STAT1 (signal transducer and activator of transcription 1)

Gene

• Entrez ID: 6772
• Gene name: Signal transducer and activator of transcription 1
• Gene symbol: STAT1
• Synonyms: CANDF7, IMD31A, IMD31B, IMD31C, ISGF-3, STAT91
• Chromosome: 2
• Chromosome location: 2q32.2
• Summary: The protein encoded by this gene is a member of the STAT protein family. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. The protein encoded by this gene can be activated by various ligands including interferon-alpha, interferon-gamma, EGF, PDGF and IL6. This protein mediates the expression of a variety of genes, which is thought to be important for cell viability in response to different cell stimuli and pathogens. The protein plays an important role in immune responses to viral, fungal and mycobacterial pathogens. Mutations in this gene are associated with Immunodeficiency 31B, 31A, and 31C. [provided by RefSeq, Jun 2020]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs41473544	C>T	Likely-benign, pathogenic, uncertain-significance	Coding sequence variant, missense variant, non coding transcript variant
rs56228116	C>T	Likely-benign, conflicting-interpretations-of-pathogenicity	Intron variant
rs137852677	A>G	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs137852678	A>G	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs137852679	C>A,T	Pathogenic	Non coding transcript variant, synonymous variant, coding sequence variant, missense variant
rs137852680	C>G	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs387906758	G>A,C	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs387906759	G>A	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs387906760	C>T	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs387906761	T>A	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs387906762	T>C	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs387906763	A>G	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs387906764	T>C	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs387906765	T>C	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs387906766	A>T	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs387906767	C>G	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs387906768	T>G	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs587776713	TC>-	Pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant
rs587776714	->T	Pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant
rs587776870	C>A	Pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs587777628	G>T	Pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs587777629	T>C	Pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs587777630	G>A	Pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs587777704	T>C	Pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs587777705	T>C	Pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs755837357	TTCT>-	Likely-pathogenic	Frameshift variant, coding sequence variant, non coding transcript variant
rs778254943	G>A	Likely-pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs796065052	C>T	Pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs863223398	T>C	Pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs886043118	T>-	Pathogenic	Coding sequence variant, frameshift variant, non coding transcript variant
rs1064794955	C>A	Likely-pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs1085307649	G>T	Likely-pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs1341038926	->C	Likely-pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant
rs1553494436	A>C	Likely-pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs1553495184	T>C	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs1553496850	T>C	Likely-pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs1553497886	T>A	Likely-pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs1559011859	T>G	Likely-pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs1559019204	C>T	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs1574636674	G>A	Likely-pathogenic	Non coding transcript variant, genic downstream transcript variant, coding sequence variant, missense variant
rs1574640523	C>A	Likely-pathogenic	Non coding transcript variant, stop gained, coding sequence variant
rs1574648928	C>G	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs1574653439	A>G	Likely-pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs1574657735	A>C	Likely-pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs1574657750	C>T	Likely-pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs1574657762	A>C	Likely-pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs1574672718	C>G	Likely-pathogenic	Non coding transcript variant, coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT000626	hsa-miR-145-5p	qRT-PCR, Luciferase reporter assay, Western blot, Microarray	20098684
MIRT021229	hsa-miR-146a-5p	Microarray	20110513
MIRT021229	hsa-miR-146a-5p	Luciferase reporter assay, qRT-PCR, Western blot	23890093
MIRT021229	hsa-miR-146a-5p	Luciferase reporter assay	23698745
MIRT021229	hsa-miR-146a-5p	qRT-PCR, Western blot	25889446
MIRT021229	hsa-miR-146a-5p	qRT-PCR	28077577
MIRT025278	hsa-miR-34a-5p	Proteomics	21566225
MIRT040456	hsa-miR-615-3p	CLASH	23622248
MIRT640316	hsa-miR-653-5p	HITS-CLIP	23824327
MIRT640317	hsa-miR-203b-3p	HITS-CLIP	23824327
MIRT640318	hsa-miR-7158-3p	HITS-CLIP	23824327
MIRT640319	hsa-miR-4693-5p	HITS-CLIP	23824327
MIRT640320	hsa-miR-5009-3p	HITS-CLIP	23824327
MIRT640321	hsa-miR-501-5p	HITS-CLIP	23824327
MIRT640322	hsa-miR-1183	HITS-CLIP	23824327
MIRT640323	hsa-miR-500a-5p	HITS-CLIP	23824327
MIRT640324	hsa-miR-605-5p	HITS-CLIP	23824327
MIRT731704	hsa-miR-140-5p	Luciferase reporter assay, Western blot	26780721
MIRT733223	hsa-miR-150-5p	Luciferase reporter assay, qRT-PCR, Western blot	26025667
MIRT733224	hsa-miR-223-3p	Luciferase reporter assay, qRT-PCR, Western blot	26025667
MIRT733720	hsa-miR-203a-3p	Immunoblot, Luciferase reporter assay, Microarray, qRT-PCR	27705947
MIRT734262	hsa-miR-450a-5p	Luciferase reporter assay, Microarray, qRT-PCR	28407302
MIRT734272	hsa-miR-155-5p	Luciferase reporter assay, Western blot	28418858

