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Protein

Growth/differentiation factor 6

Gene

Gdf6

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Growth factor that controls proliferation and cellular differentiation in the retina and bone formation. Plays a key role in regulating apoptosis during retinal development. Establishes dorsal-ventral positional information in the retina and controls the formation of the retinotectal map (PubMed:23307924). Required for normal formation of bones and joints in the limbs, skull, digits and axial skeleton. Plays a key role in establishing boundaries between skeletal elements during development. Regulation of GDF6 expression seems to be a mechanism for evolving species-specific changes in skeletal strucutres (PubMed:26774823). Seems to positively regulates differentiation of chondrogenic tissue through the growth factor receptors subunits BMPR1A, BMPR1B, BMPR2 and ACVR2A, leading to the activation of SMAD1-SMAD5-SMAD8 complex. The regulation of chondrogenic differentiation is inhibited by NOG (PubMed:12606286, PubMed:16049014). Also involved in the induction of adipogenesis from mesenchymal stem cells. This mechanism acts through the growth factor receptors subunits BMPR1A, BMPR2 and ACVR2A and the activation of SMAD1-SMAD5-SMAD8 complex and MAPK14/p38 (PubMed:23527555).5 Publications

GO - Molecular functioni

  • protein homodimerization activity Source: MGI

GO - Biological processi

  • activin receptor signaling pathway Source: MGI
  • apoptotic process Source: UniProtKB
  • BMP signaling pathway Source: UniProtKB
  • fat cell differentiation Source: UniProtKB
  • growth Source: InterPro
  • pathway-restricted SMAD protein phosphorylation Source: MGI
  • positive regulation of chondrocyte differentiation Source: UniProtKB
  • positive regulation of neuron differentiation Source: MGI
  • positive regulation of p38MAPK cascade Source: UniProtKB
  • positive regulation of pathway-restricted SMAD protein phosphorylation Source: MGI
  • positive regulation of transcription, DNA-templated Source: MGI
  • retinal cell apoptotic process Source: UniProtKB
  • SMAD protein signal transduction Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Cytokine, Developmental protein, Growth factor

Keywords - Biological processi

Apoptosis

Names & Taxonomyi

Protein namesi
Recommended name:
Growth/differentiation factor 6
Short name:
GDF-6
Alternative name(s):
Bone morphogenetic protein 13
Short name:
BMP-13
Growth/differentiation factor 16
Gene namesi
Name:Gdf6
Synonyms:Bmp13, Gdf-6, Gdf16
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:95689. Gdf6.

Subcellular locationi

  • Secreted By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Disruption phenotypei

Mice lacking GDF6 display photoreceptor degeneration. Animals exhibit abnormal electroretinograms with up to 66% decreases in the bipolar cell-driven b-wave and 54% decreases in the photoreceptor-mediated a-wave amplitudes, as well as 3 to 27% reduced photopic flicker fusion. The lengths, but not the widths, of dermal flat bones in the skull and the digits are significantly shorter than in wild type (PubMed:26774823).2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2222Sequence analysisAdd
BLAST
Propeptidei23 – 334312Sequence analysisPRO_0000342207Add
BLAST
Chaini335 – 454120Growth/differentiation factor 6PRO_0000033919Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi117 – 1171N-linked (GlcNAc...)Sequence analysis
Disulfide bondi353 ↔ 419By similarity
Disulfide bondi382 ↔ 451By similarity
Disulfide bondi386 ↔ 453By similarity
Disulfide bondi418 – 418InterchainBy similarity

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP43028.
PRIDEiP43028.

PTM databases

iPTMnetiP43028.

Expressioni

Tissue specificityi

Expressed in different subsets of developing joints.1 Publication

Inductioni

Strongly up-regulated in tibialis anterior muscles after denervation.1 Publication

Gene expression databases

BgeeiP43028.
CleanExiMM_GDF6.
ExpressionAtlasiP43028. baseline and differential.

