STA5A_RAT
ID STA5A_RAT Reviewed; 793 AA.
AC Q62771;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 25-MAY-2022, entry version 159.
DE RecName: Full=Signal transducer and activator of transcription 5A;
DE AltName: Full=Mammary gland factor;
GN Name=Stat5a; Synonyms=Mgf;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS STAT5A1 AND STAT5A2).
RC TISSUE=Mammary gland;
RX PubMed=8584036; DOI=10.1210/mend.9.11.8584036;
RA Kazansky A.V., Raught B., Lindsey S.M., Wang Y.-F., Rosen J.M.;
RT "Regulation of mammary gland factor/Stat5a during mammary gland
RT development.";
RL Mol. Endocrinol. 9:1598-1609(1995).
RN [2]
RP FUNCTION, AND PHOSPHORYLATION AT TYR-694 IN RESPONSE TO CONSTITUTIVELY
RP ACTIVATED FGFR3.
RX PubMed=19088846; DOI=10.1371/journal.pone.0003961;
RA Krejci P., Salazar L., Kashiwada T.A., Chlebova K., Salasova A.,
RA Thompson L.M., Bryja V., Kozubik A., Wilcox W.R.;
RT "Analysis of STAT1 activation by six FGFR3 mutants associated with skeletal
RT dysplasia undermines dominant role of STAT1 in FGFR3 signaling in
RT cartilage.";
RL PLoS ONE 3:E3961-E3961(2008).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-694 AND SER-779, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Carries out a dual function: signal transduction and
CC activation of transcription. Mediates cellular responses to the
CC cytokine KITLG/SCF and other growth factors. May mediate cellular
CC responses to activated FGFR1, FGFR2, FGFR3 and FGFR4. Binds to the GAS
CC element and activates PRL-induced transcription. Regulates the
CC expression of milk proteins during lactation.
CC {ECO:0000269|PubMed:19088846}.
CC -!- SUBUNIT: Forms a homodimer or a heterodimer with a related family
CC member. Binds NR3C1. Interacts with NCOA1 and SOCS7. Interacts with
CC ERBB4 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC Note=Mostly cytoplasmic during pregnancy, whereas it becomes
CC predominantly nuclear during early lactation. It is translocated into
CC the nucleus in response to phosphorylation (By similarity).
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Stat5A1;
CC IsoId=Q62771-1; Sequence=Displayed;
CC Name=Stat5A2;
CC IsoId=Q62771-2; Sequence=VSP_006288, VSP_006289;
CC -!- TISSUE SPECIFICITY: Expressed in heart, lung, and weakly in muscle.
CC -!- DEVELOPMENTAL STAGE: Detected both in virgin rats and after mammary
CC gland involution. The level of STAT5A increases constantly during
CC pregnancy, but decreases at the onset of lactation and remains lows
CC throughout lactation.
CC -!- PTM: ISGylated. {ECO:0000250|UniProtKB:P42230}.
CC -!- PTM: Tyrosine phosphorylated in response to KITLG/SCF, IL2, IL3, IL7,
CC IL15, CSF2/GMCSF, GH1, PRL, EPO and THPO (By similarity). Activated KIT
CC promotes phosphorylation on tyrosine residues and subsequent
CC translocation to the nucleus (By similarity). Tyrosine phosphorylated
CC in response to constitutively activated FGFR1, FGFR2, FGFR3 and FGFR4
CC (PubMed:22673903). Tyrosine phosphorylation is required for DNA-binding
CC activity and dimerization. Serine phosphorylation is also required for
CC maximal transcriptional activity (By similarity). Tyrosine
CC phosphorylated in response to signaling via activated FLT3; wild-type
CC FLT3 results in much weaker phosphorylation than constitutively
CC activated mutant FLT3. Alternatively, can be phosphorylated by JAK2 at
CC Tyr-694 (By similarity). {ECO:0000250|UniProtKB:P40763,
CC ECO:0000250|UniProtKB:P42229, ECO:0000250|UniProtKB:P42230}.
CC -!- SIMILARITY: Belongs to the transcription factor STAT family.
CC {ECO:0000305}.
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DR EMBL; U24175; AAA98843.1; -; mRNA.
DR RefSeq; NP_058760.1; NM_017064.1. [Q62771-1]
DR AlphaFoldDB; Q62771; -.
DR SMR; Q62771; -.
DR BioGRID; 247025; 3.
DR STRING; 10116.ENSRNOP00000026662; -.
DR iPTMnet; Q62771; -.
DR PhosphoSitePlus; Q62771; -.
DR jPOST; Q62771; -.
DR PaxDb; Q62771; -.
DR GeneID; 24918; -.
DR KEGG; rno:24918; -.
DR UCSC; RGD:3773; rat. [Q62771-1]
DR CTD; 6776; -.
DR RGD; 3773; Stat5a.
DR eggNOG; KOG3667; Eukaryota.
DR InParanoid; Q62771; -.
DR OrthoDB; 327469at2759; -.
DR Reactome; R-RNO-1251985; Nuclear signaling by ERBB4.
DR Reactome; R-RNO-1266695; Interleukin-7 signaling.
DR Reactome; R-RNO-1433557; Signaling by SCF-KIT.
DR Reactome; R-RNO-186763; Downstream signal transduction.
DR Reactome; R-RNO-512988; Interleukin-3, Interleukin-5 and GM-CSF signaling.
DR Reactome; R-RNO-8854691; Interleukin-20 family signaling.
DR Reactome; R-RNO-8983432; Interleukin-15 signaling.
DR Reactome; R-RNO-8985947; Interleukin-9 signaling.
DR Reactome; R-RNO-9020558; Interleukin-2 signaling.
DR Reactome; R-RNO-9020958; Interleukin-21 signaling.
DR Reactome; R-RNO-982772; Growth hormone receptor signaling.
DR PRO; PR:Q62771; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0003677; F:DNA binding; ISO:RGD.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:RGD.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0003690; F:double-stranded DNA binding; IDA:RGD.
DR GO; GO:0042301; F:phosphate ion binding; ISO:RGD.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:RGD.
DR GO; GO:0071345; P:cellular response to cytokine stimulus; IDA:MGI.
DR GO; GO:0097011; P:cellular response to granulocyte macrophage colony-stimulating factor stimulus; ISO:RGD.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IDA:MGI.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; ISO:RGD.
DR GO; GO:0006952; P:defense response; IBA:GO_Central.
DR GO; GO:0046543; P:development of secondary female sexual characteristics; ISO:RGD.
DR GO; GO:0046544; P:development of secondary male sexual characteristics; ISO:RGD.
DR GO; GO:0060742; P:epithelial cell differentiation involved in prostate gland development; ISO:RGD.
DR GO; GO:0007565; P:female pregnancy; ISO:RGD.
DR GO; GO:0060397; P:growth hormone receptor signaling pathway via JAK-STAT; ISO:RGD.
DR GO; GO:0007595; P:lactation; IEP:RGD.
DR GO; GO:0019915; P:lipid storage; ISO:RGD.
DR GO; GO:0001553; P:luteinization; ISO:RGD.
DR GO; GO:0030879; P:mammary gland development; ISO:RGD.
DR GO; GO:0061180; P:mammary gland epithelium development; ISO:RGD.
DR GO; GO:0060056; P:mammary gland involution; IDA:RGD.
DR GO; GO:0048609; P:multicellular organismal reproductive process; IEP:RGD.
DR GO; GO:0001779; P:natural killer cell differentiation; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
DR GO; GO:0045647; P:negative regulation of erythrocyte differentiation; ISO:RGD.
DR GO; GO:0033026; P:negative regulation of mast cell apoptotic process; ISO:RGD.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISO:RGD.
DR GO; GO:0048541; P:Peyer's patch development; ISO:RGD.
DR GO; GO:0042104; P:positive regulation of activated T cell proliferation; ISO:RGD.
DR GO; GO:0045579; P:positive regulation of B cell differentiation; ISO:RGD.
DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; ISO:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISO:RGD.
DR GO; GO:0045588; P:positive regulation of gamma-delta T cell differentiation; ISO:RGD.
DR GO; GO:0050729; P:positive regulation of inflammatory response; ISO:RGD.
DR GO; GO:0032743; P:positive regulation of interleukin-2 production; ISO:RGD.
DR GO; GO:0045621; P:positive regulation of lymphocyte differentiation; ISO:RGD.
DR GO; GO:0060376; P:positive regulation of mast cell differentiation; ISO:RGD.
DR GO; GO:0070668; P:positive regulation of mast cell proliferation; ISO:RGD.
DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; ISO:RGD.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; ISO:RGD.
DR GO; GO:0032825; P:positive regulation of natural killer cell differentiation; ISO:RGD.
DR GO; GO:0045954; P:positive regulation of natural killer cell mediated cytotoxicity; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0060740; P:prostate gland epithelium morphogenesis; ISO:RGD.
DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; IDA:RGD.
DR GO; GO:0038026; P:reelin-mediated signaling pathway; ISO:RGD.
DR GO; GO:0030155; P:regulation of cell adhesion; ISO:RGD.
DR GO; GO:0042127; P:regulation of cell population proliferation; IBA:GO_Central.
DR GO; GO:0030856; P:regulation of epithelial cell differentiation; ISO:RGD.
DR GO; GO:0040014; P:regulation of multicellular organism growth; ISO:RGD.
DR GO; GO:0019218; P:regulation of steroid metabolic process; ISO:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; TAS:RGD.
DR GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
DR GO; GO:0043434; P:response to peptide hormone; ISO:RGD.
DR GO; GO:0033077; P:T cell differentiation in thymus; ISO:RGD.
DR GO; GO:0043029; P:T cell homeostasis; ISO:RGD.
DR GO; GO:0019530; P:taurine metabolic process; ISO:RGD.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IDA:RGD.
DR Gene3D; 1.10.532.10; -; 1.
DR Gene3D; 2.60.40.630; -; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR008967; p53-like_TF_DNA-bd.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR001217; STAT.
DR InterPro; IPR035858; STAT5a/5b.
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; PTHR11801; 1.
DR PANTHER; PTHR11801:SF47; PTHR11801:SF47; 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 SMART; SM00252; SH2; 1.
DR SMART; SM00964; STAT_int; 1.
DR SUPFAM; SSF47655; SSF47655; 1.
DR SUPFAM; SSF48092; SSF48092; 1.
DR SUPFAM; SSF49417; SSF49417; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR PROSITE; PS50001; SH2; 1.
PE 1: Evidence at protein level;
KW Activator; Alternative splicing; Cytoplasm; DNA-binding; Lactation;
KW Nucleus; Phosphoprotein; Reference proteome; SH2 domain; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..793
FT /note="Signal transducer and activator of transcription 5A"
FT /id="PRO_0000182426"
FT DOMAIN 589..686
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 772..793
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 90
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P42229"
FT MOD_RES 128
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P42229"
FT MOD_RES 682
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P42229"
FT MOD_RES 694
FT /note="Phosphotyrosine; by JAK2"
FT /evidence="ECO:0000269|PubMed:19088846,
FT ECO:0007744|PubMed:22673903"
FT MOD_RES 779
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT VAR_SEQ 740
FT /note="N -> K (in isoform Stat5A2)"
FT /evidence="ECO:0000303|PubMed:8584036"
FT /id="VSP_006288"
FT VAR_SEQ 741..793
FT /note="Missing (in isoform Stat5A2)"
FT /evidence="ECO:0000303|PubMed:8584036"
FT /id="VSP_006289"
SQ SEQUENCE 793 AA; 90833 MW; C0C34EE3F5879FB5 CRC64;
MAGWIQAQQL QGDALRQMQV LYGQHFPIEV RHYLAQWIES QPWDAIDLDN PQDRGQATQL
LEGLVQELQK KAEHQVGEDG FVLKIKLGHY ATQLQNTYDR CPMELVRCIR HILYNEQRLV
REANNCSSPA GVLVDAMSQK HLQINQTFEE LRLITQDTES ELKKLQQTQE YFIIQYQESL
RIQAQFGQLA QLNPQERMSR ETALQQKQVS LETWLQREAQ TLQQYRVELV EKHQKTLQLL
RKQQTIILDD ELIQWKRGQQ LAGNGGPPEG SLDVLQSWCE KLAEIIWQNR QQIRRAEHLC
QQLPIPGPVE EMLAEVNATI TDIISALVTS TFIIEKQPPQ VLKTQTKFAA TVRLLVGGKL
NVHMNPPQVK ATIISEQQAK SLLKNENTRN DYSGEILNNC CVMEYHQATG TLSAHFRNMS
LKRIKRADRR GAESVTEEKF TVLFESQFSV GSNELVFQVK TLSLPVVVIV HGSQDHNATA
TVLWDNAFAE PGRVPFAVPD KVLWPQLCEA LNMKFKAEVQ SNRGLTKENL VFLAQKLFNR
RSNHLEDYNS MSVSWSQFNR ENLPGWNYTF WQWFDGVMEV LKKHHKPHWN DGAILGFVNK
QQAHDLLINK PDGTFLLRFS DSEIGGITIA WKFDSPDRNL WNLKPFTTRD FSIRSLADRL
GDLNYLIYVF PDRPKDEVFA KYYTPVLAKA VDGYVKPQIK QVVPEFVNAS ADAGANATYM
DQAPSPVVCP QAHYNMYPPN PDPVLDQDGE FDLDETMDVA RHVEELLRRP MDSLDPRLSP
PAGLFTSARS SLS
