P12109 (CO6A1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Collagen alpha-1(VI) chain

Gene names

Name:

COL6A1

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	1028 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	Collagen VI acts as a cell-binding protein.
Subunit structure	Trimers composed of three different chains: alpha-1(VI), alpha-2(VI), and alpha-3(VI) or alpha-5(VI) or alpha-6(VI).
Subcellular location	Secreted › extracellular space › extracellular matrix By similarity.
Post-translational modification	Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.
Involvement in disease	Bethlem myopathy (BM) [MIM:158810]: A benign autosomal dominant proximal myopathy characterized by early childhood onset and joint contractures most frequently affecting the elbows and ankles. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13 Ref.14 Ref.16 Ref.17 Ullrich congenital muscular dystrophy (UCMD) [MIM:254090]: UCMD is a congenital myopathy characterized by muscle weakness and multiple joint contractures, generally noted at birth or early infancy. The clinical course is more severe than in Bethlem myopathy. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.15 Ref.16 Ref.18
Sequence similarities	Belongs to the type VI collagen family. Contains 3 VWFA domains.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Extracellular matrix Secreted
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Collagen Repeat Signal
PTM	Glycoprotein Hydroxylation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	axon guidance Traceable author statement. Source: Reactome cell adhesion Non-traceable author statement. Source: UniProtKB cellular response to amino acid stimulus Inferred from electronic annotation. Source: Compara extracellular matrix organization Traceable author statement. Source: Reactome protein heterotrimerization Inferred from physical interaction PubMed 18400749. Source: MGI
Cellular_component	collagen type VI Non-traceable author statement Ref.1. Source: UniProtKB endoplasmic reticulum lumen Traceable author statement. Source: Reactome protein complex Inferred from physical interaction PubMed 18400749. Source: MGI sarcolemma Inferred from electronic annotation. Source: Compara transport vesicle Traceable author statement. Source: Reactome
Molecular_function	platelet-derived growth factor binding Inferred from direct assay PubMed 8900172. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 19	19
	Chain	20 – 1028	1009	Collagen alpha-1(VI) chain		PRO_0000005758
Regions
	Domain	37 – 235	199	VWFA 1
	Domain	615 – 805	191	VWFA 2
	Domain	829 – 1021	193	VWFA 3
	Region	20 – 256	237	N-terminal globular domain
	Region	257 – 592	336	Triple-helical region
	Region	593 – 1028	436	C-terminal globular domain
	Motif	262 – 264	3	Cell attachment site
	Motif	442 – 444	3	Cell attachment site
	Motif	478 – 480	3	Cell attachment site
Amino acid modifications
	Glycosylation	212	1	N-linked (GlcNAc...) Ref.11
	Glycosylation	516	1	N-linked (GlcNAc...) Ref.11
	Glycosylation	537	1	N-linked (GlcNAc...) Potential
	Glycosylation	804	1	N-linked (GlcNAc...) Ref.11
	Glycosylation	896	1	N-linked (GlcNAc...) Ref.11
Natural variations
	Natural variant	116	1	S → N in BM. Ref.15 Ref.16 Corresponds to variant rs11553519 [ dbSNP | Ensembl ].		VAR_058213
	Natural variant	121	1	K → R in BM. Ref.14		VAR_013580
	Natural variant	272	1	G → D in BM. Ref.17		VAR_058214
	Natural variant	274	1	P → L in BM. Ref.16		VAR_058215
	Natural variant	275	1	G → R in BM. Ref.17		VAR_058216
	Natural variant	281	1	G → R in UCMD. Ref.16		VAR_058217
	Natural variant	284	1	G → R in UCMD; fibroblasts with the mutation assembled and secreted normal collagen VI microfibrils; cell adhesion of heterozygous Arg-284 fibroblasts is markedly decreased but can be rescued by the addition of normal collagen VI. Ref.15 Ref.16 Ref.18		VAR_058218
	Natural variant	290	1	G → R in BM and UCMD. Ref.15 Ref.16 Ref.17		VAR_058219
	Natural variant	305	1	G → V in BM. Ref.13		VAR_013581
	Natural variant	332	1	G → S. Corresponds to variant rs11701912 [ dbSNP | Ensembl ].		VAR_058220
	Natural variant	341	1	G → D in BM. Ref.14		VAR_013582
	Natural variant	341	1	G → V in BM. Ref.16 Ref.17		VAR_058221
	Natural variant	439	1	R → Q. Corresponds to variant rs35059000 [ dbSNP | Ensembl ].		VAR_048763
	Natural variant	571	1	K → T in BM. Ref.16		VAR_058222
	Natural variant	850	1	R → H. Ref.16 Corresponds to variant rs1053312 [ dbSNP | Ensembl ].		VAR_048764
	Natural variant	881	1	T → M. Ref.16		VAR_058223
	Natural variant	890	1	S → L. Ref.15 Ref.16 Corresponds to variant rs13051496 [ dbSNP | Ensembl ].		VAR_058224
Experimental info
	Sequence conflict	387 – 388	2	SS → AR in M20776. Ref.6
	Sequence conflict	387 – 388	2	SS → AR in AAB20835. Ref.7
	Sequence conflict	396 – 397	2	QP → PA in M20776. Ref.6
	Sequence conflict	396 – 397	2	QP → PA in AAB20835. Ref.7
	Sequence conflict	438	1	T → P in M20776. Ref.6
	Sequence conflict	835 – 839	5	DGSAS → EPPPD in CAA33889. Ref.1
	Sequence conflict	997	1	A → P in CAA67576. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	P12109 [UniParc]. Last modified February 6, 2007. Version 3. Checksum: 04AFF538002A01CD	FASTA	1,028	108,529
	10 20 30 40 50 60 MRAARALLPL LLQACWTAAQ DEPETPRAVA FQDCPVDLFF VLDTSESVAL RLKPYGALVD 70 80 90 100 110 120 KVKSFTKRFI DNLRDRYYRC DRNLVWNAGA LHYSDEVEII QGLTRMPGGR DALKSSVDAV 130 140 150 160 170 180 KYFGKGTYTD CAIKKGLEQL LVGGSHLKEN KYLIVVTDGH PLEGYKEPCG GLEDAVNEAK 190 200 210 220 230 240 HLGVKVFSVA ITPDHLEPRL SIIATDHTYR RNFTAADWGQ SRDAEEAISQ TIDTIVDMIK 250 260 270 280 290 300 NNVEQVCCSF ECQPARGPPG LRGDPGFEGE RGKPGLPGEK GEAGDPGRPG DLGPVGYQGM 310 320 330 340 350 360 KGEKGSRGEK GSRGPKGYKG EKGKRGIDGV DGVKGEMGYP GLPGCKGSPG FDGIQGPPGP 370 380 390 400 410 420 KGDPGAFGLK GEKGEPGADG EAGRPGSSGP SGDEGQPGEP GPPGEKGEAG DEGNPGPDGA 430 440 450 460 470 480 PGERGGPGER GPRGTPGTRG PRGDPGEAGP QGDQGREGPV GVPGDPGEAG PIGPKGYRGD 490 500 510 520 530 540 EGPPGSEGAR GAPGPAGPPG DPGLMGERGE DGPAGNGTEG FPGFPGYPGN RGAPGINGTK 550 560 570 580 590 600 GYPGLKGDEG EAGDPGDDNN DIAPRGVKGA KGYRGPEGPQ GPPGHQGPPG PDECEILDII 610 620 630 640 650 660 MKMCSCCECK CGPIDLLFVL DSSESIGLQN FEIAKDFVVK VIDRLSRDEL VKFEPGQSYA 670 680 690 700 710 720 GVVQYSHSQM QEHVSLRSPS IRNVQELKEA IKSLQWMAGG TFTGEALQYT RDQLLPPSPN 730 740 750 760 770 780 NRIALVITDG RSDTQRDTTP LNVLCSPGIQ VVSVGIKDVF DFIPGSDQLN VISCQGLAPS 790 800 810 820 830 840 QGRPGLSLVK ENYAELLEDA FLKNVTAQIC IDKKCPDYTC PITFSSPADI TILLDGSASV 850 860 870 880 890 900 GSHNFDTTKR FAKRLAERFL TAGRTDPAHD VRVAVVQYSG TGQQRPERAS LQFLQNYTAL 910 920 930 940 950 960 ASAVDAMDFI NDATDVNDAL GYVTRFYREA SSGAAKKRLL LFSDGNSQGA TPAAIEKAVQ 970 980 990 1000 1010 1020 EAQRAGIEIF VVVVGRQVNE PHIRVLVTGK TAEYDVAYGE SHLFRVPSYQ ALLRGVFHQT VSRKVALG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence analysis of alpha 1(VI) and alpha 2(VI) chains of human type VI collagen reveals internal triplication of globular domains similar to the A domains of von Willebrand factor and two alpha 2(VI) chain variants that differ in the carboxy terminus." Chu M.-L., Pan T.-C., Conway D., Kuo H.J., Glanville R.W., Timpl R., Mann K., Deutzmann R. EMBO J. 8:1939-1946(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE. Tissue: Fibroblast.
[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]. Tissue: Kidney and Ovary.
