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 27-MAR-2024, entry version 224. 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 RETRACTED PAPER. 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 RETRACTION NOTICE OF PUBMED:11773439, 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 [11] 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 [12] 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 [13] 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 [14] 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 [15] 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 [16] 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 [17] 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 [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="https://atlasgeneticsoncology.org/gene/217/STAT5B"; 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; 103. DR ComplexPortal; CPX-6044; STAT3/STAT5B complex. DR ComplexPortal; CPX-6045; STAT5A/STAT5B complex. DR CORUM; P51692; -. DR IntAct; P51692; 130. 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; 9606-ENSP00000293328; -. DR PeptideAtlas; P51692; -. DR ProteomicsDB; 56378; -. DR Pumba; P51692; -. DR Antibodypedia; 3804; 1080 antibodies from 43 providers. DR DNASU; 6777; -. DR Ensembl; ENST00000293328.8; ENSP00000293328.3; ENSG00000173757.11. DR Ensembl; ENST00000415845.2; ENSP00000398379.2; ENSG00000173757.11. DR Ensembl; ENST00000698776.1; ENSP00000513923.1; ENSG00000173757.11. DR Ensembl; ENST00000698777.1; ENSP00000513924.1; ENSG00000173757.11. 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 AGR; HGNC:11367; -. 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; ENSGT01080000257420; -. DR HOGENOM; CLU_014189_2_2_1; -. DR InParanoid; P51692; -. DR OMA; WIEEKMW; -. DR OrthoDB; 7823at2759; -. 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; 52 hits in 1190 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 207 other cell types or tissues. DR ExpressionAtlas; P51692; baseline and differential. 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; NAS: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 CDD; cd16855; STAT5_CCD; 1. DR CDD; cd16849; STAT5_DBD; 1. DR Gene3D; 1.10.238.10; EF-hand; 1. DR Gene3D; 3.30.505.10; SH2 domain; 1. DR Gene3D; 1.20.1050.20; STAT transcription factor, all-alpha domain; 1. DR Gene3D; 2.60.40.630; STAT transcription factor, DNA-binding domain; 1. DR Gene3D; 1.10.532.10; STAT transcription factor, N-terminal domain; 1. DR InterPro; IPR008967; p53-like_TF_DNA-bd_sf. DR InterPro; IPR000980; SH2. DR InterPro; IPR036860; SH2_dom_sf. DR InterPro; IPR001217; STAT. DR InterPro; IPR046994; STAT5_CCD. DR InterPro; IPR035858; STAT5a/5b_DBD. DR InterPro; IPR035886; STAT5b_SH2. DR InterPro; IPR048988; STAT_linker. 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; SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION; 1. DR PANTHER; PTHR11801:SF39; SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION 5B; 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 Pfam; PF21354; STAT_linker; 1. DR SMART; SM00252; SH2; 1. DR SMART; SM00964; STAT_int; 1. DR SUPFAM; SSF49417; p53-like transcription factors; 1. DR SUPFAM; SSF55550; SH2 domain; 1. DR SUPFAM; SSF47655; STAT; 1. DR SUPFAM; SSF48092; Transcription factor STAT-4 N-domain; 1. DR PROSITE; PS50001; SH2; 1. DR Genevisible; P51692; HS. 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 FT hormone-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 //