ID   TYK2_MOUSE              Reviewed;        1184 AA.
AC   Q9R117; O88431; Q3TXE3; Q52KQ2; Q8VE41;
DT   11-JUL-2001, integrated into UniProtKB/Swiss-Prot.
DT   31-JAN-2018, sequence version 3.
DT   24-JAN-2024, entry version 190.
DE   RecName: Full=Non-receptor tyrosine-protein kinase TYK2;
DE            EC=2.7.10.2;
GN   Name=Tyk2 {ECO:0000312|EMBL:AAD49423.1};
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=129/Sv; TISSUE=Liver;
RX   PubMed=11070173; DOI=10.1016/s1074-7613(00)00054-6;
RA   Karaghiosoff M., Neubauer H., Lassnig C., Kovarik P., Schindler H.,
RA   Pircher H., McCoy B., Bogdan C., Decker T., Brem G., Pfeffer K.,
RA   Mueller M.;
RT   "Partial impairment of cytokine responses in Tyk2-deficient mice.";
RL   Immunity 13:549-560(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J {ECO:0000312|EMBL:BAE34973.1};
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Eye;
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   [6]
RP   PROTEIN SEQUENCE OF 736-741, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC   STRAIN=OF1; TISSUE=Hippocampus;
RA   Lubec G., Sunyer B., Chen W.-Q.;
RL   Submitted (JAN-2009) to UniProtKB.
RN   [7]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=11070174; DOI=10.1016/s1074-7613(00)00055-8;
RA   Shimoda K., Kato K., Aoki K., Matsuda T., Miyamoto A., Shibamori M.,
RA   Yamashita M., Numata A., Takase K., Kobayashi S., Shibata S., Asano Y.,
RA   Gondo H., Sekiguchi K., Nakayama K., Nakayama T., Okamura T., Okamura S.,
RA   Niho Y., Nakayama K.;
RT   "Tyk2 plays a restricted role in IFN alpha signaling, although it is
RT   required for IL-12-mediated T cell function.";
RL   Immunity 13:561-571(2000).
RN   [8]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-604, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Mast cell;
RX   PubMed=17947660; DOI=10.4049/jimmunol.179.9.5864;
RA   Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,
RA   Kawakami T., Salomon A.R.;
RT   "Quantitative time-resolved phosphoproteomic analysis of mast cell
RT   signaling.";
RL   J. Immunol. 179:5864-5876(2007).
RN   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-525, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Kidney, Lung, and Spleen;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [10]
RP   FUNCTION IN STAT6 ACTIVATION.
RX   PubMed=22859374; DOI=10.1096/fj.12-211755;
RA   Zhang X., Zhang Y., Tao B., Wang D., Cheng H., Wang K., Zhou R., Xie Q.,
RA   Ke Y.;
RT   "Docking protein Gab2 regulates mucin expression and goblet cell
RT   hyperplasia through TYK2/STAT6 pathway.";
RL   FASEB J. 26:4603-4613(2012).
RN   [11]
RP   X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 884-1174 IN COMPLEX WITH
RP   INHIBITOR.
RX   PubMed=22995073; DOI=10.1186/1472-6807-12-22;
RA   Argiriadi M.A., Goedken E.R., Banach D., Borhani D.W., Burchat A.,
RA   Dixon R.W., Marcotte D., Overmeyer G., Pivorunas V., Sadhukhan R.,
RA   Sousa S., Moore N.S., Tomlinson M., Voss J., Wang L., Wishart N.,
RA   Woller K., Talanian R.V.;
RT   "Enabling structure-based drug design of Tyk2 through co-crystallization
RT   with a stabilizing aminoindazole inhibitor.";
RL   BMC Struct. Biol. 12:22-22(2012).
