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P42230

- STA5A_MOUSE

UniProt

P42230 - STA5A_MOUSE

Protein

Signal transducer and activator of transcription 5A

Gene

Stat5a

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 148 (01 Oct 2014)
      Sequence version 1 (01 Nov 1995)
      Previous versions | rss
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    Functioni

    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.2 Publications

    GO - Molecular functioni

    1. calcium ion binding Source: InterPro
    2. DNA binding Source: MGI
    3. protein binding Source: IntAct
    4. protein phosphatase binding Source: UniProtKB
    5. RNA polymerase II core promoter sequence-specific DNA binding Source: MGI
    6. sequence-specific DNA binding transcription factor activity Source: InterPro
    7. signal transducer activity Source: MGI

    GO - Biological processi

    1. 2-oxoglutarate metabolic process Source: BHF-UCL
    2. allantoin metabolic process Source: BHF-UCL
    3. cellular response to granulocyte macrophage colony-stimulating factor stimulus Source: MGI
    4. citrate metabolic process Source: BHF-UCL
    5. creatine metabolic process Source: BHF-UCL
    6. creatinine metabolic process Source: BHF-UCL
    7. cytokine-mediated signaling pathway Source: MGI
    8. development of secondary female sexual characteristics Source: MGI
    9. development of secondary male sexual characteristics Source: MGI
    10. epithelial cell differentiation involved in prostate gland development Source: MGI
    11. fatty acid metabolic process Source: BHF-UCL
    12. female pregnancy Source: MGI
    13. isoleucine metabolic process Source: BHF-UCL
    14. JAK-STAT cascade Source: MGI
    15. JAK-STAT cascade involved in growth hormone signaling pathway Source: BHF-UCL
    16. lactation Source: MGI
    17. lipid storage Source: MGI
    18. luteinization Source: MGI
    19. mammary gland development Source: MGI
    20. mammary gland epithelium development Source: MGI
    21. natural killer cell differentiation Source: MGI
    22. negative regulation of apoptotic process Source: MGI
    23. negative regulation of erythrocyte differentiation Source: MGI
    24. negative regulation of mast cell apoptotic process Source: MGI
    25. oxaloacetate metabolic process Source: BHF-UCL
    26. peptidyl-tyrosine phosphorylation Source: MGI
    27. Peyer's patch development Source: MGI
    28. positive regulation of activated T cell proliferation Source: MGI
    29. positive regulation of B cell differentiation Source: MGI
    30. positive regulation of cell proliferation Source: MGI
    31. positive regulation of gamma-delta T cell differentiation Source: MGI
    32. positive regulation of inflammatory response Source: MGI
    33. positive regulation of interleukin-2 biosynthetic process Source: MGI
    34. positive regulation of lymphocyte differentiation Source: MGI
    35. positive regulation of mast cell differentiation Source: MGI
    36. positive regulation of mast cell proliferation Source: MGI
    37. positive regulation of mitotic cell cycle Source: MGI
    38. positive regulation of multicellular organism growth Source: MGI
    39. positive regulation of natural killer cell differentiation Source: MGI
    40. positive regulation of natural killer cell mediated cytotoxicity Source: MGI
    41. positive regulation of transcription from RNA polymerase II promoter Source: MGI
    42. prolactin signaling pathway Source: UniProtKB
    43. prostate gland epithelium morphogenesis Source: MGI
    44. regulation of cell adhesion Source: MGI
    45. regulation of epithelial cell differentiation Source: MGI
    46. regulation of multicellular organism growth Source: BHF-UCL
    47. regulation of steroid metabolic process Source: MGI
    48. regulation of transcription from RNA polymerase II promoter Source: MGI
    49. response to peptide hormone Source: MGI
    50. succinate metabolic process Source: BHF-UCL
    51. taurine metabolic process Source: BHF-UCL
    52. T cell differentiation in thymus Source: MGI
    53. T cell homeostasis Source: MGI
    54. transcription, DNA-templated Source: UniProtKB-KW
    55. valine metabolic process Source: BHF-UCL

