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	PTPRJ	Q12913	Y	905	dephosphorylation	SIGNORDEPOD	DEPOD:16778204 SIGNOR:16778204
RET	PTPRJ	Q12913	Y	1,062	dephosphorylation	SIGNORDEPOD	DEPOD:16778204 SIGNOR:16778204
RET	PTPRJ	Q12913	Y	905	phosphorylation	SIGNOR_ProtMapperKEAProtMapper	ProtMapper:16778204 KEA:11713247
RET	PTPRJ	Q12913	Y	1,062	phosphorylation	SIGNOR_ProtMapperKEAProtMapper	ProtMapper:16778204 KEA: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:17050626 ProtMapper:15966897 ProtMapper:20682772 KEA:11886862 ProtMapper:11886862 SIGNOR:20682772
RET	PTK2	Q05397	Y	905	phosphorylation	phosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPSIGNORProtMapperSIGNOR_ProtMapperPhosphoSitePhosphoSite_ProtMapper	ProtMapper:21454698 SIGNOR: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)
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	STAT1	P42224	Yes	Yes	No	Li2012REACH_ProtMapperSIGNORProtMapper	ProtMapper:27994058 SIGNOR:27994058 ProtMapper:15297606
PTPRF	P10586	RET	P07949	Yes	No	Yes	SIGNOR_ProtMapperSIGNORProtMapper	SIGNOR:11121408 ProtMapper:11121408
CBLC	Q9ULV8	RET	P07949	Yes	No	Yes	WangSIGNOR	SIGNOR:24466333
RET	P07949	MK01	P28482	Yes	Yes	No	WangBEL-Large-Corpus_ProtMapperphosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPiPTMnetPhosphoPointSIGNORProtMapperHPRDPhosphoSite_KEAKEAHPRD_KEASIGNOR_ProtMapperPhosphoSiteHPRD-phosPhosphoSite_ProtMapper	HPRD-phos:19415658 SIGNOR:16153436 ProtMapper:16153436 KEA:16094384 HPRD:16153436 HPRD-phos:18669648 PhosphoSite:11826406 KEA:16153436 ProtMapper:18707149 ProtMapper:18669648 ProtMapper:19415658 PhosphoSite:21455180 PhosphoSite:21842857 PhosphoSite:21109534 PhosphoSite:11522288 ProtMapper:17016520 HPRD-phos:18578522 HPRD-phos:20068231 PhosphoSite:12388769 HPRD-phos:16153436 PhosphoSite:16156666 ProtMapper:18691976 ProtMapper:17389395 HPRD-phos:18452278 KEA:1378617 PhosphoSite:12571246 KEA:15972258 ProtMapper:19651622 KEA:15592455 KEA:15935618 HPRD-phos:19901323 HPRD-phos:18707149 HPRD-phos:17389395 ProtMapper:18578522 ProtMapper:16497976 ProtMapper:19901323 HPRD-phos:18691976 PhosphoSite:11522789 ProtMapper:20068231 HPRD-phos:16497976 KEA:11971971 PhosphoSite:28450419 KEA:91184134 ProtMapper:18452278 HPRD-phos:19651622 HPRD-phos:17016520
RET	P07949	AKT1	P31749	Yes	Yes	No	PhosphoSite_MIMPMIMPHPRD_MIMPPhosphoSite_norefSIGNORiPTMnetProtMapperKEAKinexus_KEASIGNOR_ProtMapperPhosphoSite_ProtMapper	SIGNOR:15994200 KEA:12600984 ProtMapper:15994200
KAPCA	P17612	RET	P07949	Yes	Yes	Yes	WangphosphoELM_MIMPPhosphoSite_MIMPMIMPNCI-PID_ProtMapperPhosphoSite_norefSIGNORiPTMnetProtMapperKinexus_KEAKEASIGNOR_ProtMapperPhosphoSite_ProtMapper	ProtMapper:17050626 ProtMapper:15966897 ProtMapper:20682772 KEA:11886862 ProtMapper:11886862 SIGNOR:20682772
NRTN	Q99748	RET	P07949	Yes	Yes	No	iTALKSIGNORHINTHPMR_talklrHPMRHPRD_LRdbtalklrHPRDRamilowski2015_Baccin2019WangRamilowski2015HPMR_LRdbReactome_LRdbHPRD_talklrBaccin2019CellinkerEMBRACEFantom5_LRdbCellTalkDBHPMR_CellinkerconnectomeDB2020LRdb	Cellinker:9192898 SIGNOR:9182803Baccin2019:91828039192898LRdb:9182803 HPMR:9192898 connectomeDB2020:9182803 connectomeDB2020:9192898 Cellinker:9182803 HINT:31535977 CellTalkDB:9182803LRdb:919HPRD:9192898 HPMR:9182803
RET	P07949	AF1L2	Q8N4X5	Yes	Yes	No	PhosphoSite_MIMPMIMPPhosphoSite_norefSIGNORiPTMnetProtMapperSIGNOR_ProtMapperPhosphoSite_ProtMapper	ProtMapper:19060924 SIGNOR:19060924
KPCA	P17252	RET	P07949	Yes	No	No	PhosphoSite_MIMPMIMPiPTMnetProtMapperPhosphoSitePhosphoSite_ProtMapper	PhosphoSite:22128160

