P51692 (STA5B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Signal transducer and activator of transcription 5B

Gene names

Name:

STAT5B

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	787 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Carries out a dual function: signal transduction and activation of transcription. Mediates cellular responses to the cytokine KITLG/SCF and other growth factors. Binds to the GAS element and activates PRL-induced transcription.
Subunit structure	Forms a homodimer or a heterodimer with a related family member. Binds NR3C1 By similarity. Interacts with NCOA1, NMI and SOCS7. Interacts (via SH2 domain) with INSR. Ref.7 Ref.9 Ref.13
Subcellular location	Cytoplasm By similarity. Nucleus By similarity. Note: Translocated into the nucleus in response to phosphorylation By similarity.
Post-translational modification	Tyrosine phosphorylated in response to signaling via activated KIT, resulting in translocation to the nucleus. Tyrosine phosphorylated in response to signaling via activated FLT3; wild-type FLT3 results in much weaker phosphorylation than constitutively activated mutant FLT3. Alternatively, can be phosporylated by JAK2. Phosphoryation at Tyr-699 by PTK6 or HCK leads to an increase of its transcriptional activity. Ref.8 Ref.10 Ref.12 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.22
Involvement in disease	Defects in STAT5B are the cause of Laron type dwarfism II (LTD2) [MIM:245590]; also known as Laron syndrome type II or Laron syndrome due to a post-receptor defect. The phenotypic features are consistent with growth hormone deficiency in the presence of normal to elevated circulating concentrations of growth hormone, and resistance to hexogeneous hormone therapy. Ref.23
Sequence similarities	Belongs to the transcription factor STAT family. Contains 1 SH2 domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	SH2 domain
Ligand	DNA-binding
Molecular function	Activator
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	2-oxoglutarate metabolic process Inferred from sequence or structural similarity. Source: BHF-UCL JAK-STAT cascade involved in growth hormone signaling pathway Inferred from direct assay. Source: BHF-UCL allantoin metabolic process Inferred from sequence or structural similarity. Source: BHF-UCL citrate metabolic process Inferred from sequence or structural similarity. Source: BHF-UCL creatine metabolic process Inferred from sequence or structural similarity. Source: BHF-UCL creatinine metabolic process Inferred from sequence or structural similarity. Source: BHF-UCL fatty acid metabolic process Inferred from sequence or structural similarity. Source: BHF-UCL isoleucine metabolic process Inferred from sequence or structural similarity. Source: BHF-UCL oxaloacetate metabolic process Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: UniProtKB response to estradiol stimulus Inferred from direct assay. Source: BHF-UCL succinate metabolic process Inferred from sequence or structural similarity. Source: BHF-UCL taurine metabolic process Inferred from sequence or structural similarity. Source: BHF-UCL valine metabolic process Inferred from sequence or structural similarity. Source: BHF-UCL
Cellular component	cytosol Traceable author statement. Source: Reactome nucleoplasm Traceable author statement. Source: Reactome
Molecular function	calcium ion binding Inferred from electronic annotation. Source: InterPro glucocorticoid receptor binding Inferred from physical interaction. Source: BHF-UCL sequence-specific DNA binding transcription factor activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DNAJA3	Q96EY1	2	EBI-1186119,EBI-356767
NMI	Q13287	7	EBI-1186119,EBI-372942

