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P42230 (STA5A_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 146. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Signal transducer and activator of transcription 5A
Alternative name(s):
Mammary gland factor
Gene names
Name:Stat5a
Synonyms:Mgf, Mpf
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length793 AA.
Sequence statusComplete.
Protein existenceEvidence 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. 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.5 Ref.7

Subunit structure

Forms a homodimer or a heterodimer with a related family member. Interacts with NCOA1 and SOCS7 By similarity. Binds NR3C1. Interacts with ERBB4. Ref.4 Ref.5 Ref.7

Subcellular location

Cytoplasm. Nucleus. Note: Translocated into the nucleus in response to phosphorylation. Ref.7

Tissue specificity

In the virgin, found in most tissues except brain and muscle. During lactation, abundantly found in mammary tissue, as well as in other secretory organs such as salivary gland and seminal vesicle.

Post-translational modification

Tyrosine phosphorylated in response to IL2, IL3, IL7, IL15, KITLG/SCF, 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 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. Tyrosine phosphorylation is required for DNA-binding activity and dimerization. Serine phosphorylation is also required for maximal transcriptional activity. Dephosphorylation on tyrosine residues by PTPN2 negatively regulates prolactin signaling pathway By similarity. Ref.6 Ref.7 Ref.8 Ref.9

ISGylated. Ref.10

Sequence similarities

Belongs to the transcription factor STAT family.

Contains 1 SH2 domain.

Ontologies

Keywords
   Biological processLactation
Transcription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   DomainSH2 domain
   LigandDNA-binding
   Molecular functionActivator
   PTMPhosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_process2-oxoglutarate metabolic process

Inferred from mutant phenotype PubMed 18648510. Source: BHF-UCL

JAK-STAT cascade

Inferred from direct assay PubMed 10485657. Source: MGI

JAK-STAT cascade involved in growth hormone signaling pathway

Inferred from direct assay PubMed 8702683. Source: BHF-UCL

Peyer's patch development

Inferred from genetic interaction PubMed 15294943. Source: MGI

T cell differentiation in thymus

Inferred from genetic interaction PubMed 15294943. Source: MGI

T cell homeostasis

Inferred from genetic interaction PubMed 10072077. Source: MGI

allantoin metabolic process

Inferred from mutant phenotype PubMed 18648510. Source: BHF-UCL

cellular response to granulocyte macrophage colony-stimulating factor stimulus

Inferred from direct assay PubMed 23610142. Source: MGI

citrate metabolic process

Inferred from mutant phenotype PubMed 18648510. Source: BHF-UCL

creatine metabolic process

Inferred from mutant phenotype PubMed 18648510. Source: BHF-UCL

creatinine metabolic process

Inferred from mutant phenotype PubMed 18648510. Source: BHF-UCL

cytokine-mediated signaling pathway

Inferred from direct assay PubMed 10485657. Source: MGI

development of secondary female sexual characteristics

Inferred from mutant phenotype PubMed 9630227. Source: MGI

development of secondary male sexual characteristics

Inferred from mutant phenotype PubMed 9630227. Source: MGI

epithelial cell differentiation involved in prostate gland development

Inferred from mutant phenotype PubMed 10908145. Source: MGI

fatty acid metabolic process

Inferred from mutant phenotype PubMed 18648510. Source: BHF-UCL

female pregnancy

Inferred from genetic interaction PubMed 15471942. Source: MGI

isoleucine metabolic process

Inferred from mutant phenotype PubMed 18648510. Source: BHF-UCL

lactation

Inferred from mutant phenotype PubMed 11706048PubMed 9630227. Source: MGI

lipid storage

Inferred from genetic interaction PubMed 9630227. Source: MGI

luteinization

Inferred from genetic interaction PubMed 9630227. Source: MGI

mammary gland development

Inferred from mutant phenotype PubMed 9630227. Source: MGI

mammary gland epithelium development

Inferred from mutant phenotype PubMed 12040017. Source: MGI

natural killer cell differentiation

Inferred from genetic interaction PubMed 10072077. Source: MGI

negative regulation of apoptotic process

Inferred from genetic interaction PubMed 10652277. Source: MGI

negative regulation of erythrocyte differentiation

Inferred from genetic interaction PubMed 10072077. Source: MGI

negative regulation of mast cell apoptotic process

Inferred from mutant phenotype PubMed 15947484. Source: MGI

oxaloacetate metabolic process

Inferred from mutant phenotype PubMed 18648510. Source: BHF-UCL

peptidyl-tyrosine phosphorylation

Inferred from direct assay PubMed 12388746. Source: MGI

positive regulation of B cell differentiation

Inferred from genetic interaction PubMed 10979977. Source: MGI

positive regulation of activated T cell proliferation

Inferred from direct assay PubMed 10072077. Source: MGI

positive regulation of cell proliferation

Inferred from direct assay PubMed 10652277. Source: MGI

positive regulation of gamma-delta T cell differentiation

Inferred from genetic interaction PubMed 15294943. Source: MGI

positive regulation of inflammatory response

Inferred from genetic interaction PubMed 10652277. Source: MGI

positive regulation of interleukin-2 biosynthetic process

Inferred from genetic interaction PubMed 10072077. Source: MGI

positive regulation of lymphocyte differentiation

Inferred from genetic interaction PubMed 15294943. Source: MGI

positive regulation of mast cell differentiation

Inferred from mutant phenotype PubMed 15947484. Source: MGI

positive regulation of mast cell proliferation

Inferred from mutant phenotype PubMed 15947484. Source: MGI

positive regulation of mitotic cell cycle

Inferred from genetic interaction PubMed 10072077. Source: MGI

positive regulation of multicellular organism growth

Inferred from genetic interaction PubMed 9630227. Source: MGI

positive regulation of natural killer cell differentiation

Inferred from mutant phenotype PubMed 9841920. Source: MGI

positive regulation of natural killer cell mediated cytotoxicity

Inferred from mutant phenotype PubMed 9841920. Source: MGI

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 19666510. Source: MGI

prolactin signaling pathway

Inferred from direct assay PubMed 11773439. Source: UniProtKB

prostate gland epithelium morphogenesis

Inferred from mutant phenotype PubMed 10908145. Source: MGI

regulation of cell adhesion

Inferred from mutant phenotype PubMed 11706048. Source: MGI

regulation of epithelial cell differentiation

Inferred from mutant phenotype PubMed 11706048. Source: MGI

regulation of multicellular organism growth

Inferred from direct assay PubMed 18648510. Source: BHF-UCL

regulation of steroid metabolic process

Inferred from genetic interaction PubMed 15471942. Source: MGI

regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 21217760. Source: MGI

response to peptide hormone

Inferred from direct assay PubMed 12388746. Source: MGI

succinate metabolic process

Inferred from mutant phenotype PubMed 18648510. Source: BHF-UCL

taurine metabolic process

Inferred from mutant phenotype PubMed 18648510. Source: BHF-UCL

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

valine metabolic process

Inferred from mutant phenotype PubMed 18648510. Source: BHF-UCL

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 11254359PubMed 14522949. Source: MGI

cytosol

Traceable author statement. Source: Reactome

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay PubMed 12456807. Source: UniProtKB

   Molecular_functionDNA binding

Inferred from direct assay PubMed 10485657PubMed 12147240PubMed 12388746. Source: MGI

RNA polymerase II core promoter sequence-specific DNA binding

Inferred from direct assay PubMed 19666510. Source: MGI

calcium ion binding

Inferred from electronic annotation. Source: InterPro

protein binding

Inferred from physical interaction PubMed 17666591PubMed 20075866. Source: IntAct

protein phosphatase binding

Inferred from physical interaction PubMed 11773439. Source: UniProtKB

sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: InterPro

signal transducer activity

Inferred from genetic interaction PubMed 10485657. Source: MGI

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

AGAP2Q99490-22EBI-617434,EBI-7737644From a different organism.
GHRP199413EBI-617434,EBI-7526279From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 793793Signal transducer and activator of transcription 5A
PRO_0000182424

Regions

Domain589 – 68698SH2

Amino acid modifications

Modified residue1281Phosphoserine By similarity
Modified residue6941Phosphotyrosine; by JAK2 By similarity

Secondary structure

........................................................................ 793
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P42230 [UniParc].

Last modified November 1, 1995. Version 1.
Checksum: 7C66E435C37624DD

FASTA79390,831
        10         20         30         40         50         60 
MAGWIQAQQL QGDALRQMQV LYGQHFPIEV RHYLAQWIES QPWDAIDLDN PQDRGQATQL 

        70         80         90        100        110        120 
LEGLVQELQK KAEHQVGEDG FLLKIKLGHY ATQLQNTYDR CPMELVRCIR HILYNEQRLV 

       130        140        150        160        170        180 
REANNCSSPA GVLVDAMSQK HLQINQRFEE LRLITQDTEN ELKKLQQTQE YFIIQYQESL 

       190        200        210        220        230        240 
RIQAQFAQLG QLNPQERMSR ETALQQKQVS LETWLQREAQ 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 VFLAQKLFNI 

       550        560        570        580        590        600 
SSNHLEDYNS MSVSWSQFNR ENLPGWNYTF WQWFDGVMEV LKKHHKPHWN DGAILGFVNK 

       610        620        630        640        650        660 
QQAHDLLINK PDGTFLLRFS DSEIGGITIA WKFDSPDRNL WNLKPFTTRD FSIRSLADRL 

       670        680        690        700        710        720 
GDLNYLIYVF PDRPKDEVFA KYYTPVLAKA VDGYVKPQIK QVVPEFVNAS TDAGASATYM 

       730        740        750        760        770        780 
DQAPSPVVCP QPHYNMYPPN PDPVLDQDGE FDLDESMDVA RHVEELLRRP MDSLDARLSP 

       790 
PAGLFTSARS SLS 

« Hide

References

[1]"Interleukin-3, granulocyte-macrophage colony stimulating factor and interleukin-5 transduce signals through two STAT5 homologs."
Mui A.L.-F., Wakao H., O'Farrell A.-M., Harada N., Miyajima A.
EMBO J. 14:1166-1175(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: C57BL/6 X A/J.
Tissue: Liver.
[2]"Cloning and expression of Stat5 and an additional homologue (Stat5b) involved in prolactin signal transduction in mouse mammary tissue."
Liu X., Robinson G.W., Gouilleux F., Groner B., Hennighausen L.
Proc. Natl. Acad. Sci. U.S.A. 92:8831-8835(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: C57BL/6.
[3]Zhou L.X., Moore R.C., Oka T.
Submitted (SEP-1995) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: C3H/HeN.
Tissue: Mammary gland.
[4]"Characterization of Stat5a and Stat5b homodimers and heterodimers and their association with the glucocortiocoid receptor in mammary cells."
Cella N., Groner B., Hynes N.E.
Mol. Cell. Biol. 18:1783-1792(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NR3C1.
[5]"ErbB4 signaling in the mammary gland is required for lobuloalveolar development and Stat5 activation during lactation."
Jones F.E., Welte T., Fu X.Y., Stern D.F.
J. Cell Biol. 147:77-88(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ERBB4.
[6]"Flt3 mutations from patients with acute myeloid leukemia induce transformation of 32D cells mediated by the Ras and STAT5 pathways."
Mizuki M., Fenski R., Halfter H., Matsumura I., Schmidt R., Muller C., Gruning W., Kratz-Albers K., Serve S., Steur C., Buchner T., Kienast J., Kanakura Y., Berdel W.E., Serve H.
Blood 96:3907-3914(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION IN RESPONSE TO FLT3 SIGNALING.
[7]"The intracellular domain of ErbB4 induces differentiation of mammary epithelial cells."
Muraoka-Cook R.S., Sandahl M., Husted C., Hunter D., Miraglia L., Feng S.M., Elenius K., Earp H.S. III
Mol. Biol. Cell 17:4118-4129(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION, SUBCELLULAR LOCATION, INTERACTION WITH ERBB4.
[8]"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] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION IN RESPONSE TO KIT SIGNALING.
[9]"Protein-tyrosine phosphatase DEP-1 controls receptor tyrosine kinase FLT3 signaling."
Arora D., Stopp S., Bohmer S.A., Schons J., Godfrey R., Masson K., Razumovskaya E., Ronnstrand L., Tanzer S., Bauer R., Bohmer F.D., Muller J.P.
J. Biol. Chem. 286:10918-10929(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION IN RESPONSE TO FLT3 SIGNALING.
[10]"ISG15 modulates development of the erythroid lineage."
Maragno A.L., Pironin M., Alcalde H., Cong X., Knobeloch K.P., Tangy F., Zhang D.E., Ghysdael J., Quang C.T.
PLoS ONE 6:E26068-E26068(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: ISGYLATION.
[11]"Structure of the unphosphorylated STAT5a dimer."
Neculai D., Neculai A.M., Verrier S., Straub K., Klumpp K., Pfitzner E., Becker S.
J. Biol. Chem. 280:40782-40787(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.21 ANGSTROMS) OF 128-712.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Z48538 mRNA. Translation: CAA88419.1.
U21103 mRNA. Translation: AAA80590.1.
U36502 mRNA. Translation: AAA78945.1.
CCDSCCDS25439.1.
PIRS54772.
RefSeqNP_035618.1. NM_011488.3.
XP_006532784.1. XM_006532721.1.
XP_006532785.1. XM_006532722.1.
UniGeneMm.277403.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1Y1UX-ray3.21A/B/C128-712[»]
ProteinModelPortalP42230.
SMRP42230. Positions 138-690.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid203525. 13 interactions.
DIPDIP-897N.
IntActP42230. 7 interactions.
MINTMINT-2576471.