Page 3 of 3Previous

Protein Complex Composition

13 records.

Component Name	Component Gene Symbols	Component UniProt ID	Stoichiometry	Database	Database IDs	References
RET-Rai complex	RET SHC3	P07949 Q92529	1:1	CompleatCORUM	Compleat:HC1196CORUM:903	15940252
RET_receptor_4	GFRA4 RET	P07949 Q9GZZ7	1:1	CellPhoneDBCellChatDBICELLNET	CellPhoneDB:RET_receptor_4	9491986
	ATP2A3 CYP51A1 DGKE DHRS7 EPHX1 ESYT1 GHDC PDE3B PDZD8 PREB RETSAT SLC27A3 TEX264 THEM6 TYW1 UPK3BL1 VRK2	B0FP48 P07099 P52429 Q13370 Q16850 Q5K4L6 Q6NUM9 Q86Y07 Q8N2G8 Q8NEN9 Q8WUY1 Q93084 Q9BSJ8 Q9HCU5 Q9NV66 Q9Y394 Q9Y6I9	0:0:0:0:0:0:0:0:0:0:0:0:0:0:0:0:0	hu.MAP
	CORO6 GLI4 HTRA4 OTUD4 RETN TRIOBP UACA VTN	P04004 P10075 P83105 Q01804 Q6QEF8 Q9BZF9 Q9H2D6 Q9HD89	0:0:0:0:0:0:0:0	hu.MAP2
	GLI4 HTRA4 OTUD4 RETN VTN	P04004 P10075 P83105 Q01804 Q9HD89	0:0:0:0:0	hu.MAP2
	GLI4 OTUD4 RAI14 RETN TRIOBP VTN	P04004 P10075 Q01804 Q9H2D6 Q9HD89 Q9P0K7	0:0:0:0:0:0	hu.MAP2
	CYP51A1 DHRS7 EPHX1 PDZD8 RETSAT	P07099 Q16850 Q6NUM9 Q8NEN9 Q9Y394	0:0:0:0:0	hu.MAP
	RET	P07949	2	PDB	PDB:7du9PDB:7ju5PDB:2ivsPDB:7ju6PDB:2x2mPDB:7runPDB:6necPDB:7du8PDB:6i82PDB:7dua
	GLI4 RETN	P10075 Q9HD89	0:0	hu.MAP2
	GHDC PDE3B RETSAT SLC27A3	Q13370 Q5K4L6 Q6NUM9 Q8N2G8	0:0:0:0	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