GDF15_HUMAN
ID GDF15_HUMAN Reviewed; 308 AA.
AC Q99988; O14629; P78360; Q9BWA0; Q9NRT0;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 3.
DT 03-AUG-2022, entry version 183.
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:0000303|PubMed:28846099};
DE AltName: Full=NSAID-activated gene 1 protein;
DE Short=NAG-1;
DE AltName: Full=NSAID-regulated gene 1 protein;
DE Short=NRG-1;
DE AltName: Full=Placental TGF-beta;
DE AltName: Full=Placental bone morphogenetic protein;
DE AltName: Full=Prostate differentiation factor;
DE Flags: Precursor;
GN Name=GDF15 {ECO:0000312|HGNC:HGNC:30142};
GN Synonyms=MIC1 {ECO:0000303|PubMed:28846099}, PDF, PLAB, PTGFB;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ASP-202.
RC TISSUE=Placenta;
RX PubMed=9375789; DOI=10.1016/s0167-4781(97)00122-x;
RA Hromas R., Hufford M., Sutton J., Xu D., Li Y., Lu L.;
RT "PLAB, a novel placental bone morphogenetic protein.";
RL Biochim. Biophys. Acta 1354:40-44(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], VARIANTS LEU-9 AND THR-48, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Fibrosarcoma;
RX PubMed=9348093; DOI=10.1093/oxfordjournals.jbchem.a021798;
RA Yokoyama-Kobayashi M., Saeki M., Sekine S., Kato S.;
RT "Human cDNA encoding a novel TGF-beta superfamily protein highly expressed
RT in placenta.";
RL J. Biochem. 122:622-626(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS LEU-9 AND THR-48.
RX PubMed=9326641; DOI=10.1073/pnas.94.21.11514;
RA Bootcov M.R., Bauskin A.R., Valenzuela S.M., Moore A.G., Bansal M.,
RA He X.Y., Zhang H.P., Donnellan M., Mahler S., Pryor K., Walsh B.J.,
RA Nicholson R.C., Fairlie W.D., Por S.B., Robbins J.M., Breit S.N.;
RT "MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of
RT the TGF-beta superfamily.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:11514-11519(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT LEU-9.
RC TISSUE=Placenta;
RX PubMed=9593718; DOI=10.1074/jbc.273.22.13760;
RA Paralkar V.M., Vail A.L., Grasser W.A., Brown T.A., Xu H., Vukicevic S.,
RA Ke H.Z., Qi H., Owen T.A., Thompson D.D.;
RT "Cloning and characterization of a novel member of the transforming growth
RT factor-beta/bone morphogenetic protein family.";
RL J. Biol. Chem. 273:13760-13767(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS LEU-9 AND THR-48.
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Muscle;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 14-308.
RX PubMed=9426002; DOI=10.1016/s0378-1119(97)00485-x;
RA Lawton L.N., de Fatima Bonaldo M., Jelenc P.C., Qiu L., Baumes S.A.,
RA Marcelino R.A., de Jesus G.M., Wellington S., Knowles J.A., Warburton D.,
RA Brown S., Soares M.B.;
RT "Identification of a novel member of the TGF-beta superfamily highly
RT expressed in human placenta.";
RL Gene 203:17-26(1997).
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 264-308.
RX PubMed=11259636; DOI=10.1124/mol.59.4.901;
RA Baek S.J., Kim K.S., Nixon J.B., Wilson L.C., Eling T.E.;
RT "Cyclooxygenase inhibitors regulate the expression of a TGF-beta
RT superfamily member that has proapoptotic and antitumorigenic activities.";
RL Mol. Pharmacol. 59:901-908(2001).
RN [12]
RP FUNCTION.
RX PubMed=23468844; DOI=10.1371/journal.pone.0055174;
RA Tsai V.W., Macia L., Johnen H., Kuffner T., Manadhar R., Joergensen S.B.,
RA Lee-Ng K.K., Zhang H.P., Wu L., Marquis C.P., Jiang L., Husaini Y., Lin S.,
RA Herzog H., Brown D.A., Sainsbury A., Breit S.N.;
RT "TGF-b superfamily cytokine MIC-1/GDF15 is a physiological appetite and
RT body weight regulator.";
RL PLoS ONE 8:E55174-E55174(2013).
