GFRAL
entrez
389400
canonical
uniprot
Q6UXV0
canonical
ensembl
ENSG00000187871
resolver
ensp
ENSP00000343636
resolver
enst
ENST00000340465
resolver
genesymbol
GFRAL
resolver
genesymbol_syn
C6orf144
resolver
hgnc
HGNC:32789
resolver
uniprot
Q5VTF6
resolver
uniprot_entry
GFRAL_HUMAN
resolver
uniprot_sec
Q5VTF6
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
MIVFIFLAMGLSLENEYTSQTNNCTYLREQCLRDANGCKHAWRVMEDACNDSDPGDPCKMRNSSYCNLSIQYLVESNFQFKECLCTDDFYCTVNKLLGKKCINKSDNVKEDKFKWNLTTRSHHGFKGMWSCLEVAEACVGDVVCNAQLASYLKACSANGNPCDLKQCQAAIRFFYQNIPFNIAQMLAFCDCAQSDIPCQQSKEALHSKTCAVNMVPPPTCLSVIRSCQNDELCRRHYRTFQSKCWQRVTRKCHEDENCISTLSKQDLTCSGSDDCKAAYIDILGTVLQVQCTCRTITQSEESLCKIFQHMLHRKSCFNYPTLSNVKGMALYTRKHANKITLTGFHSPFNGEVIYAAMCMTVTCGILLLVMVKLRTSRISSKARDPSSIQIPGEL
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:36630958). 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:36630958). The GDF15-GFRAL aversive response is triggered by stresses, such as anticancer drugs (camptothecin or cisplatin), cancers or drugs such as metformin (PubMed:32661391). 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:31535977, PubMed:32661391). Ligand-binding activates GFRAL-expressing neurons localized in the area postrema and nucleus tractus solitarius of the brainstem (By similarity). The GDF15-GFRAL signal induces expression of genes involved in metabolism, such as lipid metabolism in adipose tissues (PubMed:32661391). {ECO:0000250|UniProtKB:Q6SJE0, ECO:0000269|PubMed:28846097, ECO:0000269|PubMed:28846098, ECO:0000269|PubMed:28846099, ECO:0000269|PubMed:28953886, ECO:0000269|PubMed:31535977, ECO:0000269|PubMed:32661391, ECO:0000269|PubMed:36630958}.
uniprot
proteins
mass_dalton
44518
uniprot
proteins
mutagenesis
MUTAGEN 261; /note="T->M: Abolished formation of a ternary complex with GDF15 and RET."; /evidence="ECO:0000269|PubMed:31535977
uniprot
proteins
post_translational_modification
PTM: Cleaved and inactivated by MMP14, inhibiting the GDF15-GFRAL aversive response. {ECO:0000269|PubMed:35177851}.
uniprot
proteins
protein_family
GDNFR family
uniprot
proteins
pubmed
12975309
uniprot
proteins
pubmed
14574404
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
28846097
uniprot
proteins
pubmed
28846098
uniprot
proteins
pubmed
28846099
uniprot
proteins
pubmed
28953886
uniprot
proteins
pubmed
29144449
uniprot
proteins
pubmed
31535977
uniprot
proteins
pubmed
32661391
uniprot
proteins
pubmed
35177851
uniprot
proteins
pubmed
36630958
uniprot
proteins
sequence_length
394
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:28953886}; Single-pass membrane protein {ECO:0000269|PubMed:28953886}; Extracellular side {ECO:0000269|PubMed:28953886}.
uniprot
proteins
transmembrane_region
TRANSMEM 352..371; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins