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Protein

Signal transducer and activator of transcription 4

Gene

STAT4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Carries out a dual function: signal transduction and activation of transcription. Involved in IL12 signaling.

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

SignaLinkiQ14765.

Names & Taxonomyi

Protein namesi
Recommended name:
Signal transducer and activator of transcription 4
Gene namesi
Name:STAT4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:11365. STAT4.

Subcellular locationi

  • Cytoplasm
  • Nucleus

  • Note: Translocated into the nucleus in response to phosphorylation.

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Systemic lupus erythematosus 11 (SLEB11)1 Publication

Disease susceptibility is associated with variations affecting the gene represented in this entry.

Disease descriptionA chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.

See also OMIM:612253
Rheumatoid arthritis (RA)1 Publication

Disease susceptibility is associated with variations affecting the gene represented in this entry.

Disease descriptionAn inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures.

See also OMIM:180300

Keywords - Diseasei

Systemic lupus erythematosus

Organism-specific databases

MIMi180300. phenotype.
612253. phenotype.
Orphaneti117. Behcet disease.
85408. Juvenile rheumatoid factor-negative polyarthritis.
85410. Oligoarticular juvenile arthritis.
93552. Pediatric systemic lupus erythematosus.
536. Systemic lupus erythematosus.
PharmGKBiPA36185.

Polymorphism and mutation databases

BioMutaiSTAT4.
DMDMi6226158.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 748748Signal transducer and activator of transcription 4PRO_0000182420Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei693 – 6931Phosphotyrosine; by JAKBy similarity

Post-translational modificationi

Tyrosine phosphorylated. Serine phosphorylation is also required for maximal transcriptional activity (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ14765.
PRIDEiQ14765.

PTM databases

PhosphoSiteiQ14765.

Expressioni

Gene expression databases

BgeeiQ14765.
CleanExiHS_STAT4.
ExpressionAtlasiQ14765. baseline and differential.
GenevisibleiQ14765. HS.

Organism-specific databases

HPAiCAB013108.
HPA001860.

Interactioni

Subunit structurei

Forms a homodimer or a heterodimer with a related family member. Interacts with ARL2BP (By similarity). The SH2 domain interacts, in vitro, with IL12RB2 via a short cytoplasmic domain.By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
LAMTOR5O435042EBI-1186538,EBI-713382

Protein-protein interaction databases

BioGridi112652. 8 interactions.
DIPiDIP-39854N.
IntActiQ14765. 7 interactions.
MINTiMINT-8020311.
STRINGi9606.ENSP00000351255.

Structurei

3D structure databases

ProteinModelPortaliQ14765.
SMRiQ14765. Positions 2-702.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini569 – 66496SH2PROSITE-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

eggNOGiNOG267627.
GeneTreeiENSGT00760000119236.
HOGENOMiHOG000220792.
HOVERGENiHBG055669.
InParanoidiQ14765.
KOiK11222.
OMAiIPMQRTH.
OrthoDBiEOG73JKTT.
PhylomeDBiQ14765.
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.
IPR029839. STAT4.
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.
PTHR11801:SF19. PTHR11801:SF19. 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.

Q14765-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSQWNQVQQL EIKFLEQVDQ FYDDNFPMEI RHLLAQWIEN QDWEAASNNE
60 70 80 90 100
TMATILLQNL LIQLDEQLGR VSKEKNLLLI HNLKRIRKVL QGKFHGNPMH
110 120 130 140 150
VAVVISNCLR EERRILAAAN MPVQGPLEKS LQSSSVSERQ RNVEHKVAAI
160 170 180 190 200
KNSVQMTEQD TKYLEDLQDE FDYRYKTIQT MDQSDKNSAM VNQEVLTLQE
210 220 230 240 250
MLNSLDFKRK EALSKMTQII HETDLLMNTM LIEELQDWKR RQQIACIGGP
260 270 280 290 300
LHNGLDQLQN CFTLLAESLF QLRRQLEKLE EQSTKMTYEG DPIPMQRTHM
310 320 330 340 350
LERVTFLIYN LFKNSFVVER QPCMPTHPQR PLVLKTLIQF TVKLRLLIKL
360 370 380 390 400
PELNYQVKVK ASIDKNVSTL SNRRFVLCGT NVKAMSIEES SNGSLSVEFR
410 420 430 440 450
HLQPKEMKSS AGGKGNEGCH MVTEELHSIT FETQICLYGL TIDLETSSLP
460 470 480 490 500
VVMISNVSQL PNAWASIIWY NVSTNDSQNL VFFNNPPPAT LSQLLEVMSW
510 520 530 540 550
QFSSYVGRGL NSDQLHMLAE KLTVQSSYSD GHLTWAKFCK EHLPGKSFTF
560 570 580 590 600
WTWLEAILDL IKKHILPLWI DGYVMGFVSK EKERLLLKDK MPGTFLLRFS
610 620 630 640 650
ESHLGGITFT WVDHSESGEV RFHSVEPYNK GRLSALPFAD ILRDYKVIMA
660 670 680 690 700
ENIPENPLKY LYPDIPKDKA FGKHYSSQPC EVSRPTERGD KGYVPSVFIP
710 720 730 740
ISTIRSDSTE PHSPSDLLPM SPSVYAVLRE NLSPTTIETA MKSPYSAE
Length:748
Mass (Da):85,941
Last modified:November 1, 1996 - v1
Checksum:i11E43803A9AF4FFA
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti365 – 3717KNVSTLS → N in AAL12164 (Ref. 3) Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti112 – 1121E → Q in a breast cancer sample; somatic mutation. 1 Publication
VAR_036002
Natural varianti115 – 1151I → V.
Corresponds to variant rs3024839 [ dbSNP | Ensembl ].
VAR_020190
Natural varianti584 – 5841R → W.
Corresponds to variant rs3024933 [ dbSNP | Ensembl ].
VAR_047939

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L78440 mRNA. Translation: AAB05605.1.
BC031212 mRNA. Translation: AAH31212.1.
AF423072 Genomic DNA. Translation: AAL12164.1.
CCDSiCCDS2310.1.
RefSeqiNP_001230764.1. NM_001243835.1.
NP_003142.1. NM_003151.3.
XP_006712782.1. XM_006712719.2.
UniGeneiHs.735572.
Hs.80642.

Genome annotation databases

EnsembliENST00000358470; ENSP00000351255; ENSG00000138378.
ENST00000392320; ENSP00000376134; ENSG00000138378.
GeneIDi6775.
KEGGihsa:6775.
UCSCiuc002usm.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L78440 mRNA. Translation: AAB05605.1.
BC031212 mRNA. Translation: AAH31212.1.
AF423072 Genomic DNA. Translation: AAL12164.1.
CCDSiCCDS2310.1.
RefSeqiNP_001230764.1. NM_001243835.1.
NP_003142.1. NM_003151.3.
XP_006712782.1. XM_006712719.2.
UniGeneiHs.735572.
Hs.80642.

3D structure databases

ProteinModelPortaliQ14765.
SMRiQ14765. Positions 2-702.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112652. 8 interactions.
DIPiDIP-39854N.
IntActiQ14765. 7 interactions.
MINTiMINT-8020311.
STRINGi9606.ENSP00000351255.

PTM databases

PhosphoSiteiQ14765.

Polymorphism and mutation databases

BioMutaiSTAT4.
DMDMi6226158.

Proteomic databases

PaxDbiQ14765.
PRIDEiQ14765.

Protocols and materials databases

DNASUi6775.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000358470; ENSP00000351255; ENSG00000138378.
ENST00000392320; ENSP00000376134; ENSG00000138378.
GeneIDi6775.
KEGGihsa:6775.
UCSCiuc002usm.2. human.

Organism-specific databases

CTDi6775.
GeneCardsiGC02M191894.
HGNCiHGNC:11365. STAT4.
HPAiCAB013108.
HPA001860.
MIMi180300. phenotype.
600558. gene.
612253. phenotype.
neXtProtiNX_Q14765.
Orphaneti117. Behcet disease.
85408. Juvenile rheumatoid factor-negative polyarthritis.
85410. Oligoarticular juvenile arthritis.
93552. Pediatric systemic lupus erythematosus.
536. Systemic lupus erythematosus.
PharmGKBiPA36185.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG267627.
GeneTreeiENSGT00760000119236.
HOGENOMiHOG000220792.
HOVERGENiHBG055669.
InParanoidiQ14765.
KOiK11222.
OMAiIPMQRTH.
OrthoDBiEOG73JKTT.
PhylomeDBiQ14765.
TreeFamiTF318648.

Enzyme and pathway databases

SignaLinkiQ14765.

Miscellaneous databases

GeneWikiiSTAT4.
GenomeRNAii6775.
NextBioi26446.
PROiQ14765.
SOURCEiSearch...

Gene expression databases

BgeeiQ14765.
CleanExiHS_STAT4.
ExpressionAtlasiQ14765. baseline and differential.
GenevisibleiQ14765. HS.

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.
IPR029839. STAT4.
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.
PTHR11801:SF19. PTHR11801:SF19. 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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The STAT amino-terminal domain mediates cooperative DNA binding and confers selective sequence recognition."
    Xu X., Sun Y.L., Hoey T.
    Submitted (AUG-1996) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Testis.
  3. SeattleSNPs variation discovery resource
    Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 91-748.
  4. "Direct interaction of STAT4 with the IL-12 receptor."
    Yao B.B., Niu P., Surowy C.S., Faltynek C.R.
    Arch. Biochem. Biophys. 368:147-155(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH IL12RB2.
  5. "Identification of a STAT4 binding site in the interleukin-12 receptor required for signaling."
    Naeger L.K., McKinney J., Salvekar A., Hoey T.
    J. Biol. Chem. 274:1875-1878(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH IL12RB2.
  6. "Cutting edge: autoimmune disease risk variant of STAT4 confers increased sensitivity to IFN-alpha in lupus patients in vivo."
    Kariuki S.N., Kirou K.A., MacDermott E.J., Barillas-Arias L., Crow M.K., Niewold T.B.
    J. Immunol. 182:34-38(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN SLEB11.
  7. Cited for: VARIANT [LARGE SCALE ANALYSIS] GLN-112.
  8. Cited for: INVOLVEMENT IN SLEB11 AND RA.

Entry informationi

Entry nameiSTAT4_HUMAN
AccessioniPrimary (citable) accession number: Q14765
Secondary accession number(s): Q96NZ6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: November 1, 1996
Last modified: June 24, 2015
This is version 151 of the entry and version 1 of the sequence. [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 2
    Human chromosome 2: 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

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.