    Keywords - Molecular functioni

    Activator

    Keywords - Biological processi

    Lactation, Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding

    Enzyme and pathway databases

    ReactomeiREACT_169390. Signaling by Leptin.
    REACT_188529. Signaling by Leptin.
    REACT_188578. Signaling by SCF-KIT.
    REACT_196460. Signaling by FGFR1 fusion mutants.
    REACT_198561. Prolactin receptor signaling.
    REACT_198574. Nuclear signaling by ERBB4.
    REACT_198614. Growth hormone receptor signaling.
    REACT_198701. Interleukin-7 signaling.
    REACT_225836. Interleukin-3, 5 and GM-CSF signaling.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Signal transducer and activator of transcription 5A
    Alternative name(s):
    Mammary gland factor
    Gene namesi
    Name:Stat5a
    Synonyms:Mgf, Mpf
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 11

    Organism-specific databases

    MGIiMGI:103036. Stat5a.

    Subcellular locationi

    Cytoplasm 1 Publication. Nucleus 1 Publication
    Note: Translocated into the nucleus in response to phosphorylation.

    GO - Cellular componenti

    1. cytoplasm Source: MGI
    2. cytosol Source: Reactome
    3. nucleoplasm Source: Reactome
    4. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 793793Signal transducer and activator of transcription 5APRO_0000182424Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei128 – 1281PhosphoserineBy similarity
    Modified residuei694 – 6941Phosphotyrosine; by JAK2By similarity

    Post-translational modificationi

    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.By similarity
    ISGylated.1 Publication

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiP42230.
    PaxDbiP42230.
    PRIDEiP42230.

    PTM databases

    PhosphoSiteiP42230.

    Expressioni

    Tissue specificityi

    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.

    Gene expression databases

    ArrayExpressiP42230.
    BgeeiP42230.
    GenevestigatoriP42230.

    Interactioni

    Subunit structurei

    Forms a homodimer or a heterodimer with a related family member. Interacts with NCOA1 and SOCS7 By similarity. Binds NR3C1. Interacts with ERBB4.By similarity3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    AGAP2Q99490-22EBI-617434,EBI-7737644From a different organism.
    GHRP199413EBI-617434,EBI-7526279From a different organism.

    Protein-protein interaction databases

    BioGridi203525. 13 interactions.
    DIPiDIP-897N.
    IntActiP42230. 7 interactions.
    MINTiMINT-2576471.

    Structurei

    Secondary structure

    1
    793
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi144 – 18138
    Turni182 – 1909
    Turni196 – 1983
    Helixi199 – 24951
    Helixi251 – 26212
    Turni263 – 2653
    Helixi273 – 30028
    Helixi309 – 33022
    Beta strandi332 – 3365
    Beta strandi340 – 3456
    Beta strandi348 – 3558
    Turni356 – 3616
    Beta strandi368 – 3758
    Helixi376 – 3838
    Beta strandi404 – 4063
    Turni407 – 4104
    Beta strandi411 – 4133
    Beta strandi415 – 4195
    Helixi435 – 4373
    Beta strandi439 – 44911
    Beta strandi451 – 4544
    Beta strandi456 – 4627
    Beta strandi466 – 4694
    Helixi475 – 48814
    Beta strandi500 – 5034
    Helixi504 – 51916
    Helixi527 – 53812
    Helixi545 – 5506
    Beta strandi552 – 5543
    Helixi555 – 5595
    Beta strandi566 – 5694
    Helixi570 – 58415
    Helixi586 – 5916
    Helixi600 – 6089
    Beta strandi615 – 6206
    Beta strandi626 – 6316
    Beta strandi641 – 6466
    Helixi648 – 6536
    Helixi656 – 6627
    Helixi675 – 6795
    Turni680 – 6823

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1Y1UX-ray3.21A/B/C128-712[»]
    ProteinModelPortaliP42230.
    SMRiP42230. Positions 138-690.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP42230.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini589 – 68698SH2PROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Belongs to the transcription factor STAT family.Curated
    Contains 1 SH2 domain.PROSITE-ProRule annotation

    Keywords - Domaini

    SH2 domain

    Phylogenomic databases

    eggNOGiNOG245085.
    HOGENOMiHOG000230988.
    HOVERGENiHBG107486.
    InParanoidiP42230.
    KOiK11223.
    OrthoDBiEOG73JKTT.
    TreeFamiTF318648.

