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   27-MAR-2024, entry version 210.
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       P29376; P29317: EPHA2; NbExp=3; IntAct=EBI-6596163, EBI-702104;
CC       P29376; P27986: PIK3R1; NbExp=3; IntAct=EBI-6596163, EBI-79464;
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; 151.
DR   IntAct; P29376; 141.
DR   MINT; P29376; -.
DR   STRING; 9606.ENSP00000263800; -.
DR   BindingDB; P29376; -.
DR   ChEMBL; CHEMBL5627; -.
DR   DrugBank; DB12010; Fostamatinib.
DR   DrugCentral; P29376; -.
DR   GuidetoPHARMACOLOGY; 1838; -.
DR   GlyCosmos; P29376; 3 sites, No reported glycans.
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; 9606-ENSP00000263800; -.
DR   PeptideAtlas; P29376; -.
DR   ProteomicsDB; 20198; -.
DR   ProteomicsDB; 54561; -. [P29376-1]
DR   ProteomicsDB; 54563; -. [P29376-3]
DR   ProteomicsDB; 54564; -. [P29376-4]
DR   Antibodypedia; 23318; 340 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   AGR; HGNC:6721; -.
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; WPFGLPE; -.
DR   OrthoDB; 1614410at2759; -.
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 1185 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 114 other cell types or tissues.
DR   ExpressionAtlas; P29376; baseline and differential.
DR   GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProt.
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; IDA:UniProt.
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:0010666; P:positive regulation of cardiac muscle cell apoptotic process; IDA:UniProtKB.
DR   GO; GO:0010976; P:positive regulation of neuron projection development; IMP:BHF-UCL.
DR   GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IMP:UniProtKB.
DR   GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc.
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; IDA:UniProt.
DR   CDD; cd05036; PTKc_ALK_LTK; 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; IPR008266; Tyr_kinase_AS.
DR   InterPro; IPR020635; Tyr_kinase_cat_dom.
DR   InterPro; IPR002011; Tyr_kinase_rcpt_2_CS.
DR   PANTHER; PTHR24416:SF294; LEUKOCYTE TYROSINE KINASE RECEPTOR; 1.
DR   PANTHER; PTHR24416; TYROSINE-PROTEIN KINASE RECEPTOR; 1.
DR   Pfam; PF12810; Gly_rich; 1.
DR   Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR   PRINTS; PR00109; TYRKINASE.
DR   SMART; SM00219; TyrKc; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 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.
DR   Genevisible; P29376; HS.
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
//