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Protein

Signal transducer and activator of transcription 1-alpha/beta

Gene

STAT1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Signal transducer and transcription activator that mediates cellular responses to interferons (IFNs), cytokine KITLG/SCF and other cytokines and other growth factors. Following type I IFN (IFN-alpha and IFN-beta) binding to cell surface receptors, signaling via protein kinases leads to activation of Jak kinases (TYK2 and JAK1) and to tyrosine phosphorylation of STAT1 and STAT2. The phosphorylated STATs dimerize and 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 IFN-stimulated genes (ISG), which drive the cell in an antiviral state. In response to type II IFN (IFN-gamma), STAT1 is tyrosine- and serine-phosphorylated. It then forms a homodimer termed IFN-gamma-activated factor (GAF), migrates into the nucleus and binds to the IFN gamma activated sequence (GAS) to drive the expression of the target genes, inducing a cellular antiviral state. Becomes activated in response to KITLG/SCF and KIT signaling. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4.5 Publications

GO - Molecular functioni

  • cadherin binding involved in cell-cell adhesion Source: BHF-UCL
  • double-stranded DNA binding Source: UniProtKB
  • enzyme binding Source: UniProtKB
  • identical protein binding Source: IntAct
  • nuclear hormone receptor binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: BHF-UCL
  • RNA polymerase II core promoter sequence-specific DNA binding Source: BHF-UCL
  • signal transducer activity Source: InterPro
  • transcription factor activity, RNA polymerase II core promoter sequence-specific Source: BHF-UCL
  • transcription factor activity, sequence-specific DNA binding Source: UniProtKB
  • tumor necrosis factor receptor binding Source: UniProtKB

GO - Biological processi

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

ReactomeiR-HSA-1059683. Interleukin-6 signaling.
R-HSA-1169408. ISG15 antiviral mechanism.
R-HSA-1433557. Signaling by SCF-KIT.
R-HSA-1839117. Signaling by cytosolic FGFR1 fusion mutants.
R-HSA-186763. Downstream signal transduction.
R-HSA-877300. Interferon gamma signaling.
R-HSA-877312. Regulation of IFNG signaling.
R-HSA-909733. Interferon alpha/beta signaling.
R-HSA-912694. Regulation of IFNA signaling.
R-HSA-982772. Growth hormone receptor signaling.
SignaLinkiP42224.
SIGNORiP42224.

Names & Taxonomyi

Protein namesi
Recommended name:
Signal transducer and activator of transcription 1-alpha/beta
Alternative name(s):
Transcription factor ISGF-3 components p91/p84
Gene namesi
Name:STAT1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:11362. STAT1.

Subcellular locationi

GO - Cellular componenti

  • axon Source: UniProtKB
  • cell-cell adherens junction Source: BHF-UCL
  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • dendrite Source: UniProtKB
  • nuclear chromatin Source: BHF-UCL
  • nucleolus Source: HPA
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
  • perinuclear region of cytoplasm Source: AgBase
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Immunodeficiency 31B (IMD31B)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by susceptibility to severe mycobacterial and viral infections. Affected individuals can develop disseminated infections and die of viral illness.
See also OMIM:613796
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti201 – 2011K → N in IMD31B; not deleterious in terms of most STAT1 functions; causes abnormal splicing out of exon 8 from most mRNAs thereby decreasing protein levels by approximately 70%. 1 Publication
Corresponds to variant rs587776870 [ dbSNP | Ensembl ].
VAR_065815
Natural varianti600 – 6001L → P in IMD31B; found in an infant who died of a viral-like illness associated with complete STAT1 deficiency. 1 Publication
Corresponds to variant rs137852678 [ dbSNP | Ensembl ].
VAR_018265
Natural varianti701 – 7011Y → C in IMD31B; disrupts transactivation activity in response to IFNG. 1 Publication
VAR_075500
Immunodeficiency 31A (IMD31A)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of Mendelian susceptibility to mycobacterial disease, a rare condition caused by impairment of interferon-gamma mediated immunity. It is characterized by predisposition to illness caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine, environmental non-tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. Other microorganisms rarely cause severe clinical disease in individuals with susceptibility to mycobacterial infections, with the exception of Salmonella which infects less than 50% of these individuals. Clinical outcome severity depends on the degree of impairment of interferon-gamma mediated immunity. Some patients die of overwhelming mycobacterial disease with lepromatous-like lesions in early childhood, whereas others develop, later in life, disseminated but curable infections with tuberculoid granulomas. IMD31A has low penetrance, and affected individuals have relatively mild disease and good prognosis. IMD31A confers a predisposition to mycobacterial infections only, with no increased susceptibility to viral infections.
See also OMIM:614892
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti320 – 3201E → Q in IMD31A; affects the DNA-binding activity of the protein. 1 Publication
Corresponds to variant rs137852680 [ dbSNP | Ensembl ].
VAR_065816
Natural varianti463 – 4631Q → H in IMD31A; affects the DNA-binding activity of the protein. 1 Publication
Corresponds to variant rs137852679 [ dbSNP | Ensembl ].
VAR_065817
Natural varianti637 – 6371K → E in IMD31A; affects both phosphorylation and DNA-binding activity; results in impaired STAT1-mediated cellular response to IFN-gamma and interleukin-27. 1 Publication
Corresponds to variant rs587777705 [ dbSNP | Ensembl ].
VAR_068713
Natural varianti673 – 6731K → R in IMD31A; impairs tyrosine phosphorylation; results in impaired STAT1-mediated cellular response to IFN-gamma and interleukin-27. 1 Publication
Corresponds to variant rs587777704 [ dbSNP | Ensembl ].
VAR_068714
Natural varianti706 – 7061L → S in IMD31A; loss of GAF and ISGF3 activation; impairs the nuclear accumulation of GAF but not of ISGF3 in heterozygous cells stimulated by IFNs; affects phosphorylation of the protein. 2 Publications
Corresponds to variant rs137852677 [ dbSNP | Ensembl ].
VAR_018266
Immunodeficiency 31C (IMD31C)5 Publications
The disease is caused by mutations affecting the gene represented in this entry. STAT1 mutations in patients with autosomal dominant candidiasis lead to defective responses of type 1 and type 17 helper T-cells, characterized by reduced production of interferon-alpha, interleukin-17, and interleukin-22. These cytokines are crucial for the antifungal defense of skin and mucosa (PubMed:21714643).1 Publication
Disease descriptionA primary immunodeficiency disorder with altered immune responses and impaired clearance of fungal infections, selective against Candida. It is characterized by persistent and/or recurrent infections of the skin, nails and mucous membranes caused by organisms of the genus Candida, mainly Candida albicans.
See also OMIM:614162
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti165 – 1651D → G in IMD31C; gain of function mutation associated with increased STAT1 phosphorylation due to impaired nuclear dephosphorylation. 2 Publications
Corresponds to variant rs387906764 [ dbSNP | Ensembl ].
VAR_065934
Natural varianti165 – 1651D → H in IMD31C. 1 Publication
Corresponds to variant rs387906767 [ dbSNP | Ensembl ].
VAR_065935
Natural varianti170 – 1701Y → N in IMD31C. 1 Publication
Corresponds to variant rs387906766 [ dbSNP | Ensembl ].
VAR_065936
Natural varianti174 – 1741C → R in IMD31C. 1 Publication
Corresponds to variant rs387906763 [ dbSNP | Ensembl ].
VAR_065937
Natural varianti179 – 1791N → K in IMD31C; gain of function; increases transactivation activity in response to IFNG. 1 Publication
Corresponds to variant rs587777628 [ dbSNP | Ensembl ].
VAR_075494
Natural varianti202 – 2021M → I in IMD31C. 1 Publication
VAR_065938
Natural varianti202 – 2021M → V in IMD31C. 1 Publication
Corresponds to variant rs387906762 [ dbSNP | Ensembl ].
VAR_065939
Natural varianti267 – 2671A → V in IMD31C. 2 Publications
Corresponds to variant rs387906759 [ dbSNP | Ensembl ].
VAR_065940
Natural varianti271 – 2711Q → P in IMD31C. 1 Publication
Corresponds to variant rs387906768 [ dbSNP | Ensembl ].
VAR_065941
Natural varianti274 – 2741R → Q in IMD31C; gain of function; increases STAT1 phosphorylation due to impaired nuclear dephosphorylation; increases transactivation activity in response to IFNG. 2 Publications
Corresponds to variant rs387906760 [ dbSNP | Ensembl ].
VAR_065942
Natural varianti274 – 2741R → W in IMD31C; gain of function; increases phosphorylation in response to IFNG, IFNA and IL27 due to a loss of dephosphorylation. 3 Publications
Corresponds to variant rs387906758 [ dbSNP | Ensembl ].
VAR_065943
Natural varianti278 – 2781K → E in IMD31C; gain of function; increases phosphorylation in response to IFNG and IFNA due to a loss of dephosphorylation. 1 Publication
VAR_075495
Natural varianti285 – 2851Q → R in IMD31C; gain of function; increases transactivation activity in response to IFNG. 1 Publication
Corresponds to variant rs587777629 [ dbSNP | Ensembl ].
VAR_075496
Natural varianti286 – 2861K → I in IMD31C. 1 Publication
Corresponds to variant rs387906761 [ dbSNP | Ensembl ].
VAR_065944
Natural varianti288 – 2881T → A in IMD31C. 1 Publication
Corresponds to variant rs387906765 [ dbSNP | Ensembl ].
VAR_065945
Natural varianti298 – 2981K → N in IMD31C; gain of function; increases basal STAT1 phosphorylation levels which are 10-20 fold higher than controls after IFNG stimulation. 1 Publication
VAR_075497
Natural varianti384 – 3841G → D in IMD31C; gain of function; increases phosphorylation in response to IFNG and IFNA due to a loss of dephosphorylation. 1 Publication
Corresponds to variant rs796065052 [ dbSNP | Ensembl ].
VAR_075498
Natural varianti385 – 3851T → M in IMD31C; gain of function; increases phosphorylation in response to IFNG, IFNA and IL27 due to a loss of dephosphorylation. 2 Publications
Corresponds to variant rs587777630 [ dbSNP | Ensembl ].
VAR_075499

