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UniProtKB - P52630 (STAT2_HUMAN)

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Protein

Signal transducer and activator of transcription 2

Gene

STAT2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 IRF9/ISGF3G 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 (PubMed:9020188, PubMed:23391734). Acts as a regulator of mitochondrial fission by modulating the phosphorylation of DNM1L at 'Ser-616' and 'Ser-637' which activate and inactivate the GTPase activity of DNM1L respectively (PubMed:26122121).3 Publications

GO - Molecular functioni

  • DNA binding Source: UniProtKB-KW
  • identical protein binding Source: IntAct
  • RNA polymerase II transcription factor activity, sequence-specific DNA binding Source: NTNU_SB
  • ubiquitin-like protein ligase binding Source: UniProtKB
View the complete GO annotation on QuickGO ...

GO - Biological processi

  • cytokine-mediated signaling pathway Source: Reactome
  • defense response to virus Source: UniProtKB
  • JAK-STAT cascade Source: ProtInc
  • regulation of mitochondrial fission Source: UniProtKB
  • regulation of protein phosphorylation Source: UniProtKB
  • regulation of transcription by RNA polymerase II Source: ProtInc
  • transcription, DNA-templated Source: UniProtKB-KW
  • type I interferon signaling pathway Source: UniProtKB
  • viral process Source: UniProtKB-KW
View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionActivator, DNA-binding
Biological processAntiviral defense, Host-virus interaction, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-8854691 Interleukin-20 family signaling
R-HSA-909733 Interferon alpha/beta signaling
R-HSA-912694 Regulation of IFNA signaling
SignaLinkiP52630
SIGNORiP52630

Names & Taxonomyi

Protein namesi
Recommended name:
Signal transducer and activator of transcription 2
Alternative name(s):
p113
Gene namesi
Name:STAT2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000170581.13
HGNCiHGNC:11363 STAT2
MIMi600556 gene
neXtProtiNX_P52630

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Immunodeficiency 44 (IMD44)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive disorder characterized by increased susceptibility to viral infection, resulting in some patients in encephalopathy and infection-associated neurologic decompensation.
See also OMIM:616636

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi374R → A: Prevents the nuclear import; when associated with A-375. 1 Publication1
Mutagenesisi375K → A: Prevents the nuclear import; when associated with A-374. 1 Publication1
Mutagenesisi409R → A: Prevents the nuclear import; when associated with A-415. 1 Publication1
Mutagenesisi415K → A: Prevents the nuclear import; when associated with A-409. 1 Publication1
Mutagenesisi690Y → F: Reduces phosphorylation of STAT1 in response to IFN-ALPHA. 1 Publication1

Organism-specific databases

DisGeNETi6773
MalaCardsiSTAT2
MIMi616636 phenotype
OpenTargetsiENSG00000170581
PharmGKBiPA36184

Polymorphism and mutation databases

BioMutaiSTAT2
DMDMi1711552

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001824131 – 851Signal transducer and activator of transcription 2Add BLAST851

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei283Phosphoserine1 Publication1
Modified residuei287Phosphoserine1 Publication1
Modified residuei294Phosphothreonine1 Publication1
Modified residuei690Phosphotyrosine; by JAK2 Publications1
Modified residuei753PhosphoserineCombined sources1
Modified residuei800PhosphothreonineCombined sources1

Post-translational modificationi

Tyrosine phosphorylated in response to IFN-alpha. Phosphorylation at Ser-287 negatively regulates the transcriptional response.4 Publications
'Lys-48'-linked ubiquitination by DCST1 leads to STAT2 proteasomal degradation.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP52630
PaxDbiP52630
PeptideAtlasiP52630
PRIDEiP52630
ProteomicsDBi56498

PTM databases

iPTMnetiP52630
PhosphoSitePlusiP52630

Expressioni

Gene expression databases

BgeeiENSG00000170581
CleanExiHS_STAT2
ExpressionAtlasiP52630 baseline and differential
GenevisibleiP52630 HS

Organism-specific databases

HPAiCAB003858
HPA018888

Interactioni

Subunit structurei

Heterodimer with STAT1 upon IFN-alpha/beta induced phosphorylation (By similarity). The heterodimer STAT1:STAT2 forms the interferon-stimulated gene factor 3 complex (ISGF3) with IRF9; interacts with IRF9 in the cytoplasm (By similarity). Interacts with CRSP2 and CRSP6 (PubMed:12509459). Can form a homodimer upon IFN-alpha induced phosphorylation (PubMed:9020188). Interacts with IFNAR1; the interaction requires the phosphorylation of IFNAR1 at 'Tyr-466' (PubMed:9121453). Interacts with IFNAR2 (PubMed:9121453). Interacts with ARL2BP (By similarity). Interacts with E3 ubiquitin ligase DCST1; the interaction results in STAT2 ubiquitin-mediated proteasomal degradation (PubMed:27782195).By similarity4 Publications
(Microbial infection) Interacts with vaccinia virus protein C6.1 Publication
(Microbial infection) Interacts with Simian virus 5 protein V.1 Publication
(Microbial infection) Interacts with Rabies virus phosphoprotein.1 Publication
(Microbial infection) Interacts with Human cytomegalovirus/HHV-5 protein UL123; this interaction promotes viral growth.1 Publication
(Microbial infection) Interacts with Dengue virus NS5; this interaction inhibits the phosphorylation of STAT2, and, when all viral proteins are present (polyprotein), targets STAT2 for degradation.2 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • ubiquitin-like protein ligase binding Source: UniProtKB
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi112650, 44 interactors
CORUMiP52630
DIPiDIP-38511N
IntActiP52630, 27 interactors
MINTiP52630
STRINGi9606.ENSP00000315768

Structurei

Secondary structure

1851
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi793 – 796Combined sources4
Helixi802 – 806Combined sources5
Turni812 – 814Combined sources3
Helixi824 – 827Combined sources4
Helixi831 – 834Combined sources4

3D structure databases

DisProtiDP00961
ProteinModelPortaliP52630
SMRiP52630
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP52630

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini572 – 667SH2PROSITE-ProRule annotationAdd BLAST96

Sequence similaritiesi

Belongs to the transcription factor STAT family.Curated

Keywords - Domaini

SH2 domain

Phylogenomic databases

eggNOGiKOG3667 Eukaryota
ENOG410XPN8 LUCA
GeneTreeiENSGT00760000119236
HOGENOMiHOG000220792
HOVERGENiHBG055669
InParanoidiP52630
KOiK11221
OMAiWFTDGAK
OrthoDBiEOG091G03O3
PhylomeDBiP52630
TreeFamiTF318648

Family and domain databases

CDDicd10373 SH2_STAT2, 1 hit
Gene3Di1.10.532.10, 1 hit
2.60.40.630, 1 hit
3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR008967 p53-like_TF_DNA-bd
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR001217 STAT
IPR022756 STAT2_C
IPR035854 STAT2_SH2
IPR036535 STAT_N_sf
IPR013800 STAT_TF_alpha
IPR015988 STAT_TF_coiled-coil
IPR013801 STAT_TF_DNA-bd
IPR012345 STAT_TF_DNA-bd_N
IPR013799 STAT_TF_prot_interaction
PANTHERiPTHR11801 PTHR11801, 1 hit
PfamiView protein in 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
SMARTiView protein in SMART
SM00252 SH2, 1 hit
SM00964 STAT_int, 1 hit
SUPFAMiSSF47655 SSF47655, 1 hit
SSF48092 SSF48092, 1 hit
SSF49417 SSF49417, 1 hit
SSF55550 SSF55550, 1 hit
PROSITEiView protein in PROSITE
PS50001 SH2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P52630-3) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

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

F
Length:851
Mass (Da):97,916
Last modified:October 1, 1996 - v1
Checksum:iE4C74674CB7A3215
GO
Isoform 2 (identifier: P52630-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     96-99: Missing.

Note: No experimental confirmation available. May be due to competing acceptor splice site.
Show »
Length:847
Mass (Da):97,457
Checksum:i3587443D40AF5E5B
GO

Sequence cautioni

The sequence AAB36226 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence AAB36227 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti240A → T in BAG59489 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01489666Q → H. Corresponds to variant dbSNP:rs2066816Ensembl.1
Natural variantiVAR_014897220L → P. Corresponds to variant dbSNP:rs2066817Ensembl.1
Natural variantiVAR_052072246C → S. Corresponds to variant dbSNP:rs2228259Ensembl.1
Natural variantiVAR_014898448T → M1 PublicationCorresponds to variant dbSNP:rs2066815EnsemblClinVar.1
Natural variantiVAR_014899464I → V1 PublicationCorresponds to variant dbSNP:rs2066811EnsemblClinVar.1
Natural variantiVAR_014900501S → I. Corresponds to variant dbSNP:rs2066809Ensembl.1
Natural variantiVAR_014901594M → I1 PublicationCorresponds to variant dbSNP:rs2066807EnsemblClinVar.1
Natural variantiVAR_019213826Q → H1 PublicationCorresponds to variant dbSNP:rs2229363EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04670596 – 99Missing in isoform 2. 1 Publication4

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
AK296939 mRNA Translation: BAG59489.1
AC025574 Genomic DNA No translation available.
BC051284 mRNA Translation: AAH51284.1
CCDSiCCDS55836.1 [P52630-4]
CCDS8917.1 [P52630-3]
PIRiA46160
RefSeqiNP_005410.1, NM_005419.3 [P52630-3]
NP_938146.1, NM_198332.1 [P52630-4]
UniGeneiHs.530595

Genome annotation databases

EnsembliENST00000314128; ENSP00000315768; ENSG00000170581 [P52630-3]
ENST00000557235; ENSP00000450751; ENSG00000170581 [P52630-4]
GeneIDi6773
KEGGihsa:6773
UCSCiuc001sld.4 human [P52630-3]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiSTAT2_HUMAN
AccessioniPrimary (citable) accession number: P52630
Secondary accession number(s): B4DLC7
, G3V2M6, Q16430, Q16431, Q9UDL4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: June 20, 2018
This is version 185 of the entry and version 1 of the sequence. See 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

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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