NTRK3_HUMAN
ID NTRK3_HUMAN Reviewed; 839 AA.
AC Q16288; B7Z4C5; E9PG56; H0YND1; O75682; Q12827; Q16289;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 2.
DT 03-AUG-2022, entry version 226.
DE RecName: Full=NT-3 growth factor receptor;
DE EC=2.7.10.1;
DE AltName: Full=GP145-TrkC;
DE Short=Trk-C;
DE AltName: Full=Neurotrophic tyrosine kinase receptor type 3;
DE AltName: Full=TrkC tyrosine kinase;
DE Flags: Precursor;
GN Name=NTRK3; Synonyms=TRKC;
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] (ISOFORMS 1 AND 3).
RC TISSUE=Fetal brain;
RX PubMed=7806211; DOI=10.1006/geno.1994.1383;
RA McGregor L.M., Baylin S.B., Griffin C.A., Hawkins A.L., Nelkin B.D.;
RT "Molecular cloning of the cDNA for human TrkC (NTRK3), chromosomal
RT assignment, and evidence for a splice variant.";
RL Genomics 22:267-272(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), AND PARTIAL PROTEIN
RP SEQUENCE.
RC TISSUE=Brain;
RX PubMed=7823156; DOI=10.1523/jneurosci.15-01-00477.1995;
RA Shelton D.L., Sutherland J., Gripp J., Camerato T., Armanini M.P.,
RA Phillips H.S., Carroll K., Spencer S.D., Levinson A.D.;
RT "Human trks: molecular cloning, tissue distribution, and expression of
RT extracellular domain immunoadhesins.";
RL J. Neurosci. 15:477-491(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9778053; DOI=10.1038/sj.onc.1202100;
RA Ichaso N., Rodriguez R.E., Martin-Zanca D., Gonzalez-Sarmiento R.;
RT "Genomic characterization of the human trkC gene.";
RL Oncogene 17:1871-1875(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
RC TISSUE=Brain;
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 [5]
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 [6]
RP FUNCTION, PHOSPHORYLATION AT TYR-516, INVOLVEMENT IN CHD, VARIANTS PHE-21;
RP VAL-71; MET-93; ILE-163; PHE-533 AND MET-817, CHARACTERIZATION OF VARIANTS
RP MET-93; ILE-163; PHE-533 AND MET-817, AND MUTAGENESIS OF LYS-572.
RX PubMed=25196463; DOI=10.1002/humu.22688;
RA Werner P., Paluru P., Simpson A.M., Latney B., Iyer R., Brodeur G.M.,
RA Goldmuntz E.;
RT "Mutations in NTRK3 suggest a novel signaling pathway in human congenital
RT heart disease.";
RL Hum. Mutat. 35:1459-1468(2014).
RN [7]
RP INTERACTION WITH PTPRS.
RX PubMed=25385546; DOI=10.1038/ncomms6209;
RA Coles C.H., Mitakidis N., Zhang P., Elegheert J., Lu W., Stoker A.W.,
RA Nakagawa T., Craig A.M., Jones E.Y., Aricescu A.R.;
RT "Structural basis for extracellular cis and trans RPTPsigma signal
RT competition in synaptogenesis.";
RL Nat. Commun. 5:5209-5209(2014).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 297-401, AND DISULFIDE BOND.
RX PubMed=10388563; DOI=10.1006/jmbi.1999.2816;
RA Ultsch M.H., Wiesmann C., Simmons L.C., Henrich J., Yang M., Reilly D.,
RA Bass S.H., de Vos A.M.;
RT "Crystal structures of the neurotrophin-binding domain of TrkA, TrkB and
RT TrkC.";
RL J. Mol. Biol. 290:149-159(1999).
RN [9]
RP VARIANTS [LARGE SCALE ANALYSIS] ARG-149; CYS-306; LEU-307; GLN-336;
RP TYR-677; GLN-678; ARG-768 AND LYS-781.
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).
RN [10]
RP VARIANTS SER-664; TYR-677; CYS-736; PRO-745 AND PHE-766.
RX PubMed=18293376; DOI=10.1002/humu.20707;
RA Marchetti A., Felicioni L., Pelosi G., Del Grammastro M., Fumagalli C.,
RA Sciarrotta M., Malatesta S., Chella A., Barassi F., Mucilli F.,
RA Camplese P., D'Antuono T., Sacco R., Buttitta F.;
RT "Frequent mutations in the neurotrophic tyrosine receptor kinase gene
RT family in large cell neuroendocrine carcinoma of the lung.";
RL Hum. Mutat. 29:609-616(2008).