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 787	787	Signal transducer and activator of transcription 5B		PRO_0000182429
Regions
	Domain	589 – 686	98	SH2
	Region	232 – 321	90	Required for interaction with NMI
Amino acid modifications
	Modified residue	128	1	Phosphoserine Ref.17 Ref.19
	Modified residue	193	1	Phosphoserine Ref.14 Ref.17 Ref.18 Ref.19
	Modified residue	699	1	Phosphotyrosine; by HCK, JAK and PTK6 Ref.8 Ref.15 Ref.16
	Modified residue	701	1	N6-acetyllysine Ref.20
Natural variations
	Natural variant	130	1	A → V. Corresponds to variant rs2277619 [ dbSNP | Ensembl ].		VAR_052074
	Natural variant	630	1	A → P in LTD2; affects activation by growth hormone or interferon-gamma. Ref.23		VAR_018728
Experimental info
	Mutagenesis	684	1	T → A: Abolishes interaction with INSR.
	Mutagenesis	699	1	Y → F: Abolishes phosphorylation by HCK. Ref.8
	Sequence conflict	230	1	A → P in AAC50491. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P51692 [UniParc]. Last modified January 16, 2004. Version 2. Checksum: AA2F1CAB20955ACA	FASTA	787	89,866
	10 20 30 40 50 60 MAVWIQAQQL QGEALHQMQA LYGQHFPIEV RHYLSQWIES QAWDSVDLDN PQENIKATQL 70 80 90 100 110 120 LEGLVQELQK KAEHQVGEDG FLLKIKLGHY ATQLQNTYDR CPMELVRCIR HILYNEQRLV 130 140 150 160 170 180 REANNGSSPA GSLADAMSQK HLQINQTFEE LRLVTQDTEN ELKKLQQTQE YFIIQYQESL 190 200 210 220 230 240 RIQAQFGPLA QLSPQERLSR ETALQQKQVS LEAWLQREAQ TLQQYRVELA EKHQKTLQLL 250 260 270 280 290 300 RKQQTIILDD ELIQWKRRQQ LAGNGGPPEG SLDVLQSWCE KLAEIIWQNR QQIRRAEHLC 310 320 330 340 350 360 QQLPIPGPVE EMLAEVNATI TDIISALVTS TFIIEKQPPQ VLKTQTKFAA TVRLLVGGKL 370 380 390 400 410 420 NVHMNPPQVK ATIISEQQAK SLLKNENTRN DYSGEILNNC CVMEYHQATG TLSAHFRNMS 430 440 450 460 470 480 LKRIKRSDRR GAESVTEEKF TILFESQFSV GGNELVFQVK TLSLPVVVIV HGSQDNNATA 490 500 510 520 530 540 TVLWDNAFAE PGRVPFAVPD KVLWPQLCEA LNMKFKAEVQ SNRGLTKENL VFLAQKLFNN 550 560 570 580 590 600 SSSHLEDYSG LSVSWSQFNR ENLPGRNYTF WQWFDGVMEV LKKHLKPHWN DGAILGFVNK 610 620 630 640 650 660 QQAHDLLINK PDGTFLLRFS DSEIGGITIA WKFDSQERMF WNLMPFTTRD FSIRSLADRL 670 680 690 700 710 720 GDLNYLIYVF PDRPKDEVYS KYYTPVPCES ATAKAVDGYV KPQIKQVVPE FVNASADAGG 730 740 750 760 770 780 GSATYMDQAP SPAVCPQAHY NMYPQNPDSV LDTDGDFDLE DTMDVARRVE ELLGRPMDSQ WIPHAQS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization and cloning of STAT5 from IM-9 cells and its activation by growth hormone." Silva C.M., Lu H., Day R.N. Mol. Endocrinol. 10:508-518(1996) [PubMed: 8732682] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	Silva C.M., Lu H. Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO 628; 717 AND 720.
[3]	"Cloning of human Stat5B. Reconstitution of interleukin-2-induced Stat5A and Stat5B DNA binding activity in COS-7 cells." Lin J.-X., Mietz J., Modi W.S., John S., Leonard W.J. J. Biol. Chem. 271:10738-10744(1996) [PubMed: 8631883] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"The structure of human STAT5A and B genes reveals two regions of nearly identical sequence and an alternative tissue specific STAT5B promoter." Ambrosio R., Fimiani G., Monfregola J., Sanzari E., De Felice N., Salerno M.C., Pignata C., D'Urso M., Ursini M.V. Gene 285:311-318(2002) [PubMed: 12039059] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lymph.
[6]	"Identification of Stat 5B as a substrate of the insulin receptor." Sawka-Verhelle D., Filloux C., Tartare-Deckert S., Mothe I., Van Obberghen E. Eur. J. Biochem. 250:411-417(1997) [PubMed: 9428692] [Abstract] Cited for: PHOSPHORYLATION BY INSR, INTERACTION WITH INSR, MUTAGENESIS OF THR-684.
