P52630 (STAT2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Signal transducer and activator of transcription 2

Alternative name(s):
p113

Gene names

Name:

STAT2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	851 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Signal transducer and activator of transcription that mediates signaling by type I IFNs (IFN-alpha and IFN-beta). Following type I IFN binding to cell surface receptors, Jak kinases (TYK2 and JAK1) are activated, leading to tyrosine phosphorylation of STAT1 and STAT2. The phosphorylated STATs dimerize, associate with ISGF3G/IRF-9 to form a complex termed ISGF3 transcription factor, that enters the nucleus. ISGF3 binds to the IFN stimulated response element (ISRE) to activate the transcription of interferon stimulated genes, which drive the cell in an antiviral state. Ref.8
Subunit structure	Interacts with ISGF3G/IRF-9 in the cytoplasm. Heterodimer with STAT1 upon IFN-alpha/beta induced phosphorylation. Interacts with CRSP2 and CRSP6. Interacts with Simian virus 5 protein V and rabies virus phosphoprotein By similarity. Can form a homodimer upon IFN-alpha induced phosphorylation. Interacts with IFNAR1; the interaction requires the phosphorylation of IFNAR1 at 'Tyr-466'. Interacts with IFNAR2. Interacts with dengue virus NS5; this interaction inhibits the phosphorylation of STAT2, and, when all viral proteins are present (polyprotein), targets STAT2 for degradation. Interacts with human cytomegalovirus/HHV-5 protein UL123; this interaction promotes viral growth. Ref.8 Ref.9 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16
Subcellular location	Cytoplasm. Nucleus. Note: Translocated into the nucleus upon activation by IFN-alpha/beta. Ref.11
Post-translational modification	Tyrosine phosphorylated in response to IFN-alpha. Ref.5 Ref.6 Ref.9
Sequence similarities	Belongs to the transcription factor STAT family. Contains 1 SH2 domain.
Sequence caution	The sequence AAB36226.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence AAB36227.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Antiviral defense Host-virus interaction Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Domain	SH2 domain
Ligand	DNA-binding
Molecular function	Activator
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	JAK-STAT cascade Traceable author statement Ref.8. Source: ProtInc defense response to virus Inferred from electronic annotation. Source: UniProtKB-KW regulation of transcription from RNA polymerase II promoter Traceable author statement Ref.8. Source: ProtInc regulation of type I interferon-mediated signaling pathway Traceable author statement. Source: Reactome transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW type I interferon-mediated signaling pathway Traceable author statement. Source: Reactome virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleoplasm Traceable author statement. Source: Reactome plasma membrane Inferred from direct assay. Source: HPA
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW calcium ion binding Inferred from electronic annotation. Source: InterPro sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: InterPro signal transducer activity Traceable author statement Ref.8. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
IFNAR2	P48551	2	EBI-1546963,EBI-958408
IRF9	Q00978	4	EBI-1546963,EBI-626526
STAT1	P42224	4	EBI-1546963,EBI-1057697

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 851

851

Signal transducer and activator of transcription 2

PRO_0000182413

Regions

Domain

572 – 667

96

SH2

Amino acid modifications

Modified residue

690

1

Phosphotyrosine; by JAK Ref.6 Ref.9

Natural variations

Natural variant

66

1

Q → H.
Corresponds to variant rs2066816 [ dbSNP | Ensembl ].

VAR_014896

Natural variant

220

1

L → P.
Corresponds to variant rs2066817 [ dbSNP | Ensembl ].

VAR_014897

Natural variant

246

1

C → S.
Corresponds to variant rs2228259 [ dbSNP | Ensembl ].

VAR_052072

Natural variant

448

1

T → M. Ref.3
Corresponds to variant rs2066815 [ dbSNP | Ensembl ].

VAR_014898

Natural variant

464

1

I → V. Ref.3
Corresponds to variant rs2066811 [ dbSNP | Ensembl ].

VAR_014899

Natural variant

501

1

S → I.
Corresponds to variant rs2066809 [ dbSNP | Ensembl ].

VAR_014900

Natural variant

594

1

M → I. Ref.3
Corresponds to variant rs2066807 [ dbSNP | Ensembl ].

VAR_014901

Natural variant

826

1

Q → H. Ref.3
Corresponds to variant rs2229363 [ dbSNP | Ensembl ].

VAR_019213

Experimental info

Mutagenesis

374

1

R → A: Prevents the nuclear import; when associated with A-375. Ref.11

Mutagenesis

375

1

K → A: Prevents the nuclear import; when associated with A-374. Ref.11

Mutagenesis

409

1

R → A: Prevents the nuclear import; when associated with A-415. Ref.11

Mutagenesis

415

1

K → A: Prevents the nuclear import; when associated with A-409. Ref.11

Mutagenesis

690

1

Y → F: Reduces phosphorylation of STAT1 in response to IFN-ALPHA. Ref.6

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

851

Helix Strand Turn

Details...

Helix

793 – 796

4

Helix

802 – 806

5

Turn

812 – 814

3

Helix

824 – 827

4

Helix

831 – 834

4

Sequences

	Sequence		Length	Mass (Da)
	P52630 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: E4C74674CB7A3215	FASTA	851	97,916
	10 20 30 40 50 60 MAQWEMLQNL DSPFQDQLHQ LYSHSLLPVD IRQYLAVWIE DQNWQEAALG SDDSKATMLF 70 80 90 100 110 120 FHFLDQLNYE CGRCSQDPES LLLQHNLRKF CRDIQPFSQD PTQLAEMIFN LLLEEKRILI 130 140 150 160 170 180 QAQRAQLEQG EPVLETPVES QQHEIESRIL DLRAMMEKLV KSISQLKDQQ DVFCFRYKIQ 190 200 210 220 230 240 AKGKTPSLDP HQTKEQKILQ ETLNELDKRR KEVLDASKAL LGRLTTLIEL LLPKLEEWKA 250 260 270 280 290 300 QQQKACIRAP IDHGLEQLET WFTAGAKLLF HLRQLLKELK GLSCLVSYQD DPLTKGVDLR 310 320 330 340 350 360 NAQVTELLQR LLHRAFVVET QPCMPQTPHR PLILKTGSKF TVRTRLLVRL QEGNESLTVE 370 380 390 400 410 420 VSIDRNPPQL QGFRKFNILT SNQKTLTPEK GQSQGLIWDF GYLTLVEQRS GGSGKGSNKG 430 440 450 460 470 480 PLGVTEELHI ISFTVKYTYQ GLKQELKTDT LPVVIISNMN QLSIAWASVL WFNLLSPNLQ 490 500 510 520 530 540 NQQFFSNPPK APWSLLGPAL SWQFSSYVGR GLNSDQLSML RNKLFGQNCR TEDPLLSWAD 550 560 570 580 590 600 FTKRESPPGK LPFWTWLDKI LELVHDHLKD LWNDGRIMGF VSRSQERRLL KKTMSGTFLL 610 620 630 640 650 660 RFSESSEGGI TCSWVEHQDD DKVLIYSVQP YTKEVLQSLP LTEIIRHYQL LTEENIPENP 670 680 690 700 710 720 LRFLYPRIPR DEAFGCYYQE KVNLQERRKY LKHRLIVVSN RQVDELQQPL ELKPEPELES 730 740 750 760 770 780 LELELGLVPE PELSLDLEPL LKAGLDLGPE LESVLESTLE PVIEPTLCMV SQTVPEPDQG 790 800 810 820 830 840 PVSQPVPEPD LPCDLRHLNT EPMEIFRNCV KIEEIMPNGD PLLAGQNTVD EVYVSRPSHF 850 YTDGPLMPSD F

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The proteins of ISGF-3, the interferon alpha-induced transcriptional activator, define a gene family involved in signal transduction." Fu X.-Y., Schindler C., Improta T., Aebersold R., Darnell J.E. Jr. Proc. Natl. Acad. Sci. U.S.A. 89:7840-7843(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
[2]	"The genomic structure of the STAT genes: multiple exons in coincident sites in Stat1 and Stat2." Yan R., Qureshi S., Zhong Z., Wen Z., Darnell J.E. Jr. Nucleic Acids Res. 23:459-463(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	NIEHS SNPs program Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS MET-448; VAL-464; ILE-594 AND HIS-826.
[4]	"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: Lung.
[5]	"A transcription factor with SH2 and SH3 domains is directly activated by an interferon alpha-induced cytoplasmic protein tyrosine kinase(s)." Fu X.Y. Cell 70:323-335(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION IN RESPONSE TO IFN-ALPHA.
[6]	"Role of STAT2 in the alpha interferon signaling pathway." Leung S., Qureshi S.A., Kerr I.M., Darnell J.E. Jr., Stark G.R. Mol. Cell. Biol. 15:1312-1317(1995) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT TYR-690, MUTAGENESIS OF TYR-690.
[7]	"Identification of alternative splicing form of Stat2." Sugiyama T., Nishio Y., Kishimoto T., Akira S. FEBS Lett. 381:191-194(1996) [PubMed] [Europe PMC] [Abstract] Cited for: POTENTIAL ALTERNATIVE SPLICING.
[8]	"Stat2 is a transcriptional activator that requires sequence-specific contacts provided by stat1 and p48 for stable interaction with DNA." Bluyssen H.A., Levy D.E. J. Biol. Chem. 272:4600-4605(1997) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBUNIT.
[9]	"Functional subdomains of STAT2 required for preassociation with the alpha interferon receptor and for signaling." Li X., Leung S., Kerr I.M., Stark G.R. Mol. Cell. Biol. 17:2048-2056(1997) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH IFNAR1 AND IFNAR2, PHOSPHORYLATION AT TYR-690.
[10]	"Viral inhibition of interferon signal transduction." Cebulla C.M., Miller D.M., Sedmak D.D. Intervirology 42:325-330(1999) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[11]	"Arginine/lysine-rich structural element is involved in interferon-induced nuclear import of STATs." Melen K., Kinnunen L., Julkunen I. J. Biol. Chem. 276:16447-16455(2001) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF ARG-374; LYS-375; ARG-409 AND LYS-415.
[12]	"Role of metazoan mediator proteins in interferon-responsive transcription." Lau J.F., Nusinzon I., Burakov D., Freedman L.P., Horvath C.M. Mol. Cell. Biol. 23:620-628(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CRSP2 AND CRSP6.
[13]	"Simian virus 5 V protein acts as an adaptor, linking DDB1 to STAT2, to facilitate the ubiquitination of STAT1." Precious B., Childs K., Fitzpatrick-Swallow V., Goodbourn S., Randall R.E. J. Virol. 79:13434-13441(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SIMIAN VIRUS 5 PROTEIN V.
[14]	"Binding STAT2 by the acidic domain of human cytomegalovirus IE1 promotes viral growth and is negatively regulated by SUMO." Huh Y.H., Kim Y.E., Kim E.T., Park J.J., Song M.J., Zhu H., Hayward G.S., Ahn J.H. J. Virol. 82:10444-10454(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HHV-5 PROTEIN UL123.
[15]	"NS5 of dengue virus mediates STAT2 binding and degradation." Ashour J., Laurent-Rolle M., Shi P.Y., Garcia-Sastre A. J. Virol. 83:5408-5418(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DENGUE VIRUS NS5.
[16]	"Dengue virus NS5 inhibits interferon-alpha signaling by blocking signal transducer and activator of transcription 2 phosphorylation." Mazzon M., Jones M., Davidson A., Chain B., Jacobs M. J. Infect. Dis. 200:1261-1270(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DENGUE VIRUS NS5.
[17]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M97934 mRNA. No translation available.
U18671 Genomic DNA. Translation: AAA98760.1.
S81491 Genomic DNA. Translation: AAB36226.1. Sequence problems.
S81491 Genomic DNA. Translation: AAB36227.1. Sequence problems.
AY525126 Genomic DNA. Translation: AAS00091.1.
BC051284 mRNA. Translation: AAH51284.1.

IPI

IPI00004312.
IPI00219076.

PIR

A46160.

RefSeq

NP_005410.1. NM_005419.3.
NP_938146.1. NM_198332.1.

UniGene

Hs.530595.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2KA4	NMR	-	B	786-838	[»]

ProteinModelPortal

P52630.

ModBase

Search...

Protein-protein interaction databases

IntAct

P52630. 17 interactions.

MINT

MINT-1526706.

STRING

9606.ENSP00000315768.

PTM databases

PhosphoSite

P52630.

Polymorphism databases

DMDM

1711552.

Proteomic databases

PaxDb

P52630.

PeptideAtlas

P52630.

PRIDE

P52630.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000314128; ENSP00000315768; ENSG00000170581.

GeneID

6773.

KEGG

hsa:6773.

UCSC

uc001slc.3. human.

Organism-specific databases

CTD

6773.

GeneCards

GC12M056735.

HGNC

HGNC:11363. STAT2.

HPA

CAB003858.
HPA018888.

MIM

600556. gene.

neXtProt

NX_P52630.

PharmGKB

PA36184.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG303257.

HOGENOM

HOG000220792.

HOVERGEN

HBG055669.

InParanoid

P52630.

KO

K11221.

OMA

WLDKILD.

OrthoDB

EOG434W5C.

PhylomeDB

P52630.

Enzyme and pathway databases

Pathway_Interaction_DB

il27pathway. IL27-mediated signaling events.

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P52630.

Bgee

P52630.

CleanEx

HS_STAT2.

Genevestigator

P52630.

GermOnline

ENSG00000170581. Homo sapiens.

Family and domain databases

Gene3D

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.

InterPro

IPR011992. EF-hand-like_dom.
IPR008967. p53-like_TF_DNA-bd.
IPR000980. SH2.
IPR022756. STAT2_C.
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]

PANTHER

PTHR11801. PTHR11801. 1 hit.

Pfam

PF00017. SH2. 1 hit.
PF12188. STAT2_C. 1 hit.
PF01017. STAT_alpha. 1 hit.
PF02864. STAT_bind. 1 hit.
PF02865. STAT_int. 1 hit.
[Graphical view]

SMART

SM00252. SH2. 1 hit.
SM00964. STAT_int. 1 hit.
[Graphical view]

SUPFAM

SSF49417. P53_like_DNA_bnd. 1 hit.
SSF47655. STAT. 1 hit.
SSF48092. STAT. 1 hit.

PROSITE

PS50001. SH2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

STAT2. human.

EvolutionaryTrace

P52630.

GenomeRNAi

6773.

NextBio

26434.

SOURCE

Search...

Entry information

Entry name

STAT2_HUMAN

Accession

Primary (citable) accession number: P52630
Secondary accession number(s): Q16430, Q16431, Q9UDL4

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	May 1, 2013
This is version 134 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.