ID TXK_MOUSE Reviewed; 527 AA. AC P42682; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1995, sequence version 1. DT 02-SEP-2026, entry version 206. DE RecName: Full=Tyrosine-protein kinase TXK; DE EC=2.7.10.2; DE AltName: Full=PTK-RL-18; DE AltName: Full=Resting lymphocyte kinase; GN Name=Txk; Synonyms=Rlk; 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=C57BL/6J; TISSUE=Thymus; RX PubMed=7579892; DOI=10.1007/bf00360659; RA Haire R.N., Litman G.W.; RT "The murine form of TXK, a novel TEC kinase expressed in thymus maps to RT chromosome 5."; RL Mamm. Genome 6:476-480(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=FVB/N; TISSUE=Thymus; RX PubMed=7542761; RA Sommers C.L., Huang K., Shores E.W., Grinberg A., Charlick D.A., RA Kozak C.A., Love P.E.; RT "Murine txk: a protein tyrosine kinase gene regulated by T cell RT activation."; RL Oncogene 11:245-251(1995). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Thymus; RX PubMed=7829530; DOI=10.1074/jbc.270.4.1928; RA Hu Q., Davidson D., Schwartzberg P.L., Macchiarini F., Lenardo M.J., RA Bluestone J.A., Matis L.A.; RT "Identification of Rlk, a novel protein tyrosine kinase with predominant RT expression in the T cell lineage."; RL J. Biol. Chem. 270:1928-1934(1995). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=C57BL/6J; TISSUE=Liver; RA Higashitsuji H., Nonoguchi K., Arii S., Furutani M., Kaneko Y., RA Nakayama H., Fujita J.; RL Submitted (DEC-1994) to the EMBL/GenBank/DDBJ databases. RN [5] RP FUNCTION, AND INTERACTION WITH SH2D2A. RX PubMed=10587356; DOI=10.1084/jem.190.11.1657; RA Rajagopal K., Sommers C.L., Decker D.C., Mitchell E.O., Korthauer U., RA Sperling A.I., Kozak C.A., Love P.E., Bluestone J.A.; RT "RIBP, a novel Rlk/Txk- and Itk-binding adaptor protein that regulates T RT cell activation."; RL J. Exp. Med. 190:1657-1668(1999). RN [6] RP FUNCTION. RX PubMed=10562318; DOI=10.1084/jem.190.10.1427; RA Sommers C.L., Rabin R.L., Grinberg A., Tsay H.C., Farber J., Love P.E.; RT "A role for the Tec family tyrosine kinase Txk in T cell activation and RT thymocyte selection."; RL J. Exp. Med. 190:1427-1438(1999). RN [7] RP ALTERNATIVE INITIATION (ISOFORM 2), SUBCELLULAR LOCATION, PALMITOYLATION, RP MUTAGENESIS OF 16-CYS--CYS-18, AND ACTIVITY REGULATION. RX PubMed=9891083; DOI=10.1128/mcb.19.2.1498; RA Debnath J., Chamorro M., Czar M.J., Schaeffer E.M., Lenardo M.J., RA Varmus H.E., Schwartzberg P.L.; RT "rlk/TXK encodes two forms of a novel cysteine string tyrosine kinase RT activated by Src family kinases."; RL Mol. Cell. Biol. 19:1498-1507(1999). RN [8] RP FUNCTION IN PHOSPHORYLATION OF LCP2. RX PubMed=10660534; DOI=10.1074/jbc.275.6.3835; RA Schneider H., Guerette B., Guntermann C., Rudd C.E.; RT "Resting lymphocyte kinase (Rlk/Txk) targets lymphoid adaptor SLP-76 in the RT cooperative activation of interleukin-2 transcription in T-cells."; RL J. Biol. Chem. 275:3835-3840(2000). RN [9] RP INTERACTION WITH FYN, PHOSPHORYLATION AT TYR-420, AND SUBCELLULAR LOCATION. RX PubMed=11353545; DOI=10.1186/1471-2172-2-3; RA Chamorro M., Czar M.J., Debnath J., Cheng G., Lenardo M.J., Varmus H.E., RA Schwartzberg P.L.; RT "Requirements for activation and RAFT localization of the T-lymphocyte RT kinase Rlk/Txk."; RL BMC Immunol. 2:3-3(2001). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-91 AND TYR-420, AND RP IDENTIFICATION BY 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 [11] RP FUNCTION. RX PubMed=18941202; DOI=10.4049/jimmunol.181.9.6125; RA Sahu N., Venegas A.M., Jankovic D., Mitzner W., Gomez-Rodriguez J., RA Cannons J.L., Sommers C., Love P., Sher A., Schwartzberg P.L., August A.; RT "Selective expression rather than specific function of Txk and Itk regulate RT Th1 and Th2 responses."; RL J. Immunol. 