    Family and domain databases

    Gene3Di1.10.238.10. 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.
    InterProiIPR011992. 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]
    PANTHERiPTHR11801. PTHR11801. 1 hit.
    PfamiPF00017. SH2. 1 hit.
    PF01017. STAT_alpha. 1 hit.
    PF02864. STAT_bind. 1 hit.
    PF02865. STAT_int. 1 hit.
    [Graphical view]
    SMARTiSM00252. SH2. 1 hit.
    SM00964. STAT_int. 1 hit.
    [Graphical view]
    SUPFAMiSSF47655. SSF47655. 1 hit.
    SSF48092. SSF48092. 1 hit.
    SSF49417. SSF49417. 1 hit.
    SSF55550. SSF55550. 1 hit.
    PROSITEiPS50001. SH2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P42230-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAGWIQAQQL QGDALRQMQV LYGQHFPIEV RHYLAQWIES QPWDAIDLDN    50
    PQDRGQATQL LEGLVQELQK KAEHQVGEDG FLLKIKLGHY ATQLQNTYDR 100
    CPMELVRCIR HILYNEQRLV REANNCSSPA GVLVDAMSQK HLQINQRFEE 150
    LRLITQDTEN ELKKLQQTQE YFIIQYQESL RIQAQFAQLG QLNPQERMSR 200
    ETALQQKQVS LETWLQREAQ TLQQYRVELA EKHQKTLQLL RKQQTIILDD 250
    ELIQWKRRQQ LAGNGGPPEG SLDVLQSWCE KLAEIIWQNR QQIRRAEHLC 300
    QQLPIPGPVE EMLAEVNATI TDIISALVTS TFIIEKQPPQ VLKTQTKFAA 350
    TVRLLVGGKL NVHMNPPQVK ATIISEQQAK SLLKNENTRN ECSGEILNNC 400
    CVMEYHQATG TLSAHFRNMS LKRIKRADRR GAESVTEEKF TVLFESQFSV 450
    GSNELVFQVK TLSLPVVVIV HGSQDHNATA TVLWDNAFAE PGRVPFAVPD 500
    KVLWPQLCEA LNMKFKAEVQ SNRGLTKENL VFLAQKLFNI SSNHLEDYNS 550
    MSVSWSQFNR ENLPGWNYTF WQWFDGVMEV LKKHHKPHWN DGAILGFVNK 600
    QQAHDLLINK PDGTFLLRFS DSEIGGITIA WKFDSPDRNL WNLKPFTTRD 650
    FSIRSLADRL GDLNYLIYVF PDRPKDEVFA KYYTPVLAKA VDGYVKPQIK 700
    QVVPEFVNAS TDAGASATYM DQAPSPVVCP QPHYNMYPPN PDPVLDQDGE 750
    FDLDESMDVA RHVEELLRRP MDSLDARLSP PAGLFTSARS SLS 793
    Length:793
    Mass (Da):90,831
    Last modified:November 1, 1995 - v1
    Checksum:i7C66E435C37624DD
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Z48538 mRNA. Translation: CAA88419.1.
    U21103 mRNA. Translation: AAA80590.1.
    U36502 mRNA. Translation: AAA78945.1.
    CCDSiCCDS25439.1.
    PIRiS54772.
    RefSeqiNP_035618.1. NM_011488.3.
    XP_006532784.1. XM_006532721.1.
    XP_006532785.1. XM_006532722.1.
    UniGeneiMm.277403.