CC -!- FUNCTION: Receptor tyrosine kinase involved in nervous system and
CC probably heart development. Upon binding of its ligand
CC NTF3/neurotrophin-3, NTRK3 autophosphorylates and activates different
CC signaling pathways, including the phosphatidylinositol 3-kinase/AKT and
CC the MAPK pathways, that control cell survival and differentiation.
CC {ECO:0000269|PubMed:25196463}.
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 -!- SUBUNIT: Exists in a dynamic equilibrium between monomeric (low
CC affinity) and dimeric (high affinity) structures (By similarity). Binds
CC SH2B2. Interacts with SQSTM1 and KIDINS220 (By similarity). Interacts
CC with PTPRS (PubMed:25385546). Interacts with MAPK8IP3/JIP3 (By
CC similarity). {ECO:0000250|UniProtKB:P04629,
CC ECO:0000250|UniProtKB:Q03351, ECO:0000269|PubMed:25385546}.
CC -!- INTERACTION:
CC Q16288; Q6PKX4: DOK6; NbExp=3; IntAct=EBI-3936704, EBI-2880244;
CC Q16288; Q99523: SORT1; NbExp=2; IntAct=EBI-3936704, EBI-1057058;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Comment=Additional isoforms seem to exist.;
CC Name=1; Synonyms=A;
CC IsoId=Q16288-1; Sequence=Displayed;
CC Name=2; Synonyms=B;
CC IsoId=Q16288-2; Sequence=VSP_002925, VSP_002926;
CC Name=3; Synonyms=C;
CC IsoId=Q16288-3; Sequence=VSP_002927;
CC Name=4; Synonyms=D;
CC IsoId=Q16288-4; Sequence=VSP_002924;
CC Name=5; Synonyms=E;
CC IsoId=Q16288-5; Sequence=VSP_002924, VSP_002927;
CC -!- TISSUE SPECIFICITY: Widely expressed but mainly in nervous tissue.
CC Isoform 2 is expressed at higher levels in adult brain than in fetal
CC brain.
CC -!- PTM: Ligand-mediated auto-phosphorylation.
CC -!- DISEASE: Note=Defects in NTRK3 are associated with susceptibility to
CC congenital heart defects (CHD). A disease characterized by congenital
CC developmental abnormalities involving structures of the heart. CHD are
CC the most common major birth defects and the leading cause of death from
CC congenital malformations. {ECO:0000269|PubMed:25196463}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Insulin receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/NTRK3ID433.html";
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DR EMBL; U05012; AAA75374.1; -; mRNA.
DR EMBL; S76475; AAB33111.1; -; mRNA.
DR EMBL; S76476; AAB33112.1; -; mRNA.
DR EMBL; AJ224521; CAA12029.1; -; Genomic_DNA.
DR EMBL; AJ224522; CAA12029.1; JOINED; Genomic_DNA.
DR EMBL; AJ224523; CAA12029.1; JOINED; Genomic_DNA.
DR EMBL; AJ224524; CAA12029.1; JOINED; Genomic_DNA.
DR EMBL; AJ224525; CAA12029.1; JOINED; Genomic_DNA.
DR EMBL; AJ224526; CAA12029.1; JOINED; Genomic_DNA.
DR EMBL; AJ224527; CAA12029.1; JOINED; Genomic_DNA.
DR EMBL; AJ224528; CAA12029.1; JOINED; Genomic_DNA.
DR EMBL; AJ224529; CAA12029.1; JOINED; Genomic_DNA.
DR EMBL; AJ224530; CAA12029.1; JOINED; Genomic_DNA.
DR EMBL; AJ224531; CAA12029.1; JOINED; Genomic_DNA.
DR EMBL; AJ224532; CAA12029.1; JOINED; Genomic_DNA.
DR EMBL; AJ224533; CAA12029.1; JOINED; Genomic_DNA.
DR EMBL; AJ224534; CAA12029.1; JOINED; Genomic_DNA.
DR EMBL; AJ224535; CAA12029.1; JOINED; Genomic_DNA.
DR EMBL; AK297160; BAH12511.1; -; mRNA.
