P42229 (STA5A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Signal transducer and activator of transcription 5A

Gene names

Name:	STAT5A
Synonyms:	STAT5

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	794 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. Mediates cellular responses to ERBB4. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4. Binds to the GAS element and activates PRL-induced transcription. Regulates the expression of milk proteins during lactation. Ref.8
Subunit structure	Forms a homodimer or a heterodimer with a related family member. Binds NR3C1 By similarity. Interacts with NCOA1 and SOCS7. Interacts with ERBB4. Ref.4 Ref.8 Ref.9
Subcellular location	Cytoplasm. Nucleus. Note: Translocated into the nucleus in response to phosphorylation. Ref.8
Post-translational modification	Tyrosine phosphorylated in response to KITLG/SCF, IL2, IL3, IL7, IL15, CSF2/GMCSF, GH1, PRL, EPO and THPO. Activated KIT promotes phosphorylation on tyrosine residues and subsequent translocation to the nucleus. Tyrosine phosphorylated in response to constitutively activated FGFR1, FGFR2, FGFR3 and FGFR4. Tyrosine phosphorylation is required for DNA-binding activity and dimerization. Serine phosphorylation is also required for maximal transcriptional activity By similarity. 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 phosphorylated by JAK2 at Tyr-694. Ref.5 Ref.6 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.16
Sequence similarities	Belongs to the transcription factor STAT family. Contains 1 SH2 domain.

Ontologies

Keywords
Biological process	Lactation Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Domain	SH2 domain
Ligand	DNA-binding
Molecular function	Activator
PTM	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 Traceable author statement. Source: ProtInc 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 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 protein binding Inferred from physical interaction. Source: UniProtKB sequence-specific DNA binding transcription factor activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 794	794	Signal transducer and activator of transcription 5A		PRO_0000182423
Regions
	Domain	589 – 686	98	SH2
Amino acid modifications
	Modified residue	193	1	Phosphoserine Ref.13
	Modified residue	372	1	Phosphothreonine Ref.12
	Modified residue	375	1	Phosphoserine Ref.12
	Modified residue	694	1	Phosphotyrosine; by JAK2 Ref.5 Ref.10 Ref.11 Ref.14
	Modified residue	780	1	Phosphoserine By similarity
Natural variations
	Natural variant	389	1	R → H. Corresponds to variant rs2230134 [ dbSNP | Ensembl ].		VAR_052073
Experimental info
	Sequence conflict	88	1	G → R in AAB06589. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P42229 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: C64237295F88CFBE	FASTA	794	90,647
	10 20 30 40 50 60 MAGWIQAQQL QGDALRQMQV LYGQHFPIEV RHYLAQWIES QPWDAIDLDN PQDRAQATQL 70 80 90 100 110 120 LEGLVQELQK KAEHQVGEDG FLLKIKLGHY ATQLQKTYDR CPLELVRCIR HILYNEQRLV 130 140 150 160 170 180 REANNCSSPA GILVDAMSQK HLQINQTFEE LRLVTQDTEN ELKKLQQTQE YFIIQYQESL 190 200 210 220 230 240 RIQAQFAQLA 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 ECSGEILNNC CVMEYHQATG TLSAHFRNMS 430 440 450 460 470 480 LKRIKRADRR GAESVTEEKF TVLFESQFSV GSNELVFQVK TLSLPVVVIV HGSQDHNATA 490 500 510 520 530 540 TVLWDNAFAE PGRVPFAVPD KVLWPQLCEA LNMKFKAEVQ SNRGLTKENL VFLAQKLFNN 550 560 570 580 590 600 SSSHLEDYSG LSVSWSQFNR ENLPGWNYTF WQWFDGVMEV LKKHHKPHWN DGAILGFVNK 610 620 630 640 650 660 QQAHDLLINK PDGTFLLRFS DSEIGGITIA WKFDSPERNL WNLKPFTTRD FSIRSLADRL 670 680 690 700 710 720 GDLSYLIYVF PDRPKDEVFS KYYTPVLAKA VDGYVKPQIK QVVPEFVNAS ADAGGSSATY 730 740 750 760 770 780 MDQAPSPAVC PQAPYNMYPQ NPDHVLDQDG EFDLDETMDV ARHVEELLRR PMDSLDSRLS 790 PPAGLFTSAR GSLS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and purification of human Stat proteins activated in response to interleukin-2." Hou J., Schindler U., Henzel W.J., Wong S.C., McKnight S.L. Immunity 2:321-329(1995) [PubMed: 7719937] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	Lin J.X., Mietz J., Modi W.S., John S., Leonard W.J. Submitted (DEC-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"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: Cervix.
[4]	"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.
[5]	"STAT5a activation mediates the epithelial to mesenchymal transition induced by oncogenic RhoA." Benitah S.A., Valeron P.F., Rui H., Lacal J.C. Mol. Biol. Cell 14:40-53(2003) [PubMed: 12529425] [Abstract] Cited for: PHOSPHORYLATION AT TYR-694 BY JAK2.
[6]	"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.
[7]	"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.
[8]	"The ERBB4/HER4 receptor tyrosine kinase regulates gene expression by functioning as a STAT5A nuclear chaperone." Williams C.C., Allison J.G., Vidal G.A., Burow M.E., Beckman B.S., Marrero L., Jones F.E. J. Cell Biol. 167:469-478(2004) [PubMed: 15534001] [Abstract] Cited for: INTERACTION WITH ERBB4, SUBCELLULAR LOCATION, FUNCTION.
[9]	"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.
[10]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-694, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"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-694, MASS SPECTROMETRY. Tissue: Lung carcinoma.
[12]	"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column." Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y. Anal. Sci. 24:161-166(2008) [PubMed: 18187866] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-372 AND SER-375, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[13]	"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.
[14]	"An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells." Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A., Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D., Wiley H.S., Qian W.-J. J. Proteome Res. 8:3852-3861(2009) [PubMed: 19534553] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-694, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[15]	"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].
[16]	"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.
+	Additional computationally mapped references.

