Names & Taxonomy

Uniprot ID:
P07949
Entry Name:
RET_HUMAN
Status:
reviewed
Protein Names:
Proto-oncogene tyrosine-protein kinase receptor Ret (EC 2.7.10.1) (Cadherin family member 12) (Proto-oncogene c-Ret) [Cleaved into: Soluble RET kinase fragment; Extracellular cell-membrane anchored RET cadherin 120 kDa fragment]
Gene Names:
RET CDHF12 CDHR16 PTC RET51
Gene Names Primary:
RET
Organism:
Homo sapiens (Human)

Structure

Length:
1114
Sequence:
MAKATSGAAGLRLLLLLLLPLLGKVALGLYFSRDAYWEKLYVDQAAGTPLLYVHALRDAPEEVPSFRLGQHLYGTYRTRLHENNWICIQEDTGLLYLNRSLDHSSWEKLSVRNRGFPLLTVYLKVFLSPTSLREGECQWPGCARVYFSFFNTSFPACSSLKPRELCFPETRPSFRIRENRPPGTFHQFRLLPVQFLCPNISVAYRLLEGEGLPFRCAPDSLEVSTRWALDREQREKYELVAVCTVHAGAREEVVMVPFPVTVYDEDDSAPTFPAGVDTASAVVEFKRKEDTVVATLRVFDADVVPASGELVRRYTSTLLPGDTWAQQTFRVEHWPNETSVQANGSFVRATVHDYRLVLNRNLSISENRTMQLAVLVNDSDFQGPGAGVLLLHFNVSVLPVSLHLPSTYSLSVSRRARRFAQIGKVCVENCQAFSGINVQYKLHSSGANCSTLGVVTSAEDTSGILFVNDTKALRRPKCAELHYMVVATDQQTSRQAQAQLLVTVEGSYVAEEAGCPLSCAVSKRRLECEECGGLGSPTGRCEWRQGDGKGITRNFSTCSPSTKTCPDGHCDVVETQDINICPQDCLRGSIVGGHEPGEPRGIKAGYGTCNCFPEEEKCFCEPEDIQDPLCDELCRTVIAAAVLFSFIVSVLLSAFCIHCYHKFAHKPPISSAEMTFRRPAQAFPVSYSSSGARRPSLDSMENQVSVDAFKILEDPKWEFPRKNLVLGKTLGEGEFGKVVKATAFHLKGRAGYTTVAVKMLKENASPSELRDLLSEFNVLKQVNHPHVIKLYGACSQDGPLLLIVEYAKYGSLRGFLRESRKVGPGYLGSGGSRNSSSLDHPDERALTMGDLISFAWQISQGMQYLAEMKLVHRDLAARNILVAEGRKMKISDFGLSRDVYEEDSYVKRSQGRIPVKWMAIESLFDHIYTTQSDVWSFGVLLWEIVTLGGNPYPGIPPERLFNLLKTGHRMERPDNCSEEMYRLMLQCWKQEPDKRPVFADISKDLEKMMVKRRDYLDLAASTPSDSLIYDDGLSEEETPLVDCNNAPLPRALPSTWIENKLYGMSDPNWPGESPVPLTRADGTNTGFPRYPNDSVYANWMLSPSAAKLMDTFDS
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Cell membrane