DR EMBL; AC009711; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC011966; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC021677; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS10340.1; -. [Q16288-3]
DR CCDS; CCDS32322.1; -. [Q16288-1]
DR CCDS; CCDS32323.1; -. [Q16288-2]
DR CCDS; CCDS58399.1; -. [Q16288-5]
DR PIR; A55178; A55178.
DR PIR; I73632; I73632.
DR PIR; I73633; I73633.
DR RefSeq; NP_001012338.1; NM_001012338.2. [Q16288-1]
DR RefSeq; NP_001307063.1; NM_001320134.1.
DR RefSeq; NP_001307064.1; NM_001320135.1.
DR RefSeq; NP_002521.2; NM_002530.3. [Q16288-3]
DR RefSeq; XP_016877742.1; XM_017022253.1.
DR PDB; 1WWC; X-ray; 1.90 A; A=297-422.
DR PDB; 3V5Q; X-ray; 2.20 A; A/B=530-832.
DR PDB; 4YMJ; X-ray; 2.00 A; A/B=530-839.
DR PDB; 6KZC; X-ray; 2.00 A; A=528-839.
DR PDB; 6KZD; X-ray; 1.71 A; A=528-839.
DR PDBsum; 1WWC; -.
DR PDBsum; 3V5Q; -.
DR PDBsum; 4YMJ; -.
DR PDBsum; 6KZC; -.
DR PDBsum; 6KZD; -.
DR AlphaFoldDB; Q16288; -.
DR SMR; Q16288; -.
DR BioGRID; 110971; 64.
DR DIP; DIP-5723N; -.
DR IntAct; Q16288; 50.
DR MINT; Q16288; -.
DR STRING; 9606.ENSP00000354207; -.
DR BindingDB; Q16288; -.
DR ChEMBL; CHEMBL5608; -.
DR DrugBank; DB11986; Entrectinib.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB14723; Larotrectinib.
DR DrugBank; DB15822; Pralsetinib.
DR DrugCentral; Q16288; -.
DR GuidetoPHARMACOLOGY; 1819; -.
DR GlyGen; Q16288; 13 sites.
DR iPTMnet; Q16288; -.
DR PhosphoSitePlus; Q16288; -.
DR BioMuta; NTRK3; -.
DR DMDM; 134035335; -.
DR MassIVE; Q16288; -.
DR MaxQB; Q16288; -.
DR PaxDb; Q16288; -.
DR PeptideAtlas; Q16288; -.
DR PRIDE; Q16288; -.
DR ProteomicsDB; 20249; -.
DR ProteomicsDB; 40524; -.
DR ProteomicsDB; 60850; -. [Q16288-1]
DR ProteomicsDB; 60851; -. [Q16288-2]
DR ProteomicsDB; 60852; -. [Q16288-3]
DR ProteomicsDB; 60853; -. [Q16288-4]
DR ABCD; Q16288; 8 sequenced antibodies.
DR Antibodypedia; 3979; 792 antibodies from 42 providers.
DR DNASU; 4916; -.
DR Ensembl; ENST00000317501.7; ENSP00000318328.3; ENSG00000140538.16. [Q16288-2]
DR Ensembl; ENST00000355254.6; ENSP00000347397.3; ENSG00000140538.16. [Q16288-5]
DR Ensembl; ENST00000357724.6; ENSP00000350356.2; ENSG00000140538.16. [Q16288-4]
DR Ensembl; ENST00000360948.6; ENSP00000354207.2; ENSG00000140538.16. [Q16288-1]
DR Ensembl; ENST00000394480.6; ENSP00000377990.1; ENSG00000140538.16. [Q16288-3]
DR Ensembl; ENST00000540489.6; ENSP00000444673.2; ENSG00000140538.16. [Q16288-2]
DR Ensembl; ENST00000557856.5; ENSP00000453959.1; ENSG00000140538.16. [Q16288-5]
DR Ensembl; ENST00000629765.2; ENSP00000485864.1; ENSG00000140538.16. [Q16288-1]
DR GeneID; 4916; -.
DR KEGG; hsa:4916; -.
DR MANE-Select; ENST00000629765.3; ENSP00000485864.1; NM_001012338.3; NP_001012338.1.
DR UCSC; uc059mwc.1; human. [Q16288-1]
DR CTD; 4916; -.
DR DisGeNET; 4916; -.
DR GeneCards; NTRK3; -.
DR HGNC; HGNC:8033; NTRK3.