[3]	"Recombinant expression and structural and binding properties of alpha 1(VI) and alpha 2(VI) chains of human collagen type VI." Tillet E., Wiedemann H., Golbik R., Pan T.-C., Zhang R.Z., Mann K., Chu M.-L., Timpl R. Eur. J. Biochem. 221:177-185(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-380 AND 383-1028.
[4]	"Human COL6A1: genomic characterization of the globular domains, structural and evolutionary comparison with COL6A2." Trikka D., Davis T., Lapenta V., Brahe C., Kessling A.M. Mamm. Genome 8:342-345(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 144-268 AND 593-1028.
[5]	"Further characterization of the three polypeptide chains of bovine and human short-chain collagen (intima collagen)." Jander R., Rauterberg J., Glanville R.W. Eur. J. Biochem. 133:39-46(1983) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 246-258.
[6]	"Amino acid sequence of the triple-helical domain of human collagen type VI." Chu M.-L., Conway D., Pan T.-C., Baldwin C., Mann K., Deutzmann R., Timpl R. J. Biol. Chem. 263:18601-18606(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 257-592.
[7]	"The exon organization of the triple-helical coding regions of the human alpha 1(VI) and alpha 2(VI) collagen genes is highly similar." Saitta B., Wang Y.-M., Renkart L., Zhang R.-Z., Pan T.-C., Timpl R., Chu M.-L. Genomics 11:145-153(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 287-592.
[8]	"Characterization of three constituent chains of collagen type VI by peptide sequences and cDNA clones." Chu M.-L., Mann K., Deutzmann R., Pribula-Conway D., Hsu-Chen C.-C., Bernard M.P., Timpl R. Eur. J. Biochem. 168:309-317(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 422-482.
[9]	"Cloning and chromosomal localization of human genes encoding the three chains of type VI collagen." Weil D., Mattei M.-G., Passage E., N'Guyen V.C., Pribula-Conway D., Mann K., Deutzmann R., Timpl R., Chu M.-L. Am. J. Hum. Genet. 42:435-445(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 422-481. Tissue: Placenta.
[10]	Lubec G., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 693-711; 737-757; 939-957 AND 991-1005, MASS SPECTROMETRY. Tissue: Fetal brain cortex.
[11]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-212; ASN-516; ASN-804 AND ASN-896, MASS SPECTROMETRY. Tissue: Liver.
[12]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]	"Type VI collagen mutations in Bethlem myopathy, an autosomal dominant myopathy with contractures." Joebsis G.J., Keizers H., Vreijling J.P., de Visser M., Speer M.C., Wolterman R.A., Baas F., Bohlhuis P.A. Nat. Genet. 14:113-115(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT BM VAL-305.
[14]	"Novel mutations in collagen VI genes: expansion of the Bethlem myopathy phenotype." Scacheri P.C., Gillanders E.M., Subramony S.H., Vedanarayanan V., Crowe C.A., Thakore N., Bingler M., Hoffman E.P. Neurology 58:593-602(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS BM ARG-121 AND ASP-341.
[15]	"Dominant and recessive COL6A1 mutations in Ullrich scleroatonic muscular dystrophy." Giusti B., Lucarini L., Pietroni V., Lucioli S., Bandinelli B., Sabatelli P., Squarzoni S., Petrini S., Gartioux C., Talim B., Roelens F., Merlini L., Topaloglu H., Bertini E., Guicheney P., Pepe G. Ann. Neurol. 58:400-410(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS UCMD ARG-284 AND ARG-290, VARIANTS ASN-116 AND LEU-890.
[16]	"Automated genomic sequence analysis of the three collagen VI genes: applications to Ullrich congenital muscular dystrophy and Bethlem myopathy." Lampe A.K., Dunn D.M., von Niederhausern A.C., Hamil C., Aoyagi A., Laval S.H., Marie S.K., Chu M.-L., Swoboda K., Muntoni F., Bonnemann C.G., Flanigan K.M., Bushby K.M.D., Weiss R.B. J. Med. Genet. 42:108-120(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS BM ASN-116; LEU-274; ARG-290; VAL-341 AND THR-571, VARIANTS UCMD ARG-281 AND ARG-284, VARIANTS HIS-850; MET-881 AND LEU-890.