Function

Function:
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.
Catalytic Activity:
ATP + a -L-tyrosine = ADP + a -L-tyrosine phosphate.
Enzyme Regulation:
ENZYME REGULATION: Repressed by 4-(3-hydroxyanilino)-quinolines derivatives, indolin-2-one-derivatives, 2-(alkylsulfanyl)-4-(3-thienyl) nicotinonitrile analogs, 3- and 4-substituted beta-carbolin-1-ones, vandetanib, motesanib, sorafenib (BAY 43-9006), cabozantinib (XL184), sunitinib, and withaferin A (WA). Inactivation by sorafenib both reduces kinase activity and promotes lysosomal degradation.
Active Site:
ACT_SITE 874 874 Proton acceptor.
Cross Reference Drug Bank:
DB08875 DB08901 DB08896 DB00398
Gene Ontology Go:
axon
cytoplasm
dendrite
early endosome
endosome membrane
integral component of plasma membrane
intracellular membrane-bounded organelle
membrane raft
neuronal cell body
plasma membrane
receptor complex
ATP binding
calcium ion binding
protein tyrosine kinase activity
receptor activity
transmembrane receptor protein tyrosine kinase activity
activation of cysteine-type endopeptidase activity involved in apoptotic process
cellular response to retinoic acid
embryonic epithelial tube formation
enteric nervous system development
homophilic cell adhesion via plasma membrane adhesion molecules
innervation
lymphocyte migration into lymphoid organs
MAPK cascade
membrane protein proteolysis
neural crest cell migration
neuron cell-cell adhesion
neuron maturation
peptidyl-tyrosine phosphorylation
Peyer's patch morphogenesis
positive regulation of cell adhesion mediated by integrin
positive regulation of cell migration
positive regulation of cell size
positive regulation of extrinsic apoptotic signaling pathway in absence of ligand
positive regulation of metanephric glomerulus development
positive regulation of neuron maturation
positive regulation of neuron projection development
positive regulation of serine phosphorylation of STAT3 protein
positive regulation of transcription, DNA-templated
posterior midgut development
protein phosphorylation
regulation of axonogenesis
regulation of cell adhesion
response to drug
response to pain
retina development in camera-type eye
signal transduction
transmembrane receptor protein tyrosine kinase signaling pathway
ureter maturation
ureteric bud development
Gene Ontology Biological Process:
activation of cysteine-type endopeptidase activity involved in apoptotic process
cellular response to retinoic acid
embryonic epithelial tube formation
enteric nervous system development
homophilic cell adhesion via plasma membrane adhesion molecules
innervation
lymphocyte migration into lymphoid organs
MAPK cascade
membrane protein proteolysis
neural crest cell migration
neuron cell-cell adhesion
neuron maturation
peptidyl-tyrosine phosphorylation
Peyer's patch morphogenesis
positive regulation of cell adhesion mediated by integrin
positive regulation of cell migration
positive regulation of cell size
positive regulation of extrinsic apoptotic signaling pathway in absence of ligand
positive regulation of metanephric glomerulus development
positive regulation of neuron maturation
positive regulation of neuron projection development
positive regulation of serine phosphorylation of STAT3 protein
positive regulation of transcription, DNA-templated
posterior midgut development
protein phosphorylation
regulation of axonogenesis
regulation of cell adhesion
response to drug
response to pain
retina development in camera-type eye
signal transduction
transmembrane receptor protein tyrosine kinase signaling pathway
ureteric bud development
ureter maturation
Gene Ontology Molecular Function:
ATP binding
calcium ion binding
protein tyrosine kinase activity
receptor activity
transmembrane receptor protein tyrosine kinase activity
Gene Ontology Cellular Component:
axon
cytoplasm
dendrite
early endosome
endosome membrane
integral component of plasma membrane
intracellular membrane-bounded organelle
membrane raft
neuronal cell body
plasma membrane
receptor complex
Keywords:
3D-structure
ATP-binding
Alternative splicing
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
Interacts With:
Q7Z3S9; P19174; Q62985; P40763

Publication

PubMed ID:
14702039 15164054 15489334 2660074 3078962 3037315 2734021 2406025 10980597 10439047 11061555 14711813 12787916 16778204 17884497 17664273 19053769 18753381 19366855 19853745 19369195 20064382 20605972 20409618 20616503 20702524 19823924 21134556 21357690 21454698 16928683 20117004 20473317 9359036 9067749 8103403 8099202 7704557 7911697 7915165 7849720 7874109 7881414 7906866 8114938 8114939 7906417 8625130 7860065 7633441 7581377 8595427 7845675 7784092 9043870 8557249 8807338 8626834 9097963 9090527 9259198 9360560 9398735 9094028 9223675 9294615 9497256 9677065 9760196 9384613 9452064 9452077 9506724 9621513 10090908 10484767 10323403 10522989 10826520 10612852 10618407 11692159 12000816 12086152 14566559 16959974 17344846 18252215 22174939