InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Ret

Summary

InnateDB Protein

IDBP-181395.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Ret

Protein Name

ret proto-oncogene

Synonyms

c-Ret; PTC; RET51; RET9;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000032201

InnateDB Gene

IDBG-181393 (Ret)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:17322904, ECO:0000269PubMed:20237269}.

Subcellular Localization

Cell membrane; Single-pass type I membrane protein. Endosome membrane {ECO:0000250}; Single-pass type I membrane protein {ECO:0000250}.

Disease Associations

Tissue Specificity

Expressed in peripheral nerve cells, hematopoietic cells and podocytes. {ECO:0000269PubMed:18753381}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 11 experimentally validated interaction(s) in this database.
They are also associated with 29 interaction(s) predicted by orthology.

Experimentally validated
Total	11 [view]
Protein-Protein	10 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	29 [view]

Gene Ontology

Molecular Function

Accession	GO Term
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:0016772	transferase activity, transferring phosphorus-containing groups

Biological Process

GO:0000165	MAPK cascade
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:0007156	homophilic cell adhesion
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:0010976	positive regulation of neuron projection development
GO:0014042	positive regulation of neuron maturation
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0030155	regulation of cell adhesion
GO:0030182	neuron differentiation
GO:0030335	positive regulation of cell migration
GO:0033619	membrane protein proteolysis
GO:0033630	positive regulation of cell adhesion mediated by integrin
GO:0035799	ureter maturation
GO:0042493	response to drug
GO:0042551	neuron maturation
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: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

Cellular Component

GO:0005887	integral component of plasma membrane
GO:0010008	endosome membrane
GO:0016020	membrane
GO:0043235	receptor complex
GO:0045121	membrane raft

Protein Structure and Domains

PDB ID

MGI:97902

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002126 Cadherin
IPR002290 Serine/threonine- /dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR015919 Cadherin-like
IPR016249 Tyrosine-protein kinase, Ret receptor
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714
PF00028

PRINTS

PR00109
PR00205

PIRSF

PIRSF000631

SMART

SM00112
SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References