STAT2 signal transducer and activator of transcription 2, 113kDa [Homo sapiens (human)] - Gene

Summary

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Official Symbol: STAT2provided by HGNC
Official Full Name: signal transducer and activator of transcription 2, 113kDaprovided by HGNC
Primary source: HGNC:11363
See related: HPRD:02778; MIM:600556
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: P113; ISGF-3; STAT113
Summary: The protein encoded by this gene is a member of the STAT protein family. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. In response to interferon (IFN), this protein forms a complex with STAT1 and IFN regulatory factor family protein p48 (ISGF3G), in which this protein acts as a transactivator, but lacks the ability to bind DNA directly. Transcription adaptor P300/CBP (EP300/CREBBP) has been shown to interact specifically with this protein, which is thought to be involved in the process of blocking IFN-alpha response by adenovirus. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]

Genomic context

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Location :: 12q13.3

Sequence :: Chromosome: 12; NC_000012.11 (56735381..56754037, complement)

See STAT2 in Epigenomics, MapViewer

Chromosome 12 - NC_000012.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

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Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

Sequencing of genomic DNA and RNA revealed a homozygous mutation in intron 4 of STAT2 that prevented correct splicing in patient cells
Title: STAT2 deficiency and susceptibility to viral illness in humans.
In systemic lupus erythematosus but not in healthy control leukocytes, Jak1 and STAT2 were constitutively phosphorylated, even in the absence of disease activity.
Title: Constitutive phosphorylation of interferon receptor A-associated signaling proteins in systemic lupus erythematosus.
STAT2 serine 287 is a novel regulatory phosphorylation site in type I interferon-induced cellular responses
Title: Identification of STAT2 serine 287 as a novel regulatory phosphorylation site in type I interferon-induced cellular responses.
These results indicate the importance that herpes simplex virus 2 has assigned to STAT2, investing significant genomic currency throughout its replicative lifecycle for continuous targeted destruction and inhibition of this protein.
Title: HSV-2 inhibits type-I interferon signaling via multiple complementary and compensatory STAT2-associated mechanisms.
A haplotype at STAT2 introgressed from neanderthals serves as a candidate of positive selection in Papua New Guinea.
Title: A haplotype at STAT2 Introgressed from neanderthals and serves as a candidate of positive selection in Papua New Guinea.
STAT2 is functionally involved in the immunosuppressive activity of hcMSCs as a novel regulator under inflammatory conditions.
Title: Gene expression profile reveals that STAT2 is involved in the immunosuppressive function of human bone marrow-derived mesenchymal stem cells.
Co-immunoprecipitation/immunoblot analyses showed that STAT2 enhanced RCAN1 ubiquitination through the ubiquitin E3 ligase FBW7..
Title: The transcription factor STAT2 enhances proteasomal degradation of RCAN1 through the ubiquitin E3 ligase FBW7.
PCBP2 stabilizes the mRNA of STAT1 and STAT2 through binding the 3'Untranslated Region (UTR) of these two molecules.
Title: PCBP2 enhances the antiviral activity of IFN-α against HCV by stabilizing the mRNA of STAT1 and STAT2.
STAT1 and STAT2 are involved in the growth inhibition of HepG2 cells induced by phosphatidylethanolamine.
Title: [STAT1 and STAT2 participate in growth inhibition of human hepatoma HepG2 cells induced by phosphatidylethanolamine].
These findings highlight the role of Kaposi's sarcoma herpesvirus vFLIP in the activation of STAT1/STAT2 and STAT-responsive cellular genes in endothelial cells.
Title: Deletion of Kaposi's sarcoma-associated herpesvirus FLICE inhibitory protein, vFLIP, from the viral genome compromises the activation of STAT1-responsive cellular genes and spindle cell formation in endothelial cells.

Submit: New GeneRIF Correction See all (59)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

NHGRI GWAS Catalog

A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1.

Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways.

Hundreds of variants clustered in genomic loci and biological pathways affect human height.

