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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

GO - Biological processi

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
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
Orphaneti431166 Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection
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 Expressed in 205 organ(s), highest expression level in oviduct epithelium
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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi112650, 45 interactors
CORUMiP52630
DIPiDIP-38511N
IntActiP52630, 28 interactors
MINTiP52630
STRINGi9606.ENSP00000315768

Structurei

Secondary structure

1851
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

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
HOVERGENiHBG071022
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

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
B4DLC8B4DLC8_HUMAN
cDNA FLJ59331, highly similar to Si...
STAT2
460Annotation score:
G3V319G3V319_HUMAN
Signal transducer and activator of ...
STAT2
65Annotation score:

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

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[»]
DisProtiDP00961
ProteinModelPortaliP52630
SMRiP52630
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112650, 45 interactors
CORUMiP52630
DIPiDIP-38511N
IntActiP52630, 28 interactors
MINTiP52630
STRINGi9606.ENSP00000315768

PTM databases

iPTMnetiP52630
PhosphoSitePlusiP52630

Polymorphism and mutation databases

BioMutaiSTAT2
DMDMi1711552

Proteomic databases

EPDiP52630
PaxDbiP52630
PeptideAtlasiP52630
PRIDEiP52630
ProteomicsDBi56498

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
EuPathDBiHostDB:ENSG00000170581.13
GeneCardsiSTAT2
HGNCiHGNC:11363 STAT2
HPAiCAB003858
HPA018888
MalaCardsiSTAT2
MIMi600556 gene
616636 phenotype
neXtProtiNX_P52630
OpenTargetsiENSG00000170581
Orphaneti431166 Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection
PharmGKBiPA36184
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3667 Eukaryota
ENOG410XPN8 LUCA
GeneTreeiENSGT00760000119236
HOGENOMiHOG000220792
HOVERGENiHBG071022
InParanoidiP52630
KOiK11221
OMAiWFTDGAK
OrthoDBiEOG091G03O3
PhylomeDBiP52630
TreeFamiTF318648

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

Miscellaneous databases

ChiTaRSiSTAT2 human
EvolutionaryTraceiP52630
GeneWikiiSTAT2
GenomeRNAii6773
PROiPR:P52630
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000170581 Expressed in 205 organ(s), highest expression level in oviduct epithelium
CleanExiHS_STAT2
ExpressionAtlasiP52630 baseline and differential
GenevisibleiP52630 HS

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
ProtoNetiSearch...

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: November 7, 2018
This is version 188 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
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