AC T01492
XX
ID T01492
XX
DT 09.05.1995 (created); ewi.
DT 17.11.2014 (updated); hna.
CO Copyright (C), QIAGEN.
XX
FA STAT1alpha
XX
SY ISGF3alpha p91; Signal Transducer and Activator of Transcription 1 p91; STAT91.
XX
OS human, Homo sapiens
OC eukaryota; animalia; metazoa; chordata; vertebrata; tetrapoda; mammalia; eutheria; primates
XX
GE G004625 STAT1; HGNC: STAT1.
XX
CL C0039; STAT; 6.2.1.0.1.1.
XX
SZ 750 AA; 87.3 kDa (cDNA) (calc.), 91 kDa (SDS)
XX
SQ MSQWYELQQLDSKFLEQVHQLYDDSFPMEIRQYLAQWLEKQDWEHAANDVSFATIRFHDL
SQ LSQLDDQYSRFSLENNFLLQHNIRKSKRNLQDNFQEDPIQMSMIIYSCLKEERKILENAQ
SQ RFNQAQSGNIQSTVMLDKQKELDSKVRNVKDKVMCIEHEIKSLEDLQDEYDFKCKTLQNR
SQ EHETNGVAKSDQKQEQLLLKKMYLMLDNKRKEVVHKIIELLNVTELTQNALINDELVEWK
SQ RRQQSACIGGPPNACLDQLQNWFTIVAESLQQVRQQLKKLEELEQKYTYEHDPITKNKQV
SQ LWDRTFSLFQQLIQSSFVVERQPCMPTHPQRPLVLKTGVQFTVKLRLLVKLQELNYNLKV
SQ KVLFDKDVNERNTVKGFRKFNILGTHTKVMNMEESTNGSLAAEFRHLQLKEQKNAGTRTN
SQ EGPLIVTEELHSLSFETQLCQPGLVIDLETTSLPVVVISNVSQLPSGWASILWYNMLVAE
SQ PRNLSFFLTPPCARWAQLSEVLSWQFSSVTKRGLNVDQLNMLGEKLLGPNASPDGLIPWT
SQ RFCKENINDKNFPFWLWIESILELIKKHLLPLWNDGCIMGFISKERERALLKDQQPGTFL
SQ LRFSESSREGAITFTWVERSQNGGEPDFHAVEPYTKKELSAVTFPDIIRNYKVMAAENIP
SQ ENPLKYLYPNIDKDHAFGKYYSRPKEAPEPMELDGPKGTGYIKTELISVSEVHPSRLQTT
SQ DNLLPMSPEEFDEVSRIVGSVEFDSMMNTV
XX
SC edited Swiss-Prot #P42224
XX
FT 1 131 
Stat dimer interaction domain [21].
FT 2 122 
PF02865; STAT protein, protein interaction domain.
FT 69 374 
PF00478; IMP dehydrogenase / GMP reductase domain.
FT 136 315 
PF01017; STAT protein, all-alpha domain.
FT 317 567 
PF02864; STAT protein, DNA binding domain.
FT 403 508 
DNA-binding specificity determining domain [6].
FT 573 651 
PF00017; SH2 domain.
FT 573 670 
PS50001; SH2.
FT 712 750 
missing in STAT1beta [8].
XX
SF tyrosine-phosphorylation;
SF subunit of ISGF-3alpha;
SF gene comprises 24 exons, exon 23 and exon 24 encode the STAT1alpha-specific C-terminus [7];
SF the same gene encodes STAT1beta (STAT84) [7] [8];
SF homo- and heterodimerization of the phosphorylated form through SH2 and phosphotyrosine [18];
SF DNA-binding domain is predicted to comprise an alpha-helix and a beta-sheet [6];
SF heterodimers STAT1alpha/beta could cooperatively bind to the tandem DNA sites and directly interact with each other forming tetramers [21];
SF N-terminal part, aa 1-131, is involved in the interactins between Stat dimers [21];
XX
FF activator;
FF mediates transduction of tyrosine phosphorylation signals to induction of interferon-stimulated gene expression [4];
FF most likely identical with SIF (c-sis-inducible factor) [13] [20] [1];
FF inducible by IFN-alpha [2] [4] [9] [11];
FF inducible by IFN-gamma [5] [10] [11];
FF inducible by growth factors and hormones [16];
FF Tyr-phosphorylation promotes formation of ISGF3 complex [2] [4] [9];
FF Tyr-phosphorylation promotes nuclear translocation [10];
FF modifying protein kinases are Jak1 (triggered by IFN-alpha and -gamma) and Jak2 (responding to IFN-gamma) [13] [14];
FF additional phosphorylation at Ser-727, possibly by MAP kinase, causes maximal transcriptional activation [19];
FF this is also stimulated by cytokines and growth factors [19];
FF cooperates with IRF-1 for IFN-gamma-dependent gene induction in myeloid cells [25];
FF PRL induces binding of STAT1alpha to the IRF-1 promoter, Tyr308 and Tyr382 of PRLR are crucial for this induction [26];
XX
IN T08887 brca1-isoform1; human, Homo sapiens.
