LTK_MOUSE
ID LTK_MOUSE Reviewed; 888 AA.
AC P08923; A2AQ22;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Leukocyte tyrosine kinase receptor {ECO:0000303|PubMed:2357970};
DE EC=2.7.10.1 {ECO:0000250|UniProtKB:P29376, ECO:0000255|PROSITE-ProRule:PRU10028};
DE Flags: Precursor;
GN Name=Ltk {ECO:0000303|PubMed:2357970};
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] (ISOFORM A), AND TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ;
RX PubMed=2357970; DOI=10.1002/j.1460-2075.1990.tb07399.x;
RA Bernards A., de la Monte S.;
RT "The ltk receptor tyrosine kinase is expressed in pre-B lymphocytes and
RT cerebral neurons and uses a non-AUG translational initiator.";
RL EMBO J. 9:2279-2287(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
RC STRAIN=BALB/cJ;
RX PubMed=1662793;
RA Haase V.H., Snijders A.J., Cooke S.M., Teng M.N., Kaul D., le Beau M.M.,
RA Bruns G.A., Bernards A.;
RT "Alternatively spliced ltk mRNA in neurons predicts a receptor with a
RT larger putative extracellular domain.";
RL Oncogene 6:2319-2325(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; B; C AND D), AND SUBCELLULAR
RP LOCATION.
RX PubMed=8380920;
RA Snijders A.J., Haase V.H., Bernards A.;
RT "Four tissue-specific mouse ltk mRNAs predict tyrosine kinases that differ
RT upstream of their transmembrane segment.";
RL Oncogene 8:27-35(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 260-888 (ISOFORM A), AND SUBCELLULAR
RP LOCATION.
RX PubMed=2836739; DOI=10.1038/333672a0;
RA Ben-Neriah Y., Bauskin A.R.;
RT "Leukocytes express a novel gene encoding a putative transmembrane protein-
RT kinase devoid of an extracellular domain.";
RL Nature 333:672-676(1988).
RN [6]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH CALNEXIN (ISOFORM A).
RX PubMed=8995435; DOI=10.1074/jbc.272.2.1297;
RA Snijders A.J., Ho S.C., Haase V.H., Pillai S., Bernards A.;
RT "A lymphocyte-specific Ltk tyrosine kinase isoform is retained in the
RT endoplasmic reticulum in association with calnexin.";
RL J. Biol. Chem. 272:1297-1301(1997).
RN [7]
RP DISRUPTION PHENOTYPE.
RX PubMed=22079349; DOI=10.1016/j.pbb.2011.10.024;
RA Weiss J.B., Xue C., Benice T., Xue L., Morris S.W., Raber J.;
RT "Anaplastic lymphoma kinase and leukocyte tyrosine kinase: functions and
RT genetic interactions in learning, memory and adult neurogenesis.";
RL Pharmacol. Biochem. Behav. 100:566-574(2012).
RN [8]
RP VARIANT GLU-746.
RC STRAIN=NZB;
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).
CC -!- FUNCTION: Receptor with a tyrosine-protein kinase activity. Following
CC activation by ALKAL1 or ALKAL2 ligands at the cell surface, transduces
CC an extracellular signal into an intracellular response. Ligand-binding
CC to the extracellular domain induces tyrosine kinase activation, leading
CC to activation of the mitogen-activated protein kinase (MAPK) pathway
CC (By similarity). Phosphorylates almost exclusively at the first
CC tyrosine of the Y-x-x-x-Y-Y motif (By similarity). The exact function
CC of this protein is not known; studies with chimeric proteins
CC demonstrate its ability to promote growth and specifically neurite
CC outgrowth, and cell survival. Involved in regulation of the secretory
CC pathway involving endoplasmic reticulum (ER) export sites (ERESs) and
CC ER to Golgi transport (By similarity). {ECO:0000250|UniProtKB:P29376,
CC ECO:0000250|UniProtKB:Q9UM73}.
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:0000250|UniProtKB:P29376, ECO:0000255|PROSITE-
CC ProRule:PRU10028};
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. Part of a
CC complex including LTK, TNK2 and GRB2, in which GRB2 promotes LTK
CC recruitment by TNK2. {ECO:0000250|UniProtKB:P29376}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:2836739,
CC ECO:0000269|PubMed:8995435}; Single-pass type I membrane protein
CC {ECO:0000255}.
CC -!- SUBCELLULAR LOCATION: [Isoform A]: Endoplasmic reticulum
CC {ECO:0000305|PubMed:8380920}. Note=Retained in the endoplasmic
CC reticulum. {ECO:0000305|PubMed:8380920}.
