Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q6KF10 (GDF6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 91. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:GDF6
Synonyms:BMP13, GDF16
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length455 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Required for normal formation of bones and joints in the limbs, skull, and axial skeleton. Plays a key role in establishing boundaries between skeletal elements during development. May signal through the growth factor receptors subunits BMPR1A, BMPR1B, BMPR2 and ACVR2A. Ref.4

Subunit structure

Homodimer; disulfide-linked By similarity.

Subcellular location

Secreted Ref.4.

Involvement in disease

Klippel-Feil syndrome 1, autosomal dominant (KFS1) [MIM:118100]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.3 Ref.5

A chromosomal aberration involving GDF6 has been found in a patient with Klippel-Feil syndrome (KFS). Paracentric inv8(q22;2q23.3). Ref.3 Ref.5

Microphthalmia, isolated, 4 (MCOP4) [MIM:613094]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5

Leber congenital amaurosis 17 (LCA17) [MIM:615360]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4

Sequence similarities

Belongs to the TGF-beta family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222 Potential
Propeptide23 – 335313 Potential
PRO_0000342206
Chain336 – 455120Growth/differentiation factor 6
PRO_0000042253

Regions

Compositional bias27 – 348Poly-Ser
Compositional bias255 – 2584Poly-Pro
Compositional bias331 – 3355Poly-Arg

Amino acid modifications

Glycosylation1141N-linked (GlcNAc...) Potential
Disulfide bond354 ↔ 420 By similarity
Disulfide bond383 ↔ 452 By similarity
Disulfide bond387 ↔ 454 By similarity
Disulfide bond419Interchain By similarity

Natural variations

Natural variant421G → V in KFS1. Ref.5
Corresponds to variant rs121909354 [ dbSNP | Ensembl ].
VAR_063024
Natural variant571D → H in LCA17; reduced protein expression associated with decrease in growth factor activity. Ref.4
VAR_070254
Natural variant1101K → E.
Corresponds to variant rs2245091 [ dbSNP | Ensembl ].
VAR_023599
Natural variant1191Q → R in MCOP4. Ref.5
Corresponds to variant rs140579014 [ dbSNP | Ensembl ].
VAR_063025
Natural variant1991A → 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. Ref.4 Ref.6
VAR_065151
Natural variant2161D → G in MCOP4. Ref.5
VAR_063026
Natural variant2491A → E in KFS1, MCOP4 and LCA17; reduced protein expression associated with decrease in growth factor activity. Ref.3 Ref.4 Ref.5
VAR_046903
Natural variant2531Q → L in MCOP4. Ref.5
VAR_063027
Natural variant2891L → P in KFS1. Ref.3
VAR_046904
Natural variant2921E → D in LCA17; increased protein expression associated with decrease in growth factor activity. Ref.4
VAR_070255
Natural variant3271P → H in MCOP4. Ref.5
VAR_063028
Natural variant4241K → R in KFS1. Ref.5
Corresponds to variant rs121909353 [ dbSNP | Ensembl ].
VAR_063029

Experimental info

Sequence conflict2551P → L in AAH43222. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q6KF10 [UniParc].

Last modified July 5, 2004. Version 1.
Checksum: F9F365B99E8C659C

FASTA45550,662
        10         20         30         40         50         60 
MDTPRVLLSA VFLISFLWDL PGFQQASISS SSSSAELGST KGMRSRKEGK MQRAPRDSDA 

        70         80         90        100        110        120 
GREGQEPQPR PQDEPRAQQP RAQEPPGRGP RVVPHEYMLS IYRTYSIAEK LGINASFFQS 

       130        140        150        160        170        180 
SKSANTITSF VDRGLDDLSH TPLRRQKYLF DVSMLSDKEE LVGAELRLFR QAPSAPWGPP 

       190        200        210        220        230        240 
AGPLHVQLFP CLSPLLLDAR TLDPQGAPPA GWEVFDVWQG LRHQPWKQLC LELRAAWGEL 

       250        260        270        280        290        300 
DAGEAEARAR GPQQPPPPDL RSLGFGRRVR PPQERALLVV FTRSQRKNLF AEMREQLGSA 

       310        320        330        340        350        360 
EAAGPGAGAE GSWPPPSGAP DARPWLPSPG RRRRRTAFAS RHGKRHGKKS RLRCSKKPLH 

       370        380        390        400        410        420 
VNFKELGWDD WIIAPLEYEA YHCEGVCDFP LRSHLEPTNH AIIQTLMNSM DPGSTPPSCC 

