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Protein

Growth/differentiation factor 6

Gene

GDF6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein 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 structures. Seems to positively regulate 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:26643732). 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 (By similarity).By similarity2 Publications

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionCytokine, Developmental protein, Growth factor
Biological processApoptosis

Enzyme and pathway databases

SignaLinkiQ6KF10
SIGNORiQ6KF10

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, GDF16
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000156466.9
HGNCiHGNC:4221 GDF6
MIMi601147 gene
neXtProtiNX_Q6KF10

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Klippel-Feil syndrome 1, autosomal dominant (KFS1)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA skeletal disorder characterized by congenital fusion of cervical vertebrae. It is due to a failure in the normal segmentation of vertebrae during the early weeks of fetal development. The clinical triad consists of short neck, low posterior hairline, and limited neck movement. Deafness is a feature in some cases and may be of sensorineural, conductive, or mixed type.
See also OMIM:118100
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06302442G → V in KFS1. 2 PublicationsCorresponds to variant dbSNP:rs121909354EnsemblClinVar.1
Natural variantiVAR_046903249A → E in KFS1, MCOP4 and LCA17; reduced protein expression associated with decrease in growth factor activity. 3 PublicationsCorresponds to variant dbSNP:rs121909352EnsemblClinVar.1
Natural variantiVAR_046904289L → P in KFS1. 1 PublicationCorresponds to variant dbSNP:rs63751220EnsemblClinVar.1
Natural variantiVAR_063029424K → R in KFS1. 1 PublicationCorresponds to variant dbSNP:rs121909353EnsemblClinVar.1
A chromosomal aberration involving GDF6 has been found in a patient with Klippel-Feil syndrome (KFS). Paracentric inv(8)(q22;2q23.3).1 Publication
Microphthalmia, isolated, 4 (MCOP4)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, and other abnormalities may also be present.
See also OMIM:613094
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_063025119Q → R in MCOP4. 1 PublicationCorresponds to variant dbSNP:rs140579014EnsemblClinVar.1
Natural variantiVAR_063026216D → G in MCOP4. 1 Publication1
Natural variantiVAR_063027253Q → L in MCOP4. 1 PublicationCorresponds to variant dbSNP:rs121909355EnsemblClinVar.1
Natural variantiVAR_063028327P → H in MCOP4. 1 PublicationCorresponds to variant dbSNP:rs121909356EnsemblClinVar.1
Leber congenital amaurosis 17 (LCA17)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or almost absent pupillary responses, photophobia, high hyperopia and keratoconus.
See also OMIM:615360
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07025457D → H in LCA17; reduced protein expression associated with decrease in growth factor activity. 1 PublicationCorresponds to variant dbSNP:rs397514725EnsemblClinVar.1
Natural variantiVAR_065151199A → T in LCA17; found also in a patient with microphthalmia isolated with coloboma type 6 carrying a mutation in GDF3; reduced protein expression associated with decrease in growth factor activity. 2 PublicationsCorresponds to variant dbSNP:rs387906794EnsemblClinVar.1
Natural variantiVAR_070255292E → D in LCA17; increased protein expression associated with decrease in growth factor activity. 1 Publication1
Multiple synostoses syndrome 4 (SYNS4)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA bone disease characterized by multiple progressive joint fusions that commonly involve proximal interphalangeal, tarsal-carpal, humeroradial and cervical spine joints. Additional features can include progressive conductive deafness and facial dysmorphism. SYNS4 inheritance is autosomal dominant.
See also OMIM:617898
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_080489429S → R in SYNS4; unknown pathological significance. 1 Publication1
Natural variantiVAR_075366444Y → N in SYNS4; increases chondrogenic activity; increases SMAD1/5/8 signaling pathway activation; not inhibited by NOG. 1 Publication1

Keywords - Diseasei

Disease mutation, Dwarfism, Leber congenital amaurosis, Microphthalmia

Organism-specific databases

DisGeNETi392255
MalaCardsiGDF6
MIMi118100 phenotype
613094 phenotype
615360 phenotype
617898 phenotype
OpenTargetsiENSG00000156466
Orphaneti98938 Colobomatous microphthalmia
2345 Isolated Klippel-Feil syndrome
65 Leber congenital amaurosis
PharmGKBiPA28636

Polymorphism and mutation databases

BioMutaiGDF6
DMDMi74748876

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 22Sequence analysisAdd BLAST22
PropeptideiPRO_000034220623 – 335Sequence analysisAdd BLAST313
ChainiPRO_0000042253336 – 455Growth/differentiation factor 6Add BLAST120

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi114N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi354 ↔ 420By similarity
Disulfide bondi383 ↔ 452By similarity
Disulfide bondi387 ↔ 454By similarity
Disulfide bondi419InterchainBy similarity

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ6KF10
PeptideAtlasiQ6KF10
PRIDEiQ6KF10
ProteomicsDBi66547

