P27658 (CO8A1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Collagen alpha-1(VIII) chain

Alternative name(s):
Endothelial collagen

Cleaved into the following chain:

1. Vastatin

Gene names

Name:	COL8A1
Synonyms:	C3orf7

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	744 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	Macromolecular component of the subendothelium. Major component of the Descemet's membrane (basement membrane) of corneal endothelial cells. Also component of the endothelia of blood vessels. Necessary for migration and proliferation of vascular smooth muscle cells and thus, has a potential role in the maintenance of vessel wall integrity and structure, in particular in atherogenesis. Ref.7 Ref.9 Vastatin, the C-terminal fragment comprising the NC1 domain, inhibits aortic endothelial cell proliferation and causes cell apoptosis. Ref.7 Ref.9
Subunit structure	Homotrimers, or heterotrimers in association with alpha 2(VIII) type collagens. Four homotrimers can form a tetrhedron stabilized by central interacting C-terminal NC1 trimers. Ref.10
Subcellular location	Secreted › extracellular space › extracellular matrix › basement membrane.
Tissue specificity	Expressed primarily in the subendothelium of large blood vessels. Also expressed in arterioles and venules in muscle, heart, kidney, spleen, umbilical cord, liver and lung and is also found in connective tissue layers around hair follicles, around nerve bundles in muscle, in the dura of the optic nerve, in cornea and sclera, and in the perichondrium of cartilaginous tissues. In the kidney, expressed in mesangial cells, glomerular endothelial cells, and tubular epithelial cells. Also expressed in mast cells, and in astrocytes during the repair process. Expressed in Descemet's membrane. Specifically expressed in peritoneal fibroblasts and mesothelial cells. Ref.5 Ref.7 Ref.8
Induction	Up-regulated during vascular injury, in atherosclerosis and in diabetes. Ref.11
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. Proteolytically cleaved by neutrophil elastase, in vitro. Proteolytic processing produces the C-terminal NC1 domain fragment, vastatin. Ref.6
Miscellaneous	Four consecutive Gly-Pro-Pro triplets are present at the C-terminus of the triple-helical region. These may provide the high thermal stability of this region.
Sequence similarities	Contains 1 C1q domain.

