LTK_HUMAN
ID LTK_HUMAN Reviewed; 864 AA.
AC P29376; A6NNJ8; B4DL89; E9PFX4;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2007, sequence version 3.
DT 03-AUG-2022, entry version 201.
DE RecName: Full=Leukocyte tyrosine kinase receptor {ECO:0000303|PubMed:1655406};
DE EC=2.7.10.1 {ECO:0000255|PROSITE-ProRule:PRU10028, ECO:0000269|PubMed:10445845, ECO:0000269|PubMed:30061385};
DE AltName: Full=Protein tyrosine kinase 1;
DE Flags: Precursor;
GN Name=LTK {ECO:0000303|PubMed:1655406, ECO:0000312|HGNC:HGNC:6721};
GN Synonyms=TYK1;
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 VARIANT GLN-42.
RC TISSUE=Placenta;
RX PubMed=7685902; DOI=10.1073/pnas.90.12.5404;
RA Toyoshima H., Kozutsumi H., Maru Y., Hagiwara K., Furaya A., Mioh H.,
RA Hanai N., Takaku F., Yazaki Y., Hirai H.;
RT "Differently spliced cDNAs of human leukocyte tyrosine kinase receptor
RT tyrosine kinase predict receptor proteins with and without a tyrosine
RT kinase domain and a soluble receptor protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:5404-5408(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=1655406; DOI=10.1002/j.1460-2075.1991.tb07841.x;
RA Krolewski J.J., Dalla-Favera R.;
RT "The ltk gene encodes a novel receptor-type protein tyrosine kinase.";
RL EMBO J. 10:2911-2919(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
RC TISSUE=Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 416-864.
RX PubMed=2320375;
RA Maru Y., Hirai H., Takaku F.;
RT "Human ltk: gene structure and preferential expression in human leukemic
RT cells.";
RL Oncogene Res. 5:199-204(1990).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 608-716, 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 [8]
RP PHOSPHORYLATION, AND MUTAGENESIS OF LYS-544.
RX PubMed=8084603;
RA Kozutsumi H., Toyoshima H., Hagiwara K., Yazaki Y., Hirai H.;
RT "Human ltk receptor tyrosine kinase binds to PLC-gamma 1, PI3-K, GAP and
RT Raf-1 in vivo.";
RL Oncogene 9:2991-2998(1994).
RN [9]
RP POSSIBLE FUNCTION, AND MUTAGENESIS OF TYR-753 AND TYR-862.
RX PubMed=9223670; DOI=10.1038/sj.onc.1201153;
RA Ueno H., Honda H., Nakamoto T., Yamagata T., Sasaki K., Miyagawa K.,
RA Mitani K., Yazaki Y., Hirai H.;
RT "The phosphatidylinositol 3' kinase pathway is required for the survival
RT signal of leukocyte tyrosine kinase.";
RL Oncogene 14:3067-3072(1997).
RN [10]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=10445845; DOI=10.1038/sj.onc.1202736;
RA Honda H., Harada K., Komuro I., Terasaki F., Ueno H., Tanaka Y.,
RA Kawamura K., Yazaki Y., Hirai H.;
RT "Heart-specific activation of LTK results in cardiac hypertrophy,
RT cardiomyocyte degeneration and gene reprogramming in transgenic mice.";
RL Oncogene 18:3821-3830(1999).
RN [11]
RP POSSIBLE INVOLVEMENT IN SUSCEPTIBILITY TO SYSTEMIC LUPUS ERYTHEMATOSUS,
RP VARIANT LYS-763, CHARACTERIZATION OF VARIANT LYS-763, AUTOPHOSPHORYLATION,
RP AND MUTAGENESIS OF GLY-750.
RX PubMed=14695357; DOI=10.1093/hmg/ddh020;
RA Li N., Nakamura K., Jiang Y., Tsurui H., Matsuoka S., Abe M., Ohtsuji M.,
RA Nishimura H., Kato K., Kawai T., Atsumi T., Koike T., Shirai T., Ueno H.,
RA Hirose S.;
RT "Gain-of-function polymorphism in mouse and human Ltk: implications for the
RT pathogenesis of systemic lupus erythematosus.";
RL Hum. Mol. Genet. 13:171-179(2004).
RN [12]
RP POSSIBLE FUNCTION.