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:11070174). Plays both structural and catalytic roles in
CC       numerous interleukins and interferons (IFN-alpha/beta) signaling (By
CC       similarity). Associates with heterodimeric cytokine receptor complexes
CC       and activates STAT family members including STAT1, STAT3, STAT4 or
CC       STAT6 (PubMed:22859374). The heterodimeric cytokine receptor complexes
CC       are composed of (1) a TYK2-associated receptor chain (IFNAR1, IL12RB1,
CC       IL10RB or IL13RA1), and (2) a second receptor chain associated either
CC       with JAK1 or JAK2 (By similarity). In response to cytokine-binding to
CC       receptors, phosphorylates and activates receptors (IFNAR1, IL12RB1,
CC       IL10RB or IL13RA1), creating docking sites for STAT members (By
CC       similarity). In turn, recruited STATs are phosphorylated by TYK2 (or
CC       JAK1/JAK2 on the second receptor chain), form homo- and heterodimers,
CC       translocate to the nucleus, and regulate cytokine/growth factor
CC       responsive genes (By similarity). Negatively regulates STAT3 activity
CC       by promototing phosphorylation at a specific tyrosine that differs from
CC       the site used for signaling (By similarity).
CC       {ECO:0000250|UniProtKB:P29597, ECO:0000269|PubMed:11070174,
CC       ECO:0000269|PubMed:22859374}.
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:0000250|UniProtKB:P29597};
CC   -!- ACTIVITY REGULATION: The protein kinase 1 domain (also termed
CC       pseudokinase domain) mediates autoinhibition of the TYK2 kinase domain.
CC       {ECO:0000250|UniProtKB:P29597}.
CC   -!- SUBUNIT: Interacts (via FERM domain) with JAKMIP1. Interacts with
CC       PIK3R1; this interaction is important for cell migration.
CC       {ECO:0000250|UniProtKB:P29597}.
CC   -!- PTM: Phosphorylation by JAK1 at Tyr-1051 and Tyr-1052 induces kinase
CC       activation. {ECO:0000250|UniProtKB:P29597}.
CC   -!- DISRUPTION PHENOTYPE: Deficient mice are viable and fertile but display
CC       multiple immunological defects, most prominently high sensitivity to
CC       infections and defective tumor surveillance. Absence of TYK2 results in
CC       increased resistance against allergic, autoimmune and inflammatory
CC       disease. {ECO:0000269|PubMed:11070174}.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC       kinase family. JAK subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAD49423.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC       Sequence=AAH94240.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC       Sequence=EDL25160.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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; AF173032; AAD49423.1; ALT_INIT; mRNA.
DR   EMBL; AF052607; AAC34580.2; -; Genomic_DNA.
DR   EMBL; AK159303; BAE34973.1; -; mRNA.
DR   EMBL; AC163637; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH466522; EDL25160.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; BC094240; AAH94240.1; ALT_INIT; mRNA.
DR   EMBL; BC019789; AAH19789.1; -; mRNA.
DR   CCDS; CCDS90510.1; -.
DR   RefSeq; NP_061263.2; NM_018793.2.
DR   RefSeq; XP_011240881.1; XM_011242579.2.
DR   PDB; 4E1Z; X-ray; 2.50 A; A=884-1174.
DR   PDB; 4E20; X-ray; 2.60 A; A=885-1174.
DR   PDBsum; 4E1Z; -.
DR   PDBsum; 4E20; -.
DR   AlphaFoldDB; Q9R117; -.
DR   EMDB; EMD-28649; -.
DR   SMR; Q9R117; -.
DR   ComplexPortal; CPX-388; Interleukin-12-receptor complex.
DR   ComplexPortal; CPX-389; Interleukin-23-receptor complex.
DR   STRING; 10090.ENSMUSP00000150354; -.
DR   BindingDB; Q9R117; -.
DR   ChEMBL; CHEMBL2321619; -.
DR   iPTMnet; Q9R117; -.
DR   PhosphoSitePlus; Q9R117; -.
DR   SwissPalm; Q9R117; -.
DR   EPD; Q9R117; -.
DR   PaxDb; 10090-ENSMUSP00000001036; -.
DR   ProteomicsDB; 298077; -.
DR   Pumba; Q9R117; -.
DR   Antibodypedia; 716; 787 antibodies from 41 providers.
DR   DNASU; 54721; -.
DR   Ensembl; ENSMUST00000214454.2; ENSMUSP00000150214.2; ENSMUSG00000032175.12.
DR   GeneID; 54721; -.
DR   KEGG; mmu:54721; -.
DR   UCSC; uc009oke.1; mouse.
DR   AGR; MGI:1929470; -.
DR   CTD; 7297; -.
DR   MGI; MGI:1929470; Tyk2.
DR   VEuPathDB; HostDB:ENSMUSG00000032175; -.
DR   eggNOG; KOG0197; Eukaryota.
DR   GeneTree; ENSGT00940000159869; -.
DR   InParanoid; Q9R117; -.
DR   OrthoDB; 1614410at2759; -.
DR   BRENDA; 2.7.10.2; 3474.
DR   Reactome; R-MMU-1059683; Interleukin-6 signaling.
DR   Reactome; R-MMU-110056; MAPK3 (ERK1) activation.
DR   Reactome; R-MMU-112411; MAPK1 (ERK2) activation.
DR   Reactome; R-MMU-6783783; Interleukin-10 signaling.
DR   Reactome; R-MMU-6785807; Interleukin-4 and Interleukin-13 signaling.
DR   Reactome; R-MMU-6788467; IL-6-type cytokine receptor ligand interactions.
DR   Reactome; R-MMU-8854691; Interleukin-20 family signaling.
DR   Reactome; R-MMU-8984722; Interleukin-35 Signalling.
DR   Reactome; R-MMU-9020591; Interleukin-12 signaling.
DR   Reactome; R-MMU-9020933; Interleukin-23 signaling.
DR   Reactome; R-MMU-9020956; Interleukin-27 signaling.
DR   Reactome; R-MMU-909733; Interferon alpha/beta signaling.
DR   Reactome; R-MMU-912694; Regulation of IFNA/IFNB signaling.
DR   Reactome; R-MMU-9674555; Signaling by CSF3 (G-CSF).
DR   Reactome; R-MMU-9705462; Inactivation of CSF3 (G-CSF) signaling.
DR   BioGRID-ORCS; 54721; 7 hits in 79 CRISPR screens.
DR   ChiTaRS; Tyk2; mouse.
DR   PRO; PR:Q9R117; -.
DR   Proteomes; UP000000589; Chromosome 9.
DR   RNAct; Q9R117; Protein.
DR   Bgee; ENSMUSG00000032175; Expressed in granulocyte and 234 other cell types or tissues.
DR   ExpressionAtlas; Q9R117; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR   GO; GO:0005856; C:cytoskeleton; IEA:InterPro.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
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; ISO:MGI.
DR   GO; GO:0005886; C:plasma membrane; NAS:ComplexPortal.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0005131; F:growth hormone receptor binding; ISO:MGI.
DR   GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; ISO:MGI.
DR   GO; GO:0004713; F:protein tyrosine kinase activity; ISO:MGI.
DR   GO; GO:0031702; F:type 1 angiotensin receptor binding; ISO:MGI.
DR   GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR   GO; GO:0008283; P:cell population proliferation; IGI:MGI.
DR   GO; GO:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central.
DR   GO; GO:0060397; P:growth hormone receptor signaling pathway via JAK-STAT; IBA:GO_Central.
DR   GO; GO:0006955; P:immune response; NAS:ComplexPortal.
DR   GO; GO:0035722; P:interleukin-12-mediated signaling pathway; ISO:MGI.
DR   GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
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; ISO:MGI.
DR   GO; GO:0051142; P:positive regulation of NK T cell proliferation; ISO:MGI.
DR   GO; GO:1900182; P:positive regulation of protein localization to nucleus; ISO:MGI.
DR   GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; ISO:MGI.
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; ISO:MGI.
DR   GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; ISO:MGI.
DR   GO; GO:0060337; P:type I interferon-mediated signaling pathway; ISO:MGI.
DR   GO; GO:0060333; P:type II interferon-mediated signaling pathway; ISO:MGI.
DR   CDD; cd05080; PTKc_Tyk2_rpt2; 1.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 2.
DR   InterPro; IPR019749; Band_41_domain.
DR   InterPro; IPR035963; FERM_2.
DR   InterPro; IPR000299; FERM_domain.
DR   InterPro; IPR041155; FERM_F1.
DR   InterPro; IPR041046; FERM_F2.
DR   InterPro; IPR041381; JAK1-3/TYK2_PHL_dom.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR017441; Protein_kinase_ATP_BS.
DR   InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR   InterPro; 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; 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.
DR   Genevisible; Q3TXE3; MM.
PE   1: Evidence at protein level;
KW   3D-structure; ATP-binding; Direct protein sequencing; Kinase;
KW   Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat; SH2 domain;
KW   Transferase; Tyrosine-protein kinase.
FT   CHAIN           1..1184
FT                   /note="Non-receptor tyrosine-protein kinase TYK2"
FT                   /id="PRO_0000088178"
FT   DOMAIN          33..430
FT                   /note="FERM"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00084"
FT   DOMAIN          449..529
FT                   /note="SH2; atypical"
FT   DOMAIN          589..866
FT                   /note="Protein kinase 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   DOMAIN          894..1166
FT                   /note="Protein kinase 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   REGION          294..368
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        327..348
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        1020
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000255|PROSITE-ProRule:PRU10028"
FT   BINDING         900..908
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         927
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   MOD_RES         295
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:P29597"
FT   MOD_RES         525
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         604
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0007744|PubMed:17947660"
FT   MOD_RES         881
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P29597"
FT   MOD_RES         1051
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000250|UniProtKB:P29597"
FT   MOD_RES         1052
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:P29597"
FT   CONFLICT        195
FT                   /note="C -> F (in Ref. 1; AAC34580)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        238
FT                   /note="H -> R (in Ref. 1; AAC34580)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        359
FT                   /note="K -> E (in Ref. 1; AAC34580)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        835
FT                   /note="S -> C (in Ref. 1; AAC34580)"
FT   CONFLICT        1103
FT                   /note="M -> T (in Ref. 1; AAC34580)"
FT   HELIX           891..893
FT                   /evidence="ECO:0007829|PDB:4E1Z"
FT   STRAND          894..902
FT                   /evidence="ECO:0007829|PDB:4E1Z"
FT   STRAND          904..913
FT                   /evidence="ECO:0007829|PDB:4E1Z"
FT   STRAND          917..919
FT                   /evidence="ECO:0007829|PDB:4E20"
FT   STRAND          922..929
FT                   /evidence="ECO:0007829|PDB:4E1Z"
FT   HELIX           935..950
FT                   /evidence="ECO:0007829|PDB:4E1Z"
FT   STRAND          959..964
