| IED ID | IndEnz0002012755 |
| Enzyme Type ID | protease012755 |
| Protein Name |
BDNF/NT-3 growth factors receptor EC 2.7.10.1 GP145-TrkB Trk-B Neurotrophic tyrosine kinase receptor type 2 TrkB tyrosine kinase Tropomyosin-related kinase B |
| Gene Name | NTRK2 TRKB |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MSSWIRWHGPAMARLWGFCWLVVGFWRAAFACPTSCKCSASRIWCSDPSPGIVAFPRLEPNSVDPENITEIFIANQKRLEIINEDDVEAYVGLRNLTIVDSGLKFVAHKAFLKNSNLQHINFTRNKLTSLSRKHFRHLDLSELILVGNPFTCSCDIMWIKTLQEAKSSPDTQDLYCLNESSKNIPLANLQIPNCGLPSANLAAPNLTVEEGKSITLSCSVAGDPVPNMYWDVGNLVSKHMNETSHTQGSLRITNISSDDSGKQISCVAENLVGEDQDSVNLTVHFAPTITFLESPTSDHHWCIPFTVKGNPKPALQWFYNGAILNESKYICTKIHVTNHTEYHGCLQLDNPTHMNNGDYTLIAKNEYGKDEKQISAHFMGWPGIDDGANPNYPDVIYEDYGTAANDIGDTTNRSNEIPSTDVTDKTGREHLSVYAVVVIASVVGFCLLVMLFLLKLARHSKFGMKGPASVISNDDDSASPLHHISNGSNTPSSSEGGPDAVIIGMTKIPVIENPQYFGITNSQLKPDTFVQHIKRHNIVLKRELGEGAFGKVFLAECYNLCPEQDKILVAVKTLKDASDNARKDFHREAELLTNLQHEHIVKFYGVCVEGDPLIMVFEYMKHGDLNKFLRAHGPDAVLMAEGNPPTELTQSQMLHIAQQIAAGMVYLASQHFVHRDLATRNCLVGENLLVKIGDFGMSRDVYSTDYYRVGGHTMLPIRWMPPESIMYRKFTTESDVWSLGVVLWEIFTYGKQPWYQLSNNEVIECITQGRVLQRPRTCPQEVYELMLGCWQREPHMRKNIKGIHTLLQNLAKASPVYLDILG |
| Enzyme Length | 822 |
| Uniprot Accession Number | Q16620 |
| Absorption | |
| Active Site | ACT_SITE 676; /note="Proton acceptor"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-ProRule:PRU10028" |
| Activity Regulation | ACTIVITY REGULATION: The neuronal activity and the influx of calcium positively regulate the kinase activity and the internalization of the receptor which are both important for active signaling. Regulated by NGFR that may control the internalization of the receptor. NGFR may also stimulate the activation by BDNF compared to NTF3 and NTF4. SH2D1A inhibits the autophosphorylation of the receptor, and alters the recruitment and activation of downstream effectors and signaling cascades. The formation of active receptors dimers able to fully transduce the ligand-mediated signal, may be negatively regulated by the formation of inactive heterodimers with the non-catalytic isoforms (By similarity). {ECO:0000250|UniProtKB:P15209, ECO:0000250|UniProtKB:Q63604}. |
| Binding Site | BINDING 572; /note=ATP; /evidence=ECO:0000255|PROSITE-ProRule:PRU00159 |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-[protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1; Evidence={ECO:0000255|PROSITE-ProRule:PRU10028, ECO:0000269|PubMed:15494731}; |
| DNA Binding | |
| EC Number | 2.7.10.1 |
| Enzyme Function | 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}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 544..552; /note=ATP; /evidence=ECO:0000255|PROSITE-ProRule:PRU00159 |
| Features | Active site (1); Alternative sequence (8); Beta strand (21); Binding site (1); Chain (1); Compositional bias (1); Disulfide bond (6); Domain (5); Glycosylation (11); Helix (17); Modified residue (5); Natural variant (11); Nucleotide binding (1); Region (2); Repeat (2); Signal peptide (1); Site (3); Topological domain (2); Transmembrane (1); Turn (4) |
| Keywords | 3D-structure;ATP-binding;Alternative splicing;Cell junction;Cell membrane;Cell projection;Cytoplasm;Developmental protein;Differentiation;Disease variant;Disulfide bond;Endosome;Epilepsy;Glycoprotein;Immunoglobulin domain;Kinase;Leucine-rich repeat;Membrane;Neurogenesis;Nucleotide-binding;Obesity;Phosphoprotein;Receptor;Reference proteome;Repeat;Signal;Synapse;Transferase;Transmembrane;Transmembrane helix;Tyrosine-protein kinase;Ubl conjugation |
| Interact With | Q03114 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: 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}. Cell junction, synapse, postsynaptic density {ECO:0000250|UniProtKB:P15209}. Note=Internalized to endosomes upon ligand-binding. {ECO:0000250|UniProtKB:P15209}. |
| Modified Residue | MOD_RES 516; /note=Phosphotyrosine; by autocatalysis; /evidence=ECO:0000250|UniProtKB:P15209; MOD_RES 702; /note=Phosphotyrosine; by autocatalysis; /evidence=ECO:0000250|UniProtKB:Q63604; MOD_RES 706; /note=Phosphotyrosine; by autocatalysis; /evidence=ECO:0000250|UniProtKB:Q63604; MOD_RES 707; /note=Phosphotyrosine; by autocatalysis; /evidence=ECO:0000250|UniProtKB:Q63604; MOD_RES 817; /note=Phosphotyrosine; by autocatalysis; /evidence=ECO:0000250|UniProtKB:Q63604 |
