CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-004314
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 BDNF/NT-3 growth factors receptor 
Protein Synonyms/Alias
 GP145-TrkB/GP95-TrkB; Trk-B; Neurotrophic tyrosine kinase receptor type 2; TrkB tyrosine kinase 
Gene Name
 Ntrk2 
Gene Synonyms/Alias
 Trkb 
Created Date
 July 27, 2013 
Organism
 Mus musculus (Mouse) 
NCBI Taxa ID
 10090 
Lysine Modification
Position
Peptide
Type
References
524GITNSQLKPDTFVQHubiquitination[1]
571DKILVAVKTLKDASDubiquitination[1]
800PHTRKNIKSIHTLLQubiquitination[1]
Reference
 [1] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023] 
Functional Description
 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. 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. Upon ligand-binding, undergoes homodimerization, autophosphorylation and activation. 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. Isoform GP95-TRKB may also play a role in neutrophin-dependent calcium signaling in glial cells and mediate communication between neurons and glia. 
Sequence Annotation
 DOMAIN 32 61 LRRNT.
 REPEAT 92 113 LRR 1.
 REPEAT 116 137 LRR 2.
 DOMAIN 148 196 LRRCT.
 DOMAIN 197 282 Ig-like C2-type 1.
 DOMAIN 301 365 Ig-like C2-type 2.
 DOMAIN 537 806 Protein kinase.
 NP_BIND 543 551 ATP (By similarity).
 ACT_SITE 675 675 Proton acceptor (By similarity).
 BINDING 571 571 ATP (By similarity).
 MOD_RES 515 515 Phosphotyrosine; by autocatalysis (By
 MOD_RES 701 701 Phosphotyrosine; by autocatalysis (By
 MOD_RES 705 705 Phosphotyrosine; by autocatalysis (By
 MOD_RES 706 706 Phosphotyrosine; by autocatalysis (By
 MOD_RES 816 816 Phosphotyrosine; by autocatalysis (By
 CARBOHYD 67 67 N-linked (GlcNAc...) (By similarity).
 CARBOHYD 95 95 N-linked (GlcNAc...) (By similarity).
 CARBOHYD 121 121 N-linked (GlcNAc...) (By similarity).
 CARBOHYD 178 178 N-linked (GlcNAc...) (By similarity).
 CARBOHYD 205 205 N-linked (GlcNAc...) (By similarity).
 CARBOHYD 241 241 N-linked (GlcNAc...) (By similarity).
 CARBOHYD 254 254 N-linked (GlcNAc...) (By similarity).
 CARBOHYD 280 280 N-linked (GlcNAc...) (By similarity).
 CARBOHYD 325 325 N-linked (GlcNAc...) (Potential).
 CARBOHYD 338 338 N-linked (GlcNAc...) (By similarity).
 CARBOHYD 411 411 N-linked (GlcNAc...) (By similarity).
 DISULFID 32 38 By similarity.
 DISULFID 36 45 By similarity.
 DISULFID 152 176 By similarity.
 DISULFID 154 194 By similarity.
 DISULFID 218 266 By similarity.
 DISULFID 302 345 By similarity.  
Keyword
 Alternative splicing; ATP-binding; Cell membrane; Complete proteome; Developmental protein; Differentiation; Disulfide bond; Endosome; Glycoprotein; Immunoglobulin domain; Kinase; Leucine-rich repeat; Membrane; Neurogenesis; Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome; Repeat; Signal; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 821 AA 
Protein Sequence
MSPWLKWHGP AMARLWGLCL LVLGFWRASL ACPTSCKCSS ARIWCTEPSP GIVAFPRLEP 60
NSVDPENITE ILIANQKRLE IINEDDVEAY VGLRNLTIVD SGLKFVAYKA FLKNSNLRHI 120
NFTRNKLTSL SRRHFRHLDL SDLILTGNPF TCSCDIMWLK TLQETKSSPD TQDLYCLNES 180
SKNMPLANLQ IPNCGLPSAR LAAPNLTVEE GKSVTLSCSV GGDPLPTLYW DVGNLVSKHM 240
NETSHTQGSL RITNISSDDS GKQISCVAEN LVGEDQDSVN LTVHFAPTIT FLESPTSDHH 300
WCIPFTVRGN PKPALQWFYN GAILNESKYI CTKIHVTNHT EYHGCLQLDN PTHMNNGDYT 360
LMAKNEYGKD ERQISAHFMG RPGVDYETNP NYPEVLYEDW TTPTDIGDTT NKSNEIPSTD 420
VADQSNREHL SVYAVVVIAS VVGFCLLVML LLLKLARHSK FGMKGPASVI SNDDDSASPL 480
HHISNGSNTP SSSEGGPDAV IIGMTKIPVI ENPQYFGITN SQLKPDTFVQ HIKRHNIVLK 540
RELGEGAFGK VFLAECYNLC PEQDKILVAV KTLKDASDNA RKDFHREAEL LTNLQHEHIV 600
KFYGVCVEGD PLIMVFEYMK HGDLNKFLRA HGPDAVLMAE GNPPTELTQS QMLHIAQQIA 660
AGMVYLASQH FVHRDLATRN CLVGENLLVK IGDFGMSRDV YSTDYYRVGG HTMLPIRWMP 720
PESIMYRKFT TESDVWSLGV VLWEIFTYGK QPWYQLSNNE VIECITQGRV LQRPRTCPQE 780
VYELMLGCWQ REPHTRKNIK SIHTLLQNLA KASPVYLDIL G 821 
Gene Ontology
 GO:0043679; C:axon terminus; IEA:Compara.
