{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q16620","secondaryAccessions":["B1ANZ4","B4DFV9","Q16675","Q59GJ1","Q8WXJ5","Q8WXJ6","Q8WXJ7"],"uniProtkbId":"NTRK2_HUMAN","entryAudit":{"firstPublicDate":"1997-11-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"1996-11-01","entryVersion":251,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"BDNF/NT-3 growth factors receptor"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15494731"}],"value":"2.7.10.1"}]},"alternativeNames":[{"fullName":{"value":"GP145-TrkB"},"shortNames":[{"value":"Trk-B"}]},{"fullName":{"value":"Neurotrophic tyrosine kinase receptor type 2"}},{"fullName":{"value":"TrkB tyrosine kinase"}},{"fullName":{"value":"Tropomyosin-related kinase B"}}],"flag":"Precursor"},"genes":[{"geneName":{"value":"NTRK2"},"synonyms":[{"value":"TRKB"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P15209"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15494731"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7574684"}],"value":"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:15494731, PubMed:7574684). 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"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:10596"},{"database":"Rhea","id":"RHEA-COMP:10136"},{"database":"Rhea","id":"RHEA-COMP:20101"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:30616"},{"database":"ChEBI","id":"CHEBI:46858"},{"database":"ChEBI","id":"CHEBI:61978"},{"database":"ChEBI","id":"CHEBI:456216"}],"ecNumber":"2.7.10.1","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU10028"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15494731"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P15209"},{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q63604"}],"value":"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)"}],"commentType":"ACTIVITY REGULATION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P04629"},{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P15209"},{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q63604"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10092678"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11738045"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35840571"}],"value":"Exists in a dynamic equilibrium between monomeric (low affinity) and dimeric (high affinity) structures. Interacts (phosphorylated upon activation by BDNF) with SHC1; mediates SHC1 phosphorylation and activation. Interacts (phosphorylated upon activation by BDNF) with PLCG1 and/or PLCG2; mediates PLCG1 phosphorylation and activation. Interacts with SH2B1 and SH2B2. Interacts with NGFR; may regulate the ligand specificity of the receptor (By similarity). Interacts with SORCS2; this interaction is important for normal targeting to post-synaptic densities in response to high-frequency stimulation (By similarity). Interacts (phosphorylated upon ligand-binding) with SH2D1A; regulates NTRK2. Interacts with SQSTM1 and KIDINS220 (By similarity). Interacts (phosphorylated upon ligand-binding) with FRS2; activates the MAPK signaling pathway (PubMed:10092678). Interacts with APPL1 (By similarity). Interacts with MAPK8IP3/JIP3 and KLC1; interaction with KLC1 is mediated by MAPK8IP3/JIP3 (By similarity). Interacts with SORL1; this interaction facilitates NTRK2 trafficking between synaptic plasma membranes, postsynaptic densities and cell soma, hence positively regulates BDNF signaling (By similarity). Interacts with SLITRK2 (PubMed:35840571)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q16620","intActId":"EBI-3904881"},"interactantTwo":{"uniProtKBAccession":"P00533","geneName":"EGFR","intActId":"EBI-297353"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q16620","intActId":"EBI-3904881"},"interactantTwo":{"uniProtKBAccession":"Q16288","geneName":"NTRK3","intActId":"EBI-3936704"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q16620","intActId":"EBI-3904881"},"interactantTwo":{"uniProtKBAccession":"Q13485","geneName":"SMAD4","intActId":"EBI-347263"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q16620","intActId":"EBI-3904881"},"interactantTwo":{"uniProtKBAccession":"Q03114","geneName":"Cdk5","intActId":"EBI-2008531"},"numberOfExperiments":3,"organismDiffer":true}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P15209"}],"value":"Internalized to endosomes upon ligand-binding"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15494731"}],"value":"Cell membrane","id":"SL-0039"},"topology":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Single-pass type I membrane protein","id":"SL-9905"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P15209"}],"value":"Endosome membrane","id":"SL-0100"},"topology":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P15209"}],"value":"Single-pass type I membrane protein","id":"SL-9905"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P15209"}],"value":"Early endosome membrane","id":"SL-0093"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q63604"}],"value":"Cell projection, axon","id":"SL-0279"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q63604"}],"value":"Cell projection, dendrite","id":"SL-0283"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q63604"}],"value":"Cytoplasm, perinuclear region","id":"SL-0198"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P15209"}],"value":"Postsynaptic density","id":"SL-0297"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"TrkB"},"synonyms":[{"value":"gp145-TrkB"}],"isoformIds":["Q16620-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"TrkB-T1"},"isoformIds":["Q16620-2"],"sequenceIds":["VSP_002901","VSP_002902"],"isoformSequenceStatus":"Described"},{"name":{"value":"TrkB-T-Shc"},"isoformIds":["Q16620-3"],"sequenceIds":["VSP_002903","VSP_002904"],"isoformSequenceStatus":"Described"},{"name":{"value":"4"},"isoformIds":["Q16620-4"],"sequenceIds":["VSP_041942"],"isoformSequenceStatus":"Described"},{"name":{"value":"5"},"isoformIds":["Q16620-5"],"sequenceIds":["VSP_041942","VSP_002903","VSP_002904"],"isoformSequenceStatus":"Described"},{"name":{"value":"TrkB-T-TK"},"isoformIds":["Q16620-6"],"sequenceIds":["VSP_042178","VSP_042179"],"isoformSequenceStatus":"Described"},{"name":{"value":"TrkB-N-T1"},"isoformIds":["Q16620-7"],"sequenceIds":["VSP_042177","VSP_002901","VSP_002902"],"isoformSequenceStatus":"Described"}],"note":{"texts":[{"value":"Additional isoforms seem to exist."}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11798182"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7936202"}],"value":"Isoform TrkB is expressed in the central and peripheral nervous system. In the central nervous system (CNS), expression is observed in the cerebral cortex, hippocampus, thalamus, choroid plexus, granular layer of the cerebellum, brain stem, and spinal cord. In the peripheral nervous system, it is expressed in many cranial ganglia, the ophthalmic nerve, the vestibular system, multiple facial structures, the submaxillary glands, and dorsal root ganglia. Isoform TrkB-T1 is mainly expressed in the brain but also detected in other tissues including pancreas, kidney and heart. Isoform TrkB-T-Shc is predominantly expressed in the brain"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7936202"}],"value":"Widely expressed in fetal brain"}],"commentType":"DEVELOPMENTAL STAGE"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15494731"}],"value":"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"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"Ubiquitinated. Undergoes polyubiquitination upon activation; regulated by NGFR. Ubiquitination regulates the internalization of the receptor (By similarity)"}],"commentType":"PTM"},{"commentType":"DISEASE","disease":{"diseaseId":"Developmental and epileptic encephalopathy 58","diseaseAccession":"DI-05170","acronym":"DEE58","description":"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.","diseaseCrossReference":{"database":"MIM","id":"617830"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29100083"}]},"note":{"texts":[{"value":"The disease may be caused by variants affecting the gene represented in this entry"}]}},{"commentType":"DISEASE","disease":{"diseaseId":"Obesity, hyperphagia, and developmental delay","diseaseAccession":"DI-03120","acronym":"OBHD","description":"A disorder characterized by early-onset obesity, hyperphagia, and severe developmental delay in motor function, speech, and language.","diseaseCrossReference":{"database":"MIM","id":"613886"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15494731"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27884935"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29100083"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"texts":[{"value":"Trk also stands for tropomyosin-related kinase since the first Trk was isolated as an oncogenic protein which was the result of a fusion between the tropomyosin gene TPM3 and NTRK1"}],"commentType":"MISCELLANEOUS"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Non-catalytic isoform"}],"commentType":"MISCELLANEOUS","molecule":"Isoform TrkB-T1"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00159"}],"value":"Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily"}],"commentType":"SIMILARITY"},{"commentType":"WEB RESOURCE","resourceName":"Atlas of Genetics and Cytogenetics in Oncology and Haematology","resourceUrl":"https://atlasgeneticsoncology.org/gene/41589/NTRK2","ftp":false}],"features":[{"type":"Signal","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":31,"modifier":"EXACT"}},"description":""},{"type":"Chain","location":{"start":{"value":32,"modifier":"EXACT"},"end":{"value":822,"modifier":"EXACT"}},"description":"BDNF/NT-3 growth factors receptor","featureId":"PRO_0000016727"},{"type":"Topological domain","location":{"start":{"value":32,"modifier":"EXACT"},"end":{"value":430,"modifier":"EXACT"}},"description":"Extracellular","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Transmembrane","location":{"start":{"value":431,"modifier":"EXACT"},"end":{"value":454,"modifier":"EXACT"}},"description":"Helical","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Topological 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