Chemistry

ChEMBLCHEMBL5513.

PTM databases

PhosphoSiteP42230.

Proteomic databases

MaxQBP42230.
PaxDbP42230.
PRIDEP42230.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000004145; ENSMUSP00000004145; ENSMUSG00000004043.
ENSMUST00000107356; ENSMUSP00000102979; ENSMUSG00000004043.
GeneID20850.
KEGGmmu:20850.
UCSCuc007lml.2. mouse.

Organism-specific databases

CTD6776.
MGIMGI:103036. Stat5a.

Phylogenomic databases

eggNOGNOG245085.
HOGENOMHOG000230988.
HOVERGENHBG107486.
InParanoidP42230.
KOK11223.
OrthoDBEOG73JKTT.
TreeFamTF318648.

Enzyme and pathway databases

ReactomeREACT_188257. Signal Transduction.
REACT_200794. Mus musculus biological processes.

Gene expression databases

ArrayExpressP42230.
BgeeP42230.
GenevestigatorP42230.

Family and domain databases

Gene3D1.10.238.10. 1 hit.
1.10.532.10. 1 hit.
1.20.1050.20. 1 hit.
2.60.40.630. 1 hit.
3.30.505.10. 1 hit.
InterProIPR011992. EF-hand-dom_pair.
IPR008967. p53-like_TF_DNA-bd.
IPR000980. SH2.
IPR001217. STAT.
IPR013800. STAT_TF_alpha.
IPR015988. STAT_TF_coiled-coil.
IPR013801. STAT_TF_DNA-bd.
IPR012345. STAT_TF_DNA-bd_sub.
IPR013799. STAT_TF_prot_interaction.
[Graphical view]
PANTHERPTHR11801. PTHR11801. 1 hit.
PfamPF00017. SH2. 1 hit.
PF01017. STAT_alpha. 1 hit.
PF02864. STAT_bind. 1 hit.
PF02865. STAT_int. 1 hit.
[Graphical view]
SMARTSM00252. SH2. 1 hit.
SM00964. STAT_int. 1 hit.
[Graphical view]
SUPFAMSSF47655. SSF47655. 1 hit.
SSF48092. SSF48092. 1 hit.
SSF49417. SSF49417. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEPS50001. SH2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP42230.
NextBio299635.
PROP42230.
SOURCESearch...

Entry information

Entry nameSTA5A_MOUSE
AccessionPrimary (citable) accession number: P42230
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: July 9, 2014
This is version 146 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot