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Protein

Signal transducer and activator of transcription 5A

Gene

STAT5A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.1 Publication

Caution

It was reported that dephosphorylation on tyrosine residues by PTPN2 would negatively regulate prolactin signaling pathway (PubMed:11773439). However, the corresponding article has been retracted (PubMed:24319783).1 Publication1 Publication

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActivator, DNA-binding
Biological processLactation, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-1170546 Prolactin receptor signaling
R-HSA-1251985 Nuclear signaling by ERBB4
R-HSA-1266695 Interleukin-7 signaling
R-HSA-1433557 Signaling by SCF-KIT
R-HSA-1839117 Signaling by cytosolic FGFR1 fusion mutants
R-HSA-186763 Downstream signal transduction
R-HSA-2586552 Signaling by Leptin
R-HSA-512988 Interleukin-3, 5 and GM-CSF signaling
R-HSA-8854691 Interleukin-20 family signaling
R-HSA-8983432 Interleukin-15 signaling
R-HSA-9020558 Interleukin-2 signaling
R-HSA-9020958 Interleukin-21 signaling
R-HSA-982772 Growth hormone receptor signaling
SignaLinkiP42229
SIGNORiP42229

Names & Taxonomyi

Protein namesi
Recommended name:
Signal transducer and activator of transcription 5A
Gene namesi
Name:STAT5A
Synonyms:STAT5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000126561.16
HGNCiHGNC:11366 STAT5A
MIMi601511 gene
neXtProtiNX_P42229

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi6776
OpenTargetsiENSG00000126561
PharmGKBiPA338

Chemistry databases

ChEMBLiCHEMBL5403

Polymorphism and mutation databases

BioMutaiSTAT5A
DMDMi1174462

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001824231 – 794Signal transducer and activator of transcription 5AAdd BLAST794

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei90PhosphotyrosineCombined sources1
Modified residuei128PhosphoserineCombined sources1
Modified residuei193PhosphoserineCombined sources1
Modified residuei682PhosphotyrosineCombined sources1
Modified residuei694Phosphotyrosine; by JAK22 Publications1
Modified residuei780PhosphoserineCombined sources1

Post-translational modificationi

Tyrosine phosphorylated in response to KITLG/SCF, IL2, IL3, IL7, IL15, CSF2/GMCSF, GH1, PRL, EPO and THPO (By similarity). Activated KIT promotes phosphorylation on tyrosine residues and subsequent translocation to the nucleus (PubMed:21135090). Tyrosine phosphorylated in response to constitutively activated FGFR1, FGFR2, FGFR3 and FGFR4 (By similarity). 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 (PubMed:14504097). Alternatively, can be phosphorylated by JAK2 at Tyr-694 (PubMed:12529425).By similarity3 Publications
ISGylated.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP42229
MaxQBiP42229
PaxDbiP42229
PeptideAtlasiP42229
PRIDEiP42229
ProteomicsDBi55495

PTM databases

iPTMnetiP42229
PhosphoSitePlusiP42229

Expressioni

Gene expression databases

BgeeiENSG00000126561
CleanExiHS_STAT5A
ExpressionAtlasiP42229 baseline and differential
GenevisibleiP42229 HS

Organism-specific databases

HPAiCAB003860
HPA027873
HPA042128
HPA049883
HPA051156

Interactioni

Subunit structurei

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

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi112653, 83 interactors
CORUMiP42229
DIPiDIP-396N
IntActiP42229, 54 interactors
MINTiP42229
STRINGi9606.ENSP00000341208

Chemistry databases

BindingDBiP42229

Structurei

3D structure databases

ProteinModelPortaliP42229
SMRiP42229
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini589 – 686SH2PROSITE-ProRule annotationAdd BLAST98

Sequence similaritiesi

Belongs to the transcription factor STAT family.Curated

Keywords - Domaini

SH2 domain

Phylogenomic databases

eggNOGiKOG3667 Eukaryota
ENOG410XPN8 LUCA
GeneTreeiENSGT00760000119236
HOGENOMiHOG000230988
HOVERGENiHBG107486
InParanoidiP42229
KOiK11223
OMAiITIAWVN
OrthoDBiEOG091G03O3
PhylomeDBiP42229
TreeFamiTF318648

Family and domain databases

Gene3Di1.10.532.10, 1 hit
2.60.40.630, 1 hit
3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR008967 p53-like_TF_DNA-bd
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR001217 STAT
IPR035858 STAT5a/5b
IPR036535 STAT_N_sf
IPR013800 STAT_TF_alpha
IPR015988 STAT_TF_coiled-coil
IPR013801 STAT_TF_DNA-bd
IPR012345 STAT_TF_DNA-bd_N
IPR013799 STAT_TF_prot_interaction
PANTHERiPTHR11801 PTHR11801, 1 hit
PTHR11801:SF47 PTHR11801:SF47, 1 hit
PfamiView protein in Pfam
PF00017 SH2, 1 hit
PF01017 STAT_alpha, 1 hit
PF02864 STAT_bind, 1 hit
PF02865 STAT_int, 1 hit
SMARTiView protein in SMART
SM00252 SH2, 1 hit
SM00964 STAT_int, 1 hit
SUPFAMiSSF47655 SSF47655, 1 hit
SSF48092 SSF48092, 1 hit
SSF49417 SSF49417, 1 hit
SSF55550 SSF55550, 1 hit
PROSITEiView protein in PROSITE
PS50001 SH2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P42229-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAGWIQAQQL QGDALRQMQV LYGQHFPIEV RHYLAQWIES QPWDAIDLDN
60 70 80 90 100
PQDRAQATQL LEGLVQELQK KAEHQVGEDG FLLKIKLGHY ATQLQKTYDR
110 120 130 140 150
CPLELVRCIR HILYNEQRLV REANNCSSPA GILVDAMSQK HLQINQTFEE
160 170 180 190 200
LRLVTQDTEN ELKKLQQTQE YFIIQYQESL RIQAQFAQLA QLSPQERLSR
210 220 230 240 250
ETALQQKQVS LEAWLQREAQ TLQQYRVELA EKHQKTLQLL RKQQTIILDD
260 270 280 290 300
ELIQWKRRQQ LAGNGGPPEG SLDVLQSWCE KLAEIIWQNR QQIRRAEHLC
310 320 330 340 350
QQLPIPGPVE EMLAEVNATI TDIISALVTS TFIIEKQPPQ VLKTQTKFAA
360 370 380 390 400
TVRLLVGGKL NVHMNPPQVK ATIISEQQAK SLLKNENTRN ECSGEILNNC
410 420 430 440 450
CVMEYHQATG TLSAHFRNMS LKRIKRADRR GAESVTEEKF TVLFESQFSV
460 470 480 490 500
GSNELVFQVK TLSLPVVVIV HGSQDHNATA TVLWDNAFAE PGRVPFAVPD
510 520 530 540 550
KVLWPQLCEA LNMKFKAEVQ SNRGLTKENL VFLAQKLFNN SSSHLEDYSG
560 570 580 590 600
LSVSWSQFNR ENLPGWNYTF WQWFDGVMEV LKKHHKPHWN DGAILGFVNK
610 620 630 640 650
QQAHDLLINK PDGTFLLRFS DSEIGGITIA WKFDSPERNL WNLKPFTTRD
660 670 680 690 700
FSIRSLADRL GDLSYLIYVF PDRPKDEVFS KYYTPVLAKA VDGYVKPQIK
710 720 730 740 750
QVVPEFVNAS ADAGGSSATY MDQAPSPAVC PQAPYNMYPQ NPDHVLDQDG
760 770 780 790
EFDLDETMDV ARHVEELLRR PMDSLDSRLS PPAGLFTSAR GSLS
Length:794
Mass (Da):90,647
Last modified:November 1, 1995 - v1
Checksum:iC64237295F88CFBE
GO
Isoform 2 (identifier: P42229-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     96-125: Missing.

Show »
Length:764
Mass (Da):86,949
Checksum:i20FC15C3CDFA26FE
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti88G → R in AAB06589 (Ref. 2) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_052073389R → H. Corresponds to variant dbSNP:rs2230134Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_05333296 – 125Missing in isoform 2. 2 PublicationsAdd BLAST30

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L41142 mRNA Translation: AAA73962.1
U43185 mRNA Translation: AAB06589.1
DQ471288 mRNA Translation: ABF17939.1
AK301457 mRNA Translation: BAH13486.1
AC087691 Genomic DNA No translation available.
AC099811 Genomic DNA No translation available.
BC027036 mRNA Translation: AAH27036.1
CCDSiCCDS11424.1 [P42229-1]
CCDS74067.1 [P42229-2]
PIRiG02317
RefSeqiNP_001275647.1, NM_001288718.1 [P42229-1]
NP_001275648.1, NM_001288719.1 [P42229-2]
NP_001275649.1, NM_001288720.1
NP_003143.2, NM_003152.3 [P42229-1]
UniGeneiHs.437058

Genome annotation databases

EnsembliENST00000345506; ENSP00000341208; ENSG00000126561 [P42229-1]
ENST00000546010; ENSP00000443107; ENSG00000126561 [P42229-2]
ENST00000590949; ENSP00000468749; ENSG00000126561 [P42229-1]
GeneIDi6776
KEGGihsa:6776
UCSCiuc002hzj.3 human [P42229-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiSTA5A_HUMAN
AccessioniPrimary (citable) accession number: P42229
Secondary accession number(s): Q1KLZ6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: July 18, 2018
This is version 188 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

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