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General description of the gene and the encoded protein(s) using information from HGNC and Ensembl, as well as predictions made by the Human Protein Atlas project.
Gene namei
Official gene symbol, which is typically a short form of the gene name, according to HGNC.
Assigned HPA protein class(es) for the encoded protein(s).
Cancer-related genes Disease related genes Enzymes FDA approved drug targets Human disease related genes Plasma proteins Transporters
Predicted locationi
All transcripts of all genes have been analyzed regarding the location(s) of corresponding protein based on prediction methods for signal peptides and transmembrane regions.
Genes with at least one transcript predicted to encode a secreted protein, according to prediction methods or to UniProt location data, have been further annotated and classified with the aim to determine if the corresponding protein(s) are secreted or actually retained in intracellular locations or membrane-attached.
Remaining genes, with no transcript predicted to encode a secreted protein, will be assigned the prediction-based location(s).
The annotated location overrules the predicted location, so that a gene encoding a predicted secreted protein that has been annotated as intracellular will have intracellular as the final location.
Gene information from Ensembl and Entrez, as well as links to available gene identifiers are displayed here. Information was retrieved from Ensembl if not indicated otherwise.
Chromosome
10
Cytoband
q11.21
Chromosome location (bp)
43077064 - 43130351
Number of transcriptsi
Number of protein-coding transcripts from the gene as defined by Ensembl.
Useful information about the protein provided by UniProt.
Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation in response to glia cell line-derived growth family factors (GDNF, NRTN, ARTN, PSPN and GDF15) 1,2,3,4,5,6,7,8,9,10. In contrast to most receptor tyrosine kinases, RET requires not only its cognate ligands but also coreceptors, for activation 11,12,13,14,15. GDNF ligands (GDNF, NRTN, ARTN, PSPN and GDF15) first bind their corresponding GDNFR coreceptors (GFRA1, GFRA2, GFRA3, GFRA4 and GFRAL, respectively), triggering RET autophosphorylation and activation, leading to activation of downstream signaling pathways, including the MAPK- and AKT-signaling pathways 16,17,18,19,20,21,22. Acts as a dependence receptor via the GDNF-GFRA1 signaling: 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 23,24. Required for the molecular mechanisms orchestration during intestine organogenesis via the ARTN-GFRA3 signaling: 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 (By similarity). Mediates, through interaction with GDF15-receptor GFRAL, GDF15-induced cell-signaling in the brainstem which triggers an aversive response, characterized by nausea, vomiting, and/or loss of appetite in response to various stresses 25,26,27. 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 28,29. Also active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage 30. Triggers the differentiation of rapidly adapting (RA) mechanoreceptors 31. Involved in the development of the neural crest (By similarity). Regulates nociceptor survival and size (By similarity). Phosphorylates PTK2/FAK1 32....show less
Molecular function (UniProt)i
Keywords assigned by UniProt to proteins due to their particular molecular function.
Kinase, Transferase, Tyrosine-protein kinase
Biological process (UniProt)i
Keywords assigned by UniProt to proteins because they are involved in a particular biological process.
Cell adhesion
Ligand (UniProt)i
Keywords assigned by UniProt to proteins because they bind, are associated with, or whose activity is dependent of some molecule.
ATP-binding, Nucleotide-binding
Gene summary (Entrez)i
Useful information about the gene from Entrez
This gene encodes a transmembrane receptor and member of the tyrosine protein kinase family of proteins. Binding of ligands such as GDNF (glial cell-line derived neurotrophic factor) and other related proteins to the encoded receptor stimulates receptor dimerization and activation of downstream signaling pathways that play a role in cell differentiation, growth, migration and survival. The encoded receptor is important in development of the nervous system, and the development of organs and tissues derived from the neural crest. This proto-oncogene can undergo oncogenic activation through both cytogenetic rearrangement and activating point mutations. Mutations in this gene are associated with Hirschsprung disease and central hypoventilation syndrome and have been identified in patients with renal agenesis. [provided by RefSeq, Sep 2017]...show less
PROTEIN INFORMATIONi
The protein information section displays alternative protein-coding transcripts (splice variants) encoded by this gene according to the Ensembl database.
The Splice variant identifier links to the Ensembl website protein summary for the selected splice variant. The data in the Swissprot and TrEMBL columns links to corresponding pages in the UniProt database.
The protein classes assigned to this protein are shown if expanding the data in the protein class column. Parent protein classes are in bold font and subclasses are listed under the parent class.
The length of the protein (amino acid residues according to Ensembl), molecular mass (kDalton), predicted signal peptide and number of predicted transmembrane region(s) according to in-house majority decision methods based on sets of predictors are also reported.
