GDF15
entrez
9518
canonical
uniprot
Q99988
canonical
ensembl
ENSG00000130513
resolver
ensp
ENSP00000252809
resolver
ensp
ENSP00000469819
resolver
ensp
ENSP00000470531
resolver
enst
ENST00000252809
resolver
enst
ENST00000595973
resolver
enst
ENST00000597765
resolver
genesymbol
GDF15
resolver
genesymbol_syn
MIC1
resolver
genesymbol_syn
PDF
resolver
genesymbol_syn
PLAB
resolver
genesymbol_syn
PTGFB
resolver
hgnc
HGNC:30142
resolver
uniprot
O14629
resolver
uniprot
P78360
resolver
uniprot
Q9BWA0
resolver
uniprot
Q9NRT0
resolver
uniprot_entry
GDF15_HUMAN
resolver
uniprot_sec
O14629
resolver
uniprot_sec
P78360
resolver
uniprot_sec
Q9BWA0
resolver
uniprot_sec
Q9NRT0
resolver
amino_acid_sequence
MPGQELRTVNGSQMLLVLLVLSWLPHGGALSLAEASRASFPGPSELHSEDSRFRELRKRYEDLLTRLRANQSWEDSNTDLVPAPAVRILTPEVRLGSGGHLHLRISRAALPEGLPEASRLHRALFRLSPTASRSWDVTRPLRRQLSLARPQAPALHLRLSPPPSQSDQLLAESSSARPQLELHLRPQAARGRRRARARNGDHCPLGPGRCCRLHTVRASLEDLGWADWVLSPREVQVTMCIGACPSQFRAANMHAQIKTSLHRLKPDTVPAPCCVPASYNPMVLIQKTDTGVSLQTYDDLLAKDCHCI
uniprot
proteins
disease_involvement
DISEASE: Hyperemesis gravidarum (HG) [MIM:620730]: An autosomal dominant condition characterized by severe nausea and vomiting in pregnancy. It occurs in up to 2% of pregnancies and leads to significant weight loss, dehydration, electrolyte imbalance, and ketonuria. It is associated with both maternal and fetal morbidity. {ECO:0000269|PubMed:29563502, ECO:0000269|PubMed:35218128, ECO:0000269|PubMed:38092039}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Hormone produced in response to various stresses to confer information about those stresses to the brain, and trigger an aversive response, characterized by nausea, vomiting, and/or loss of appetite (PubMed:23468844, PubMed:24971956, PubMed:28846097, PubMed:28846098, PubMed:28846099, PubMed:28953886, PubMed:29046435, PubMed:30639358, PubMed:31875646, PubMed:33589633, PubMed:38092039). 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:30639358, PubMed:33589633, PubMed:38092039). Acts by binding to its receptor, GFRAL, activating GFRAL-expressing neurons localized in the area postrema and nucleus tractus solitarius of the brainstem (PubMed:28846097, PubMed:28846098, PubMed:28846099, PubMed:28953886, PubMed:31535977). It then triggers the activation of neurons localized within the parabrachial nucleus and central amygdala, which constitutes part of the 'emergency circuit' that shapes responses to stressful conditions (PubMed:28953886). The GDF15-GFRAL signal induces expression of genes involved in metabolism, such as lipid metabolism in adipose tissues (PubMed:31402172). Required for avoidance behavior in response to food allergens: induced downstream of mast cell activation to promote aversion and minimize harmful effects of exposure to noxious substances (By similarity). In addition to suppress appetite, also promotes weight loss by enhancing energy expenditure in muscle: acts by increasing calcium futile cycling in muscle (By similarity). Contributes to the effect of metformin, an anti-diabetic drug, on appetite reduction and weight loss: produced in the kidney in response to metformin treatment, thereby activating the GDF15-GFRAL response, leading to reduced appetite and weight (PubMed:31875646, PubMed:37060902). The contribution of GDF15 to weight loss following metformin treatment is however limited and subject to discussion (PubMed:36001956). Produced in response to anticancer drugs, such as camptothecin or cisplatin, promoting nausea, vomiting and contributing to malnutrition (By similarity). Overproduced in many cancers, promoting anorexia in cancer (cachexia) (PubMed:32661391). Responsible for the risk of nausea and vomiting during pregnancy: high levels of GDF15 during pregnancy, mostly originating from the fetus, are associated with increased nausea and vomiting (PubMed:38092039). Maternal sensitivity to nausea is probably determined by pre-pregnancy exposure to GDF15, women with naturally high level of GDF15 being less susceptible to nausea than women with low levels of GDF15 before pregnancy (PubMed:38092039). Promotes metabolic adaptation in response to systemic inflammation caused by bacterial and viral infections in order to promote tissue tolerance and prevent tissue damage (PubMed:31402172). Required for tissue tolerance in response to myocardial infarction by acting as an inhibitor of leukocyte integring activation, thereby protecting against cardiac rupture (By similarity). Inhibits growth hormone signaling on hepatocytes (By similarity). {ECO:0000250|UniProtKB:Q9Z0J7, ECO:0000269|PubMed:23468844, ECO:0000269|PubMed:24971956, ECO:0000269|PubMed:28846097, ECO:0000269|PubMed:28846098, ECO:0000269|PubMed:28846099, ECO:0000269|PubMed:28953886, ECO:0000269|PubMed:29046435, ECO:0000269|PubMed:30639358, ECO:0000269|PubMed:31402172, ECO:0000269|PubMed:31535977, ECO:0000269|PubMed:31875646, ECO:0000269|PubMed:32661391, ECO:0000269|PubMed:33589633, ECO:0000269|PubMed:36001956, ECO:0000269|PubMed:37060902, ECO:0000269|PubMed:38092039}.
uniprot
proteins
mass_dalton
34140
uniprot
proteins
mutagenesis
MUTAGEN 225; /note="W->A: No effect on interaction with GFRAL. Attenuates GDF15-mediated food-intake inhibition."; /evidence="ECO:0000269|PubMed:28846097"; MUTAGEN 228; /note="W->E: Abolished formation of a ternary complex with GFRAL and RET."; /evidence="ECO:0000269|PubMed:31535977"; MUTAGEN 283; /note="V->A: Reduces cellular signaling mediated by GFRAL and RET."; /evidence="ECO:0000269|PubMed:28953886"; MUTAGEN 283; /note="V->R: Abolishes interaction with GFRAL. Abolishes RET phosphorylation and cellular signaling mediated by GFRAL and RET."; /evidence="ECO:0000269|PubMed:28846099"; MUTAGEN 285; /note="I->A: Reduces cellular signaling mediated by GFRAL and RET. Abolishes interaction with GFRAL and GDF15-mediated food-intake inhibition."; /evidence="ECO:0000269|PubMed:28846097, ECO:0000269|PubMed:28953886"; MUTAGEN 297; /note="Y->E: Abolished formation of a ternary complex with GFRAL and RET."; /evidence="ECO:0000269|PubMed:31535977
uniprot
proteins
protein_family
TGF-beta family
uniprot
proteins
pubmed
11259636
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15057824
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
23468844
uniprot
proteins
pubmed
24971956
uniprot
proteins
pubmed
28572090
uniprot
proteins
pubmed
28846097
uniprot
proteins
pubmed
28846098
uniprot
proteins
pubmed
28846099
uniprot
proteins
pubmed
28953886
uniprot
proteins
pubmed
29046435
uniprot
proteins
pubmed
29144449
uniprot
proteins
pubmed
29563502
uniprot
proteins
pubmed
30639358
uniprot
proteins
pubmed
31402172
uniprot
proteins
pubmed
31535977
uniprot
proteins
pubmed
31875646
uniprot
proteins
pubmed
32661391
uniprot
proteins
pubmed
32694673
uniprot
proteins
pubmed
33207247
uniprot
proteins
pubmed
33589633
uniprot
proteins
pubmed
35218128
uniprot
proteins
pubmed
36001956
uniprot
proteins
pubmed
36630958
uniprot
proteins
pubmed
37060902
uniprot
proteins
pubmed
38056430
uniprot
proteins
pubmed
38092039
uniprot
proteins
pubmed
9326641
uniprot
proteins
pubmed
9348093
uniprot
proteins
pubmed
9375789
uniprot
proteins
pubmed
9426002
uniprot
proteins
pubmed
9593718
uniprot
proteins
sequence_length
308
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:28572090, ECO:0000269|PubMed:29046435, ECO:0000269|PubMed:31875646, ECO:0000269|PubMed:32694673, ECO:0000269|PubMed:38092039}. Note=Secreted in the plasma. {ECO:0000269|PubMed:28572090, ECO:0000269|PubMed:29046435}.
uniprot
proteins