FT                   /evidence="ECO:0007829|PDB:4E1Z"
FT   STRAND          971..976
FT                   /evidence="ECO:0007829|PDB:4E1Z"
FT   HELIX           983..986
FT                   /evidence="ECO:0007829|PDB:4E1Z"
FT   HELIX           987..989
FT                   /evidence="ECO:0007829|PDB:4E1Z"
FT   HELIX           994..1013
FT                   /evidence="ECO:0007829|PDB:4E1Z"
FT   HELIX           1023..1025
FT                   /evidence="ECO:0007829|PDB:4E1Z"
FT   STRAND          1026..1028
FT                   /evidence="ECO:0007829|PDB:4E1Z"
FT   HELIX           1030..1032
FT                   /evidence="ECO:0007829|PDB:4E1Z"
FT   STRAND          1034..1036
FT                   /evidence="ECO:0007829|PDB:4E1Z"
FT   STRAND          1050..1053
FT                   /evidence="ECO:0007829|PDB:4E1Z"
FT   STRAND          1058..1060
FT                   /evidence="ECO:0007829|PDB:4E1Z"
FT   HELIX           1062..1064
FT                   /evidence="ECO:0007829|PDB:4E1Z"
FT   HELIX           1067..1071
FT                   /evidence="ECO:0007829|PDB:4E1Z"
FT   STRAND          1074..1076
FT                   /evidence="ECO:0007829|PDB:4E1Z"
FT   HELIX           1077..1092
FT                   /evidence="ECO:0007829|PDB:4E1Z"
FT   TURN            1093..1095
FT                   /evidence="ECO:0007829|PDB:4E1Z"
FT   HELIX           1097..1099
FT                   /evidence="ECO:0007829|PDB:4E20"
FT   HELIX           1101..1109
FT                   /evidence="ECO:0007829|PDB:4E1Z"
FT   HELIX           1114..1127
FT                   /evidence="ECO:0007829|PDB:4E1Z"
FT   HELIX           1139..1148
FT                   /evidence="ECO:0007829|PDB:4E1Z"
FT   HELIX           1153..1155
FT                   /evidence="ECO:0007829|PDB:4E1Z"
FT   HELIX           1159..1172
FT                   /evidence="ECO:0007829|PDB:4E1Z"
SQ   SEQUENCE   1184 AA;  133315 MW;  2B42052073463AC8 CRC64;
     MVGTMPLCGR RAILEDSKAD GTEAQPLVPT GCLMVLLHWP GPEGGEPWVT FSQTSLTAEE
     VCIHIAHKVG ITPPCLNLFA LYNAQAKVWL PPNHILDTSQ DMNLYFRMRF YFRNWHGMNP
     QEPAVYRCGF PGAETSSDRA EQGVQLLDSA SFEYLFEQGK HEFMNDVVSL RDLSSEEEIH
     HFKNESLGMA FLHLCHLALS RGVPLEEMAR EISFKNCIPH SFRQHIRQHN VLTRLRLHRV
     FRRFLRAFRP GHLSQQVVMV KYLATLERLA PRFGSERIPV CHLEVLAQPE RDPCYIQNSG
     QTAGDPGPEL PSGPPTHEVL VTGTGGIQWH PLQTQESERG NSRGNPHGSR SGKKPKAPKA
     GEHLTESPQE PPWTYFCDFQ DISHVVLKER RVHIHLQDNK CLLLCLCSQA EALSFVALVD
     GYFRLTADSS HYLCHEVAPP RLVTSIQNGI HGPLMDPFVQ AKLWPEDGLY LIQWSTSHLH
     RLILTVAHRN PAFSNGPRGL RLRKFPITQQ PGAFVLDGWG RSFASLGDLR LALQGCSLRA
     GDDCFPLHHC CLPRPREISN LVIMRGSRAH TRPLNLSQLS FHRVHQDEIT QLSHLGQGTR
     TNVYEGLLRV GGPDEGKVDN GCPPEPGGTS GQQLRVVLKV LDPSHHDIAL AFYETASLMS
     QVSHMHLAFL HGVCVRGSEN IIVTEFVEHG PLDVWLRRQR GQVPMTWKMV VAQQLASALS
     YLEDKNLVHG NVCGRNILLA RLGLEEGTNP FIKLSDPGVG QGALSREERV ERIPWTAPEC
     LSGGTSSLGT ATDMWGFGAT LLEICFDGEA PLQGRGPSEK ERFYTKKHQL PEPSSPELAT
     LTRQCLTYEP AQRPSFRTIL RDLTRLQPQN LVGTSAVNSD SPASDPTVFH KRYLKKIRDL
     GEGHFGKVSL YCYDPTNDGT GEMVAVKALK EGCGPQLRSG WQREIEILRT LYHEHIVKYK
     GCCEDQGEKS VQLVMEYVPL GSLRDYLPRH CVGLAQLLLF AQQICEGMAY LHAQHYIHRD
     LAARNVLLDN DRLVKIGDFG LAKAVPEGHE YYRVREDGDS PVFWYAPECL KECKFYYASD
     VWSFGVTLYE LLTYCDSNQS PHMKFTELIG HTQGQMTVLR LTELLERGER LPRPDRCPCE
     IYHLMKNCWE TEASFRPTFQ NLVPILQTAQ EKYQGQVPSV FSVC
//