dbPTM

RET_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	RET_MOUSE
UniProt AC	P35546
Protein Name	Proto-oncogene tyrosine-protein kinase receptor Ret
Gene Name	Ret
Organism	Mus musculus (Mouse).
Sequence Length	1115
Subcellular Localization	Cell membrane Single-pass type I membrane protein. Endosome membrane Single-pass type I membrane protein .
Protein Description	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. Mediates, through interaction with GDF15-receptor GFRAL, GDF15-induced cell-signaling in the brainstem which induces inhibition of food-intake. Activates MAPK- and AKT-signaling pathways. [PubMed: 28846099]
Protein Sequence	MAKATSGAAGLGLKLILLLPLLGEAPLGLYFSRDAYWERLYVDQPAGTPLLYVHALRDAPGEVPSFRLGQHLYGVYRTRLHENDWIRINETTGLLYLNQSLDHSSWEQLSIRNGGFPLLTIFLQVFLGSTAQREGECHWPGCTRVYFSFINDTFPNCSSFKAQDLCIPETAVSFRVRENRPPGTFYHFHMLPVQFLCPNISVKYSLLGGDSLPFRCDPDCLEVSTRWALDRELREKYVLEALCIVAGPGANKETVTLSFPVTVYDEDDSAPTFSGGVGTASAVVEFKRKEGTVVATLQVFDADVVPASGELVRRYTNTLLSGDSWAQQTFRVEHSPIETLVQVNNNSVRATMHNYKLILNRSLSISESRVLQLAVLVNDSDFQGPGAGGILVLHFNVSVLPVTLNLPRAYSFPVNKRARRYAQIGKVCVENCQEFSGVSIQYKLQPSSINCTALGVVTSPEDTSGTLFVNDTEALRRPECTKLQYTVVATDRQTRRQTQASLVVTVEGTSITEEVGCPKSCAVNKRRPECEECGGLGSPTGRCEWRQGDGKGITRNFSTCSPSTRTCPDGHCDAVESRDANICPQDCLRADIVGGHERGERQGIKAGYGICNCFPDEKKCFCEPEDSQGPLCDALCRTIITAALFSLIISILLSIFCVCHHHKHGHKPPIASAEMTFCRPAQGFPISYSSSGTRRPSLDSTENQVPVDSFKIPEDPKWEFPRKNLVLGKTLGEGEFGKVVKATAFRLKGRAGYTTVAVKMLKENASQSELRDLLSEFNLLKQVNHPHVIKLYGACSQDGPLLLIVEYAKYGSLRGFLRDSRKIGPAYVSGGGSRNSSSLDHPDERVLTMGDLISFAWQISRGMQYLAEMKLVHRDLAARNILVAEGRKMKISDFGLSRDVYEEDSYVKKSKGRIPVKWMAIESLFDHIYTTQSDVWSFGVLLWEIVTLGGNPYPGIPPERLFNLLKTGHRMERPDNCSEEMYRLMLQCWKQEPDKRPVFADISKDLEKMMVKSRDYLDLAASTPSDSLLYDDGLSEEETPLVDCNNAPLPRSLPSTWIENKLYGMSDPNWPGESPVPLTRADGTSTGFPRYANDSVYANWMVSPSAAKLMDTFDS

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
89	N-linked_Glycosylation	ENDWIRINETTGLLY CCCCEEEECCCCEEE	30.61	-
98	N-linked_Glycosylation	TTGLLYLNQSLDHSS CCCEEEEECCCCCCC	18.81	-
110	Phosphorylation	HSSWEQLSIRNGGFP CCCCHHHHCCCCCCC	21.13	22942356
151	N-linked_Glycosylation	RVYFSFINDTFPNCS EEEEEECCCCCCCCH	40.01	-
156	N-linked_Glycosylation	FINDTFPNCSSFKAQ ECCCCCCCCHHCCCC	33.83	-
170	Phosphorylation	QDLCIPETAVSFRVR CCCCCCCCEEEEEEE	27.31	24719451
199	N-linked_Glycosylation	PVQFLCPNISVKYSL EHEECCCCEEEEEEE	37.86	-
345	N-linked_Glycosylation	ETLVQVNNNSVRATM CEEEEECCCCCEEEE	43.21	-
360	N-linked_Glycosylation	HNYKLILNRSLSISE ECEEEHHHCCCCCCH	25.22	-
378	N-linked_Glycosylation	LQLAVLVNDSDFQGP EEEEEEECCCCCCCC	38.62	-
396	N-linked_Glycosylation	GILVLHFNVSVLPVT CEEEEEEEEEEEEEE	17.88	-
450	N-linked_Glycosylation	KLQPSSINCTALGVV EECCCCCEEEEEEEE	21.02	-
470	N-linked_Glycosylation	TSGTLFVNDTEALRR CCCEEEECCHHHHHC	43.05	-
501	Phosphorylation	TRRQTQASLVVTVEG CCCCEEEEEEEEEEC	16.33	-
556	N-linked_Glycosylation	DGKGITRNFSTCSPS CCCCCCCCEECCCCC	26.94	-
697	Phosphorylation	SSGTRRPSLDSTENQ CCCCCCCCCCCCCCC	42.89	25521595
700	Phosphorylation	TRRPSLDSTENQVPV CCCCCCCCCCCCCCC	42.80	28066266
701	Phosphorylation	RRPSLDSTENQVPVD CCCCCCCCCCCCCCC	38.33	28066266
753	Phosphorylation	RLKGRAGYTTVAVKM EECCCCCCHHHHHHH	9.76	21454597
754	Phosphorylation	LKGRAGYTTVAVKML ECCCCCCHHHHHHHH	17.55	21454597
807	Phosphorylation	PLLLIVEYAKYGSLR CEEEEEEHHHHCCHH	9.48	-
810	Phosphorylation	LIVEYAKYGSLRGFL EEEEHHHHCCHHHHH	12.08	-
812	Phosphorylation	VEYAKYGSLRGFLRD EEHHHHCCHHHHHHC	16.29	28059163
820	Phosphorylation	LRGFLRDSRKIGPAY HHHHHHCCCCCCCEE	29.10	28059163
821	Methylation	RGFLRDSRKIGPAYV HHHHHCCCCCCCEEE	38.61	-
827	Phosphorylation	SRKIGPAYVSGGGSR CCCCCCEEECCCCCC	9.78	28066266
829	Phosphorylation	KIGPAYVSGGGSRNS CCCCEEECCCCCCCC	21.03	28066266
833	Phosphorylation	AYVSGGGSRNSSSLD EEECCCCCCCCCCCC	31.40	28066266
836	Phosphorylation	SGGGSRNSSSLDHPD CCCCCCCCCCCCCCC	21.86	28066266
837	Phosphorylation	GGGSRNSSSLDHPDE CCCCCCCCCCCCCCC	38.17	28066266
838	Phosphorylation	GGSRNSSSLDHPDER CCCCCCCCCCCCCCE	37.32	28066266
897	Phosphorylation	KISDFGLSRDVYEED EHHHCCCCCCCCCCC	27.15	28066266
901	Phosphorylation	FGLSRDVYEEDSYVK CCCCCCCCCCCHHCC	20.21	28066266
905	Phosphorylation	RDVYEEDSYVKKSKG CCCCCCCHHCCCCCC	34.80	28066266
906	Phosphorylation	DVYEEDSYVKKSKGR CCCCCCHHCCCCCCC	28.72	28066266
982	Phosphorylation	DNCSEEMYRLMLQCW CCCCHHHHHHHHHHH	12.13	16484222
1016	Phosphorylation	MMVKSRDYLDLAAST HHHHCHHHHHHHCCC	10.87	16484222
1052	Phosphorylation	NNAPLPRSLPSTWIE CCCCCCCCCCCHHHC	42.57	28066266
1063	Phosphorylation	TWIENKLYGMSDPNW HHHCCCCCCCCCCCC	16.64	12087092
1086	Phosphorylation	TRADGTSTGFPRYAN CCCCCCCCCCCCCCC	42.55	28059163
1091	Phosphorylation	TSTGFPRYANDSVYA CCCCCCCCCCCCEEC	15.25	-
1097	Phosphorylation	RYANDSVYANWMVSP CCCCCCEECCEEECH	9.73	-

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
1016	Y	Phosphorylation	Kinase	RET	P35546	PSP
1063	Y	Phosphorylation	Kinase	RET	P35546	PSP

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
Oops, there are no descriptions of PTM sites of RET_MOUSE !!

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of RET_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference	Domain-Domain Interactions
PARK7_MOUSE	Park7	genetic	20386724

Drug and Disease Associations

Kegg Drug
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of RET_MOUSE

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Structural basis for the specific recognition of RET by the Dok1phosphotyrosine binding domain."; Shi N., Ye S., Bartlam M., Yang M., Wu J., Liu Y., Sun F., Han X.,Peng X., Qiang B., Yuan J., Rao Z.; J. Biol. Chem. 279:4962-4969(2004). Cited for: X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 1055-1067, ANDPHOSPHORYLATION AT TYR-1063.	14607833 [Abstract]