Mouse Gene Ret (ENSMUST00000032201.7) from GENCODE VM23 Comprehensive Transcript Set (only Basic displayed by default)
  Description: Mus musculus ret proto-oncogene (Ret), transcript variant 2, mRNA. (from RefSeq NM_009050)
Gencode Transcript: ENSMUST00000032201.7
Gencode Gene: ENSMUSG00000030110.13
Transcript (Including UTRs)
   Position: mm10 chr6:118,151,745-118,197,133 Size: 45,389 Total Exon Count: 20 Strand: -
Coding Region
   Position: mm10 chr6:118,153,853-118,197,133 Size: 43,281 Coding Exon Count: 20 

Page IndexSequence and LinksUniProtKB CommentsPrimersCTDRNA Structure
Protein StructureOther SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther Names
Model InformationMethods
Data last updated at UCSC: 2019-09-19

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr6:118,151,745-118,197,133)mRNA (may differ from genome)Protein (1115 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGeneCardsMGI
PubMedReactomeSOURCEUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: RET_MOUSE
DESCRIPTION: RecName: Full=Proto-oncogene tyrosine-protein kinase receptor Ret; EC=2.7.10.1; AltName: Full=Proto-oncogene c-Ret; Contains: RecName: Full=Soluble RET kinase fragment; Contains: RecName: Full=Extracellular cell-membrane anchored RET cadherin 120 kDa fragment; Flags: Precursor;
FUNCTION: 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.
CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
ENZYME REGULATION: Repressed by withaferin A (WA).
SUBUNIT: Interacts (not phosphorylated) with CC PTK2/FAK1 (via FERM domain). Extracellular cell-membrane anchored RET cadherin fragments form complex in neurons with reduced trophic status, preferentially at the contact sites between somas. Interacts with AIP in the pituitary gland; this interaction prevents the formation of the AIP-survivin complex (By similarity). Phosphorylated form interacts with the PBT domain of DOK2, DOK4 and DOK5. The phosphorylated form interacts with PLCG1 and GRB7. Binds to ARTN.
INTERACTION: Q60629:Epha5; NbExp=5; IntAct=EBI-5548911, EBI-1267609;
SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endosome membrane; Single-pass type I membrane protein (By similarity).
TISSUE SPECIFICITY: Expressed in peripheral nerve cells and hematopoietic cells.
PTM: Autophosphorylated on C-terminal tyrosine residues upon ligand stimulation. Dephosphorylated by PTPRJ on Tyr-906, Tyr-1016 and Tyr-1063 (By similarity).
PTM: Proteolytically cleaved by caspase-3. The soluble RET kinase fragment is able to induce cell death. The extracellular cell- membrane anchored RET cadherin fragment accelerates cell adhesion in sympathetic neurons (By similarity).
DISRUPTION PHENOTYPE: Exclusive loss in nociceptors results in a reduction in nociceptor number and size with a reduced epidermal innervation, but increased sensitivity to cold and increased formalin-induced pain.
MISCELLANEOUS: Treatment with withaferin A (WA) leads tumor regression in medullary thyroid carcinomas (MTC).
SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein kinase family.
SIMILARITY: Contains 1 cadherin domain.
SIMILARITY: Contains 1 protein kinase domain.

-  Primer design for this transcript
 

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Click here to load the transcript sequence and exon structure into Primer3Plus

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To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene
  • D001564 Benzo(a)pyrene
  • C452423 N-(4-bromo-2-fluorophenyl)-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazolin-4-amine
  • D013749 Tetrachlorodibenzodioxin
  • D014212 Tretinoin
  • C008261 lead acetate
  • D015632 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • D015655 1-Methyl-4-phenylpyridinium
  • C029497 2,3-bis(3'-hydroxybenzyl)butyrolactone
  • C108123 4-amino-5-(4-methylphenyl)-7-(tert-butyl)pyrazolo(3,4-d)pyrimidine
  • C545373 AP24534
          more ... click here to view the complete list

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
3' UTR -603.202108-0.286 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR002126 - Cadherin
IPR015919 - Cadherin-like
IPR011009 - Kinase-like_dom
IPR000719 - Prot_kinase_cat_dom
IPR017441 - Protein_kinase_ATP_BS
IPR001245 - Ser-Thr/Tyr_kinase_cat_dom
IPR008266 - Tyr_kinase_AS
IPR020635 - Tyr_kinase_cat_dom
IPR016249 - Tyr_kinase_Ret_rcpt

Pfam Domains:
PF00028 - Cadherin domain
PF00069 - Protein kinase domain
PF07714 - Protein tyrosine kinase

SCOP Domains:
49313 - Cadherin-like
56112 - Protein kinase-like (PK-like)

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1UEF - X-ray


ModBase Predicted Comparative 3D Structure on P35546
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
HumanRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologGenome BrowserNo orthologNo ortholog
Gene Details     
Gene Sorter     
GenBankRGDEnsemblEnsembl  
Protein SequenceProtein Sequence Protein Sequence  
AlignmentAlignment Alignment  

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
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:0016301 kinase activity
GO:0016740 transferase activity

