 AND VAL-478,
RP FUNCTION, HOMODIMERIZATION, AND SUBCELLULAR LOCATION.
RX PubMed=29844444; DOI=10.1038/s41467-018-04521-0;
RA Klammt J., Neumann D., Gevers E.F., Andrew S.F., Schwartz I.D.,
RA Rockstroh D., Colombo R., Sanchez M.A., Vokurkova D., Kowalczyk J.,
RA Metherell L.A., Rosenfeld R.G., Pfaeffle R., Dattani M.T., Dauber A.,
RA Hwa V.;
RT "Dominant-negative STAT5B mutations cause growth hormone insensitivity with
RT short stature and mild immune dysregulation.";
RL Nat. Commun. 9:2105-2105(2018).
RN [29]
RP VARIANT GHISID1 PRO-630.
RX PubMed=13679528; DOI=10.1056/nejmoa022926;
RA Kofoed E.M., Hwa V., Little B., Woods K.A., Buckway C.K., Tsubaki J.,
RA Pratt K.L., Bezrodnik L., Jasper H., Tepper A., Heinrich J.J.,
RA Rosenfeld R.G.;
RT "Growth hormone insensitivity associated with a STAT5b mutation.";
RL N. Engl. J. Med. 349:1139-1147(2003).
RN [30]
RP VARIANT GHISID1 SER-646, AND CHARACTERIZATION OF VARIANT GHISID1 SER-646.
RX PubMed=22419735; DOI=10.1210/jc.2011-2554;
RA Scaglia P.A., Martinez A.S., Feigerlova E., Bezrodnik L., Gaillard M.I.,
RA Di Giovanni D., Ballerini M.G., Jasper H.G., Heinrich J.J., Fang P.,
RA Domene H.M., Rosenfeld R.G., Hwa V.;
RT "A Novel Missense Mutation in the SH2 Domain of the STAT5B Gene Results in
RT a transcriptionally inactive STAT5b associated with severe IGF-I
RT deficiency, immune dysfunction, and lack of pulmonary disease.";
RL J. Clin. Endocrinol. Metab. 97:E830-839(2012).
CC -!- FUNCTION: Carries out a dual function: signal transduction and
CC activation of transcription (PubMed:29844444). Mediates cellular
CC responses to the cytokine KITLG/SCF and other growth factors. Binds to
CC the GAS element and activates PRL-induced transcription. Positively
CC regulates hematopoietic/erythroid differentiation.
CC {ECO:0000269|PubMed:20702587, ECO:0000269|PubMed:29844444,
CC ECO:0000269|PubMed:8732682}.
CC -!- SUBUNIT: Upon activation, forms homodimers (PubMed:29844444). Forms
CC also heterodimers with related family members. Binds NR3C1 (By
CC similarity). Interacts with NCOA1 (PubMed:12954634). Interacts with NMI
CC (PubMed:9989503). Interacts with SOCS7 (PubMed:15677474). Interacts
CC (via SH2 domain) with INSR (PubMed:9428692). Interacts with CPEB3; this
CC inhibits STAT5B-mediated transcriptional activation (PubMed:20639532).
CC {ECO:0000250|UniProtKB:P42232, ECO:0000269|PubMed:12954634,
CC ECO:0000269|PubMed:15677474, ECO:0000269|PubMed:20639532,
CC ECO:0000269|PubMed:29844444, ECO:0000269|PubMed:9428692,
CC ECO:0000269|PubMed:9989503}.
