Reviewed, UniProtKB/Swiss-Prot Q14765 (STAT4_HUMAN)

Names and origin

Protein names

Recommended name:
    Signal transducer and activator of transcription 4

Gene names

Name:

STAT4

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	748 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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 By similarity. The SH2 domain interacts, in vitro, with IL12RB2 via a short cytoplasmic domain.
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	Genetic variations in STAT4 are associated with susceptibility to systemic lupus erythematosus type 11 (SLEB11) [MIM:612253]. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a complex genetic basis. SLE is an inflammatory, and often febrile multisystemic disorder of connective tissue characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is thought to represent a failure of the regulatory mechanisms of the autoimmune system. Ref.7 Genetic variations in STAT4 are associated with susceptibility to rheumatoid arthritis (RA) [MIM:180300]. Rheumatoid arthritis is a complex, multifactorial disorder. It is one of the most common autoimmune diseases and it is characterized by inflammation of synovial tissue and joint destruction.
Sequence similarities	Belongs to the transcription factor STAT family. Contains 1 SH2 domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Disease	Systemic lupus erythematosus
Domain	SH2 domain
Ligand	DNA-binding
Molecular function	Activator
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	JAK-STAT cascade Traceable author statement. Source: ProtInc regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: InterPro transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from direct assay. Source: HPA
Molecular function	calcium ion binding Inferred from electronic annotation. Source: InterPro protein binding Inferred from physical interaction. Source: IntAct signal transducer activity Inferred from electronic annotation. Source: InterPro transcription factor activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
NMI	Q13287	1	EBI-1186538,EBI-372942

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 748	748	Signal transducer and activator of transcription 4		PRO_0000182420
Regions
	Domain	569 – 664	96	SH2
Amino acid modifications
	Modified residue	693	1	Phosphotyrosine; by JAK By similarity
	Modified residue	721	1	Phosphoserine By similarity
Natural variations
	Natural variant	112	1	E → Q in a breast cancer sample; somatic mutation. Ref.6		VAR_036002
	Natural variant	115	1	I → V: dbSNP rs3024839.		VAR_020190
	Natural variant	584	1	R → W: dbSNP rs3024933.		VAR_047939
Experimental info
	Sequence conflict	365 – 371	7	KNVSTLS → N in AAL12164. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q14765-1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 11E43803A9AF4FFA	FASTA	748	85,941
	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

References

	« Hide 'large scale' referencesShow '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: 15489334] [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: 10415122] [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: 9890938] [Abstract] Cited for: INTERACTION WITH IL12RB2.
[6]	"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. , 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: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] GLN-112.
[7]	"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. , Amos C.I., Criswell L.A., Seldin M.F., Kastner D.L., Gregersen P.K. N. Engl. J. Med. 357:977-986(2007) [PubMed: 17804842] [Abstract] Cited for: INVOLVEMENT IN SLEB11 AND RA.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Cross-references

Sequence databases
EMBLGenBankDDBJ	L78440 mRNA. Translation: AAB05605.1. BC031212 mRNA. Translation: AAH31212.1. AF423072 Genomic DNA. Translation: AAL12164.1.
IPI	IPI00000106.
RefSeq	NP_003142.1.
UniGene	Hs.80642
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q14765. 1 interaction.
STRING	Q14765.
PTM databases
PhosphoSite	Q14765.
Proteomic databases
PRIDE	Q14765.
Genome annotation databases
Ensembl	ENST00000358470; ENSP00000351255; ENSG00000138378; Homo sapiens. [Genome view] ENST00000392320; ENSP00000376134; ENSG00000138378; Homo sapiens. [Genome view]
GeneID	6775.
KEGG	hsa:6775.
UCSC	uc002usm.1. human.
Organism-specific databases
CTD	6775.
GeneCards	GC02M191602.
H-InvDB	HIX0002684.
HGNC	HGNC:11365. STAT4.
HPA	CAB013108. HPA001860.
MIM	180300. phenotype. 600558. gene. 612253. phenotype.
PharmGKB	PA36185.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q14765.
HOVERGEN	Q14765.
OMA	MKSSAGS
OrthoDB	EOG9V19K9
Enzyme and pathway databases
Pathway_Interaction_DB	cd8tcrdownstreampathway. Downstream signaling in naive CD8+ T cells. il12_stat4pathway. IL12 signaling mediated by STAT4. il12_2pathway. IL12-mediated signaling events. il23pathway. IL23-mediated signaling events. il27pathway. IL27-mediated signaling events.
Gene expression databases
ArrayExpress	Q14765.
Bgee	Q14765.
CleanEx	HS_STAT4.
Genevestigator	Q14765.
GermOnline	ENSG00000138378. Homo sapiens.
Family and domain databases
InterPro	IPR011992. EF-Hand_type. IPR008967. p53-like_TF_DNA-bd. IPR000980. SH2. IPR013800. STAT_TF_alpha. IPR015988. STAT_TF_coiled-coil. IPR001217. STAT_TF_core. IPR013801. STAT_TF_DNA-bd. IPR012345. STAT_TF_DNA-bd_sub. IPR013799. STAT_TF_prot_interaction. [Graphical view]
Gene3D	G3DSA:1.10.238.10. EF-Hand_type. 1 hit. G3DSA:3.30.505.10. SH2. 1 hit. G3DSA:1.20.1050.20. STAT_alpha. 1 hit. G3DSA:2.60.40.630. STAT_DNA_bd_sub. 1 hit. G3DSA:1.10.532.10. STAT_protein_interaction. 1 hit.
PANTHER	PTHR11801. STAT. 1 hit.
Pfam	PF00017. SH2. 1 hit. PF01017. STAT_alpha. 1 hit. PF02864. STAT_bind. 1 hit. PF02865. STAT_int. 1 hit. [Graphical view]
SMART	SM00252. SH2. 1 hit. [Graphical view]
PROSITE	PS50001. SH2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	26446.
SOURCE	Search...

Entry information

Entry name

STAT4_HUMAN

Accession

Primary (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:	November 24, 2009
This is version 97 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.