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 24-JUL-2024, entry version 238. 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"; CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/tyk2/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 ComplexPortal; CPX-623; Interleukin-6 receptor-ligand complex. DR ComplexPortal; CPX-624; Interleukin-4 receptor-ligand type-2 complex. DR ComplexPortal; CPX-742; Interleukin-10 receptor-ligand complex. DR ComplexPortal; CPX-8836; Interleukin-27 receptor-ligand complex. DR CORUM; P29597; -. DR DIP; DIP-1062N; -. DR IntAct; P29597; 95. 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; 750 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 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: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 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 //