GDF15_MACFA
ID GDF15_MACFA Reviewed; 308 AA.
AC G7PWZ3;
DT 23-MAY-2018, integrated into UniProtKB/Swiss-Prot.
DT 25-JAN-2012, sequence version 1.
DT 25-MAY-2022, entry version 33.
DE RecName: Full=Growth/differentiation factor 15 {ECO:0000305};
DE Short=GDF-15 {ECO:0000305};
DE AltName: Full=Macrophage inhibitory cytokine 1 {ECO:0000305};
DE Short=MIC-1 {ECO:0000305};
DE Flags: Precursor;
GN Name=GDF15 {ECO:0000250|UniProtKB:Q99988};
GN Synonyms=MIC1 {ECO:0000250|UniProtKB:Q99988};
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541 {ECO:0000312|Proteomes:UP000009130};
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CE-4 {ECO:0000312|EMBL:EHH59367.1};
RX PubMed=22002653; DOI=10.1038/nbt.1992;
RA Yan G., Zhang G., Fang X., Zhang Y., Li C., Ling F., Cooper D.N., Li Q.,
RA Li Y., van Gool A.J., Du H., Chen J., Chen R., Zhang P., Huang Z.,
RA Thompson J.R., Meng Y., Bai Y., Wang J., Zhuo M., Wang T., Huang Y.,
RA Wei L., Li J., Wang Z., Hu H., Yang P., Le L., Stenson P.D., Li B., Liu X.,
RA Ball E.V., An N., Huang Q., Zhang Y., Fan W., Zhang X., Li Y., Wang W.,
RA Katze M.G., Su B., Nielsen R., Yang H., Wang J., Wang X., Wang J.;
RT "Genome sequencing and comparison of two nonhuman primate animal models,
RT the cynomolgus and Chinese rhesus macaques.";
RL Nat. Biotechnol. 29:1019-1023(2011).
RN [2]
RP FUNCTION.
RX PubMed=28846097; DOI=10.1038/nm.4392;
RA Mullican S.E., Lin-Schmidt X., Chin C.N., Chavez J.A., Furman J.L.,
RA Armstrong A.A., Beck S.C., South V.J., Dinh T.Q., Cash-Mason T.D.,
RA Cavanaugh C.R., Nelson S., Huang C., Hunter M.J., Rangwala S.M.;
RT "GFRAL is the receptor for GDF15 and the ligand promotes weight loss in
RT mice and nonhuman primates.";
RL Nat. Med. 23:1150-1157(2017).
RN [3]
RP INDUCTION BY OBESITY, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND
RP FUNCTION.
RX PubMed=29046435; DOI=10.1126/scitranslmed.aan8732;
RA Xiong Y., Walker K., Min X., Hale C., Tran T., Komorowski R., Yang J.,
RA Davda J., Nuanmanee N., Kemp D., Wang X., Liu H., Miller S., Lee K.J.,
RA Wang Z., Veniant M.M.;
RT "Long-acting MIC-1/GDF15 molecules to treat obesity: Evidence from mice to
RT monkeys.";
RL Sci. Transl. Med. 9:0-0(2017).
CC -!- FUNCTION: Regulates food intake, energy expenditure and body weight in
CC response to metabolic and toxin-induced stresses. Binds to its
CC receptor, GFRAL, and activates GFRAL-expressing neurons localized in
CC the area postrema and nucleus tractus solitarius of the brainstem. It
CC then triggers the activation of neurons localized within the
CC parabrachial nucleus and central amygdala, which constitutes part of
CC the 'emergency circuit' that shapes feeding responses to stressful
CC conditions (PubMed:28846097). On hepatocytes, inhibits growth hormone
CC signaling (By similarity). {ECO:0000250|UniProtKB:Q9Z0J7,
CC ECO:0000269|PubMed:28846097}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (By similarity). Interacts with
CC GFRAL; ligand of GFRAL which mediates GDF15 internalization and
CC cellular signaling through interaction with RET (By similarity).
CC {ECO:0000250|UniProtKB:Q99988}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:29046435}.
CC -!- TISSUE SPECIFICITY: Detected in plasma (at protein level).
CC {ECO:0000269|PubMed:29046435}.
CC -!- INDUCTION: Expression is up-regulated by obesity.
CC {ECO:0000269|PubMed:29046435}.
CC -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; CM001294; EHH59367.1; -; Genomic_DNA.
DR AlphaFoldDB; G7PWZ3; -.
DR SMR; G7PWZ3; -.
DR STRING; 9541.XP_005588496.1; -.
DR eggNOG; KOG3900; Eukaryota.
DR Proteomes; UP000009130; Chromosome 19.
DR Proteomes; UP000233100; Unplaced.
DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
DR GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0060400; P:negative regulation of growth hormone receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0040015; P:negative regulation of multicellular organism growth; ISS:UniProtKB.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISS:UniProtKB.
DR GO; GO:0002023; P:reduction of food intake in response to dietary excess; IDA:UniProtKB.
DR Gene3D; 2.10.90.10; -; 1.
DR InterPro; IPR029034; Cystine-knot_cytokine.
DR InterPro; IPR001839; TGF-b_C.
DR InterPro; IPR015615; TGF-beta-rel.
DR PANTHER; PTHR11848; PTHR11848; 1.
DR Pfam; PF00019; TGF_beta; 1.
DR SMART; SM00204; TGFB; 1.
DR SUPFAM; SSF57501; SSF57501; 1.
DR PROSITE; PS51362; TGF_BETA_2; 1.
PE 1: Evidence at protein level;
KW Cleavage on pair of basic residues; Cytokine; Disulfide bond; Glycoprotein;
KW Growth factor; Reference proteome; Secreted; Signal.
FT SIGNAL 1..29
FT /evidence="ECO:0000255"
FT PROPEP 30..192
FT /evidence="ECO:0000255"
FT /id="PRO_0000444321"
FT CHAIN 193..308
FT /note="Growth/differentiation factor 15"
FT /id="PRO_0000444322"
FT REGION 152..179
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 161..179
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 70
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 203..210
FT /evidence="ECO:0000250|UniProtKB:Q99988"
FT DISULFID 211..274
FT /evidence="ECO:0000250|UniProtKB:Q99988"
FT DISULFID 240..305
FT /evidence="ECO:0000250|UniProtKB:Q99988"
FT DISULFID 244..307
FT /evidence="ECO:0000250|UniProtKB:Q99988"
FT DISULFID 273
FT /note="Interchain"
FT /evidence="ECO:0000250"
SQ SEQUENCE 308 AA; 34425 MW; C66D4F3A0F259FE3 CRC64;
MPGQELKTLN GSQMLLVLLV LLWPPHGGAV SLAEASRASF PGPSDLHSED SRFRELRKRY
EDLLTRLRAN QSWEDSNTDL IQAPEVRILT PEVRLGSGGH LHLRISRAVL PEGLPEACRI
HRALFRLSPT ASRSRDVTRP LRRQLRLARP QAPALHLRLS PPPSQSDQLL VKSSSSRPQL
ALHLRPRASR GRRRARARNG DRCPLGPGRC CRLHTVHASL EDLGWADWVL SPREVQVTMC
IGACPSQFRE ANMHAQIKMN LHRLKPDTVP APCCVPASYN PMVLIQKTDT GVSLQTYDDL
LAKDCHCV