Web resources

Wikipedia

STAT5 entry

Cross-references

Sequence databases
EMBL GenBank DDBJ	L41142 mRNA. Translation: AAA73962.1. U43185 mRNA. Translation: AAB06589.1. BC027036 mRNA. Translation: AAH27036.1.
IPI	IPI00030783.
PIR	G02317.
RefSeq	NP_003143.2. NM_003152.3.
UniGene	Hs.437058.
3D structure databases
ProteinModelPortal	P42229.
SMR	P42229. Positions 2-690.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-396N.
IntAct	P42229. 20 interactions.
MINT	MINT-223002.
STRING	P42229.
PTM databases
PhosphoSite	P42229.
Polymorphism databases
DMDM	1174462.
Proteomic databases
PeptideAtlas	P42229.
PRIDE	P42229.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000345506; ENSP00000341208; ENSG00000126561. ENST00000452307; ENSP00000400320; ENSG00000126561.
GeneID	6776.
KEGG	hsa:6776.
UCSC	uc002hzj.1. human.
Organism-specific databases
CTD	6776.
GeneCards	GC17P040348.
H-InvDB	HIX0013838.
HGNC	HGNC:11366. STAT5A.
HPA	CAB003860. HPA027873.
MIM	601511. gene.
neXtProt	NX_P42229.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG11190.
HOGENOM	HBG445514.
HOVERGEN	HBG107486.
InParanoid	P42229.
OMA	DSPERNL.
OrthoDB	EOG457560.
PhylomeDB	P42229.
Enzyme and pathway databases
Pathway_Interaction_DB	angiopoietinreceptor_pathway. Angiopoietin receptor Tie2-mediated signaling. epopathway. EPO signaling pathway. il12_2pathway. IL12-mediated signaling events. il2_stat5pathway. IL2 signaling events mediated by STAT5. il2_1pathway. IL2-mediated signaling events. il23pathway. IL23-mediated signaling events. il27pathway. IL27-mediated signaling events. il4_2pathway. IL4-mediated signaling events. pdgfrbpathway. PDGFR-beta signaling pathway. ptp1bpathway. Signaling events mediated by PTP1B. kitpathway. Signaling events mediated by Stem cell factor receptor (c-Kit). pi3kplctrkpathway. Trk receptor signaling mediated by PI3K and PLC-gamma.
Reactome	REACT_111102. Signal Transduction. REACT_6900. Immune System.
Gene expression databases
ArrayExpress	P42229.
Bgee	P42229.
CleanEx	HS_STAT5A.
Genevestigator	P42229.
GermOnline	ENSG00000126561. 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	K11223.
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
NextBio	26450.
SOURCE	Search...

Entry information

Entry name

STA5A_HUMAN

Accession

Primary (citable) accession number: P42229

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	January 25, 2012
This is version 121 of the entry and version 1 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.