| Post Translational Modification | PTM: Phosphorylated. Undergoes ligand-mediated autophosphorylation that is required for interaction with SHC1 and PLCG1 and other downstream effectors. Isoform TrkB-T-Shc is not phosphorylated. {ECO:0000269|PubMed:15494731}.; PTM: Ubiquitinated. Undergoes polyubiquitination upon activation; regulated by NGFR. Ubiquitination regulates the internalization of the receptor (By similarity). {ECO:0000250}. |
| Signal Peptide | SIGNAL 1..31 |
| Structure 3D | NMR spectroscopy (1); X-ray crystallography (7) |
| Cross Reference PDB | 1HCF; 1WWB; 2MFQ; 4ASZ; 4AT3; 4AT4; 4AT5; 5MO9; |
| Mapped Pubmed ID | 10196222; 10486198; 10490030; 10533983; 10579907; 10631974; 11248116; 11263982; 11432792; 11536331; 11784714; 11849294; 11855816; 12367511; 12663749; 12719654; 12808116; 12912764; 12921913; 1375038; 15024057; 15389758; 15637590; 15647480; 15657181; 15838534; 16051641; 1649702; 16573649; 16648150; 16697063; 16713371; 16713586; 16786155; 16805430; 16862449; 16964397; 17008023; 17200667; 17341134; 17570738; 17616679; 17674765; 17720314; 17873329; 17884018; 17889702; 17918233; 17971243; 18075316; 18201274; 18203754; 18253057; 18286198; 18319596; 18428117; 18511296; 18534558; 18595003; 18637190; 18678285; 18727839; 18959266; 18992902; 19018715; 19086053; 19087522; 19124685; 19156168; 19170129; 19268276; 19307055; 19363525; 19365399; 19386345; 19403818; 19417027; 19453261; 19488044; 19548263; 19598235; 19635108; 19641488; 19741136; 19765683; 19801649; 19816090; 19844206; 19874574; 19879330; 19885622; 19913121; 19927149; 20014955; 20064930; 20083228; 20101235; 20124106; 20132184; 20156366; 20186105; 20202475; 20219210; 20368433; 20379614; 20428771; 20463055; 20468064; 20610389; 20615547; 20628086; 20662941; 20694504; 20703101; 20811716; 20877300; 20878119; 21047554; 21079983; 21102451; 21126736; 21187387; 21192928; 21215389; 21223646; 21239439; 21242122; 21295543; 21330466; 21379385; 21414899; 21419569; 21426646; 21481795; 21552290; 21612826; 21615729; 21670725; 21711518; 21739244; 21750702; 21795612; 21802740; 21849537; 21849550; 21966426; 21988832; 21999199; 22020324; 22028443; 22209410; 22258407; 22269274; 22322843; 22341689; 22343487; 22361863; 22393127; 22425982; 22426239; 22490895; 22609366; 22710966; 22719055; 22886570; 22902478; 22906736; 22939624; 23058367; 23064382; 23086941; 23124249; 23137999; 23185507; 23277131; 23315174; 23332094; 23416450; 23420490; 23422506; 23424281; 23598407; 23656788; 23831349; 23861540; 23869086; 23936232; 24047966; 24069289; 24086766; 24116072; 24321270; 24372023; 24403123; 24470253; 24498100; 24531713; 24549576; 24606918; 24612679; 24658140; 24802768; 24853179; 24867303; 24950379; 24959744; 24982195; 24984919; 24991961; 25037567; 25110312; 25143381; 25210182; 25241761; 25288805; 25450229; 25456007; 25512530; 25633318; 25700942; 25751398; 25796564; 25896770; 26122862; 26284337; 26410307; 26410934; 26459250; 26462037; 26481038; 26515594; 26617738; 26641254; 26657794; 26797418; 26820170; 26978740; 27048022; 27278006; 27385098; 27402815; 27519317; 27662840; 28012455; 28205449; 28213521; 28215291; 28215305; 28230291; 28351853; 28423707; 28446206; 28497343; 28550723; 28604655; 28604807; 28612959; 28719467; 28739680; 28863320; 28870922; 28923922; 28938915; 29059151; 29109000; 29345295; 29466871; 29683819; 29748024; 29767567; 30066929; 30133147; 30242240; 30258047; 30276917; 30304550; 30308049; 30366959; 30641914; 30848386; 31071716; 31255912; 31268127; 31298409; 31349032; 31711978; 31792356; 31820346; 31871300; 31941116; 32149119; 32277855; 32315394; 32350920; 32351633; 32390303; 32422149; 32532995; 32911446; 32931807; 32941187; 33094812; 33112285; 33144287; 33222311; 33248386; 33288548; 33302387; 33524004; 33643311; 33749030; 34281873; 34416224; 34425480; 34493726; 34610834; 34743199; 7982951; 8106527; 9648856; 9728915; |
| Motif | |
| Gene Encoded By | |
| Mass | 91,999 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:10596 |
| Cross Reference Brenda | 2.7.10.1; |