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Protein

Signal transducer and activator of transcription 2

Gene

STAT2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

GO - Biological processi

  • 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 from RNA polymerase II promoter Source: ProtInc
  • regulation of type I interferon-mediated signaling pathway Source: Reactome
  • transcription, DNA-templated Source: UniProtKB-KW
  • type I interferon signaling pathway Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Antiviral defense, Host-virus interaction, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000170581-MONOMER.
ReactomeiR-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:11363. STAT2.

Subcellular locationi

  • Cytoplasm
  • Nucleus

  • Note: Translocated into the nucleus upon activation by IFN-alpha/beta.

GO - Cellular componenti

Complete GO annotation...

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.
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

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP52630.
PaxDbiP52630.
PeptideAtlasiP52630.
PRIDEiP52630.

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. The heterodimer STAT1:STAT2 forms the interferon-stimulated gene factor 3 complex (ISGF3) with IRF9; interacts with IRF9 in the cytoplasm. Interacts with CRSP2 and CRSP6. 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 ARL2BP. 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. Interacts with Simian virus 5 protein V and rabies virus phosphoprotein.7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-1546963,EBI-1546963
IFNAR1P171815EBI-1546963,EBI-1547250
IFNAR2P485514EBI-1546963,EBI-958408
IRF9Q009786EBI-1546963,EBI-626526
P/VP0C7744EBI-1546963,EBI-3650423From a different organism.
P/VP112072EBI-1546963,EBI-6148694From a different organism.
STAT1P4222414EBI-1546963,EBI-1057697

Protein-protein interaction databases

BioGridi112650. 41 interactors.
DIPiDIP-38511N.
IntActiP52630. 25 interactors.
MINTiMINT-1526706.
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

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2KA4NMR-B786-838[»]
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
Contains 1 SH2 domain.PROSITE-ProRule annotation

Keywords - Domaini

SH2 domain

Phylogenomic databases

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

Family and domain databases

Gene3Di1.10.238.10. 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.
InterProiIPR011992. EF-hand-dom_pair.
IPR008967. p53-like_TF_DNA-bd.
IPR000980. SH2.
IPR001217. STAT.
IPR022756. STAT2_C.
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]
PANTHERiPTHR11801. PTHR11801. 2 hits.
PfamiPF00017. 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]
SMARTiSM00252. SH2. 1 hit.
SM00964. STAT_int. 1 hit.
[Graphical view]
SUPFAMiSSF47655. SSF47655. 1 hit.
SSF48092. SSF48092. 1 hit.
SSF49417. SSF49417. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEiPS50001. SH2. 1 hit.
[Graphical view]

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 rs2066816dbSNPEnsembl.1
Natural variantiVAR_014897220L → P.Corresponds to variant rs2066817dbSNPEnsembl.1
Natural variantiVAR_052072246C → S.Corresponds to variant rs2228259dbSNPEnsembl.1
Natural variantiVAR_014898448T → M.1 PublicationCorresponds to variant rs2066815dbSNPEnsembl.1
Natural variantiVAR_014899464I → V.1 PublicationCorresponds to variant rs2066811dbSNPEnsembl.1
Natural variantiVAR_014900501S → I.Corresponds to variant rs2066809dbSNPEnsembl.1
Natural variantiVAR_014901594M → I.1 PublicationCorresponds to variant rs2066807dbSNPEnsembl.1
Natural variantiVAR_019213826Q → H.1 PublicationCorresponds to variant rs2229363dbSNPEnsembl.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

Cross-referencesi

Web resourcesi

NIEHS-SNPs

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2KA4NMR-B786-838[»]
ProteinModelPortaliP52630.
SMRiP52630.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112650. 41 interactors.
DIPiDIP-38511N.
IntActiP52630. 25 interactors.
MINTiMINT-1526706.
STRINGi9606.ENSP00000315768.

PTM databases

iPTMnetiP52630.
PhosphoSitePlusiP52630.

Polymorphism and mutation databases

BioMutaiSTAT2.
DMDMi1711552.

Proteomic databases

EPDiP52630.
PaxDbiP52630.
PeptideAtlasiP52630.
PRIDEiP52630.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi6773.
DisGeNETi6773.
GeneCardsiSTAT2.
HGNCiHGNC:11363. STAT2.
HPAiCAB003858.
HPA018888.
MIMi600556. gene.
616636. phenotype.
neXtProtiNX_P52630.
OpenTargetsiENSG00000170581.
PharmGKBiPA36184.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000170581-MONOMER.
ReactomeiR-HSA-909733. Interferon alpha/beta signaling.
R-HSA-912694. Regulation of IFNA signaling.
SignaLinkiP52630.
SIGNORiP52630.

Miscellaneous databases

ChiTaRSiSTAT2. human.
EvolutionaryTraceiP52630.
GeneWikiiSTAT2.
GenomeRNAii6773.
PROiP52630.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000170581.
CleanExiHS_STAT2.
ExpressionAtlasiP52630. baseline and differential.
GenevisibleiP52630. HS.

Family and domain databases

Gene3Di1.10.238.10. 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.
InterProiIPR011992. EF-hand-dom_pair.
IPR008967. p53-like_TF_DNA-bd.
IPR000980. SH2.
IPR001217. STAT.
IPR022756. STAT2_C.
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]
PANTHERiPTHR11801. PTHR11801. 2 hits.
PfamiPF00017. 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]
SMARTiSM00252. SH2. 1 hit.
SM00964. STAT_int. 1 hit.
[Graphical view]
SUPFAMiSSF47655. SSF47655. 1 hit.
SSF48092. SSF48092. 1 hit.
SSF49417. SSF49417. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEiPS50001. SH2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSTAT2_HUMAN
AccessioniPrimary (citable) accession number: P52630
Secondary accession number(s): B4DLC7
, G3V2M6, Q16430, Q16431, Q9UDL4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: November 2, 2016
This is version 170 of the entry and version 1 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.