PTM databases

iPTMnetiQ6KF10
PhosphoSitePlusiQ6KF10

Expressioni

Gene expression databases

BgeeiENSG00000156466 Expressed in 67 organ(s), highest expression level in placenta
CleanExiHS_GDF6
ExpressionAtlasiQ6KF10 baseline and differential

Organism-specific databases

HPAiHPA045206

Interactioni

Subunit structurei

Homodimer; disulfide-linked.By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi134147, 3 interactors
IntActiQ6KF10, 1 interactor
STRINGi9606.ENSP00000287020

Structurei

3D structure databases

ProteinModelPortaliQ6KF10
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi27 – 34Poly-Ser8
Compositional biasi255 – 258Poly-Pro4
Compositional biasi331 – 335Poly-Arg5

Sequence similaritiesi

Belongs to the TGF-beta family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3900 Eukaryota
ENOG410XT8Z LUCA
GeneTreeiENSGT00760000118883
HOGENOMiHOG000231514
HOVERGENiHBG107938
InParanoidiQ6KF10
KOiK20012
OMAiMNSMDPN
OrthoDBiEOG091G09KP
PhylomeDBiQ6KF10
TreeFamiTF316134

Family and domain databases

Gene3Di2.10.90.10, 1 hit
InterProiView protein in InterPro
IPR029034 Cystine-knot_cytokine
IPR001839 TGF-b_C
IPR001111 TGF-b_propeptide
IPR015615 TGF-beta-rel
IPR017948 TGFb_CS
PANTHERiPTHR11848 PTHR11848, 1 hit
PfamiView protein in Pfam
PF00019 TGF_beta, 1 hit
PF00688 TGFb_propeptide, 1 hit
SMARTiView protein in SMART
SM00204 TGFB, 1 hit
SUPFAMiSSF57501 SSF57501, 1 hit
PROSITEiView protein in PROSITE
PS00250 TGF_BETA_1, 1 hit
PS51362 TGF_BETA_2, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

Q6KF10-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MDTPRVLLSA VFLISFLWDL PGFQQASISS SSSSAELGST KGMRSRKEGK
60 70 80 90 100
MQRAPRDSDA GREGQEPQPR PQDEPRAQQP RAQEPPGRGP RVVPHEYMLS
110 120 130 140 150
IYRTYSIAEK LGINASFFQS SKSANTITSF VDRGLDDLSH TPLRRQKYLF
160 170 180 190 200
DVSMLSDKEE LVGAELRLFR QAPSAPWGPP AGPLHVQLFP CLSPLLLDAR
210 220 230 240 250
TLDPQGAPPA GWEVFDVWQG LRHQPWKQLC LELRAAWGEL DAGEAEARAR
260 270 280 290 300
GPQQPPPPDL RSLGFGRRVR PPQERALLVV FTRSQRKNLF AEMREQLGSA
310 320 330 340 350
EAAGPGAGAE GSWPPPSGAP DARPWLPSPG RRRRRTAFAS RHGKRHGKKS
360 370 380 390 400
RLRCSKKPLH VNFKELGWDD WIIAPLEYEA YHCEGVCDFP LRSHLEPTNH
410 420 430 440 450
AIIQTLMNSM DPGSTPPSCC VPTKLTPISI LYIDAGNNVV YKQYEDMVVE

SCGCR
Length:455
Mass (Da):50,662
Last modified:July 5, 2004 - v1
Checksum:iF9F365B99E8C659C
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0PK22A0PK22_HUMAN
GDF6 protein
GDF6
271Annotation score:
A0A087X0X2A0A087X0X2_HUMAN
Growth/differentiation factor 6
GDF6
353Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti255P → L in AAH43222 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06302442G → V in KFS1. 2 PublicationsCorresponds to variant dbSNP:rs121909354EnsemblClinVar.1
Natural variantiVAR_07025457D → H in LCA17; reduced protein expression associated with decrease in growth factor activity. 1 PublicationCorresponds to variant dbSNP:rs397514725EnsemblClinVar.1
Natural variantiVAR_023599110K → E. Corresponds to variant dbSNP:rs2245091Ensembl.1
Natural variantiVAR_063025119Q → R in MCOP4. 1 PublicationCorresponds to variant dbSNP:rs140579014EnsemblClinVar.1
Natural variantiVAR_065151199A → T in LCA17; found also in a patient with microphthalmia isolated with coloboma type 6 carrying a mutation in GDF3; reduced protein expression associated with decrease in growth factor activity. 2 PublicationsCorresponds to variant dbSNP:rs387906794EnsemblClinVar.1
Natural variantiVAR_063026216D → G in MCOP4. 1 Publication1
Natural variantiVAR_046903249A → E in KFS1, MCOP4 and LCA17; reduced protein expression associated with decrease in growth factor activity. 3 PublicationsCorresponds to variant dbSNP:rs121909352EnsemblClinVar.1
Natural variantiVAR_063027253Q → L in MCOP4. 1 PublicationCorresponds to variant dbSNP:rs121909355EnsemblClinVar.1
Natural variantiVAR_046904289L → P in KFS1. 1 PublicationCorresponds to variant dbSNP:rs63751220EnsemblClinVar.1
Natural variantiVAR_070255292E → D in LCA17; increased protein expression associated with decrease in growth factor activity. 1 Publication1
Natural variantiVAR_063028327P → H in MCOP4. 1 PublicationCorresponds to variant dbSNP:rs121909356EnsemblClinVar.1
Natural variantiVAR_063029424K → R in KFS1. 1 PublicationCorresponds to variant dbSNP:rs121909353EnsemblClinVar.1
Natural variantiVAR_080489429S → R in SYNS4; unknown pathological significance. 1 Publication1
Natural variantiVAR_075366444Y → N in SYNS4; increases chondrogenic activity; increases SMAD1/5/8 signaling pathway activation; not inhibited by NOG. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ537424 mRNA Translation: CAD60934.1
BC043222 mRNA Translation: AAH43222.1
CCDSiCCDS34926.1
RefSeqiNP_001001557.1, NM_001001557.3
UniGeneiHs.492277