[7]	"Functional association of Nmi with Stat5 and Stat1 in IL-2- and IFNgamma-mediated signaling." Zhu M.-H., John S., Berg M., Leonard W.J. Cell 96:121-130(1999) [PubMed: 9989503] [Abstract] Cited for: INTERACTION WITH NMI.
[8]	"The Src family kinase Hck couples BCR/ABL to STAT5 activation in myeloid leukemia cells." Klejman A., Schreiner S.J., Nieborowska-Skorska M., Slupianek A., Wilson M., Smithgall T.E., Skorski T. EMBO J. 21:5766-5774(2002) [PubMed: 12411494] [Abstract] Cited for: PHOSPHORYLATION AT TYR-699, MUTAGENESIS OF TYR-699.
[9]	"NCoA-1/SRC-1 is an essential coactivator of STAT5 that binds to the FDL motif in the alpha-helical region of the STAT5 transactivation domain." Litterst C.M., Kliem S., Marilley D., Pfitzner E. J. Biol. Chem. 278:45340-45351(2003) [PubMed: 12954634] [Abstract] Cited for: INTERACTION WITH NCOA1.
[10]	"FLT3 mutations in the activation loop of tyrosine kinase domain are frequently found in infant ALL with MLL rearrangements and pediatric ALL with hyperdiploidy." Taketani T., Taki T., Sugita K., Furuichi Y., Ishii E., Hanada R., Tsuchida M., Sugita K., Ida K., Hayashi Y. Blood 103:1085-1088(2004) [PubMed: 14504097] [Abstract] Cited for: PHOSPHORYLATION IN RESPONSE TO FLT3 SIGNALING.
[11]	"Signal transduction via the stem cell factor receptor/c-Kit." Ronnstrand L. Cell. Mol. Life Sci. 61:2535-2548(2004) [PubMed: 15526160] [Abstract] Cited for: REVIEW ON ROLE IN KIT SIGNALING.
[12]	"Tyrosine 813 is a site of JAK2 autophosphorylation critical for activation of JAK2 by SH2-B beta." Kurzer J.H., Argetsinger L.S., Zhou Y.J., Kouadio J.L., O'Shea J.J., Carter-Su C. Mol. Cell. Biol. 24:4557-4570(2004) [PubMed: 15121872] [Abstract] Cited for: PHOSPHORYLATION BY JAK2.
[13]	"Suppressor of cytokine signaling 7 inhibits prolactin, growth hormone, and leptin signaling by interacting with STAT5 or STAT3 and attenuating their nuclear translocation." Martens N., Uzan G., Wery M., Hooghe R., Hooghe-Peters E.L., Gertler A. J. Biol. Chem. 280:13817-13823(2005) [PubMed: 15677474] [Abstract] Cited for: INTERACTION WITH SOCS7.
[14]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-193, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[15]	"Signal transducer and activator of transcription 5b: a new target of breast tumor kinase/protein tyrosine kinase 6." Weaver A.M., Silva C.M. Breast Cancer Res. 9:R79-R79(2007) [PubMed: 17997837] [Abstract] Cited for: PHOSPHORYLATION AT TYR-699 BY PTK6.
[16]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-699, MASS SPECTROMETRY. Tissue: Lung carcinoma.
[17]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-128 AND SER-193, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[18]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-193, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[19]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-128 AND SER-193, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[20]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-701, MASS SPECTROMETRY.
[21]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[22]	"Mechanisms of STAT protein activation by oncogenic KIT mutants in neoplastic mast cells." Chaix A., Lopez S., Voisset E., Gros L., Dubreuil P., De Sepulveda P. J. Biol. Chem. 286:5956-5966(2011) [PubMed: 21135090] [Abstract] Cited for: PHOSPHORYLATION IN RESPONSE TO KIT SIGNALING.
[23]	"Growth hormone insensitivity associated with a STAT5b mutation." Kofoed E.M., Hwa V., Little B., Woods K.A., Buckway C.K., Tsubaki J., Pratt K.L., Bezrodnik L., Jasper H., Tepper A., Heinrich J.J., Rosenfeld R.G. N. Engl. J. Med. 349:1139-1147(2003) [PubMed: 13679528] [Abstract] Cited for: VARIANT LTD2 PRO-630.
+	Additional computationally mapped references.

