Protein detail
RET
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]
Protein symbol RET | UniProt ID | EVMP score 0.38 |
Frequency 1 | Transmembrane count 1 | Protein classification Cancer-related genesDisease related genesEnzymesFDA approved drug targetsHuman disease related genesPlasma proteinsPredicted intracellular proteinsPredicted membrane proteinsTransporters |
Basic Information
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]
Protein Class
Cancer-related genesDisease related genesEnzymesFDA approved drug targetsHuman disease related genesPlasma proteinsPredicted intracellular proteinsPredicted membrane proteinsTransporters
Protein Function
- Human disease related genes:Cancers:Cancers of the lung and pleura
- Predicted intracellular proteins
- Human disease related genes:Congenital malformations:Congenital malformations of the digestive system
- ENZYME proteins:Transferases
- Human disease related genes:Cancers:Cancers of endocrine organs
- Enzymes
- Cancer-related genes:Candidate cancer biomarkers
- Transporters:Accessory Factors Involved in Transport
- Kinases:Tyr protein kinases
- Disease related genes
- FDA approved drug targets:Small molecule drugs
Transmembrane
636..657; Helical
Transmembrane Count
1
Ensembl
Entrez Gene Symbol
Gene Synonym
CDHF12CDHR16HSCR1MEN2AMEN2BMTC1PTCRET51
Gene Description
Ret proto-oncogene
Chromosome
10
Position
43077064-43130351
Frequency
1
EVMP Score
0.38
Fluorescence & Localization
Tissue SpecificintestineCell SpecificColonocytesBlood Cell SpecificneutrophilBlood Lineage Specificgranulocytes
Function & Pathway
Protein Function
- Human disease related genes:Cancers:Cancers of the lung and pleura
- Predicted intracellular proteins
- Human disease related genes:Congenital malformations:Congenital malformations of the digestive system
- ENZYME proteins:Transferases
- Human disease related genes:Cancers:Cancers of endocrine organs
- Enzymes
- Cancer-related genes:Candidate cancer biomarkers
- Transporters:Accessory Factors Involved in Transport
- Kinases:Tyr protein kinases
- Disease related genes
- FDA approved drug targets:Small molecule drugs
Cellular Component
Molecular Function
Biological Process
KEGG
Reactome
- R-hsa-9830364 formation of the nephric duct
- R-hsa-9830674 formation of the ureteric bud
- R-hsa-9830369 kidney development
- R-hsa-5684996 mapk1 mapk3 signaling
- R-hsa-5683057 mapk family signaling cascades
- R-hsa-9675108 nervous system development
- R-hsa-9768919 npas4 regulates expression of target genes
- R-hsa-8853659 ret signaling
- R-hsa-73857 rna polymerase ii transcription
- R-hsa-9634815 transcriptional regulation by npas4
Canonical Pathways
- M138 Pid thrombin par4 pathway
- M204 Pid rhodopsin pathway
- M252 Pid il8 cxcr1 pathway
Mediation Categories
Adhesion and uptake mediationClinical-translation mediationFusion and delivery mediationImmune mediationReceptor-signaling mediation
Relations & Evidence
Enzyme-Mediated Modification
25 records.
| Substrate Gene Symbol | Enzyme Gene Symbol | Enzyme UniProt ID | Residue Type | Residue Offset | Modification | Database | References |
|---|---|---|---|---|---|---|---|
| RET | PTPRJ | Q12913 | Y | 905 | dephosphorylation | SIGNORDEPOD | DEPOD:16778204SIGNOR:16778204 |
| RET | PTPRJ | Q12913 | Y | 1,062 | dephosphorylation | SIGNORDEPOD | DEPOD:16778204SIGNOR:16778204 |
| RET | PTPRJ | Q12913 | Y | 905 | phosphorylation | SIGNOR_ProtMapperKEAProtMapper | ProtMapper:16778204KEA:11713247 |
| RET | PTPRJ | Q12913 | Y | 1,062 | phosphorylation | SIGNOR_ProtMapperKEAProtMapper | ProtMapper:16778204KEA:11886862 |
| RET | PTPRJ | Q12913 | Y | 1,015 | phosphorylation | KEA | KEA:11713247 |
| RET | PTPRF | P10586 | Y | 1,062 | dephosphorylation | SIGNOR | SIGNOR:11121408 |
| RET | PTPRF | P10586 | Y | 1,062 | phosphorylation | SIGNOR_ProtMapperProtMapper | ProtMapper:11121408 |
| RET | PRKACA | P17612 | S | 696 | phosphorylation | phosphoELM_MIMPPhosphoSite_MIMPMIMPNCI-PID_ProtMapperSIGNORProtMapperKEASIGNOR_ProtMapperPhosphoSitePhosphoSite_ProtMapper | ProtMapper:17050626ProtMapper:15966897ProtMapper:20682772KEA:11886862ProtMapper:11886862SIGNOR:20682772 |
| RET | PTK2 | Q05397 | Y | 905 | phosphorylation | phosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPSIGNORProtMapperSIGNOR_ProtMapperPhosphoSitePhosphoSite_ProtMapper | ProtMapper:21454698SIGNOR:21454698 |
| RET | PTK2 | Q05397 | Y | 1,062 | phosphorylation | RLIMS-P_ProtMapperProtMapper | ProtMapper:25409876 |
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Ligand-Receptor Signaling
63 records.
