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   02-OCT-2024, entry version 239.
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:10542297, PubMed:10995743, PubMed:7657660, PubMed:7813427,
CC       PubMed:8232552). 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:10542297,
CC       PubMed:25762719, PubMed:7526154, PubMed:7813427). 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:10542297,
CC       PubMed:25762719, PubMed:7657660). 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; Q3LI67: KRTAP6-3; NbExp=3; IntAct=EBI-1383454, EBI-22311199;
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=TYK2; Note=tyrosine kinase 2;
CC       URL="https://databases.lovd.nl/shared/genes/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; 156.
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   ComplexPortal; CPX-623; IL6-mIL6RA-mIL-6ST receptor-ligand classical signalling complex.
DR   ComplexPortal; CPX-624; Interleukin-4 receptor-ligand type-2 complex.
DR   ComplexPortal; CPX-742; Interleukin-10 receptor-ligand complex.
DR   ComplexPortal; CPX-844; Interleukin-13 receptor-ligand alpha 1 complex.
DR   ComplexPortal; CPX-8836; Interleukin-27 receptor-ligand complex.
DR   ComplexPortal; CPX-8967; IL6-sIL6RA-mIL6ST receptor-ligand trans-signalling complex.
DR   ComplexPortal; CPX-8968; mIL6-mIL6RA receptor-ligand cluster-signalling complex.
DR   ComplexPortal; CPX-8969; IL6-sIL6RA-sIL6ST buffering ligand-receptor complex.
DR   CORUM; P29597; -.
DR   DIP; DIP-1062N; -.
DR   IntAct; P29597; 111.
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; DB11763; Momelotinib.
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   jPOST; P29597; -.
DR   MassIVE; P29597; -.
DR   PaxDb; 9606-ENSP00000431885; -.
DR   PeptideAtlas; P29597; -.
DR   ProteomicsDB; 54601; -.
DR   Pumba; P29597; -.
DR   Antibodypedia; 716; 763 antibodies from 42 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   Reactome; R-HSA-9725370; Signaling by ALK fusions and activated point mutants.
DR   Reactome; R-HSA-9833109; Evasion by RSV of host interferon 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   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:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IC:UniProt.
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:0007259; P:cell surface receptor signaling pathway via JAK-STAT; IDA:UniProtKB.
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:0140105; P:interleukin-10-mediated signaling pathway; IDA:UniProt.
DR   GO; GO:0035722; P:interleukin-12-mediated signaling pathway; IDA:UniProt.
DR   GO; GO:0038155; P:interleukin-23-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: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; IPR051286; JAK.
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   Pfam; PF21990; SH2_1; 1.
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   Proteomics identification; Reference proteome; Repeat; SH2 domain;
KW   Transferase; 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
//