RET - Proto-oncogene tyrosine-protein kinase receptor Ret - human protein (Function)
 
Home Recent activites arrow-down favorite My favorites arrow-down favorite My labels arrow-down Downloads
Back to ...  
Publication View
Protein
Gene
References

 
RET »  Proto-oncogene tyrosine-protein kinase receptor Ret   [ EC 2.7.10.1 ]
 
Protein also known as:  Cadherin family member 12. Cleaved into:  Extracellular cell-membrane anchored RET cadherin 120 kDa fragment; Soluble RET kinase fragment.
Gene name:  RET
Entry whose protein(s) existence is based on evidence at protein level
extend overview
1 230 2
GENE REF ISO

Function

 show evidences
Overview 
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.  
5
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
Calcium ion bindingdefinition[GO:0005509]  
1
  • IDAFlyBase
Protein bindingdefinition[GO:0005515]  
3
  • IPIUniProtKB
  • IPIIntAct
Protein tyrosine kinase activitydefinition[GO:0004713]  
1
  • TASPINC
Receptor activitydefinition[GO:0004872]  
1
  • TASPINC
Transmembrane receptor protein tyrosine kinase activitydefinition[GO:0004714]  
  • IEAEC 2 GO
GO biological process 
Isoform  Iso 2   Activation of cysteine-type endopeptidase activity involved in apoptotic processdefinition[GO:0006919]  
1
  • IMPUniProtKB
Cellular response to retinoic aciddefinition[GO:0071300]  
1
  • IMPBHF-UCL
Embryonic epithelial tube formationdefinition[GO:0001838] silver  
  • IEAOrtholog Compara
Enteric nervous system developmentdefinition[GO:0048484] silver  
  • IEAOrtholog Compara
Homophilic cell adhesiondefinition[GO:0007156] silver  
  • IEAInterPro 2 GO
Innervationdefinition[GO:0060384] silver  
  • IEAOrtholog Compara
Lymphocyte migration into lymphoid organsdefinition[GO:0097021]  
  • ISSOrtholog Curator
MAPK cascadedefinition[GO:0000165] silver  
  • IEAOrtholog Compara
Membrane protein proteolysisdefinition[GO:0033619]  
1
  • IDAUniProtKB
Neural crest cell migrationdefinition[GO:0001755] silver  
  • IEAOrtholog Compara
Neuron cell-cell adhesiondefinition[GO:0007158]  
1
  • IMPUniProtKB
Neuron maturationdefinition[GO:0042551] silver  
  • IEAOrtholog Compara
Peptidyl-tyrosine phosphorylationdefinition[GO:0018108]  
1
  • TASGOC
  • IEAEC 2 GO
  • IEAInterPro 2 GO
  • IEAUniProtKB KW
Peyer's patch morphogenesisdefinition[GO:0061146]  
  • ISSOrtholog Curator
Positive regulation of cell adhesion mediated by integrindefinition[GO:0033630]  
1
  • IDAUniProtKB
Positive regulation of cell migrationdefinition[GO:0030335]  
1
  • IDAUniProtKB
Positive regulation of cell sizedefinition[GO:0045793] silver  
  • IEAOrtholog Compara
Positive regulation of extrinsic apoptotic signaling pathway in absence of liganddefinition[GO:2001241]  
2
  • TASUniProtKB
Positive regulation of metanephric glomerulus developmentdefinition[GO:0072300]  
1
  • ISSUniProtKB
Positive regulation of neuron maturationdefinition[GO:0014042] silver  
  • IEAOrtholog Compara
Positive regulation of neuron projection developmentdefinition[GO:0010976]  
1
  • IMPBHF-UCL
Positive regulation of transcription, DNA-templateddefinition[GO:0045893]  
1
  • ISSUniProtKB
Posterior midgut developmentdefinition[GO:0007497]  
1
  • TASPINC
Protein phosphorylationdefinition[GO:0006468]  
1
  • TASPINC
Regulation of axonogenesisdefinition[GO:0050770] silver  
  • IEAOrtholog Compara
Regulation of cell adhesiondefinition[GO:0030155]  
1
  • IDAUniProtKB
Response to drugdefinition[GO:0042493] silver  
  • IEAOrtholog Compara
Response to paindefinition[GO:0048265]  
  • ISSOrtholog Curator
Retina development in camera-type eyedefinition[GO:0060041] silver  
  • IEAOrtholog Compara
Signal transductiondefinition[GO:0007165]  
1
  • TASPINC
Transmembrane receptor protein tyrosine kinase signaling pathwaydefinition[GO:0007169] silver  
  • IEAOrtholog Compara
Ureter maturationdefinition[GO:0035799] silver  
  • IEAOrtholog Compara
Ureteric bud developmentdefinition[GO:0001657] silver  
  • IEAOrtholog Compara
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.10.1: ATP + a [protein]-L-tyrosine ADP + a [protein]-L-tyrosine phosphate.  
  • CuratedUniProtKB
It is regulated in the following manner
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.  
7
  • CuratedUniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Endocytosis  hsa04144+5979  
Pathways in cancer  hsa05200+5979  
Thyroid cancer  hsa05216+5979  
Note 
Treatment with withaferin A (WA) leads tumor regression in medullary thyroid carcinomas (MTC).  
  • CuratedUniProtKB
 

Keywords

Biological process 
Cell adhesion  definition   [KW-0130]
Molecular function 
Kinase  definition   [KW-0418]
Transferase  definition   [KW-0808]
Tyrosine-protein kinase  definition   [KW-0829]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: RET_proto-oncogene
GenomeRNAi: 5979
PRO: PR:P07949
Chemistry
GuidetoPHARMACOLOGY: 2185