CC -!- SUBCELLULAR LOCATION: [Isoform B]: Endoplasmic reticulum
CC {ECO:0000305|PubMed:8380920}. Note=Retained in the endoplasmic
CC reticulum. {ECO:0000305|PubMed:8380920}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=4;
CC Comment=Additional isoforms seem to exist.;
CC Name=D {ECO:0000303|PubMed:8380920};
CC IsoId=P08923-1; Sequence=Displayed;
CC Name=A {ECO:0000303|PubMed:8380920};
CC IsoId=P08923-2; Sequence=VSP_002950, VSP_002951, VSP_002952;
CC Name=B {ECO:0000303|PubMed:8380920};
CC IsoId=P08923-3; Sequence=VSP_002950, VSP_002951;
CC Name=C {ECO:0000303|PubMed:8380920};
CC IsoId=P08923-4; Sequence=VSP_002952;
CC -!- TISSUE SPECIFICITY: Subsets of lymphoid and neuronal cells.
CC {ECO:0000269|PubMed:2357970}.
CC -!- PTM: Phosphorylated at tyrosine residues by autocatalysis, which
CC activates kinase activity. {ECO:0000250|UniProtKB:P29376}.
CC -!- DISRUPTION PHENOTYPE: Mice do not show any decrease in newborn neurons
CC (PubMed:22079349). Mice lacking both Alk and Ltk show a strong
CC reduction in newborn neurons (PubMed:22079349).
CC {ECO:0000269|PubMed:22079349}.
CC -!- MISCELLANEOUS: [Isoform D]: May be produced by alternative promoter
CC usage.
CC -!- MISCELLANEOUS: [Isoform A]: May be produced by alternative promoter
CC usage. Starts at a CUG codon. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform B]: May be produced by alternative promoter
CC usage. Starts at a CUG codon. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Insulin receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA30793.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; X52621; CAA36848.1; -; mRNA.
DR EMBL; M90470; AAA39451.1; -; mRNA.
DR EMBL; AL844536; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; X07984; CAA30793.1; ALT_INIT; mRNA.
DR CCDS; CCDS16608.1; -. [P08923-1]
DR CCDS; CCDS16609.1; -. [P08923-4]
DR CCDS; CCDS50674.1; -. [P08923-2]
DR PIR; I58378; I58378.
DR PIR; S12792; S12792.
DR RefSeq; NP_976220.2; NM_203345.2. [P08923-1]
DR RefSeq; NP_996824.1; NM_206941.1. [P08923-3]
DR RefSeq; NP_996825.2; NM_206942.2. [P08923-4]
DR AlphaFoldDB; P08923; -.
DR SMR; P08923; -.
DR STRING; 10090.ENSMUSP00000028759; -.
DR GlyGen; P08923; 2 sites.
DR iPTMnet; P08923; -.
DR PhosphoSitePlus; P08923; -.
DR MaxQB; P08923; -.
DR PaxDb; P08923; -.
DR PRIDE; P08923; -.
DR Antibodypedia; 23318; 300 antibodies from 32 providers.
DR DNASU; 17005; -.
DR Ensembl; ENSMUST00000028759; ENSMUSP00000028759; ENSMUSG00000027297. [P08923-1]
DR Ensembl; ENSMUST00000082130; ENSMUSP00000080774; ENSMUSG00000027297. [P08923-4]
DR GeneID; 17005; -.
DR KEGG; mmu:17005; -.
DR UCSC; uc008lug.1; mouse. [P08923-3]
DR UCSC; uc008lui.1; mouse. [P08923-1]
DR UCSC; uc008luj.1; mouse. [P08923-4]
DR CTD; 4058; -.
DR MGI; MGI:96840; Ltk.
DR VEuPathDB; HostDB:ENSMUSG00000027297; -.
DR eggNOG; KOG1095; Eukaryota.
DR GeneTree; ENSGT00940000162680; -.
DR InParanoid; P08923; -.
DR OMA; IRRHPNC; -.
DR PhylomeDB; P08923; -.
DR TreeFam; TF351636; -.
DR BRENDA; 2.7.10.1; 3474.
DR BioGRID-ORCS; 17005; 1 hit in 76 CRISPR screens.
DR PRO; PR:P08923; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; P08923; protein.
DR Bgee; ENSMUSG00000027297; Expressed in perirhinal cortex and 87 other tissues.
DR ExpressionAtlas; P08923; baseline and differential.
DR Genevisible; P08923; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IDA:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:0030298; F:receptor signaling protein tyrosine kinase activator activity; ISS:UniProtKB.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0008283; P:cell population proliferation; ISS:UniProtKB.
DR GO; GO:0071300; P:cellular response to retinoic acid; ISO:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; ISS:UniProtKB.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; ISS:UniProtKB.
DR GO; GO:0010666; P:positive regulation of cardiac muscle cell apoptotic process; ISO:MGI.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; ISS: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: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 Alternative promoter usage; Alternative splicing; ATP-binding;
KW Cell membrane; Disulfide bond; Endoplasmic reticulum; Glycoprotein; Kinase;
KW Membrane; Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome;
KW Signal; Transferase; Transmembrane; Transmembrane helix;
KW Tyrosine-protein kinase.