    Genome annotation databases

    EnsembliENSMUST00000004145; ENSMUSP00000004145; ENSMUSG00000004043.
    ENSMUST00000107356; ENSMUSP00000102979; ENSMUSG00000004043.
    GeneIDi20850.
    KEGGimmu:20850.
    UCSCiuc007lml.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Z48538 mRNA. Translation: CAA88419.1 .
    U21103 mRNA. Translation: AAA80590.1 .
    U36502 mRNA. Translation: AAA78945.1 .
    CCDSi CCDS25439.1.
    PIRi S54772.
    RefSeqi NP_035618.1. NM_011488.3.
    XP_006532784.1. XM_006532721.1.
    XP_006532785.1. XM_006532722.1.
    UniGenei Mm.277403.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1Y1U X-ray 3.21 A/B/C 128-712 [» ]
    ProteinModelPortali P42230.
    SMRi P42230. Positions 138-690.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 203525. 13 interactions.
    DIPi DIP-897N.
    IntActi P42230. 7 interactions.
    MINTi MINT-2576471.

    Chemistry

    ChEMBLi CHEMBL5513.

    PTM databases

    PhosphoSitei P42230.

    Proteomic databases

    MaxQBi P42230.
    PaxDbi P42230.
    PRIDEi P42230.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000004145 ; ENSMUSP00000004145 ; ENSMUSG00000004043 .
    ENSMUST00000107356 ; ENSMUSP00000102979 ; ENSMUSG00000004043 .
    GeneIDi 20850.
    KEGGi mmu:20850.
    UCSCi uc007lml.2. mouse.

    Organism-specific databases

    CTDi 6776.
    MGIi MGI:103036. Stat5a.

    Phylogenomic databases

    eggNOGi NOG245085.
    HOGENOMi HOG000230988.
    HOVERGENi HBG107486.
    InParanoidi P42230.
    KOi K11223.
    OrthoDBi EOG73JKTT.
    TreeFami TF318648.

    Enzyme and pathway databases

    Reactomei REACT_169390. Signaling by Leptin.
    REACT_188529. Signaling by Leptin.
    REACT_188578. Signaling by SCF-KIT.
    REACT_196460. Signaling by FGFR1 fusion mutants.
    REACT_198561. Prolactin receptor signaling.
    REACT_198574. Nuclear signaling by ERBB4.
    REACT_198614. Growth hormone receptor signaling.
    REACT_198701. Interleukin-7 signaling.
    REACT_225836. Interleukin-3, 5 and GM-CSF signaling.

    Miscellaneous databases

    EvolutionaryTracei P42230.
    NextBioi 299635.
    PROi P42230.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P42230.
    Bgeei P42230.
    Genevestigatori P42230.

    Family and domain databases

    Gene3Di 1.10.238.10. 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.
    InterProi IPR011992. 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 ]
    PANTHERi PTHR11801. PTHR11801. 1 hit.
    Pfami PF00017. SH2. 1 hit.
    PF01017. STAT_alpha. 1 hit.
    PF02864. STAT_bind. 1 hit.
    PF02865. STAT_int. 1 hit.
    [Graphical view ]
    SMARTi SM00252. SH2. 1 hit.
    SM00964. STAT_int. 1 hit.
    [Graphical view ]
    SUPFAMi SSF47655. SSF47655. 1 hit.
    SSF48092. SSF48092. 1 hit.
    SSF49417. SSF49417. 1 hit.
    SSF55550. SSF55550. 1 hit.
    PROSITEi PS50001. SH2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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. Cited for: PHOSPHORYLATION IN RESPONSE TO FLT3 SIGNALING.
    10. Cited for: ISGYLATION.
    11. Cited for: X-RAY CRYSTALLOGRAPHY (3.21 ANGSTROMS) OF 128-712.

    Entry informationi

    Entry nameiSTA5A_MOUSE
    AccessioniPrimary (citable) accession number: P42230
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1995
    Last sequence update: November 1, 1995
    Last modified: October 1, 2014
    This is version 148 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3