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Q14765 (STAT4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 138. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Signal transducer and activator of transcription 4
Gene names
Name:STAT4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length748 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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

Subunit structure

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. Ref.4 Ref.5

Subcellular location

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

Post-translational modification

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

Involvement in disease

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. Ref.6 Ref.8

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. Ref.8

Sequence similarities

Belongs to the transcription factor STAT family.

Contains 1 SH2 domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 748748Signal transducer and activator of transcription 4
PRO_0000182420

Regions

Domain569 – 66496SH2

Amino acid modifications

Modified residue6931Phosphotyrosine; by JAK By similarity

Natural variations

Natural variant1121E → Q in a breast cancer sample; somatic mutation. Ref.7
VAR_036002
Natural variant1151I → V.
Corresponds to variant rs3024839 [ dbSNP | Ensembl ].
VAR_020190
Natural variant5841R → W.
Corresponds to variant rs3024933 [ dbSNP | Ensembl ].
VAR_047939

Experimental info

Sequence conflict365 – 3717KNVSTLS → N in AAL12164. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Q14765 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 11E43803A9AF4FFA

FASTA74885,941
        10         20         30         40         50         60 
MSQWNQVQQL EIKFLEQVDQ FYDDNFPMEI RHLLAQWIEN QDWEAASNNE TMATILLQNL 

        70         80         90        100        110        120 
LIQLDEQLGR VSKEKNLLLI HNLKRIRKVL QGKFHGNPMH VAVVISNCLR EERRILAAAN 

       130        140        150        160        170        180 
MPVQGPLEKS LQSSSVSERQ RNVEHKVAAI KNSVQMTEQD TKYLEDLQDE FDYRYKTIQT 

       190        200        210        220        230        240 
MDQSDKNSAM VNQEVLTLQE MLNSLDFKRK EALSKMTQII HETDLLMNTM LIEELQDWKR 

       250        260        270        280        290        300 
RQQIACIGGP LHNGLDQLQN CFTLLAESLF QLRRQLEKLE EQSTKMTYEG DPIPMQRTHM 

       310        320        330        340        350        360 
LERVTFLIYN LFKNSFVVER QPCMPTHPQR PLVLKTLIQF TVKLRLLIKL PELNYQVKVK 

       370        380        390        400        410        420 
ASIDKNVSTL SNRRFVLCGT NVKAMSIEES SNGSLSVEFR HLQPKEMKSS AGGKGNEGCH 

       430        440        450        460        470        480 
MVTEELHSIT FETQICLYGL TIDLETSSLP VVMISNVSQL PNAWASIIWY NVSTNDSQNL 

       490        500        510        520        530        540 
VFFNNPPPAT LSQLLEVMSW QFSSYVGRGL NSDQLHMLAE KLTVQSSYSD GHLTWAKFCK 

       550        560        570        580        590        600 
EHLPGKSFTF WTWLEAILDL IKKHILPLWI DGYVMGFVSK EKERLLLKDK MPGTFLLRFS 

       610        620        630        640        650        660 
ESHLGGITFT WVDHSESGEV RFHSVEPYNK GRLSALPFAD ILRDYKVIMA ENIPENPLKY 

       670        680        690        700        710        720 
LYPDIPKDKA FGKHYSSQPC EVSRPTERGD KGYVPSVFIP ISTIRSDSTE PHSPSDLLPM 

       730        740 
SPSVYAVLRE NLSPTTIETA MKSPYSAE 

« Hide

References

« Hide 'large scale' references
[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]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] GLN-112.
[8]"STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus."
Remmers E.F., Plenge R.M., Lee A.T., Graham R.R., Hom G., Behrens T.W., de Bakker P.I.W., Le J.M., Lee H.-S., Batliwalla F., Li W., Masters S.L., Booty M.G., Carulli J.P., Padyukov L., Alfredsson L., Klareskog L., Chen W.V. expand/collapse author list , Amos C.I., Criswell L.A., Seldin M.F., Kastner D.L., Gregersen P.K.
N. Engl. J. Med. 357:977-986(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SLEB11 AND RA.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L78440 mRNA. Translation: AAB05605.1.
BC031212 mRNA. Translation: AAH31212.1.
AF423072 Genomic DNA. Translation: AAL12164.1.
RefSeqNP_001230764.1. NM_001243835.1.
NP_003142.1. NM_003151.3.
UniGeneHs.735572.
Hs.80642.

3D structure databases

ProteinModelPortalQ14765.
SMRQ14765. Positions 2-702.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112652. 6 interactions.
DIPDIP-39854N.
IntActQ14765. 4 interactions.
MINTMINT-8020311.
STRING9606.ENSP00000351255.

PTM databases

PhosphoSiteQ14765.

Polymorphism databases

DMDM6226158.

Proteomic databases

PaxDbQ14765.
PRIDEQ14765.

Protocols and materials databases

DNASU6775.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000358470; ENSP00000351255; ENSG00000138378.
ENST00000392320; ENSP00000376134; ENSG00000138378.
GeneID6775.
KEGGhsa:6775.
UCSCuc002usm.2. human.

Organism-specific databases

CTD6775.
GeneCardsGC02M191894.
HGNCHGNC:11365. STAT4.
HPACAB013108.
HPA001860.
MIM180300. phenotype.
600558. gene.
612253. phenotype.
neXtProtNX_Q14765.
Orphanet117. Behcet disease.
85408. Juvenile rheumatoid factor-negative polyarthritis.
85410. Oligoarticular juvenile arthritis.
93552. Pediatric systemic lupus erythematosus.
536. Systemic lupus erythematosus.
PharmGKBPA36185.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG267627.
HOGENOMHOG000220792.
HOVERGENHBG055669.
InParanoidQ14765.
KOK11222.
OMAGNEGCHM.
OrthoDBEOG73JKTT.
PhylomeDBQ14765.
TreeFamTF318648.

Enzyme and pathway databases

SignaLinkQ14765.

Gene expression databases

ArrayExpressQ14765.
BgeeQ14765.
CleanExHS_STAT4.
GenevestigatorQ14765.

Family and domain databases

Gene3D1.10.238.10. 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.
InterProIPR011992. 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]
PANTHERPTHR11801. PTHR11801. 1 hit.
PfamPF00017. SH2. 1 hit.
PF01017. STAT_alpha. 1 hit.
PF02864. STAT_bind. 1 hit.
PF02865. STAT_int. 1 hit.
[Graphical view]
SMARTSM00252. SH2. 1 hit.
SM00964. STAT_int. 1 hit.
[Graphical view]
SUPFAMSSF47655. SSF47655. 1 hit.
SSF48092. SSF48092. 1 hit.
SSF49417. SSF49417. 1 hit.
PROSITEPS50001. SH2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiSTAT4.
GenomeRNAi6775.
NextBio26446.
PROQ14765.
SOURCESearch...

Entry information

Entry nameSTAT4_HUMAN
AccessionPrimary (citable) accession number: Q14765
Secondary accession number(s): Q96NZ6
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: November 1, 1996
Last modified: March 19, 2014
This is version 138 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM