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 P07949	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

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

Ensembl

ENSG00000165731

Entrez Gene Symbol

RET

Gene Synonym

CDHF12CDHR16HSCR1MEN2AMEN2BMTC1PTCRET51

Gene Description

Ret proto-oncogene

Chromosome

Position

43077064-43130351

Frequency

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

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	SRC	P12931	Y	1,096	phosphorylation	Li2012
RET	SRC	P12931	Y	905	phosphorylation	phosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPProtMapperKEALi2012PhosphoSitePhosphoSite_ProtMapper	KEA:17570479 KEA:11713247
RET	PRKCA	P17252	T	675	phosphorylation	PhosphoSite_MIMPMIMPProtMapperPhosphoSitePhosphoSite_ProtMapper
RET	TNK2	Q07912	Y	791	phosphorylation	PhosphoNetworks
RET	TNK2	Q07912	Y	1,062	phosphorylation	PhosphoNetworks
RET	DDR2	Q16832	Y	900	phosphorylation	PhosphoNetworks
RET	DDR2	Q16832	Y	905	phosphorylation	PhosphoNetworks
RET	GRB14	Q14449	Y	905	phosphorylation	REACH_ProtMapperProtMapper	ProtMapper:22158039
RET	GDNF	P39905	Y	1,062	phosphorylation	REACH_ProtMapperSparser_ProtMapperProtMapper	ProtMapper:22751117 ProtMapper:23429478 ProtMapper:25684228
RET	GDNF	P39905	Y	1,015	phosphorylation	Sparser_ProtMapperProtMapper	ProtMapper:25684228

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Ligand-Receptor Signaling

63 records.

Category	Parent	Database	Transmitter	Receiver	Secreted	Plasma Membrane (Transmembrane)	Plasma Membrane (Peripheral)
receptor	receptor	HPMR	No	Yes	No	Yes	No
receptor	receptor	ICELLNET	No	Yes	No	Yes	No
receptor	receptor	CellTalkDB	No	Yes	No	Yes	No
receptor	receptor	Surfaceome	No	Yes	No	Yes	No
receptor	receptor	Ramilowski2015	No	Yes	No	Yes	No
receptor	receptor	LRdb	No	Yes	No	Yes	No
receptor	receptor	Baccin2019	No	Yes	No	Yes	No
receptor	receptor	SignaLink_function	No	Yes	No	Yes	No
kinase	receptor	Almen2009	No	Yes	No	Yes	No
growth_factor	receptor	Baccin2019	No	Yes	No	Yes	No

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Regulatory Interaction Network

29 records.

Source Protein Symbol	Source UniProt ID	Target Protein Symbol	Target UniProt ID	Is Directed	Is Stimulation	Is Inhibition	Database	References
RET	P07949	SHC1	P29353	Yes	Yes	No	WangPhosphoPointSIGNORHPRDHINTSignaLink3Li2012SPIKE_LCSPIKE	SPIKE:16189514 SPIKE_LC:9393871 SPIKE:9393871 SPIKE_LC:15677445 HINT:15677445 SPIKE_LC:9047383 SPIKE:9047383 SignaLink3:8183561 HPRD:8183561 SIGNOR:8183561 SPIKE:15677445 SignaLink3:23331499 HINT:9047384 SPIKE_LC:16189514 HPRD:9047384 SignaLink3:9047384
GDNF	P39905	RET	P07949	Yes	Yes	No	iTALKSIGNORProtMapperHINTSignaLink3HPMR_talklrHPMRHPRD_LRdbtalklrHPRDRamilowski2015_Baccin2019WangRamilowski2015HPMR_LRdbReactome_LRdbHPRD_talklrBaccin2019CellinkerREACH_ProtMapperSTRING_talklrFantom5_LRdbCellTalkDBSparser_ProtMapperHPMR_CellinkerconnectomeDB2020LRdb	LRdb:8674117 Cellinker:9182803 SIGNOR:9182803 Baccin2019:9482105 SignaLink3:8674117 connectomeDB2020:14514671 connectomeDB2020:8674117 ProtMapper:22751117 HINT:31535977 CellTalkDB:9182803 LRdb:9482105 Baccin2019:8674117 ProtMapper:23429478 HPMR:11106404 ProtMapper:25675305 LRdb:14514671 SignaLink3:23331499 Cellinker:9482105 ProtMapper:25684228 HPRD:8674117 HPMR:14514671 Cellinker:14514671 Cellinker:8674117 LRdb:9182803 connectomeDB2020:9182803 connectomeDB2020:9482105 Baccin2019:14514671 Baccin2019:9182803
RET	P07949	DOK6	Q6PKX4	Yes	Yes	No	PhosphoPointSIGNORHPRDSignaLink3Wang	SignaLink3:18988627 SignaLink3:15286081 HPRD:15286081 SIGNOR:15286081 SignaLink3:23331499 SignaLink3:21071413
RET	P07949	GRB10	Q13322	Yes	Yes	No	PhosphoPointSIGNORHPRDHINTSignaLink3Lit-BM-17	HPRD:7665556 Lit-BM-17:7665556 SignaLink3:23331499 SignaLink3:7665556 HINT:28794017 SIGNOR:8631863 HINT:7665556
RET	P07949	STAT3	P40763	Yes	Yes	No	HPRD_MIMPProtMapperRLIMS-P_ProtMapperPhosphoSite_KEASignaLink3phosphoELM_KEALit-BM-17HPRDWangBEL-Large-Corpus_ProtMapperphosphoELM_MIMPPhosphoSite_MIMPMIMPPhosphoPointKEABioGRIDREACH_ProtMapperSparser_ProtMapperSPIKE_LC	KEA:8272872 KEA:12626508 KEA:9582023 SignaLink3:15485908 HPRD:11536047 KEA:11940572 SPIKE_LC:16189514 KEA:9083098 HPRD:12637586 ProtMapper:15212693 KEA:11850821 KEA:12244095 SignaLink3:12637586 BioGRID:11536047 KEA:9305919 HPRD:15485908 KEA:10918587 KEA:8626374 BioGRID:12637586 KEA:15592455 Lit-BM-17:11536047 SignaLink3:23331499 Lit-BM-17:15485908 KEA:11350938 ProtMapper:17209045 ProtMapper:12637586 Lit-BM-17:25241761 KEA:11294897 ProtMapper:25047660 KEA:14551213 Lit-BM-17:12637586 SignaLink3:11536047 KEA:9566874 KEA:11429593 KEA:12576423
RET	P07949	DOK4	Q8TEW6	Yes	Yes	No	PhosphoPointSIGNORHPRDSignaLink3Wang	SIGNOR:11470823 SignaLink3:11470823 SignaLink3:23331499 HPRD:11470823
RET	P07949	DOK5	Q9P104	Yes	Yes	No	SIGNORPhosphoPointHPRDSignaLink3BioGRID	SIGNOR:11470823 BioGRID:15286081 SignaLink3:15286081 SignaLink3:11470823 SignaLink3:23331499 HPRD:11470823
RET	P07949	GRAP	Q13588	Yes	Yes	No	SignaLink3	SignaLink3:8183561 SignaLink3:23331499
RET	P07949	GFRA1	P56159	Yes	Yes	No	WangPhosphoPointSIGNORHPRDHINTSignaLink3BioGRIDCellinkerSPIKE_LC	SIGNOR:10829012 SignaLink3:10829012 HINT:20473317 HINT:9192898 BioGRID:9192898 HINT:10829012 HINT:31535977 HPRD:10774729 SignaLink3:23331499 Cellinker:9883723 SPIKE_LC:16189514
RET	P07949	FRS2	Q8WU20	Yes	Yes	No	WangPhosphoPointSIGNORHPRDSignaLink3SPIKE_LC	HPRD:11360177 SignaLink3:11390647 SIGNOR:11360177 SignaLink3:23331499 SignaLink3:11360177 SPIKE_LC:16189514