CC -!- INTERACTION:
CC P51692; P00519: ABL1; NbExp=2; IntAct=EBI-1186119, EBI-375543;
CC P51692; P38936: CDKN1A; NbExp=3; IntAct=EBI-1186119, EBI-375077;
CC P51692; Q13111: CHAF1A; NbExp=3; IntAct=EBI-1186119, EBI-1020839;
CC P51692; Q96EY1: DNAJA3; NbExp=2; IntAct=EBI-1186119, EBI-356767;
CC P51692; I6L957: HNRNPA2B1; NbExp=3; IntAct=EBI-1186119, EBI-1642515;
CC P51692; Q8TCE9: LGALS14; NbExp=3; IntAct=EBI-1186119, EBI-10274069;
CC P51692; P61968: LMO4; NbExp=3; IntAct=EBI-1186119, EBI-2798728;
CC P51692; Q71SY5: MED25; NbExp=3; IntAct=EBI-1186119, EBI-394558;
CC P51692; P82932: MRPS6; NbExp=3; IntAct=EBI-1186119, EBI-716172;
CC P51692; Q13287: NMI; NbExp=7; IntAct=EBI-1186119, EBI-372942;
CC P51692; Q92569: PIK3R3; NbExp=3; IntAct=EBI-1186119, EBI-79893;
CC P51692; Q09028: RBBP4; NbExp=3; IntAct=EBI-1186119, EBI-620823;
CC P51692; Q99469: STAC; NbExp=3; IntAct=EBI-1186119, EBI-2652799;
CC P51692; P51692: STAT5B; NbExp=4; IntAct=EBI-1186119, EBI-1186119;
CC P51692; P51687: SUOX; NbExp=3; IntAct=EBI-1186119, EBI-3921347;
CC P51692; Q96PN8: TSSK3; NbExp=3; IntAct=EBI-1186119, EBI-3918381;
CC P51692; O75604: USP2; NbExp=3; IntAct=EBI-1186119, EBI-743272;
CC P51692; Q86VK4-3: ZNF410; NbExp=3; IntAct=EBI-1186119, EBI-11741890;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:29844444}. Nucleus
CC {ECO:0000269|PubMed:29844444}. Note=Translocated into the nucleus in
CC response to phosphorylation. {ECO:0000269|PubMed:29844444}.
CC -!- PTM: Tyrosine phosphorylated in response to signaling via activated
CC KIT, resulting in translocation to the nucleus. Tyrosine phosphorylated
CC in response to signaling via activated FLT3; wild-type FLT3 results in
CC much weaker phosphorylation than constitutively activated mutant FLT3.
CC Alternatively, can be phosphorylated by JAK2. Phosphorylation at Tyr-
CC 699 by PTK6 or HCK leads to an increase of its transcriptional
CC activity. {ECO:0000269|PubMed:12411494, ECO:0000269|PubMed:14504097,
CC ECO:0000269|PubMed:15121872, ECO:0000269|PubMed:17997837,
CC ECO:0000269|PubMed:21135090, ECO:0000269|PubMed:9428692}.
CC -!- DISEASE: Growth hormone insensitivity syndrome with immune
CC dysregulation 1, autosomal recessive (GHISID1) [MIM:245590]: An
CC autosomal recessive form of growth hormone insensitivity syndrome, a
CC congenital disease characterized by short stature, growth hormone
CC deficiency in the presence of normal to elevated circulating
CC concentrations of growth hormone, resistance to exogeneous growth
CC hormone therapy, and recurrent infections. Most, but not all, patients
CC have features of immune dysregulation. {ECO:0000269|PubMed:13679528,
CC ECO:0000269|PubMed:15827093, ECO:0000269|PubMed:22419735}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Growth hormone insensitivity syndrome with immune
CC dysregulation 2, autosomal dominant (GHISID2) [MIM:618985]: An
CC autosomal dominant form of growth hormone insensitivity syndrome, a
CC congenital disease characterized by short stature, growth hormone
CC deficiency in the presence of normal to elevated circulating
CC concentrations of growth hormone, resistance to exogeneous growth
CC hormone therapy, and recurrent infections. GHISID2 patients usually
CC have delayed bone age, delayed puberty, and decreased serum IGF1. Some
CC patients may have features of mild immune dysregulation, such as
CC eczema, increased serum IgE, asthma, or celiac disease.
CC {ECO:0000269|PubMed:29844444}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the transcription factor STAT family.
CC {ECO:0000305}.
CC -!- CAUTION: It was reported that dephosphorylation on tyrosine residues by
CC PTPN2 would negatively regulate prolactin signaling pathway
CC (PubMed:11773439). However, the corresponding article has been
CC retracted (PubMed:24319783). {ECO:0000269|PubMed:11773439,
CC ECO:0000303|PubMed:24319783}.
CC -!- WEB RESOURCE: Name=STAT5Bbase; Note=STAT5B mutation db;
CC URL="http://structure.bmc.lu.se/idbase/STAT5Bbase/";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=STAT5 entry;
CC URL="https://en.wikipedia.org/wiki/STAT5";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/STAT5BID217ch17q21.html";
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; U48730; AAC50485.2; -; mRNA.
DR EMBL; U47686; AAC50491.1; -; mRNA.
DR EMBL; AJ412888; CAD19638.1; -; Genomic_DNA.
DR EMBL; AJ412889; CAD19638.1; JOINED; Genomic_DNA.
DR EMBL; AJ412890; CAD19638.1; JOINED; Genomic_DNA.
DR EMBL; AJ412891; CAD19638.1; JOINED; Genomic_DNA.
DR EMBL; AJ412892; CAD19638.1; JOINED; Genomic_DNA.
DR EMBL; AJ412893; CAD19638.1; JOINED; Genomic_DNA.
DR EMBL; AJ412894; CAD19638.1; JOINED; Genomic_DNA.
DR EMBL; AJ412895; CAD19638.1; JOINED; Genomic_DNA.
DR EMBL; AJ412896; CAD19638.1; JOINED; Genomic_DNA.
DR EMBL; AJ412897; CAD19638.1; JOINED; Genomic_DNA.
DR EMBL; AJ412898; CAD19638.1; JOINED; Genomic_DNA.
DR EMBL; AJ412899; CAD19638.1; JOINED; Genomic_DNA.
DR EMBL; BC065227; AAH65227.1; -; mRNA.
DR CCDS; CCDS11423.1; -.
DR RefSeq; NP_036580.2; NM_012448.3.
DR PDB; 6MBW; X-ray; 3.29 A; A/B=136-703.
DR PDB; 6MBZ; X-ray; 3.21 A; A/B=136-703.
DR PDBsum; 6MBW; -.
DR PDBsum; 6MBZ; -.
DR AlphaFoldDB; P51692; -.
DR SMR; P51692; -.
DR BioGRID; 112654; 95.
DR ComplexPortal; CPX-6044; STAT3/STAT5B complex.
DR ComplexPortal; CPX-6045; STAT5A/STAT5B complex.
DR CORUM; P51692; -.
DR IntAct; P51692; 129.
DR MINT; P51692; -.
DR STRING; 9606.ENSP00000293328; -.
DR BindingDB; P51692; -.
DR ChEMBL; CHEMBL5817; -.
DR DrugBank; DB01254; Dasatinib.
DR GlyGen; P51692; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P51692; -.
DR PhosphoSitePlus; P51692; -.
DR BioMuta; STAT5B; -.
DR DMDM; 41019536; -.
DR CPTAC; CPTAC-1638; -.
DR EPD; P51692; -.
DR jPOST; P51692; -.
DR MassIVE; P51692; -.
DR MaxQB; P51692; -.
DR PaxDb; P51692; -.
DR PeptideAtlas; P51692; -.
DR PRIDE; P51692; -.
DR ProteomicsDB; 56378; -.
DR Antibodypedia; 3804; 947 antibodies from 43 providers.
DR DNASU; 6777; -.
DR Ensembl; ENST00000293328.8; ENSP00000293328.3; ENSG00000173757.10.
DR GeneID; 6777; -.
DR KEGG; hsa:6777; -.
DR MANE-Select; ENST00000293328.8; ENSP00000293328.3; NM_012448.4; NP_036580.2.
DR UCSC; uc002hzh.4; human.
DR CTD; 6777; -.
DR DisGeNET; 6777; -.
DR GeneCards; STAT5B; -.
DR HGNC; HGNC:11367; STAT5B.
DR HPA; ENSG00000173757; Low tissue specificity.
DR MalaCards; STAT5B; -.
DR MIM; 245590; phenotype.
DR MIM; 604260; gene.
DR MIM; 618985; phenotype.
DR neXtProt; NX_P51692; -.
DR OpenTargets; ENSG00000173757; -.
DR Orphanet; 520; Acute promyelocytic leukemia.
DR Orphanet; 220465; Laron syndrome with immunodeficiency.
DR PharmGKB; PA36186; -.
DR VEuPathDB; HostDB:ENSG00000173757; -.
DR eggNOG; KOG3667; Eukaryota.
DR GeneTree; ENSGT01050000244952; -.
DR HOGENOM; CLU_014189_2_2_1; -.