RN [13]
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND INVOLVEMENT IN DISEASE.
RX PubMed=28572090; DOI=10.15252/emmm.201707604;
RA Wang T., Liu J., McDonald C., Lupino K., Zhai X., Wilkins B.J.,
RA Hakonarson H., Pei L.;
RT "GDF15 is a heart-derived hormone that regulates body growth.";
RL EMBO Mol. Med. 9:1150-1164(2017).
RN [14]
RP FUNCTION, INTERACTION WITH GFRAL, AND MUTAGENESIS OF TRP-225 AND ILE-285.
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 [15]
RP FUNCTION, INTERACTION WITH GFRAL, AND MUTAGENESIS OF VAL-283.
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 [16]
RP FUNCTION, AND INTERACTION WITH GFRAL.
RX PubMed=28846098; DOI=10.1038/nm.4393;
RA Emmerson P.J., Wang F., Du Y., Liu Q., Pickard R.T., Gonciarz M.D.,
RA Coskun T., Hamang M.J., Sindelar D.K., Ballman K.K., Foltz L.A.,
RA Muppidi A., Alsina-Fernandez J., Barnard G.C., Tang J.X., Liu X., Mao X.,
RA Siegel R., Sloan J.H., Mitchell P.J., Zhang B.B., Gimeno R.E., Shan B.,
RA Wu X.;
RT "The metabolic effects of GDF15 are mediated by the orphan receptor
RT GFRAL.";
RL Nat. Med. 23:1215-1219(2017).
RN [17] {ECO:0007744|PDB:5VZ3, ECO:0007744|PDB:5VZ4}
RP X-RAY CRYSTALLOGRAPHY (1.97 ANGSTROMS) OF 197-308 IN COMPLEX WITH GFRAL,
RP INTERACTION WITH GFRAL, FUNCTION, AND MUTAGENESIS OF VAL-283 AND ILE-285.
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 [18]
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 [19] {ECO:0007744|PDB:5VT2}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 197-308, FUNCTION, SUBUNIT,
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 (PubMed:28953886,
CC PubMed:28846097, PubMed:28846098, PubMed:28846099, PubMed:23468844,
CC PubMed:29046435). Binds to its receptor, GFRAL, and activates GFRAL-
CC expressing neurons localized in the area postrema and nucleus tractus
CC solitarius of the brainstem (PubMed:28953886, PubMed:28846097,
CC PubMed:28846098, PubMed:28846099). It then triggers the activation of
CC neurons localized within the parabrachial nucleus and central amygdala,
CC which constitutes part of the 'emergency circuit' that shapes feeding
CC responses to stressful conditions (PubMed:28953886). On hepatocytes,
CC inhibits growth hormone signaling (By similarity).
CC {ECO:0000250|UniProtKB:Q9Z0J7, ECO:0000269|PubMed:23468844,
CC ECO:0000269|PubMed:28846097, ECO:0000269|PubMed:28846098,
CC ECO:0000269|PubMed:28846099, ECO:0000269|PubMed:28953886,
CC ECO:0000269|PubMed:29046435}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (PubMed:29046435). Interacts with
CC GFRAL; ligand of GFRAL which mediates GDF15 internalization and
CC cellular signaling through interaction with RET (PubMed:28953886,
CC PubMed:28846097, PubMed:28846098, PubMed:28846099).
CC {ECO:0000269|PubMed:28846097, ECO:0000269|PubMed:28846098,
CC ECO:0000269|PubMed:28846099, ECO:0000269|PubMed:28953886,
CC ECO:0000269|PubMed:29046435}.
CC -!- INTERACTION:
CC Q99988; Q13185: CBX3; NbExp=3; IntAct=EBI-2116863, EBI-78176;
CC Q99988; Q6UXV0: GFRAL; NbExp=2; IntAct=EBI-2116863, EBI-27112718;
CC Q99988; P49639: HOXA1; NbExp=3; IntAct=EBI-2116863, EBI-740785;
CC Q99988; P59991: KRTAP12-2; NbExp=3; IntAct=EBI-2116863, EBI-10176379;
CC Q99988; Q99750: MDFI; NbExp=5; IntAct=EBI-2116863, EBI-724076;
CC Q99988; Q9Y6A5: TACC3; NbExp=3; IntAct=EBI-2116863, EBI-2554984;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:28572090,
CC ECO:0000269|PubMed:29046435}.
CC -!- TISSUE SPECIFICITY: Highly expressed in placenta, with lower levels in
CC prostate and colon and some expression in kidney (PubMed:9348093).
CC Detected in plasma (at protein level) (PubMed:28572090,
CC PubMed:29046435). {ECO:0000269|PubMed:28572090,
CC ECO:0000269|PubMed:29046435, ECO:0000269|PubMed:9348093}.
CC -!- INDUCTION: Expression is up-regulated by obesity.
CC {ECO:0000269|PubMed:29046435}.
CC -!- DISEASE: Note=Plasma levels are increased in children with concomitant
CC heart disease and failure to thrive but not in children with heart
CC disease and normal body weight. {ECO:0000269|PubMed:28572090}.
CC -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/GDF15ID40701ch19p13.html";
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DR EMBL; U88323; AAB88913.1; -; mRNA.
DR EMBL; AB000584; BAA19151.1; -; mRNA.
DR EMBL; AF019770; AAB88673.1; -; mRNA.
DR EMBL; AF003934; AAC24456.1; -; mRNA.
DR EMBL; AK291530; BAF84219.1; -; mRNA.
DR EMBL; BT019465; AAV38272.1; -; mRNA.
DR EMBL; AC008397; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471106; EAW84694.1; -; Genomic_DNA.
DR EMBL; BC000529; AAH00529.1; -; mRNA.
DR EMBL; BC008962; AAH08962.1; -; mRNA.
DR EMBL; AF008303; AAC39537.1; -; Genomic_DNA.
DR EMBL; AF173860; AAF89834.1; -; mRNA.
DR CCDS; CCDS12376.1; -.
DR PIR; JC5697; JC5697.
DR RefSeq; NP_004855.2; NM_004864.3.
DR PDB; 5VT2; X-ray; 2.30 A; A/B=197-308.
DR PDB; 5VZ3; X-ray; 1.97 A; A=197-308.
DR PDB; 5VZ4; X-ray; 2.20 A; A=197-308.
DR PDB; 6Q2J; EM; 4.10 A; A/B=197-308.
DR PDBsum; 5VT2; -.
DR PDBsum; 5VZ3; -.
DR PDBsum; 5VZ4; -.
DR PDBsum; 6Q2J; -.
DR AlphaFoldDB; Q99988; -.
DR SMR; Q99988; -.
DR BioGRID; 114895; 93.
DR CORUM; Q99988; -.
DR IntAct; Q99988; 22.
DR MINT; Q99988; -.
DR STRING; 9606.ENSP00000252809; -.
DR ChEMBL; CHEMBL3120039; -.
DR GlyGen; Q99988; 2 sites.
DR iPTMnet; Q99988; -.
DR PhosphoSitePlus; Q99988; -.
DR BioMuta; GDF15; -.
DR DMDM; 313104195; -.
DR EPD; Q99988; -.
DR jPOST; Q99988; -.
DR MassIVE; Q99988; -.
DR MaxQB; Q99988; -.
DR PaxDb; Q99988; -.
DR PeptideAtlas; Q99988; -.
DR PRIDE; Q99988; -.
DR ProteomicsDB; 78564; -.
DR Antibodypedia; 2781; 907 antibodies from 40 providers.
DR DNASU; 9518; -.
DR Ensembl; ENST00000252809.3; ENSP00000252809.3; ENSG00000130513.7.
DR Ensembl; ENST00000595973.3; ENSP00000470531.3; ENSG00000130513.7.