Ontologies

Keywords
Biological process	Angiogenesis Cell adhesion
Cellular component	Basement membrane Extracellular matrix Secreted
Domain	Collagen Repeat Signal
PTM	Hydroxylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	angiogenesis Inferred from electronic annotation. Source: UniProtKB-KW camera-type eye morphogenesis Inferred from electronic annotation. Source: Compara cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW epithelial cell proliferation Inferred from electronic annotation. Source: Compara extracellular matrix organization Traceable author statement. Source: Reactome positive regulation of cell-substrate adhesion Inferred from electronic annotation. Source: Compara
Cellular_component	basement membrane Inferred from electronic annotation. Source: UniProtKB-SubCell collagen type VIII Traceable author statement Ref.1. Source: ProtInc endoplasmic reticulum lumen Traceable author statement. Source: Reactome
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 27	27	Potential
	Chain	28 – 744	717	Collagen alpha-1(VIII) chain		PRO_0000005762
	Chain	572 – 744	173	Vastatin		PRO_0000390484
Regions
	Domain	611 – 744	134	C1q
	Region	29 – 117	89	Nonhelical region (NC2)
	Region	118 – 571	454	Triple-helical region (COL1)
	Region	572 – 744	173	Nonhelical region (NC1)
Experimental info
	Sequence conflict	262	1	P → L in CAA40748. Ref.1
	Sequence conflict	297	1	P → R in CAA40748. Ref.1
	Sequence conflict	344	1	P → A in CAA40748. Ref.1
	Sequence conflict	382	1	A → S in CAA40748. Ref.1
	Sequence conflict	388	1	P → S in CAA40748. Ref.1
	Sequence conflict	454	1	L → F in CAA40748. Ref.1
	Sequence conflict	464	1	A → H in CAA40748. Ref.1
	Sequence conflict	601	1	Y → T in CAA40748. Ref.1
	Sequence conflict	631	1	A → G in CAA40748. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P27658 [UniParc]. Last modified July 11, 2002. Version 2. Checksum: 2BC1B0955DE2C9A3	FASTA	744	73,364
	10 20 30 40 50 60 MAVLPGPLQL LGVLLTISLS SIRLIQAGAY YGIKPLPPQI PPQMPPQIPQ YQPLGQQVPH 70 80 90 100 110 120 MPLAKDGLAM GKEMPHLQYG KEYPHLPQYM KEIQPAPRMG KEAVPKKGKE IPLASLRGEQ 130 140 150 160 170 180 GPRGEPGPRG PPGPPGLPGH GIPGIKGKPG PQGYPGVGKP GMPGMPGKPG AMGMPGAKGE 190 200 210 220 230 240 IGQKGEIGPM GIPGPQGPPG PHGLPGIGKP GGPGLPGQPG PKGDRGPKGL PGPQGLRGPK 250 260 270 280 290 300 GDKGFGMPGA PGVKGPPGMH GPPGPVGLPG VGKPGVTGFP GPQGPLGKPG APGEPGPQGP 310 320 330 340 350 360 IGVPGVQGPP GIPGIGKPGQ DGIPGQPGFP GGKGEQGLPG LPGPPGLPGI GKPGFPGPKG 370 380 390 400 410 420 DRGMGGVPGA LGPRGEKGPI GAPGIGGPPG EPGLPGIPGP MGPPGAIGFP GPKGEGGIVG 430 440 450 460 470 480 PQGPPGPKGE PGLQGFPGKP GFLGEVGPPG MRGLPGPIGP KGEAGQKGVP GLPGVPGLLG 490 500 510 520 530 540 PKGEPGIPGD QGLQGPPGIP GIGGPSGPIG PPGIPGPKGE PGLPGPPGFP GIGKPGVAGL 550 560 570 580 590 600 HGPPGKPGAL GPQGQPGLPG PPGPPGPPGP PAVMPPTPPP QGEYLPDMGL GIDGVKPPHA 610 620 630 640 650 660 YGAKKGKNGG PAYEMPAFTA ELTAPFPPVG APVKFNKLLY NGRQNYNPQT GIFTCEVPGV 670 680 690 700 710 720 YYFAYHVHCK GGNVWVALFK NNEPVMYTYD EYKKGFLDQA SGSAVLLLRP GDRVFLQMPS 730 740 EQAAGLYAGQ YVHSSFSGYL LYPM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The complete primary structure of the human alpha 1 (VIII) chain and assignment of its gene (COL8A1) to chromosome 3." Muragaki Y., Mattei M.-G., Yamaguchi N., Olsen B.R., Ninomiya Y. Eur. J. Biochem. 197:615-622(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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: Lung.
[5]	"Distribution of type VIII collagen in tissues: an immunohistochemical study." Kittelberger R., Davis P.F., Flynn D.W., Greenhill N.S. Connect. Tissue Res. 24:303-318(1990) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[6]	"Cleavage of type VIII collagen by human neutrophil elastase." Kittelberger R., Neale T.J., Francky K.T., Greenhill N.S., Gibson G.J. Biochim. Biophys. Acta 1139:295-299(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEOLYTIC PROCESSING.