FT SIGNAL 1..16
FT /evidence="ECO:0000255"
FT CHAIN 17..888
FT /note="Leukocyte tyrosine kinase receptor"
FT /id="PRO_0000016739"
FT TOPO_DOM 17..421
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 422..446
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 447..888
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 506..782
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 226..294
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 857..888
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 235..249
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 873..888
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 639
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 512..520
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 540
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 672
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT CARBOHYD 377
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 409
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 73..86
FT /evidence="ECO:0000250|UniProtKB:P29376"
FT DISULFID 168..179
FT /evidence="ECO:0000250|UniProtKB:P29376"
FT DISULFID 297..319
FT /evidence="ECO:0000250|UniProtKB:P29376"
FT VAR_SEQ 1..251
FT /note="Missing (in isoform A and isoform B)"
FT /evidence="ECO:0000303|PubMed:1662793,
FT ECO:0000303|PubMed:2357970, ECO:0000303|PubMed:2836739,
FT ECO:0000303|PubMed:8380920"
FT /id="VSP_002950"
FT VAR_SEQ 252
FT /note="L -> M (in isoform A and isoform B)"
FT /evidence="ECO:0000303|PubMed:1662793,
FT ECO:0000303|PubMed:2357970, ECO:0000303|PubMed:2836739,
FT ECO:0000303|PubMed:8380920"
FT /id="VSP_002951"
FT VAR_SEQ 271..331
FT /note="Missing (in isoform A and isoform C)"
FT /evidence="ECO:0000303|PubMed:1662793,
FT ECO:0000303|PubMed:2357970, ECO:0000303|PubMed:2836739,
FT ECO:0000303|PubMed:8380920"
FT /id="VSP_002952"
FT VARIANT 746
FT /note="G -> E"
FT /evidence="ECO:0000269|PubMed:14695357"
FT CONFLICT 26
FT /note="T -> A (in Ref. 3; AAA39451)"
FT /evidence="ECO:0000305"
FT CONFLICT 113
FT /note="V -> A (in Ref. 3; AAA39451)"
FT /evidence="ECO:0000305"
FT CONFLICT 789
FT /note="V -> M (in Ref. 2; CAA36848 and 3; AAA39451)"
FT /evidence="ECO:0000305"
FT CONFLICT 875
FT /note="H -> Q (in Ref. 2; CAA36848 and 3; AAA39451)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 888 AA; 94471 MW; 7D204A474DEF0AC6 CRC64;
MGCSHRLLLW LGAAGTILCS NSEFQTPFLT PSLLPVLVLN SQEQKVTPTP SKLEPASLPN
PLGTRGPWVF NTCGASGRSG PTQTQCDGAY TGSSVMVTVG AAGPLKGVQL WRVPDTGQYL
ISAYGAAGGK GAQNHLSRAH GIFLSAVFFL RRGEPVYILV GQQGQDACPG GSPESQLVCL
GESGEHATTY GTERIPGWRR WAGGGGGGGG ATSIFRLRAG EPEPLLVAAG GGGRSYRRRP
DRGRTQAVPE RLETRAAAPG SGGRGGAAGG GSGWTSRAHS PQAGRSPREG AEGGEGCAEA
WAALRWAAAG GFGGGGGACA AGGGGGGYRG GDTSESDLLW ADGEDGTSFV HPSGELYLQP
LAVTEGHGEV EIRKHPNCSH CPFKDCQWQA ELWTAECTCP EGTELAVDNV TCMDLPTTAS
PLILMGAVVA ALALSLLMMC AVLILVNQKC QGLWGTRLPG PELELSKLRS SAIRTAPNPY
YCQVGLSPAQ PWPLPPGLTE VSPANVTLLR ALGHGAFGEV YEGLVTGLPG DSSPLPVAIK
TLPELCSHQD ELDFLMEALI ISKFSHQNIV RCVGLSFRSA PRLILLELMS GGDMKSFLRH
SRPHPGQLAP LTMQDLLQLA QDIAQGCHYL EENHFIHRDI AARNCLLSCS GASRVAKIGD
FGMARDIYQA SYYRKGGRTL LPVKWMPPEA LLEGLFTSKT DSWSFGVLLW EIFSLGYMPY
PGHTNQEVLD FIATGNRMDP PRNCPGPVYR IMTQCWQHQP ELRPDFGSIL ERIQYCTQDP
DVLNSPLPVE PGPILEEEEA SRLGNRSLEG LRSPKPLELS SQNLKSWGGG LLGSWLPSGL
KTLKPRCLQP QNIWNPTYGS WTPRGPQGED TGIEHCNGSS SSSIPGIQ