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi110 – 1101K → R: Sumoylated. 1 Publication
Mutagenesisi701 – 7011Y → E: Not phosphorylated at S-708 upon IFNB induction. 2 Publications
Mutagenesisi701 – 7011Y → F: No effect on basal sumoylation. Enhances sumoylation in the presence of MAPK stimulation. Phosphorylated at S-708 upon IFNB induction. 2 Publications
Mutagenesisi703 – 7031K → R: Abolishes sumoylation by SUMO1. Increased IFN-gamma-mediated transactivation. 2 Publications
Mutagenesisi708 – 7081S → A: Phosphorylated at Y-701 upon IFNB induction. 1 Publication
Mutagenesisi708 – 7081S → D: Not phosphorylated at Y-701 upon IFNB induction. 1 Publication
Mutagenesisi727 – 7271S → A: Decreased transcriptional activation. No effect on basal sumoylation. No enhancement of sumoylation on MAPK stimulation. No PRKCD-induced apoptosis. Upon IFNB induction, phosphorylated at Y-701 but not at S-708. 3 Publications
Mutagenesisi727 – 7271S → D: No change in enhancement of MAPK-induced sumoylation. Basal interaction with PIAS1. Interaction with PIAS1 increased on MAPK stimulation. 3 Publications
Mutagenesisi727 – 7271S → E: No change in enhancement of MAPK-induced sumoylation. 3 Publications

Keywords - Diseasei

Disease mutation

Organism-specific databases

MalaCardsiSTAT1.
MIMi613796. phenotype.
614162. phenotype.
614892. phenotype.
Orphaneti391487. Autoimmune enteropathy and endocrinopathy-susceptibility to chronic infections syndrome.
1334. Chronic mucocutaneous candidosis.
319595. Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency.
391311. Susceptibility to viral and mycobacterial infections.
PharmGKBiPA36183.

Chemistry

ChEMBLiCHEMBL6101.

Polymorphism and mutation databases

BioMutaiSTAT1.
DMDMi2507413.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedCombined sources
Chaini2 – 750749Signal transducer and activator of transcription 1-alpha/betaPRO_0000182410Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserineCombined sources
Modified residuei701 – 7011Phosphotyrosine; by JAK1, JAK2 or TYK25 Publications
Cross-linki703 – 703Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate
Cross-linki703 – 703Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternateCombined sources
Modified residuei708 – 7081Phosphoserine; by IKKE1 Publication
Modified residuei727 – 7271Phosphoserine; by MAPK14Combined sources5 Publications
Modified residuei745 – 7451Phosphoserine; by IKKEBy similarity

Post-translational modificationi

Phosphorylated on tyrosine and serine residues in response to a variety of cytokines/growth hormones including IFN-alpha, IFN-gamma, PDGF and EGF. Activated KIT promotes phosphorylation on tyrosine residues and subsequent translocation to the nucleus. Upon EGF stimulation, phosphorylation on Tyr-701 (lacking in beta form) by JAK1, JAK2 or TYK2 promotes dimerization and subsequent translocation to the nucleus. Growth hormone (GH) activates STAT1 signaling only via JAK2. Tyrosine phosphorylated in response to constitutively activated FGFR1, FGFR2, FGFR3 and FGFR4. Phosphorylation on Ser-727 by several kinases including MAPK14, ERK1/2 and CAMKII on IFN-gamma stimulation, regulates STAT1 transcriptional activity. Phosphorylation on Ser-727 promotes sumoylation though increasing interaction with PIAS. Phosphorylation on Ser-727 by PRKCD induces apoptosis in response to DNA-damaging agents. Phosphorylated on tyrosine residues when PTK2/FAK1 is activated; most likely this is catalyzed by a SRC family kinase. Dephosphorylation on tyrosine residues by PTPN2 negatively regulates interferon-mediated signaling. Upon viral infection or IFN induction, phosphorylation on Ser-708 occurs much later than phosphorylation on Tyr-701 and is required for the binding of ISGF3 on the ISREs of a subset of IFN-stimulated genes IKBKE-dependent. Phosphorylation at Tyr-701 and Ser-708 are mutually exclusive, phosphorylation at Ser-708 requires previous dephosphorylation of Tyr-701.8 Publications
Sumoylated with SUMO1, SUMO2 and SUMO3. Sumoylation is enhanced by IFN-gamma-induced phosphorylation on Ser-727, and by interaction with PIAS proteins. Enhances the transactivation activity.5 Publications
ISGylated.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP42224.
MaxQBiP42224.
PaxDbiP42224.
PeptideAtlasiP42224.
PRIDEiP42224.

