ID TXK_HUMAN Reviewed; 527 AA. AC P42681; Q14220; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 17-OCT-2006, sequence version 3. DT 24-JAN-2024, entry version 208. DE RecName: Full=Tyrosine-protein kinase TXK; DE EC=2.7.10.2 {ECO:0000269|PubMed:17177976}; DE AltName: Full=Protein-tyrosine kinase 4; DE AltName: Full=Resting lymphocyte kinase; GN Name=TXK; Synonyms=PTK4, RLK; 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], VARIANT HIS-45, AND TISSUE SPECIFICITY. RC TISSUE=Blood; RX PubMed=7951233; DOI=10.1093/hmg/3.6.897; RA Haire R.N., Ohta Y., Lewis J.E., Fu S.M., Kroisel P.M., Litman G.W.; RT "TXK, a novel human tyrosine kinase expressed in T cells shares sequence RT identity with Tec family kinases and maps to 4p12."; RL Hum. Mol. Genet. 3:897-901(1994). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC TISSUE=Blood; RX PubMed=8632917; RA Ohta Y., Haire R.N., Amemiya C.T., Litman R.T., Trager T., Riess O., RA Litman G.W.; RT "Human Txk: genomic organization, structure and contiguous physical linkage RT with the Tec gene."; RL Oncogene 12:937-942(1996). RN [3] RP FUNCTION IN PHOSPHORYLATION OF CTLA4, AND MUTAGENESIS OF LYS-299. RX PubMed=9813138; DOI=10.1006/bbrc.1998.9559; RA Schneider H., Schwartzberg P.L., Rudd C.E.; RT "Resting lymphocyte kinase (Rlk/Txk) phosphorylates the YVKM motif and RT regulates PI 3-kinase binding to T-cell antigen CTLA-4."; RL Biochem. Biophys. Res. Commun. 252:14-19(1998). RN [4] RP TISSUE SPECIFICITY, AND FUNCTION. RX PubMed=10523612; DOI=10.1084/jem.190.8.1147; RA Kashiwakura J., Suzuki N., Nagafuchi H., Takeno M., Takeba Y., RA Shimoyama Y., Sakane T.; RT "Txk, a nonreceptor tyrosine kinase of the Tec family, is expressed in T RT helper type 1 cells and regulates interferon gamma production in human T RT lymphocytes."; RL J. Exp. Med. 190:1147-1154(1999). RN [5] RP FUNCTION IN PHOSPHORYLATION OF PLCG1. RX PubMed=11564877; DOI=10.1128/mcb.21.20.6939-6950.2001; RA Veri M.C., DeBell K.E., Seminario M.C., DiBaldassarre A., Reischl I., RA Rawat R., Graham L., Noviello C., Rellahan B.L., Miscia S., Wange R.L., RA Bonvini E.; RT "Membrane raft-dependent regulation of phospholipase Cgamma-1 activation in RT T lymphocytes."; RL Mol. Cell. Biol. 21:6939-6950(2001). RN [6] RP AUTOPHOSPHORYLATION, PHOSPHORYLATION AT TYR-91 AND TYR-420, ACTIVITY RP REGULATION, AND MUTAGENESIS OF TYR-91. RX PubMed=12081135; DOI=10.1248/bpb.25.718; RA Kashiwakura J., Suzuki N., Takeno M., Itoh S., Oku T., Sakane T., RA Nakajin S., Toyoshima S.; RT "Evidence of autophosphorylation in Txk: Y91 is an autophosphorylation RT site."; RL Biol. Pharm. Bull. 25:718-721(2002). RN [7] RP FUNCTION. RX PubMed=11859127; DOI=10.4049/jimmunol.168.5.2365; RA Takeba Y., Nagafuchi H., Takeno M., Kashiwakura J., Suzuki N.; RT "Txk, a member of nonreceptor tyrosine kinase of Tec family, acts as a Th1 RT cell-specific transcription factor and regulates IFN-gamma gene RT transcription."; RL J. Immunol. 168:2365-2370(2002). RN [8] RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH PARP1 AND EEF1A1, AND RP SUBCELLULAR LOCATION. RX PubMed=17177976; DOI=10.1111/j.1365-2249.2006.03249.x; RA Maruyama T., Nara K., Yoshikawa H., Suzuki N.; RT "Txk, a member of the non-receptor tyrosine kinase of the Tec family, forms RT a complex with poly(ADP-ribose) polymerase 1 and elongation factor 1alpha RT and regulates interferon-gamma gene transcription in Th1 cells."; RL Clin. Exp. Immunol. 