RX PubMed=18849880; DOI=10.1097/wnr.0b013e3283186bf8;
RA Yamada S., Nomura T., Takano K., Fujita S., Miyake M., Miyake J.;
RT "Expression of a chimeric CSF1R-LTK mediates ligand-dependent neurite
RT outgrowth.";
RL NeuroReport 19:1733-1738(2008).
RN [13]
RP INTERACTION WITH GRB2 AND TNK2.
RX PubMed=19815557; DOI=10.1074/jbc.m109.072660;
RA Pao-Chun L., Chan P.M., Chan W., Manser E.;
RT "Cytoplasmic ACK1 interaction with multiple receptor tyrosine kinases is
RT mediated by Grb2: an analysis of ACK1 effects on Axl signaling.";
RL J. Biol. Chem. 284:34954-34963(2009).
RN [14]
RP FUNCTION IN REGULATION OF THE SECRETORY PATHWAY.
RX PubMed=20548102; DOI=10.1083/jcb.200912082;
RA Farhan H., Wendeler M.W., Mitrovic S., Fava E., Silberberg Y., Sharan R.,
RA Zerial M., Hauri H.P.;
RT "MAPK signaling to the early secretory pathway revealed by
RT kinase/phosphatase functional screening.";
RL J. Cell Biol. 189:997-1011(2010).
RN [15]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=30061385; DOI=10.1073/pnas.1807881115;
RA Reshetnyak A.V., Mohanty J., Tome F., Puleo D.E., Plotnikov A.N., Ahmed M.,
RA Kaur N., Poliakov A., Cinnaiyan A.M., Lax I., Schlessinger J.;
RT "Identification of a biologically active fragment of ALK and LTK-Ligand 2
RT (augmentor-alpha).";
RL Proc. Natl. Acad. Sci. U.S.A. 115:8340-8345(2018).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (1.30 ANGSTROMS) OF 63-378 IN COMPLEX WITH ALKAL1,
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND MUTAGENESIS OF ARG-241.
RX PubMed=34646012; DOI=10.1038/s41586-021-03959-5;
RA De Munck S., Provost M., Kurikawa M., Omori I., Mukohyama J., Felix J.,
RA Bloch Y., Abdel-Wahab O., Bazan J.F., Yoshimi A., Savvides S.N.;
RT "Structural basis of cytokine-mediated activation of ALK family
RT receptors.";
RL Nature 600:143-147(2021).
RN [17]
RP VARIANTS [LARGE SCALE ANALYSIS] GLN-42; ARG-384; ASN-535; SER-569; GLN-673;
RP SER-745 AND SER-838.
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: Receptor with a tyrosine-protein kinase activity
CC (PubMed:10445845, PubMed:20548102, PubMed:30061385). Following
CC activation by ALKAL1 or ALKAL2 ligands at the cell surface, transduces
CC an extracellular signal into an intracellular response
CC (PubMed:30061385, PubMed:34646012). Ligand-binding to the extracellular
CC domain induces tyrosine kinase activation, leading to activation of the
CC mitogen-activated protein kinase (MAPK) pathway (PubMed:20548102).
CC Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-
CC Y-Y motif (By similarity). The exact function of this protein is not
CC known; studies with chimeric proteins demonstrate its ability to
CC promote growth and specifically neurite outgrowth, and cell survival
CC (PubMed:9223670, PubMed:18849880). Involved in regulation of the
CC secretory pathway involving endoplasmic reticulum (ER) export sites
CC (ERESs) and ER to Golgi transport (PubMed:20548102).
CC {ECO:0000250|UniProtKB:Q9UM73, ECO:0000269|PubMed:10445845,
CC ECO:0000269|PubMed:18849880, ECO:0000269|PubMed:20548102,
CC ECO:0000269|PubMed:30061385, ECO:0000269|PubMed:34646012,
CC ECO:0000269|PubMed:9223670}.
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=2.7.10.1;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028,
CC ECO:0000269|PubMed:10445845, ECO:0000269|PubMed:30061385};
CC -!- ACTIVITY REGULATION: Activated by ligand-binding, leading to
CC homodimerization and autophosphorylation.
CC {ECO:0000250|UniProtKB:Q9UM73}.
