GDF15

Protein identityUniProt · HPA

UniProt accession

Q99988

Gene

GDF15

Ensembl

ENSG00000130513

Chromosome

19

Canonical length

308 aa

Protein class

Cancer-related genes, Disease related genes, Plasma proteins, Predicted secreted proteins

Subcellular location

Golgi apparatus

Secretome location

Secreted to blood

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. The protein is expressed in a broad range of cell types, acts as a pleiotropic cytokine and is involved in the stress response program of cells after cellular injury. Increased protein levels are associated with disease states such as tissue hypoxia, inflammation, acute injury and oxidative stress. [provided by RefSeq, Aug 2016]

Canonical amino-acid sequenceUniProt

308 residues, UniProt reviewed canonical sequence.

>Q99988|GDF15
     1  MPGQELRTVN GSQMLLVLLV LSWLPHGGAL SLAEASRASF PGPSELHSED SRFRELRKRY
    61  EDLLTRLRAN QSWEDSNTDL VPAPAVRILT PEVRLGSGGH LHLRISRAAL PEGLPEASRL
   121  HRALFRLSPT ASRSWDVTRP LRRQLSLARP QAPALHLRLS PPPSQSDQLL AESSSARPQL
   181  ELHLRPQAAR GRRRARARNG DHCPLGPGRC CRLHTVRASL EDLGWADWVL SPREVQVTMC
   241  IGACPSQFRA ANMHAQIKTS LHRLKPDTVP APCCVPASYN PMVLIQKTDT GVSLQTYDDL
   301  LAKDCHCI

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GDF15 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.42

Highest tissue expression

328 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GDF15.

Disease | AllUniProt

Conditions GDF15 is implicated in, by any mechanism.

• Hyperemesis gravidarum (HG) MIM:620730

ReferencesPubMed · IEDB

Publications for GDF15 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.87

gnomAD pLI

0

gnomAD missense Z

0.29

DepMap mean gene effect

0.09

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cell surface receptor protein serine/threonine kinase signaling pathway
• cell-cell signaling
• cellular response to chemical stress
• GDF15-GFRAL signaling pathway
• negative regulation of appetite
• negative regulation of growth hormone receptor signaling pathway
• negative regulation of leukocyte migration
• negative regulation of multicellular organism growth
• negative regulation of SMAD protein signal transduction
• negative regulation of transforming growth factor beta receptor signaling pathway
• positive regulation of fatty acid oxidation
• positive regulation of MAPK cascade
• positive regulation of myoblast fusion
• positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
• reduction of food intake in response to dietary excess
• response to metformin
• signal transduction
• transforming growth factor beta receptor signaling pathway

Molecular functions

• cytokine activity
• growth factor activity
• hormone activity
• protein homodimerization activity

Cellular components

• cytoplasm
• extracellular exosome
• extracellular region
• extracellular space
• Golgi apparatus
• nucleus

Protein domainsUniProt · Pfam · InterPro

• Transforming growth factor-beta, C-terminal
• Transforming growth factor-beta-like
• Cystine-knot cytokine
• Transforming growth factor beta like domain

KeywordsUniProt

• Cleavage on pair of basic residues
• Cytokine
• Disulfide bond
• Glycoprotein
• Hormone
• Secreted
• Signal

InteractionsUniProt · HPA

Protein binding partners of GDF15 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• GFRAL
• RET