[17]	"Detection of common and private mutations in the COL6A1 gene of patients with Bethlem myopathy." Lucioli S., Giusti B., Mercuri E., Vanegas O.C., Lucarini L., Pietroni V., Urtizberea A., Ben Yaou R., de Visser M., van der Kooi A.J., Boennemann C., Iannaccone S.T., Merlini L., Bushby K., Muntoni F., Bertini E., Chu M.-L., Pepe G. Neurology 64:1931-1937(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS BM ASP-272; ARG-275; ARG-290 AND VAL-341.
[18]	"Reduced cell anchorage may cause sarcolemma-specific collagen VI deficiency in Ullrich disease." Kawahara G., Okada M., Morone N., Ibarra C.A., Nonaka I., Noguchi S., Hayashi Y.K., Nishino I. Neurology 69:1043-1049(2007) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANT UCMD ARG-284.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	X15879 mRNA. Translation: CAA33888.1. X15880 mRNA. Translation: CAA33889.1. BC005159 mRNA. Translation: AAH05159.2. BC052575 mRNA. Translation: AAH52575.1. X99109 Genomic DNA. Translation: CAA67559.1. X99135, X99136 Genomic DNA. Translation: CAA67576.1. M20776 mRNA. No translation available. S75420 , S75385, S75388, S75390, S75392, S75394, S75396, S75398, S75400, S75402, S75404, S75406, S75408, S75410, S75412, S75414, S75416, S75418 Genomic DNA. Translation: AAB20835.2. X06194 mRNA. Translation: CAA29555.1. M27447 mRNA. Translation: AAA52055.1.
IPI	IPI00291136.
PIR	CGHU1A. S05377.
RefSeq	NP_001839.2. NM_001848.2.
UniGene	Hs.474053.
3D structure databases
ProteinModelPortal	P12109.
ModBase	Search...
Protein-protein interaction databases
IntAct	P12109. 4 interactions.
STRING	9606.ENSP00000355180.
PTM databases
PhosphoSite	P12109.
Polymorphism databases
DMDM	125987811.
2D gel databases
REPRODUCTION-2DPAGE	IPI00291136. P12109.
Proteomic databases
PaxDb	P12109.
PeptideAtlas	P12109.
PRIDE	P12109.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000361866; ENSP00000355180; ENSG00000142156.
GeneID	1291.
KEGG	hsa:1291.
UCSC	uc002zhu.1. human.
Organism-specific databases
CTD	1291.
GeneCards	GC21P047401.
HGNC	HGNC:2211. COL6A1.
HPA	HPA019142. HPA029401.
MIM	120220. gene. 158810. phenotype. 254090. phenotype.
neXtProt	NX_P12109.
Orphanet	610. Bethlem myopathy. 75840. Congenital muscular dystrophy, Ullrich type.
PharmGKB	PA26727.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG256042.
HOVERGEN	HBG095954.
InParanoid	P12109.
KO	K06238.
OMA	VKENYAE.
OrthoDB	EOG4WWRHX.
PhylomeDB	P12109.
Enzyme and pathway databases
Reactome	REACT_111045. Developmental Biology. REACT_111102. Signal Transduction. REACT_118779. Extracellular matrix organization.
Gene expression databases
ArrayExpress	P12109.
Bgee	P12109.
CleanEx	HS_COL6A1.
Genevestigator	P12109.
GermOnline	ENSG00000142156. Homo sapiens.
Family and domain databases
InterPro	IPR008160. Collagen. IPR002035. VWF_A. [Graphical view]
Pfam	PF01391. Collagen. 6 hits. PF00092. VWA. 3 hits. [Graphical view]
SMART	SM00327. VWA. 3 hits. [Graphical view]
PROSITE	PS50234. VWFA. 3 hits. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	COL6A1. human.
DrugBank	DB00039. Palifermin.
GenomeRNAi	1291.
NextBio	5227.
PMAP-CutDB	P12109.
SOURCE	Search...

Entry information

Entry name

CO6A1_HUMAN

Accession

Primary (citable) accession number: P12109
Secondary accession number(s): O00117 , O00118, Q14040, Q14041, Q16258, Q7Z645, Q9BSA8

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	February 6, 2007
Last modified:	May 1, 2013
This is version 143 of the entry and version 3 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.