DR HPA; ENSG00000140538; Tissue enhanced (brain).
DR MalaCards; NTRK3; -.
DR MIM; 191316; gene.
DR neXtProt; NX_Q16288; -.
DR OpenTargets; ENSG00000140538; -.
DR Orphanet; 2665; Congenital mesoblastic nephroma.
DR Orphanet; 146; Differentiated thyroid carcinoma.
DR Orphanet; 2030; Fibrosarcoma.
DR PharmGKB; PA31819; -.
DR VEuPathDB; HostDB:ENSG00000140538; -.
DR eggNOG; KOG1026; Eukaryota.
DR GeneTree; ENSGT00940000155645; -.
DR HOGENOM; CLU_000288_74_1_1; -.
DR InParanoid; Q16288; -.
DR OMA; RXVGGHT; -.
DR OrthoDB; 754662at2759; -.
DR PhylomeDB; Q16288; -.
DR TreeFam; TF106465; -.
DR BRENDA; 2.7.10.1; 2681.
DR PathwayCommons; Q16288; -.
DR Reactome; R-HSA-388844; Receptor-type tyrosine-protein phosphatases.
DR Reactome; R-HSA-9034013; NTF3 activates NTRK3 signaling.
DR Reactome; R-HSA-9034015; Signaling by NTRK3 (TRKC).
DR Reactome; R-HSA-9034793; Activated NTRK3 signals through PLCG1.
DR Reactome; R-HSA-9034864; Activated NTRK3 signals through RAS.
DR Reactome; R-HSA-9603381; Activated NTRK3 signals through PI3K.
DR Reactome; R-HSA-9603505; NTRK3 as a dependence receptor.
DR SignaLink; Q16288; -.
DR SIGNOR; Q16288; -.
DR BioGRID-ORCS; 4916; 12 hits in 1105 CRISPR screens.
DR ChiTaRS; NTRK3; human.
DR EvolutionaryTrace; Q16288; -.
DR GeneWiki; TrkC_receptor; -.
DR GenomeRNAi; 4916; -.
DR Pharos; Q16288; Tclin.
DR PRO; PR:Q16288; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q16288; protein.
DR Bgee; ENSG00000140538; Expressed in Brodmann (1909) area 10 and 173 other tissues.
DR ExpressionAtlas; Q16288; baseline and differential.
DR Genevisible; Q16288; HS.
DR GO; GO:0030424; C:axon; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0043235; C:receptor complex; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005004; F:GPI-linked ephrin receptor activity; IEA:Ensembl.
DR GO; GO:0043121; F:neurotrophin binding; IBA:GO_Central.
DR GO; GO:0005030; F:neurotrophin receptor activity; IDA:BHF-UCL.
DR GO; GO:0002039; F:p53 binding; IPI:BHF-UCL.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0090630; P:activation of GTPase activity; IDA:BHF-UCL.
DR GO; GO:0032148; P:activation of protein kinase B activity; IDA:BHF-UCL.
DR GO; GO:1990090; P:cellular response to nerve growth factor stimulus; IBA:GO_Central.
DR GO; GO:0071300; P:cellular response to retinoic acid; IEA:Ensembl.
DR GO; GO:0090102; P:cochlea development; IEA:Ensembl.
DR GO; GO:0007507; P:heart development; IMP:UniProtKB.
DR GO; GO:0048712; P:negative regulation of astrocyte differentiation; IEA:Ensembl.
DR GO; GO:0060548; P:negative regulation of cell death; IEA:Ensembl.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IDA:BHF-UCL.
DR GO; GO:0048665; P:neuron fate specification; IEA:Ensembl.
DR GO; GO:0001764; P:neuron migration; IEA:Ensembl.
DR GO; GO:2000251; P:positive regulation of actin cytoskeleton reorganization; IDA:BHF-UCL.
DR GO; GO:0030335; P:positive regulation of cell migration; IDA:BHF-UCL.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:BHF-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:BHF-UCL.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IDA:BHF-UCL.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IBA:GO_Central.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:BHF-UCL.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IBA:GO_Central.
DR GO; GO:0050927; P:positive regulation of positive chemotaxis; IDA:BHF-UCL.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; TAS:BHF-UCL.
DR GO; GO:0099151; P:regulation of postsynaptic density assembly; IEA:Ensembl.
DR GO; GO:1905606; P:regulation of presynapse assembly; IEA:Ensembl.
