Gfral
entrez
404194
canonical
uniprot
Q6SJE0
canonical
ensembl
ENSMUSG00000059383
resolver
ensp
ENSMUSP00000074421
resolver
genesymbol
Gfral
resolver
genesymbol_syn
Gral
resolver
uniprot
Q6SJD9
resolver
uniprot_entry
GFRAL_MOUSE
resolver
uniprot_sec
Q6SJD9
resolver
activity_regulation
ACTIVITY REGULATION: Specifically inhibited by 3P10 monoclonal antibody (PubMed:32661391). Strongly activated by LY3463251, a long-acting and stable agonist composed of GDF15 conjugated monomeric human IgG4 Fc (PubMed:36630958). {ECO:0000269|PubMed:32661391, ECO:0000269|PubMed:36630958}.
uniprot
proteins
amino_acid_sequence
MLVFIFLAVTLSSENESSSQTNDCAHLIQKCLIDANGCEQSWRSMEDTCLTPGDSCKINNSLHCNLSIQALVEKNFQFKECLCMDDLHCTVNKLFGKKCTNKTDNMEKDNKDKWNLTTTPFYHGFKQMQSCLEVTEACVGDVVCNAQLALYLKACSANGNLCDVKHCQAAIRFFYQNMPFNTAQMLAFCDCAQSDIPCQQSKETLHSKPCALNIVPPPTCLSVIHTCRNDELCRTHYRTFQTECWPHITGKCHEDETCISMLGKQDLTCSGSESCRAAFLGTFGTVLQVPCACRGVTQAEEHVCMIFQHMLHSKSCFNYPTPNVKDISSYEKKNSKEITLTGFNSFFNGELLYVVVCMAVTCGILFLVMLKLRIQSEKRDPSSIEIAGGVIIQ
uniprot
proteins
function
FUNCTION: Brainstem-restricted receptor for GDF15 hormone, which triggers an aversive response, characterized by nausea, vomiting, and/or loss of appetite in response to various stresses (PubMed:28846097, PubMed:28846098, PubMed:28846099, PubMed:28953886, PubMed:31152154, PubMed:31928886, PubMed:32723474, PubMed:33593916, PubMed:35202387, PubMed:36630958, PubMed:37380764). The aversive response is both required to reduce continuing exposure to those stresses at the time of exposure and to promote avoidance behavior in the future (PubMed:28846097, PubMed:28846098, PubMed:28846099, PubMed:28953886, PubMed:31928886, PubMed:32723474, PubMed:33593916, PubMed:35202387, PubMed:36630958). The GDF15-GFRAL aversive response is triggered by stresses, such as anticancer drugs (camptothecin or cisplatin), cancers or drugs such as metformin (PubMed:31875646, PubMed:31928886, PubMed:32661391, PubMed:32723474). Upon interaction with its ligand, GDF15, mediates the GDF15-induced autophosphorylation and activation of the RET tyrosine kinase receptor, leading to activation of MAPK- and AKT- signaling pathways (PubMed:28846098, PubMed:28846099, PubMed:32723474, PubMed:33593916). Ligand-binding activates GFRAL-expressing neurons localized in the area postrema and nucleus tractus solitarius of the brainstem (PubMed:28846098, PubMed:28846099, PubMed:31152154, PubMed:32723474). The GDF15-GFRAL signal induces expression of genes involved in metabolism, such as lipid metabolism in adipose tissues (PubMed:32661391). {ECO:0000269|PubMed:28846097, ECO:0000269|PubMed:28846098, ECO:0000269|PubMed:28846099, ECO:0000269|PubMed:28953886, ECO:0000269|PubMed:31152154, ECO:0000269|PubMed:31875646, ECO:0000269|PubMed:31928886, ECO:0000269|PubMed:32661391, ECO:0000269|PubMed:32723474, ECO:0000269|PubMed:33593916, ECO:0000269|PubMed:35202387, ECO:0000269|PubMed:36630958, ECO:0000269|PubMed:37380764}.
uniprot
proteins
mass_dalton
43964
uniprot
proteins
post_translational_modification
PTM: Cleaved and inactivated by MMP14, inhibiting the GDF15-GFRAL aversive response. {ECO:0000305|PubMed:35177851}.
uniprot
proteins
protein_family
GDNFR family
uniprot
proteins
pubmed
28846097
uniprot
proteins
pubmed
28846098
uniprot
proteins
pubmed
28846099
uniprot
proteins
pubmed
28953886
uniprot
proteins
pubmed
29144449
uniprot
proteins
pubmed
31152154
uniprot
proteins
pubmed
31875646
uniprot
proteins
pubmed
31928886
uniprot
proteins
pubmed
32661391
uniprot
proteins
pubmed
32723474
uniprot
proteins
pubmed
33593916
uniprot
proteins
pubmed
35177851
uniprot
proteins
pubmed
35202387
uniprot
proteins
pubmed
36630958
uniprot
proteins
pubmed
37380764
uniprot
proteins
sequence_length
393
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q6UXV0}; Single-pass membrane protein {ECO:0000305}; Extracellular side {ECO:0000305}.
uniprot
proteins
transmembrane_region
TRANSMEM 350..370; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins