ID  Q16620;
PN  BDNF/NT-3 growth factors receptor;
GN  NTRK2;
OS  9606;
SL  Nucleus Position: SL-0198;
SL  Comments: Cell membrane {ECO:0000269|PubMed:15494731}; Single-pass type I membrane protein {ECO:0000305}. Endosome membrane {ECO:0000250|UniProtKB:P15209}; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P15209}. Early endosome membrane {ECO:0000250|UniProtKB:P15209}. Cell projection, axon {ECO:0000250|UniProtKB:Q63604}. Cell projection, dendrite {ECO:0000250|UniProtKB:Q63604}. Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:Q63604}. Postsynaptic density {ECO:0000250|UniProtKB:P15209}. Note=Internalized to endosomes upon ligand-binding. {ECO:0000250|UniProtKB:P15209}.
DR  UNIPROT: Q16620;
DR  UNIPROT: B1ANZ4;
DR  UNIPROT: B4DFV9;
DR  UNIPROT: Q16675;
DR  UNIPROT: Q59GJ1;
DR  UNIPROT: Q8WXJ5;
DR  UNIPROT: Q8WXJ6;
DR  UNIPROT: Q8WXJ7;
DR  PDB: 1HCF;
DR  PDB: 1WWB;
DR  PDB: 2MFQ;
DR  PDB: 4ASZ;
DR  PDB: 4AT3;
DR  PDB: 4AT4;
DR  PDB: 4AT5;
DR  PDB: 5MO9;
DR  Pfam: PF07679;
DR  Pfam: PF13855;
DR  Pfam: PF16920;
DR  Pfam: PF01462;
DR  Pfam: PF07714;
DR  PROSITE: PS50835;
DR  PROSITE: PS00107;
DR  PROSITE: PS50011;
DR  PROSITE: PS00109;
DR  PROSITE: PS00239;
DR  OMIM: 600456;
DR  OMIM: 613886;
DR  OMIM: 617830;
DR  DisGeNET: 4915;
DE  Function: Receptor tyrosine kinase involved in the development and the maturation of the central and the peripheral nervous systems through regulation of neuron survival, proliferation, migration, differentiation, and synapse formation and plasticity (By similarity). Receptor for BDNF/brain-derived neurotrophic factor and NTF4/neurotrophin-4. Alternatively can also bind NTF3/neurotrophin-3 which is less efficient in activating the receptor but regulates neuron survival through NTRK2 (PubMed:7574684, PubMed:15494731). Upon ligand- binding, undergoes homodimerization, autophosphorylation and activation (PubMed:15494731). Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades. Through SHC1, FRS2, SH2B1, SH2B2 activates the GRB2-Ras-MAPK cascade that regulates for instance neuronal differentiation including neurite outgrowth. Through the same effectors controls the Ras-PI3 kinase-AKT1 signaling cascade that mainly regulates growth and survival. Through PLCG1 and the downstream protein kinase C-regulated pathways controls synaptic plasticity. Thereby, plays a role in learning and memory by regulating both short term synaptic function and long-term potentiation. PLCG1 also leads to NF-Kappa-B activation and the transcription of genes involved in cell survival. Hence, it is able to suppress anoikis, the apoptosis resulting from loss of cell-matrix interactions. May also play a role in neutrophin-dependent calcium signaling in glial cells and mediate communication between neurons and glia. {ECO:0000250|UniProtKB:P15209, ECO:0000269|PubMed:15494731, ECO:0000269|PubMed:7574684}.
DE  Disease: Developmental and epileptic encephalopathy 58 (DEE58) [MIM:617830]: A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE58 is an autosomal dominant condition characterized by onset of refractory seizures in the first days or months of life. {ECO:0000269|PubMed:29100083}. Note=The disease may be caused by variants affecting the gene represented in this entry. Obesity, hyperphagia, and developmental delay (OBHD) [MIM:613886]: A disorder characterized by early-onset obesity, hyperphagia, and severe developmental delay in motor function, speech, and language. {ECO:0000269|PubMed:15494731, ECO:0000269|PubMed:27884935, ECO:0000269|PubMed:29100083}. Note=The disease is caused by variants affecting the gene represented in this entry.