IN T04074 brca1; human, Homo sapiens.
IN T34781 ErbB1; human, Homo sapiens.
IN T21984 p300; human, Homo sapiens.
IN T01492 STAT1alpha; human, Homo sapiens.
IN T01575 STAT1alpha; mouse, Mus musculus.
IN T01573 STAT1beta; human, Homo sapiens.
IN T01494 STAT2; human, Homo sapiens.
XX
MX M00224 V$STAT1_01.
MX M00492 V$STAT1_02.
MX M00496 V$STAT1_03.
MX M07064 V$STAT1_Q4.
MX M01823 V$STAT1_Q6.
MX M00223 V$STAT_01.
MX M00777 V$STAT_Q6.
XX
BS R23951.
BS R14657.
BS R14658.
BS R25433.
BS R25882.
BS R60664.
BS R13559.
BS R25885.
BS R26338.
BS R26291.
BS R04223.
BS R13215.
BS R13241.
BS R25843.
BS R64910.
BS R26474.
BS R14714.
BS R15735.
BS R04650.
BS R04651.
XX
DR TRANSPATH: MO000019506.
DR TRANSCOMPEL: C00300.
DR TRANSCOMPEL: C00386.
DR EMBL: M97935;
DR UniProtKB: P42224-1;
XX
RN [1]; RE0000446.
RX PUBMED: 1901265.
RA Decker T., Lew D. J., Mirkowitch J., Darnell J. E.
RT Cytoplasmic activation of GAF, an IFN-gamma-regulated DNA-binding factor
RL EMBO J. 10:927-932 (1991).
RN [2]; RE0002946.
RX PUBMED: 1280824.
RA Gutch M. J., Daly C., Reich N. C.
RT Tyrosine phosphorylation is required for activation of an alpha interferon-stimulated transcription factor
RL Proc. Natl. Acad. Sci. USA 89:11411-11415 (1992).
RN [3]; RE0003468.
RX PUBMED: 8306959.
RA Pine R., Canova A., Schindler C.
RT Tyrosine phosphorylated p91 binds to a single element in the ISGF2/IRF-1 promoter to mediate induction by IFNalpha and IFNgamma, and is likely to autoregulate the p91 gene
RL EMBO J. 13:158-167 (1994).
RN [4]; RE0003478.
RX PUBMED: 1638633.
RA Fu X.-Y.
RT A transcription factor with SH2 and SH3 domains is directly activated by an interferon alpha-induced cytoplasmic protein tyrosine kinase(s)
RL Cell 70:323-335 (1992).
RN [5]; RE0003479.
RX PUBMED: 7680098.
RA Igarashi K., David M., Finbloom D., Larner A. C.
RT In vitro activation of the transcription factor gamma interferon activation factor by gamma interferon: evidence for a tyrosine phosphatase/kinase signalling cascade
RL Mol. Cell. Biol. 13:1634- 1640 (1993).
RN [6]; RE0003481.
RX PUBMED: 7774815.
RA Horvath C. M., Wen Z., Darnell jr J. E.
RT A STAT protein domain that determines DNA sequence recognition suggests a novel DNA-binding domain
RL Genes Dev. 9:984-994 (1995).
RN [7]; RE0003482.
RX PUBMED: 7885841.
RA Yan R., Qureshi S., Zhong Z., Wen Z., Darnell jr J. E.
RT The genomic structure of the STAT genes: multiple exons in coincident sites in Stat1 and Stat2
RL Nucleic Acids Res. 23:459-463 (1995).
RN [8]; RE0003489.
RX PUBMED: 1502203.