147:164-175(2007). RN [9] RP REVIEW ON FUNCTION. RX PubMed=19290923; DOI=10.1111/j.1600-065x.2008.00757.x; RA Readinger J.A., Mueller K.L., Venegas A.M., Horai R., Schwartzberg P.L.; RT "Tec kinases regulate T-lymphocyte development and function: new insights RT into the roles of Itk and Rlk/Txk."; RL Immunol. Rev. 228:93-114(2009). RN [10] RP STRUCTURE BY NMR OF 140-251. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the SH2 domain of human tyrosine-protein kinase RT TXK."; RL Submitted (OCT-2006) to the PDB data bank. RN [11] RP VARIANTS [LARGE SCALE ANALYSIS] HIS-45; CYS-63 AND GLN-336. 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: Non-receptor tyrosine kinase that plays a redundant role with CC ITK in regulation of the adaptive immune response. Regulates the CC development, function and differentiation of conventional T-cells and CC nonconventional NKT-cells. When antigen presenting cells (APC) activate CC T-cell receptor (TCR), a series of phosphorylation leads to the CC recruitment of TXK to the cell membrane, where it is phosphorylated at CC Tyr-420. Phosphorylation leads to TXK full activation. Contributes also CC to signaling from many receptors and participates in multiple CC downstream pathways, including regulation of the actin cytoskeleton. CC Like ITK, can phosphorylate PLCG1, leading to its localization in lipid CC rafts and activation, followed by subsequent cleavage of its CC substrates. In turn, the endoplasmic reticulum releases calcium in the CC cytoplasm and the nuclear activator of activated T-cells (NFAT) CC translocates into the nucleus to perform its transcriptional duty. CC Plays a role in the positive regulation of IFNG transcription in T- CC helper 1 cells as part of an IFNG promoter-binding complex with PARP1 CC and EEF1A1 (PubMed:11859127, PubMed:17177976). Within the complex, CC phosphorylates both PARP1 and EEF1A1 (PubMed:17177976). Phosphorylates CC also key sites in LCP2 leading to the up-regulation of Th1 preferred CC cytokine IL-2. Phosphorylates 'Tyr-201' of CTLA4 which leads to the CC association of PI-3 kinase with the CTLA4 receptor. CC {ECO:0000269|PubMed:10523612, ECO:0000269|PubMed:11564877, CC ECO:0000269|PubMed:11859127, ECO:0000269|PubMed:17177976, CC ECO:0000269|PubMed:9813138}. 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:17177976}; CC -!- ACTIVITY REGULATION: Activated by phosphorylation by FYN. CC {ECO:0000269|PubMed:12081135}. CC -!- SUBUNIT: Interacts with PARP1 and EEF1A1 (PubMed:17177976). Interacts CC with SH2D2A (By similarity). Interacts with FYN (By similarity). CC {ECO:0000250|UniProtKB:P42682, ECO:0000269|PubMed:17177976}. CC -!- INTERACTION: CC P42681; Q8NA61-2: CBY2; NbExp=3; IntAct=EBI-7877438, EBI-11524851; CC P42681; P46108: CRK; NbExp=3; IntAct=EBI-7877438, EBI-886; CC P42681; O60496: DOK2; NbExp=3; IntAct=EBI-7877438, EBI-1046024; CC P42681; Q16828: DUSP6; NbExp=3; IntAct=EBI-7877438, EBI-746870; CC P42681; Q5JST6: EFHC2; NbExp=3; IntAct=EBI-7877438, EBI-2349927; CC P42681; Q13322-4: GRB10; NbExp=3; IntAct=EBI-7877438, EBI-12353035; CC P42681; P62993: GRB2; NbExp=3; IntAct=EBI-7877438, EBI-401755; CC P42681; Q13422-7: IKZF1; NbExp=3; IntAct=EBI-7877438, EBI-11522367; CC P42681; Q9H2S9: IKZF4; NbExp=3; IntAct=EBI-7877438, EBI-1640423; CC P42681; O75564-2: JRK; NbExp=3; IntAct=EBI-7877438, EBI-17181882; CC P42681; P10721: KIT; NbExp=3; IntAct=EBI-7877438, EBI-1379503; CC P42681; O43639: NCK2; NbExp=3; IntAct=EBI-7877438, EBI-713635; CC P42681; P27986-2: PIK3R1; NbExp=3; IntAct=EBI-7877438, EBI-9090282; CC P42681; Q9GZV8: PRDM14; NbExp=3; IntAct=EBI-7877438, EBI-3957793; CC P42681; Q9NYW8: RBAK; NbExp=3; IntAct=EBI-7877438, EBI-1210429; CC P42681; O14543: SOCS3; NbExp=3; IntAct=EBI-7877438, EBI-714146; CC P42681; O14544: SOCS6; NbExp=3; IntAct=EBI-7877438, EBI-3929549; CC P42681; Q9UGK3: STAP2; NbExp=3; IntAct=EBI-7877438, EBI-1553984; CC P42681; Q8IZW8: TNS4; NbExp=3; IntAct=EBI-7877438, EBI-7543499; CC P42681; Q96SQ5: ZNF587; NbExp=3; IntAct=EBI-7877438, EBI-6427977; CC P42681; Q3KQV3: ZNF792; NbExp=3; IntAct=EBI-7877438, EBI-10240849; CC P42681; Q9Y2P0: ZNF835; NbExp=3; IntAct=EBI-7877438, EBI-5667516; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17177976}. Nucleus CC {ECO:0000269|PubMed:17177976}. Cell membrane CC {ECO:0000269|PubMed:17177976}; Peripheral membrane protein CC {ECO:0000269|PubMed:17177976}. Note=Localizes in the vicinity of cell CC surface receptors in the plasma membrane after receptor stimulation. CC Translocates into the nucleus and enhances IFN-gamma gene transcription CC in T-cells. CC -!- TISSUE SPECIFICITY: Expressed in T-cells and some myeloid cell lines. CC Expressed in Th1/Th0 cells with IFN-gamma-producing potential. CC {ECO:0000269|PubMed:10523612, ECO:0000269|PubMed:7951233}. CC -!- PTM: Phosphorylated at Tyr-420 by FYN. Autophosphorylation at Tyr-91 is CC critical for the activation of TXK, leading to the up-regulation of CC IFN-gamma gene transcription. {ECO:0000269|PubMed:12081135}. CC -!- PTM: The cysteine string at the N-terminus is palmitoylated and CC required for the proper subcellular location. {ECO:0000250}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. TEC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}. CC -!- CAUTION: Unlike the other TEC subfamily members, TXK is activated CC independently of the activity of phosphatidylinositol 3-kinase, CC consistent with its lack of a PH domain. Membrane association is CC performed through palmitoylation at the N-terminus. {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; L27071; AAA74557.1; -; mRNA. DR EMBL; U34379; AAB60412.1; -; Genomic_DNA. DR EMBL; U34367; AAB60412.1; JOINED; Genomic_DNA. DR EMBL; U34368; AAB60412.1; JOINED; Genomic_DNA. DR EMBL; U34369; AAB60412.1; JOINED; Genomic_DNA. DR EMBL; U34370; AAB60412.1; JOINED; Genomic_DNA. DR EMBL; U34371; AAB60412.1; JOINED; Genomic_DNA. DR EMBL; U34372; AAB60412.1; JOINED; Genomic_DNA. DR EMBL; U34373; AAB60412.1; JOINED; Genomic_DNA. DR EMBL; U34374; AAB60412.1; JOINED; Genomic_DNA. DR EMBL; U34375; AAB60412.1; JOINED; Genomic_DNA. DR EMBL; U34376; AAB60412.1; JOINED; Genomic_DNA. DR EMBL; U34377; AAB60412.1; JOINED; Genomic_DNA. DR EMBL; U34378; AAB60412.1; JOINED; Genomic_DNA. DR CCDS; CCDS3480.1; -. DR PIR; I84483; I84483. DR RefSeq; NP_003319.2; NM_003328.2. DR PDB; 2DM0; NMR; -; A=140-251. DR PDBsum; 2DM0; -. DR AlphaFoldDB; P42681; -. DR SMR; P42681; -. DR BioGRID; 113145; 39. DR IntAct; P42681; 85. DR MINT; P42681; -. DR STRING; 9606.ENSP00000264316; -. DR BindingDB; P42681; -. DR ChEMBL; CHEMBL4367; -. DR DrugBank; DB12010; Fostamatinib. DR DrugBank; DB15035; Zanubrutinib. DR