GDF3_MOUSE
ID GDF3_MOUSE Reviewed; 366 AA.
AC Q07104; Q3TUX1;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Growth/differentiation factor 3;
DE Short=GDF-3;
DE AltName: Full=VG-1-related protein 2;
DE Flags: Precursor;
GN Name=Gdf3; Synonyms=Gdf-3, Vgr-2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=8429021; DOI=10.1016/s0021-9258(18)53714-5;
RA McPherron A.C., Lee S.-J.;
RT "GDF-3 and GDF-9: two new members of the transforming growth factor-beta
RT superfamily containing a novel pattern of cysteines.";
RL J. Biol. Chem. 268:3444-3449(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=1480182; DOI=10.1210/mend.6.11.1480182;
RA Jones C.M., Simon-Chazottes D., Guenet J.-L., Hogan B.L.;
RT "Isolation of Vgr-2, a novel member of the transforming growth factor-beta-
RT related gene family.";
RL Mol. Endocrinol. 6:1961-1968(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Bone marrow;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND INDUCTION.
RX PubMed=11396990; DOI=10.1006/cyto.2001.0864;
RA Witthuhn B.A., Bernlohr D.A.;
RT "Upregulation of bone morphogenetic protein GDF-3/Vgr-2 expression in
RT adipose tissue of FABP4/aP2 null mice.";
RL Cytokine 14:129-135(2001).
RN [5]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=16368929; DOI=10.1242/dev.02210;
RA Chen C., Ware S.M., Sato A., Houston-Hawkins D.E., Habas R., Matzuk M.M.,
RA Shen M.M., Brown C.W.;
RT "The Vg1-related protein Gdf3 acts in a Nodal signaling pathway in the pre-
RT gastrulation mouse embryo.";
RL Development 133:319-329(2006).
RN [6]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=17936261; DOI=10.1016/j.ydbio.2007.08.060;
RA Andersson O., Bertolino P., Ibanez C.F.;
RT "Distinct and cooperative roles of mammalian Vg1 homologs GDF1 and GDF3
RT during early embryonic development.";
RL Dev. Biol. 311:500-511(2007).
RN [7]
RP DISRUPTION PHENOTYPE, FUNCTION, TISSUE SPECIFICITY, AND LIGAND FOR ACVR1C.
RX PubMed=18480259; DOI=10.1073/pnas.0800272105;
RA Andersson O., Korach-Andre M., Reissmann E., Ibanez C.F., Bertolino P.;
RT "Growth/differentiation factor 3 signals through ALK7 and regulates
RT accumulation of adipose tissue and diet-induced obesity.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:7252-7256(2008).
CC -!- FUNCTION: Growth factor involved in early embryonic development and
CC adipose-tissue homeostasis. During embryogenesis controls formation of
CC anterior visceral endoderm and mesoderm and the establishment of
CC anterior-posterior identity through a receptor complex comprising the
CC receptor ACVR1B and the coreceptor TDGF1/Cripto (PubMed:16368929,
CC PubMed:17936261). Regulates adipose-tissue homeostasis and energy
CC balance under nutrient overload in part by signaling through the
CC receptor complex based on ACVR1C and TDGF1/Cripto.
CC {ECO:0000269|PubMed:16368929, ECO:0000269|PubMed:17936261,
CC ECO:0000269|PubMed:18480259}.
CC -!- SUBUNIT: Homodimer. Heterodimer (Potential). But, in contrast to other
CC members of this family, cannot be disulfide-linked. {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q9NR23}.
CC Cytoplasm {ECO:0000250|UniProtKB:Q9NR23}. Note=Mainly accumulated in
CC the cytoplasm. {ECO:0000250|UniProtKB:Q9NR23}.
CC -!- TISSUE SPECIFICITY: Primarily in adult bone marrow, spleen, thymus and
CC adipose tissue. {ECO:0000269|PubMed:1480182,
CC ECO:0000269|PubMed:18480259, ECO:0000269|PubMed:8429021}.
CC -!- INDUCTION: Markedly increased in an obese-mouse model lacking adipocyte
CC fatty acid-binding protein FABP4. {ECO:0000269|PubMed:11396990}.
CC -!- PTM: Synthesized as large precursor molecule that undergo proteolytic
CC cleavage, releasing the pro-domain from the active, receptor binding,
CC C-terminal region of the molecule. {ECO:0000250|UniProtKB:Q9NR23}.
CC -!- DISRUPTION PHENOTYPE: Embryonic lethality in one-third of the mutant
CC embryos because of pregastrulation developmental malformations.
CC However, the majority of mutants survive until adulthood without any
CC overt abnormality (PubMed:17936261, PubMed:16368929). Mutant mice shown
CC resistance to diet-induced obesity (PubMed:18480259).
CC {ECO:0000269|PubMed:16368929, ECO:0000269|PubMed:17936261,
CC ECO:0000269|PubMed:18480259}.
CC -!- MISCELLANEOUS: In contrast to other members of this family, cannot be
CC disulfide-linked due to an atypical cysteine knot configuration, where
CC the fourth cysteine is missing. This fourth cysteine is involved in an
CC inter-molecular bridge to stabilize the active form of homodimeric or
CC heterodimeric signaling molecules. {ECO:0000250|UniProtKB:Q9NR23}.
CC -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
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DR EMBL; L06443; AAA53034.1; -; mRNA.
DR EMBL; S52658; AAB24876.1; -; mRNA.
DR EMBL; AK152457; BAE31235.1; -; mRNA.
DR EMBL; AK160533; BAE35850.1; -; mRNA.
DR CCDS; CCDS20499.1; -.
DR PIR; A45402; A45402.
DR PIR; A46607; A46607.
DR RefSeq; NP_032134.2; NM_008108.5.
DR AlphaFoldDB; Q07104; -.
DR SMR; Q07104; -.
DR BioGRID; 199887; 1.
DR STRING; 10090.ENSMUSP00000032211; -.
DR GlyGen; Q07104; 2 sites.
DR iPTMnet; Q07104; -.
DR PhosphoSitePlus; Q07104; -.
DR PaxDb; Q07104; -.
DR PeptideAtlas; Q07104; -.
DR PRIDE; Q07104; -.
DR Antibodypedia; 11440; 424 antibodies from 32 providers.
DR DNASU; 14562; -.
DR Ensembl; ENSMUST00000032211; ENSMUSP00000032211; ENSMUSG00000030117.
DR GeneID; 14562; -.
DR KEGG; mmu:14562; -.
DR UCSC; uc009dpm.1; mouse.
DR CTD; 9573; -.
DR MGI; MGI:95686; Gdf3.
DR VEuPathDB; HostDB:ENSMUSG00000030117; -.
DR eggNOG; KOG3900; Eukaryota.
DR GeneTree; ENSGT00940000162534; -.
DR HOGENOM; CLU_020515_4_0_1; -.
DR InParanoid; Q07104; -.
DR OMA; NYCHGDC; -.
DR OrthoDB; 919690at2759; -.
DR PhylomeDB; Q07104; -.
DR TreeFam; TF351789; -.
DR BioGRID-ORCS; 14562; 0 hits in 71 CRISPR screens.
DR PRO; PR:Q07104; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q07104; protein.
DR Bgee; ENSMUSG00000030117; Expressed in morula and 34 other tissues.
DR Genevisible; Q07104; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:CAFA.
DR GO; GO:0005615; C:extracellular space; 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:0019901; F:protein kinase binding; ISS:CAFA.
DR GO; GO:0030509; P:BMP signaling pathway; IBA:GO_Central.
DR GO; GO:0007492; P:endoderm development; IMP:MGI.
DR GO; GO:0001654; P:eye development; ISS:UniProtKB.
DR GO; GO:0048859; P:formation of anatomical boundary; IMP:MGI.
DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
DR GO; GO:0007498; P:mesoderm development; IMP:MGI.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; ISS:CAFA.
DR GO; GO:0045605; P:negative regulation of epidermal cell differentiation; ISS:CAFA.
DR GO; GO:0045662; P:negative regulation of myoblast differentiation; IMP:MGI.
DR GO; GO:0030903; P:notochord development; IMP:MGI.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; IMP:BHF-UCL.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IBA:GO_Central.
DR GO; GO:0090009; P:primitive streak formation; IMP:MGI.
DR GO; GO:0010453; P:regulation of cell fate commitment; ISS:CAFA.
DR GO; GO:0002021; P:response to dietary excess; IMP:MGI.
DR GO; GO:0007165; P:signal transduction; IMP:MGI.
DR GO; GO:0001501; P:skeletal system development; ISS:UniProtKB.
DR GO; GO:0060395; P:SMAD protein signal transduction; IBA:GO_Central.
DR GO; GO:0032525; P:somite rostral/caudal axis specification; IMP:MGI.
DR Gene3D; 2.10.90.10; -; 1.
DR InterPro; IPR029034; Cystine-knot_cytokine.
DR InterPro; IPR001839; TGF-b_C.
DR InterPro; IPR001111; TGF-b_propeptide.
DR InterPro; IPR015615; TGF-beta-rel.
DR InterPro; IPR017948; TGFb_CS.
DR PANTHER; PTHR11848; PTHR11848; 1.
DR Pfam; PF00019; TGF_beta; 1.
DR Pfam; PF00688; TGFb_propeptide; 1.
DR SMART; SM00204; TGFB; 1.
DR SUPFAM; SSF57501; SSF57501; 1.
DR PROSITE; PS00250; TGF_BETA_1; 1.
DR PROSITE; PS51362; TGF_BETA_2; 1.
PE 1: Evidence at protein level;
KW Cytokine; Cytoplasm; Developmental protein; Disulfide bond; Glycoprotein;
KW Growth factor; Reference proteome; Secreted; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT PROPEP 23..252
FT /evidence="ECO:0000255"
FT /id="PRO_0000033910"
FT CHAIN 253..366
FT /note="Growth/differentiation factor 3"
FT /id="PRO_0000033911"
FT CARBOHYD 113
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 308
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 266..331
FT /evidence="ECO:0000250"
FT DISULFID 295..363
FT /evidence="ECO:0000250"
FT DISULFID 299..365
FT /evidence="ECO:0000250"
FT CONFLICT 165
FT /note="G -> R (in Ref. 2; AAB24876)"
FT /evidence="ECO:0000305"
FT CONFLICT 167..168
FT /note="LL -> FV (in Ref. 2; AAB24876)"
FT /evidence="ECO:0000305"
FT CONFLICT 225
FT /note="R -> P (in Ref. 1; AAA53034 and 2; AAB24876)"
FT /evidence="ECO:0000305"
FT CONFLICT 313
FT /note="A -> R (in Ref. 2; AAB24876)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 366 AA; 41586 MW; 3DCD7CB8F9470293 CRC64;
MQPYQRLLAL GFLLLTLPWG QTSEFQDSDL LQFLGLEKAP SPHRFQPVPR VLRKIIRARE
AAAASGASQD LCYVKELGVR GNLLQLLPDQ GFFLNTQKPF QDGSCLQKVL YFNLSAIKEK
AKLTMAQLTL DLGPRSYYNL RPELVVALSV VQDRGVWGRS HPKVGRLLFL RSVPGPQGQL
QFNLQGALKD WSSNRLKNLD LHLEILVKED RYSRVTVQPE NPCDRLLRSL HASLLVVTLN
PKHCHPSSRK RRAAISVPKG FCRNFCHRHQ LFINFQDLGW HKWVIAPKGF MANYCHGECP
FSMTTYLNSS NYAFMQALMH MADPKVPKAV CVPTKLSPIS MLYQDSDKNV ILRHYEDMVV
DECGCG