PTM databases

iPTMnetiP42224.
PhosphoSiteiP42224.
SwissPalmiP42224.

Miscellaneous databases

PMAP-CutDBP42224.

Expressioni

Gene expression databases

BgeeiENSG00000115415.
CleanExiHS_STAT1.
ExpressionAtlasiP42224. baseline and differential.
GenevisibleiP42224. HS.

Organism-specific databases

HPAiCAB004049.
HPA000931.
HPA000982.

Interactioni

Subunit structurei

Isoform alpha homodimerizes upon IFN-gamma induced phosphorylation. Heterodimer with STAT2 upon IFN-alpha/beta induced phosphorylation. The heterodimer STAT1:STAT2 forms the interferon-stimulated gene factor 3 complex (ISGF3) with IRF9. Interacts (phosphorylated at Ser 727) with PIAS1 (dimethylated on arginine); the interaction results in release of STAT1 from its target gene. Interacts with IFNAR1; the interaction requires the phosphorylation of IFNAR1 at 'Tyr-466'. Interacts with IFNAR2, NMI, PTK2/FAK1 and SRC. Interacts with ERBB4 (phosphorylated). Interacts with Sendai virus C', C, Y1 and Y2 proteins, Nipah virus P, V and W proteins, and rabies virus phosphoprotein preventing activation of ISRE and GAS promoter. Interacts with HCV core protein; the interaction results in STAT1 degradation.9 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself4EBI-1057697,EBI-1057697
P03255-12EBI-1057697,EBI-6692439From a different organism.
P03255-22EBI-1057697,EBI-6859460From a different organism.
P266645EBI-1057697,EBI-6941357From a different organism.
P279582EBI-1057697,EBI-6377335From a different organism.
DDB1Q165312EBI-1057697,EBI-350322
DDX58O957864EBI-1057697,EBI-995350
E2F1Q010942EBI-1057697,EBI-448924
EGFRP005336EBI-1057697,EBI-297353
EIF1ADQ8N9N84EBI-1057697,EBI-750700
ERBB2P046263EBI-1057697,EBI-641062
FOSP011006EBI-1057697,EBI-852851
H1LP072393EBI-1057697,EBI-7789600From a different organism.
IFNAR1P171812EBI-1057697,EBI-1547250
IFNAR2P485512EBI-1057697,EBI-958408
IFNGR1P152604EBI-1057697,EBI-1030755
MAVSQ7Z4343EBI-1057697,EBI-995373
OTUD4Q018043EBI-1057697,EBI-1054396
RXRAP197932EBI-1057697,EBI-78598
STAT2P5263014EBI-1057697,EBI-1546963
STAT3P407633EBI-1057697,EBI-518675

GO - Molecular functioni

  • cadherin binding involved in cell-cell adhesion Source: BHF-UCL
  • enzyme binding Source: UniProtKB
  • identical protein binding Source: IntAct
  • nuclear hormone receptor binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • tumor necrosis factor receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi112649. 146 interactions.
DIPiDIP-46140N.
IntActiP42224. 68 interactions.
MINTiMINT-120840.
STRINGi9606.ENSP00000354394.

Chemistry

BindingDBiP42224.