 GO:0009986; C:cell surface; IEA:Compara.
 GO:0005829; C:cytosol; IDA:MGI.
 GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
 GO:0060076; C:excitatory synapse; IEA:Compara.
 GO:0030426; C:growth cone; IEA:Compara.
 GO:0005887; C:integral to plasma membrane; ISS:UniProtKB.
 GO:0043025; C:neuronal cell body; IEA:Compara.
 GO:0014069; C:postsynaptic density; IEA:Compara.
 GO:0045211; C:postsynaptic membrane; IDA:MGI.
 GO:0048786; C:presynaptic active zone; IEA:Compara.
 GO:0043195; C:terminal bouton; IDA:MGI.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0048403; F:brain-derived neurotrophic factor binding; IDA:UniProtKB.
 GO:0060175; F:brain-derived neurotrophic factor-activated receptor activity; IDA:UniProtKB.
 GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
 GO:0007568; P:aging; IEA:Compara.
 GO:0035584; P:calcium-mediated signaling using intracellular calcium source; IMP:UniProtKB.
 GO:0021954; P:central nervous system neuron development; IMP:UniProtKB.
 GO:0021987; P:cerebral cortex development; IMP:UniProtKB.
 GO:0007631; P:feeding behavior; IMP:MGI.
 GO:0014047; P:glutamate secretion; IPI:MGI.
 GO:0007612; P:learning; IMP:UniProtKB.
 GO:0007616; P:long-term memory; IEA:Compara.
 GO:0060291; P:long-term synaptic potentiation; IMP:UniProtKB.
 GO:0042490; P:mechanoreceptor differentiation; IMP:MGI.
 GO:2000811; P:negative regulation of anoikis; IDA:UniProtKB.
 GO:0043524; P:negative regulation of neuron apoptotic process; ISS:UniProtKB.
 GO:0007528; P:neuromuscular junction development; IMP:MGI.
 GO:0001764; P:neuron migration; IMP:UniProtKB.
 GO:0048709; P:oligodendrocyte differentiation; IMP:UniProtKB.
 GO:0048935; P:peripheral nervous system neuron development; IMP:UniProtKB.
 GO:0050772; P:positive regulation of axonogenesis; ISS:UniProtKB.
 GO:0008284; P:positive regulation of cell proliferation; ISS:UniProtKB.
 GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
 GO:0043410; P:positive regulation of MAPK cascade; ISS:UniProtKB.
 GO:0010976; P:positive regulation of neuron projection development; IDA:UniProtKB.
 GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase cascade; ISS:UniProtKB.
 GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; IEA:Compara.
 GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
 GO:0050773; P:regulation of dendrite development; IEA:Compara.
 GO:0019222; P:regulation of metabolic process; IMP:MGI.
 GO:0046928; P:regulation of neurotransmitter secretion; IEA:Compara.
 GO:0051896; P:regulation of protein kinase B signaling cascade; IMP:UniProtKB.
 GO:0032314; P:regulation of Rac GTPase activity; IDA:UniProtKB.
 GO:0010996; P:response to auditory stimulus; IEA:Compara.
 GO:0046548; P:retinal rod cell development; IMP:MGI.
 GO:0001570; P:vasculogenesis; IMP:MGI. 
Interpro
 IPR000483; Cys-rich_flank_reg_C.
 IPR007110; Ig-like_dom.
 IPR013783; Ig-like_fold.
 IPR013098; Ig_I-set.
 IPR003598; Ig_sub2.
 IPR011009; Kinase-like_dom.
 IPR000372; LRR-contain_N.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
 IPR020455; Tyr_kin_neurotrophic_rcpt_2.
 IPR008266; Tyr_kinase_AS.
 IPR020635; Tyr_kinase_cat_dom.
 IPR020777; Tyr_kinase_NGF_rcpt.
 IPR002011; Tyr_kinase_rcpt_2_CS. 
Pfam
 PF07679; I-set
 PF01462; LRRNT
 PF07714; Pkinase_Tyr 
SMART
 SM00408; IGc2
 SM00082; LRRCT
 SM00013; LRRNT
 SM00219; TyrKc 
PROSITE
 PS50835; IG_LIKE
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00109; PROTEIN_KINASE_TYR
 PS00239; RECEPTOR_TYR_KIN_II 
PRINTS
 PR01939; NTKRECEPTOR.
 PR01941; NTKRECEPTOR2.
 PR00109; TYRKINASE.