181:6125-6131(2008). RN [12] 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). 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. Also contributes 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 (By similarity). Within the complex, phosphorylates both CC PARP1 and EEF1A1 (By similarity). Also phosphorylates key sites in LCP2 CC leading to the up-regulation of Th1 preferred cytokine IL-2. CC Phosphorylates 'Tyr-201' of CTLA4 which leads to the association of PI- CC 3 kinase with the CTLA4 receptor. {ECO:0000250|UniProtKB:P42681, CC ECO:0000269|PubMed:10562318, ECO:0000269|PubMed:10587356, CC ECO:0000269|PubMed:10660534, ECO:0000269|PubMed:18941202}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + CC ADP + H(+); Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- CC COMP:20101, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, CC ChEBI:CHEBI:61978, ChEBI:CHEBI:456216; EC=2.7.10.2; CC Evidence={ECO:0000250|UniProtKB:P42681}; CC -!- ACTIVITY REGULATION: Activated by phosphorylation by FYN. CC {ECO:0000269|PubMed:9891083}. CC -!- SUBUNIT: Interacts with PARP1 and EEF1A1 (By similarity). Interacts CC with SH2D2A (PubMed:10587356). Interacts with FYN (PubMed:11353545). CC {ECO:0000250|UniProtKB:P42681, ECO:0000269|PubMed:10587356, CC ECO:0000269|PubMed:11353545}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}. CC Cell membrane; Peripheral membrane protein. Note=Localizes in the CC vicinity of cell surface receptors in the plasma membrane after CC receptor stimulation. Translocates into the nucleus and enhances IFN- CC gamma gene transcription in T-cells. {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative initiation; Named isoforms=2; CC Name=1; CC IsoId=P42682-1; Sequence=Displayed; CC Name=2; CC IsoId=P42682-2; Sequence=VSP_041923; CC -!- TISSUE SPECIFICITY: Expressed in early thymocytes, T-cells and mast CC cells. 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:0000250}. CC -!- PTM: The cysteine string at the N-terminus is palmitoylated and CC required for the proper subcellular location. CC {ECO:0000269|PubMed:9891083}. CC -!- MISCELLANEOUS: [Isoform 2]: Produced by alternative initiation at Met- CC 55 of isoform 1. {ECO:0000305}. 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; U16145; AAC52264.1; -; mRNA. DR EMBL; U19607; AAA86698.1; -; mRNA. DR EMBL; L35268; AAA67039.1; -; mRNA. DR EMBL; D43964; BAA07900.1; -; mRNA. DR CCDS; CCDS51514.1; -. [P42682-1] DR CCDS; CCDS80298.1; -. [P42682-2] DR PIR; I49133; I49133. DR RefSeq; NP_001116226.1; NM_001122754.2. [P42682-1] DR RefSeq; NP_001276424.1; NM_001289495.1. [P42682-2] DR RefSeq; XP_011239024.1; XM_011240722.1. [P42682-2] DR AlphaFoldDB; P42682; -. DR BMRB; P42682; -. DR SMR; P42682; -. DR BioGRID; 204388; 14. DR FunCoup; P42682; 1327. DR STRING; 10090.ENSMUSP00000129397; -. DR iPTMnet; P42682; -. DR PhosphoSitePlus; P42682; -. DR SwissPalm; P42682; -. DR PaxDb; 10090-ENSMUSP00000129397; -. DR ProteomicsDB; 298039; -. [P42682-1] DR ProteomicsDB; 298040; -. [P42682-2] DR Pumba; P42682; -. DR Antibodypedia; 23802; 278 antibodies from 34 providers. DR DNASU; 22165; -. DR Ensembl; ENSMUST00000113604.10; ENSMUSP00000109234.4; ENSMUSG00000054892.15. [P42682-1] DR Ensembl; ENSMUST00000198464.3; ENSMUSP00000143002.2; ENSMUSG00000054892.15. [P42682-2] DR GeneID; 22165; -. DR KEGG; mmu:22165; -. DR UCSC; uc008xrx.3; mouse. [P42682-1] DR AGR; MGI:102960; -. DR CTD; 7294; -. DR MGI; MGI:102960; Txk. DR VEuPathDB; HostDB:ENSMUSG00000054892; -. DR eggNOG; KOG0197; Eukaryota. DR GeneTree; ENSGT00940000160857; -. DR InParanoid; P42682; -. DR OrthoDB; 4062651at2759; -. DR PhylomeDB; P42682; -. DR BRENDA; 2.7.10.2; 3474. DR Reactome; R-MMU-2871809; FCERI mediated Ca+2 mobilization. DR BioGRID-ORCS; 22165; 1 hit