DR GO; GO:0051896; P:regulation of protein kinase B signaling; IBA:GO_Central.
DR GO; GO:0048678; P:response to axon injury; IEA:Ensembl.
DR GO; GO:0051412; P:response to corticosterone; IEA:Ensembl.
DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IDA:BHF-UCL.
DR Gene3D; 2.60.40.10; -; 2.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR000483; Cys-rich_flank_reg_C.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013098; Ig_I-set.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR013151; Immunoglobulin.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR000372; LRRNT.
DR InterPro; IPR020777; NTRK.
DR InterPro; IPR020446; NTRK3.
DR InterPro; IPR031635; NTRK_LRRCT.
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 Pfam; PF07679; I-set; 1.
DR Pfam; PF00047; ig; 1.
DR Pfam; PF13855; LRR_8; 1.
DR Pfam; PF16920; LRRCT_2; 1.
DR Pfam; PF01462; LRRNT; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PRINTS; PR01939; NTKRECEPTOR.
DR PRINTS; PR01942; NTKRECEPTOR3.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00409; IG; 1.
DR SMART; SM00082; LRRCT; 1.
DR SMART; SM00013; LRRNT; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF48726; SSF48726; 2.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
DR PROSITE; PS51450; LRR; 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; Developmental protein;
KW Differentiation; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Immunoglobulin domain; Kinase; Leucine-rich repeat; Membrane; Neurogenesis;
KW Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome; Repeat;
KW Signal; Transferase; Transmembrane; Transmembrane helix;
KW Tyrosine-protein kinase.
FT SIGNAL 1..31
FT CHAIN 32..839
FT /note="NT-3 growth factor receptor"
FT /id="PRO_0000016731"
FT TOPO_DOM 32..429
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 430..453
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 454..839
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 104..125
FT /note="LRR 1"
FT REPEAT 128..149
FT /note="LRR 2"
FT DOMAIN 160..209
FT /note="LRRCT"
FT DOMAIN 210..300
FT /note="Ig-like C2-type 1"
FT DOMAIN 309..382
FT /note="Ig-like C2-type 2"
FT DOMAIN 538..839
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 679
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 544..552
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 572
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 516
FT /note="Interaction with SHC1"
FT /evidence="ECO:0000250"
FT SITE 834
FT /note="Interaction with PLC-gamma-1"
FT /evidence="ECO:0000250"
FT MOD_RES 493
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6VNS1"
FT MOD_RES 516
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:25196463"
FT MOD_RES 705
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 709
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 710
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT CARBOHYD 72
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 79
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 133
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 163
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 203
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 218
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 232
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 259
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 267
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 272
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 294
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 375
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 388
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 32..38
FT /evidence="ECO:0000250|UniProtKB:Q91044"
FT DISULFID 36..45
FT /evidence="ECO:0000250|UniProtKB:Q91044"
FT DISULFID 164..189
FT /evidence="ECO:0000250|UniProtKB:Q91044"
FT DISULFID 166..207
FT /evidence="ECO:0000250|UniProtKB:Q91044"
FT DISULFID 231..284
FT /evidence="ECO:0000250|UniProtKB:Q91044"
FT DISULFID 320..362
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:10388563, ECO:0007744|PDB:1WWC"
FT VAR_SEQ 402..410
