STAT1
entrez
6772
canonical
uniprot
P42224
canonical
ensembl
ENSG00000115415
resolver
ensp
ENSP00000354394
resolver
ensp
ENSP00000376136
resolver
ensp
ENSP00000438703
resolver
ensp
ENSP00000500982
resolver
ensp
ENSP00000501145
resolver
ensp
ENSP00000513583
resolver
ensp
ENSP00000513587
resolver
ensp
ENSP00000526985
resolver
ensp
ENSP00000620439
resolver
ensp
ENSP00000620440
resolver
ensp
ENSP00000706532
resolver
enst
ENST00000673777
resolver
enst
ENST00000673942
resolver
enst
ENST00000698142
resolver
genesymbol
STAT1
resolver
hgnc
HGNC:11362
resolver
uniprot
A0A669KB68
resolver
uniprot
A0A8V8TN81
resolver
uniprot
A8K989
resolver
uniprot
B2RCA0
resolver
uniprot
D2KFR8
resolver
uniprot
D3DPI7
resolver
uniprot
Q53S88
resolver
uniprot
Q53XW4
resolver
uniprot
Q68D00
resolver
uniprot
Q9UDL5
resolver
uniprot_entry
A0A669KB68_HUMAN
resolver
uniprot_entry
A0A8V8TN81_HUMAN
resolver
uniprot_entry
STAT1_HUMAN
resolver
uniprot_sec
A8K989
resolver
uniprot_sec
B2RCA0
resolver
uniprot_sec
D2KFR8
resolver
uniprot_sec
D3DPI7
resolver
uniprot_sec
Q53S88
resolver
uniprot_sec
Q53XW4
resolver
uniprot_sec
Q68D00
resolver
uniprot_sec
Q9UDL5
resolver
amino_acid_sequence
MSQWYELQQLDSKFLEQVHQLYDDSFPMEIRQYLAQWLEKQDWEHAANDVSFATIRFHDLLSQLDDQYSRFSLENNFLLQHNIRKSKRNLQDNFQEDPIQMSMIIYSCLKEERKILENAQRFNQAQSGNIQSTVMLDKQKELDSKVRNVKDKVMCIEHEIKSLEDLQDEYDFKCKTLQNREHETNGVAKSDQKQEQLLLKKMYLMLDNKRKEVVHKIIELLNVTELTQNALINDELVEWKRRQQSACIGGPPNACLDQLQNWFTIVAESLQQVRQQLKKLEELEQKYTYEHDPITKNKQVLWDRTFSLFQQLIQSSFVVERQPCMPTHPQRPLVLKTGVQFTVKLRLLVKLQELNYNLKVKVLFDKDVNERNTVKGFRKFNILGTHTKVMNMEESTNGSLAAEFRHLQLKEQKNAGTRTNEGPLIVTEELHSLSFETQLCQPGLVIDLETTSLPVVVISNVSQLPSGWASILWYNMLVAEPRNLSFFLTPPCARWAQLSEVLSWQFSSVTKRGLNVDQLNMLGEKLLGPNASPDGLIPWTRFCKENINDKNFPFWLWIESILELIKKHLLPLWNDGCIMGFISKERERALLKDQQPGTFLLRFSESSREGAITFTWVERSQNGGEPDFHAVEPYTKKELSAVTFPDIIRNYKVMAAENIPENPLKYLYPNIDKDHAFGKYYSRPKEAPEPMELDGPKGTGYIKTELISVSEVHPSRLQTTDNLLPMSPEEFDEVSRIVGSVEFDSMMNTV
uniprot
proteins
disease_involvement
DISEASE: Immunodeficiency 31B (IMD31B) [MIM:613796]: A disorder characterized by susceptibility to severe mycobacterial and viral infections. Affected individuals can develop disseminated infections and die of viral illness. {ECO:0000269|PubMed:12590259, ECO:0000269|PubMed:20841510, ECO:0000269|PubMed:23709754}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Immunodeficiency 31A (IMD31A) [MIM:614892]: A 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. {ECO:0000269|PubMed:11452125, ECO:0000269|PubMed:16934001, ECO:0000269|PubMed:22573496}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Immunodeficiency 31C (IMD31C) [MIM:614162]: A 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. {ECO:0000269|PubMed:21714643, ECO:0000269|PubMed:21727188, ECO:0000269|PubMed:23709754, ECO:0000269|PubMed:25288569, ECO:0000269|PubMed:26514428}. Note=The disease is caused by variants 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). {ECO:0000269|PubMed:21714643}.
