GDF6_RAT
ID GDF6_RAT Reviewed; 452 AA.
AC Q6HA10; Q8K4X4;
DT 11-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=Growth/differentiation factor 6;
DE Short=GDF-6;
DE AltName: Full=Bone morphogenetic protein 13;
DE Short=BMP-13;
DE AltName: Full=Growth/differentiation factor 16;
DE Flags: Precursor;
GN Name=Gdf6; Synonyms=Bmp13, Gdf16;
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 [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RA Guo J.H.;
RT "Cloning of human Gdf16 and associated analysis.";
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 372-438.
RC TISSUE=Tooth;
RA Oida S., Morotome Y., Nakamura T., Terashima T.;
RT "Molecular cloning of PCR amplified BMP-related genes (GDF-5, 6 and 7) from
RT rat tooth cells using modified pBluescript SK+ Vector.";
RL J. Hard Tissue Biol. 6:16-20(1997).
CC -!- FUNCTION: Growth factor that controls proliferation and cellular
CC differentiation in the retina and bone formation. Plays a key role in
CC regulating apoptosis during retinal development. Establishes dorsal-
CC ventral positional information in the retina and controls the formation
CC of the retinotectal map. Required for normal formation of bones and
CC joints in the limbs, skull, digits and axial skeleton. Plays a key role
CC in establishing boundaries between skeletal elements during
CC development. Regulation of GDF6 expression seems to be a mechanism for
CC evolving species-specific changes in skeletal structures. Seems to
CC positively regulate differentiation of chondrogenic tissue through the
CC growth factor receptors subunits BMPR1A, BMPR1B, BMPR2 and ACVR2A,
CC leading to the activation of SMAD1-SMAD5-SMAD8 complex. The regulation
CC of chondrogenic differentiation is inhibited by NOG. Also involved in
CC the induction of adipogenesis from mesenchymal stem cells. This
CC mechanism acts through the growth factor receptors subunits BMPR1A,
CC BMPR2 and ACVR2A and the activation of SMAD1-SMAD5-SMAD8 complex and
CC MAPK14/p38. {ECO:0000250|UniProtKB:P43028,
CC ECO:0000250|UniProtKB:Q6KF10}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. {ECO:0000250|UniProtKB:P39905}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q6KF10}.
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; AJ537426; CAD60936.2; -; mRNA.
DR EMBL; AB087405; BAC02714.1; -; mRNA.
DR RefSeq; NP_001013056.1; NM_001013038.1.
DR AlphaFoldDB; Q6HA10; -.
DR SMR; Q6HA10; -.
DR STRING; 10116.ENSRNOP00000010266; -.
DR GlyGen; Q6HA10; 1 site.
DR PaxDb; Q6HA10; -.
DR Ensembl; ENSRNOT00000101359; ENSRNOP00000082414; ENSRNOG00000067800.
DR GeneID; 252834; -.
DR KEGG; rno:252834; -.
DR UCSC; RGD:620104; rat.
DR CTD; 392255; -.
DR RGD; 620104; Gdf6.
DR eggNOG; KOG3900; Eukaryota.
DR GeneTree; ENSGT00940000162274; -.
DR HOGENOM; CLU_020515_0_0_1; -.
DR InParanoid; Q6HA10; -.
DR OMA; KKSKYRC; -.
DR OrthoDB; 749511at2759; -.
DR PhylomeDB; Q6HA10; -.
DR TreeFam; TF316134; -.
DR PRO; PR:Q6HA10; -.
DR Proteomes; UP000002494; Chromosome 5.
DR Bgee; ENSRNOG00000007810; Expressed in esophagus and 2 other tissues.
DR Genevisible; Q6HA10; RN.
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:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0032924; P:activin receptor signaling pathway; ISO:RGD.
DR GO; GO:0006915; P:apoptotic process; ISS:UniProtKB.
DR GO; GO:0030509; P:BMP signaling pathway; ISS:UniProtKB.
DR GO; GO:0035788; P:cell migration involved in metanephros development; ISO:RGD.
DR GO; GO:0045444; P:fat cell differentiation; ISS:UniProtKB.
DR GO; GO:0001656; P:metanephros development; ISO:RGD.
DR GO; GO:0060389; P:pathway-restricted SMAD protein phosphorylation; ISO:RGD.
DR GO; GO:0032332; P:positive regulation of chondrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; ISO:RGD.
DR GO; GO:1900745; P:positive regulation of p38MAPK cascade; ISS:UniProtKB.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:1990009; P:retinal cell apoptotic process; ISS:UniProtKB.
DR GO; GO:0060395; P:SMAD protein signal transduction; ISS:UniProtKB.
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 2: Evidence at transcript level;
KW Apoptosis; Cleavage on pair of basic residues; Cytokine;
KW Developmental protein; Disulfide bond; Glycoprotein; Growth factor;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT PROPEP 23..332
FT /evidence="ECO:0000255"
FT /id="PRO_0000342208"
FT CHAIN 333..452
FT /note="Growth/differentiation factor 6"
FT /id="PRO_0000042254"
FT REGION 29..93
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 244..267
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 301..348
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 38..74
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 331..348
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 115
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 351..417
FT /evidence="ECO:0000250|UniProtKB:P39905"
FT DISULFID 380..449
FT /evidence="ECO:0000250|UniProtKB:P39905"
FT DISULFID 384..451
FT /evidence="ECO:0000250|UniProtKB:P39905"
FT DISULFID 416
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:P39905"
SQ SEQUENCE 452 AA; 51013 MW; DF756875E4C1B52A CRC64;
MDTPRVLLWA IFLISFLWDL PGFQQASISS SSSTELDSTK DVENRKGGKM QRTPQESAEG
RTPKEHRPRP NELRRRLPGQ SLGQEPPGRG PRVVPHEYML SIYRTYSIAE KLGINASFFQ
SSKSANTITS FVDRGLDDLS HTPLRRQKYL FDVSTLSDKE ELVGAELRLY RQAPPTPWGP
QTRPLHLQLF PCLSPLLLDS RTLDPQGPTE AGWEVFDVWQ VLRPQPWKQL CLELRAVWGE
LDARDSGARP RGPQQSPPLD LRSLGFGRRV RPPQERALLV VFTRSQRKNL FTEMHEQLGS
AEAAGAEGSW PAPSGAPDAG SWLPSPGRRR RRTALSSRHG KRHGKKSRLR CSRKPLHVNF
KELGWDDWII APLEYEAYHC EGVCDFPLRS HLEPTNHAII QTLMNSMDPG STPPSCCVPT
KLTPISILYI DAGNNVVYKQ YEDMVVESCG CR