Biological Process:
GO:0000165 MAPK cascade
GO:0000187 activation of MAPK activity
GO:0001657 ureteric bud development
GO:0001755 neural crest cell migration
GO:0001838 embryonic epithelial tube formation
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:0007169 transmembrane receptor protein tyrosine kinase signaling pathway
GO:0007399 nervous system development
GO:0009653 anatomical structure morphogenesis
GO:0010628 positive regulation of gene expression
GO:0010976 positive regulation of neuron projection development
GO:0014042 positive regulation of neuron maturation
GO:0016310 phosphorylation
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0030155 regulation of cell adhesion
GO:0030182 neuron differentiation
GO:0030335 positive regulation of cell migration
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:0035799 ureter maturation
GO:0035860 glial cell-derived neurotrophic factor receptor signaling pathway
GO:0042493 response to drug
GO:0042551 neuron maturation
GO:0043410 positive regulation of MAPK cascade
GO:0045793 positive regulation of cell size
GO:0045893 positive regulation of transcription, DNA-templated
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:2001241 positive regulation of extrinsic apoptotic signaling pathway in absence of ligand
GO:0033139 regulation of peptidyl-serine phosphorylation of STAT protein

Cellular Component:
GO:0005768 endosome
GO:0005769 early endosome
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0010008 endosome membrane
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0030424 axon
GO:0030425 dendrite
GO:0043025 neuronal cell body
GO:0043231 intracellular membrane-bounded organelle
GO:0043235 receptor complex
GO:0045121 membrane raft
GO:0098797 plasma membrane protein complex


-  Descriptions from all associated GenBank mRNAs
  AK162564 - Mus musculus 16 days neonate cerebellum cDNA, RIKEN full-length enriched library, clone:9630013F18 product:unclassifiable, full insert sequence.
AF209436 - Mus musculus c-ret proto-oncogene mRNA, complete cds.
X67812 - M.musculus mRNA for ret proto-oncogene.
AK084977 - Mus musculus 13 days embryo lung cDNA, RIKEN full-length enriched library, clone:D430020M16 product:ret proto-oncogene, full insert sequence.
AK044686 - Mus musculus adult retina cDNA, RIKEN full-length enriched library, clone:A930033C15 product:ret proto-oncogene, full insert sequence.
BC059012 - Mus musculus ret proto-oncogene, mRNA (cDNA clone MGC:69638 IMAGE:6849696), complete cds.
AK051633 - Mus musculus 12 days embryo spinal ganglion cDNA, RIKEN full-length enriched library, clone:D130061D12 product:ret proto-oncogene, full insert sequence.
AY326397 - Mus musculus ret proto-oncogene isoform Ret9 mRNA, complete cds.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
mmu04144 - Endocytosis
mmu05200 - Pathways in cancer
mmu05216 - Thyroid cancer

Reactome (by CSHL, EBI, and GO)

Protein P35546 (Reactome details) participates in the following event(s):

R-MMU-8853745 RET binds GFRA1,GFRA3
R-MMU-8871226 RET binds GFRA1,GFRA2
R-MMU-8871227 RET binds GFRA4
R-MMU-8853800 ARTN binds RET:GFRA1,GFRA3
R-MMU-8853789 GDNF,NRTN bind RET:GFRA1,GFRA2
R-MMU-8853801 PSPN binds RET:GFRA4
R-MMU-8853762 RET dimerizes
R-MMU-8853737 2x p-5Y-RET:GDNF:GFRA complexes bind SHC1
R-MMU-8853753 2x p-5Y-RET:GDNF:GFRA complexes bind GRB7,10
R-MMU-8853755 2x p-5Y-RET:GDNF:GFRA complexes bind PLCgamma1
R-MMU-8854899 2x p-5Y-RET:GDNF:GFRA complexes bind GRB2-1:SOS1
R-MMU-8855564 2x p-5Y-RET:GDNF:GFRA complexes bind FRS2
R-MMU-8855617 2x p-5Y-RET:GDNF:GFRA complexes binds DOK1,DOK2,DOK4,DOK5,DOK6
R-MMU-8855747 2x p-5Y-RET:GDNF:GFRA complexes bind SRC1, RAP1GAP
R-MMU-8855915 2x p-5Y-RET:GDNF:GFRA complexes bind RET interactors
R-MMU-8853792 RET tyrosine phosphorylation
R-MMU-8853734 2x p-5Y-RET:GDNF:GFRA complexes:p-Y349,Y350,Y427-SHC1 binds GRB2-1:SOS1
R-MMU-5672965 RAS GEFs promote RAS nucleotide exchange
R-MMU-8855508 p-5Y-GAB in RET-GRB2-GAB complexes binds PTPN11
R-MMU-8853659 RET signaling
R-MMU-422475 Axon guidance
R-MMU-1266738 Developmental Biology
R-MMU-5673001 RAF/MAP kinase cascade
R-MMU-5684996 MAPK1/MAPK3 signaling
R-MMU-5683057 MAPK family signaling cascades
R-MMU-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: NM_009050, P35546, Q8BQ34, Q9QXH9, RET_MOUSE, uc009dlm.1, uc009dlm.2
UCSC ID: uc009dlm.2
RefSeq Accession: NM_009050
Protein: P35546 (aka RET_MOUSE)
CCDS: CCDS39608.1, CCDS20470.1

-  Gene Model Information
  Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.