in 79 CRISPR screens. DR PRO; PR:P42682; -. DR Proteomes; UP000000589; Chromosome 5. DR RNAct; P42682; protein. DR Bgee; ENSMUSG00000054892; Expressed in thymus and 39 other cell types or tissues. DR ExpressionAtlas; P42682; baseline and differential. DR GO; GO:0005737; C:cytoplasm; ISO:GO_Central. DR GO; GO:0005829; C:cytosol; ISO:GO_Central. DR GO; GO:0005730; C:nucleolus; ISO:GO_Central. DR GO; GO:0005654; C:nucleoplasm; ISO:GO_Central. DR GO; GO:0005634; C:nucleus; ISO:GO_Central. DR GO; GO:0005886; C:plasma membrane; ISO:GO_Central. DR GO; GO:0005524; F:ATP binding; IEA:InterPro. DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IBA:GO_Central. DR GO; GO:0004713; F:protein tyrosine kinase activity; ISS:UniProtKB. DR GO; GO:0002250; P:adaptive immune response; IMP:UniProtKB. DR GO; GO:0001865; P:NK T cell differentiation; IGI:MGI. DR GO; GO:0001819; P:positive regulation of cytokine production; IMP:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:GO_Central. DR GO; GO:0032729; P:positive regulation of type II interferon production; ISO:GO_Central. DR GO; GO:0060335; P:positive regulation of type II interferon-mediated signaling pathway; ISO:GO_Central. DR GO; GO:0046777; P:protein autophosphorylation; ISO:GO_Central. DR GO; GO:0006468; P:protein phosphorylation; ISO:GO_Central. DR GO; GO:0050852; P:T cell receptor signaling pathway; IMP:UniProtKB. DR CDD; cd10398; SH2_Tec_Txk; 1. DR CDD; cd11907; SH3_TXK; 1. DR FunFam; 1.10.510.10:FF:000052; Tyrosine-protein kinase; 1. DR FunFam; 3.30.200.20:FF:000053; Tyrosine-protein kinase; 1. DR FunFam; 3.30.505.10:FF:000045; Tyrosine-protein kinase; 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; IPR050198; Non-receptor_tyrosine_kinases. 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 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. PE 1: Evidence at protein level; KW Adaptive immunity; Alternative initiation; ATP-binding; Cell membrane; KW Cytoplasm; Immunity; Kinase; Lipoprotein; Membrane; Nucleotide-binding; KW Nucleus; Palmitate; Phosphoprotein; Reference proteome; SH2 domain; KW SH3 domain; Transcription; Transcription regulation; Transferase; KW Tyrosine-protein kinase. FT CHAIN 1..527 FT /note="Tyrosine-protein kinase TXK" FT /id="PRO_0000088176" 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 58..81 FT /note="Disordered" 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:0007744|PubMed:17947660" FT MOD_RES 420 FT /note="Phosphotyrosine; by FYN and autocatalysis" FT /evidence="ECO:0000269|PubMed:11353545, FT ECO:0007744|PubMed:17947660" FT VAR_SEQ 1..54 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_041923" FT MUTAGEN 16..18 FT /note="CCC->SLA: Reduces palmitoylation and leads to FT nuclear localization." FT /evidence="ECO:0000269|PubMed:9891083" FT CONFLICT 3..4 FT /note="LS -> SF (in Ref. 4; BAA07900)" FT /evidence="ECO:0000305" FT CONFLICT 6 FT /note="Y -> D (in Ref. 4; BAA07900)" FT /evidence="ECO:0000305" FT CONFLICT 272 FT /note="A -> T (in Ref. 4; BAA07900)" FT /evidence="ECO:0000305" FT CONFLICT 497 FT /note="R -> S (in Ref. 4; BAA07900)" FT /evidence="ECO:0000305" SQ SEQUENCE 527 AA; 61108 MW; D3A32C09B3A201FA CRC64; MILSSYSSFQ SVLCCCCCRC SVQKRQVRTQ ISLSREEELS EKHSQRQRPW FAKLMGKTQS NRGGVQPSKR KPLPPLPQEP PDERIQVKAL YDFLPREPGN LALKRAEEYL ILERCDPHWW KARDRFGNEG LIPSNYVTEN RLANLEIYEW YHKNITRNQT ERLLRQEAKE GAFIVRDSRH LGSYTISVFT RARRHTQSSI KHYQIKKNDS GQWYITERHL FPSVPELIQY HQYNAAGLIS RLRYPIGLLG SCLPATSGFS YEKWEIDPSE LAFVKEIGSG QFGVVHLGEW RAHIPVAIKA INEGSMSEED FIEEAKVMMK LSHSRLVQLY GVCIQQKPLY IVTEFMENGC LLDYLRERKG QLQKALLLSM CQDICEGMAY LERSCYIHRD LAARNCLVSS ACVVKISDFG MARYVLDDEY ISSSGAKFPV KWCPPEVFHF NKYSSKSDVW SFGVLMWEVF TEGKMPFENK SNLQVVEAIS QGFRLYRPHL APMTIYRVMY SCWHESPKGR PTFAELLQVL TEIAETW //