Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Growth/differentiation factor 6

Gene

GDF6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 strucutres. 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: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

  • activin receptor signaling pathway Source: BHF-UCL
  • apoptotic process Source: UniProtKB
  • BMP signaling pathway Source: BHF-UCL
  • cell development Source: GO_Central
  • fat cell differentiation Source: UniProtKB
  • growth Source: InterPro
  • pathway-restricted SMAD protein phosphorylation Source: BHF-UCL
  • positive regulation of chondrocyte differentiation Source: UniProtKB
  • positive regulation of neuron differentiation Source: Ensembl
  • positive regulation of p38MAPK cascade Source: UniProtKB
  • positive regulation of pathway-restricted SMAD protein phosphorylation Source: BHF-UCL
  • positive regulation of transcription, DNA-templated Source: BHF-UCL
  • regulation of apoptotic process Source: GO_Central
  • regulation of MAPK cascade Source: GO_Central
  • 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

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

HGNCiHGNC:4221. GDF6.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

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 rs121909354dbSNPEnsembl.1
Natural variantiVAR_046903249A → E in KFS1, MCOP4 and LCA17; reduced protein expression associated with decrease in growth factor activity. 3 PublicationsCorresponds to variant rs121909352dbSNPEnsembl.1
Natural variantiVAR_046904289L → P in KFS1. 1 PublicationCorresponds to variant rs63751220dbSNPEnsembl.1
Natural variantiVAR_063029424K → R in KFS1. 1 PublicationCorresponds to variant rs121909353dbSNPEnsembl.1

A chromosomal aberration involving GDF6 has been found in a patient with Klippel-Feil syndrome (KFS). Paracentric inv(8)(q22;2q23.3).

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 rs140579014dbSNPEnsembl.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 rs121909352dbSNPEnsembl.1
Natural variantiVAR_063027253Q → L in MCOP4. 1 PublicationCorresponds to variant rs121909355dbSNPEnsembl.1
Natural variantiVAR_063028327P → H in MCOP4. 1 PublicationCorresponds to variant rs121909356dbSNPEnsembl.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 rs397514725dbSNPEnsembl.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 rs387906794dbSNPEnsembl.1
Natural variantiVAR_046903249A → E in KFS1, MCOP4 and LCA17; reduced protein expression associated with decrease in growth factor activity. 3 PublicationsCorresponds to variant rs121909352dbSNPEnsembl.1
Natural variantiVAR_070255292E → D in LCA17; increased protein expression associated with decrease in growth factor activity. 1 Publication1

Defects in POP1 may be the cause of multiple synostoses syndrome (SYNS). SYNS is a bone disease characterized by multiple progressive joint fusions that commonly involve proximal interphalangeal, tarsal-carpal joints. Additional features can include progressive conductive deafness.

Keywords - Diseasei

Disease mutation, Dwarfism, Leber congenital amaurosis, Microphthalmia

Organism-specific databases

DisGeNETi392255.
MalaCardsiGDF6.
MIMi118100. phenotype.
613094. phenotype.
615360. 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...)Sequence 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.

PTM databases

iPTMnetiQ6KF10.
PhosphoSitePlusiQ6KF10.

Expressioni

Gene expression databases

BgeeiENSG00000156466.
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.
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.
OMAiFTRSQRK.
OrthoDBiEOG091G09KP.
PhylomeDBiQ6KF10.
TreeFamiTF316134.

Family and domain databases

Gene3Di2.10.90.10. 1 hit.
InterProiIPR029034. Cystine-knot_cytokine.
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]
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.

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

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 rs121909354dbSNPEnsembl.1
Natural variantiVAR_07025457D → H in LCA17; reduced protein expression associated with decrease in growth factor activity. 1 PublicationCorresponds to variant rs397514725dbSNPEnsembl.1
Natural variantiVAR_023599110K → E.Corresponds to variant rs2245091dbSNPEnsembl.1
Natural variantiVAR_063025119Q → R in MCOP4. 1 PublicationCorresponds to variant rs140579014dbSNPEnsembl.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 rs387906794dbSNPEnsembl.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 rs121909352dbSNPEnsembl.1
Natural variantiVAR_063027253Q → L in MCOP4. 1 PublicationCorresponds to variant rs121909355dbSNPEnsembl.1
Natural variantiVAR_046904289L → P in KFS1. 1 PublicationCorresponds to variant rs63751220dbSNPEnsembl.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 rs121909356dbSNPEnsembl.1
Natural variantiVAR_063029424K → R in KFS1. 1 PublicationCorresponds to variant rs121909353dbSNPEnsembl.1
Natural variantiVAR_075366444Y → N Probable disease-associated mutation found in patients with multiple synostoses syndrome; 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

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.
STRINGi9606.ENSP00000287020.

PTM databases

iPTMnetiQ6KF10.
PhosphoSitePlusiQ6KF10.

Polymorphism and mutation databases

BioMutaiGDF6.
DMDMi74748876.

Proteomic databases

PaxDbiQ6KF10.
PeptideAtlasiQ6KF10.
PRIDEiQ6KF10.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi392255.
DisGeNETi392255.
GeneCardsiGDF6.
HGNCiHGNC:4221. GDF6.
HPAiHPA045206.
MalaCardsiGDF6.
MIMi118100. phenotype.
601147. gene.
613094. phenotype.
615360. 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.
OMAiFTRSQRK.
OrthoDBiEOG091G09KP.
PhylomeDBiQ6KF10.
TreeFamiTF316134.

Enzyme and pathway databases

SignaLinkiQ6KF10.
SIGNORiQ6KF10.

Miscellaneous databases

GeneWikiiGDF6.
GenomeRNAii392255.
PROiQ6KF10.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000156466.
CleanExiHS_GDF6.
ExpressionAtlasiQ6KF10. baseline and differential.

Family and domain databases

Gene3Di2.10.90.10. 1 hit.
InterProiIPR029034. Cystine-knot_cytokine.
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]
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...

Entry informationi

Entry nameiGDF6_HUMAN
AccessioniPrimary (citable) accession number: Q6KF10
Secondary accession number(s): Q6PI58
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 11, 2005
Last sequence update: July 5, 2004
Last modified: November 2, 2016
This is version 111 of the entry and version 1 of the sequence. [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. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  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. 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.