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BDNF/NT-3 growth factors receptor; EC=2.7.10.1; neurotrophic tyrosine kinase receptor type 2; TrkB tyrosine kinase; GP145-TrkB; Trk-B (NTRK2 TRKB)
Function:
- receptor for brain-derived neurotrophic factor (BDNF), neurotrophin-3 & neurotrophin-4/5 but not nerve growth factor (NGF)
- role in development &/or maintenance of the nervous system
- tyrosine-protein kinase receptor
- substrates for the TRK receptors include: SHC1, PI-3 kinase, & PLC- gamma-1
- dynamic equilibrium between monomeric (low affinity) & dimeric (high affinity) structures
- binds SH2B2
- interacts with SQSTM1 & ARMS (putative)
- ligand-mediated auto-phosphorylation
Structure:
- belongs to the protein kinase superfamily, Tyr protein kinase family, insulin receptor subfamily
- contains 2 Ig-like C2-type domains (immunoglobulin-like)
- contains 2 LRR repeats (leucine-rich repeats)
- contains 1 protein kinase domain
Compartment: membrane
Alternative splicing: named isoforms=3
Expression:
- isoform TrkB is widely expressed, mainly in nervous tissue
- in the CNS, expression is observed in the cerebral cortex, hippocampus, thalamus, choroid plexus, granular layer of the cerebellum, brain stem, & 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, & dorsal root ganglia
- isoform TrkB-T1 is expressed in multiple tissues, mainly in brain, pancreas, kidney & heart
- isoform TrkB-T-Shc is predominantly expressed in brain
Interactions
molecular events
Related
NTRK2 or TRKB proto-oncogene
Specific
trk B proto-oncogene protein (gp95trkB)
General
glycoprotein
leucine-rich repeat-containing protein (LRRC)
phosphoprotein
tropomyosin receptor kinase (trk) proto-oncogene protein (NTRK)
Properties
SIZE: entity length = 822 aa
MW = 92 kD
COMPARTMENT: cellular membrane
STATE: active state
MOTIF: signal sequence {1-31}
cysteine residue {C32}
MODIFICATION: cysteine residue {C38}
cysteine residue {C36}
MODIFICATION: cysteine residue {C45}
cysteine residue {C38}
MODIFICATION: cysteine residue {C32}
cysteine residue {C45}
MODIFICATION: cysteine residue {C36}
N-glycosylation site {N67}
leucine-rich repeat
SITE: 72-93
MOTIF: leucine residue (SEVERAL)
N-glycosylation site {N95}
leucine-rich repeat
SITE: 96-117
MOTIF: leucine residue (SEVERAL)
N-glycosylation site {N121}
cysteine residue {C152}
MODIFICATION: cysteine residue {C176}
cysteine residue {C154}
MODIFICATION: cysteine residue {C194}
cysteine residue {C176}
MODIFICATION: cysteine residue {C152}
N-glycosylation site {N178}
cysteine residue {C194}
MODIFICATION: cysteine residue {C154}
immunoglobulin superfamily domain {197-282}
MOTIF: N-glycosylation site {N205}
cysteine residue {C218}
MODIFICATION: cysteine residue {C266}
N-glycosylation site {N241}
N-glycosylation site {N254}
cysteine residue {C266}
MODIFICATION: cysteine residue {C218}
N-glycosylation site {N280}
immunoglobulin superfamily domain {295-365}
MOTIF: cysteine residue {C302}
MODIFICATION: cysteine residue {C345}
N-glycosylation site {N325}
N-glycosylation site {N338}
cysteine residue {C345}
MODIFICATION: cysteine residue {C302}
N-glycosylation site {N412}
transmembrane domain {431-454}
tyrosine residue {516}
Tyr phosphorylation site {Y516}
kinase domain
SITE: 538-807
MOTIF: ATP-binding site
NAME: ATP-binding site
SITE: 544-552
ATP-binding site
NAME: ATP-binding site
SITE: 572-572
aspartate residue {D676}
Tyr phosphorylation site {Y702}
Tyr phosphorylation site {Y706}
Tyr phosphorylation site {Y707}
tyrosine residue {817}
Tyr phosphorylation site {Y817}
Database Correlations
OMIM 600456
MORBIDMAP 600456
UniProt Q16620
PFAM correlations
KEGG correlations
References
- UniProt :accession Q16620
- Klein R, Conway D, Parada LF, Barbacid M.
The trkB tyrosine protein kinase gene codes for a second
neurogenic receptor that lacks the catalytic kinase domain.
Cell. 1990 May 18;61(4):647-56.
PMID: 2160854