DrugCentral; P42681; -. DR GuidetoPHARMACOLOGY; 2268; -. DR iPTMnet; P42681; -. DR PhosphoSitePlus; P42681; -. DR BioMuta; TXK; -. DR DMDM; 116242835; -. DR MassIVE; P42681; -. DR PaxDb; 9606-ENSP00000264316; -. DR PeptideAtlas; P42681; -. DR ProteomicsDB; 55527; -. DR Antibodypedia; 23802; 288 antibodies from 34 providers. DR DNASU; 7294; -. DR Ensembl; ENST00000264316.9; ENSP00000264316.4; ENSG00000074966.11. DR GeneID; 7294; -. DR KEGG; hsa:7294; -. DR MANE-Select; ENST00000264316.9; ENSP00000264316.4; NM_003328.3; NP_003319.2. DR UCSC; uc003gxx.4; human. DR AGR; HGNC:12434; -. DR CTD; 7294; -. DR DisGeNET; 7294; -. DR GeneCards; TXK; -. DR HGNC; HGNC:12434; TXK. DR HPA; ENSG00000074966; Tissue enhanced (epididymis, lymphoid tissue). DR MIM; 600058; gene. DR neXtProt; NX_P42681; -. DR OpenTargets; ENSG00000074966; -. DR PharmGKB; PA37090; -. DR VEuPathDB; HostDB:ENSG00000074966; -. DR eggNOG; KOG0197; Eukaryota. DR GeneTree; ENSGT00940000160857; -. DR HOGENOM; CLU_000288_7_2_1; -. DR InParanoid; P42681; -. DR OMA; KHYQIKS; -. DR OrthoDB; 1614410at2759; -. DR PhylomeDB; P42681; -. DR TreeFam; TF351634; -. DR BRENDA; 2.7.10.2; 2681. DR PathwayCommons; P42681; -. DR Reactome; R-HSA-2871809; FCERI mediated Ca+2 mobilization. DR SignaLink; P42681; -. DR SIGNOR; P42681; -. DR BioGRID-ORCS; 7294; 21 hits in 1187 CRISPR screens. DR ChiTaRS; TXK; human. DR EvolutionaryTrace; P42681; -. DR GeneWiki; TXK_(gene); -. DR GenomeRNAi; 7294; -. DR Pharos; P42681; Tchem. DR PRO; PR:P42681; -. DR Proteomes; UP000005640; Chromosome 4. DR RNAct; P42681; Protein. DR Bgee; ENSG00000074966; Expressed in granulocyte and 109 other cell types or tissues. DR ExpressionAtlas; P42681; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IBA:GO_Central. DR GO; GO:0007202; P:activation of phospholipase C activity; ISS:UniProtKB. DR GO; GO:0002250; P:adaptive immune response; ISS:UniProtKB. DR GO; GO:0007229; P:integrin-mediated signaling pathway; IBA:GO_Central. DR GO; GO:0001819; P:positive regulation of cytokine production; ISS:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB. DR GO; GO:0032729; P:positive regulation of type II interferon production; IDA:UniProtKB. DR GO; GO:0060335; P:positive regulation of type II interferon-mediated signaling pathway; IDA:UniProtKB. DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB. DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB. DR GO; GO:0010468; P:regulation of gene expression; IDA:GO_Central. DR GO; GO:0010543; P:regulation of platelet activation; IBA:GO_Central. DR GO; GO:0050852; P:T cell receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0042246; P:tissue regeneration; IBA:GO_Central. DR CDD; cd05059; PTKc_Tec_like; 1. DR CDD; cd10398; SH2_Tec_Txk; 1. DR CDD; cd11907; SH3_TXK; 1. DR Gene3D; 3.30.505.10; SH2 domain; 1. DR Gene3D; 2.30.30.40; SH3 Domains; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. 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; IPR036028; SH3-like_dom_sf. DR InterPro; IPR001452; SH3_domain. DR InterPro; IPR035870; Txk_SH2. DR InterPro; IPR035579; TXK_SH3. DR InterPro; IPR008266; Tyr_kinase_AS. DR InterPro; IPR020635; Tyr_kinase_cat_dom. DR PANTHER; PTHR24418; TYROSINE-PROTEIN KINASE; 1. DR PANTHER; PTHR24418:SF247; TYROSINE-PROTEIN KINASE TXK; 1. DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1. DR Pfam; PF00017; SH2; 1. DR Pfam; PF00018; SH3_1; 1. DR PRINTS; PR00401; SH2DOMAIN. DR PRINTS; PR00109; TYRKINASE. DR SMART; SM00252; SH2; 1. DR SMART; SM00326; SH3; 1. DR SMART; SM00219; TyrKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF55550; SH2 domain; 1. DR SUPFAM; SSF50044; SH3-domain; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. DR PROSITE; PS50001; SH2; 1. DR PROSITE; PS50002; SH3; 1. DR Genevisible; P42681; HS. PE 1: Evidence at protein level; KW 3D-structure; Adaptive immunity; ATP-binding; Cell membrane; Cytoplasm; KW Immunity; Kinase; Lipoprotein; Membrane; Nucleotide-binding; Nucleus; KW Palmitate; Phosphoprotein; Reference proteome; SH2 domain; SH3 domain; KW Transcription; Transcription regulation; Transferase; KW Tyrosine-protein kinase. FT CHAIN 1..527 FT /note="Tyrosine-protein kinase TXK" FT /id="PRO_0000088175" FT DOMAIN 82..142 FT /note="SH3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT DOMAIN 150..246 FT /note="SH2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191" FT DOMAIN 271..527 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 35..79 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 68..73 FT /note="Nuclear localization signal" FT /evidence="ECO:0000255" FT COMPBIAS 47..66 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 390 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10028" FT BINDING 277..285 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 299 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 91 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:12081135" FT MOD_RES 420 FT /note="Phosphotyrosine; by FYN and autocatalysis" FT /evidence="ECO:0000269|PubMed:12081135" FT VARIANT 45 FT /note="R -> H (in dbSNP:rs7658300)" FT /evidence="ECO:0000269|PubMed:17344846, FT ECO:0000269|PubMed:7951233" FT /id="VAR_028368" FT VARIANT 63 FT /note="R -> C (in dbSNP:rs41265727)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041869" FT VARIANT 336 FT /note="R -> Q (in dbSNP:rs11724347)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_028369" FT MUTAGEN 91 FT /note="Y->A: Reduces expression levels if IFN-gamma." FT /evidence="ECO:0000269|PubMed:12081135" FT MUTAGEN 299 FT /note="K->A: Impairs kinase activity." FT /evidence="ECO:0000269|PubMed:9813138" FT STRAND 148..151 FT /evidence="ECO:0007829|PDB:2DM0" FT HELIX 157..167 FT /evidence="ECO:0007829|PDB:2DM0" FT STRAND 175..178 FT /evidence="ECO:0007829|PDB:2DM0" FT STRAND 181..189 FT /evidence="ECO:0007829|PDB:2DM0" FT STRAND 193..197 FT /evidence="ECO:0007829|PDB:2DM0" FT STRAND 200..207 FT /evidence="ECO:0007829|PDB:2DM0" FT STRAND 213..218 FT /evidence="ECO:0007829|PDB:2DM0" FT HELIX 224..231 FT /evidence="ECO:0007829|PDB:2DM0" FT STRAND 237..239 FT /evidence="ECO:0007829|PDB:2DM0" SQ SEQUENCE 527 AA; 61258 MW; BCCA081F4155CAA6 CRC64; MILSSYNTIQ SVFCCCCCCS VQKRQMRTQI SLSTDEELPE KYTQRRRPWL SQLSNKKQSN TGRVQPSKRK PLPPLPPSEV AEEKIQVKAL YDFLPREPCN LALRRAEEYL ILEKYNPHWW KARDRLGNEG LIPSNYVTEN KITNLEIYEW YHRNITRNQA EHLLRQESKE GAFIVRDSRH LGSYTISVFM GARRSTEAAI KHYQIKKNDS GQWYVAERHA FQSIPELIWY HQHNAAGLMT RLRYPVGLMG SCLPATAGFS YEKWEIDPSE LAFIKEIGSG QFGVVHLGEW RSHIQVAIKA INEGSMSEED FIEEAKVMMK LSHSKLVQLY GVCIQRKPLY IVTEFMENGC LLNYLRENKG KLRKEMLLSV CQDICEGMEY LERNGYIHRD LAARNCLVSS TCIVKISDFG MTRYVLDDEY VSSFGAKFPI KWSPPEVFLF NKYSSKSDVW SFGVLMWEVF TEGKMPFENK SNLQVVEAIS EGFRLYRPHL APMSIYEVMY SCWHEKPEGR PTFAELLRAV TEIAETW //