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Database: UniProt
Entry: GDF15_RAT
LinkDB: GDF15_RAT
Original site: GDF15_RAT 
ID   GDF15_RAT               Reviewed;         303 AA.
AC   Q9Z0J6;
DT   21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1999, sequence version 1.
DT   27-MAR-2024, entry version 116.
DE   RecName: Full=Growth/differentiation factor 15;
DE            Short=GDF-15;
DE   Flags: Precursor;
GN   Name=Gdf15; Synonyms=Sbf;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA   Boettner M., Laaff M., Suter-Crazzolara C.;
RT   "Identification of a novel member of the TGFbeta superfamily.";
RL   Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   FUNCTION.
RX   PubMed=28953886; DOI=10.1038/nature24042;
RA   Hsu J.Y., Crawley S., Chen M., Ayupova D.A., Lindhout D.A., Higbee J.,
RA   Kutach A., Joo W., Gao Z., Fu D., To C., Mondal K., Li B., Kekatpure A.,
RA   Wang M., Laird T., Horner G., Chan J., McEntee M., Lopez M.,
RA   Lakshminarasimhan D., White A., Wang S.P., Yao J., Yie J., Matern H.,
RA   Solloway M., Haldankar R., Parsons T., Tang J., Shen W.D., Alice Chen Y.,
RA   Tian H., Allan B.B.;
RT   "Non-homeostatic body weight regulation through a brainstem-restricted
RT   receptor for GDF15.";
RL   Nature 550:255-259(2017).
RN   [3]
RP   ERRATUM OF PUBMED:28953886.
RX   PubMed=29144449; DOI=10.1038/nature24481;
RA   Hsu J.Y., Crawley S., Chen M., Ayupova D.A., Lindhout D.A., Higbee J.,
RA   Kutach A., Joo W., Gao Z., Fu D., To C., Mondal K., Li B., Kekatpure A.,
RA   Wang M., Laird T., Horner G., Chan J., McEntee M., Lopez M.,
RA   Lakshminarasimhan D., White A., Wang S.P., Yao J., Yie J., Matern H.,
RA   Solloway M., Haldankar R., Parsons T., Tang J., Shen W.D., Alice Chen Y.,
RA   Tian H., Allan B.B.;
RT   "Non-homeostatic body weight regulation through a brainstem-restricted
RT   receptor for GDF15.";
RL   Nature 551:398-398(2017).
RN   [4]
RP   FUNCTION.
RX   PubMed=28846099; DOI=10.1038/nm.4394;
RA   Yang L., Chang C.C., Sun Z., Madsen D., Zhu H., Padkjaer S.B., Wu X.,
RA   Huang T., Hultman K., Paulsen S.J., Wang J., Bugge A., Frantzen J.B.,
RA   Noergaard P., Jeppesen J.F., Yang Z., Secher A., Chen H., Li X., John L.M.,
RA   Shan B., He Z., Gao X., Su J., Hansen K.T., Yang W., Joergensen S.B.;
RT   "GFRAL is the receptor for GDF15 and is required for the anti-obesity
RT   effects of the ligand.";
RL   Nat. Med. 23:1158-1166(2017).
RN   [5]
RP   INDUCTION BY OBESITY, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
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 (Probable). On hepatocytes, inhibits growth hormone
CC       signaling (By similarity). {ECO:0000250|UniProtKB:Q9Z0J7,
CC       ECO:0000305|PubMed:28846099, ECO:0000305|PubMed:28953886}.
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, ECO:0000250|UniProtKB:Q9Z0J7}.
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}.
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DR   EMBL; AJ011969; CAA09891.1; -; Genomic_DNA.
DR   EMBL; AJ011970; CAA09891.1; JOINED; Genomic_DNA.
DR   RefSeq; NP_062089.1; NM_019216.2.
DR   AlphaFoldDB; Q9Z0J6; -.
DR   SMR; Q9Z0J6; -.
DR   STRING; 10116.ENSRNOP00000026652; -.
DR   GlyCosmos; Q9Z0J6; 1 site, No reported glycans.
DR   GlyGen; Q9Z0J6; 1 site.
DR   PhosphoSitePlus; Q9Z0J6; -.
DR   PaxDb; 10116-ENSRNOP00000026652; -.
DR   GeneID; 29455; -.
DR   KEGG; rno:29455; -.
DR   UCSC; RGD:2674; rat.
DR   AGR; RGD:2674; -.
DR   CTD; 9518; -.
DR   RGD; 2674; Gdf15.
DR   eggNOG; KOG3900; Eukaryota.
DR   InParanoid; Q9Z0J6; -.
DR   OrthoDB; 3015718at2759; -.
DR   PhylomeDB; Q9Z0J6; -.
DR   PRO; PR:Q9Z0J6; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR   GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
DR   GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR   GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR   GO; GO:0035860; P:glial cell-derived neurotrophic factor receptor signaling pathway; ISS:UniProtKB.
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:0043410; P:positive regulation of MAPK cascade; ISS:UniProtKB.
DR   GO; GO:1901741; P:positive regulation of myoblast fusion; ISO:RGD.
DR   GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISS:UniProtKB.
DR   GO; GO:0002023; P:reduction of food intake in response to dietary excess; ISS:UniProtKB.
DR   GO; GO:0060395; P:SMAD protein signal transduction; ISS:UniProtKB.
DR   Gene3D; 2.10.90.10; Cystine-knot cytokines; 1.
DR   InterPro; IPR029034; Cystine-knot_cytokine.
DR   InterPro; IPR001839; TGF-b_C.
DR   InterPro; IPR015615; TGF-beta-rel.
DR   PANTHER; PTHR11848:SF78; GROWTH_DIFFERENTIATION FACTOR 15; 1.
DR   PANTHER; PTHR11848; TGF-BETA FAMILY; 1.
DR   Pfam; PF00019; TGF_beta; 1.
DR   SMART; SM00204; TGFB; 1.
DR   SUPFAM; SSF57501; Cystine-knot cytokines; 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..30
FT                   /evidence="ECO:0000255"
FT   PROPEP          31..188
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000033996"
FT   CHAIN           189..303
FT                   /note="Growth/differentiation factor 15"
FT                   /id="PRO_0000033997"
FT   CARBOHYD        71
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        198..205
FT                   /evidence="ECO:0000250|UniProtKB:Q99988"
FT   DISULFID        206..269
FT                   /evidence="ECO:0000250|UniProtKB:Q99988"
FT   DISULFID        235..300
FT                   /evidence="ECO:0000250|UniProtKB:Q99988"
FT   DISULFID        239..302
FT                   /evidence="ECO:0000250|UniProtKB:Q99988"
FT   DISULFID        268
FT                   /note="Interchain"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   303 AA;  33439 MW;  FA828BE79C1052C9 CRC64;
     MALRALHAQP TGGPQLRFLL FLLLLLLLLS WPSQGDALAL PEQRRSLSES QLNPDELRGR
     FQDLLSRLHA NQSREDSNSE PTPDPAVRIL SPEVRLGSHG RLLLRVNRAS LTQGLPEAYR
     VHRALLLLTP SSRPWDITRP LQRAISLQGP HARALRLRLA PPPDLAVLPS GGARLELHLR
     SAAGRGRRSA HLHPRDSCPL GPGRCCHLET VQATLEDLGW SDWVLSPRQL QLSMCVGECP
     HLYRSANTHA LIKARLHGLQ PDRVPAPCCV PSSYTPVVLM HRTDSGVSLQ TYDDLVAQGC
     HCA
//
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