Q6KF10 (GDF6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Growth/differentiation factor 6
Short name=GDF-6

Alternative name(s):
Growth/differentiation factor 16

Gene names

Name:	GDF6
Synonyms:	GDF16

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	455 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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 By similarity.
Subunit structure	Homodimer; disulfide-linked By similarity.
Subcellular location	Secreted Probable.
Involvement in disease	Klippel-Feil syndrome 1 (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.4 A chromosomal aberration involving GDF6 has been found in a patient with Klippel-Feil syndrome (KFS). Paracentric inv8(q22;2q23.3). Ref.3 Ref.4 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, cataract and other abnormalities like cataract may also be present. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4
Sequence similarities	Belongs to the TGF-beta family.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Chromosomal rearrangement Polymorphism
Disease	Disease mutation Dwarfism Microphthalmia
Domain	Signal
Molecular function	Cytokine Growth factor
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	BMP signaling pathway Inferred from direct assay PubMed 16049014. Source: BHF-UCL activin receptor signaling pathway Inferred from direct assay PubMed 16049014. Source: BHF-UCL growth Inferred from electronic annotation. Source: InterPro pathway-restricted SMAD protein phosphorylation Inferred from direct assay PubMed 16049014. Source: BHF-UCL positive regulation of neuron differentiation Inferred from electronic annotation. Source: Compara positive regulation of pathway-restricted SMAD protein phosphorylation Inferred from direct assay PubMed 16049014. Source: BHF-UCL positive regulation of transcription, DNA-dependent Inferred from direct assay PubMed 16049014. Source: BHF-UCL
Cellular_component	extracellular space Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 22	22	Potential
	Propeptide	23 – 330	308	Potential		PRO_0000342206
	Chain	336 – 455	120	Growth/differentiation factor 6		PRO_0000042253
Regions
	Compositional bias	27 – 34	8	Poly-Ser
	Compositional bias	255 – 258	4	Poly-Pro
	Compositional bias	331 – 335	5	Poly-Arg
Amino acid modifications
	Glycosylation	114	1	N-linked (GlcNAc...) Potential
	Disulfide bond	354 ↔ 420		By similarity
	Disulfide bond	383 ↔ 452		By similarity
	Disulfide bond	387 ↔ 454		By similarity
	Disulfide bond	419		Interchain By similarity
Natural variations
	Natural variant	42	1	G → V in KFS1. Ref.4		VAR_063024
	Natural variant	110	1	K → E. Corresponds to variant rs2245091 [ dbSNP | Ensembl ].		VAR_023599
	Natural variant	119	1	Q → R in MCOP4. Ref.4		VAR_063025
	Natural variant	199	1	A → T Found in a patient with microphthalmia isolated with coloboma type 6 carrying a mutation in GDF3. Ref.5		VAR_065151
	Natural variant	216	1	D → G in MCOP4. Ref.4		VAR_063026
	Natural variant	249	1	A → E in KFS1 and MCOP4. Ref.3 Ref.4		VAR_046903
	Natural variant	253	1	Q → L in MCOP4. Ref.4		VAR_063027
	Natural variant	289	1	L → P in KFS1. Ref.3		VAR_046904
	Natural variant	327	1	P → H in MCOP4. Ref.4		VAR_063028
	Natural variant	424	1	K → R in KFS1. Ref.4		VAR_063029
Experimental info
	Sequence conflict	255	1	P → L in AAH43222. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q6KF10 [UniParc]. Last modified July 5, 2004. Version 1. Checksum: F9F365B99E8C659C	FASTA	455	50,662
	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

References

	« Hide 'large scale' referencesShow '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]	"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. , 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.
[5]	"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.
IPI	IPI00419815.
RefSeq	NP_001001557.1. NM_001001557.2.
UniGene	Hs.492277.
3D structure databases
ProteinModelPortal	Q6KF10.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000287020.
Polymorphism databases
DMDM	74748876.
Proteomic databases
PaxDb	Q6KF10.
PRIDE	Q6KF10.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000287020; ENSP00000287020; ENSG00000156466.
GeneID	392255.
KEGG	hsa:392255.
UCSC	uc003yhp.3. human.
Organism-specific databases
CTD	392255.
GeneCards	GC08M097223.
HGNC	HGNC:4221. GDF6.
HPA	HPA045206.
MIM	118100. phenotype. 601147. gene. 613094. phenotype.
neXtProt	NX_Q6KF10.
Orphanet	98938. Colobomatous microphthalmia. 2345. Isolated Klippel-Feil syndrome.
PharmGKB	PA28636.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG317866.
HOGENOM	HOG000231514.
HOVERGEN	HBG107938.
InParanoid	Q6KF10.
KO	K04664.
OMA	FTRSQRK.
OrthoDB	EOG4S4PG9.
PhylomeDB	Q6KF10.
Gene expression databases
Bgee	Q6KF10.
CleanEx	HS_GDF6.
Genevestigator	Q6KF10.
Family and domain databases
InterPro	IPR001839. TGF-b_C. IPR001111. TGF-b_N. IPR015615. TGF-beta-rel. IPR017948. TGFb_CS. [Graphical view]
PANTHER	PTHR11848. PTHR11848. 1 hit.
Pfam	PF00019. TGF_beta. 1 hit. PF00688. TGFb_propeptide. 1 hit. [Graphical view]
SMART	SM00204. TGFB. 1 hit. [Graphical view]
PROSITE	PS00250. TGF_BETA_1. 1 hit. PS51362. TGF_BETA_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	392255.
NextBio	105028.
SOURCE	Search...

Entry information

Entry name

GDF6_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 81 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.