ID TYK2_HUMAN Reviewed; 1187 AA.
AC P29597; Q6QB10; Q96CH0;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 07-DEC-2004, sequence version 3.
DT 27-MAR-2024, entry version 236.
DE RecName: Full=Non-receptor tyrosine-protein kinase TYK2;
DE EC=2.7.10.2 {ECO:0000269|PubMed:10542297, ECO:0000269|PubMed:7526154};
GN Name=TYK2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS PHE-362 AND SER-684.
RX PubMed=2216457;
RA Firmbach-Kraft I., Byers M., Shows T., Dalla-Favera R., Krolewski J.J.;
RT "TYK2, prototype of a novel class of non-receptor tyrosine kinase genes.";
RL Oncogene 5:1329-1336(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS HIS-4; HIS-197; PHE-362;
RP SER-363 AND SER-684.
RG SeattleSNPs variation discovery resource;
RL Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 289-1187.
RX PubMed=1386289; DOI=10.1016/0092-8674(92)90105-l;
RA Velazquez L., Fellous M., Stark G.R., Pellegrini S.;
RT "A protein tyrosine kinase in the interferon alpha/beta signaling
RT pathway.";
RL Cell 70:313-322(1992).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1007-1162, AND TISSUE SPECIFICITY.
RX PubMed=2156206;
RA Krolewski J.J., Lee R., Eddy R., Shows T.B., Dalla-Favera R.;
RT "Identification and chromosomal mapping of new human tyrosine kinase
RT genes.";
RL Oncogene 5:277-282(1990).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1025-1082.
RX PubMed=2247464; DOI=10.1073/pnas.87.22.8913;
RA Partanen J., Maekelae T.P., Alitalo R., Lehvaeslaiho H., Alitalo K.;
RT "Putative tyrosine kinases expressed in K-562 human leukemia cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:8913-8917(1990).
RN [7]
RP FUNCTION, AND PHOSPHORYLATION.
RX PubMed=8232552; DOI=10.1038/366129a0;
RA Mueller M., Briscoe J., Laxton C., Guschin D., Ziemiecki A.,
RA Silvennoinen O., Harpur A.G., Barbieri G., Witthuhn B.A., Schindler C.;
RT "The protein tyrosine kinase JAK1 complements defects in interferon-
RT alpha/beta and -gamma signal transduction.";
RL Nature 366:129-135(1993).
RN [8]
RP FUNCTION.
RX PubMed=7813427; DOI=10.1002/j.1460-2075.1994.tb06932.x;
RA Abramovich C., Shulman L.M., Ratovitski E., Harroch S., Tovey M., Eid P.,
RA Revel M.;
RT "Differential tyrosine phosphorylation of the IFNAR chain of the type I
RT interferon receptor and of an associated surface protein in response to
RT IFN-alpha and IFN-beta.";
RL EMBO J. 13:5871-5877(1994).
RN [9]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=7526154; DOI=10.1128/mcb.14.12.8133-8142.1994;
RA Colamonici O., Yan H., Domanski P., Handa R., Smalley D., Mullersman J.,
RA Witte M., Krishnan K., Krolewski J.;
RT "Direct binding to and tyrosine phosphorylation of the alpha subunit of the
RT type I interferon receptor by p135tyk2 tyrosine kinase.";
RL Mol. Cell. Biol. 14:8133-8142(1994).
RN [10]
RP FUNCTION.
RX PubMed=7657660; DOI=10.1074/jbc.270.35.20775;
RA Quelle F.W., Thierfelder W., Witthuhn B.A., Tang B., Cohen S., Ihle J.N.;
RT "Phosphorylation and activation of the DNA binding activity of purified
RT Stat1 by the Janus protein-tyrosine kinases and the epidermal growth factor
RT receptor.";
RL J. Biol. Chem. 270:20775-20780(1995).
RN [11]
RP FUNCTION, AND PHOSPHORYLATION.
RX PubMed=7638186; DOI=10.1073/pnas.92.16.7307;
RA Bacon C.M., Petricoin E.F. III, Ortaldo J.R., Rees R.C., Larner A.C.,
RA Johnston J.A., O'Shea J.J.;
RT "Interleukin 12 induces tyrosine phosphorylation and activation of STAT4 in
RT human lymphocytes.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:7307-7311(1995).
RN [12]
RP FUNCTION, MUTAGENESIS OF LYS-930; TYR-1054; TYR-1055; TYR-1145 AND
RP TYR-1176, AND PHOSPHORYLATION AT TYR-1054 AND TYR-1055.
RX PubMed=8702790; DOI=10.1074/jbc.271.34.20494;
RA Gauzzi M.C., Velazquez L., McKendry R., Mogensen K.E., Fellous M.,
RA Pellegrini S.;
RT "Interferon-alpha-dependent activation of Tyk2 requires phosphorylation of
RT positive regulatory tyrosines by another kinase.";
RL J. Biol. Chem. 271:20494-20500(1996).
RN [13]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=10542297; DOI=10.1074/jbc.274.45.32507;
RA Rani M.R., Leaman D.W., Han Y., Leung S., Croze E., Fish E.N., Wolfman A.,
RA Ransohoff R.M.;
RT "Catalytically active TYK2 is essential for interferon-beta-mediated
RT phosphorylation of STAT3 and interferon-alpha receptor-1 (IFNAR-1) but not
RT for activation of phosphoinositol 3-kinase.";
RL J. Biol. Chem. 274:32507-32511(1999).
RN [14]
RP INTERACTION WITH PAPILLOMAVIRUS VIRUS PROTEIN E6 (MICROBIAL INFECTION).
RX PubMed=10523853; DOI=10.1038/sj.onc.1202960;
RA Li S., Labrecque S., Gauzzi M.C., Cuddihy A.R., Wong A.H., Pellegrini S.,
RA Matlashewski G.J., Koromilas A.E.;
RT "The human papilloma virus (HPV)-18 E6 oncoprotein physically associates
RT with Tyk2 and impairs Jak-STAT activation by interferon-alpha.";
RL Oncogene 18:5727-5737(1999).
RN [15]
RP FUNCTION IN CELL MIGRATION, AND INTERACTION WITH PIK3R1.
RX PubMed=10995743; DOI=10.1074/jbc.m003626200;
RA Kusch A., Tkachuk S., Haller H., Dietz R., Gulba D.C., Lipp M., Dumler I.;
RT "Urokinase stimulates human vascular smooth muscle cell migration via a
RT phosphatidylinositol 3-kinase-Tyk2 interaction.";
RL J. Biol. Chem. 275:39466-39473(2000).
RN [16]
RP INTERACTION WITH JAKMIP1.
RX PubMed=15277531; DOI=10.1074/jbc.m401915200;
RA Steindler C., Li Z., Algarte M., Alcover A., Libri V., Ragimbeau J.,
RA Pellegrini S.;
RT "Jamip1 (marlin-1) defines a family of proteins interacting with Janus
RT kinases and microtubules.";
RL J. Biol. Chem. 279:43168-43177(2004).
RN [17]
RP INVOLVEMENT IN IMD35.
RX PubMed=17088085; DOI=10.1016/j.immuni.2006.09.009;
RA Minegishi Y., Saito M., Morio T., Watanabe K., Agematsu K., Tsuchiya S.,
RA Takada H., Hara T., Kawamura N., Ariga T., Kaneko H., Kondo N., Tsuge I.,
RA Yachie A., Sakiyama Y., Iwata T., Bessho F., Ohishi T., Joh K., Imai K.,
RA Kogawa K., Shinohara M., Fujieda M., Wakiguchi H., Pasic S., Abinun M.,
RA Ochs H.D., Renner E.D., Jansson A., Belohradsky B.H., Metin A., Shimizu N.,
RA Mizutani S., Miyawaki T., Nonoyama S., Karasuyama H.;
RT "Human tyrosine kinase 2 deficiency reveals its requisite roles in multiple
RT cytokine signals involved in innate and acquired immunity.";
RL Immunity 25:745-755(2006).
RN [18]
RP INTERACTION WITH EPSTEIN-BARR VIRUS PROTEIN LMP1 (MICROBIAL INFECTION).
RX PubMed=16987978; DOI=10.1128/jvi.01570-06;
RA Geiger T.R., Martin J.M.;
RT "The Epstein-Barr virus-encoded LMP-1 oncoprotein negatively affects Tyk2
RT phosphorylation and interferon signaling in human B cells.";
RL J. Virol. 80:11638-11650(2006).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-292 AND SER-884, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-292 AND SER-884, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-292 AND SER-499, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [22]
RP FUNCTION.
RX PubMed=29162862; DOI=10.1038/s41598-017-15912-6;
RA Mori R., Wauman J., Icardi L., Van der Heyden J., De Cauwer L., Peelman F.,
RA De Bosscher K., Tavernier J.;
RT "TYK2-induced phosphorylation of Y640 suppresses STAT3 transcriptional
RT activity.";
RL Sci. Rep. 7:15919-15919(2017).
RN [23]
RP INTERACTION WITH EPSTEIN-BARR VIRUS TEGUMENT PROTEIN BGLF2 (MICROBIAL
RP INFECTION).
RX PubMed=32213613; DOI=10.1128/jvi.00258-20;
RA Liu X., Sadaoka T., Krogmann T., Cohen J.I.;
RT "Epstein-Barr Virus (EBV) Tegument Protein BGLF2 Suppresses Type I
RT Interferon Signaling To Promote EBV Reactivation.";
RL J. Virol. 94:0-0(2020).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 888-1182 IN COMPLEX WITH
RP INHIBITOR, AND PHOSPHORYLATION AT TYR-1054.
RX PubMed=20478313; DOI=10.1016/j.jmb.2010.05.020;
RA Chrencik J.E., Patny A., Leung I.K., Korniski B., Emmons T.L., Hall T.,
RA Weinberg R.A., Gormley J.A., Williams J.M., Day J.E., Hirsch J.L.,
RA Kiefer J.R., Leone J.W., Fischer H.D., Sommers C.D., Huang H.C.,
RA Jacobsen E.J., Tenbrink R.E., Tomasselli A.G., Benson T.E.;
RT "Structural and thermodynamic characterization of the TYK2 and JAK3 kinase
RT domains in complex with CP-690550 and CMP-6.";
RL J. Mol. Biol. 400:413-433(2010).
RN [25] {ECO:0007744|PDB:4WOV}
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 575-869, FUNCTION, AND ACTIVITY
RP REGULATION.
RX PubMed=25762719; DOI=10.1074/jbc.m114.619502;
RA Tokarski J.S., Zupa-Fernandez A., Tredup J.A., Pike K., Chang C., Xie D.,
RA Cheng L., Pedicord D., Muckelbauer J., Johnson S.R., Wu S., Edavettal S.C.,
RA Hong Y., Witmer M.R., Elkin L.L., Blat Y., Pitts W.J., Weinstein D.S.,
RA Burke J.R.;
RT "Tyrosine Kinase 2-mediated Signal Transduction in T Lymphocytes Is Blocked
RT by Pharmacological Stabilization of Its Pseudokinase Domain.";
RL J. Biol. Chem. 290:11061-11074(2015).
RN [26] {ECO:0007744|PDB:4OLI}
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 566-1187, PHOSPHORYLATION,
RP ACTIVITY REGULATION, AND MUTAGENESIS OF ASP-1023.
RX PubMed=24843152; DOI=10.1073/pnas.1401180111;
RA Lupardus P.J., Ultsch M., Wallweber H., Bir Kohli P., Johnson A.R.,
RA Eigenbrot C.;
RT "Structure of the pseudokinase-kinase domains from protein kinase TYK2
RT reveals a mechanism for Janus kinase (JAK) autoinhibition.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:8025-8030(2014).
RN [27]
RP VARIANTS [LARGE SCALE ANALYSIS] PHE-362; SER-363; MET-386; SER-684;
RP TRP-703; ARG-732; VAL-928; ALA-1104 AND GLY-1163.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Tyrosine kinase of the non-receptor type involved in numerous
CC cytokines and interferons signaling, which regulates cell growth,
CC development, cell migration, innate and adaptive immunity
CC (PubMed:8232552, PubMed:7813427, PubMed:7657660, PubMed:10995743,
CC PubMed:10542297). Plays both structural and catalytic roles in numerous
CC interleukins and interferons (IFN-alpha/beta) signaling
CC (PubMed:10542297). Associates with heterodimeric cytokine receptor
CC complexes and activates STAT family members including STAT1, STAT3,
CC STAT4 or STAT6 (PubMed:10542297, PubMed:7638186). The heterodimeric
CC cytokine receptor complexes are composed of (1) a TYK2-associated
CC receptor chain (IFNAR1, IL12RB1, IL10RB or IL13RA1), and (2) a second
CC receptor chain associated either with JAK1 or JAK2 (PubMed:7813427,
CC PubMed:10542297, PubMed:7526154, PubMed:25762719). In response to
CC cytokine-binding to receptors, phosphorylates and activates receptors
CC (IFNAR1, IL12RB1, IL10RB or IL13RA1), creating docking sites for STAT
CC members (PubMed:7526154, PubMed:7657660). In turn, recruited STATs are
CC phosphorylated by TYK2 (or JAK1/JAK2 on the second receptor chain),
CC form homo- and heterodimers, translocate to the nucleus, and regulate
CC cytokine/growth factor responsive genes (PubMed:7657660,
CC PubMed:10542297, PubMed:25762719). Negatively regulates STAT3 activity
CC by promototing phosphorylation at a specific tyrosine that differs from
CC the site used for signaling (PubMed:29162862).
CC {ECO:0000269|PubMed:10542297, ECO:0000269|PubMed:10995743,
CC ECO:0000269|PubMed:25762719, ECO:0000269|PubMed:29162862,
CC ECO:0000269|PubMed:7526154, ECO:0000269|PubMed:7638186,
CC ECO:0000269|PubMed:7657660, ECO:0000269|PubMed:7813427,
CC ECO:0000269|PubMed:8232552}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2;
CC Evidence={ECO:0000269|PubMed:10542297, ECO:0000269|PubMed:7526154};
CC -!- ACTIVITY REGULATION: The protein kinase 1 domain (also termed
CC pseudokinase domain) mediates autoinhibition of the TYK2 kinase domain.
CC {ECO:0000269|PubMed:24843152, ECO:0000269|PubMed:25762719}.
CC -!- SUBUNIT: Interacts (via FERM domain) with JAKMIP1 (PubMed:15277531,
CC PubMed:20478313). Interacts with PIK3R1; this interaction is important
CC for cell migration (PubMed:10995743). {ECO:0000269|PubMed:10995743,
CC ECO:0000269|PubMed:15277531, ECO:0000269|PubMed:20478313}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Epstein-Barr virus
CC protein LMP1; this interaction inhibits TYK2-mediated interferon
CC signaling. {ECO:0000269|PubMed:16987978}.
CC -!- SUBUNIT: (Microbial infection) Interacts with papillomavirus-18 protein
CC E6; this interaction impairs JAK-STAT activation by interferon-alpha.
CC {ECO:0000269|PubMed:10523853}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Epstein-Barr virus (EBV)
CC tegument protein BGLF2; this interaction participates in the inhibition
CC of type I IFN signaling by the virus. {ECO:0000269|PubMed:32213613}.
CC -!- INTERACTION:
CC P29597; O95994: AGR2; NbExp=5; IntAct=EBI-1383454, EBI-712648;
CC P29597; Q9ULX6: AKAP8L; NbExp=3; IntAct=EBI-1383454, EBI-357530;
CC P29597; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-1383454, EBI-3867333;
CC P29597; Q13643: FHL3; NbExp=6; IntAct=EBI-1383454, EBI-741101;
CC P29597; A6NEM1: GOLGA6L9; NbExp=3; IntAct=EBI-1383454, EBI-5916454;
CC P29597; P61978: HNRNPK; NbExp=4; IntAct=EBI-1383454, EBI-304185;
CC P29597; P61978-2: HNRNPK; NbExp=3; IntAct=EBI-1383454, EBI-7060731;
CC P29597; P08238: HSP90AB1; NbExp=2; IntAct=EBI-1383454, EBI-352572;
CC P29597; P17181-1: IFNAR1; NbExp=3; IntAct=EBI-1383454, EBI-16099379;
CC P29597; O60674: JAK2; NbExp=2; IntAct=EBI-1383454, EBI-518647;
CC P29597; Q5VWX1: KHDRBS2; NbExp=7; IntAct=EBI-1383454, EBI-742808;
CC P29597; O75525: KHDRBS3; NbExp=3; IntAct=EBI-1383454, EBI-722504;
CC P29597; Q15323: KRT31; NbExp=3; IntAct=EBI-1383454, EBI-948001;
CC P29597; Q6A162: KRT40; NbExp=3; IntAct=EBI-1383454, EBI-10171697;
CC P29597; Q9NQX1-2: PRDM5; NbExp=3; IntAct=EBI-1383454, EBI-12859340;
CC P29597; P52630: STAT2; NbExp=4; IntAct=EBI-1383454, EBI-1546963;
CC P29597; Q05BL1: TP53BP2; NbExp=3; IntAct=EBI-1383454, EBI-11952721;
CC P29597; Q9BUZ4: TRAF4; NbExp=3; IntAct=EBI-1383454, EBI-3650647;
CC -!- TISSUE SPECIFICITY: Observed in all cell lines analyzed. Expressed in a
CC variety of lymphoid and non-lymphoid cell lines.
CC {ECO:0000269|PubMed:2156206}.
CC -!- PTM: Phosphorylated (PubMed:7638186). Phosphorylation by JAK1 at Tyr-
CC 1054 and Tyr-1055 induces kinase activation (PubMed:8232552,
CC PubMed:8702790). {ECO:0000269|PubMed:7638186,
CC ECO:0000269|PubMed:8702790, ECO:0000305|PubMed:8232552}.
CC -!- DISEASE: Immunodeficiency 35 (IMD35) [MIM:611521]: A primary
CC immunodeficiency characterized by recurrent skin abscesses, pneumonia,
CC and highly elevated serum IgE. {ECO:0000269|PubMed:17088085}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. JAK subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC -!- WEB RESOURCE: Name=TYK2base; Note=TYK2 mutation db;
CC URL="http://structure.bmc.lu.se/idbase/TYK2base/";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/tyk2/";
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DR EMBL; X54637; CAA38449.1; -; mRNA.
DR EMBL; AY549314; AAS37680.1; -; Genomic_DNA.
DR EMBL; BC014243; AAH14243.1; -; mRNA.
DR CCDS; CCDS12236.1; -.
DR PIR; S12127; TVHUY2.
DR RefSeq; NP_003322.3; NM_003331.4.
DR RefSeq; XP_011526547.1; XM_011528245.1.
DR PDB; 3LXN; X-ray; 2.50 A; A=888-1182.
DR PDB; 3LXP; X-ray; 1.65 A; A=888-1182.
DR PDB; 3NYX; X-ray; 2.50 A; A=885-1176.
DR PDB; 3NZ0; X-ray; 2.00 A; A=885-1176.
DR PDB; 3ZON; X-ray; 2.15 A; A=541-873.
DR PDB; 4GFO; X-ray; 2.30 A; A=884-1176.
DR PDB; 4GIH; X-ray; 2.00 A; A=885-1176.
DR PDB; 4GII; X-ray; 2.31 A; A=885-1176.
DR PDB; 4GJ2; X-ray; 2.40 A; A=885-1176.
DR PDB; 4GJ3; X-ray; 2.50 A; A=885-1176.
DR PDB; 4GVJ; X-ray; 2.03 A; A=885-1176.
DR PDB; 4OLI; X-ray; 2.80 A; A=566-1187.
DR PDB; 4PO6; X-ray; 1.99 A; A=23-583.
DR PDB; 4PY1; X-ray; 2.16 A; A=888-1182.
DR PDB; 4WOV; X-ray; 1.80 A; A/B=575-869.
DR PDB; 5C01; X-ray; 2.15 A; A/B=556-871.
DR PDB; 5C03; X-ray; 1.90 A; A/B=556-871.
DR PDB; 5F1Z; X-ray; 2.65 A; A=884-1176.
DR PDB; 5F20; X-ray; 2.91 A; A=884-1176.
DR PDB; 5TKD; X-ray; 1.92 A; A/B=575-869.
DR PDB; 5WAL; X-ray; 2.45 A; A=884-1176.
DR PDB; 6AAM; X-ray; 1.98 A; A=888-1182.
DR PDB; 6DBK; X-ray; 2.00 A; A=888-1182.
DR PDB; 6DBM; X-ray; 2.37 A; A=888-1182.
DR PDB; 6NSL; X-ray; 2.15 A; A/B=575-869.
DR PDB; 6NZE; X-ray; 1.96 A; A/B=575-869.
DR PDB; 6NZF; X-ray; 2.39 A; A/B=575-869.
DR PDB; 6NZH; X-ray; 2.73 A; A/B=575-869.
DR PDB; 6NZP; X-ray; 2.35 A; A/B=575-869.
DR PDB; 6NZQ; X-ray; 2.11 A; A/B=575-869.
DR PDB; 6NZR; X-ray; 2.56 A; A/B=575-869.
DR PDB; 6OVA; X-ray; 2.50 A; A=884-1176.
DR PDB; 6VNS; X-ray; 2.09 A; A=888-1182.
DR PDB; 6VNV; X-ray; 2.15 A; A=888-1182.
DR PDB; 6VNX; X-ray; 2.18 A; A=888-1182.
DR PDB; 6VNY; X-ray; 2.30 A; A=888-1182.
DR PDB; 6X8F; X-ray; 2.15 A; A/C=888-1182.
DR PDB; 6X8G; X-ray; 2.21 A; A=888-1182.
DR PDB; 7AX4; X-ray; 2.12 A; A/B=575-869.
DR PDB; 7K7O; X-ray; 2.82 A; A/B=575-869.
DR PDB; 7K7Q; X-ray; 2.27 A; A/B=575-869.
DR PDB; 7UYR; X-ray; 2.15 A; A=889-1177.
DR PDB; 7UYS; X-ray; 2.15 A; A=889-1177.
DR PDB; 7UYT; X-ray; 2.14 A; A=889-1177.
DR PDB; 7UYU; X-ray; 2.05 A; A=889-1177.
DR PDB; 8EXN; X-ray; 2.15 A; D=1048-1062.
DR PDB; 8EYC; X-ray; 2.99 A; C=1048-1062.
DR PDB; 8S98; X-ray; 1.87 A; A/B/C=575-869.
DR PDB; 8S99; X-ray; 1.71 A; A/B/C=575-869.
DR PDB; 8S9A; X-ray; 1.83 A; A/B/C=575-869.
DR PDB; 8TB5; X-ray; 2.32 A; A/B=566-870.
DR PDB; 8TB6; X-ray; 1.96 A; A/B=566-870.
DR PDBsum; 3LXN; -.
DR PDBsum; 3LXP; -.
DR PDBsum; 3NYX; -.
DR PDBsum; 3NZ0; -.
DR PDBsum; 3ZON; -.
DR PDBsum; 4GFO; -.
DR PDBsum; 4GIH; -.
DR PDBsum; 4GII; -.
DR PDBsum; 4GJ2; -.
DR PDBsum; 4GJ3; -.
DR PDBsum; 4GVJ; -.
DR PDBsum; 4OLI; -.
DR PDBsum; 4PO6; -.
DR PDBsum; 4PY1; -.
DR PDBsum; 4WOV; -.
DR PDBsum; 5C01; -.
DR PDBsum; 5C03; -.
DR PDBsum; 5F1Z; -.
DR PDBsum; 5F20; -.
DR PDBsum; 5TKD; -.
DR PDBsum; 5WAL; -.
DR PDBsum; 6AAM; -.
DR PDBsum; 6DBK; -.
DR PDBsum; 6DBM; -.
DR PDBsum; 6NSL; -.
DR PDBsum; 6NZE; -.
DR PDBsum; 6NZF; -.
DR PDBsum; 6NZH; -.
DR PDBsum; 6NZP; -.
DR PDBsum; 6NZQ; -.
DR PDBsum; 6NZR; -.
DR PDBsum; 6OVA; -.
DR PDBsum; 6VNS; -.
DR PDBsum; 6VNV; -.
DR PDBsum; 6VNX; -.
DR PDBsum; 6VNY; -.
DR PDBsum; 6X8F; -.
DR PDBsum; 6X8G; -.
DR PDBsum; 7AX4; -.
DR PDBsum; 7K7O; -.
DR PDBsum; 7K7Q; -.
DR PDBsum; 7UYR; -.
DR PDBsum; 7UYS; -.
DR PDBsum; 7UYT; -.
DR PDBsum; 7UYU; -.
DR PDBsum; 8EXN; -.
DR PDBsum; 8EYC; -.
DR PDBsum; 8S98; -.
DR PDBsum; 8S99; -.
DR PDBsum; 8S9A; -.
DR PDBsum; 8TB5; -.
DR PDBsum; 8TB6; -.
DR AlphaFoldDB; P29597; -.
DR SMR; P29597; -.
DR BioGRID; 113148; 155.
DR ComplexPortal; CPX-382; Interleukin-12-receptor complex.
DR ComplexPortal; CPX-383; Interleukin-23-receptor complex.
DR ComplexPortal; CPX-5995; Interferon alpha receptor-ligand complex, IFNA2 variant.
DR ComplexPortal; CPX-5996; Interferon alpha receptor-ligand complex, IFNA1 variant.
DR ComplexPortal; CPX-5997; Interferon alpha receptor-ligand complex, IFNA7 variant.
DR ComplexPortal; CPX-5998; Interferon alpha receptor-ligand complex, IFNA4 variant.
DR ComplexPortal; CPX-5999; Interferon alpha receptor-ligand complex, IFNA5 variant.
DR ComplexPortal; CPX-6000; Interferon alpha receptor-ligand complex, IFNA6 variant.
DR ComplexPortal; CPX-6001; Interferon alpha receptor-ligand complex, IFNA8 variant.
DR ComplexPortal; CPX-6002; Interferon alpha receptor-ligand complex, IFNA10 variant.
DR ComplexPortal; CPX-6003; Interferon alpha receptor-ligand complex, IFNA14 variant.
DR ComplexPortal; CPX-6004; Interferon alpha receptor-ligand complex, IFNA16 variant.
DR ComplexPortal; CPX-6005; Interferon alpha receptor-ligand complex, IFNA17 variant.
DR ComplexPortal; CPX-6006; Interferon alpha receptor-ligand complex, IFNA21 variant.
DR ComplexPortal; CPX-6007; Interferon beta receptor-ligand complex.
DR ComplexPortal; CPX-6008; Interferon epsilon receptor-ligand complex.
DR ComplexPortal; CPX-6009; Interferon kappa receptor-ligand complex.
DR ComplexPortal; CPX-6010; Interferon omega receptor-ligand complex.
DR ComplexPortal; CPX-6011; Interferon lambda receptor-ligand complex, IFNL1 variant.
DR ComplexPortal; CPX-6012; Interferon lambda receptor-ligand complex, IFNL2 variant.
DR ComplexPortal; CPX-6013; Interferon lambda receptor-ligand complex, IFNL3 variant.
DR ComplexPortal; CPX-6014; Interferon lambda receptor-ligand complex, IFNL4 variant.
DR CORUM; P29597; -.
DR DIP; DIP-1062N; -.
DR IntAct; P29597; 94.
DR MINT; P29597; -.
DR STRING; 9606.ENSP00000431885; -.
DR BindingDB; P29597; -.
DR ChEMBL; CHEMBL3553; -.
DR DrugBank; DB04716; 2-tert-butyl-9-fluoro-1,6-dihydrobenzo[h]imidazo[4,5-f]isoquinolin-7-one.
DR DrugBank; DB14973; Abrocitinib.
DR DrugBank; DB11817; Baricitinib.
DR DrugBank; DB16650; Deucravacitinib.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB08877; Ruxolitinib.
DR DrugBank; DB08895; Tofacitinib.
DR DrugCentral; P29597; -.
DR GuidetoPHARMACOLOGY; 2269; -.
DR GlyGen; P29597; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P29597; -.
DR PhosphoSitePlus; P29597; -.
DR BioMuta; TYK2; -.
DR DMDM; 56405328; -.
DR CPTAC; CPTAC-2821; -.
DR CPTAC; CPTAC-3206; -.
DR CPTAC; CPTAC-3207; -.
DR EPD; P29597; -.
DR jPOST; P29597; -.
DR MassIVE; P29597; -.
DR MaxQB; P29597; -.
DR PaxDb; 9606-ENSP00000431885; -.
DR PeptideAtlas; P29597; -.
DR ProteomicsDB; 54601; -.
DR Pumba; P29597; -.
DR Antibodypedia; 716; 787 antibodies from 41 providers.
DR DNASU; 7297; -.
DR Ensembl; ENST00000525621.6; ENSP00000431885.1; ENSG00000105397.15.
DR Ensembl; ENST00000531836.6; ENSP00000436175.2; ENSG00000105397.15.
DR GeneID; 7297; -.
DR KEGG; hsa:7297; -.
DR MANE-Select; ENST00000525621.6; ENSP00000431885.1; NM_003331.5; NP_003322.3.
DR UCSC; uc002moc.5; human.
DR AGR; HGNC:12440; -.
DR CTD; 7297; -.
DR DisGeNET; 7297; -.
DR GeneCards; TYK2; -.
DR HGNC; HGNC:12440; TYK2.
DR HPA; ENSG00000105397; Low tissue specificity.
DR MalaCards; TYK2; -.
DR MIM; 176941; gene.
DR MIM; 611521; phenotype.
DR neXtProt; NX_P29597; -.
DR OpenTargets; ENSG00000105397; -.
DR Orphanet; 98842; Lymphomatoid papulosis.
DR Orphanet; 300865; Primary cutaneous anaplastic large cell lymphoma.
DR Orphanet; 331226; Susceptibility to infection due to TYK2 deficiency.
DR PharmGKB; PA37094; -.
DR VEuPathDB; HostDB:ENSG00000105397; -.
DR eggNOG; KOG0197; Eukaryota.
DR GeneTree; ENSGT00940000159869; -.
DR InParanoid; P29597; -.
DR OMA; QAKHEFV; -.
DR OrthoDB; 1614410at2759; -.
DR PhylomeDB; P29597; -.
DR TreeFam; TF327041; -.
DR BRENDA; 2.7.10.2; 2681.
DR PathwayCommons; P29597; -.
DR Reactome; R-HSA-1059683; Interleukin-6 signaling.
DR Reactome; R-HSA-110056; MAPK3 (ERK1) activation.
DR Reactome; R-HSA-112411; MAPK1 (ERK2) activation.
DR Reactome; R-HSA-449836; Other interleukin signaling.
DR Reactome; R-HSA-6783783; Interleukin-10 signaling.
DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling.
DR Reactome; R-HSA-6788467; IL-6-type cytokine receptor ligand interactions.
DR Reactome; R-HSA-8854691; Interleukin-20 family signaling.
DR Reactome; R-HSA-8984722; Interleukin-35 Signalling.
DR Reactome; R-HSA-9020591; Interleukin-12 signaling.
DR Reactome; R-HSA-9020933; Interleukin-23 signaling.
DR Reactome; R-HSA-9020956; Interleukin-27 signaling.
DR Reactome; R-HSA-909733; Interferon alpha/beta signaling.
DR Reactome; R-HSA-912694; Regulation of IFNA/IFNB signaling.
DR Reactome; R-HSA-9674555; Signaling by CSF3 (G-CSF).
DR Reactome; R-HSA-9679191; Potential therapeutics for SARS.
DR Reactome; R-HSA-9705462; Inactivation of CSF3 (G-CSF) signaling.
DR Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses.
DR SignaLink; P29597; -.
DR SIGNOR; P29597; -.
DR BioGRID-ORCS; 7297; 22 hits in 1198 CRISPR screens.
DR ChiTaRS; TYK2; human.
DR EvolutionaryTrace; P29597; -.
DR GeneWiki; Tyrosine_kinase_2; -.
DR GenomeRNAi; 7297; -.
DR Pharos; P29597; Tclin.
DR PRO; PR:P29597; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P29597; Protein.
DR Bgee; ENSG00000105397; Expressed in granulocyte and 195 other cell types or tissues.
DR ExpressionAtlas; P29597; baseline and differential.
DR Genevisible; P29597; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; IC:UniProt.
DR GO; GO:0005856; C:cytoskeleton; IEA:InterPro.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0019897; C:extrinsic component of plasma membrane; TAS:UniProt.
DR GO; GO:0042022; C:interleukin-12 receptor complex; NAS:ComplexPortal.
DR GO; GO:0072536; C:interleukin-23 receptor complex; NAS:ComplexPortal.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; TAS:UniProt.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005131; F:growth hormone receptor binding; IPI:BHF-UCL.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProt.
DR GO; GO:0031702; F:type 1 angiotensin receptor binding; IEA:Ensembl.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0098586; P:cellular response to virus; NAS:ComplexPortal.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0060397; P:growth hormone receptor signaling pathway via JAK-STAT; IBA:GO_Central.
DR GO; GO:0006955; P:immune response; NAS:ComplexPortal.
DR GO; GO:0035722; P:interleukin-12-mediated signaling pathway; IDA:UniProt.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0032740; P:positive regulation of interleukin-17 production; NAS:ComplexPortal.
DR GO; GO:0032819; P:positive regulation of natural killer cell proliferation; IDA:ComplexPortal.
DR GO; GO:0051142; P:positive regulation of NK T cell proliferation; IDA:ComplexPortal.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; IDA:UniProt.
DR GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; IDA:ComplexPortal.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; IDA:ComplexPortal.
DR GO; GO:2000318; P:positive regulation of T-helper 17 type immune response; NAS:ComplexPortal.
DR GO; GO:0032729; P:positive regulation of type II interferon production; IDA:ComplexPortal.
DR GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc.
DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; IDA:UniProtKB.
DR GO; GO:0060337; P:type I interferon-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0060333; P:type II interferon-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0038196; P:type III interferon-mediated signaling pathway; NAS:ComplexPortal.
DR CDD; cd05076; PTK_Tyk2_rpt1; 1.
DR CDD; cd05080; PTKc_Tyk2_rpt2; 1.
DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 2.
DR InterPro; IPR019749; Band_41_domain.
DR InterPro; IPR035963; FERM_2.
DR InterPro; IPR000299; FERM_domain.
DR InterPro; IPR041155; FERM_F1.
DR InterPro; IPR041046; FERM_F2.
DR InterPro; IPR041381; JAK1-3/TYK2_PHL_dom.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR InterPro; IPR016251; Tyr_kinase_non-rcpt_Jak/Tyk2.
DR InterPro; IPR016045; Tyr_kinase_non-rcpt_TYK2_N.
DR PANTHER; PTHR45807:SF6; NON-RECEPTOR TYROSINE-PROTEIN KINASE TYK2; 1.
DR PANTHER; PTHR45807; TYROSINE-PROTEIN KINASE HOPSCOTCH; 1.
DR Pfam; PF18379; FERM_F1; 1.
DR Pfam; PF18377; FERM_F2; 1.
DR Pfam; PF17887; Jak1_Phl; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 2.
DR PIRSF; PIRSF000636; TyrPK_Jak; 1.
DR PRINTS; PR01823; JANUSKINASE.
DR PRINTS; PR00109; TYRKINASE.
DR PRINTS; PR01827; YKINASETYK2.
DR SMART; SM00295; B41; 1.
DR SMART; SM00252; SH2; 1.
DR SMART; SM00219; TyrKc; 2.
DR SUPFAM; SSF50729; PH domain-like; 1.
DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 2.
DR SUPFAM; SSF47031; Second domain of FERM; 1.
DR SUPFAM; SSF55550; SH2 domain; 1.
DR PROSITE; PS50057; FERM_3; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 2.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Kinase; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Repeat; SH2 domain; Transferase;
KW Tyrosine-protein kinase.
FT CHAIN 1..1187
FT /note="Non-receptor tyrosine-protein kinase TYK2"
FT /id="PRO_0000088177"
FT DOMAIN 26..431
FT /note="FERM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00084"
FT DOMAIN 450..529
FT /note="SH2; atypical"
FT DOMAIN 589..875
FT /note="Protein kinase 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 897..1176
FT /note="Protein kinase 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 335..366
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 610..629
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1023
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 903..911
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 930
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 292
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163"
FT MOD_RES 499
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 525
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9R117"
FT MOD_RES 604
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9R117"
FT MOD_RES 884
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 1054
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:20478313,
FT ECO:0000269|PubMed:8702790"
FT MOD_RES 1055
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:8702790"
FT VARIANT 4
FT /note="R -> H (in dbSNP:rs12720343)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_020597"
FT VARIANT 81
FT /note="A -> V (in dbSNP:rs1049619)"
FT /id="VAR_037797"
FT VARIANT 197
FT /note="R -> H (in dbSNP:rs12720263)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_020598"
FT VARIANT 362
FT /note="V -> F (in dbSNP:rs2304256)"
FT /evidence="ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:2216457, ECO:0000269|Ref.2"
FT /id="VAR_020599"
FT VARIANT 363
FT /note="G -> S (in dbSNP:rs2304255)"
FT /evidence="ECO:0000269|PubMed:17344846, ECO:0000269|Ref.2"
FT /id="VAR_020600"
FT VARIANT 386
FT /note="V -> M (in dbSNP:rs55956017)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041870"
FT VARIANT 442
FT /note="R -> Q (in dbSNP:rs2304254)"
FT /id="VAR_037798"
FT VARIANT 684
FT /note="I -> S (in dbSNP:rs12720356)"
FT /evidence="ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:2216457, ECO:0000269|Ref.2"
FT /id="VAR_020286"
FT VARIANT 703
FT /note="R -> W (in dbSNP:rs55882956)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041871"
FT VARIANT 732
FT /note="H -> R (in a colorectal adenocarcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041872"
FT VARIANT 820
FT /note="P -> H (in dbSNP:rs34046749)"
FT /id="VAR_037799"
FT VARIANT 928
FT /note="A -> V (in dbSNP:rs35018800)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041873"
FT VARIANT 1104
FT /note="P -> A (in dbSNP:rs34536443)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041874"
FT VARIANT 1163
FT /note="E -> G (in dbSNP:rs55886939)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041875"
FT MUTAGEN 930
FT /note="K->R: Complete loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:8702790"
FT MUTAGEN 1023
FT /note="D->N: Complete loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:24843152"
FT MUTAGEN 1054
FT /note="Y->F: Reduces basal catalytic activity and abolishes
FT IFN-dependent activation."
