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Protein

Growth/differentiation factor 15

Gene

GDF15

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Regulates food intake, energy expenditure and body weight in response to metabolic and toxin-induced stresses (PubMed:28953886, PubMed:28846097, PubMed:28846098, PubMed:28846099, PubMed:23468844, PubMed:29046435). Binds to its receptor, GFRAL, and activates GFRAL-expressing neurons localized in the area postrema and nucleus tractus solitarius of the brainstem (PubMed:28953886, PubMed:28846097, PubMed:28846098, PubMed:28846099). It then triggers the activation of neurons localized within the parabrachial nucleus and central amygdala, which contitutes part of the 'emergency circuit' that shapes feeding responses to stressful conditions (PubMed:28953886). On hepatocytes, inhibits growth hormone signaling (By similarity).By similarity6 Publications

GO - Molecular functioni

  • cytokine activity Source: GO_Central
  • growth factor activity Source: UniProtKB-KW
  • protein homodimerization activity Source: UniProtKB
  • transforming growth factor beta receptor binding Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionCytokine, Growth factor

Enzyme and pathway databases

SIGNORiQ99988

Names & Taxonomyi

Protein namesi
Recommended name:
Growth/differentiation factor 15Curated
Short name:
GDF-15Curated
Alternative name(s):
Macrophage inhibitory cytokine 1Curated
Short name:
MIC-11 Publication
NSAID-activated gene 1 protein
Short name:
NAG-1
NSAID-regulated gene 1 protein
Short name:
NRG-1
Placental TGF-beta
Placental bone morphogenetic protein
Prostate differentiation factor
Gene namesi
Name:GDF15Imported
Synonyms:MIC11 Publication, PDF, PLAB, PTGFB
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000130513.6
HGNCiHGNC:30142 GDF15
MIMi605312 gene
neXtProtiNX_Q99988

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Plasma levels are increased in children with concomitant heart disease and failure to thrive but not in children with heart disease and normal body weight.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi225W → A: No effect on interaction with GFRAL. Attenuates GDF15-mediated food-intake inhibition. 1 Publication1
Mutagenesisi283V → A: Reduces cellular signaling mediated by GFRAL and RET. 1 Publication1
Mutagenesisi283V → R: Abolishes interaction with GFRAL. Abolishes RET phosphorylation and cellular signaling mediated by GFRAL and RET. 1 Publication1
Mutagenesisi285I → A: Reduces cellular signaling mediated by GFRAL and RET. Abolishes interaction with GFRAL and GDF15-mediated food-intake inhibition. 2 Publications1

Organism-specific databases

DisGeNETi9518
OpenTargetsiENSG00000130513
PharmGKBiPA134866647

Chemistry databases

ChEMBLiCHEMBL3120039

Polymorphism and mutation databases

BioMutaiGDF15
DMDMi313104195

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 29Sequence analysisAdd BLAST29
PropeptideiPRO_000003399230 – 194Sequence analysisAdd BLAST165
ChainiPRO_0000033993195 – 308Growth/differentiation factor 15Add BLAST114

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi70N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi203 ↔ 210Combined sources2 Publications
Disulfide bondi211 ↔ 274Combined sources2 Publications
Disulfide bondi240 ↔ 305Combined sources2 Publications
Disulfide bondi244 ↔ 307Combined sources2 Publications
Disulfide bondi273InterchainCombined sources1 Publication

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ99988
MaxQBiQ99988
PaxDbiQ99988
PeptideAtlasiQ99988
PRIDEiQ99988
ProteomicsDBi78564

PTM databases

iPTMnetiQ99988
PhosphoSitePlusiQ99988

Expressioni

Tissue specificityi

Highly expressed in placenta, with lower levels in prostate and colon and some expression in kidney (PubMed:9348093). Detected in plasma (at protein level) (PubMed:28572090, PubMed:29046435).3 Publications

Inductioni

Expression is up-regulated by obesity.1 Publication

Gene expression databases

BgeeiENSG00000130513 Expressed in 142 organ(s), highest expression level in chorionic villus
CleanExiHS_GDF15
ExpressionAtlasiQ99988 baseline and differential
GenevisibleiQ99988 HS

Organism-specific databases

HPAiCAB062554
HPA011191
HPA070957

Interactioni

Subunit structurei

Homodimer; disulfide-linked (PubMed:29046435). Interacts with GFRAL; ligand of GFRAL which mediates GDF15 internalization and cellular signaling through interaction with RET (PubMed:28953886, PubMed:28846097, PubMed:28846098, PubMed:28846099).5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MDFIQ997504EBI-2116863,EBI-724076

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114895, 13 interactors
IntActiQ99988, 15 interactors
STRINGi9606.ENSP00000252809

Structurei

Secondary structure

1308
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ99988
SMRiQ99988
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the TGF-beta family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3900 Eukaryota
ENOG410XT8Z LUCA
GeneTreeiENSGT00910000143982
HOGENOMiHOG000143379
HOVERGENiHBG051718
InParanoidiQ99988
KOiK05504
OMAiLGWADWV
OrthoDBiEOG091G0IUS
PhylomeDBiQ99988
TreeFamiTF351787

Family and domain databases

Gene3Di2.10.90.10, 1 hit
InterProiView protein in InterPro
IPR029034 Cystine-knot_cytokine
IPR001839 TGF-b_C
IPR015615 TGF-beta-rel
PANTHERiPTHR11848 PTHR11848, 1 hit
PfamiView protein in Pfam
PF00019 TGF_beta, 1 hit
SMARTiView protein in SMART
SM00204 TGFB, 1 hit
SUPFAMiSSF57501 SSF57501, 1 hit
PROSITEiView protein in PROSITE
PS51362 TGF_BETA_2, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

Q99988-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MPGQELRTVN GSQMLLVLLV LSWLPHGGAL SLAEASRASF PGPSELHSED
60 70 80 90 100
SRFRELRKRY EDLLTRLRAN QSWEDSNTDL VPAPAVRILT PEVRLGSGGH
110 120 130 140 150
LHLRISRAAL PEGLPEASRL HRALFRLSPT ASRSWDVTRP LRRQLSLARP
160 170 180 190 200
QAPALHLRLS PPPSQSDQLL AESSSARPQL ELHLRPQAAR GRRRARARNG
210 220 230 240 250
DHCPLGPGRC CRLHTVRASL EDLGWADWVL SPREVQVTMC IGACPSQFRA
260 270 280 290 300
ANMHAQIKTS LHRLKPDTVP APCCVPASYN PMVLIQKTDT GVSLQTYDDL

LAKDCHCI
Length:308
Mass (Da):34,140
Last modified:November 30, 2010 - v3
Checksum:i2FF3959021B95238
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0A0MTT8A0A0A0MTT8_HUMAN
Growth/differentiation factor 15
GDF15
113Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti269V → E in AAB88913 (PubMed:9375789).Curated1
Sequence conflicti288T → A in AAF89834 (PubMed:9426002).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0476469V → L4 PublicationsCorresponds to variant dbSNP:rs1059519Ensembl.1
Natural variantiVAR_01038648S → T3 PublicationsCorresponds to variant dbSNP:rs1059369Ensembl.1
Natural variantiVAR_047647202H → D1 PublicationCorresponds to variant dbSNP:rs1058587Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U88323 mRNA Translation: AAB88913.1
AB000584 mRNA Translation: BAA19151.1
AF019770 mRNA Translation: AAB88673.1
AF003934 mRNA Translation: AAC24456.1
AK291530 mRNA Translation: BAF84219.1
BT019465 mRNA Translation: AAV38272.1
AC008397 Genomic DNA No translation available.
CH471106 Genomic DNA Translation: EAW84694.1
BC000529 mRNA Translation: AAH00529.1
BC008962 mRNA Translation: AAH08962.1
AF008303 Genomic DNA Translation: AAC39537.1
AF173860 mRNA Translation: AAF89834.1
CCDSiCCDS12376.1
PIRiJC5697
RefSeqiNP_004855.2, NM_004864.3
UniGeneiHs.616962

Genome annotation databases

EnsembliENST00000252809; ENSP00000252809; ENSG00000130513
GeneIDi9518
KEGGihsa:9518
UCSCiuc002niv.2 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U88323 mRNA Translation: AAB88913.1
AB000584 mRNA Translation: BAA19151.1
AF019770 mRNA Translation: AAB88673.1
AF003934 mRNA Translation: AAC24456.1
AK291530 mRNA Translation: BAF84219.1
BT019465 mRNA Translation: AAV38272.1
AC008397 Genomic DNA No translation available.
CH471106 Genomic DNA Translation: EAW84694.1
BC000529 mRNA Translation: AAH00529.1
BC008962 mRNA Translation: AAH08962.1
AF008303 Genomic DNA Translation: AAC39537.1
AF173860 mRNA Translation: AAF89834.1
CCDSiCCDS12376.1
PIRiJC5697
RefSeqiNP_004855.2, NM_004864.3
UniGeneiHs.616962

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5VT2X-ray2.30A/B197-308[»]
5VZ3X-ray1.97A197-308[»]
5VZ4X-ray2.20A197-308[»]
ProteinModelPortaliQ99988
SMRiQ99988
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114895, 13 interactors
IntActiQ99988, 15 interactors
STRINGi9606.ENSP00000252809

Chemistry databases

ChEMBLiCHEMBL3120039

PTM databases

iPTMnetiQ99988
PhosphoSitePlusiQ99988

Polymorphism and mutation databases

BioMutaiGDF15
DMDMi313104195

Proteomic databases

EPDiQ99988
MaxQBiQ99988
PaxDbiQ99988
PeptideAtlasiQ99988
PRIDEiQ99988
ProteomicsDBi78564

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000252809; ENSP00000252809; ENSG00000130513
GeneIDi9518
KEGGihsa:9518
UCSCiuc002niv.2 human

Organism-specific databases

CTDi9518
DisGeNETi9518
EuPathDBiHostDB:ENSG00000130513.6
GeneCardsiGDF15
H-InvDBiHIX0014912
HGNCiHGNC:30142 GDF15
HPAiCAB062554
HPA011191
HPA070957
MIMi605312 gene
neXtProtiNX_Q99988
OpenTargetsiENSG00000130513
PharmGKBiPA134866647
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3900 Eukaryota
ENOG410XT8Z LUCA
GeneTreeiENSGT00910000143982
HOGENOMiHOG000143379
HOVERGENiHBG051718
InParanoidiQ99988
KOiK05504
OMAiLGWADWV
OrthoDBiEOG091G0IUS
PhylomeDBiQ99988
TreeFamiTF351787

Enzyme and pathway databases

SIGNORiQ99988

Miscellaneous databases

ChiTaRSiGDF15 human
GeneWikiiGDF15
GenomeRNAii9518
PROiPR:Q99988
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000130513 Expressed in 142 organ(s), highest expression level in chorionic villus
CleanExiHS_GDF15
ExpressionAtlasiQ99988 baseline and differential
GenevisibleiQ99988 HS

Family and domain databases

Gene3Di2.10.90.10, 1 hit
InterProiView protein in InterPro
IPR029034 Cystine-knot_cytokine
IPR001839 TGF-b_C
IPR015615 TGF-beta-rel
PANTHERiPTHR11848 PTHR11848, 1 hit
PfamiView protein in Pfam
PF00019 TGF_beta, 1 hit
SMARTiView protein in SMART
SM00204 TGFB, 1 hit
SUPFAMiSSF57501 SSF57501, 1 hit
PROSITEiView protein in PROSITE
PS51362 TGF_BETA_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiGDF15_HUMAN
AccessioniPrimary (citable) accession number: Q99988
Secondary accession number(s): O14629
, P78360, Q9BWA0, Q9NRT0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: November 30, 2010
Last modified: October 10, 2018
This is version 162 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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Main funding by: National Institutes of Health

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