RA Schindler C., Fu X.-Y., Improta T., Aebersold R., Darnell J. E.
RT Protein of ISGF3: One gene encodes the 91-and 84-kDa ISGF-3 proteins that are activated by interferon alpha
RL Proc. Natl. Acad. Sci. USA 89:7836-7839 (1992).
RN [9]; RE0003490.
RX PUBMED: 1496401.
RA Schindler C., Shuai K., Prezioso V. R., Darnell J. E.
RT Interferon-dependent tyrosine phosphorylation of a latent cytoplasmic transcription factor
RL Science 257:809-813 (1992).
RN [10]; RE0003491.
RX PUBMED: 1281555.
RA Shuai K., Schindler C., Prezioso V. R., Darnell J. E.
RT Activation of transcription by IFN-gamma tyrosine phosphorylation of a 91-kDa DNA binding protein
RL Science 258:1808-1812 (1992).
RN [11]; RE0003492.
RX PUBMED: 7688129.
RA Khan K. D., Shuai K., Lindwall G., Maher S. E., Darnell J. E., Bothwell A. L. M.
RT Induction of the Ly-6A/E gene by interferon alpha/beta and gamma requires a DNA element to which a tyrosine phosphorylated 91-kDa protein binds
RL Proc. Natl. Acad. Sci. USA 90:6806-6810 (1993).
RN [12]; RE0003493.
RX PUBMED: 8378773.
RA Larner A. C., David M., Feldman G. M., Igarashi K.-I., Hackett R. H., Webb D. S. A., Sweitzer S.M., Petricoin III E. F., Finbloom D. S.
RT Tyrosine phosphorylation of DNA binding proteins by multiple cytokines
RL Science 261:1730-1733 (1993).
RN [13]; RE0003495.
RX PUBMED: 7504784.
RA Shuai K., Ziemiecki A., Wilks A. F., Harpur A. G., Sadowski H. B., Gilman M. Z., Darnell J. E.
RT Polypeptide signalling to the nucleus through tyrosine phosphorylation of Jak and Stat proteins
RL Nature 366:580-583 (1993).
RN [14]; RE0003496.
RX PUBMED: 7690989.
RA Shuai K., Stark G. R., Kerr I. M., Darnell J. E.
RT A single phosphotyrosine residue of Stat91 required for gene activation by interferon-gamma
RL Science 261:1744-1746 (1993).
RN [15]; RE0003498.
RX PUBMED: 8378775.
RA Silvennoinen O., Schindler C., Schlessinger J., Levy D. E.
RT Ras-independent growth factor signaling by transcription factor tyrosine phosphorylation
RL Science 261:1736-1744 (1993).
RN [16]; RE0003499.
RX PUBMED: 8397445.
RA Sadowski H. B., Shuai K., Darnell J. E., Gilman M. Z.
RT A common nuclear signal transduction pathway activated by growth factor and cytokine receptors
RL Science 261:1739-1744 (1993).
RN [17]; RE0003504.
RX PUBMED: 7545930.
RA Zhong Z., Wen Z., Darnell J. E.
RT Stat3 and Stat4: members of the family of signal transducers and activators of transcription
RL Proc. Natl. Acad. Sci. USA 91:4806-4810 (1994).
RN [18]; RE0003505.
RX PUBMED: 7510216.
RA Shuai K., Horvath C. M., Huang L. H. T., Qureshi S. A., Cowburn D., Darnell J. E.
RT Interferon activation of the transcription factor Stat91 involves dimerization through SH2-phosphotyrosyl peptide interactions
RL Cell 76:821-828 (1994).
RN [19]; RE0003507.
RX PUBMED: 7543024.
RA Wen Z., Zhong Z., Darnell J. E.
RT Maximal activation of transcription by Stat1 and Stat3 requires both tyrosine and serine phosophorylation
RL Cell 82:241-250 (1995).
RN [20]; RE0003523.
RX PUBMED: 8321202.
RA Kanno Y., Kozak C. A., Schindler C., Driggers P. H., Ennist D. L., Gleason S. L., Darnell J. E., Ozato K.
RT The genomic structure of the murine ICSBP gene reveals the presence of the gamma-interferon-responsive element, to which an ISGF3alpha subunit (or similar) molecule binds
RL Mol. Cell. Biol. 13:3951-3963 (1993).
RN [21]; RE0006012.
RX PUBMED: 8896455.
RA Vinkemeier U., Cohen S. L., Moarefi I., Chait B. T., Kuriyan J., Darnell jr J. E.
RT DNA binding of in vitro activated Stat1alpha, Stat1beta and truncated Stat1: interaction between NH2-terminal domains stabilizes binding of two dimers to tandem DNA sites
RL EMBO J. 15:5616-5626 (1996).
RN [22]; RE0010993.
RX PUBMED: 7569900.
RA David M., Petricoin III E., Benjamin C., Pine R., Weber M. J., Larner A. C.
RT Requirement for MAP kinase (ERK2) activity in interferon alpha- and interferon beta-stimulated gene expression through STAT proteins.
RL Science 269:1721-1723 (1995).
RN [23]; RE0012679.
RX PUBMED: 8605876.
RA Yan H., Krishnan K., Greenlund A. C., Gupta S., Lim J. T. E., Schreiber R. D., Schindler C. W., Krolewski J. J.
RT Phosphorylated interferon-alpha receptor 1 subunit (IFNaR1) acts as a docking site for the latent form of the 113 kDa STAT2 protein
RL EMBO J. 15:1064-1074 (1996).
RN [24]; RE0017512.
RX PUBMED: 10792030.
RA Ouchi T., Lee S. W., Ouchi M., Aaronson S. A., Horvath C. M.
RT Collaboration of signal transducer and activator of transcription 1 (STAT1) and BRCA1 in differential regulation of IFN-gamma target genes.
RL Proc. Natl. Acad. Sci. USA 97:5208-5213 (2000).
RN [25]; RE0023149.
RX PUBMED: 11781315.
RA Kumatori A., Yang D., Suzuki S., Nakamura M.
RT Cooperation of STAT-1 and IRF-1 in interferon-gamma-induced transcription of the gp91(phox) gene.
RL J. Biol. Chem. 277:9103-9111 (2002).
RN [26]; RE0024921.
RX PUBMED: 9259325.
RA Wang Y., O'Neal K. D., Yu-Lee L.
RT Multiple prolactin (PRL) receptor cytoplasmic residues and Stat1 mediate PRL signaling to the interferon regulatory factor-1 promoter.
RL Mol. Endocrinol. 11:1353-1364 (1997).
RN [27]; RE0026427.
RX PUBMED: 10748192.
RA Gamero A. M., Larner A. C.
RT Signaling via the T cell antigen receptor induces phosphorylation of stat1 on serine 727
RL J. Biol. Chem. 275:16574-8 (2000).
RN [28]; RE0027727.
RX PUBMED: 10558875.
RA Runge D. M., Runge D., Foth H., Strom S. C., Michalopoulos G. K.
RT STAT 1alpha/1beta, STAT 3 and STAT 5: expression and association with c-MET and EGF-receptor in long-term cultures of human hepatocytes.
RL Biochem. Biophys. Res. Commun. 265:376-81 (1999).
RN [29]; RE0028451.
RX PUBMED: 9452495.
RA Ratovitski E. A., Kotzbauer P. T., Milbrandt J., Lowenstein C. J., Burrow C. R.
RT Midkine induces tumor cell proliferation and binds to a high affinity signaling receptor associated with JAK tyrosine kinases.
RL J. Biol. Chem. 273:3654-60 (1998).
RN [30]; RE0033178.
RX PUBMED: 14645718.
RA Nusinzon I., Horvath C. M.
RT Interferon-stimulated transcription and innate antiviral immunity require deacetylase activity and histone deacetylase 1.
RL Proc. Natl. Acad. Sci. USA 100:14742-7 (2003).
RN [31]; RE0049934.
RX PUBMED: 15825084.
RA Lin W., Choe W. H., Hiasa Y., Kamegaya Y., Blackard J. T., Schmidt E. V., Chung R. T.
RT Hepatitis C virus expression suppresses interferon signaling by degrading STAT1.
RL Gastroenterology 128:1034-1041 (2005).
RN [32]; RE0052420.
RX PUBMED: 8961260.
RA Liu X., Robinson G. W., Hennighausen L.
RT Activation of Stat5a and Stat5b by tyrosine phosphorylation is tightly linked to mammary gland differentiation.
RL Mol. Endocrinol. 10:1496-1506 (1996).
RN [33]; RE0055106.
RX PUBMED: 18635538.