DE  Reference Proteome: Yes;
DE  Interaction: P00533; IntAct: EBI-9689644; Score: 0.55
DE  Interaction: Q03001; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q10567; IntAct: EBI-3904879; Score: 0.37
DE  Interaction: P62487; IntAct: EBI-3911957; Score: 0.37
DE  Interaction: Q9HAN9; IntAct: EBI-3919655; Score: 0.37
DE  Interaction: Q16620; IntAct: EBI-5650732; Score: 0.49
DE  Interaction: P08238; IntAct: EBI-6424683; Score: 0.40
DE  Interaction: P34130; IntAct: EBI-6590946; Score: 0.41
DE  Interaction: P14618; IntAct: EBI-9354703; Score: 0.44
DE  Interaction: Q99523; IntAct: EBI-9828457; Score: 0.44
DE  Interaction: Q03114; IntAct: EBI-15624658; Score: 0.56
DE  Interaction: P04150; IntAct: EBI-15750128; Score: 0.40
DE  Interaction: P78352; IntAct: EBI-16037188; Score: 0.40
DE  Interaction: Q96QK1; IntAct: EBI-27081124; Score: 0.35
DE  Interaction: P19174; IntAct: EBI-32719199; Score: 0.42
DE  Interaction: Q16543; IntAct: EBI-32719199; Score: 0.42
DE  Interaction: P08754; IntAct: EBI-32719199; Score: 0.35
DE  Interaction: Q8WU20; IntAct: EBI-32719199; Score: 0.42
DE  Interaction: P62158; IntAct: EBI-32719199; Score: 0.35
DE  Interaction: Q16288; IntAct: EBI-32719212; Score: 0.54
DE  Interaction: Q3V6T2; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q9UPS8; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q9H3R5; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q86YF9; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q92738; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q8IYB1; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q16625; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: P50851; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q12923; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q96RT1; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q9H3P7; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q5VUB5; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q6WCQ1; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q15334; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q8TEW0; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: A8MVW0; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: P27448; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q9NNW5; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: O00459; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: O95487; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q9ULH0; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q13480; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q9Y6M7; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q9H792; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q9H2D6; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q99618; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: P29317; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q86X29; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: P20020; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: A7KAX9; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q9Y2I1; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q15643; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q04721; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: O14964; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q86W92; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: P16333; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q8TDM6; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q15437; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q9UM54; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q8TAA9; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q9HCM4; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: P27986; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q9C0B5; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q9HD26; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q6ZVF9; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q9H2J7; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q02487; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q14254; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: P62993; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: O95490; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: P41743; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q658P3; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: O75052; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q9HDC5; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q9P2D6; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q9UKG1; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q6P995; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q9UBH6; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q13136; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q9BXF6; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q9UET6; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q9UNF0; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: O75886; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q9Y5Z9; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q6NSJ2; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: O95292; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: O15013; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q92569; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q9Y4J8; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q99959; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q9H8Y8; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: P42338; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: O14639; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q8N4C8; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q8N350; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q4KWH8; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q9C004; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q9H0W5; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q9H939; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q8NE01; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q08357; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: P62873; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q6P996; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: O95405; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: O00170; IntAct: EBI-32724423; Score: 0.27
DE  Interaction: Q06124; IntAct: EBI-32724423; Score: 0.27
GO  GO:0070161;
GO  GO:0030424;
GO  GO:0043679;
GO  GO:0005829;
GO  GO:0030425;
GO  GO:0043197;
GO  GO:0005769;
GO  GO:0031901;
GO  GO:0005887;
GO  GO:0048471;
GO  GO:0005886;
GO  GO:0014069;
GO  GO:0043235;
GO  GO:0043195;
GO  GO:0005524;
GO  GO:0048403;
GO  GO:0060175;
GO  GO:0043121;
GO  GO:0005030;
GO  GO:0002020;
GO  GO:0042803;
GO  GO:0004714;
GO  GO:0031547;
GO  GO:0071230;
GO  GO:1990416;
GO  GO:1990090;
GO  GO:0021954;
GO  GO:0021987;
GO  GO:0007623;
GO  GO:0007631;
GO  GO:0014047;
GO  GO:0007612;
GO  GO:0060291;
GO  GO:0042490;
GO  GO:0022011;
GO  GO:1902430;
GO  GO:2000811;
GO  GO:0043524;
GO  GO:0030182;
GO  GO:0001764;
GO  GO:0019227;
GO  GO:0048709;
GO  GO:0018105;
GO  GO:0048935;
GO  GO:0050772;
GO  GO:0008284;
GO  GO:0010628;
GO  GO:0033674;
GO  GO:0043410;
GO  GO:0010976;
GO  GO:0033138;
GO  GO:0014068;
GO  GO:0001934;
GO  GO:0051965;
GO  GO:0046777;
GO  GO:0043087;
GO  GO:0051896;
GO  GO:0046548;
GO  GO:0099183;
GO  GO:0099551;
GO  GO:0007169;
GO  GO:0001570;
TP  Membrane Topology: Transmembrane; Source: UniProt - Sequence Analysis {ECO:0000255};
SQ  MSSWIRWHGPAMARLWGFCWLVVGFWRAAFACPTSCKCSASRIWCSDPSPGIVAFPRLEPNSVDPENITEIFIANQKRLE
SQ  IINEDDVEAYVGLRNLTIVDSGLKFVAHKAFLKNSNLQHINFTRNKLTSLSRKHFRHLDLSELILVGNPFTCSCDIMWIK
SQ  TLQEAKSSPDTQDLYCLNESSKNIPLANLQIPNCGLPSANLAAPNLTVEEGKSITLSCSVAGDPVPNMYWDVGNLVSKHM
SQ  NETSHTQGSLRITNISSDDSGKQISCVAENLVGEDQDSVNLTVHFAPTITFLESPTSDHHWCIPFTVKGNPKPALQWFYN
SQ  GAILNESKYICTKIHVTNHTEYHGCLQLDNPTHMNNGDYTLIAKNEYGKDEKQISAHFMGWPGIDDGANPNYPDVIYEDY
SQ  GTAANDIGDTTNRSNEIPSTDVTDKTGREHLSVYAVVVIASVVGFCLLVMLFLLKLARHSKFGMKGPASVISNDDDSASP
SQ  LHHISNGSNTPSSSEGGPDAVIIGMTKIPVIENPQYFGITNSQLKPDTFVQHIKRHNIVLKRELGEGAFGKVFLAECYNL
SQ  CPEQDKILVAVKTLKDASDNARKDFHREAELLTNLQHEHIVKFYGVCVEGDPLIMVFEYMKHGDLNKFLRAHGPDAVLMA
SQ  EGNPPTELTQSQMLHIAQQIAAGMVYLASQHFVHRDLATRNCLVGENLLVKIGDFGMSRDVYSTDYYRVGGHTMLPIRWM
SQ  PPESIMYRKFTTESDVWSLGVVLWEIFTYGKQPWYQLSNNEVIECITQGRVLQRPRTCPQEVYELMLGCWQREPHMRKNI
SQ  KGIHTLLQNLAKASPVYLDILG
//