Structurei

Secondary structure

1
750
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi3 – 75Combined sources
Helixi12 – 2110Combined sources
Beta strandi23 – 264Combined sources
Helixi28 – 336Combined sources
Helixi35 – 406Combined sources
Helixi43 – 464Combined sources
Helixi50 – 7324Combined sources
Helixi77 – 9418Combined sources
Helixi99 – 12022Combined sources
Helixi121 – 1255Combined sources
Helixi137 – 17943Combined sources
Helixi189 – 1924Combined sources
Helixi193 – 1953Combined sources
Helixi198 – 24750Combined sources
Helixi257 – 28630Combined sources
Helixi293 – 31624Combined sources
Beta strandi317 – 3215Combined sources
Beta strandi334 – 3363Combined sources
Beta strandi339 – 3479Combined sources
Helixi352 – 3543Combined sources
Turni355 – 3573Combined sources
Beta strandi359 – 3657Combined sources
Helixi370 – 3734Combined sources
Beta strandi374 – 3763Combined sources
Beta strandi380 – 3823Combined sources
Beta strandi386 – 3894Combined sources
Beta strandi391 – 3955Combined sources
Turni396 – 3983Combined sources
Beta strandi399 – 40810Combined sources
Beta strandi421 – 4255Combined sources
Beta strandi433 – 4419Combined sources
Beta strandi444 – 4518Combined sources
Beta strandi455 – 4606Combined sources
Helixi461 – 4633Combined sources
Helixi464 – 47714Combined sources
Helixi486 – 4883Combined sources
Helixi495 – 50915Combined sources
Helixi516 – 52611Combined sources
Helixi539 – 5435Combined sources
Beta strandi550 – 5523Combined sources
Helixi554 – 56815Combined sources
Helixi570 – 5745Combined sources
Helixi584 – 5907Combined sources
Turni591 – 5933Combined sources
Beta strandi601 – 6033Combined sources
Beta strandi612 – 6165Combined sources
Beta strandi621 – 6244Combined sources
Beta strandi627 – 6315Combined sources
Helixi636 – 6405Combined sources
Helixi644 – 6496Combined sources
Beta strandi657 – 6593Combined sources
Helixi673 – 6775Combined sources
Turni678 – 6803Combined sources
Helixi728 – 73811Combined sources
Turni739 – 7424Combined sources
Helixi743 – 7453Combined sources
Turni746 – 7483Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1BF5X-ray2.90A136-710[»]
1YVLX-ray3.00A/B1-683[»]
2KA6NMR-B710-750[»]
3WWTX-ray2.00A1-126[»]
ProteinModelPortaliP42224.
SMRiP42224. Positions 1-750.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP42224.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini573 – 67098SH2PROSITE-ProRule annotationAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili136 – 3171821 PublicationAdd
BLAST

Sequence similaritiesi

Belongs to the transcription factor STAT family.Curated
Contains 1 SH2 domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil, SH2 domain

Phylogenomic databases

eggNOGiKOG3667. Eukaryota.
ENOG410XPN8. LUCA.
GeneTreeiENSGT00760000119236.
HOVERGENiHBG055669.
InParanoidiP42224.
KOiK11220.
OMAiWYNMLTT.
OrthoDBiEOG091G03O3.
PhylomeDBiP42224.
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.
IPR022752. STAT1_TAZ2-bd_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. 1 hit.
PfamiPF00017. SH2. 1 hit.
PF12162. STAT1_TAZ2bind. 1 hit.
PF01017. STAT_alpha. 1 hit.
PF02864. STAT_bind. 1 hit.
PF02865. STAT_int. 1 hit.
[Graphical view]
SMARTiSM00964. 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.

Sequence processingi: The displayed sequence is further processed into a mature form.

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

Isoform Alpha (identifier: P42224-1) [UniParc]FASTAAdd to basket
Also known as: p91

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
MSQWYELQQL DSKFLEQVHQ LYDDSFPMEI RQYLAQWLEK QDWEHAANDV
60 70 80 90 100
SFATIRFHDL LSQLDDQYSR FSLENNFLLQ HNIRKSKRNL QDNFQEDPIQ
110 120 130 140 150
MSMIIYSCLK EERKILENAQ RFNQAQSGNI QSTVMLDKQK ELDSKVRNVK
160 170 180 190 200
DKVMCIEHEI KSLEDLQDEY DFKCKTLQNR EHETNGVAKS DQKQEQLLLK
210 220 230 240 250
KMYLMLDNKR KEVVHKIIEL LNVTELTQNA LINDELVEWK RRQQSACIGG
260 270 280 290 300
PPNACLDQLQ NWFTIVAESL QQVRQQLKKL EELEQKYTYE HDPITKNKQV
310 320 330 340 350
LWDRTFSLFQ QLIQSSFVVE RQPCMPTHPQ RPLVLKTGVQ FTVKLRLLVK
360 370 380 390 400
LQELNYNLKV KVLFDKDVNE RNTVKGFRKF NILGTHTKVM NMEESTNGSL
410 420 430 440 450
AAEFRHLQLK EQKNAGTRTN EGPLIVTEEL HSLSFETQLC QPGLVIDLET
460 470 480 490 500
TSLPVVVISN VSQLPSGWAS ILWYNMLVAE PRNLSFFLTP PCARWAQLSE
510 520 530 540 550
VLSWQFSSVT KRGLNVDQLN MLGEKLLGPN ASPDGLIPWT RFCKENINDK
560 570 580 590 600
NFPFWLWIES ILELIKKHLL PLWNDGCIMG FISKERERAL LKDQQPGTFL
610 620 630 640 650
LRFSESSREG AITFTWVERS QNGGEPDFHA VEPYTKKELS AVTFPDIIRN
660 670 680 690 700
YKVMAAENIP ENPLKYLYPN IDKDHAFGKY YSRPKEAPEP MELDGPKGTG
710 720 730 740 750
YIKTELISVS EVHPSRLQTT DNLLPMSPEE FDEVSRIVGS VEFDSMMNTV
Length:750
Mass (Da):87,335
Last modified:November 1, 1997 - v2
Checksum:i054A813522364BA6
GO
Isoform Beta (identifier: P42224-2) [UniParc]FASTAAdd to basket
Also known as: p84

The sequence of this isoform differs from the canonical sequence as follows:
     713-750: Missing.