FT /evidence="ECO:0000269|PubMed:8702790"
FT MUTAGEN 1055
FT /note="Y->F: Reduces basal catalytic activity and abolishes
FT IFN-dependent activation."
FT /evidence="ECO:0000269|PubMed:8702790"
FT MUTAGEN 1145
FT /note="Y->F: Does not affect phosphorylation state and
FT enzymatic activity."
FT /evidence="ECO:0000269|PubMed:8702790"
FT MUTAGEN 1176
FT /note="Y->F: Does not affect phosphorylation state and
FT enzymatic activity."
FT /evidence="ECO:0000269|PubMed:8702790"
FT CONFLICT 869
FT /note="L -> V (in Ref. 1; CAA38449)"
FT /evidence="ECO:0000305"
FT CONFLICT 882
FT /note="P -> R (in Ref. 1; CAA38449)"
FT /evidence="ECO:0000305"
FT CONFLICT 887..888
FT /note="SD -> VG (in Ref. 1; CAA38449)"
FT /evidence="ECO:0000305"
FT CONFLICT 891
FT /note="V -> T (in Ref. 1; CAA38449)"
FT /evidence="ECO:0000305"
FT CONFLICT 1016
FT /note="A -> S (in Ref. 3; AAH14243)"
FT /evidence="ECO:0000305"
FT CONFLICT 1017..1018
FT /note="QH -> HD (in Ref. 1; CAA38449)"
FT /evidence="ECO:0000305"
FT STRAND 28..31
FT /evidence="ECO:0007829|PDB:4PO6"
FT STRAND 42..46
FT /evidence="ECO:0007829|PDB:4PO6"
FT STRAND 49..52
FT /evidence="ECO:0007829|PDB:4PO6"
FT HELIX 53..64
FT /evidence="ECO:0007829|PDB:4PO6"
FT HELIX 68..73
FT /evidence="ECO:0007829|PDB:4PO6"
FT STRAND 74..78
FT /evidence="ECO:0007829|PDB:4PO6"
FT TURN 79..82
FT /evidence="ECO:0007829|PDB:4PO6"
FT STRAND 83..85
FT /evidence="ECO:0007829|PDB:4PO6"
FT STRAND 90..92
FT /evidence="ECO:0007829|PDB:4PO6"
FT TURN 93..98
FT /evidence="ECO:0007829|PDB:4PO6"
FT STRAND 101..105
FT /evidence="ECO:0007829|PDB:4PO6"
FT TURN 110..113
FT /evidence="ECO:0007829|PDB:4PO6"
FT STRAND 122..124
FT /evidence="ECO:0007829|PDB:4PO6"
FT HELIX 146..161
FT /evidence="ECO:0007829|PDB:4PO6"
FT HELIX 167..169
FT /evidence="ECO:0007829|PDB:4PO6"
FT HELIX 173..198
FT /evidence="ECO:0007829|PDB:4PO6"
FT HELIX 202..208
FT /evidence="ECO:0007829|PDB:4PO6"
FT HELIX 211..213
FT /evidence="ECO:0007829|PDB:4PO6"
FT HELIX 217..225
FT /evidence="ECO:0007829|PDB:4PO6"
FT HELIX 228..243
FT /evidence="ECO:0007829|PDB:4PO6"
FT HELIX 252..266
FT /evidence="ECO:0007829|PDB:4PO6"
FT TURN 268..271
FT /evidence="ECO:0007829|PDB:4PO6"
FT STRAND 273..284
FT /evidence="ECO:0007829|PDB:4PO6"
FT HELIX 285..287
FT /evidence="ECO:0007829|PDB:4PO6"
FT STRAND 314..319
FT /evidence="ECO:0007829|PDB:4PO6"
FT TURN 320..322
FT /evidence="ECO:0007829|PDB:4PO6"
FT STRAND 323..328
FT /evidence="ECO:0007829|PDB:4PO6"
FT STRAND 375..378
FT /evidence="ECO:0007829|PDB:4PO6"
FT HELIX 380..382
FT /evidence="ECO:0007829|PDB:4PO6"
FT STRAND 383..389
FT /evidence="ECO:0007829|PDB:4PO6"
FT STRAND 392..397
FT /evidence="ECO:0007829|PDB:4PO6"
FT STRAND 400..406
FT /evidence="ECO:0007829|PDB:4PO6"
FT HELIX 410..427
FT /evidence="ECO:0007829|PDB:4PO6"
FT HELIX 436..438
FT /evidence="ECO:0007829|PDB:4PO6"
FT HELIX 441..449
FT /evidence="ECO:0007829|PDB:4PO6"
FT HELIX 457..464
FT /evidence="ECO:0007829|PDB:4PO6"
FT STRAND 470..475
FT /evidence="ECO:0007829|PDB:4PO6"
FT STRAND 483..492
FT /evidence="ECO:0007829|PDB:4PO6"
FT STRAND 498..508
FT /evidence="ECO:0007829|PDB:4PO6"
FT STRAND 514..516
FT /evidence="ECO:0007829|PDB:4PO6"
FT STRAND 523..525
FT /evidence="ECO:0007829|PDB:4PO6"
FT HELIX 526..533
FT /evidence="ECO:0007829|PDB:4PO6"
FT STRAND 537..540
FT /evidence="ECO:0007829|PDB:4PO6"
FT STRAND 543..546
FT /evidence="ECO:0007829|PDB:4PO6"
FT STRAND 562..565
FT /evidence="ECO:0007829|PDB:4PO6"
FT HELIX 586..588
FT /evidence="ECO:0007829|PDB:8S99"
FT STRAND 589..598
FT /evidence="ECO:0007829|PDB:8S99"
FT STRAND 601..609
FT /evidence="ECO:0007829|PDB:8S99"
FT STRAND 636..644
FT /evidence="ECO:0007829|PDB:8S99"
FT HELIX 649..663
FT /evidence="ECO:0007829|PDB:8S99"
FT STRAND 673..679
FT /evidence="ECO:0007829|PDB:8S99"
FT STRAND 682..688
FT /evidence="ECO:0007829|PDB:8S99"
FT HELIX 695..701
FT /evidence="ECO:0007829|PDB:8S99"
