CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-002571
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Proto-oncogene tyrosine-protein kinase receptor Ret 
Protein Synonyms/Alias
 Cadherin family member 12; Proto-oncogene c-Ret; Soluble RET kinase fragment; Extracellular cell-membrane anchored RET cadherin 120 kDa fragment 
Gene Name
 RET 
Gene Synonyms/Alias
 CDHF12; CDHR16; PTC; RET51 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
108LDHSSWEKLSVRNRGubiquitination[1]
907YEEDSYVKRSQGRIPubiquitination[1]
Reference
 [1] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661] 
Functional Description
 Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell derived neurotrophic factor family ligands. Phosphorylates PTK2/FAK1. Regulates both cell death/survival balance and positional information. Required for the molecular mechanisms orchestration during intestine organogenesis; involved in the development of enteric nervous system and renal organogenesis during embryonic life, and promotes the formation of Peyer's patch-like structures, a major component of the gut- associated lymphoid tissue. Modulates cell adhesion via its cleavage by caspase in sympathetic neurons and mediates cell migration in an integrin (e.g. ITGB1 and ITGB3)-dependent manner. Involved in the development of the neural crest. Active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage. Acts as a dependence receptor; in the presence of the ligand GDNF in somatotrophs (within pituitary), promotes survival and down regulates growth hormone (GH) production, but triggers apoptosis in absence of GDNF. Regulates nociceptor survival and size. Triggers the differentiation of rapidly adapting (RA) mechanoreceptors. Mediator of several diseases such as neuroendocrine cancers; these diseases are characterized by aberrant integrins-regulated cell migration. 
Sequence Annotation
 DOMAIN 168 272 Cadherin.
 DOMAIN 724 1016 Protein kinase.
 NP_BIND 730 738 ATP (By similarity).
 REGION 805 807 Inhibitors binding.
 ACT_SITE 874 874 Proton acceptor (By similarity).
 BINDING 758 758 ATP (By similarity).
 BINDING 892 892 Inhibitors.
 MOD_RES 696 696 Phosphoserine.
 MOD_RES 806 806 Phosphotyrosine; by autocatalysis.
 MOD_RES 809 809 Phosphotyrosine; by autocatalysis.
 MOD_RES 900 900 Phosphotyrosine; by autocatalysis.
 MOD_RES 905 905 Phosphotyrosine; by autocatalysis.
 MOD_RES 981 981 Phosphotyrosine; by autocatalysis.
 MOD_RES 1015 1015 Phosphotyrosine; by autocatalysis.
 MOD_RES 1062 1062 Phosphotyrosine; by autocatalysis.
 MOD_RES 1090 1090 Phosphotyrosine; by autocatalysis.
 MOD_RES 1096 1096 Phosphotyrosine; by autocatalysis.
 CARBOHYD 98 98 N-linked (GlcNAc...) (Potential).
 CARBOHYD 151 151 N-linked (GlcNAc...).
 CARBOHYD 199 199 N-linked (GlcNAc...) (Potential).
 CARBOHYD 336 336 N-linked (GlcNAc...) (Potential).
 CARBOHYD 343 343 N-linked (GlcNAc...) (Potential).
 CARBOHYD 361 361 N-linked (GlcNAc...) (Potential).
 CARBOHYD 367 367 N-linked (GlcNAc...) (Potential).
 CARBOHYD 377 377 N-linked (GlcNAc...) (Potential).
 CARBOHYD 394 394 N-linked (GlcNAc...) (Potential).
 CARBOHYD 448 448 N-linked (GlcNAc...) (Potential).
 CARBOHYD 468 468 N-linked (GlcNAc...) (Potential).
 CARBOHYD 554 554 N-linked (GlcNAc...) (Potential).