CC -!- SUBUNIT: Homodimer; homodimerizes following ligand-binding
CC (PubMed:34646012). Part of a complex including LTK, TNK2 and GRB2, in
CC which GRB2 promotes LTK recruitment by TNK2 (PubMed:19815557).
CC {ECO:0000269|PubMed:19815557, ECO:0000269|PubMed:34646012}.
CC -!- INTERACTION:
CC P29376; Q6UXT8: ALKAL1; NbExp=3; IntAct=EBI-6596163, EBI-11691642;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:34646012};
CC Single-pass type I membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Comment=Additional isoforms seem to exist.;
CC Name=Lambda P2;
CC IsoId=P29376-1; Sequence=Displayed;
CC Name=Lambda P1;
CC IsoId=P29376-2; Sequence=VSP_002946, VSP_002947;
CC Name=Lambda P3;
CC IsoId=P29376-3; Sequence=VSP_002948, VSP_002949;
CC Name=2;
CC IsoId=P29376-4; Sequence=VSP_035109;
CC Name=5;
CC IsoId=P29376-5; Sequence=VSP_035109, VSP_044521;
CC -!- TISSUE SPECIFICITY: Expressed in non-hematopoietic cell lines and
CC T- and B-cell lines. {ECO:0000269|PubMed:2156206}.
CC -!- PTM: Phosphorylated at tyrosine residues by autocatalysis, which
CC activates kinase activity. {ECO:0000269|PubMed:14695357}.
CC -!- DISEASE: Note=Genetic variations in LTK that cause up-regulation of the
CC PI3K pathway may possibly contribute to susceptibility to abnormal
CC proliferation of self-reactive B-cells and, therefore, to systemic
CC lupus erythematosus (SLE) (PubMed:14695357). SLE is a chronic,
CC inflammatory and often febrile multisystemic disorder of connective
CC tissue, thought to represent a failure of the regulatory mechanisms of
CC the autoimmune system (PubMed:14695357). {ECO:0000269|PubMed:14695357}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Insulin receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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DR EMBL; D16105; BAA03679.1; -; mRNA.
DR EMBL; X60702; CAA43113.1; -; mRNA.
DR EMBL; AK296892; BAG59451.1; -; mRNA.
DR EMBL; AC016134; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC087721; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471125; EAW92496.1; -; Genomic_DNA.
DR EMBL; X52213; CAA36460.1; -; mRNA.
DR CCDS; CCDS10077.1; -. [P29376-1]
DR CCDS; CCDS10078.1; -. [P29376-4]
DR CCDS; CCDS45237.1; -. [P29376-5]
DR PIR; A48266; A48266.
DR RefSeq; NP_001129157.1; NM_001135685.1. [P29376-5]
DR RefSeq; NP_002335.2; NM_002344.5. [P29376-1]
DR RefSeq; NP_996844.1; NM_206961.3. [P29376-4]
DR PDB; 7NX0; X-ray; 1.95 A; B/C=63-378.
DR PDB; 7NX1; X-ray; 1.30 A; A=63-378.
DR PDBsum; 7NX0; -.
DR PDBsum; 7NX1; -.
DR AlphaFoldDB; P29376; -.
DR SMR; P29376; -.
DR BioGRID; 110236; 16.
DR IntAct; P29376; 7.
DR MINT; P29376; -.
DR STRING; 9606.ENSP00000263800; -.
DR BindingDB; P29376; -.
DR ChEMBL; CHEMBL5627; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; P29376; -.
DR GuidetoPHARMACOLOGY; 1838; -.
DR GlyGen; P29376; 3 sites.
DR iPTMnet; P29376; -.
DR PhosphoSitePlus; P29376; -.
DR BioMuta; LTK; -.
DR DMDM; 143811416; -.
DR jPOST; P29376; -.
DR MassIVE; P29376; -.
DR PaxDb; P29376; -.
DR PeptideAtlas; P29376; -.
DR PRIDE; P29376; -.
DR ProteomicsDB; 20198; -.
DR ProteomicsDB; 54561; -. [P29376-1]
DR ProteomicsDB; 54563; -. [P29376-3]
DR ProteomicsDB; 54564; -. [P29376-4]
DR Antibodypedia; 23318; 300 antibodies from 32 providers.
DR DNASU; 4058; -.