Web resources

STAT5Bbase

STAT5B mutation db

Wikipedia

STAT5 entry

Cross-references

Sequence databases
EMBL GenBank DDBJ	U48730 mRNA. Translation: AAC50485.2. U47686 mRNA. Translation: AAC50491.1. AJ412888 , AJ412889, AJ412890, AJ412891, AJ412892, AJ412893, AJ412894, AJ412895, AJ412896, AJ412897, AJ412898, AJ412899 Genomic DNA. Translation: CAD19638.1. BC065227 mRNA. Translation: AAH65227.1.
IPI	IPI00103415.
RefSeq	NP_036580.2. NM_012448.3.
UniGene	Hs.595276.
3D structure databases
ProteinModelPortal	P51692.
SMR	P51692. Positions 2-686.
ModBase	Search...
Protein-protein interaction databases
IntAct	P51692. 11 interactions.
MINT	MINT-132900.
STRING	P51692.
PTM databases
PhosphoSite	P51692.
Polymorphism databases
DMDM	41019536.
Proteomic databases
PeptideAtlas	P51692.
PRIDE	P51692.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000293328; ENSP00000293328; ENSG00000173757.
GeneID	6777.
KEGG	hsa:6777.
UCSC	uc002hzh.1. human.
Organism-specific databases
CTD	6777.
GeneCards	GC17M040351.
H-InvDB	HIX0202465.
HGNC	HGNC:11367. STAT5B.
HPA	CAB004298.
MIM	245590. phenotype. 604260. gene.
neXtProt	NX_P51692.
Orphanet	220465. Laron syndrome with immunodeficiency.
PharmGKB	PA36186.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG15775.
HOVERGEN	HBG107486.
InParanoid	P51692.
OMA	VREATNS.
OrthoDB	EOG457560.
PhylomeDB	P51692.
Enzyme and pathway databases
Pathway_Interaction_DB	angiopoietinreceptor_pathway. Angiopoietin receptor Tie2-mediated signaling. epopathway. EPO signaling pathway. fgf_pathway. FGF signaling pathway. il2_stat5pathway. IL2 signaling events mediated by STAT5. il2_1pathway. IL2-mediated signaling events. il4_2pathway. IL4-mediated signaling events. pdgfrbpathway. PDGFR-beta signaling pathway. ptp1bpathway. Signaling events mediated by PTP1B.
Reactome	REACT_111102. Signal Transduction. REACT_6900. Immune System.
Gene expression databases
ArrayExpress	P51692.
Bgee	P51692.
CleanEx	HS_STAT5B.
Genevestigator	P51692.
GermOnline	ENSG00000173757. Homo sapiens.
Family and domain databases
InterPro	IPR011992. EF-hand-like_dom. IPR008967. p53-like_TF_DNA-bd. IPR000980. SH2. IPR013800. STAT_TF_alpha. IPR015988. STAT_TF_coiled-coil. IPR001217. STAT_TF_core. IPR013801. STAT_TF_DNA-bd. IPR012345. STAT_TF_DNA-bd_sub. IPR013799. STAT_TF_prot_interaction. [Graphical view]
Gene3D	G3DSA:1.10.238.10. EF-Hand_type. 1 hit. G3DSA:3.30.505.10. SH2. 1 hit. G3DSA:1.20.1050.20. STAT_alpha. 1 hit. G3DSA:2.60.40.630. STAT_DNA_bd_sub. 1 hit. G3DSA:1.10.532.10. STAT_protein_interaction. 1 hit.
KO	K11224.
PANTHER	PTHR11801. STAT. 1 hit.
Pfam	PF00017. SH2. 1 hit. PF01017. STAT_alpha. 1 hit. PF02864. STAT_bind. 1 hit. PF02865. STAT_int. 1 hit. [Graphical view]
SMART	SM00252. SH2. 1 hit. SM00964. STAT_int. 1 hit. [Graphical view]
SUPFAM	SSF49417. P53_like_DNA_bnd. 1 hit. SSF47655. STAT. 1 hit. SSF48092. STAT. 1 hit.
PROSITE	PS50001. SH2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB01254. Dasatinib.
NextBio	26454.
PMAP-CutDB	P51692.
SOURCE	Search...

Entry information

Entry name

STA5B_HUMAN

Accession

Primary (citable) accession number: P51692
Secondary accession number(s): Q8WWS8

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	January 16, 2004
Last modified:	January 25, 2012
This is version 122 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.