DR InParanoid; P51692; -.
DR OMA; HYNMYTQ; -.
DR OrthoDB; 327469at2759; -.
DR PhylomeDB; P51692; -.
DR TreeFam; TF318648; -.
DR PathwayCommons; P51692; -.
DR Reactome; R-HSA-1170546; Prolactin receptor signaling.
DR Reactome; R-HSA-1266695; Interleukin-7 signaling.
DR Reactome; R-HSA-1433557; Signaling by SCF-KIT.
DR Reactome; R-HSA-1839117; Signaling by cytosolic FGFR1 fusion mutants.
DR Reactome; R-HSA-186763; Downstream signal transduction.
DR Reactome; R-HSA-2586552; Signaling by Leptin.
DR Reactome; R-HSA-512988; Interleukin-3, Interleukin-5 and GM-CSF signaling.
DR Reactome; R-HSA-8854691; Interleukin-20 family signaling.
DR Reactome; R-HSA-8983432; Interleukin-15 signaling.
DR Reactome; R-HSA-8985947; Interleukin-9 signaling.
DR Reactome; R-HSA-9020558; Interleukin-2 signaling.
DR Reactome; R-HSA-9020958; Interleukin-21 signaling.
DR Reactome; R-HSA-9027283; Erythropoietin activates STAT5.
DR Reactome; R-HSA-9645135; STAT5 Activation.
DR Reactome; R-HSA-9670439; Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants.
DR Reactome; R-HSA-9674555; Signaling by CSF3 (G-CSF).
DR Reactome; R-HSA-9702518; STAT5 activation downstream of FLT3 ITD mutants.
DR Reactome; R-HSA-9703465; Signaling by FLT3 fusion proteins.
DR Reactome; R-HSA-9705462; Inactivation of CSF3 (G-CSF) signaling.
DR Reactome; R-HSA-982772; Growth hormone receptor signaling.
DR SignaLink; P51692; -.
DR SIGNOR; P51692; -.
DR BioGRID-ORCS; 6777; 47 hits in 1109 CRISPR screens.
DR ChiTaRS; STAT5B; human.
DR GeneWiki; STAT5B; -.
DR GenomeRNAi; 6777; -.
DR Pharos; P51692; Tchem.
DR PRO; PR:P51692; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P51692; protein.
DR Bgee; ENSG00000173757; Expressed in blood and 205 other tissues.
DR ExpressionAtlas; P51692; baseline and differential.
DR Genevisible; P51692; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IC:ComplexPortal.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; TAS:ProtInc.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0035259; F:nuclear glucocorticoid receptor binding; IPI:BHF-UCL.
DR GO; GO:0046983; F:protein dimerization activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0050798; P:activated T cell proliferation; IEA:Ensembl.
DR GO; GO:0030183; P:B cell differentiation; IEA:Ensembl.
DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; ISS:UniProtKB.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; ISS:UniProtKB.
DR GO; GO:0032870; P:cellular response to hormone stimulus; IDA:BHF-UCL.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0006952; P:defense response; IBA:GO_Central.
DR GO; GO:0046543; P:development of secondary female sexual characteristics; IEA:Ensembl.
DR GO; GO:0046544; P:development of secondary male sexual characteristics; IEA:Ensembl.
DR GO; GO:0030218; P:erythrocyte differentiation; IEA:Ensembl.
DR GO; GO:0007565; P:female pregnancy; IEA:Ensembl.
DR GO; GO:0042492; P:gamma-delta T cell differentiation; IEA:Ensembl.
DR GO; GO:0060397; P:growth hormone receptor signaling pathway via JAK-STAT; IDA:BHF-UCL.
DR GO; GO:0007595; P:lactation; IEA:Ensembl.
DR GO; GO:0019915; P:lipid storage; IEA:Ensembl.
DR GO; GO:0001553; P:luteinization; IEA:Ensembl.
DR GO; GO:0097531; P:mast cell migration; IEA:Ensembl.
DR GO; GO:0000278; P:mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0033028; P:myeloid cell apoptotic process; IEA:Ensembl.
DR GO; GO:0001779; P:natural killer cell differentiation; IEA:Ensembl.
DR GO; GO:0042267; P:natural killer cell mediated cytotoxicity; IEA:Ensembl.
DR GO; GO:0001787; P:natural killer cell proliferation; IEA:Ensembl.
DR GO; GO:0045647; P:negative regulation of erythrocyte differentiation; IEA:Ensembl.
DR GO; GO:0033033; P:negative regulation of myeloid cell apoptotic process; IEA:Ensembl.
DR GO; GO:0048541; P:Peyer's patch development; IEA:Ensembl.
DR GO; GO:0042104; P:positive regulation of activated T cell proliferation; IEA:Ensembl.
DR GO; GO:0045579; P:positive regulation of B cell differentiation; IEA:Ensembl.
DR GO; GO:0045648; P:positive regulation of erythrocyte differentiation; IDA:UniProtKB.
DR GO; GO:0045588; P:positive regulation of gamma-delta T cell differentiation; IEA:Ensembl.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IEA:Ensembl.
DR GO; GO:0032743; P:positive regulation of interleukin-2 production; IEA:Ensembl.
DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; IEA:Ensembl.
DR GO; GO:0032825; P:positive regulation of natural killer cell differentiation; IEA:Ensembl.
DR GO; GO:0045954; P:positive regulation of natural killer cell mediated cytotoxicity; IEA:Ensembl.
DR GO; GO:0032819; P:positive regulation of natural killer cell proliferation; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0042448; P:progesterone metabolic process; IEA:Ensembl.
DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; IBA:GO_Central.
DR GO; GO:0042127; P:regulation of cell population proliferation; IBA:GO_Central.
DR GO; GO:0030856; P:regulation of epithelial cell differentiation; IEA:Ensembl.
DR GO; GO:0040014; P:regulation of multicellular organism growth; ISS:BHF-UCL.
DR GO; GO:0019218; P:regulation of steroid metabolic process; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0032355; P:response to estradiol; IDA:BHF-UCL.
DR GO; GO:0070672; P:response to interleukin-15; IEA:Ensembl.
DR GO; GO:0070669; P:response to interleukin-2; IEA:Ensembl.
DR GO; GO:0070670; P:response to interleukin-4; IEA:Ensembl.
DR GO; GO:0043434; P:response to peptide hormone; IBA:GO_Central.
DR GO; GO:0033077; P:T cell differentiation in thymus; IEA:Ensembl.
DR GO; GO:0043029; P:T cell homeostasis; IEA:Ensembl.
DR GO; GO:0019530; P:taurine metabolic process; ISS:BHF-UCL.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl.
DR CDD; cd10420; SH2_STAT5b; 1.
DR Gene3D; 1.10.532.10; -; 1.
DR Gene3D; 2.60.40.630; -; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR008967; p53-like_TF_DNA-bd.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR001217; STAT.
DR InterPro; IPR035858; STAT5a/5b.
DR InterPro; IPR035886; STAT5b_SH2.
DR InterPro; IPR036535; STAT_N_sf.
DR InterPro; IPR013800; STAT_TF_alpha.
DR InterPro; IPR015988; STAT_TF_coiled-coil.
DR InterPro; IPR013801; STAT_TF_DNA-bd.
DR InterPro; IPR012345; STAT_TF_DNA-bd_N.
DR InterPro; IPR013799; STAT_TF_prot_interaction.
DR PANTHER; PTHR11801; PTHR11801; 1.
DR PANTHER; PTHR11801:SF47; PTHR11801:SF47; 1.
DR Pfam; PF00017; SH2; 1.
DR Pfam; PF01017; STAT_alpha; 1.
DR Pfam; PF02864; STAT_bind; 1.
DR Pfam; PF02865; STAT_int; 1.
DR SMART; SM00252; SH2; 1.
DR SMART; SM00964; STAT_int; 1.
DR SUPFAM; SSF47655; SSF47655; 1.
DR SUPFAM; SSF48092; SSF48092; 1.
DR SUPFAM; SSF49417; SSF49417; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR PROSITE; PS50001; SH2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Cytoplasm; Disease variant; DNA-binding; Dwarfism;
KW Nucleus; Phosphoprotein; Reference proteome; SH2 domain; Transcription;
KW Transcription regulation.
FT CHAIN 1..787
FT /note="Signal transducer and activator of transcription 5B"
FT /id="PRO_0000182429"
FT DOMAIN 589..686
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 232..321
FT /note="Required for interaction with NMI"
FT /evidence="ECO:0000269|PubMed:9989503"
FT MOD_RES 90
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 128
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 193
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 682
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P42229"
FT MOD_RES 699
FT /note="Phosphotyrosine; by HCK, JAK and PTK6"
FT /evidence="ECO:0000269|PubMed:12411494,
FT ECO:0000269|PubMed:17997837"
FT VARIANT 130
FT /note="A -> V (in dbSNP:rs2277619)"
FT /id="VAR_052074"
FT VARIANT 177
FT /note="Q -> P (in GHISID2; exhibits strong growth hormone-
FT induced phosphorylation, but no subsequent nuclear
FT localization; when forming homodimers with the wild-type
FT protein, may also prevent its nuclear localization
FT following growth hormone-stimulation; dbSNP:rs1555549674)"
FT /evidence="ECO:0000269|PubMed:29844444"
FT /id="VAR_085463"
FT VARIANT 474
FT /note="Q -> R (in GHISID2; loss of DNA-binding ability;
FT when forming homodimers with the wild-type protein, may
FT prevent wild-type binding to DNA; consequently, disruption
FT of transcriptional activity; dbSNP:rs1555548680)"
FT /evidence="ECO:0000269|PubMed:29844444"
FT /id="VAR_085464"
FT VARIANT 478
FT /note="A -> V (in GHISID2; loss of DNA-binding ability;
FT when forming homodimers with the wild-type protein, may
FT prevent wild-type binding to DNA; consequently, disruption
FT of transcriptional activity; dbSNP:rs1555548678)"
FT /evidence="ECO:0000269|PubMed:29844444"
FT /id="VAR_085465"
FT VARIANT 630
FT /note="A -> P (in GHISID1; affects activation by growth
FT hormone or interferon-gamma; dbSNP:rs121908501)"
FT /evidence="ECO:0000269|PubMed:13679528"
FT /id="VAR_018728"
FT VARIANT 646
FT /note="F -> S (in GHISID1; transcriptionally inactive)"
FT /evidence="ECO:0000269|PubMed:22419735"
FT /id="VAR_067368"
FT MUTAGEN 684
FT /note="T->A: Abolishes interaction with INSR."
FT /evidence="ECO:0000269|PubMed:9428692"
FT MUTAGEN 699
FT /note="Y->F: Abolishes phosphorylation by HCK."
FT /evidence="ECO:0000269|PubMed:12411494"
FT CONFLICT 230
FT /note="A -> P (in Ref. 2; AAC50491)"
FT /evidence="ECO:0000305"
FT HELIX 141..182
FT /evidence="ECO:0007829|PDB:6MBZ"
FT HELIX 194..249
FT /evidence="ECO:0007829|PDB:6MBZ"
FT HELIX 251..262
FT /evidence="ECO:0007829|PDB:6MBZ"
FT TURN 263..265
FT /evidence="ECO:0007829|PDB:6MBZ"
FT HELIX 273..302
FT /evidence="ECO:0007829|PDB:6MBZ"
FT HELIX 309..330
FT /evidence="ECO:0007829|PDB:6MBZ"
FT STRAND 332..336
FT /evidence="ECO:0007829|PDB:6MBZ"
FT STRAND 340..343
FT /evidence="ECO:0007829|PDB:6MBZ"
FT STRAND 347..354
FT /evidence="ECO:0007829|PDB:6MBZ"
FT TURN 355..364
FT /evidence="ECO:0007829|PDB:6MBZ"
FT STRAND 368..375
FT /evidence="ECO:0007829|PDB:6MBZ"
FT HELIX 376..383
FT /evidence="ECO:0007829|PDB:6MBZ"
FT STRAND 400..402
FT /evidence="ECO:0007829|PDB:6MBW"
FT STRAND 404..406
FT /evidence="ECO:0007829|PDB:6MBZ"
FT TURN 407..410
FT /evidence="ECO:0007829|PDB:6MBZ"
FT STRAND 411..421
FT /evidence="ECO:0007829|PDB:6MBZ"
FT TURN 435..437
FT /evidence="ECO:0007829|PDB:6MBZ"
FT STRAND 440..449
FT /evidence="ECO:0007829|PDB:6MBZ"
FT TURN 451..454
FT /evidence="ECO:0007829|PDB:6MBW"
FT STRAND 456..462
FT /evidence="ECO:0007829|PDB:6MBZ"
FT STRAND 468..471
FT /evidence="ECO:0007829|PDB:6MBZ"
FT HELIX 472..488
FT /evidence="ECO:0007829|PDB:6MBZ"
FT STRAND 500..503
FT /evidence="ECO:0007829|PDB:6MBW"
FT HELIX 504..519
FT /evidence="ECO:0007829|PDB:6MBZ"
FT HELIX 527..537
FT /evidence="ECO:0007829|PDB:6MBZ"
FT HELIX 545..548
FT /evidence="ECO:0007829|PDB:6MBZ"
FT STRAND 552..554
FT /evidence="ECO:0007829|PDB:6MBW"
FT HELIX 555..559
FT /evidence="ECO:0007829|PDB:6MBZ"
FT STRAND 564..567
FT /evidence="ECO:0007829|PDB:6MBW"
FT HELIX 569..583
FT /evidence="ECO:0007829|PDB:6MBZ"
FT HELIX 586..590
FT /evidence="ECO:0007829|PDB:6MBZ"
FT HELIX 600..608
FT /evidence="ECO:0007829|PDB:6MBZ"
FT STRAND 614..619
FT /evidence="ECO:0007829|PDB:6MBZ"
FT STRAND 621..623
FT /evidence="ECO:0007829|PDB:6MBZ"
FT STRAND 627..631
FT /evidence="ECO:0007829|PDB:6MBZ"
FT HELIX 636..638
FT /evidence="ECO:0007829|PDB:6MBZ"
FT HELIX 648..653
FT /evidence="ECO:0007829|PDB:6MBZ"
FT HELIX 656..662
FT /evidence="ECO:0007829|PDB:6MBZ"
FT STRAND 668..672
FT /evidence="ECO:0007829|PDB:6MBZ"
FT HELIX 675..679
FT /evidence="ECO:0007829|PDB:6MBZ"
FT TURN 680..682
FT /evidence="ECO:0007829|PDB:6MBZ"
SQ SEQUENCE 787 AA; 89866 MW; AA2F1CAB20955ACA CRC64;
MAVWIQAQQL QGEALHQMQA LYGQHFPIEV RHYLSQWIES QAWDSVDLDN PQENIKATQL
LEGLVQELQK KAEHQVGEDG FLLKIKLGHY ATQLQNTYDR CPMELVRCIR HILYNEQRLV
REANNGSSPA GSLADAMSQK HLQINQTFEE LRLVTQDTEN ELKKLQQTQE YFIIQYQESL
RIQAQFGPLA QLSPQERLSR ETALQQKQVS LEAWLQREAQ TLQQYRVELA EKHQKTLQLL
RKQQTIILDD ELIQWKRRQQ LAGNGGPPEG SLDVLQSWCE KLAEIIWQNR QQIRRAEHLC
QQLPIPGPVE EMLAEVNATI TDIISALVTS TFIIEKQPPQ VLKTQTKFAA TVRLLVGGKL
NVHMNPPQVK ATIISEQQAK SLLKNENTRN DYSGEILNNC CVMEYHQATG TLSAHFRNMS
LKRIKRSDRR GAESVTEEKF TILFESQFSV GGNELVFQVK TLSLPVVVIV HGSQDNNATA
TVLWDNAFAE PGRVPFAVPD KVLWPQLCEA LNMKFKAEVQ SNRGLTKENL VFLAQKLFNN
SSSHLEDYSG LSVSWSQFNR ENLPGRNYTF WQWFDGVMEV LKKHLKPHWN DGAILGFVNK
QQAHDLLINK PDGTFLLRFS DSEIGGITIA WKFDSQERMF WNLMPFTTRD FSIRSLADRL
GDLNYLIYVF PDRPKDEVYS KYYTPVPCES ATAKAVDGYV KPQIKQVVPE FVNASADAGG
GSATYMDQAP SPAVCPQAHY NMYPQNPDSV LDTDGDFDLE DTMDVARRVE ELLGRPMDSQ
WIPHAQS