 DISULFID 137 142  
Keyword
 3D-structure; Alternative splicing; ATP-binding; Cell adhesion; Cell membrane; Chromosomal rearrangement; Complete proteome; Disease mutation; Disulfide bond; Endosome; Glycoprotein; Hirschsprung disease; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Polymorphism; Proto-oncogene; Reference proteome; Signal; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1114 AA 
Protein Sequence
MAKATSGAAG LRLLLLLLLP LLGKVALGLY FSRDAYWEKL YVDQAAGTPL LYVHALRDAP 60
EEVPSFRLGQ HLYGTYRTRL HENNWICIQE DTGLLYLNRS LDHSSWEKLS VRNRGFPLLT 120
VYLKVFLSPT SLREGECQWP GCARVYFSFF NTSFPACSSL KPRELCFPET RPSFRIRENR 180
PPGTFHQFRL LPVQFLCPNI SVAYRLLEGE GLPFRCAPDS LEVSTRWALD REQREKYELV 240
AVCTVHAGAR EEVVMVPFPV TVYDEDDSAP TFPAGVDTAS AVVEFKRKED TVVATLRVFD 300
ADVVPASGEL VRRYTSTLLP GDTWAQQTFR VEHWPNETSV QANGSFVRAT VHDYRLVLNR 360
NLSISENRTM QLAVLVNDSD FQGPGAGVLL LHFNVSVLPV SLHLPSTYSL SVSRRARRFA 420
QIGKVCVENC QAFSGINVQY KLHSSGANCS TLGVVTSAED TSGILFVNDT KALRRPKCAE 480
LHYMVVATDQ QTSRQAQAQL LVTVEGSYVA EEAGCPLSCA VSKRRLECEE CGGLGSPTGR 540
CEWRQGDGKG ITRNFSTCSP STKTCPDGHC DVVETQDINI CPQDCLRGSI VGGHEPGEPR 600
GIKAGYGTCN CFPEEEKCFC EPEDIQDPLC DELCRTVIAA AVLFSFIVSV LLSAFCIHCY 660
HKFAHKPPIS SAEMTFRRPA QAFPVSYSSS GARRPSLDSM ENQVSVDAFK ILEDPKWEFP 720
RKNLVLGKTL GEGEFGKVVK ATAFHLKGRA GYTTVAVKML KENASPSELR DLLSEFNVLK 780
QVNHPHVIKL YGACSQDGPL LLIVEYAKYG SLRGFLRESR KVGPGYLGSG GSRNSSSLDH 840
PDERALTMGD LISFAWQISQ GMQYLAEMKL VHRDLAARNI LVAEGRKMKI SDFGLSRDVY 900
EEDSYVKRSQ GRIPVKWMAI ESLFDHIYTT QSDVWSFGVL LWEIVTLGGN PYPGIPPERL 960
FNLLKTGHRM ERPDNCSEEM YRLMLQCWKQ EPDKRPVFAD ISKDLEKMMV KRRDYLDLAA 1020
STPSDSLIYD DGLSEEETPL VDCNNAPLPR ALPSTWIENK LYGMSDPNWP GESPVPLTRA 1080
DGTNTGFPRY PNDSVYANWM LSPSAAKLMD TFDS 1114 
Gene Ontology
 GO:0010008; C:endosome membrane; IDA:UniProtKB.
 GO:0005887; C:integral to plasma membrane; IDA:UniProtKB.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0005509; F:calcium ion binding; IDA:FlyBase.
 GO:0004713; F:protein tyrosine kinase activity; TAS:ProtInc.
 GO:0004872; F:receptor activity; TAS:ProtInc.
 GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IEA:EC.
 GO:0071300; P:cellular response to retinoic acid; IMP:BHF-UCL.
 GO:0001838; P:embryonic epithelial tube formation; IEA:Compara.
 GO:0048484; P:enteric nervous system development; IEA:Compara.
 GO:0007156; P:homophilic cell adhesion; IEA:InterPro.
 GO:0097021; P:lymphocyte migration into lymphoid organs; ISS:UniProtKB.
 GO:0000165; P:MAPK cascade; IEA:Compara.
 GO:0033619; P:membrane protein proteolysis; IDA:UniProtKB.
 GO:0001755; P:neural crest cell migration; IEA:Compara.
 GO:0007158; P:neuron cell-cell adhesion; IMP:UniProtKB.
 GO:0042551; P:neuron maturation; IEA:Compara.
 GO:0061146; P:Peyer's patch morphogenesis; ISS:UniProtKB.
 GO:0033630; P:positive regulation of cell adhesion mediated by integrin; IDA:UniProtKB.
 GO:0030335; P:positive regulation of cell migration; IDA:UniProtKB.
 GO:2001241; P:positive regulation of extrinsic apoptotic signaling pathway in absence of ligand; IMP:UniProtKB.
 GO:0072300; P:positive regulation of metanephric glomerulus development; ISS:UniProtKB.
 GO:0010976; P:positive regulation of neuron projection development; IMP:BHF-UCL.
 GO:0045893; P:positive regulation of transcription, DNA-dependent; ISS:UniProtKB.
 GO:0007497; P:posterior midgut development; TAS:ProtInc.
 GO:0048265; P:response to pain; ISS:UniProtKB.
 GO:0007165; P:signal transduction; TAS:ProtInc.
 GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IEA:Compara.
 GO:0035799; P:ureter maturation; IEA:Compara.
 GO:0001657; P:ureteric bud development; IEA:Compara. 
Interpro
 IPR002126; Cadherin.
 IPR015919; Cadherin-like.
 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.
 IPR016249; Tyr_kinase_Ret_rcpt. 
Pfam
 PF00028; Cadherin
 PF07714; Pkinase_Tyr 
SMART
 SM00112; CA
 SM00219; TyrKc 
PROSITE
 PS50268; CADHERIN_2
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00109; PROTEIN_KINASE_TYR 
PRINTS
 PR00109; TYRKINASE.