RA Kubota T., Matsuoka M., Chang T. H., Tailor P., Sasaki T., Tashiro M., Kato A., Ozato K.
RT Virus infection triggers SUMOylation of IRF3 and IRF7, leading to the negative regulation of type I interferon gene expression.
RL J. Biol. Chem. 283:25660-25670 (2008).
RN [34]; RE0064873.
RX PUBMED: 18566411.
RA Liu X., Ye L., Bai Y., Mojidi H., Simister N. E., Zhu X.
RT Activation of the JAK/STAT-1 signaling pathway by IFN-gamma can down-regulate functional expression of the MHC class I-related neonatal Fc receptor for IgG.
RL J. Immunol. 181:449-463 (2008).
RN [35]; RE0065261.
RX PUBMED: 17404288.
RA Waiboci L. W., Ahmed C. M., Mujtaba M. G., Flowers L. O., Martin J. P., Haider M. I., Johnson H. M.
RT Both the suppressor of cytokine signaling 1 (SOCS-1) kinase inhibitory region and SOCS-1 mimetic bind to JAK2 autophosphorylation site: implications for the development of a SOCS-1 antagonist.
RL J. Immunol. 178:5058-5068 (2007).
RN [36]; RE0065562.
RX PUBMED: 11972023.
RA Nair J. S., DaFonseca C. J., Tjernberg A., Sun W., Darnell JE J. r., Chait B. T., Zhang J. J.
RT Requirement of Ca2+ and CaMKII for Stat1 Ser-727 phosphorylation in response to IFN-gamma.
RL Proc. Natl. Acad. Sci. USA 99:5971-5976 (2002).
RN [37]; RE0066328.
RX PUBMED: 17167270.
RA Buttmann M., Berberich-Siebelt F., Serfling E., Rieckmann P.
RT Interferon-beta is a potent inducer of interferon regulatory factor-1/2-dependent IP-10/CXCL10 expression in primary human endothelial cells.
RL J. Vasc. Res. 44:51-60 (2007).
RN [38]; RE0066398.
RX PUBMED: 7531704.
RA Velazquez L., Mogensen K. E., Barbieri G., Fellous M., Uze G., Pellegrini S.
RT Distinct domains of the protein tyrosine kinase tyk2 required for binding of interferon-alpha/beta and for signal transduction.
RL J. Biol. Chem. 270:3327-3334 (1995).
RN [39]; RE0066436.
RX PUBMED: 8617715.
RA David M., Petricoin E 3. r. d., Larner A. C.
RT Activation of protein kinase A inhibits interferon induction of the Jak/Stat pathway in U266 cells.
RL J. Biol. Chem. 271:4585-4588 (1996).
RN [40]; RE0068701.
RX PUBMED: 20833730.
RA Clarke D. L., Clifford R. L., Jindarat S., Proud D., Pang L., Belvisi M., Knox A. J.
RT TNFalpha and IFNgamma synergistically enhance transcriptional activation of CXCL10 in human airway smooth muscle cells via STAT-1, NF-kappaB, and the transcriptional coactivator CREB-binding protein.
RL J. Biol. Chem. 285:29101-29110 (2010).
RN [41]; RE0068847.
RX PUBMED: 15850793.
RA Brand S., Zitzmann K., Dambacher J., Beigel F., Olszak T., Vlotides G., Eichhorst S. T., Goke B., Diepolder H., Auernhammer C. J.
RT SOCS-1 inhibits expression of the antiviral proteins 2',5'-OAS and MxA induced by the novel interferon-lambdas IL-28A and IL-29.
RL Biochem. Biophys. Res. Commun. 331:543-548 (2005).
RN [42]; RE0069456.
RX PUBMED: 19404962.
RA Kok S. H., Hong C. Y., Kuo M. Y., Wang C. C., Hou K. L., Lin Y. T., Galson D. L., Lin S. K.
RT Oncostatin M-induced CCL2 transcription in osteoblastic cells is mediated by multiple levels of STAT-1 and STAT-3 signaling: an implication for the pathogenesis of arthritis.
RL Arthritis Rheum. 60:1451-1462 (2009).
RN [43]; RE0070000.
RX PUBMED: 12517937.
RA Dondi E., Rogge L., Lutfalla G., Uze G., Pellegrini S.
RT Down-modulation of responses to type I IFN upon T cell activation.
RL J. Immunol. 170:749-756 (2003).
XX
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