TXK_MOUSE
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 03-AUG-2022, entry version 188.
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. 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 (By similarity). Within the complex, phosphorylates both
CC PARP1 and EEF1A1 (By similarity). Phosphorylates also 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=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: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}.
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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 STRING; 10090.ENSMUSP00000129397; -.
DR iPTMnet; P42682; -.
DR PhosphoSitePlus; P42682; -.
DR SwissPalm; P42682; -.
DR jPOST; P42682; -.
DR PaxDb; P42682; -.
DR PRIDE; P42682; -.
DR ProteomicsDB; 298039; -. [P42682-1]
DR ProteomicsDB; 298040; -. [P42682-2]
DR Antibodypedia; 23802; 274 antibodies from 34 providers.
DR DNASU; 22165; -.
DR Ensembl; ENSMUST00000113604; ENSMUSP00000109234; ENSMUSG00000054892. [P42682-1]
DR Ensembl; ENSMUST00000198464; ENSMUSP00000143002; ENSMUSG00000054892. [P42682-2]
DR GeneID; 22165; -.
DR KEGG; mmu:22165; -.
DR UCSC; uc008xrx.3; mouse. [P42682-1]
DR CTD; 7294; -.
DR MGI; MGI:102960; Txk.
DR VEuPathDB; HostDB:ENSMUSG00000054892; -.
DR eggNOG; KOG0197; Eukaryota.
DR GeneTree; ENSGT00940000160857; -.
DR InParanoid; P42682; -.
DR OrthoDB; 1047190at2759; -.
DR PhylomeDB; P42682; -.
DR TreeFam; TF351634; -.
DR BRENDA; 2.7.10.2; 3474.
DR Reactome; R-MMU-2871809; FCERI mediated Ca+2 mobilization.
DR BioGRID-ORCS; 22165; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Txk; mouse.
DR PRO; PR:P42682; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; P42682; protein.
DR Bgee; ENSMUSG00000054892; Expressed in thymus and 38 other tissues.
DR ExpressionAtlas; P42682; baseline and differential.
DR Genevisible; P42682; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
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:0004713; F:protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0007202; P:activation of phospholipase C activity; IMP:UniProtKB.
DR GO; GO:0002250; P:adaptive immune response; IMP:UniProtKB.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; IBA:GO_Central.
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:0032729; P:positive regulation of interferon-gamma production; ISO:MGI.
DR GO; GO:0060335; P:positive regulation of interferon-gamma-mediated signaling pathway; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0046777; P:protein autophosphorylation; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; ISO:MGI.
DR GO; GO:0010468; P:regulation of gene expression; ISO:MGI.
DR GO; GO:0010543; P:regulation of platelet activation; IBA:GO_Central.
DR GO; GO:0050852; P:T cell receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0042246; P:tissue regeneration; IBA:GO_Central.
DR CDD; cd10398; SH2_Tec_Txk; 1.
DR CDD; cd11907; SH3_TXK; 1.
DR Gene3D; 3.30.505.10; -; 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 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; SSF50044; SSF50044; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR SUPFAM; SSF56112; SSF56112; 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