DR Ensembl; ENST00000263800.11; ENSP00000263800.6; ENSG00000062524.16. [P29376-1]
DR Ensembl; ENST00000355166.9; ENSP00000347293.5; ENSG00000062524.16. [P29376-4]
DR Ensembl; ENST00000453182.2; ENSP00000392196.2; ENSG00000062524.16. [P29376-5]
DR GeneID; 4058; -.
DR KEGG; hsa:4058; -.
DR MANE-Select; ENST00000263800.11; ENSP00000263800.6; NM_002344.6; NP_002335.2.
DR UCSC; uc001zoa.4; human. [P29376-1]
DR CTD; 4058; -.
DR DisGeNET; 4058; -.
DR GeneCards; LTK; -.
DR HGNC; HGNC:6721; LTK.
DR HPA; ENSG00000062524; Tissue enhanced (intestine, lung, salivary gland).
DR MIM; 151520; gene.
DR neXtProt; NX_P29376; -.
DR OpenTargets; ENSG00000062524; -.
DR PharmGKB; PA30483; -.
DR VEuPathDB; HostDB:ENSG00000062524; -.
DR eggNOG; KOG1095; Eukaryota.
DR GeneTree; ENSGT00940000162680; -.
DR InParanoid; P29376; -.
DR OMA; IRRHPNC; -.
DR OrthoDB; 40108at2759; -.
DR PhylomeDB; P29376; -.
DR TreeFam; TF351636; -.
DR BRENDA; 2.7.10.1; 2681.
DR PathwayCommons; P29376; -.
DR SignaLink; P29376; -.
DR SIGNOR; P29376; -.
DR BioGRID-ORCS; 4058; 9 hits in 1106 CRISPR screens.
DR GeneWiki; Leukocyte_receptor_tyrosine_kinase; -.
DR GenomeRNAi; 4058; -.
DR Pharos; P29376; Tclin.
DR PRO; PR:P29376; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; P29376; protein.
DR Bgee; ENSG00000062524; Expressed in mucosa of transverse colon and 112 other tissues.
DR ExpressionAtlas; P29376; baseline and differential.
DR Genevisible; P29376; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:ProtInc.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
DR GO; GO:0004713; F:protein tyrosine kinase activity; TAS:ProtInc.
DR GO; GO:0030298; F:receptor signaling protein tyrosine kinase activator activity; IDA:UniProtKB.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0008283; P:cell population proliferation; IDA:UniProtKB.
DR GO; GO:0071300; P:cellular response to retinoic acid; IMP:BHF-UCL.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; IDA:UniProtKB.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; IMP:UniProtKB.
DR GO; GO:0010666; P:positive regulation of cardiac muscle cell apoptotic process; IDA:UniProtKB.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IMP:BHF-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; IBA:GO_Central.
DR GO; GO:0045664; P:regulation of neuron differentiation; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR026984; LTK.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR InterPro; IPR002011; Tyr_kinase_rcpt_2_CS.
DR PANTHER; PTHR24416:SF294; PTHR24416:SF294; 2.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00219; TyrKc; 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; PS00239; RECEPTOR_TYR_KIN_II; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cell membrane;
KW Disulfide bond; Glycoprotein; Kinase; Membrane; Nucleotide-binding;
KW Phosphoprotein; Receptor; Reference proteome; Signal;
KW Systemic lupus erythematosus; Transferase; Transmembrane;
KW Transmembrane helix; Tyrosine-protein kinase.
FT SIGNAL 1..16
FT /evidence="ECO:0000255"
FT CHAIN 17..864
FT /note="Leukocyte tyrosine kinase receptor"
FT /id="PRO_0000016738"
FT TOPO_DOM 17..424
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 425..449
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 450..864
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 510..786
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 30..64
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 239..297
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 790..830
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 842..864
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 240..254
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 848..864
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 643
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 516..524
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 544
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 676
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT CARBOHYD 257
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 380
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 412
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 73..86
FT /evidence="ECO:0000269|PubMed:34646012,
FT ECO:0007744|PDB:7NX0"
FT DISULFID 168..179
FT /evidence="ECO:0000269|PubMed:34646012,
FT ECO:0007744|PDB:7NX0"
FT DISULFID 300..322
FT /evidence="ECO:0000269|PubMed:34646012,
FT ECO:0007744|PDB:7NX0"
FT VAR_SEQ 170
FT /note="G -> VAAASGDGAAPAPGARAAWGPGERAFLGAGSPAQRGEAPGPRRFPPP
FT LPAG (in isoform Lambda P1)"
FT /evidence="ECO:0000305"
FT /id="VSP_002946"
FT VAR_SEQ 171..864
FT /note="Missing (in isoform Lambda P1)"
FT /evidence="ECO:0000305"
FT /id="VSP_002947"
FT VAR_SEQ 274..334
FT /note="Missing (in isoform 2 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:1655406"
FT /id="VSP_035109"
FT VAR_SEQ 448
FT /note="L -> GTKRLAGTVDSRLLLSSELGWVSAAGSRRQ (in isoform
FT Lambda P3)"
FT /evidence="ECO:0000305"
FT /id="VSP_002948"
FT VAR_SEQ 449..864
FT /note="Missing (in isoform Lambda P3)"
FT /evidence="ECO:0000305"
FT /id="VSP_002949"
FT VAR_SEQ 449..544
FT /note="VKQKKWQGLQEMRLPSPELELSKLRTSAIRTAPNPYYCQVGLGPAQSWPLPP
FT GVTEVSPANVTLLRALGHGAFGEVYEGLVIGLPGDSSPLQVAIK -> GGAWPGPVLAS
FT ATRCHRGFPSQCYSAQ (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044521"
FT VARIANT 42
FT /note="R -> Q (in dbSNP:rs2305030)"
FT /evidence="ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:7685902"
FT /id="VAR_031569"
FT VARIANT 384
FT /note="C -> R (in dbSNP:rs55683312)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_046106"
FT VARIANT 535
FT /note="D -> N (in dbSNP:rs35932273)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_046107"
FT VARIANT 569
FT /note="R -> S (in dbSNP:rs148513655)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_046108"
FT VARIANT 673
FT /note="R -> Q (in dbSNP:rs55876255)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_046109"
FT VARIANT 745
FT /note="P -> S (in dbSNP:rs55900837)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_046110"
FT VARIANT 763
FT /note="E -> K (may possibly contribute to susceptibility to
FT systemic lupus erythematosus; increases autophosphorylation
FT and interaction with PI3-kinase subunit p85;
FT dbSNP:rs76282169)"
FT /evidence="ECO:0000269|PubMed:14695357"
FT /id="VAR_065465"
FT VARIANT 838
FT /note="P -> S (in dbSNP:rs56367146)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_046111"
FT MUTAGEN 241
FT /note="R->A: Abolished homodimerization following
FT interaction with ALKAL1."
FT /evidence="ECO:0000269|PubMed:34646012"
FT MUTAGEN 544
FT /note="K->M: Loss of interaction with PLCG1, PI3-kinase
FT subunit p85, Ras GTPase-activating protein and RAF1."
FT /evidence="ECO:0000269|PubMed:8084603"
FT MUTAGEN 750
FT /note="G->E: Increases autophosphorylation and interaction
FT with PI3-kinase subunit p85 (demonstrated with chimeric
FT EGFR-LTK)."
FT /evidence="ECO:0000269|PubMed:14695357"
FT MUTAGEN 753
FT /note="Y->F: Abolishes interaction with PI3-kinase subunit
FT p85, impairs PI3 kinase activity and leads to apoptosis
FT (demonstrated with chimeric EGFR-LTK)."
FT /evidence="ECO:0000269|PubMed:9223670"
FT MUTAGEN 862
FT /note="Y->F: Impairs phosphorylation of CBLC (demonstrated
FT with chimeric EGFR-LTK)."
FT /evidence="ECO:0000269|PubMed:9223670"
FT CONFLICT 106
FT /note="R -> G (in Ref. 3; BAG59451)"
FT /evidence="ECO:0000305"
FT CONFLICT 220
FT /note="V -> L (in Ref. 2; CAA43113)"
FT /evidence="ECO:0000305"
FT CONFLICT 449
FT /note="V -> GTKRLAGTVDSRLLLSM (in Ref. 6; CAA36460)"
FT /evidence="ECO:0000305"
FT CONFLICT 652..654
FT /note="SCA -> MR (in Ref. 6; CAA36460)"
FT /evidence="ECO:0000305"
FT STRAND 67..70
FT /evidence="ECO:0007829|PDB:7NX1"
FT STRAND 77..79
FT /evidence="ECO:0007829|PDB:7NX0"
FT HELIX 83..90
FT /evidence="ECO:0007829|PDB:7NX1"
FT STRAND 98..100
FT /evidence="ECO:0007829|PDB:7NX1"
FT HELIX 103..105
FT /evidence="ECO:0007829|PDB:7NX1"
FT STRAND 109..112
FT /evidence="ECO:0007829|PDB:7NX1"
FT STRAND 115..124
FT /evidence="ECO:0007829|PDB:7NX1"
FT STRAND 141..150
FT /evidence="ECO:0007829|PDB:7NX1"
FT STRAND 155..159
FT /evidence="ECO:0007829|PDB:7NX1"
FT STRAND 167..169
FT /evidence="ECO:0007829|PDB:7NX1"
FT HELIX 173..179
FT /evidence="ECO:0007829|PDB:7NX1"
FT HELIX 185..189
FT /evidence="ECO:0007829|PDB:7NX0"
FT STRAND 215..221
FT /evidence="ECO:0007829|PDB:7NX1"
FT STRAND 224..231
FT /evidence="ECO:0007829|PDB:7NX1"
FT STRAND 269..271
FT /evidence="ECO:0007829|PDB:7NX1"
FT HELIX 290..292
FT /evidence="ECO:0007829|PDB:7NX1"
FT HELIX 301..307
FT /evidence="ECO:0007829|PDB:7NX1"
FT TURN 315..317
FT /evidence="ECO:0007829|PDB:7NX1"
FT STRAND 322..324
FT /evidence="ECO:0007829|PDB:7NX1"
FT STRAND 330..332
FT /evidence="ECO:0007829|PDB:7NX1"
FT STRAND 350..353
FT /evidence="ECO:0007829|PDB:7NX0"
FT STRAND 357..359
FT /evidence="ECO:0007829|PDB:7NX1"
FT STRAND 364..367
FT /evidence="ECO:0007829|PDB:7NX1"
FT STRAND 372..377
FT /evidence="ECO:0007829|PDB:7NX1"
SQ SEQUENCE 864 AA; 91681 MW; 0617F378AA04298E CRC64;
MGCWGQLLVW FGAAGAILCS SPGSQETFLR SSPLPLASPS PRDPKVSAPP SILEPASPLN
SPGTEGSWLF STCGASGRHG PTQTQCDGAY AGTSVVVTVG AAGQLRGVQL WRVPGPGQYL
ISAYGAAGGK GAKNHLSRAH GVFVSAIFSL GLGESLYILV GQQGEDACPG GSPESQLVCL
GESRAVEEHA AMDGSEGVPG SRRWAGGGGG GGGATYVFRV RAGELEPLLV AAGGGGRAYL
RPRDRGRTQA SPEKLENRSE APGSGGRGGA AGGGGGWTSR APSPQAGRSL QEGAEGGQGC
SEAWATLGWA AAGGFGGGGG ACTAGGGGGG YRGGDASETD NLWADGEDGV SFIHPSSELF
LQPLAVTENH GEVEIRRHLN CSHCPLRDCQ WQAELQLAEC LCPEGMELAV DNVTCMDLHK
PPGPLVLMVA VVATSTLSLL MVCGVLILVK QKKWQGLQEM RLPSPELELS KLRTSAIRTA
PNPYYCQVGL GPAQSWPLPP GVTEVSPANV TLLRALGHGA FGEVYEGLVI GLPGDSSPLQ
VAIKTLPELC SPQDELDFLM EALIISKFRH QNIVRCVGLS LRATPRLILL ELMSGGDMKS
FLRHSRPHLG QPSPLVMRDL LQLAQDIAQG CHYLEENHFI HRDIAARNCL LSCAGPSRVA
KIGDFGMARD IYRASYYRRG DRALLPVKWM PPEAFLEGIF TSKTDSWSFG VLLWEIFSLG
YMPYPGRTNQ EVLDFVVGGG RMDPPRGCPG PVYRIMTQCW QHEPELRPSF ASILERLQYC
TQDPDVLNSL LPMELGPTPE EEGTSGLGNR SLECLRPPQP QELSPEKLKS WGGSPLGPWL
SSGLKPLKSR GLQPQNLWNP TYRS