       430        440        450 
VPTKLTPISI LYIDAGNNVV YKQYEDMVVE SCGCR 

« Hide

References

« Hide 'large scale' references
[1]"Cloning of human GDF16 and functional associated analysis."
Guo J.H.
Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Hindbrain.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 255-455.
Tissue: Testis.
[3]"Mutations in GDF6 are associated with vertebral segmentation defects in Klippel-Feil syndrome."
Tassabehji M., Fang Z.M., Hilton E.N., McGaughran J., Zhao Z., de Bock C.E., Howard E., Malass M., Donnai D., Diwan A., Manson F.D.C., Murrell D., Clarke R.A.
Hum. Mutat. 29:1017-1027(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: CHROMOSOMAL REARRANGEMENT, VARIANTS KFS1 GLU-249 AND PRO-289.
[4]"Contribution of growth differentiation factor 6-dependent cell survival to early-onset retinal dystrophies."
Asai-Coakwell M., March L., Dai X.H., Duval M., Lopez I., French C.R., Famulski J., De Baere E., Francis P.J., Sundaresan P., Sauve Y., Koenekoop R.K., Berry F.B., Allison W.T., Waskiewicz A.J., Lehmann O.J.
Hum. Mol. Genet. 22:1432-1442(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, VARIANTS LCA17 HIS-57; THR-199; GLU-249 AND ASP-292, CHARACTERIZATION OF VARIANTS LCA17 HIS-57; THR-199; GLU-249 AND ASP-292.
[5]"Incomplete penetrance and phenotypic variability characterize Gdf6-attributable oculo-skeletal phenotypes."
Asai-Coakwell M., French C.R., Ye M., Garcha K., Bigot K., Perera A.G., Staehling-Hampton K., Mema S.C., Chanda B., Mushegian A., Bamforth S., Doschak M.R., Li G., Dobbs M.B., Giampietro P.F., Brooks B.P., Vijayalakshmi P., Sauve Y. expand/collapse author list , Abitbol M., Sundaresan P., van Heyningen V., Pourquie O., Underhill T.M., Waskiewicz A.J., Lehmann O.J.
Hum. Mol. Genet. 18:1110-1121(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MCOP4 ARG-119; GLY-216; GLU-249; LEU-253 AND HIS-327, VARIANTS KFS1 VAL-42 AND ARG-424.
[6]"Mutation of the bone morphogenetic protein GDF3 causes ocular and skeletal anomalies."
Ye M., Berry-Wynne K.M., Asai-Coakwell M., Sundaresan P., Footz T., French C.R., Abitbol M., Fleisch V.C., Corbett N., Allison W.T., Drummond G., Walter M.A., Underhill T.M., Waskiewicz A.J., Lehmann O.J.
Hum. Mol. Genet. 19:287-298(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT THR-199.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ537424 mRNA. Translation: CAD60934.1.
BC043222 mRNA. Translation: AAH43222.1.
RefSeqNP_001001557.1. NM_001001557.2.
UniGeneHs.492277.

3D structure databases

ProteinModelPortalQ6KF10.
SMRQ6KF10. Positions 353-455.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid134147. 3 interactions.
STRING9606.ENSP00000287020.

Polymorphism databases

DMDM74748876.

Proteomic databases

PaxDbQ6KF10.
PRIDEQ6KF10.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000287020; ENSP00000287020; ENSG00000156466.
GeneID392255.
KEGGhsa:392255.
UCSCuc003yhp.3. human.

Organism-specific databases

CTD392255.
GeneCardsGC08M097223.
HGNCHGNC:4221. GDF6.
HPAHPA045206.
MIM118100. phenotype.
601147. gene.
613094. phenotype.
615360. phenotype.
neXtProtNX_Q6KF10.
Orphanet98938. Colobomatous microphthalmia.
2345. Isolated Klippel-Feil syndrome.
65. Leber congenital amaurosis.
PharmGKBPA28636.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG317866.
HOGENOMHOG000231514.
HOVERGENHBG107938.
InParanoidQ6KF10.
KOK04664.
OMAFTRSQRK.
OrthoDBEOG7WMCK0.
PhylomeDBQ6KF10.
TreeFamTF316134.

Enzyme and pathway databases

SignaLinkQ6KF10.

Gene expression databases

BgeeQ6KF10.
CleanExHS_GDF6.
GenevestigatorQ6KF10.

Family and domain databases

InterProIPR001839. TGF-b_C.
IPR001111. TGF-b_N.
IPR015615. TGF-beta-rel.
IPR017948. TGFb_CS.
[Graphical view]
PANTHERPTHR11848. PTHR11848. 1 hit.
PfamPF00019. TGF_beta. 1 hit.
PF00688. TGFb_propeptide. 1 hit.
[Graphical view]
SMARTSM00204. TGFB. 1 hit.
[Graphical view]
PROSITEPS00250. TGF_BETA_1. 1 hit.
PS51362. TGF_BETA_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiGDF6.
GenomeRNAi392255.
NextBio105028.
PROQ6KF10.
SOURCESearch...

Entry information

Entry nameGDF6_HUMAN
AccessionPrimary (citable) accession number: Q6KF10
Secondary accession number(s): Q6PI58
Entry history
Integrated into UniProtKB/Swiss-Prot: October 11, 2005
Last sequence update: July 5, 2004
Last modified: April 16, 2014
This is version 91 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM