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GDF3_XENLA
ID   GDF3_XENLA              Reviewed;         354 AA.
AC   Q9YGV1; Q8JH95;
DT   06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1999, sequence version 1.
DT   03-AUG-2022, entry version 92.
DE   RecName: Full=Growth/differentiation factor 3;
DE            Short=Gdf-3;
DE   AltName: Full=Derriere protein;
DE   Flags: Precursor;
GN   Name=gdf3;
GN   Synonyms=derriere {ECO:0000303|PubMed:10068640,
GN   ECO:0000303|PubMed:11256621, ECO:0000303|PubMed:12070085,
GN   ECO:0000303|PubMed:12361977, ECO:0000303|PubMed:15530392};
OS   Xenopus laevis (African clawed frog).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC   Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX   NCBI_TaxID=8355;
RN   [1] {ECO:0000305, ECO:0000312|EMBL:AAD19837.1}
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL
RP   STAGE, INDUCTION, AND MUTAGENESIS OF 237-ARG--ARG-240.
RC   TISSUE=Embryo {ECO:0000269|PubMed:10068640};
RX   PubMed=10068640; DOI=10.1242/dev.126.7.1467;
RA   Sun B.I., Bush S.M., Collins-Racie L.A., LaVallie E.R.,
RA   DiBlasio-Smith E.A., Wolfman N.M., McCoy J.M., Sive H.L.;
RT   "derriere: a TGF-beta family member required for posterior development in
RT   Xenopus.";
RL   Development 126:1467-1482(1999).
RN   [2] {ECO:0000312|EMBL:AAH73508.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Gastrula {ECO:0000312|EMBL:AAH73508.1};
RG   NIH - Xenopus Gene Collection (XGC) project;
RL   Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN   [3] {ECO:0000305, ECO:0000312|EMBL:AAM88864.1}
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-85, FUNCTION, AND INDUCTION.
RX   PubMed=12361977; DOI=10.1242/dev.129.20.4867;
RA   White R.J., Sun B.I., Sive H.L., Smith J.C.;
RT   "Direct and indirect regulation of derriere, a Xenopus mesoderm-inducing
RT   factor, by VegT.";
RL   Development 129:4867-4876(2002).
RN   [4] {ECO:0000305}
RP   FUNCTION, SUBCELLULAR LOCATION, INDUCTION, AND MUTAGENESIS OF
RP   237-ARG--ARG-240.
RX   PubMed=11256621; DOI=10.1093/embo-reports/kvd008;
RA   Hanafusa H., Masuyama N., Kusakabe M., Shibuya H., Nishida E.;
RT   "The TGF-beta family member derriere is involved in regulation of the
RT   establishment of left-right asymmetry.";
RL   EMBO Rep. 1:32-39(2000).
RN   [5] {ECO:0000305}
RP   FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, HOMODIMERIZATION,
RP   INTERACTION WITH BMP4 AND NODAL2, AND MUTAGENESIS OF 237-ARG--ARG-240.
RX   PubMed=12070085; DOI=10.1242/dev.129.13.3089;
RA   Eimon P.M., Harland R.M.;
RT   "Effects of heterodimerization and proteolytic processing on Derriere and
RT   Nodal activity: implications for mesoderm induction in Xenopus.";
RL   Development 129:3089-3103(2002).
RN   [6] {ECO:0000305}
RP   INDUCTION.
RX   PubMed=15530392; DOI=10.1016/j.cub.2004.10.020;
RA   Williams P.H., Hagemann A., Gonzalez-Gaitan M., Smith J.C.;
RT   "Visualizing long-range movement of the morphogen Xnr2 in the Xenopus
RT   embryo.";
RL   Curr. Biol. 14:1916-1923(2004).
CC   -!- FUNCTION: Required for posterior mesoderm formation during
CC       embryogenesis. Acts indirectly to suppress head formation by altering
CC       mesodermal patterning. Also involved in the establishment of left-right
CC       axis asymmetry, acting upstream of nodal/nr-1. Can exert long-range
CC       effects in the embryo. {ECO:0000269|PubMed:10068640,
CC       ECO:0000269|PubMed:11256621, ECO:0000269|PubMed:12070085,
CC       ECO:0000269|PubMed:12361977}.
CC   -!- SUBUNIT: Homodimer; disulfide-linked. Also forms heterodimers with
CC       other TGF-beta family members including nodal2/nr-2 and bmp4.
CC       {ECO:0000269|PubMed:12070085}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:11256621}. Cytoplasm
CC       {ECO:0000250|UniProtKB:Q9NR23}.
CC   -!- TISSUE SPECIFICITY: Initially expressed throughout the presumptive
CC       embryonic mesendoderm with subsequent localization to the posterior
CC       mesoderm. {ECO:0000269|PubMed:10068640, ECO:0000269|PubMed:12070085}.
CC   -!- DEVELOPMENTAL STAGE: First detected at late blastula (stage 8.5-9).
CC       Expression then increases with levels peaking during gastrulation
CC       before tapering off by neurulation (stage 13).
CC       {ECO:0000269|PubMed:10068640, ECO:0000269|PubMed:12070085}.
CC   -!- INDUCTION: By mesoderm-inducing factors including activin, basic
CC       fibroblast growth factor, nodal2/nr-2, dvr1/vg1, vegt and t/bra.
CC       Autoinduced by derriere itself. {ECO:0000269|PubMed:10068640,
CC       ECO:0000269|PubMed:11256621, ECO:0000269|PubMed:12361977,
CC       ECO:0000269|PubMed:15530392}.
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   -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000255}.
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DR   EMBL; AF065135; AAD19837.1; -; mRNA.
DR   EMBL; BC073508; AAH73508.1; -; mRNA.
DR   EMBL; AF527059; AAM88864.1; -; Genomic_DNA.
DR   RefSeq; NP_001080966.1; NM_001087497.1.
DR   AlphaFoldDB; Q9YGV1; -.
DR   SMR; Q9YGV1; -.
DR   GeneID; 394305; -.
DR   KEGG; xla:394305; -.
DR   CTD; 394305; -.
DR   Xenbase; XB-GENE-865693; gdf3.S.
DR   OrthoDB; 919690at2759; -.
DR   Proteomes; UP000186698; Chromosome 1S.
DR   Bgee; 394305; Expressed in gastrula and 4 other tissues.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0005576; C:extracellular region; IDA: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:0016015; F:morphogen activity; IMP:UniProtKB.
DR   GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR   GO; GO:0009952; P:anterior/posterior pattern specification; IMP:UniProtKB.
DR   GO; GO:0007368; P:determination of left/right symmetry; IMP:UniProtKB.
DR   GO; GO:0070986; P:left/right axis specification; IMP:BHF-UCL.
DR   GO; GO:0001707; P:mesoderm formation; IMP:UniProtKB.
DR   GO; GO:0048332; P:mesoderm morphogenesis; IMP:UniProtKB.
DR   GO; GO:0048339; P:paraxial mesoderm development; IEP:BHF-UCL.
DR   GO; GO:1900224; P:positive regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry; IMP:BHF-UCL.
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   Cleavage on pair of basic residues; Cytokine; Cytoplasm;
KW   Developmental protein; Disulfide bond; Glycoprotein; Growth factor;
KW   Reference proteome; Secreted; Signal.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   PROPEP          21..240
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000274249"
FT   CHAIN           241..354
FT                   /note="Growth/differentiation factor 3"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000274250"
FT   CARBOHYD        175
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        206
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        253..319
FT                   /evidence="ECO:0000250|UniProtKB:P09534"
FT   DISULFID        282..351
FT                   /evidence="ECO:0000250|UniProtKB:P09534"
FT   DISULFID        286..353
FT                   /evidence="ECO:0000250|UniProtKB:P09534"
FT   DISULFID        318
FT                   /note="Interchain"
FT                   /evidence="ECO:0000250|UniProtKB:P09534"
FT   MUTAGEN         237..240
FT                   /note="RAKR->GVDG: Does not undergo cleavage and is not
FT                   secreted. When overexpressed, acts as a dominant negative
FT                   to disrupt derriere function, nodal signaling, processing
FT                   and secretion of other TGF-beta members, posterior
FT                   development and left-right asymmetry. Completely inhibits
FT                   mesoderm formation."
FT                   /evidence="ECO:0000269|PubMed:10068640,
FT                   ECO:0000269|PubMed:11256621, ECO:0000269|PubMed:12070085"
SQ   SEQUENCE   354 AA;  40317 MW;  879CAE9A23F2E42F CRC64;
     MAELWLSLSC MFSLLLLTNS SPLTFQERML LKALGLNTRP NPIAPAPVPK SLRDIFEKGI
     NQDNPCMMEG FGVPGNIVRS YRDQGTIAAI EEPQGSLCLK KFLFFDLSAV ENKEQLTLGQ
     LEIKFKHNTY YGQQFHLRLY RTLQLSLKGM RDSKMNRKLL VTQSFRLLHK SLYFNLTKVA
     EDWKNPEKNM GLILEIYASS ELAGGNRSFV VCEPIQSFIY TSLLTVSLDP SNCKTQRAKR
     STHSSPPTPS NICKKRRLYI DFKDVGWQNW VIAPRGYMAN YCHGECPYPL TEMLRGTNHA
     VLQTLVHSVE PENTPLPCCA PTKLSPISML YYDNNDNVVL RHYEDMVVDE CGCK
 
 
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