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Protein Complex Composition

13 records.

Component Gene Symbols	Component UniProt ID	Stoichiometry	Database
DHRS7 RETSAT SLC27A3 THEM6	Q5K4L6 Q6NUM9 Q8WUY1 Q9Y394	0:0:0:0	hu.MAP
LAPTM4B RETREG1 SLCO6A1	Q86UG4 Q86VI4 Q9H6L5	0:0:0	hu.MAP2
LAPTM4B RETREG1	Q86VI4 Q9H6L5	0:0	hu.MAP

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Isolation & Detection Technology

1 record.

EV Isolation Method	Detection Method	Number of References	References
Differential UltracentrifugationDensity Gradient CentrifugationSize Exclusion Chromatography	Mass spectrometry	6	32284825 29436780 30646616 30950185 38321535 32089743

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

Breast cancer Colon cancer Colorectal cancer Indeterminate colitis Lung cancer Mature B-cell lymphoma Multiple myeloma Myelodysplastic syndrome Neurodegenerative disorder Solid tumour/cancer Thrombocytopenia Thyroid cancer

Biomarker

Phase 2; Phase 1/2; Approved; Phase 1; Terminated

Drug Targets

FDA approved drug targets

Drugs

BARASERTIB-HQPA NINTEDANIB ESYLATE AST-487 AGERAFENIB NULL GW441756X ALISERTIB ZM447439 REGORAFENIB MOTESANIB SITRAVATINIB CYC-116 PONATINIB JAK2 INHIBITOR AZD1480 SUNITINIB SELPERCATINIB IMATINIB ALECTINIB LESTAURTINIB VANDETANIB CABOZANTINIB S-MALATE PRALSETINIB RET INHIBITOR EP0031 VEPAFESTINIB AZD1480 QUIZARTINIB DOVITINIB SP-600125 CHEMBL:CHEMBL546797 NERVE GROWTH FACTOR NVP-TAE684 LINIFANIB RET INHIBITOR TY-1091 VOLASERTIB RET INHIBITOR HS-10365 GENISTEIN AMUVATINIB TYROSINE KINASE INHIBITOR CEDIRANIB SB220025 LAPATINIB OMIPALISIB BARASERTIB CP-547632 PALBOCICLIB SORAFENIB TOZASERTIB TRAMETINIB DIMETHYL SULFOXIDE PD-0166285 PAZOPANIB PF-562271 ENTRECTINIB HESPERADIN TAMATINIB ERLOTINIB HISTONE DEACETYLASE INHIBITOR TRETINOIN GSK-3179106 CEP-2563 TETRADECANOYLPHORBOL ACETATE RET INHIBITOR FHND5071 LENVATINIB EVEROLIMUS ALECTINIB HYDROCHLORIDE MITOQUINONE MESYLATE SAPANISERTIB ILORASERTIB ENMD-2076 ROMIPLOSTIM RET INHIBITOR APS03118 SNS-314 RG-1530 BOS-589 CENISERTIB DEXAMETHASONE JNJ-7706621 AT9283 ENBEZOTINIB RECOMBINANT CHEMOKINE TANESPIMYCIN CHEMBL:CHEMBL1997335

Antibody

CAB002581 HPA008356 HPA008495

Interaction Protein

ENSG00000110395ENSG00000146648ENSG00000160867ENSG00000171094

Interaction Count

Interaction Dataset

intact_biogrid