Transcription factors

Transcription factor	Regulation	Reference
BRCA1	Activation	17374731
CIITA	Unknown	12052885
CREB5	Repression	21132541
EGF	Unknown	11939722
GTF3A	Unknown	12364590
MCM5	Unknown	11248027
NR3C1	Repression	17016446
PIAS1	Unknown	17940994;19136629
RELA	Unknown	25040843
REST	Repression	23598529
STAT2	Unknown	21498520
STAT3	Activation	22693070
STAT6	Repression	19440213
TP53	Unknown	12364590

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	ISS
GO:0000785	Component	Chromatin	IDA	18035482
GO:0000785	Component	Chromatin	ISA
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA	21873635
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA	18035482, 21268089
GO:0000979	Function	RNA polymerase II core promoter sequence-specific DNA binding	IDA	23386060, 28753426
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IBA	21873635
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IDA	21268089
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0001937	Process	Negative regulation of endothelial cell proliferation	IMP	16585190
GO:0002053	Process	Positive regulation of mesenchymal cell proliferation	ISS
GO:0002230	Process	Positive regulation of defense response to virus by host	IGI	26479788
GO:0002230	Process	Positive regulation of defense response to virus by host	IMP	26479788
GO:0003340	Process	Negative regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis	ISS
GO:0003690	Function	Double-stranded DNA binding	IDA	9630226
GO:0003700	Function	DNA-binding transcription factor activity	IDA	10973496, 23386060
GO:0005164	Function	Tumor necrosis factor receptor binding	IPI	10848577
GO:0005515	Function	Protein binding	IPI	8156998, 8605877, 8662591, 9121453, 9881977, 10848577, 11238845, 12070153, 12788789, 12867595, 15780933, 15825084, 16189514, 16273093, 16306601, 16531398, 16940534, 17275127, 17596301, 17923090, 20195357, 21903422, 21988832, 24065129, 24360797, 24658140, 25241761, 25416956, 25609649
GO:0005634	Component	Nucleus	IDA	10692450, 10973496, 15825084, 16306601, 21268089, 23386060, 28753426
GO:0005634	Component	Nucleus	IDA	26479788
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005730	Component	Nucleolus	IDA
GO:0005737	Component	Cytoplasm	IDA	10692450, 10973496, 15825084, 17275127, 23386060, 26479788, 27796300, 28753426
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	TAS
GO:0006952	Process	Defense response	IBA	21873635
GO:0007221	Process	Positive regulation of transcription of Notch receptor target	TAS
GO:0007259	Process	Receptor signaling pathway via JAK-STAT	IBA	21873635
GO:0007259	Process	Receptor signaling pathway via JAK-STAT	IDA	22002246
GO:0008015	Process	Blood circulation	ISS
GO:0010742	Process	Macrophage derived foam cell differentiation	IDA	26504087
GO:0016032	Process	Viral process	IEA
GO:0016525	Process	Negative regulation of angiogenesis	IMP	16585190
GO:0019221	Process	Cytokine-mediated signaling pathway	IBA	21873635
GO:0019221	Process	Cytokine-mediated signaling pathway	TAS
GO:0019899	Function	Enzyme binding	IPI	22002246, 26479788
GO:0030424	Component	Axon	ISS
GO:0030425	Component	Dendrite	ISS
GO:0032727	Process	Positive regulation of interferon-alpha production	IDA	28753426
GO:0032991	Component	Protein-containing complex	IDA	26479788
GO:0033209	Process	Tumor necrosis factor-mediated signaling pathway	IDA	10848577
GO:0034097	Process	Response to cytokine	ISS
GO:0035035	Function	Histone acetyltransferase binding	IPI	26479788
GO:0035257	Function	Nuclear hormone receptor binding	IPI	26504087
GO:0035456	Process	Response to interferon-beta	IMP	24882218
GO:0035458	Process	Cellular response to interferon-beta	IMP	18035482
GO:0038113	Process	Interleukin-9-mediated signaling pathway	TAS
GO:0038114	Process	Interleukin-21-mediated signaling pathway	TAS
GO:0042127	Process	Regulation of cell population proliferation	IBA	21873635
GO:0042393	Function	Histone binding	IPI	26479788
GO:0042802	Function	Identical protein binding	IPI	8605877, 9630226
GO:0042803	Function	Protein homodimerization activity	IDA	9630226, 28753426
GO:0042981	Process	Regulation of apoptotic process	TAS	12108949
GO:0043124	Process	Negative regulation of I-kappaB kinase/NF-kappaB signaling	IMP	10848577
GO:0043434	Process	Response to peptide hormone	IBA	21873635
GO:0043434	Process	Response to peptide hormone	ISS
GO:0043542	Process	Endothelial cell migration	IMP	16585190
GO:0044389	Function	Ubiquitin-like protein ligase binding	IPI	26479788
GO:0045296	Function	Cadherin binding	HDA	25468996
GO:0045648	Process	Positive regulation of erythrocyte differentiation	IMP	28283061
GO:0045893	Process	Positive regulation of transcription, DNA-templated	IDA	10973496
GO:0045893	Process	Positive regulation of transcription, DNA-templated	IGI	26479788
GO:0045893	Process	Positive regulation of transcription, DNA-templated	IMP	26479788
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IMP	18035482
GO:0046725	Process	Negative regulation by virus of viral protein levels in host cell	IMP	15825084
GO:0048471	Component	Perinuclear region of cytoplasm	IDA	17275127
GO:0048661	Process	Positive regulation of smooth muscle cell proliferation	ISS
GO:0051591	Process	Response to cAMP	ISS
GO:0051607	Process	Defense response to virus	IDA	28753426
GO:0060333	Process	Interferon-gamma-mediated signaling pathway	IDA	21268089
GO:0060333	Process	Interferon-gamma-mediated signaling pathway	IMP	26479788
GO:0060333	Process	Interferon-gamma-mediated signaling pathway	ISS
GO:0060333	Process	Interferon-gamma-mediated signaling pathway	TAS
GO:0060334	Process	Regulation of interferon-gamma-mediated signaling pathway	TAS
GO:0060337	Process	Type I interferon signaling pathway	IBA	21873635
GO:0060337	Process	Type I interferon signaling pathway	IDA	23386060
GO:0060337	Process	Type I interferon signaling pathway	ISS
GO:0060337	Process	Type I interferon signaling pathway	TAS
GO:0061326	Process	Renal tubule development	IMP	20861313
GO:0070102	Process	Interleukin-6-mediated signaling pathway	TAS
GO:0070106	Process	Interleukin-27-mediated signaling pathway	TAS
GO:0070491	Function	Repressing transcription factor binding	IPI	23386060
GO:0070757	Process	Interleukin-35-mediated signaling pathway	TAS
GO:0071346	Process	Cellular response to interferon-gamma	IDA	23386060
GO:0072136	Process	Metanephric mesenchymal cell proliferation involved in metanephros development	ISS
GO:0072162	Process	Metanephric mesenchymal cell differentiation	ISS
GO:0072308	Process	Negative regulation of metanephric nephron tubule epithelial cell differentiation	ISS
GO:1990841	Function	Promoter-specific chromatin binding	IDA	26479788

Other IDs

• MIM: 600555
• HGNC: 11362
• e!Ensembl: ENSG00000115415

Protein

• UniProt ID: P42224
• Protein name: Signal transducer and activator of transcription 1-alpha/beta (Transcription factor ISGF-3 components p91/p84)
• Protein function: 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 (PubMed:28753426). 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 (PubMed:26479788). 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.
• PDB: 1BF5, 1YVL, 2KA6, 3WWT
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF02865	STAT_int	2 → 120	STAT protein, protein interaction domain	Domain
  PF01017	STAT_alpha	139 → 309	STAT protein, all-alpha domain	Family
  PF02864	STAT_bind	321 → 458	STAT protein, DNA binding domain	Domain
  PF00017	SH2	573 → 657	SH2 domain	Domain
  PF12162	STAT1_TAZ2bind	715 → 739	STAT1 TAZ2 binding domain	Motif

• Sequence:

  MSQWYELQQLDSKFLEQVHQLYDDSFPMEIRQYLAQWLEKQDWEHAANDVSFATIRFHDL
  LSQLDDQYSRFSLENNFLLQHNIRKSKRNLQDNFQEDPIQMSMIIYSCLKEERKILENAQ
  RFNQAQSGNIQSTVMLDKQKELDSKVRNVKDKVMCIEHEIKSLEDLQDEYDFKCKTLQNR
  EHETNGVAKSDQKQEQLLLKKMYLMLDNKRKEVVHKIIELLNVTELTQNALINDELVEWK
  RRQQSACIGGPPNACLDQLQNWFTIVAESLQQVRQQLKKLEELEQKYTYEHDPITKNKQV
  LWDRTFSLFQQLIQSSFVVERQPCMPTHPQRPLVLKTGVQFTVKLRLLVKLQELNYNLKV
  KVLFDKDVNERNTVKGFRKFNILGTHTKVMNMEESTNGSLAAEFRHLQLKEQKNAGTRTN
  EGPLIVTEELHSLSFETQLCQPGLVIDLETTSLPVVVISNVSQLPSGWASILWYNMLVAE
  PRNLSFFLTPPCARWAQLSEVLSWQFSSVTKRGLNVDQLNMLGEKLLGPNASPDGLIPWT
  RFCKENINDKNFPFWLWIESILELIKKHLLPLWNDGCIMGFISKERERALLKDQQPGTFL
  LRFSESSREGAITFTWVERSQNGGEPDFHAVEPYTKKELSAVTFPDIIRNYKVMAAENIP
  ENPLKYLYPNIDKDHAFGKYYSRPKEAPEPMELDGPKGTGYIKTELISVSEVHPSRLQTT
  DNLLPMSPEEFDEVSRIVGSVEFDSMMNTV

• Sequence length: 750