Show »
Length:712
Mass (Da):83,043
Checksum:i31408601223700BB
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti46 – 461A → T in ADA59516 (Ref. 2) Curated
Sequence conflicti307 – 3071S → G in BAF85293 (PubMed:14702039).Curated
Sequence conflicti718 – 7181Q → R in CAH18430 (PubMed:17974005).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti30 – 301I → T.
Corresponds to variant rs34255470 [ dbSNP | Ensembl ].
VAR_034521
Natural varianti165 – 1651D → G in IMD31C; gain of function mutation associated with increased STAT1 phosphorylation due to impaired nuclear dephosphorylation. 2 Publications
Corresponds to variant rs387906764 [ dbSNP | Ensembl ].
VAR_065934
Natural varianti165 – 1651D → H in IMD31C. 1 Publication
Corresponds to variant rs387906767 [ dbSNP | Ensembl ].
VAR_065935
Natural varianti170 – 1701Y → N in IMD31C. 1 Publication
Corresponds to variant rs387906766 [ dbSNP | Ensembl ].
VAR_065936
Natural varianti174 – 1741C → R in IMD31C. 1 Publication
Corresponds to variant rs387906763 [ dbSNP | Ensembl ].
VAR_065937
Natural varianti179 – 1791N → K in IMD31C; gain of function; increases transactivation activity in response to IFNG. 1 Publication
Corresponds to variant rs587777628 [ dbSNP | Ensembl ].
VAR_075494
Natural varianti201 – 2011K → N in IMD31B; not deleterious in terms of most STAT1 functions; causes abnormal splicing out of exon 8 from most mRNAs thereby decreasing protein levels by approximately 70%. 1 Publication
Corresponds to variant rs587776870 [ dbSNP | Ensembl ].
VAR_065815
Natural varianti202 – 2021M → I in IMD31C. 1 Publication
VAR_065938
Natural varianti202 – 2021M → V in IMD31C. 1 Publication
Corresponds to variant rs387906762 [ dbSNP | Ensembl ].
VAR_065939
Natural varianti267 – 2671A → V in IMD31C. 2 Publications
Corresponds to variant rs387906759 [ dbSNP | Ensembl ].
VAR_065940
Natural varianti271 – 2711Q → P in IMD31C. 1 Publication
Corresponds to variant rs387906768 [ dbSNP | Ensembl ].
VAR_065941
Natural varianti274 – 2741R → Q in IMD31C; gain of function; increases STAT1 phosphorylation due to impaired nuclear dephosphorylation; increases transactivation activity in response to IFNG. 2 Publications
Corresponds to variant rs387906760 [ dbSNP | Ensembl ].
VAR_065942
Natural varianti274 – 2741R → W in IMD31C; gain of function; increases phosphorylation in response to IFNG, IFNA and IL27 due to a loss of dephosphorylation. 3 Publications
Corresponds to variant rs387906758 [ dbSNP | Ensembl ].
VAR_065943
Natural varianti278 – 2781K → E in IMD31C; gain of function; increases phosphorylation in response to IFNG and IFNA due to a loss of dephosphorylation. 1 Publication
VAR_075495
Natural varianti285 – 2851Q → R in IMD31C; gain of function; increases transactivation activity in response to IFNG. 1 Publication
Corresponds to variant rs587777629 [ dbSNP | Ensembl ].
VAR_075496
Natural varianti286 – 2861K → I in IMD31C. 1 Publication
Corresponds to variant rs387906761 [ dbSNP | Ensembl ].
VAR_065944
Natural varianti288 – 2881T → A in IMD31C. 1 Publication
Corresponds to variant rs387906765 [ dbSNP | Ensembl ].
VAR_065945
Natural varianti298 – 2981K → N in IMD31C; gain of function; increases basal STAT1 phosphorylation levels which are 10-20 fold higher than controls after IFNG stimulation. 1 Publication
VAR_075497
Natural varianti320 – 3201E → Q in IMD31A; affects the DNA-binding activity of the protein. 1 Publication
Corresponds to variant rs137852680 [ dbSNP | Ensembl ].
VAR_065816
Natural varianti384 – 3841G → D in IMD31C; gain of function; increases phosphorylation in response to IFNG and IFNA due to a loss of dephosphorylation. 1 Publication
Corresponds to variant rs796065052 [ dbSNP | Ensembl ].
VAR_075498
Natural varianti385 – 3851T → M in IMD31C; gain of function; increases phosphorylation in response to IFNG, IFNA and IL27 due to a loss of dephosphorylation. 2 Publications
Corresponds to variant rs587777630 [ dbSNP | Ensembl ].
VAR_075499
Natural varianti463 – 4631Q → H in IMD31A; affects the DNA-binding activity of the protein. 1 Publication
Corresponds to variant rs137852679 [ dbSNP | Ensembl ].
VAR_065817
Natural varianti491 – 4911P → A in a breast cancer sample; somatic mutation. 1 Publication
VAR_036001
Natural varianti600 – 6001L → P in IMD31B; found in an infant who died of a viral-like illness associated with complete STAT1 deficiency. 1 Publication
Corresponds to variant rs137852678 [ dbSNP | Ensembl ].
VAR_018265
Natural varianti637 – 6371K → E in IMD31A; affects both phosphorylation and DNA-binding activity; results in impaired STAT1-mediated cellular response to IFN-gamma and interleukin-27. 1 Publication
Corresponds to variant rs587777705 [ dbSNP | Ensembl ].
VAR_068713
Natural varianti673 – 6731K → R in IMD31A; impairs tyrosine phosphorylation; results in impaired STAT1-mediated cellular response to IFN-gamma and interleukin-27. 1 Publication
Corresponds to variant rs587777704 [ dbSNP | Ensembl ].
VAR_068714
Natural varianti701 – 7011Y → C in IMD31B; disrupts transactivation activity in response to IFNG. 1 Publication
VAR_075500
Natural varianti706 – 7061L → S in IMD31A; loss of GAF and ISGF3 activation; impairs the nuclear accumulation of GAF but not of ISGF3 in heterozygous cells stimulated by IFNs; affects phosphorylation of the protein. 2 Publications
Corresponds to variant rs137852677 [ dbSNP | Ensembl ].
VAR_018266

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei713 – 75038Missing in isoform Beta. 2 PublicationsVSP_006282Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M97935 mRNA. Translation: AAB64012.1.
M97936 mRNA. No translation available.
GU211347 mRNA. Translation: ADA59516.1.
AY865620 Genomic DNA. Translation: AAW56072.1.
AK292604 mRNA. Translation: BAF85293.1.
AK315002 mRNA. Translation: BAG37497.1.
CR749636 mRNA. Translation: CAH18430.1.
BT007241 mRNA. Translation: AAP35905.1.
AC067945 Genomic DNA. Translation: AAY24183.1.
CH471058 Genomic DNA. Translation: EAX10850.1.
CH471058 Genomic DNA. Translation: EAX10851.1.
CH471058 Genomic DNA. Translation: EAX10852.1.
CH471058 Genomic DNA. Translation: EAX10855.1.
BC002704 mRNA. Translation: AAH02704.1.
U18662 Genomic DNA. No translation available.
U18663 Genomic DNA. No translation available.
U18664 Genomic DNA. No translation available.
U18665 Genomic DNA. No translation available.
U18666 Genomic DNA. No translation available.
U18667 Genomic DNA. No translation available.
U18668 Genomic DNA. No translation available.
U18669 Genomic DNA. No translation available.
U18670 Genomic DNA. No translation available.
CCDSiCCDS2309.1. [P42224-1]
CCDS42793.1. [P42224-2]
PIRiA46159.
RefSeqiNP_009330.1. NM_007315.3. [P42224-1]
NP_644671.1. NM_139266.2. [P42224-2]
XP_006712781.1. XM_006712718.1. [P42224-1]
UniGeneiHs.642990.
Hs.743244.

Genome annotation databases

EnsembliENST00000361099; ENSP00000354394; ENSG00000115415. [P42224-1]
ENST00000392322; ENSP00000376136; ENSG00000115415. [P42224-2]
ENST00000409465; ENSP00000386244; ENSG00000115415. [P42224-1]
GeneIDi6772.
KEGGihsa:6772.
UCSCiuc002usj.3. human. [P42224-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs
STAT1base

STAT1 mutation db

Wikipedia

STAT1 entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M97935 mRNA. Translation: AAB64012.1.
M97936 mRNA. No translation available.
GU211347 mRNA. Translation: ADA59516.1.
AY865620 Genomic DNA. Translation: AAW56072.1.
AK292604 mRNA. Translation: BAF85293.1.
AK315002 mRNA. Translation: BAG37497.1.
CR749636 mRNA. Translation: CAH18430.1.
BT007241 mRNA. Translation: AAP35905.1.
AC067945 Genomic DNA. Translation: AAY24183.1.
CH471058 Genomic DNA. Translation: EAX10850.1.
CH471058 Genomic DNA. Translation: EAX10851.1.
CH471058 Genomic DNA. Translation: EAX10852.1.
CH471058 Genomic DNA. Translation: EAX10855.1.
BC002704 mRNA. Translation: AAH02704.1.
U18662 Genomic DNA. No translation available.
U18663 Genomic DNA. No translation available.
U18664 Genomic DNA. No translation available.
U18665 Genomic DNA. No translation available.
U18666 Genomic DNA. No translation available.
U18667 Genomic DNA. No translation available.
U18668 Genomic DNA. No translation available.
U18669 Genomic DNA. No translation available.
U18670 Genomic DNA. No translation available.
CCDSiCCDS2309.1. [P42224-1]
CCDS42793.1. [P42224-2]
PIRiA46159.
RefSeqiNP_009330.1. NM_007315.3. [P42224-1]
NP_644671.1. NM_139266.2. [P42224-2]
XP_006712781.1. XM_006712718.1. [P42224-1]
UniGeneiHs.642990.
Hs.743244.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1BF5X-ray2.90A136-710[»]
1YVLX-ray3.00A/B1-683[»]
2KA6NMR-B710-750[»]
3WWTX-ray2.00A1-126[»]
ProteinModelPortaliP42224.
SMRiP42224. Positions 1-750.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112649. 146 interactions.
DIPiDIP-46140N.
IntActiP42224. 68 interactions.
MINTiMINT-120840.
STRINGi9606.ENSP00000354394.

Chemistry

BindingDBiP42224.
ChEMBLiCHEMBL6101.

PTM databases

iPTMnetiP42224.
PhosphoSiteiP42224.
SwissPalmiP42224.

Polymorphism and mutation databases

BioMutaiSTAT1.
DMDMi2507413.

Proteomic databases

EPDiP42224.
MaxQBiP42224.
PaxDbiP42224.
PeptideAtlasiP42224.
PRIDEiP42224.

Protocols and materials databases

DNASUi6772.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000361099; ENSP00000354394; ENSG00000115415. [P42224-1]
ENST00000392322; ENSP00000376136; ENSG00000115415. [P42224-2]
ENST00000409465; ENSP00000386244; ENSG00000115415. [P42224-1]
GeneIDi6772.
KEGGihsa:6772.
UCSCiuc002usj.3. human. [P42224-1]

Organism-specific databases

CTDi6772.
GeneCardsiSTAT1.
HGNCiHGNC:11362. STAT1.
HPAiCAB004049.
HPA000931.
HPA000982.
MalaCardsiSTAT1.
MIMi600555. gene.
613796. phenotype.
614162. phenotype.
614892. phenotype.
neXtProtiNX_P42224.
Orphaneti391487. Autoimmune enteropathy and endocrinopathy-susceptibility to chronic infections syndrome.
1334. Chronic mucocutaneous candidosis.
319595. Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency.
391311. Susceptibility to viral and mycobacterial infections.
PharmGKBiPA36183.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3667. Eukaryota.
ENOG410XPN8. LUCA.
GeneTreeiENSGT00760000119236.
HOVERGENiHBG055669.
InParanoidiP42224.
KOiK11220.
OMAiWYNMLTT.
OrthoDBiEOG091G03O3.
PhylomeDBiP42224.
TreeFamiTF318648.

Enzyme and pathway databases

ReactomeiR-HSA-1059683. Interleukin-6 signaling.
R-HSA-1169408. ISG15 antiviral mechanism.
R-HSA-1433557. Signaling by SCF-KIT.
R-HSA-1839117. Signaling by cytosolic FGFR1 fusion mutants.
R-HSA-186763. Downstream signal transduction.
R-HSA-877300. Interferon gamma signaling.
R-HSA-877312. Regulation of IFNG signaling.
R-HSA-909733. Interferon alpha/beta signaling.
R-HSA-912694. Regulation of IFNA signaling.
R-HSA-982772. Growth hormone receptor signaling.
SignaLinkiP42224.
SIGNORiP42224.

Miscellaneous databases

ChiTaRSiSTAT1. human.
EvolutionaryTraceiP42224.
GeneWikiiSTAT1.
GenomeRNAii6772.
PMAP-CutDBP42224.
PROiP42224.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000115415.
CleanExiHS_STAT1.
ExpressionAtlasiP42224. baseline and differential.
GenevisibleiP42224. 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.
IPR022752. STAT1_TAZ2-bd_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. 1 hit.
PfamiPF00017. SH2. 1 hit.
PF12162. STAT1_TAZ2bind. 1 hit.
PF01017. STAT_alpha. 1 hit.
PF02864. STAT_bind. 1 hit.
PF02865. STAT_int. 1 hit.
[Graphical view]
SMARTiSM00964. 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 nameiSTAT1_HUMAN
AccessioniPrimary (citable) accession number: P42224
Secondary accession number(s): A8K989
, B2RCA0, D2KFR8, D3DPI7, Q53S88, Q53XW4, Q68D00, Q9UDL5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1997
Last modified: September 7, 2016
This is version 200 of the entry and version 2 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 2
    Human chromosome 2: 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.