CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-006538
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; Slow nerve growth factor receptor; p140-TrkA; Trk-A 
Gene Name
 Ntrk1 
Gene Synonyms/Alias
 Trk; Trka 
Created Date
 July 27, 2013 
Organism
 Rattus norvegicus (Rat) 
NCBI Taxa ID
 10116 
Lysine Modification
Position
Peptide
Type
References
485SLSPTEGKGSGLQGHubiquitination[1, 2]
Reference
 [1] Lysine 63 polyubiquitination of the nerve growth factor receptor TrkA directs internalization and signaling.
 Geetha T, Jiang J, Wooten MW.
 Mol Cell. 2005 Oct 28;20(2):301-12. [PMID: 16246731]
 [2] Identification of a consensus site for TRAF6/p62 polyubiquitination.
 Jadhav T, Geetha T, Jiang J, Wooten MW.
 Biochem Biophys Res Commun. 2008 Jul 4;371(3):521-4. [PMID: 18457658] 
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 148 219 LRRCT.
 DOMAIN 196 285 Ig-like C2-type 1.
 DOMAIN 295 368 Ig-like C2-type 2.
 DOMAIN 513 784 Protein kinase.
 NP_BIND 519 527 ATP (By similarity).
 REGION 472 493 Interaction with SQSTM1.
 ACT_SITE 653 653 Proton acceptor (By similarity).
 BINDING 547 547 ATP (By similarity).
 MOD_RES 499 499 Phosphotyrosine; by autocatalysis (By
 MOD_RES 679 679 Phosphotyrosine; by autocatalysis (By
 MOD_RES 683 683 Phosphotyrosine; by autocatalysis (By
 MOD_RES 684 684 Phosphotyrosine; by autocatalysis (By
 MOD_RES 794 794 Phosphotyrosine; by autocatalysis (By
 CARBOHYD 67 67 N-linked (GlcNAc...) (Potential).
 CARBOHYD 121 121 N-linked (GlcNAc...) (Potential).
 CARBOHYD 190 190 N-linked (GlcNAc...) (Potential).
 CARBOHYD 204 204 N-linked (GlcNAc...) (Potential).
 CARBOHYD 255 255 N-linked (GlcNAc...) (Potential).
 CARBOHYD 264 264 N-linked (GlcNAc...) (Potential).
 CARBOHYD 320 320 N-linked (GlcNAc...) (Potential).
 CARBOHYD 325 325 N-linked (GlcNAc...) (Potential).
 CARBOHYD 341 341 N-linked (GlcNAc...) (Potential).
 CARBOHYD 361 361 N-linked (GlcNAc...) (Potential).
 CARBOHYD 404 404 N-linked (GlcNAc...) (Potential).
 DISULFID 154 193 By similarity.
 DISULFID 217 267 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
 799 AA 
Protein Sequence
MLRGQRHGQL GWHRPAAGLG GLVTSLMLAC ACAASCRETC CPVGPSGLRC TRAGTLNTLR 60
GLRGAGNLTE LYVENQRDLQ RLEFEDLQGL GELRSLTIVK SGLRFVAPDA FHFTPRLSHL 120
NLSSNALESL SWKTVQGLSL QDLTLSGNPL HCSCALLWLQ RWEQEDLCGV YTQKLQGSGS 180
GDQFLPLGHN NSCGVPSVKI QMPNDSVEVG DDVFLQCQVE GQALQQADWI LTELEGTATM 240
KKSGDLPSLG LTLVNVTSDL NKKNVTCWAE NDVGRAEVSV QVSVSFPASV HLGKAVEQHH 300
WCIPFSVDGQ PAPSLRWFFN GSVLNETSFI FTQFLESALT NETMRHGCLR LNQPTHVNNG 360
NYTLLAANPY GQAAASIMAA FMDNPFEFNP EDPIPVSFSP VDTNSTSRDP VEKKDETPFG 420
VSVAVGLAVS AALFLSALLL VLNKCGQRSK FGINRPAVLA PEDGLAMSLH FMTLGGSSLS 480
PTEGKGSGLQ GHIMENPQYF SDTCVHHIKR QDIILKWELG EGAFGKVFLA ECYNLLNDQD 540
KMLVAVKALK ETSENARQDF HREAELLTML QHQHIVRFFG VCTEGGPLLM VFEYMRHGDL 600
NRFLRSHGPD AKLLAGGEDV APGPLGLGQL LAVASQVAAG MVYLASLHFV HRDLATRNCL 660
VGQGLVVKIG DFGMSRDIYS TDYYRVGGRT MLPIRWMPPE SILYRKFSTE SDVWSFGVVL 720
WEIFTYGKQP WYQLSNTEAI ECITQGRELE RPRACPPDVY AIMRGCWQRE PQQRLSMKDV 780
HARLQALAQA PPSYLDVLG 799 
Gene Ontology
 GO:0030424; C:axon; IDA:RGD.
 GO:0009986; C:cell surface; IDA:MGI.
 GO:0031410; C:cytoplasmic vesicle; IDA:RGD.
 GO:0030425; C:dendrite; IDA:RGD.
 GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
 GO:0000139; C:Golgi membrane; TAS:Reactome.
 GO:0005887; C:integral to plasma membrane; ISS:UniProtKB.
 GO:0043025; C:neuronal cell body; IDA:RGD.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0048406; F:nerve growth factor binding; ISS:UniProtKB.
 GO:0010465; F:nerve growth factor receptor activity; ISS:UniProtKB.
 GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
 GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; ISS:UniProtKB.
 GO:0007568; P:aging; IEP:RGD.
 GO:0007411; P:axon guidance; IMP:RGD.
 GO:0060385; P:axonogenesis involved in innervation; ISS:UniProtKB.
 GO:0030183; P:B cell differentiation; IEA:Compara.
 GO:0071316; P:cellular response to nicotine; IDA:RGD.
 GO:0050966; P:detection of mechanical stimulus involved in sensory perception of pain; IMP:RGD.
 GO:0050965; P:detection of temperature stimulus involved in sensory perception of pain; IMP:RGD.
 GO:0010623; P:developmental programmed cell death; IDA:UniProtKB.
 GO:0007611; P:learning or memory; IMP:RGD.
 GO:0042490; P:mechanoreceptor differentiation; IEA:Compara.
 GO:0008285; P:negative regulation of cell proliferation; ISS:UniProtKB.
 GO:0043524; P:negative regulation of neuron apoptotic process; IMP:RGD.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; ISS:UniProtKB.
 GO:0021553; P:olfactory nerve development; IEP:RGD.
 GO:0045766; P:positive regulation of angiogenesis; IEA:Compara.
 GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
 GO:0010976; P:positive regulation of neuron projection development; ISS:UniProtKB.
 GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
 GO:0043068; P:positive regulation of programmed cell death; IDA:UniProtKB.
 GO:0032320; P:positive regulation of Ras GTPase activity; ISS:UniProtKB.
 GO:0046579; P:positive regulation of Ras protein signal transduction; ISS:UniProtKB.
 GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; IMP:RGD.
 GO:0046777; P:protein autophosphorylation; IDA:MGI.
 GO:0014823; P:response to activity; IDA:RGD.
 GO:0048678; P:response to axon injury; IEP:RGD.
 GO:0042493; P:response to drug; IDA:RGD.
 GO:0051602; P:response to electrical stimulus; IDA:RGD.
 GO:0045471; P:response to ethanol; IEP:RGD.
 GO:0051599; P:response to hydrostatic pressure; IEP:RGD.
 GO:0031667; P:response to nutrient levels; IDA:RGD.
 GO:0009314; P:response to radiation; IEP:RGD.
 GO:0060009; P:Sertoli cell development; IMP:RGD.
 GO:0048485; P:sympathetic nervous system development; ISS:UniProtKB. 
Interpro
 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
 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.