HIV-1 protein interactions

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Protein	Gene	Interaction	Pubs
Nef, p27	nef	TRAF2 and TRAF6 proteins are required for the HIV-1 Nef-induced tyrosine phosphorylation of STAT1 and STAT2 proteins. Both myristoylation and acidic cluster of Nef are essential to induce the tyrosine phosphorylation	PubMed

Go to the HIV-1, Human Protein Interaction Database

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
NP_005410.1	NP_001420.1	EP300	BIND	PubMed	Stat2 interacts with p300.
NP_005410.1	NP_006075.3	IRF9	BIND	PubMed	Stat2 interacts with p48. This interaction is modelled on a demonstrated interaction between stat2 from an unspecified species and human p48.
NP_005410.1		STAT1	BIND	PubMed	STAT1 interacts with STAT2.
P52630	Q92793	CREBBP	HPRD	PubMed
P52630	P61073	CXCR4	HPRD	PubMed
P52630	Q13547	HDAC1	HPRD	PubMed
P52630	P17181	IFNAR1	HPRD	PubMed
P52630	P48551	IFNAR2	HPRD	PubMed
P52630	Q00978	IRF9	HPRD	PubMed
P52630	P23458	JAK1	HPRD	PubMed
P52630	O60674	JAK2	HPRD	PubMed
P52630	O60244	MED14	HPRD	PubMed
P52630	P51532	SMARCA4	HPRD	PubMed
P52630	P42224	STAT1	HPRD	PubMed
P52630	P42226	STAT6	HPRD	PubMed
P52630	P29597	TYK2	HPRD	PubMed
BioGRID:112650	BioGRID:107777	CREBBP	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:112650	BioGRID:108309	ELAVL1	BioGRID	PubMed	Affinity Capture-RNA
BioGRID:112650	BioGRID:108347	EP300	BioGRID	PubMed	Reconstituted Complex
BioGRID:112650	BioGRID:108625	FNTA	BioGRID	PubMed	Two-hybrid
BioGRID:112650	BioGRID:108823	GAA	BioGRID	PubMed	Two-hybrid
BioGRID:112650	BioGRID:119613	HDAC7	BioGRID	PubMed	Negative Genetic
BioGRID:112650	BioGRID:109552	HSP90AA1	BioGRID	PubMed	Affinity Capture-Luminescence
BioGRID:112650	BioGRID:109547	HSPB1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112650	BioGRID:109676	IFNAR1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:112650	BioGRID:109677	IFNAR2	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:112650	BioGRID:115652	IRF9	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:112650	BioGRID:120807	IWS1	BioGRID	PubMed	Two-hybrid
BioGRID:112650	BioGRID:114699	MED14	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:112650	BioGRID:108161	RCAN1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112650	BioGRID:112481	SMARCA4	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:112650	BioGRID:112483	SMARCC1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112650	BioGRID:112485	SMARCC2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112650	BioGRID:112489	SMARCE1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112650	BioGRID:112649	STAT1	BioGRID	PubMed	Affinity Capture-Western; Co-localization; Co-purification; Reconstituted Complex
BioGRID:112650	BioGRID:112655	STAT6	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112650	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS

Pathways from BioSystems

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Adipogenesis, organism-specific biosystem (from WikiPathways)
Adipogenesis, organism-specific biosystemThe different classess of factors involved in adipogenesis are shown. Adipogenesis is the process by which fat cells differentiate from predadipocytes to adipocytes (fat cells). Adipose tissue, compo...
CXCR4-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
CXCR4-mediated signaling events, organism-specific biosystem
CXCR4-mediated signaling events
Chemokine signaling pathway, organism-specific biosystem (from KEGG)
Chemokine signaling pathway, organism-specific biosystemInflammatory immune response requires the recruitment of leukocytes to the site of inflammation upon foreign insult. Chemokines are small chemoattractant peptides that provide directional cues for th...
Chemokine signaling pathway, conserved biosystem (from KEGG)
Chemokine signaling pathway, conserved biosystemInflammatory immune response requires the recruitment of leukocytes to the site of inflammation upon foreign insult. Chemokines are small chemoattractant peptides that provide directional cues for th...
Cytokine Signaling in Immune system, organism-specific biosystem (from REACTOME)
Cytokine Signaling in Immune system, organism-specific biosystemCytokines are small proteins that regulate and mediate immunity, inflammation, and hematopoiesis. They are secreted in response to immune stimuli, and usually act briefly, locally, at very low concen...
EGFR1 Signaling Pathway, organism-specific biosystem (from WikiPathways)
EGFR1 Signaling Pathway, organism-specific biosystemThe androgen receptor is a member of the nuclear receptor family of ligand activated transcription factors. These receptors bind to steroid hormones, thyroid hormone, retinoids and vitamin D among ot...
Hepatitis B, organism-specific biosystem (from KEGG)
Hepatitis B, organism-specific biosystemHepatitis B virus (HBV) is an enveloped virus and contains a partially double-stranded relaxed circular DNA (RC-DNA) genome. After entry into hepatocytes, HBV RC-DNA is transported to the nucleus and...
Hepatitis C, organism-specific biosystem (from KEGG)
Hepatitis C, organism-specific biosystemHepatitis C virus (HCV) is a major cause of chronic liver disease. The HCV employ several strategies to perturb host cell immunity. After invasion, HCV RNA genome functions directly as an mRNA in the...
Hepatitis C, conserved biosystem (from KEGG)
Hepatitis C, conserved biosystemHepatitis C virus (HCV) is a major cause of chronic liver disease. The HCV employ several strategies to perturb host cell immunity. After invasion, HCV RNA genome functions directly as an mRNA in the...
Herpes simplex infection, organism-specific biosystem (from KEGG)
Herpes simplex infection, organism-specific biosystemHerpes simplex virus (HSV) infections are very common worldwide, with the prevalence of HSV-1 reaching up to 80%-90%. Primary infection with HSV takes place in the mucosa, followed by the establishme...
Herpes simplex infection, conserved biosystem (from KEGG)
Herpes simplex infection, conserved biosystemHerpes simplex virus (HSV) infections are very common worldwide, with the prevalence of HSV-1 reaching up to 80%-90%. Primary infection with HSV takes place in the mucosa, followed by the establishme...
IL27-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
IL27-mediated signaling events, organism-specific biosystem
IL27-mediated signaling events
Immune System, organism-specific biosystem (from REACTOME)
Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
Influenza A, organism-specific biosystem (from KEGG)
Influenza A, organism-specific biosystemInfluenza is a contagious respiratory disease caused by influenza virus infection. Influenza A virus is responsible for both annual seasonal epidemics and periodic worldwide pandemics. Novel strains ...
Influenza A, conserved biosystem (from KEGG)
Influenza A, conserved biosystemInfluenza is a contagious respiratory disease caused by influenza virus infection. Influenza A virus is responsible for both annual seasonal epidemics and periodic worldwide pandemics. Novel strains ...
Interferon Signaling, organism-specific biosystem (from REACTOME)
Interferon Signaling, organism-specific biosystemInterferons (IFNs) are cytokines that play a central role in initiating immune responses, especially antiviral and antitumor effects. There are three types of IFNs:Type I (IFN-alpha, -beta and others...
Interferon alpha/beta signaling, organism-specific biosystem (from REACTOME)
Interferon alpha/beta signaling, organism-specific biosystemType I interferons (IFNs) are composed of various genes including IFN alpha (IFNA), beta (IFNB), omega, epsilon, and kappa. In humans the IFNA genes are composed of more than 13 subfamily genes, wher...
Jak-STAT signaling pathway, organism-specific biosystem (from KEGG)
Jak-STAT signaling pathway, organism-specific biosystemThe Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway is one of a handful of pleiotropic cascades used to transduce a multitude of signals for development and homeost...
Jak-STAT signaling pathway, conserved biosystem (from KEGG)
Jak-STAT signaling pathway, conserved biosystemThe Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway is one of a handful of pleiotropic cascades used to transduce a multitude of signals for development and homeost...
Measles, organism-specific biosystem (from KEGG)
Measles, organism-specific biosystemMeasles virus (MV) is highly contagious virus that leads infant death worldwide. Humans are the unique natural reservoir for this virus. It causes severe immunosuppression favouring secondary bacteri...
Measles, conserved biosystem (from KEGG)
Measles, conserved biosystemMeasles virus (MV) is highly contagious virus that leads infant death worldwide. Humans are the unique natural reservoir for this virus. It causes severe immunosuppression favouring secondary bacteri...
Osteoclast differentiation, organism-specific biosystem (from KEGG)
Osteoclast differentiation, organism-specific biosystemThe osteoclasts, multinucleared cells originating from the hematopoietic monocyte-macrophage lineage, are responsible for bone resorption. Osteoclastogenesis is mainly regulated by signaling pathways...
Osteoclast differentiation, conserved biosystem (from KEGG)
Osteoclast differentiation, conserved biosystemThe osteoclasts, multinucleared cells originating from the hematopoietic monocyte-macrophage lineage, are responsible for bone resorption. Osteoclastogenesis is mainly regulated by signaling pathways...
Regulation of IFNA signaling, organism-specific biosystem (from REACTOME)
Regulation of IFNA signaling, organism-specific biosystemThere are several proteins and mechanisms involved in controlling the extent of ligand stimulation of IFNA/B signaling. These mechanisms can effect every step of the IFNA/B cascade. Dephosphorylation...
Type II interferon signaling (IFNG), organism-specific biosystem (from WikiPathways)
Type II interferon signaling (IFNG), organism-specific biosystemAdapted from Raza et al. (2008). This pathway is initiated by IFNG binding to its receptor and a subsequent phosphorylation cascade involving a number of the JAK and STAT family of proteins. Several ...
Type III interferon signaling, organism-specific biosystem (from WikiPathways)
Type III interferon signaling, organism-specific biosystemThe recently identified type III interferon group consists of three IFN-? (lambda) genes encoding molecules called IFN-?1, IFN-?2 and IFN-?3 (also called IL29, IL28A and IL28B respectively). These IF...

General gene information

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Markers

D10S275 (e-PCR)
- UniSTS:147992

RH99119 (e-PCR)
- UniSTS:89141

RH40514 (e-PCR)
- UniSTS:88665

G67915 (e-PCR)
- UniSTS:225647

G67921 (e-PCR)
- UniSTS:225648

G67923 (e-PCR)
- UniSTS:225649

G67924 (e-PCR)
- UniSTS:225650

G67925 (e-PCR)
- UniSTS:225651

G67927 (e-PCR)
- UniSTS:225652

D1S1425 (e-PCR)
- UniSTS:149621

G67917 (e-PCR)
- UniSTS:225653

G67916 (e-PCR)
- UniSTS:225654

G67920 (e-PCR)
- UniSTS:225655

G67922 (e-PCR)
- UniSTS:225656

G67918 (e-PCR)
- UniSTS:225657

G67919 (e-PCR)
- UniSTS:225658

G67926 (e-PCR)
- UniSTS:225659

RH36905 (e-PCR)
- UniSTS:87932

D12S1878 (e-PCR)
- UniSTS:43396

GDB:335751 (e-PCR)
- UniSTS:156601

STAT2_258 (e-PCR)
- UniSTS:281034

STS-L27050 (e-PCR)
- UniSTS:73938

RH80815 (e-PCR)
- UniSTS:90585

Homology

Homologs of the STAT2 gene: The STAT2 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, and rat.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
DNA binding	IEA Inferred from Electronic Annotation more info
calcium ion binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
sequence-specific DNA binding transcription factor activity	IEA Inferred from Electronic Annotation more info
signal transducer activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
JAK-STAT cascade	TAS Traceable Author Statement more info	PubMed
cytokine-mediated signaling pathway	TAS Traceable Author Statement more info
defense response to virus	IEA Inferred from Electronic Annotation more info
regulation of transcription from RNA polymerase II promoter	TAS Traceable Author Statement more info	PubMed
regulation of type I interferon-mediated signaling pathway	TAS Traceable Author Statement more info
transcription, DNA-dependent	IEA Inferred from Electronic Annotation more info
type I interferon-mediated signaling pathway	TAS Traceable Author Statement more info
virus-host interaction	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
cytoplasm	IDA Inferred from Direct Assay more info
cytosol	TAS Traceable Author Statement more info
nucleoplasm	TAS Traceable Author Statement more info
plasma membrane	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: signal transducer and activator of transcription 2

Names: signal transducer and activator of transcription 2; interferon alpha induced transcriptional activator

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_005419.3 → NP_005410.1 signal transducer and activator of transcription 2 isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

BC051284, DB482283

Consensus CDS

CCDS8917.1

UniProtKB/Swiss-Prot

P52630

Conserved Domains (5) summary

pfam01017
Location:139 – 314
Blast Score: 429

STAT_alpha; STAT protein, all-alpha domain

pfam02864
Location:316 – 566
Blast Score: 901

STAT_bind; STAT protein, DNA binding domain

pfam12188
Location:783 – 838
Blast Score: 271

STAT2_C; Signal transducer and activator of transcription 2 C terminal

smart00964
Location:2 – 124
Blast Score: 391

STAT_int; STAT protein, protein interaction domain

cd10373
Location:556 – 704
Blast Score: 796

SH2_STAT2; Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) 2 proteins
NM_198332.1 → NP_938146.1 signal transducer and activator of transcription 2 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site, compared to variant 1. The resulting isoform (2) lacks an internal 4-aa segment, compared to isoform 1.

Source sequence(s)

AK296939, BC051284, DB482283

Consensus CDS

CCDS55836.1

UniProtKB/TrEMBL

B4DLC7

UniProtKB/TrEMBL

G3V2M6

UniProtKB/Swiss-Prot

P52630

Conserved Domains (5) summary

pfam01017
Location:135 – 310
Blast Score: 429

STAT_alpha; STAT protein, all-alpha domain

pfam02864
Location:312 – 562
Blast Score: 902

STAT_bind; STAT protein, DNA binding domain

pfam12188
Location:779 – 834
Blast Score: 271

STAT2_C; Signal transducer and activator of transcription 2 C terminal

smart00964
Location:2 – 120
Blast Score: 379

STAT_int; STAT protein, protein interaction domain

cd10373
Location:552 – 700
Blast Score: 796

SH2_STAT2; Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) 2 proteins

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000012.11 Reference GRCh37.p10 Primary Assembly

Range

56735381..56754037, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000144.1 Alternate HuRef

Range

53774045..53793077, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018923.1 Alternate CHM1_1.0

Range

56569601..56588168, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01008423.1 (5278..22393)	None
genomic	ABBA01008424.1	None
genomic	AC025574.19 (31811..50339)	None
genomic	AMYH01004504.1 (61156..79723)	None
genomic	AY525126.1	AAS00091.1
genomic	CH471054.1	EAW96934.1
		EAW96935.1
		EAW96936.1
		EAW96937.1
genomic	CS542453.1	CAM91176.1
genomic	S81491.1	AAB36225.2
		AAB36226.1
		AAB36227.1
genomic	U18671.1	AAA98760.1
mRNA	AK094039.1	None
mRNA	AK295052.1	BAG58101.1
mRNA	AK295114.1	BAG58143.1
mRNA	AK296939.1	BAG59489.1
mRNA	AK296940.1	BAG59490.1
mRNA	AK308051.1	None
mRNA	AK310727.1	None
mRNA	AK316516.1	BAH14887.1
mRNA	BC006092.1	AAH06092.1
mRNA	BC051284.1	AAH51284.1
mRNA	BX640607.1	CAE45713.1
mRNA	CD684210.1	None
mRNA	DB482283.1	None
mRNA	M97934.1	None