P07949 [Direct mapping] Proto-oncogene tyrosine-protein kinase receptor Ret Soluble RET kinase fragment Extracellular cell-membrane anchored RET cadherin 120 kDa fragment
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Enzymes ENZYME proteins Transferases Kinases Tyr protein kinases Transporters Accessory Factors Involved in Transport Predicted membrane proteins Prediction method-based Membrane proteins predicted by MDM MEMSAT3 predicted membrane proteins MEMSAT-SVM predicted membrane proteins Phobius predicted membrane proteins SCAMPI predicted membrane proteins SPOCTOPUS predicted membrane proteins THUMBUP predicted membrane proteins TMHMM predicted membrane proteins # TM segments-based 1TM proteins predicted by MDM Plasma proteins Cancer-related genes Candidate cancer biomarkers COSMIC somatic mutations in cancer genes COSMIC Somatic Mutations COSMIC Nonsense Mutations COSMIC Missense Mutations COSMIC Germline Mutations COSMIC Frameshift Mutations COSMIC Translocations Disease related genes FDA approved drug targets Small molecule drugs Human disease related genes Cancers Cancers of the lung and pleura Cancers of endocrine organs Congenital malformations Congenital malformations of the digestive system Mapped to neXtProt neXtProt - Evidence at protein level Protein evidence (Kim et al 2014) Protein evidence (Ezkurdia et al 2014) DeepTMHMM predicted membrane proteins
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GO:0000166[nucleotide binding] GO:0004672[protein kinase activity] GO:0004713[protein tyrosine kinase activity] GO:0004714[transmembrane receptor protein tyrosine kinase activity] GO:0005509[calcium ion binding] GO:0005515[protein binding] GO:0005524[ATP binding] GO:0005768[endosome] GO:0005886[plasma membrane] GO:0006468[protein phosphorylation] GO:0006919[activation of cysteine-type endopeptidase activity involved in apoptotic process] GO:0007155[cell adhesion] GO:0007156[homophilic cell adhesion via plasma membrane adhesion molecules] GO:0007158[neuron cell-cell adhesion] GO:0007165[signal transduction] GO:0007169[transmembrane receptor protein tyrosine kinase signaling pathway] GO:0007411[axon guidance] GO:0007497[posterior midgut development] GO:0010008[endosome membrane] GO:0010976[positive regulation of neuron projection development] GO:0016020[membrane] GO:0016301[kinase activity] GO:0016310[phosphorylation] GO:0016740[transferase activity] GO:0018108[peptidyl-tyrosine phosphorylation] GO:0030155[regulation of cell adhesion] GO:0030335[positive regulation of cell migration] GO:0030424[axon] GO:0033619[membrane protein proteolysis] GO:0033630[positive regulation of cell adhesion mediated by integrin] GO:0033674[positive regulation of kinase activity] GO:0035860[glial cell-derived neurotrophic factor receptor signaling pathway] GO:0038023[signaling receptor activity] GO:0043235[receptor complex] GO:0043410[positive regulation of MAPK cascade] GO:0045893[positive regulation of DNA-templated transcription] GO:0048265[response to pain] GO:0051897[positive regulation of protein kinase B signaling] GO:0061146[Peyer's patch morphogenesis] GO:0071300[cellular response to retinoic acid] GO:0072300[positive regulation of metanephric glomerulus development] GO:0097021[lymphocyte migration into lymphoid organs] GO:0098797[plasma membrane protein complex] GO:2001241[positive regulation of extrinsic apoptotic signaling pathway in absence of ligand]
P07949 [Direct mapping] Proto-oncogene tyrosine-protein kinase receptor Ret Soluble RET kinase fragment Extracellular cell-membrane anchored RET cadherin 120 kDa fragment
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A0A024R7T2 [Target identity:100%; Query identity:100%] Proto-oncogene tyrosine-protein kinase receptor Ret
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Enzymes ENZYME proteins Transferases Kinases Tyr protein kinases Transporters Accessory Factors Involved in Transport Predicted membrane proteins Prediction method-based Membrane proteins predicted by MDM MEMSAT3 predicted membrane proteins MEMSAT-SVM predicted membrane proteins Phobius predicted membrane proteins SCAMPI predicted membrane proteins SPOCTOPUS predicted membrane proteins THUMBUP predicted membrane proteins TMHMM predicted membrane proteins # TM segments-based 1TM proteins predicted by MDM Plasma proteins Cancer-related genes Candidate cancer biomarkers COSMIC somatic mutations in cancer genes COSMIC Somatic Mutations COSMIC Nonsense Mutations COSMIC Missense Mutations COSMIC Germline Mutations COSMIC Frameshift Mutations COSMIC Translocations Disease related genes FDA approved drug targets Small molecule drugs Human disease related genes Cancers Cancers of the lung and pleura Cancers of endocrine organs Congenital malformations Congenital malformations of the digestive system Mapped to neXtProt neXtProt - Evidence at protein level Protein evidence (Kim et al 2014) Protein evidence (Ezkurdia et al 2014) DeepTMHMM predicted membrane proteins
