CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-002137
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 High affinity nerve growth factor receptor 
Protein Synonyms/Alias
 Neurotrophic tyrosine kinase receptor type 1; TRK1-transforming tyrosine kinase protein; Tropomyosin-related kinase A; Tyrosine kinase receptor; Tyrosine kinase receptor A; Trk-A; gp140trk; p140-TrkA 
Gene Name
 NTRK1 
Gene Synonyms/Alias
 MTC; TRK; TRKA 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
482SLSPTEGKGSGLQGHubiquitination[1]
Reference
 [1] Computational identification of ubiquitylation sites from protein sequences.
 Tung CW, Ho SY.
 BMC Bioinformatics. 2008 Jul 15;9:310. [PMID: 18625080] 
Functional Description
 Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympathetic and nervous neurons. High affinity receptor for NGF which is its primary ligand, it can also bind and be activated by NTF3/neurotrophin-3. However, NTF3 only supports axonal extension through NTRK1 but has no effect on neuron survival. Upon dimeric NGF 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 driving cell survival and differentiation. Through SHC1 and FRS2 activates a GRB2-Ras-MAPK cascade that regulates cell differentiation and survival. Through PLCG1 controls NF-Kappa-B activation and the transcription of genes involved in cell survival. Through SHC1 and SH2B1 controls a Ras- PI3 kinase-AKT1 signaling cascade that is also regulating survival. In absence of ligand and activation, may promote cell death, making the survival of neurons dependent on trophic factors. 
Sequence Annotation
 REPEAT 90 113 LRR 1.
 REPEAT 116 137 LRR 2.
 DOMAIN 148 193 LRRCT.
 DOMAIN 194 283 Ig-like C2-type 1.
 DOMAIN 299 365 Ig-like C2-type 2.
 DOMAIN 510 781 Protein kinase.
 NP_BIND 516 524 ATP (By similarity).
 REGION 469 490 Interaction with SQSTM1 (By similarity).
 ACT_SITE 650 650 Proton acceptor (By similarity).
 BINDING 544 544 ATP (By similarity).
 MOD_RES 496 496 Phosphotyrosine; by autocatalysis.
 MOD_RES 676 676 Phosphotyrosine; by autocatalysis.
 MOD_RES 680 680 Phosphotyrosine; by autocatalysis.
 MOD_RES 681 681 Phosphotyrosine; by autocatalysis.
 MOD_RES 791 791 Phosphotyrosine; by autocatalysis.
 CARBOHYD 67 67 N-linked (GlcNAc...) (Potential).
 CARBOHYD 95 95 N-linked (GlcNAc...).
 CARBOHYD 121 121 N-linked (GlcNAc...).
 CARBOHYD 188 188 N-linked (GlcNAc...).
 CARBOHYD 202 202 N-linked (GlcNAc...) (Potential).
 CARBOHYD 253 253 N-linked (GlcNAc...) (Potential).
 CARBOHYD 262 262 N-linked (GlcNAc...).
 CARBOHYD 281 281 N-linked (GlcNAc...).
 CARBOHYD 318 318 N-linked (GlcNAc...) (Potential).
 CARBOHYD 323 323 N-linked (GlcNAc...) (Potential).
 CARBOHYD 338 338 N-linked (GlcNAc...) (Potential).
 CARBOHYD 358 358 N-linked (GlcNAc...).
 CARBOHYD 401 401 N-linked (GlcNAc...) (Potential).
 DISULFID 154 191
 DISULFID 215 265  
Keyword
 3D-structure; Alternative splicing; ATP-binding; Cell membrane; Chromosomal rearrangement; Complete proteome; Developmental protein; Differentiation; Disease mutation; Disulfide bond; Endosome; Glycoprotein; Immunoglobulin domain; Kinase; Leucine-rich repeat; Membrane; Neurogenesis; Nucleotide-binding; Phosphoprotein; Polymorphism; Proto-oncogene; Receptor; Reference proteome; Repeat; Signal; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 796 AA 
Protein Sequence
MLRGGRRGQL GWHSWAAGPG SLLAWLILAS AGAAPCPDAC CPHGSSGLRC TRDGALDSLH 60
HLPGAENLTE LYIENQQHLQ HLELRDLRGL GELRNLTIVK SGLRFVAPDA FHFTPRLSRL 120
NLSFNALESL SWKTVQGLSL QELVLSGNPL HCSCALRWLQ RWEEEGLGGV PEQKLQCHGQ 180
GPLAHMPNAS CGVPTLKVQV PNASVDVGDD VLLRCQVEGR GLEQAGWILT ELEQSATVMK 240
SGGLPSLGLT LANVTSDLNR KNVTCWAEND VGRAEVSVQV NVSFPASVQL HTAVEMHHWC 300
IPFSVDGQPA PSLRWLFNGS VLNETSFIFT EFLEPAANET VRHGCLRLNQ PTHVNNGNYT 360
LLAANPFGQA SASIMAAFMD NPFEFNPEDP IPVSFSPVDT NSTSGDPVEK KDETPFGVSV 420
AVGLAVFACL FLSTLLLVLN KCGRRNKFGI NRPAVLAPED GLAMSLHFMT LGGSSLSPTE 480
GKGSGLQGHI IENPQYFSDA CVHHIKRRDI VLKWELGEGA FGKVFLAECH NLLPEQDKML 540
VAVKALKEAS ESARQDFQRE AELLTMLQHQ HIVRFFGVCT EGRPLLMVFE YMRHGDLNRF 600
LRSHGPDAKL LAGGEDVAPG PLGLGQLLAV ASQVAAGMVY LAGLHFVHRD LATRNCLVGQ 660
GLVVKIGDFG MSRDIYSTDY YRVGGRTMLP IRWMPPESIL YRKFTTESDV WSFGVVLWEI 720
FTYGKQPWYQ LSNTEAIDCI TQGRELERPR ACPPEVYAIM RGCWQREPQQ RHSIKDVHAR 780
LQALAQAPPV YLDVLG 796 
Gene Ontology
 GO:0030424; C:axon; IEA:Compara.
 GO:0009986; C:cell surface; IEA:Compara.
 GO:0031410; C:cytoplasmic vesicle; IEA:Compara.
 GO:0030425; C:dendrite; IEA:Compara.
 GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
 GO:0005768; C:endosome; TAS:Reactome.
 GO:0005887; C:integral to plasma membrane; IDA:UniProtKB.
 GO:0043025; C:neuronal cell body; IEA:Compara.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0048406; F:nerve growth factor binding; IDA:UniProtKB.
 GO:0010465; F:nerve growth factor receptor activity; IDA:UniProtKB.
 GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
 GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IDA:UniProtKB.
 GO:0007190; P:activation of adenylate cyclase activity; TAS:Reactome.
 GO:0000186; P:activation of MAPKK activity; TAS:Reactome.
 GO:0007202; P:activation of phospholipase C activity; TAS:Reactome.
 GO:0007568; P:aging; IEA:Compara.
 GO:0007411; P:axon guidance; IEA:Compara.
 GO:0060385; P:axonogenesis involved in innervation; ISS:UniProtKB.
 GO:0030183; P:B cell differentiation; IEA:Compara.
 GO:0071316; P:cellular response to nicotine; IEA:Compara.
 GO:0050966; P:detection of mechanical stimulus involved in sensory perception of pain; IEA:Compara.
 GO:0050965; P:detection of temperature stimulus involved in sensory perception of pain; IEA:Compara.
 GO:0010623; P:developmental programmed cell death; ISS:UniProtKB.
 GO:0007611; P:learning or memory; IEA:Compara.
 GO:0042490; P:mechanoreceptor differentiation; IEA:Compara.
 GO:0008285; P:negative regulation of cell proliferation; IDA:UniProtKB.
 GO:0043524; P:negative regulation of neuron apoptotic process; ISS:UniProtKB.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; IDA:UniProtKB.
 GO:0021553; P:olfactory nerve development; IEA:Compara.
 GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:Reactome.
 GO:0045766; P:positive regulation of angiogenesis; IDA:UniProtKB.
 GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB.
 GO:0010976; P:positive regulation of neuron projection development; IDA:UniProtKB.
 GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
 GO:0043068; P:positive regulation of programmed cell death; ISS:UniProtKB.
 GO:0032320; P:positive regulation of Ras GTPase activity; IDA:UniProtKB.
 GO:0046579; P:positive regulation of Ras protein signal transduction; IDA:UniProtKB.
 GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; IEA:Compara.
 GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
 GO:0007265; P:Ras protein signal transduction; TAS:Reactome.
 GO:0014823; P:response to activity; IEA:Compara.
 GO:0048678; P:response to axon injury; IEA:Compara.
 GO:0042493; P:response to drug; IEA:Compara.
 GO:0051602; P:response to electrical stimulus; IEA:Compara.
 GO:0045471; P:response to ethanol; IEA:Compara.
 GO:0051599; P:response to hydrostatic pressure; IEA:Compara.
 GO:0031667; P:response to nutrient levels; IEA:Compara.
 GO:0009314; P:response to radiation; IEA:Compara.
 GO:0060009; P:Sertoli cell development; IEA:Compara.
 GO:0048485; P:sympathetic nervous system development; ISS:UniProtKB. 
Interpro
 IPR000483; Cys-rich_flank_reg_C.
 IPR007110; Ig-like_dom.
 IPR013783; Ig-like_fold.
 IPR003599; Ig_sub.
 IPR011009; Kinase-like_dom.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
 IPR008266; Tyr_kinase_AS.
 IPR020635; Tyr_kinase_cat_dom.
 IPR020461; Tyr_kinase_neurotrophic_rcpt_1.
 IPR020777; Tyr_kinase_NGF_rcpt.
 IPR002011; Tyr_kinase_rcpt_2_CS. 
Pfam
 PF07714; Pkinase_Tyr 
SMART
 SM00409; IG
 SM00082; LRRCT
 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.
 PR01940; NTKRECEPTOR1.
 PR00109; TYRKINASE.