DR Ensembl; ENST00000597765.2; ENSP00000469819.2; ENSG00000130513.7.
DR GeneID; 9518; -.
DR KEGG; hsa:9518; -.
DR MANE-Select; ENST00000252809.3; ENSP00000252809.3; NM_004864.4; NP_004855.2.
DR UCSC; uc002niv.2; human.
DR CTD; 9518; -.
DR DisGeNET; 9518; -.
DR GeneCards; GDF15; -.
DR HGNC; HGNC:30142; GDF15.
DR HPA; ENSG00000130513; Tissue enhanced (kidney, urinary bladder).
DR MIM; 605312; gene.
DR neXtProt; NX_Q99988; -.
DR OpenTargets; ENSG00000130513; -.
DR PharmGKB; PA134866647; -.
DR VEuPathDB; HostDB:ENSG00000130513; -.
DR eggNOG; KOG3900; Eukaryota.
DR GeneTree; ENSGT00940000161872; -.
DR HOGENOM; CLU_064099_1_0_1; -.
DR InParanoid; Q99988; -.
DR OMA; RCCRLHT; -.
DR OrthoDB; 776672at2759; -.
DR PhylomeDB; Q99988; -.
DR TreeFam; TF351787; -.
DR PathwayCommons; Q99988; -.
DR SignaLink; Q99988; -.
DR SIGNOR; Q99988; -.
DR BioGRID-ORCS; 9518; 6 hits in 1082 CRISPR screens.
DR ChiTaRS; GDF15; human.
DR GeneWiki; GDF15; -.
DR GenomeRNAi; 9518; -.
DR Pharos; Q99988; Tbio.
DR PRO; PR:Q99988; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q99988; protein.
DR Bgee; ENSG00000130513; Expressed in metanephros cortex and 131 other tissues.
DR ExpressionAtlas; Q99988; baseline and differential.
DR Genevisible; Q99988; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0070700; F:BMP receptor binding; IBA:GO_Central.
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:0030509; P:BMP signaling pathway; IBA:GO_Central.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0035860; P:glial cell-derived neurotrophic factor receptor signaling pathway; IDA: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; IDA:GO_Central.
DR GO; GO:1901741; P:positive regulation of myoblast fusion; IEA:Ensembl.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IBA:GO_Central.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IDA:UniProtKB.
DR GO; GO:0002023; P:reduction of food intake in response to dietary excess; IDA:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0060395; P:SMAD protein signal transduction; IDA:UniProtKB.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; TAS:ProtInc.
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 3D-structure; Cleavage on pair of basic residues; Cytokine; Disulfide bond;
KW Glycoprotein; Growth factor; Reference proteome; Secreted; Signal.
FT SIGNAL 1..29
FT /evidence="ECO:0000255"
FT PROPEP 30..194
FT /evidence="ECO:0000255"
FT /id="PRO_0000033992"
FT CHAIN 195..308
FT /note="Growth/differentiation factor 15"
FT /id="PRO_0000033993"
FT REGION 152..177
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 161..175
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:0000269|PubMed:28953886,
FT ECO:0000269|PubMed:29046435, ECO:0007744|PDB:5VT2,
FT ECO:0007744|PDB:5VZ3, ECO:0007744|PDB:5VZ4"
FT DISULFID 211..274
FT /evidence="ECO:0000269|PubMed:28953886,
FT ECO:0000269|PubMed:29046435, ECO:0007744|PDB:5VT2,
FT ECO:0007744|PDB:5VZ3, ECO:0007744|PDB:5VZ4"
FT DISULFID 240..305
FT /evidence="ECO:0000269|PubMed:28953886,
FT ECO:0000269|PubMed:29046435, ECO:0007744|PDB:5VT2,
FT ECO:0007744|PDB:5VZ3, ECO:0007744|PDB:5VZ4"
FT DISULFID 244..307
FT /evidence="ECO:0000269|PubMed:28953886,
FT ECO:0000269|PubMed:29046435, ECO:0007744|PDB:5VT2,
FT ECO:0007744|PDB:5VZ3, ECO:0007744|PDB:5VZ4"
FT DISULFID 273
FT /note="Interchain"
FT /evidence="ECO:0000269|PubMed:29046435,
FT ECO:0007744|PDB:5VT2"
FT VARIANT 9
FT /note="V -> L (in dbSNP:rs1059519)"
FT /evidence="ECO:0000269|PubMed:9326641,
FT ECO:0000269|PubMed:9348093, ECO:0000269|PubMed:9593718,
FT ECO:0000269|Ref.5"
FT /id="VAR_047646"
FT VARIANT 48
FT /note="S -> T (in dbSNP:rs1059369)"
FT /evidence="ECO:0000269|PubMed:9326641,
FT ECO:0000269|PubMed:9348093, ECO:0000269|Ref.5"
FT /id="VAR_010386"
FT VARIANT 202
FT /note="H -> D (in dbSNP:rs1058587)"
FT /evidence="ECO:0000269|PubMed:9375789"
FT /id="VAR_047647"
FT MUTAGEN 225
FT /note="W->A: No effect on interaction with GFRAL.
FT Attenuates GDF15-mediated food-intake inhibition."
FT /evidence="ECO:0000269|PubMed:28846097"
FT MUTAGEN 283
FT /note="V->A: Reduces cellular signaling mediated by GFRAL
FT and RET."
FT /evidence="ECO:0000269|PubMed:28953886"
FT MUTAGEN 283
FT /note="V->R: Abolishes interaction with GFRAL. Abolishes
FT RET phosphorylation and cellular signaling mediated by
FT GFRAL and RET."
FT /evidence="ECO:0000269|PubMed:28846099"
FT MUTAGEN 285
FT /note="I->A: Reduces cellular signaling mediated by GFRAL
FT and RET. Abolishes interaction with GFRAL and GDF15-
FT mediated food-intake inhibition."
FT /evidence="ECO:0000269|PubMed:28846097,
FT ECO:0000269|PubMed:28953886"
FT CONFLICT 269
FT /note="V -> E (in Ref. 1; AAB88913)"
FT /evidence="ECO:0000305"
FT CONFLICT 288
FT /note="T -> A (in Ref. 10; AAF89834)"
FT /evidence="ECO:0000305"
FT STRAND 204..219
FT /evidence="ECO:0007829|PDB:5VZ3"
FT TURN 220..224
FT /evidence="ECO:0007829|PDB:5VZ3"
FT TURN 226..228
FT /evidence="ECO:0007829|PDB:5VZ3"
FT STRAND 229..231
FT /evidence="ECO:0007829|PDB:5VZ3"
FT STRAND 233..243
FT /evidence="ECO:0007829|PDB:5VZ3"
FT STRAND 248..250
FT /evidence="ECO:0007829|PDB:5VZ3"
FT HELIX 253..264
FT /evidence="ECO:0007829|PDB:5VZ3"
FT TURN 266..268
FT /evidence="ECO:0007829|PDB:5VZ3"
FT STRAND 273..287
FT /evidence="ECO:0007829|PDB:5VZ3"
FT STRAND 289..308
FT /evidence="ECO:0007829|PDB:5VZ3"
SQ SEQUENCE 308 AA; 34140 MW; 2FF3959021B95238 CRC64;
MPGQELRTVN GSQMLLVLLV LSWLPHGGAL SLAEASRASF PGPSELHSED SRFRELRKRY
EDLLTRLRAN QSWEDSNTDL VPAPAVRILT PEVRLGSGGH LHLRISRAAL PEGLPEASRL
HRALFRLSPT ASRSWDVTRP LRRQLSLARP QAPALHLRLS PPPSQSDQLL AESSSARPQL
ELHLRPQAAR GRRRARARNG DHCPLGPGRC CRLHTVRASL EDLGWADWVL SPREVQVTMC
IGACPSQFRA ANMHAQIKTS LHRLKPDTVP APCCVPASYN PMVLIQKTDT GVSLQTYDDL
LAKDCHCI