uniprot
proteins
function
FUNCTION: Signal transducer and transcription activator that mediates cellular responses to interferons (IFNs), cytokine KITLG/SCF and other cytokines and other growth factors (PubMed:12764129, PubMed:12855578, PubMed:15322115, PubMed:23940278, PubMed:34508746, PubMed:35568036, PubMed:9724754, PubMed:32814877). 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, PubMed:35568036). 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 (PubMed:28753426, PubMed:35568036). 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 (PubMed:8156998). Becomes activated in response to KITLG/SCF and KIT signaling (PubMed:15526160). May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4 (PubMed:19088846). Following bacterial lipopolysaccharide (LPS)-induced TLR4 endocytosis, phosphorylated at Thr-749 by IKBKB which promotes binding of STAT1 to the 5'-TTTGAGGC-3' sequence in the ARID5A promoter, resulting in transcriptional activation of ARID5A and subsequent ARID5A-mediated stabilization of IL6 (PubMed:32209697). Phosphorylation at Thr-749 also promotes binding of STAT1 to the 5'-TTTGAGTC-3' sequence in the IL12B promoter and activation of IL12B transcription (PubMed:32209697). Involved in food tolerance in small intestine: associates with the Gasdermin-D, p13 cleavage product (13 kDa GSDMD) and promotes transcription of CIITA, inducing type 1 regulatory T (Tr1) cells in upper small intestine (By similarity). {ECO:0000250|UniProtKB:P42225, ECO:0000269|PubMed:12764129, ECO:0000269|PubMed:12855578, ECO:0000269|PubMed:15322115, ECO:0000269|PubMed:19088846, ECO:0000269|PubMed:23940278, ECO:0000269|PubMed:26479788, ECO:0000269|PubMed:28753426, ECO:0000269|PubMed:32209697, ECO:0000269|PubMed:32814877, ECO:0000269|PubMed:34508746, ECO:0000269|PubMed:35568036, ECO:0000269|PubMed:8156998, ECO:0000269|PubMed:9724754, ECO:0000303|PubMed:15526160}.
uniprot
proteins
mass_dalton
87335
uniprot
proteins
mutagenesis
MUTAGEN 110; /note="K->R: Sumoylated. Loss of RNF220-mediated ubiquitination."; /evidence="ECO:0000269|PubMed:12764129, ECO:0000269|PubMed:32814877"; MUTAGEN 114; /note="K->A: No effect on IFN-alpha-induced STAT1 phosphorylation and nuclear translocation."; /evidence="ECO:0000269|PubMed:28753426"; MUTAGEN 175; /note="K->A: No effect on IFN-alpha-induced STAT1 phosphorylation and nuclear translocation."; /evidence="ECO:0000269|PubMed:28753426"; MUTAGEN 296; /note="K->A: No effect on IFN-alpha-induced STAT1 phosphorylation and nuclear translocation."; /evidence="ECO:0000269|PubMed:28753426"; MUTAGEN 366; /note="K->A: No effect on IFN-alpha-induced STAT1 phosphorylation and nuclear translocation."; /evidence="ECO:0000269|PubMed:28753426"; MUTAGEN 525; /note="K->A: Strongly reduced IFN-alpha-induced STAT1 phosphorylation and nuclear translocation. Does not affect ability to homodimerize."; /evidence="ECO:0000269|PubMed:28753426"; MUTAGEN 636..637; /note="KK->AA: No effect on IFN-alpha-induced STAT1 phosphorylation and nuclear translocation."; /evidence="ECO:0000269|PubMed:28753426"; MUTAGEN 656..658; /note="AEN->CEC: Enhances STAT1 nuclear translocation and interferon (IFN)-stimulated gene (ISG) expression in response to IFN-beta stimulation. Reduces viral load in infected cultured cells."; /evidence="ECO:0000269|PubMed:26479788"; MUTAGEN 657; /note="E->Q: Loss of ADP-ribosylation and increased Tyr-701 phosphorylation; when associated with Q-705."; /evidence="ECO:0000269|PubMed:27796300"; MUTAGEN 665; /note="K->A: No effect on IFN-alpha-induced STAT1 phosphorylation and nuclear translocation."; /evidence="ECO:0000269|PubMed:28753426"; MUTAGEN 701; /note="Y->A: No effect on transcriptional activation of ARID5A."; /evidence="ECO:0000269|PubMed:32209697"; MUTAGEN 701; /note="Y->E: Not phosphorylated at S-708 upon IFNB induction."; /evidence="ECO:0000269|PubMed:17897103, ECO:0000269|PubMed:22065572"; MUTAGEN 701; /note="Y->F: No effect on basal sumoylation. Enhances sumoylation in the presence of MAPK stimulation. Phosphorylated at S-708 upon IFNB induction."; /evidence="ECO:0000269|PubMed:17897103, ECO:0000269|PubMed:22065572"; MUTAGEN 703; /note="K->R: Abolishes sumoylation by SUMO1. Increased IFN-gamma-mediated transactivation."; /evidence="ECO:0000269|PubMed:12764129, ECO:0000269|PubMed:12855578"; MUTAGEN 704; /note="T->A: No effect on transcriptional activation of ARID5A."; /evidence="ECO:0000269|PubMed:32209697"; MUTAGEN 705; /note="E->Q: Loss of ADP-ribosylation and increased Tyr-701 phosphorylation; when associated with Q-657."; /evidence="ECO:0000269|PubMed:27796300"; MUTAGEN 708; /note="S->A: Phosphorylated at Y-701 upon IFNB induction. No effect on transcriptional activation of ARID5A."; /evidence="ECO:0000269|PubMed:22065572, ECO:0000269|PubMed:32209697"; MUTAGEN 708; /note="S->D: Not phosphorylated at Y-701 upon IFNB induction."; /evidence="ECO:0000269|PubMed:22065572"; MUTAGEN 710; /note="S->A: No effect on transcriptional activation of ARID5A."; /evidence="ECO:0000269|PubMed:32209697"; MUTAGEN 715; /note="S->A: No effect on transcriptional activation of ARID5A."; /evidence="ECO:0000269|PubMed:32209697"; MUTAGEN 719; /note="T->A: No effect on transcriptional activation of ARID5A."; /evidence="ECO:0000269|PubMed:32209697"; MUTAGEN 720; /note="T->A: No effect on transcriptional activation of ARID5A."; /evidence="ECO:0000269|PubMed:32209697"; MUTAGEN 724; /note="L->A: Impaired phosphorylation at S-727."; /evidence="ECO:0000269|PubMed:16257975"; MUTAGEN 727; /note="S->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. No effect on transcriptional activation of ARID5A."; /evidence="ECO:0000269|PubMed:15322115, ECO:0000269|PubMed:17897103, ECO:0000269|PubMed:22065572, ECO:0000269|PubMed:32209697"; MUTAGEN 727; /note="S->D: No change in enhancement of MAPK-induced sumoylation. Basal interaction with PIAS1. Interaction with PIAS1 increased on MAPK stimulation."; /evidence="ECO:0000269|PubMed:15322115, ECO:0000269|PubMed:17897103, ECO:0000269|PubMed:22065572"; MUTAGEN 727; /note="S->E: No change in enhancement of MAPK-induced sumoylation."; /evidence="ECO:0000269|PubMed:15322115, ECO:0000269|PubMed:17897103, ECO:0000269|PubMed:22065572"; MUTAGEN 735; /note="S->A: No effect on transcriptional activation of ARID5A."; /evidence="ECO:0000269|PubMed:32209697"; MUTAGEN 740; /note="S->A: No effect on transcriptional activation of ARID5A."; /evidence="ECO:0000269|PubMed:32209697"; MUTAGEN 745; /note="S->A: No effect on transcriptional activation of ARID5A."; /evidence="ECO:0000269|PubMed:32209697"; MUTAGEN 749; /note="T->A: Reduced transcriptional activation of ARID5A and IL12B. No effect on nuclear translocation. Abolishes IKKB-mediated phosphorylation at this position."; /evidence="ECO:0000269|PubMed:32209697, ECO:0000269|PubMed:38621137"; MUTAGEN 749; /note="T->E: Phosphomimetic mutant; no effect on transcriptional activation of ARID5A or IL12B. No effect on nuclear translocation."; /evidence="ECO:0000269|PubMed:32209697
uniprot
proteins
post_translational_modification
PTM: Deubiquitinated by USP13; leading to STAT1 stabilization and positive regulation of type I and type II IFN signalings. {ECO:0000269|PubMed:23940278}.; PTM: Phosphorylated on tyrosine and serine residues in response to a variety of cytokines/growth hormones including IFN-alpha, IFN-gamma, PDGF and EGF (PubMed:26479788, PubMed:28753426). Activated KIT promotes phosphorylation on tyrosine residues and subsequent translocation to the nucleus (PubMed:21135090). Upon EGF stimulation, phosphorylation on Tyr-701 (lacking in beta form) by JAK1, JAK2 or TYK2 promotes dimerization and subsequent translocation to the nucleus (PubMed:28753426, PubMed:7657660). Growth hormone (GH) activates STAT1 signaling only via JAK2 (PubMed:7657660). Tyrosine phosphorylated in response to constitutively activated FGFR1, FGFR2, FGFR3 and FGFR4 (PubMed:17561467, PubMed:19088846). Phosphorylation on Ser-727 by several kinases including MAPK14, ERK1/2, CAMK2/CAMKII and CK2 in response to IFN-gamma stimulation, is required for maximal transcriptional activity (PubMed:15322115, PubMed:16799645, PubMed:17897103, PubMed:7543024). Phosphorylated on Ser-727 by CAMK2/CAMKII in response to IFN-gamma stimulation and calcium mobilization, promoting activity (PubMed:11972023, PubMed:16257975). Phosphorylated by CAMK2/CAMKII in response to IFN-beta stimulation and calcium mobilization in epithelial cells, promoting activity (PubMed:35568036). Phosphorylation on Ser-727 promotes sumoylation though increasing interaction with PIAS (PubMed:17897103). Phosphorylation on Ser-727 by PRKCD induces apoptosis in response to DNA-damaging agents (PubMed:15322115). Phosphorylated on tyrosine residues when PTK2/FAK1 is activated; most likely this is catalyzed by a SRC family kinase (PubMed:11278462). Dephosphorylation on tyrosine residues by PTPN2 negatively regulates interferon-mediated signaling (PubMed:12138178). 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 (PubMed:22065572). Phosphorylation at Tyr-701 and Ser-708 are mutually exclusive, phosphorylation at Ser-708 requires previous dephosphorylation of Tyr-701 (PubMed:22065572). Phosphorylation at Thr-749 by IKBKB/IKKB promotes transcriptional activation of ARID5A and IL12B by STAT1 (PubMed:32209697). Phosphorylation at Thr-749 restricts interferon signaling and anti-inflammatory responses and promotes innate inflammatory responses (By similarity). {ECO:0000250|UniProtKB:P42225, ECO:0000269|PubMed:11278462, ECO:0000269|PubMed:11972023, ECO:0000269|PubMed:12138178, ECO:0000269|PubMed:15322115, ECO:0000269|PubMed:16257975, ECO:0000269|PubMed:16799645, ECO:0000269|PubMed:17561467, ECO:0000269|PubMed:17897103, ECO:0000269|PubMed:19088846, ECO:0000269|PubMed:21135090, ECO:0000269|PubMed:22065572, ECO:0000269|PubMed:26479788, ECO:0000269|PubMed:28753426, ECO:0000269|PubMed:32209697, ECO:0000269|PubMed:35568036, ECO:0000269|PubMed:7543024, ECO:0000269|PubMed:7657660}.; PTM: 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. {ECO:0000269|PubMed:15322115, ECO:0000269|PubMed:17897103, ECO:0000269|PubMed:21135090, ECO:0000269|PubMed:22065572, ECO:0000269|PubMed:7543024}.; PTM: ISGylated. {ECO:0000269|PubMed:16139798}.; PTM: Mono-ADP-ribosylated at Glu-657 and Glu-705 by PARP14; ADP-ribosylation prevents phosphorylation at Tyr-701 (PubMed:27796300). However, the role of ADP-ribosylation in the prevention of phosphorylation has been called into question and the lack of phosphorylation may be due to sumoylation of Lys-703 (PubMed:29858569). {ECO:0000269|PubMed:27796300, ECO:0000305|PubMed:29858569}.; PTM: Monomethylated at Lys-525 by SETD2; monomethylation is necessary for phosphorylation at Tyr-701, translocation into the nucleus and activation of the antiviral defense. {ECO:0000269|PubMed:28753426}.; PTM: 'Lys-63'-linked polyubiquitinated at Lys-110 by RNF220; leading to enhanced STAT1 activation and innate immune responses. {ECO:0000269|PubMed:32814877}.; PTM: (Microbial infection) Ubiquitinated by Herpes simplex virus 2 E3 ubiquitin ligase ICP22. {ECO:0000269|PubMed:32699158}.
uniprot
proteins
protein_family
Transcription factor STAT family
uniprot
proteins
pubmed
10702714
uniprot
proteins
pubmed
11278462
uniprot
proteins
pubmed
11442634
uniprot
proteins
pubmed
11452125
uniprot
proteins
pubmed
11972023
uniprot
proteins
pubmed
12138178
uniprot
proteins
pubmed
12590259
uniprot
proteins
pubmed
12764129
uniprot
proteins
pubmed
12855578
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
1502203
uniprot
proteins
pubmed
15140960
uniprot
proteins
pubmed
15322115
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15526160
uniprot
proteins
pubmed
15815621
uniprot
proteins
pubmed
15825084
uniprot
proteins
pubmed
16139798
uniprot
proteins
pubmed
16257975
uniprot
proteins
pubmed
1638633
uniprot
proteins
pubmed
16799645
uniprot
proteins
pubmed
16934001
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
17311277
uniprot
proteins
pubmed
17561467
uniprot
proteins
pubmed
17686504
uniprot
proteins
pubmed
17897103
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
18721752
uniprot
proteins
pubmed
19088846
uniprot
proteins
pubmed
19136629
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20841510
uniprot
proteins
pubmed
21135090
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21714643
uniprot
proteins
pubmed
21724836
uniprot
proteins
pubmed
21727188
uniprot
proteins
pubmed
22065572
uniprot
proteins
pubmed
22223895
uniprot
proteins
pubmed
22383882
uniprot
proteins
pubmed
22573496
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23709754
uniprot
proteins
pubmed
23940278
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25114211
uniprot
proteins
pubmed
25288569
uniprot
proteins
pubmed
26479788
uniprot
proteins
pubmed
26514428
uniprot
proteins
pubmed
27796300
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
28753426
uniprot
proteins
pubmed
29858569
uniprot
proteins
pubmed
32209697
uniprot
proteins
pubmed
32581091
uniprot
proteins
pubmed
32699158
uniprot
proteins
pubmed
32814877
uniprot
proteins
pubmed
34319780
uniprot
proteins
pubmed
34508746
uniprot
proteins
pubmed
35568036
uniprot
proteins
pubmed
38621137
uniprot
proteins
pubmed
7543024
uniprot
proteins
pubmed
7657660
uniprot
proteins
pubmed
7885841
uniprot
proteins
pubmed
8156998
uniprot
proteins
pubmed
8605877
uniprot
proteins
pubmed
9121453
uniprot
proteins
pubmed
9630226
uniprot
proteins
pubmed
9724754
uniprot
proteins
pubmed
9989503
uniprot
proteins
sequence_length
750
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15322115, ECO:0000269|PubMed:26479788, ECO:0000269|PubMed:27796300, ECO:0000269|PubMed:28753426, ECO:0000269|PubMed:32209697}. Nucleus {ECO:0000269|PubMed:15322115, ECO:0000269|PubMed:26479788, ECO:0000269|PubMed:28753426, ECO:0000269|PubMed:32209697}. Note=Translocated into the nucleus upon tyrosine phosphorylation and dimerization, in response to IFN-gamma and signaling by activated FGFR1, FGFR2, FGFR3 or FGFR4 (PubMed:15322115). Monomethylation at Lys-525 is required for phosphorylation at Tyr-701 and translocation into the nucleus (PubMed:28753426). Translocates into the nucleus in response to interferon-beta stimulation (PubMed:26479788). {ECO:0000269|PubMed:15322115, ECO:0000269|PubMed:26479788, ECO:0000269|PubMed:28753426}.
uniprot
proteins