FT TURN 702..704
FT /evidence="ECO:0007829|PDB:8S99"
FT HELIX 708..728
FT /evidence="ECO:0007829|PDB:8S99"
FT HELIX 737..739
FT /evidence="ECO:0007829|PDB:8S99"
FT STRAND 740..744
FT /evidence="ECO:0007829|PDB:8S99"
FT STRAND 754..757
FT /evidence="ECO:0007829|PDB:8S99"
FT HELIX 764..766
FT /evidence="ECO:0007829|PDB:8S99"
FT HELIX 769..774
FT /evidence="ECO:0007829|PDB:8S99"
FT TURN 775..778
FT /evidence="ECO:0007829|PDB:8S99"
FT HELIX 781..783
FT /evidence="ECO:0007829|PDB:8S99"
FT HELIX 794..808
FT /evidence="ECO:0007829|PDB:8S99"
FT TURN 809..811
FT /evidence="ECO:0007829|PDB:8S99"
FT TURN 814..817
FT /evidence="ECO:0007829|PDB:8S99"
FT HELIX 820..828
FT /evidence="ECO:0007829|PDB:8S99"
FT HELIX 839..848
FT /evidence="ECO:0007829|PDB:8S99"
FT HELIX 853..855
FT /evidence="ECO:0007829|PDB:8S99"
FT HELIX 859..866
FT /evidence="ECO:0007829|PDB:8S99"
FT HELIX 894..896
FT /evidence="ECO:0007829|PDB:3LXP"
FT STRAND 897..905
FT /evidence="ECO:0007829|PDB:3LXP"
FT STRAND 907..916
FT /evidence="ECO:0007829|PDB:3LXP"
FT STRAND 920..922
FT /evidence="ECO:0007829|PDB:3NZ0"
FT STRAND 925..932
FT /evidence="ECO:0007829|PDB:3LXP"
FT HELIX 938..953
FT /evidence="ECO:0007829|PDB:3LXP"
FT STRAND 962..968
FT /evidence="ECO:0007829|PDB:3LXP"
FT TURN 969..972
FT /evidence="ECO:0007829|PDB:3LXP"
FT STRAND 973..978
FT /evidence="ECO:0007829|PDB:3LXP"
FT HELIX 986..989
FT /evidence="ECO:0007829|PDB:3LXP"
FT HELIX 990..992
FT /evidence="ECO:0007829|PDB:3LXP"
FT HELIX 997..1016
FT /evidence="ECO:0007829|PDB:3LXP"
FT HELIX 1026..1028
FT /evidence="ECO:0007829|PDB:3LXP"
FT STRAND 1029..1031
FT /evidence="ECO:0007829|PDB:3LXP"
FT STRAND 1037..1039
FT /evidence="ECO:0007829|PDB:3LXP"
FT HELIX 1042..1044
FT /evidence="ECO:0007829|PDB:3LXP"
FT STRAND 1053..1056
FT /evidence="ECO:0007829|PDB:3LXP"
FT STRAND 1059..1061
FT /evidence="ECO:0007829|PDB:7UYT"
FT HELIX 1065..1067
FT /evidence="ECO:0007829|PDB:3LXP"
FT HELIX 1070..1075
FT /evidence="ECO:0007829|PDB:3LXP"
FT STRAND 1077..1079
FT /evidence="ECO:0007829|PDB:3LXP"
FT HELIX 1080..1095
FT /evidence="ECO:0007829|PDB:3LXP"
FT TURN 1096..1098
FT /evidence="ECO:0007829|PDB:3LXP"
FT HELIX 1100..1102
FT /evidence="ECO:0007829|PDB:3LXP"
FT HELIX 1104..1112
FT /evidence="ECO:0007829|PDB:3LXP"
FT HELIX 1117..1129
FT /evidence="ECO:0007829|PDB:3LXP"
FT HELIX 1142..1151
FT /evidence="ECO:0007829|PDB:3LXP"
FT HELIX 1156..1158
FT /evidence="ECO:0007829|PDB:3LXP"
FT HELIX 1162..1177
FT /evidence="ECO:0007829|PDB:3LXP"
SQ SEQUENCE 1187 AA; 133650 MW; F76C25D6A919EDBC CRC64;
MPLRHWGMAR GSKPVGDGAQ PMAAMGGLKV LLHWAGPGGG EPWVTFSESS LTAEEVCIHI
AHKVGITPPC FNLFALFDAQ AQVWLPPNHI LEIPRDASLM LYFRIRFYFR NWHGMNPREP
AVYRCGPPGT EASSDQTAQG MQLLDPASFE YLFEQGKHEF VNDVASLWEL STEEEIHHFK
NESLGMAFLH LCHLALRHGI PLEEVAKKTS FKDCIPRSFR RHIRQHSALT RLRLRNVFRR
FLRDFQPGRL SQQMVMVKYL ATLERLAPRF GTERVPVCHL RLLAQAEGEP CYIRDSGVAP
TDPGPESAAG PPTHEVLVTG TGGIQWWPVE EEVNKEEGSS GSSGRNPQAS LFGKKAKAHK
AVGQPADRPR EPLWAYFCDF RDITHVVLKE HCVSIHRQDN KCLELSLPSR AAALSFVSLV
DGYFRLTADS SHYLCHEVAP PRLVMSIRDG IHGPLLEPFV QAKLRPEDGL YLIHWSTSHP
YRLILTVAQR SQAPDGMQSL RLRKFPIEQQ DGAFVLEGWG RSFPSVRELG AALQGCLLRA
GDDCFSLRRC CLPQPGETSN LIIMRGARAS PRTLNLSQLS FHRVDQKEIT QLSHLGQGTR
TNVYEGRLRV EGSGDPEEGK MDDEDPLVPG RDRGQELRVV LKVLDPSHHD IALAFYETAS
LMSQVSHTHL AFVHGVCVRG PENIMVTEYV EHGPLDVWLR RERGHVPMAW KMVVAQQLAS
ALSYLENKNL VHGNVCGRNI LLARLGLAEG TSPFIKLSDP GVGLGALSRE ERVERIPWLA
PECLPGGANS LSTAMDKWGF GATLLEICFD GEAPLQSRSP SEKEHFYQRQ HRLPEPSCPQ
LATLTSQCLT YEPTQRPSFR TILRDLTRLQ PHNLADVLTV NPDSPASDPT VFHKRYLKKI
RDLGEGHFGK VSLYCYDPTN DGTGEMVAVK ALKADCGPQH RSGWKQEIDI LRTLYHEHII
KYKGCCEDQG EKSLQLVMEY VPLGSLRDYL PRHSIGLAQL LLFAQQICEG MAYLHAQHYI
HRDLAARNVL LDNDRLVKIG DFGLAKAVPE GHEYYRVRED GDSPVFWYAP ECLKEYKFYY
ASDVWSFGVT LYELLTHCDS SQSPPTKFLE LIGIAQGQMT VLRLTELLER GERLPRPDKC
PCEVYHLMKN CWETEASFRP TFENLIPILK TVHEKYQGQA PSVFSVC
//