FT /note="ESTDNFILF -> V (in isoform 4 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_002924"
FT VAR_SEQ 529..612
FT /note="YVQHIKRRDIVLKRELGEGAFGKVFLAECYNLSPTKDKMLVAVKALKDPTLA
FT ARKDFQREAELLTNLQHEHIVKFYGVCGDGDP -> WVFSNIDNHGILNLKDNRDHLVP
FT STHYIYEEPEVQSGEVSYPRSHGFREIMLNPISLPGHSKPLNHGIYVEDVNVYFSKGRH
FT GF (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:7823156"
FT /id="VSP_002925"
FT VAR_SEQ 613..839
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:7823156"
FT /id="VSP_002926"
FT VAR_SEQ 712..725
FT /note="Missing (in isoform 3 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:7806211, ECO:0000303|PubMed:7823156"
FT /id="VSP_002927"
FT VARIANT 21
FT /note="V -> F (in dbSNP:rs200822610)"
FT /evidence="ECO:0000269|PubMed:25196463"
FT /id="VAR_074601"
FT VARIANT 71
FT /note="I -> V (found in patients with CHD; unknown
FT pathological significance; dbSNP:rs200923715)"
FT /evidence="ECO:0000269|PubMed:25196463"
FT /id="VAR_074602"
FT VARIANT 93
FT /note="T -> M (probable disease-associated variant found in
FT patients with CHD; associated with CHD susceptibility;
FT significantly reduced autophosphorylation; decreased NTRK3
FT signaling associated with decreased apoptosis in absence of
FT NTF3; dbSNP:rs147992979)"
FT /evidence="ECO:0000269|PubMed:25196463"
FT /id="VAR_074603"
FT VARIANT 149
FT /note="T -> R (in a gastric adenocarcinoma sample; somatic
FT mutation; dbSNP:rs368222977)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041471"
FT VARIANT 163
FT /note="N -> I (found in patients with CHD; unknown
FT pathological significance; no change in
FT autophosphorylation; no effect on NTRK3 signaling;
FT dbSNP:rs547862658)"
FT /evidence="ECO:0000269|PubMed:25196463"
FT /id="VAR_074604"
FT VARIANT 306
FT /note="R -> C (in dbSNP:rs56386352)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041472"
FT VARIANT 307
FT /note="V -> L (in a lung adenocarcinoma sample; somatic
FT mutation; dbSNP:rs1388363572)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041473"
FT VARIANT 336
FT /note="L -> Q (in a lung adenocarcinoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041474"
FT VARIANT 533
FT /note="I -> F (probable disease-associated variant found in
FT patients with CHD; associated with CHD susceptibility; no
FT change in autophosphorylation; changed NTRK3 signaling with
FT decreased apoptosis in absence of NTF3; dbSNP:rs869112057)"
FT /evidence="ECO:0000269|PubMed:25196463"
FT /id="VAR_074605"
FT VARIANT 664
FT /note="A -> S (in a lung carcinoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:18293376"
FT /id="VAR_046521"
FT VARIANT 677
FT /note="H -> Y (in a lung adenocarcinoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:18293376"
FT /id="VAR_041475"
FT VARIANT 678
FT /note="R -> Q (in dbSNP:rs55890138)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041476"
FT VARIANT 735
FT /note="R -> F (in a lung large cell carcinoma sample;
FT somatic mutation; requires 2 nucleotide substitutions)"
FT /id="VAR_046770"
FT VARIANT 736
FT /note="W -> C (in a lung carcinoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:18293376"
FT /id="VAR_046522"
FT VARIANT 745
FT /note="R -> P (in a lung carcinoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:18293376"
FT /id="VAR_046523"
FT VARIANT 766
FT /note="Y -> F (in a lung carcinoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:18293376"
FT /id="VAR_046524"
FT VARIANT 768
FT /note="K -> R (in dbSNP:rs55770052)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_046771"
FT VARIANT 781
FT /note="E -> K (in dbSNP:rs56393451)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_046772"
FT VARIANT 817
FT /note="I -> M (probable disease-associated variant found in
FT patients with CHD; associated with CHD susceptibility; no
FT change in autophosphorylation; changed NTRK3 signaling with
FT decreased apoptosis in absence of NTF3; dbSNP:rs869209165)"
FT /evidence="ECO:0000269|PubMed:25196463"
FT /id="VAR_074606"
FT MUTAGEN 572
FT /note="K->N: Loss of autophosphorylation and loss of NTRK3
FT signaling."
FT /evidence="ECO:0000269|PubMed:25196463"
FT CONFLICT 65
FT /note="S -> G (in Ref. 4; BAH12511)"
FT /evidence="ECO:0000305"
FT CONFLICT 70
FT /note="S -> N (in Ref. 2; AAB33111/AAB33112)"
FT /evidence="ECO:0000305"
FT CONFLICT 635
FT /note="D -> N (in Ref. 1; AAA75374)"
FT /evidence="ECO:0000305"
FT STRAND 318..326
FT /evidence="ECO:0007829|PDB:1WWC"
FT STRAND 332..337
FT /evidence="ECO:0007829|PDB:1WWC"
FT STRAND 345..354
FT /evidence="ECO:0007829|PDB:1WWC"
FT STRAND 356..367
FT /evidence="ECO:0007829|PDB:1WWC"
FT HELIX 370..372
FT /evidence="ECO:0007829|PDB:1WWC"
FT STRAND 374..382
FT /evidence="ECO:0007829|PDB:1WWC"
FT STRAND 385..393
FT /evidence="ECO:0007829|PDB:1WWC"
FT HELIX 535..537
FT /evidence="ECO:0007829|PDB:6KZD"
FT STRAND 538..547
FT /evidence="ECO:0007829|PDB:6KZD"
FT STRAND 550..559
FT /evidence="ECO:0007829|PDB:6KZD"
FT STRAND 567..576
FT /evidence="ECO:0007829|PDB:6KZD"
FT HELIX 579..594
FT /evidence="ECO:0007829|PDB:6KZD"
FT STRAND 603..606
FT /evidence="ECO:0007829|PDB:6KZD"
FT STRAND 609..618
FT /evidence="ECO:0007829|PDB:6KZD"
FT HELIX 625..631
FT /evidence="ECO:0007829|PDB:6KZD"
FT HELIX 653..672
FT /evidence="ECO:0007829|PDB:6KZD"
FT HELIX 682..684
FT /evidence="ECO:0007829|PDB:6KZD"
FT STRAND 685..687
FT /evidence="ECO:0007829|PDB:6KZD"
FT HELIX 689..691
FT /evidence="ECO:0007829|PDB:6KZD"
FT STRAND 693..695
FT /evidence="ECO:0007829|PDB:6KZD"
FT STRAND 700..704
FT /evidence="ECO:0007829|PDB:6KZD"
FT HELIX 706..708
FT /evidence="ECO:0007829|PDB:4YMJ"
FT HELIX 734..736
FT /evidence="ECO:0007829|PDB:6KZD"
FT HELIX 739..744
FT /evidence="ECO:0007829|PDB:6KZD"
FT HELIX 749..764
FT /evidence="ECO:0007829|PDB:6KZD"
FT TURN 765..767
FT /evidence="ECO:0007829|PDB:6KZD"
FT TURN 770..773
FT /evidence="ECO:0007829|PDB:6KZD"
FT HELIX 776..784
FT /evidence="ECO:0007829|PDB:6KZD"
FT HELIX 797..806
FT /evidence="ECO:0007829|PDB:6KZD"
FT HELIX 811..813
FT /evidence="ECO:0007829|PDB:6KZD"
FT HELIX 817..827
FT /evidence="ECO:0007829|PDB:6KZD"
SQ SEQUENCE 839 AA; 94428 MW; 7FE8846830083C08 CRC64;
MDVSLCPAKC SFWRIFLLGS VWLDYVGSVL ACPANCVCSK TEINCRRPDD GNLFPLLEGQ
DSGNSNGNAS INITDISRNI TSIHIENWRS LHTLNAVDME LYTGLQKLTI KNSGLRSIQP
RAFAKNPHLR YINLSSNRLT TLSWQLFQTL SLRELQLEQN FFNCSCDIRW MQLWQEQGEA
KLNSQNLYCI NADGSQLPLF RMNISQCDLP EISVSHVNLT VREGDNAVIT CNGSGSPLPD
VDWIVTGLQS INTHQTNLNW TNVHAINLTL VNVTSEDNGF TLTCIAENVV GMSNASVALT
VYYPPRVVSL EEPELRLEHC IEFVVRGNPP PTLHWLHNGQ PLRESKIIHV EYYQEGEISE
GCLLFNKPTH YNNGNYTLIA KNPLGTANQT INGHFLKEPF PESTDNFILF DEVSPTPPIT
VTHKPEEDTF GVSIAVGLAA FACVLLVVLF VMINKYGRRS KFGMKGPVAV ISGEEDSASP
LHHINHGITT PSSLDAGPDT VVIGMTRIPV IENPQYFRQG HNCHKPDTYV QHIKRRDIVL
KRELGEGAFG KVFLAECYNL SPTKDKMLVA VKALKDPTLA ARKDFQREAE LLTNLQHEHI
VKFYGVCGDG DPLIMVFEYM KHGDLNKFLR AHGPDAMILV DGQPRQAKGE LGLSQMLHIA
SQIASGMVYL ASQHFVHRDL ATRNCLVGAN LLVKIGDFGM SRDVYSTDYY RLFNPSGNDF
CIWCEVGGHT MLPIRWMPPE SIMYRKFTTE SDVWSFGVIL WEIFTYGKQP WFQLSNTEVI
ECITQGRVLE RPRVCPKEVY DVMLGCWQRE PQQRLNIKEI YKILHALGKA TPIYLDILG