| Category | Parent | Database | Transmitter | Receiver | Secreted | Plasma Membrane (Transmembrane) | Plasma Membrane (Peripheral) |
|---|---|---|---|---|---|---|---|
| kinase | receptor | Surfaceome | No | Yes | No | Yes | No |
| growth_factor | receptor | ICELLNET | No | Yes | No | Yes | No |
| growth_factor_gdnf_family | receptor | ICELLNET | No | Yes | No | Yes | No |
| receptor | receptor | OmniPath | No | Yes | No | Yes | No |
| extracellular | extracellular | HPMR | No | No | No | Yes | No |
| extracellular | extracellular | OmniPath | No | No | No | Yes | No |
| intracellular | intracellular | LOCATE | No | No | No | Yes | No |
| intracellular | intracellular | ComPPI | No | No | No | Yes | No |
| intracellular | intracellular | GO_Intercell | No | No | No | Yes | No |
| intracellular | intracellular | UniProt_location | No | No | No | Yes | No |
Regulatory Interaction Network
29 records.
Protein Complex Composition
13 records.
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Sequence, Structure & Domains
Sequences
Length
1,114
Mass
124,319
Sequence
MAKATSGAAGLRLLLLLLLPLLGKVALGLYFSRDAYWEKLYVDQAAGTPLLYVHALRDAPEEVPSFRLGQHLYGTYRTRLHENNWICIQEDTGLLYLNRSLDHSSWEKLSVRNRGFPLLTVYLKVFLSPTSLREGECQWPGCARVYFSFFNTSFPACSSLKPRELCFPETRPSFRIRENRPPGTFHQFRLLPVQFLCPNISVAYRLLEGEGLPFRCAPDSLEVSTRWALDREQREKYELVAVCTVHAGAREEVVMVPFPVTVYDEDDSAPTFPAGVDTASAVVEFKRKEDTVVATLRVFDADVVPASGELVRRYTSTLLPGDTWAQQTFRVEHWPNETSVQANGSFVRATVHDYRLVLNRNLSISENRTMQLAVLVNDSDFQGPGAGVLLLHFNVSVLPVSLHLPSTYSLSVSRRARRFAQIGKVCVENCQAFSGINVQYKLHSSGANCSTLGVVTSAEDTSGILFVNDTKALRRPKCAELHYMVVATDQQTSRQAQAQLLVTVEGSYVAEEAGCPLSCAVSKRRLECEECGGLGSPTGRCEWRQGDGKGITRNFSTCSPSTKTCPDGHCDVVETQDINICPQDCLRGSIVGGHEPGEPRGIKAGYGTCNCFPEEEKCFCEPEDIQDPLCDELCRTVIAAAVLFSFIVSVLLSAFCIHCYHKFAHKPPISSAEMTFRRPAQAFPVSYSSSGARRPSLDSMENQVSVDAFKILEDPKWEFPRKNLVLGKTLGEGEFGKVVKATAFHLKGRAGYTTVAVKMLKENASPSELRDLLSEFNVLKQVNHPHVIKLYGACSQDGPLLLIVEYAKYGSLRGFLRESRKVGPGYLGSGGSRNSSSLDHPDERALTMGDLISFAWQISQGMQYLAEMKLVHRDLAARNILVAEGRKMKISDFGLSRDVYEEDSYVKRSQGRIPVKWMAIESLFDHIYTTQSDVWSFGVLLWEIVTLGGNPYPGIPPERLFNLLKTGHRMERPDNCSEEMYRLMLQCWKQEPDKRPVFADISKDLEKMMVKRRDYLDLAASTPSDSLIYDDGLSEEETPLVDCNNAPLPRALPSTWIENKLYGMSDPNWPGESPVPLTRADGTNTGFPRYPNDSVYANWMLSPSAAKLMDTFDS
Alternative Products
Event=Alternative splicing; Named isoforms=2; Name=1; Synonyms=RET51; IsoId=P07949-1; Sequence=Displayed; Name=2; Synonyms=RET9; IsoId=P07949-2; Sequence=VSP_040735
Alternative Sequence
1064..1114; MSDPNWPGESPVPLTRADGTNTGFPRYPNDSVYANWMLSPSAAKLMDTFDS -> RISHAFTRF (in isoform 2)
3D Structural Models
Turn
90..92; 139..141; 231..233; 715..717; 900..902
Helix
75..77; 103..111; 157..159; 162..166; 191..196; 705..710; 721..723; 746..748; 766..781; 812..819; 848..867; 877..879; 884..886; 893..895; 915..917; 920..925; 930..945; 957..959; 960..965; 978..987; 992..994; 998..1010
Beta Strand
30..32; 34..41; 49..52; 70..73; 79..82; 85..88; 94..99; 120..126; 142..152; 174..178; 184..187; 202..208; 212..215; 222..227; 235..245; 252..263; 724..733; 736..744; 751..759; 790..794; 796..798; 801..805; 822..826; 844..846; 880..883; 887..890
3D Structure
Electron microscopy (7); X-ray crystallography (27)
Domain & Motif Annotations
Domain (FT)
168..272; Cadherin; 724..1016; Protein kinase
Region
29..153; Cadherin-like region 1 (CLD1); 265..379; Cadherin-like region 3 (CLD3); 405..506; Cadherin-like region 4 (CLD4)
Protein Families
- Protein kinase superfamily
- Tyr protein kinase family
Sequence Similarities
Belongs to the protein kinase superfamily. Tyr protein kinase family.
Clinical Relevance
Disease Involvement
Cancer-related genesDisease variantFDA approved drug targetsHirschsprung diseaseProto-oncogene
Related Diseases
Biomarker
Phase 2; Phase 1/2; Approved; Phase 1; Terminated
Drug Targets
FDA approved drug targets
Drugs
BARASERTIB-HQPANINTEDANIB ESYLATEAST-487AGERAFENIBNULLGW441756XALISERTIBZM447439REGORAFENIBMOTESANIBSITRAVATINIBCYC-116PONATINIBJAK2 INHIBITOR AZD1480SUNITINIBSELPERCATINIBIMATINIBALECTINIBLESTAURTINIBVANDETANIBCABOZANTINIB S-MALATEPRALSETINIBRET INHIBITOR EP0031VEPAFESTINIBAZD1480QUIZARTINIBDOVITINIBSP-600125CHEMBL:CHEMBL546797NERVE GROWTH FACTORNVP-TAE684LINIFANIBRET INHIBITOR TY-1091VOLASERTIBRET INHIBITOR HS-10365GENISTEINAMUVATINIBTYROSINE KINASE INHIBITORCEDIRANIBSB220025LAPATINIBOMIPALISIBBARASERTIBCP-547632PALBOCICLIBSORAFENIBTOZASERTIBTRAMETINIB DIMETHYL SULFOXIDEPD-0166285PAZOPANIBPF-562271ENTRECTINIBHESPERADINTAMATINIBERLOTINIBHISTONE DEACETYLASE INHIBITORTRETINOINGSK-3179106CEP-2563TETRADECANOYLPHORBOL ACETATERET INHIBITOR FHND5071LENVATINIBEVEROLIMUSALECTINIB HYDROCHLORIDEMITOQUINONE MESYLATESAPANISERTIBILORASERTIBENMD-2076ROMIPLOSTIMRET INHIBITOR APS03118SNS-314RG-1530BOS-589CENISERTIBDEXAMETHASONEJNJ-7706621AT9283ENBEZOTINIBRECOMBINANT CHEMOKINETANESPIMYCINCHEMBL:CHEMBL1997335
Interaction Protein
ENSG00000110395ENSG00000146648ENSG00000160867ENSG00000171094
Interaction Count
4
Interaction Dataset
intact_biogrid