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GO:0000165[MAPK cascade] GO:0000166[nucleotide binding] GO:0001657[ureteric bud development] GO:0001755[neural crest cell migration] GO:0001838[embryonic epithelial tube formation] GO:0004672[protein kinase activity] GO:0004713[protein tyrosine kinase activity] GO:0004714[transmembrane receptor protein tyrosine kinase activity] GO:0005509[calcium ion binding] GO:0005515[protein binding] GO:0005524[ATP binding] GO:0005768[endosome] GO:0005769[early endosome] GO:0005886[plasma membrane] GO:0006468[protein phosphorylation] GO:0007155[cell adhesion] GO:0007156[homophilic cell adhesion via plasma membrane adhesion molecules] GO:0007158[neuron cell-cell adhesion] GO:0007165[signal transduction] GO:0007169[transmembrane receptor protein tyrosine kinase signaling pathway] GO:0007399[nervous system development] GO:0007411[axon guidance] GO:0007497[posterior midgut development] GO:0009410[response to xenobiotic stimulus] GO:0010008[endosome membrane] GO:0010628[positive regulation of gene expression] GO:0010976[positive regulation of neuron projection development] GO:0014042[positive regulation of neuron maturation] GO:0016020[membrane] GO:0016301[kinase activity] GO:0016310[phosphorylation] GO:0016740[transferase activity] GO:0018108[peptidyl-tyrosine phosphorylation] GO:0030155[regulation of cell adhesion] GO:0030182[neuron differentiation] GO:0030335[positive regulation of cell migration] GO:0030424[axon] GO:0030425[dendrite] GO:0033141[positive regulation of peptidyl-serine phosphorylation of STAT protein] GO:0033619[membrane protein proteolysis] GO:0033630[positive regulation of cell adhesion mediated by integrin] GO:0033674[positive regulation of kinase activity] GO:0035799[ureter maturation] GO:0035860[glial cell-derived neurotrophic factor receptor signaling pathway] GO:0038023[signaling receptor activity] GO:0042551[neuron maturation] GO:0043025[neuronal cell body] GO:0043235[receptor complex] GO:0043410[positive regulation of MAPK cascade] GO:0045121[membrane raft] GO:0045793[positive regulation of cell size] GO:0045893[positive regulation of DNA-templated transcription] GO:0048265[response to pain] GO:0048484[enteric nervous system development] GO:0050770[regulation of axonogenesis] GO:0051897[positive regulation of protein kinase B signaling] GO:0060041[retina development in camera-type eye] GO:0060384[innervation] GO:0061146[Peyer's patch morphogenesis] GO:0071300[cellular response to retinoic acid] GO:0072300[positive regulation of metanephric glomerulus development] GO:0097021[lymphocyte migration into lymphoid organs] GO:0098797[plasma membrane protein complex] GO:2001241[positive regulation of extrinsic apoptotic signaling pathway in absence of ligand]
A0A1W2PPN7 [Direct mapping] Proto-oncogene tyrosine-protein kinase receptor Ret
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Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Cancer-related genes COSMIC somatic mutations in cancer genes COSMIC Somatic Mutations COSMIC Nonsense Mutations COSMIC Missense Mutations COSMIC Germline Mutations COSMIC Frameshift Mutations COSMIC Translocations Human disease related genes Cancers Cancers of the lung and pleura Cancers of endocrine organs Congenital malformations Congenital malformations of the digestive system Protein evidence (Ezkurdia et al 2014)
A0A1W2PSA1 [Direct mapping] Proto-oncogene tyrosine-protein kinase receptor Ret
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SCAMPI predicted membrane proteins SPOCTOPUS predicted membrane proteins THUMBUP predicted membrane proteins Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Cancer-related genes COSMIC somatic mutations in cancer genes COSMIC Somatic Mutations COSMIC Nonsense Mutations COSMIC Missense Mutations COSMIC Germline Mutations COSMIC Frameshift Mutations COSMIC Translocations Human disease related genes Cancers Cancers of the lung and pleura Cancers of endocrine organs Congenital malformations Congenital malformations of the digestive system Protein evidence (Ezkurdia et al 2014)
A0A804HIK7 [Direct mapping] Proto-oncogene tyrosine-protein kinase receptor Ret
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Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Cancer-related genes COSMIC somatic mutations in cancer genes COSMIC Somatic Mutations COSMIC Nonsense Mutations COSMIC Missense Mutations COSMIC Germline Mutations COSMIC Frameshift Mutations COSMIC Translocations Human disease related genes Cancers Cancers of the lung and pleura Cancers of endocrine organs Congenital malformations Congenital malformations of the digestive system Protein evidence (Ezkurdia et al 2014)
The Human Protein Atlas project is funded