[7]	"Human mast cells produce type VIII collagen in vivo." Ruger B., Dunbar P.R., Hasan Q., Sawada H., Kittelberger R., Greenhill N., Neale T.J. Int. J. Exp. Pathol. 75:397-404(1994) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, POSSIBLE FUNCTION.
[8]	"The alpha1(VIII) and alpha2(VIII) collagen chains form two distinct homotrimeric proteins in vivo." Greenhill N.S., Ruger B.M., Hasan Q., Davis P.F. Matrix Biol. 19:19-28(2000) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[9]	"NC1 domain of human type VIII collagen (alpha 1) inhibits bovine aortic endothelial cell proliferation and causes cell apoptosis." Xu R., Yao Z.-Y., Xin L., Zhang Q., Li T.-P., Gan R.-B. Biochem. Biophys. Res. Commun. 289:264-268(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION OF VASTATIN.
[10]	"Expression and supramolecular assembly of recombinant alpha1(viii) and alpha2(viii) collagen homotrimers." Stephan S., Sherratt M.J., Hodson N., Shuttleworth C.A., Kielty C.M. J. Biol. Chem. 279:21469-21477(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SUBUNIT.
[11]	"Collagen type VIII expression in human diabetic nephropathy." Gerth J., Cohen C.D., Hopfer U., Lindenmeyer M.T., Sommer M., Grone H.J., Wolf G. Eur. J. Clin. Invest. 37:767-773(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X57527 mRNA. Translation: CAA40748.1. BT009917 mRNA. Translation: AAP88919.1. CH471052 Genomic DNA. Translation: EAW79837.1. CH471052 Genomic DNA. Translation: EAW79838.1. CH471052 Genomic DNA. Translation: EAW79840.1. BC013581 mRNA. Translation: AAH13581.1.
IPI	IPI00219000.
PIR	S15435.
RefSeq	NP_001841.2. NM_001850.4. NP_065084.2. NM_020351.3.
UniGene	Hs.654548. Hs.740617.
3D structure databases
ProteinModelPortal	P27658.
ModBase	Search...
Protein-protein interaction databases
IntAct	P27658. 5 interactions.
MINT	MINT-2857732.
STRING	9606.ENSP00000261037.
PTM databases
PhosphoSite	P27658.
Polymorphism databases
DMDM	21903375.
Proteomic databases
PaxDb	P27658.
PRIDE	P27658.
Protocols and materials databases
DNASU	1295.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000261037; ENSP00000261037; ENSG00000144810. ENST00000273342; ENSP00000273342; ENSG00000144810.
GeneID	1295.
KEGG	hsa:1295.
UCSC	uc003dtg.1. human.
Organism-specific databases
CTD	1295.
GeneCards	GC03P099357.
HGNC	HGNC:2215. COL8A1.
HPA	HPA053107.
MIM	120251. gene.
neXtProt	NX_P27658.
PharmGKB	PA26731.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG114228.
HOGENOM	HOG000085653.
HOVERGEN	HBG108220.
InParanoid	P27658.
OMA	TCEVPGV.
OrthoDB	EOG4DJJXP.
PhylomeDB	P27658.
Enzyme and pathway databases
Reactome	REACT_118779. Extracellular matrix organization.
Gene expression databases
ArrayExpress	P27658.
Bgee	P27658.
CleanEx	HS_COL8A1.
Genevestigator	P27658.
GermOnline	ENSG00000144810. Homo sapiens.
Family and domain databases
Gene3D	2.60.120.40. 1 hit.
InterPro	IPR001073. C1q. IPR008160. Collagen. IPR008983. Tumour_necrosis_fac-like_dom. [Graphical view]
Pfam	PF00386. C1q. 1 hit. PF01391. Collagen. 4 hits. [Graphical view]
PRINTS	PR00007. COMPLEMNTC1Q.
SMART	SM00110. C1Q. 1 hit. [Graphical view]
SUPFAM	SSF49842. TNF_like. 1 hit.
PROSITE	PS50871. C1Q. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	1295.
NextBio	5255.
SOURCE	Search...

Entry information

Entry name

CO8A1_HUMAN

Accession

Primary (citable) accession number: P27658
Secondary accession number(s): D3DN42, Q53XI6, Q96D07

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	July 11, 2002
Last modified:	May 1, 2013
This is version 132 of the entry and version 2 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.