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Q14765

- STAT4_HUMAN

UniProt

Q14765 - STAT4_HUMAN

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Protein
Signal transducer and activator of transcription 4
Gene
STAT4
Organism
Homo sapiens (Human)
Status
Reviewed - 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

  1. calcium ion binding Source: InterPro
  2. sequence-specific DNA binding Source: Ensembl
  3. sequence-specific DNA binding transcription factor activity Source: ProtInc
  4. signal transducer activity Source: InterPro

GO - Biological processi

  1. JAK-STAT cascade Source: ProtInc
  2. cell proliferation Source: Ensembl
  3. cytokine-mediated signaling pathway Source: Ensembl
  4. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
  5. protein phosphorylation Source: Ensembl
  6. transcription, DNA-templated Source: UniProtKB-KW
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: Chromosome 2

Organism-specific databases

HGNCiHGNC:11365. STAT4.

Subcellular locationi

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

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-SubCell
  2. nucleus Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Systemic lupus erythematosus 11 (SLEB11) [MIM:612253]: A 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.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.2 Publications
Rheumatoid arthritis (RA) [MIM:180300]: An 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.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.1 Publication

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.

PTM / Processingi

Molecule processing

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

Amino acid modifications

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

Post-translational modificationi

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

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ14765.
PRIDEiQ14765.

PTM databases

PhosphoSiteiQ14765.

Expressioni

Gene expression databases

ArrayExpressiQ14765.
BgeeiQ14765.
CleanExiHS_STAT4.
GenevestigatoriQ14765.

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.2 Publications

Protein-protein interaction databases

BioGridi112652. 7 interactions.
DIPiDIP-39854N.
IntActiQ14765. 4 interactions.
MINTiMINT-8020311.
STRINGi9606.ENSP00000351255.

Structurei

3D structure databases

ProteinModelPortaliQ14765.
SMRiQ14765. Positions 2-702.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini569 – 66496SH2
Add
BLAST

Sequence similaritiesi

Contains 1 SH2 domain.

Keywords - Domaini

SH2 domain

Phylogenomic databases

eggNOGiNOG267627.
HOGENOMiHOG000220792.
HOVERGENiHBG055669.
InParanoidiQ14765.
KOiK11222.
OMAiGNEGCHM.
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.
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.

Q14765-1 [UniParc]FASTAAdd to Basket

« Hide

MSQWNQVQQL EIKFLEQVDQ FYDDNFPMEI RHLLAQWIEN QDWEAASNNE    50
TMATILLQNL LIQLDEQLGR VSKEKNLLLI HNLKRIRKVL QGKFHGNPMH 100
VAVVISNCLR EERRILAAAN MPVQGPLEKS LQSSSVSERQ RNVEHKVAAI 150
KNSVQMTEQD TKYLEDLQDE FDYRYKTIQT MDQSDKNSAM VNQEVLTLQE 200
MLNSLDFKRK EALSKMTQII HETDLLMNTM LIEELQDWKR RQQIACIGGP 250
LHNGLDQLQN CFTLLAESLF QLRRQLEKLE EQSTKMTYEG DPIPMQRTHM 300
LERVTFLIYN LFKNSFVVER QPCMPTHPQR PLVLKTLIQF TVKLRLLIKL 350
PELNYQVKVK ASIDKNVSTL SNRRFVLCGT NVKAMSIEES SNGSLSVEFR 400
HLQPKEMKSS AGGKGNEGCH MVTEELHSIT FETQICLYGL TIDLETSSLP 450
VVMISNVSQL PNAWASIIWY NVSTNDSQNL VFFNNPPPAT LSQLLEVMSW 500
QFSSYVGRGL NSDQLHMLAE KLTVQSSYSD GHLTWAKFCK EHLPGKSFTF 550
WTWLEAILDL IKKHILPLWI DGYVMGFVSK EKERLLLKDK MPGTFLLRFS 600
ESHLGGITFT WVDHSESGEV RFHSVEPYNK GRLSALPFAD ILRDYKVIMA 650
ENIPENPLKY LYPDIPKDKA FGKHYSSQPC EVSRPTERGD KGYVPSVFIP 700
ISTIRSDSTE PHSPSDLLPM SPSVYAVLRE NLSPTTIETA MKSPYSAE 748
Length:748
Mass (Da):85,941
Last modified:November 1, 1996 - v1
Checksum:i11E43803A9AF4FFA
GO

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 conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti365 – 3717KNVSTLS → N in AAL12164. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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_006712719.1.
UniGeneiHs.735572.
Hs.80642.

Genome annotation databases

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

Polymorphism databases

DMDMi6226158.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

SeattleSNPs

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
L78440 mRNA. Translation: AAB05605.1 .
BC031212 mRNA. Translation: AAH31212.1 .
AF423072 Genomic DNA. Translation: AAL12164.1 .
CCDSi CCDS2310.1.
RefSeqi NP_001230764.1. NM_001243835.1.
NP_003142.1. NM_003151.3.
XP_006712782.1. XM_006712719.1.
UniGenei Hs.735572.
Hs.80642.

3D structure databases

ProteinModelPortali Q14765.
SMRi Q14765. Positions 2-702.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 112652. 7 interactions.
DIPi DIP-39854N.
IntActi Q14765. 4 interactions.
MINTi MINT-8020311.
STRINGi 9606.ENSP00000351255.

PTM databases

PhosphoSitei Q14765.

Polymorphism databases

DMDMi 6226158.

Proteomic databases

PaxDbi Q14765.
PRIDEi Q14765.

Protocols and materials databases

DNASUi 6775.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000358470 ; ENSP00000351255 ; ENSG00000138378 .
ENST00000392320 ; ENSP00000376134 ; ENSG00000138378 .
GeneIDi 6775.
KEGGi hsa:6775.
UCSCi uc002usm.2. human.

Organism-specific databases

CTDi 6775.
GeneCardsi GC02M191894.
HGNCi HGNC:11365. STAT4.
HPAi CAB013108.
HPA001860.
MIMi 180300. phenotype.
600558. gene.
612253. phenotype.
neXtProti NX_Q14765.
Orphaneti 117. Behcet disease.
85408. Juvenile rheumatoid factor-negative polyarthritis.
85410. Oligoarticular juvenile arthritis.
93552. Pediatric systemic lupus erythematosus.
536. Systemic lupus erythematosus.
PharmGKBi PA36185.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG267627.
HOGENOMi HOG000220792.
HOVERGENi HBG055669.
InParanoidi Q14765.
KOi K11222.
OMAi GNEGCHM.
OrthoDBi EOG73JKTT.
PhylomeDBi Q14765.
TreeFami TF318648.

Enzyme and pathway databases

SignaLinki Q14765.

Miscellaneous databases

GeneWikii STAT4.
GenomeRNAii 6775.
NextBioi 26446.
PROi Q14765.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q14765.
Bgeei Q14765.
CleanExi HS_STAT4.
Genevestigatori Q14765.

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

« 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: September 3, 2014
This is version 143 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

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