Interactioni

Subunit structurei

Homodimer; disulfide-linked.By similarity

GO - Molecular functioni

  • protein homodimerization activity Source: MGI

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000062884.

Structurei

3D structure databases

ProteinModelPortaliP43028.
SMRiP43028. Positions 352-454.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi27 – 359Poly-Ser
Compositional biasi330 – 3345Poly-Arg

Sequence similaritiesi

Belongs to the TGF-beta family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3900. Eukaryota.
ENOG410XT8Z. LUCA.
GeneTreeiENSGT00760000118883.
HOGENOMiHOG000231514.
HOVERGENiHBG107938.
InParanoidiP43028.
KOiK20012.
OMAiFTRSQRK.
OrthoDBiEOG7WMCK0.
PhylomeDBiP43028.
TreeFamiTF316134.

Family and domain databases

Gene3Di2.10.90.10. 1 hit.
InterProiIPR029034. Cystine-knot_cytokine.
IPR002405. Inhibin_asu.
IPR001839. TGF-b_C.
IPR001111. TGF-b_N.
IPR015615. TGF-beta-rel.
IPR017948. TGFb_CS.
[Graphical view]
PANTHERiPTHR11848. PTHR11848. 2 hits.
PfamiPF00019. TGF_beta. 1 hit.
PF00688. TGFb_propeptide. 1 hit.
[Graphical view]
PRINTSiPR00669. INHIBINA.
SMARTiSM00204. TGFB. 1 hit.
[Graphical view]
SUPFAMiSSF57501. SSF57501. 1 hit.
PROSITEiPS00250. TGF_BETA_1. 1 hit.
PS51362. TGF_BETA_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P43028-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDTPRVLLWA IFLISFLWDL PGFQQASISS SSSSSTELDS TKDVGNRKEG
60 70 80 90 100
KMQRTPQESA EGRTPPEHGL RQKDLRRRPP GQHQGQEPPG RGLRVVPHEY
110 120 130 140 150
MLSIYKTYSI AEKLGINASF FQSSKSANTI TSFVDRGLDD LSHTPLRRQK
160 170 180 190 200
YLFDVSTLSD KEELVGAELR LYRQAPPTPW GLPARPLHLQ LFPCLSPLLL
210 220 230 240 250
DARTLDPQGP TQAGWEVFDV WQGLRPQPWK QLCLELRAAW GELDAGDTGA
260 270 280 290 300
RARGPQQPPP LDLRSLGFGR RVRPPQERAL LVVFTRSQRK NLFTEMHEQL
310 320 330 340 350
GSAEAAGAEG SWPAPSGSPD AGSWLPSPGR RRRRTAFASR HGKRHGKKSR
360 370 380 390 400
LRCSRKPLHV NFKELGWDDW IIAPLEYEAY HCEGVCDFPL RSHLEPTNHA
410 420 430 440 450
IIQTLMNSMD PGSTPPSCCV PTKLTPISIL YIDAGNNVVY KQYEDMVVES

CGCR
Length:454
Mass (Da):50,942
Last modified:October 11, 2005 - v2
Checksum:i5A3FADDA539CCB38
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ537425 mRNA. Translation: CAD60935.1.
U08338 Unassigned DNA. Translation: AAA18779.1.
CCDSiCCDS17960.1.
PIRiS43295.
RefSeqiNP_038554.1. NM_013526.1.
UniGeneiMm.302555.

Genome annotation databases

EnsembliENSMUST00000057613; ENSMUSP00000062884; ENSMUSG00000051279.
GeneIDi242316.
KEGGimmu:242316.
UCSCiuc008ryt.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ537425 mRNA. Translation: CAD60935.1.
U08338 Unassigned DNA. Translation: AAA18779.1.
CCDSiCCDS17960.1.
PIRiS43295.
RefSeqiNP_038554.1. NM_013526.1.
UniGeneiMm.302555.

3D structure databases

ProteinModelPortaliP43028.
SMRiP43028. Positions 352-454.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000062884.

PTM databases

iPTMnetiP43028.

Proteomic databases

PaxDbiP43028.
PRIDEiP43028.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000057613; ENSMUSP00000062884; ENSMUSG00000051279.
GeneIDi242316.
KEGGimmu:242316.
UCSCiuc008ryt.1. mouse.

Organism-specific databases

CTDi392255.
MGIiMGI:95689. Gdf6.

Phylogenomic databases

eggNOGiKOG3900. Eukaryota.
ENOG410XT8Z. LUCA.
GeneTreeiENSGT00760000118883.
HOGENOMiHOG000231514.
HOVERGENiHBG107938.
InParanoidiP43028.
KOiK20012.
OMAiFTRSQRK.
OrthoDBiEOG7WMCK0.
PhylomeDBiP43028.
TreeFamiTF316134.

Miscellaneous databases

PROiP43028.
SOURCEiSearch...

Gene expression databases

BgeeiP43028.
CleanExiMM_GDF6.
ExpressionAtlasiP43028. baseline and differential.

Family and domain databases

Gene3Di2.10.90.10. 1 hit.
InterProiIPR029034. Cystine-knot_cytokine.
IPR002405. Inhibin_asu.
IPR001839. TGF-b_C.
IPR001111. TGF-b_N.
IPR015615. TGF-beta-rel.
IPR017948. TGFb_CS.
[Graphical view]
PANTHERiPTHR11848. PTHR11848. 2 hits.
PfamiPF00019. TGF_beta. 1 hit.
PF00688. TGFb_propeptide. 1 hit.
[Graphical view]
PRINTSiPR00669. INHIBINA.
SMARTiSM00204. TGFB. 1 hit.
[Graphical view]
SUPFAMiSSF57501. SSF57501. 1 hit.
PROSITEiPS00250. TGF_BETA_1. 1 hit.
PS51362. TGF_BETA_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Cloning of human GDF16 and functional assocatied analysis."
    Guo J.H.
    Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Kunming.
    Tissue: Brain.
  2. "Limb alterations in brachypodism mice due to mutations in a new member of the TGF beta-superfamily."
    Storm E.E., Huynh T.V., Copeland N.G., Jenkins N.A., Kingsley D.M., Lee S.-J.
    Nature 368:639-643(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 330-454.
    Strain: BALB/cJ.
    Tissue: Liver.
  3. "Multiple joint and skeletal patterning defects caused by single and double mutations in the mouse Gdf6 and Gdf5 genes."
    Settle S.H. Jr., Rountree R.B., Sinha A., Thacker A., Higgins K., Kingsley D.M.
    Dev. Biol. 254:116-130(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY.
  4. "Identification of receptors and signaling pathways for orphan bone morphogenetic protein/growth differentiation factor ligands based on genomic analyses."
    Mazerbourg S., Sangkuhl K., Luo C.-W., Sudo S., Klein C., Hsueh A.J.W.
    J. Biol. Chem. 280:32122-32132(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, IDENTIFICATION OF RECEPTORS.
  5. "Gdf6 induces commitment of pluripotent mesenchymal C3H10T1/2 cells to the adipocyte lineage."
    Wang S.S., Huang H.Y., Chen S.Z., Li X., Zhang W.T., Tang Q.Q.
    FEBS J. 280:2644-2651(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  6. Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  7. Cited for: INDUCTION.
  8. "Evolving new skeletal traits by cis-regulatory changes in bone morphogenetic proteins."
    Indjeian V.B., Kingman G.A., Jones F.C., Guenther C.A., Grimwood J., Schmutz J., Myers R.M., Kingsley D.M.
    Cell 164:45-56(2016) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.

Entry informationi

Entry nameiGDF6_MOUSE
AccessioniPrimary (citable) accession number: P43028
Secondary accession number(s): Q70UT4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: October 11, 2005
Last modified: June 8, 2016
This is version 121 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.