Genome annotation databases

EnsembliENST00000287020; ENSP00000287020; ENSG00000156466
GeneIDi392255
KEGGihsa:392255
UCSCiuc003yhp.3 human

Keywords - Coding sequence diversityi

Chromosomal rearrangement, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ537424 mRNA Translation: CAD60934.1
BC043222 mRNA Translation: AAH43222.1
CCDSiCCDS34926.1
RefSeqiNP_001001557.1, NM_001001557.3
UniGeneiHs.492277

3D structure databases

ProteinModelPortaliQ6KF10
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi134147, 3 interactors
IntActiQ6KF10, 1 interactor
STRINGi9606.ENSP00000287020

PTM databases

iPTMnetiQ6KF10
PhosphoSitePlusiQ6KF10

Polymorphism and mutation databases

BioMutaiGDF6
DMDMi74748876

Proteomic databases

PaxDbiQ6KF10
PeptideAtlasiQ6KF10
PRIDEiQ6KF10
ProteomicsDBi66547

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000287020; ENSP00000287020; ENSG00000156466
GeneIDi392255
KEGGihsa:392255
UCSCiuc003yhp.3 human

Organism-specific databases

CTDi392255
DisGeNETi392255
EuPathDBiHostDB:ENSG00000156466.9
GeneCardsiGDF6
HGNCiHGNC:4221 GDF6
HPAiHPA045206
MalaCardsiGDF6
MIMi118100 phenotype
601147 gene
613094 phenotype
615360 phenotype
617898 phenotype
neXtProtiNX_Q6KF10
OpenTargetsiENSG00000156466
Orphaneti98938 Colobomatous microphthalmia
2345 Isolated Klippel-Feil syndrome
65 Leber congenital amaurosis
PharmGKBiPA28636
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3900 Eukaryota
ENOG410XT8Z LUCA
GeneTreeiENSGT00760000118883
HOGENOMiHOG000231514
HOVERGENiHBG107938
InParanoidiQ6KF10
KOiK20012
OMAiMNSMDPN
OrthoDBiEOG091G09KP
PhylomeDBiQ6KF10
TreeFamiTF316134

Enzyme and pathway databases

SignaLinkiQ6KF10
SIGNORiQ6KF10

Miscellaneous databases

GeneWikiiGDF6
GenomeRNAii392255
PROiPR:Q6KF10
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000156466 Expressed in 67 organ(s), highest expression level in placenta
CleanExiHS_GDF6
ExpressionAtlasiQ6KF10 baseline and differential

Family and domain databases

Gene3Di2.10.90.10, 1 hit
InterProiView protein in InterPro
IPR029034 Cystine-knot_cytokine
IPR001839 TGF-b_C
IPR001111 TGF-b_propeptide
IPR015615 TGF-beta-rel
IPR017948 TGFb_CS
PANTHERiPTHR11848 PTHR11848, 1 hit
PfamiView protein in Pfam
PF00019 TGF_beta, 1 hit
PF00688 TGFb_propeptide, 1 hit
SMARTiView protein in SMART
SM00204 TGFB, 1 hit
SUPFAMiSSF57501 SSF57501, 1 hit
PROSITEiView protein in PROSITE
PS00250 TGF_BETA_1, 1 hit
PS51362 TGF_BETA_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiGDF6_HUMAN
AccessioniPrimary (citable) accession number: Q6KF10
Secondary accession number(s): Q6PI58
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 11, 2005
Last sequence update: July 5, 2004
Last modified: November 7, 2018
This is version 120 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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