P25067 (CO8A2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Collagen alpha-2(VIII) chain

Alternative name(s):
Endothelial collagen

Gene names

Name:

COL8A2

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	703 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 By similarity.
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.7
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. Ref.6 Ref.8
Induction	Some up-regulation in diabetic nephropathy. Ref.8
Post-translational modification	Proteolytically cleaved by neutrophil elastase, in vitro. Ref.5 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	Corneal dystrophy, Fuchs endothelial, 1 (FECD1) [MIM:136800]: A corneal disease caused by loss of endothelium of the central cornea. It is characterized by focal wart-like guttata that arise from Descemet membrane and develop in the central cornea, epithelial blisters, reduced vision and pain. Descemet membrane is thickened by abnormal collagenous deposition. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Corneal dystrophy, posterior polymorphous, 2 (PPCD2) [MIM:609140]: A rare mild subtype of posterior corneal dystrophy characterized by alterations of Descemet membrane presenting as vesicles, opacities or band-like lesions on slit-lamp examination and specular microscopy. Affected patient typically are asymptomatic. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9
Sequence similarities	Contains 1 C1q domain.
Sequence caution	The sequence BAB84955.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Angiogenesis Cell adhesion
Cellular component	Basement membrane Extracellular matrix Secreted
Coding sequence diversity	Polymorphism
Disease	Corneal dystrophy Disease mutation
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-cell adhesion Non-traceable author statement Ref.4. Source: UniProtKB epithelial cell proliferation Inferred from electronic annotation. Source: Compara extracellular matrix organization Non-traceable author statement Ref.4. Source: UniProtKB
Cellular_component	basement membrane Non-traceable author statement Ref.4. Source: UniProtKB collagen Inferred from electronic annotation. Source: UniProtKB-KW endoplasmic reticulum lumen Traceable author statement. Source: Reactome
Molecular_function	extracellular matrix structural constituent Non-traceable author statement Ref.4. Source: UniProtKB protein binding, bridging Non-traceable author statement Ref.4. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 28	28	Potential
	Chain	29 – 703	675	Collagen alpha-2(VIII) chain		PRO_0000005835
Regions
	Domain	570 – 703	134	C1q
	Region	29 – 76	48	Nonhelical region (NC2)
	Region	77 – 536	460	Triple-helical region
	Region	537 – 703	167	Nonhelical region (NC1)
Natural variations
	Natural variant	3	1	G → R. Ref.9		VAR_017893
	Natural variant	155	1	R → Q in FECD1; identified as a polymorphism in the Japanese population. Ref.9 Ref.10		VAR_017894
	Natural variant	304	1	R → Q in FECD1. Ref.9		VAR_017895
	Natural variant	357	1	G → R in FECD1; uncertain pathogenicity. Ref.9		VAR_017896
	Natural variant	434	1	R → H in FECD1. Ref.9		VAR_017897
	Natural variant	455	1	Q → K in FECD1 and PPCD2. Ref.9		VAR_017898
	Natural variant	502	1	T → M. Ref.10		VAR_021387
	Natural variant	575	1	P → L in FECD1; uncertain pathogenicity. Ref.9		VAR_017899
	Natural variant	645	1	T → I. Ref.9		VAR_017900
Experimental info
	Sequence conflict	88	1	R → W in AAA62822. Ref.4
	Sequence conflict	102	1	M → H in AAA62822. Ref.4
	Sequence conflict	133	1	K → N in AAA62822. Ref.4
	Sequence conflict	347	1	E → D in AAA62822. Ref.4
	Sequence conflict	377 – 378	2	PK → LR in AAA62822. Ref.4
	Sequence conflict	506	1	T → R in AAA62822. Ref.4
	Sequence conflict	523	1	P → L in AAA62822. Ref.4
	Sequence conflict	529 – 531	3	Missing in AAA62822. Ref.4
	Sequence conflict	585	1	F → L in AAA62822. Ref.4
	Sequence conflict	677	1	M → I in AAA62822. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	P25067 [UniParc]. Last modified March 15, 2004. Version 2. Checksum: 84BD7CBDBDECD466	FASTA	703	67,244
	10 20 30 40 50 60 MLGTLTPLSS LLLLLLVLVL GCGPRASSGG GAGGAAGYAP VKYIQPMQKG PVGPPFREGK 70 80 90 100 110 120 GQYLEMPLPL LPMDLKGEPG PPGKPGPRGP PGPPGFPGKP GMGKPGLHGQ PGPAGPPGFS 130 140 150 160 170 180 RMGKAGPPGL PGKVGPPGQP GLRGEPGIRG DQGLRGPPGP PGLPGPSGIT IPGKPGAQGV 190 200 210 220 230 240 PGPPGFQGEP GPQGEPGPPG DRGLKGDNGV GQPGLPGAPG QGGAPGPPGL PGPAGLGKPG 250 260 270 280 290 300 LDGLPGAPGD KGESGPPGVP GPRGEPGAVG PKGPPGVDGV GVPGAAGLPG PQGPSGAKGE 310 320 330 340 350 360 PGTRGPPGLI GPTGYGMPGL PGPKGDRGPA GVPGLLGDRG EPGEDGEPGE QGPQGLGGPP 370 380 390 400 410 420 GLPGSAGLPG RRGPPGPKGE AGPGGPPGVP GIRGDQGPSG LAGKPGVPGE RGLPGAHGPP 430 440 450 460 470 480 GPTGPKGEPG FTGRPGGPGV AGALGQKGDL GLPGQPGLRG PSGIPGLQGP AGPIGPQGLP 490 500 510 520 530 540 GLKGEPGLPG PPGEGRAGEP GTAGPTGPPG VPGSPGITGP PGPPGPPGPP GAPGAFDETG 550 560 570 580 590 600 IAGLHLPNGG VEGAVLGKGG KPQFGLGELS AHATPAFTAV LTSPFPASGM PVKFDRTLYN 610 620 630 640 650 660 GHSGYNPATG IFTCPVGGVY YFAYHVHVKG TNVWVALYKN NVPATYTYDE YKKGYLDQAS 670 680 690 700 GGAVLQLRPN DQVWVQMPSD QANGLYSTEY IHSSFSGFLL CPT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Spleen.
[2]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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 alpha 2(VIII) collagen gene. A novel member of the short chain collagen family located on the human chromosome 1." Muragaki Y., Jacenko O., Apte S., Mattei M.-G., Ninomiya Y., Olsen B.R. J. Biol. Chem. 266:7721-7727(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 66-703.
[5]	"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.
[6]	"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.
[7]	"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.
[8]	"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: TISSUE SPECIFICITY, INDUCTION.
[9]	"Missense mutations in COL8A2, the gene encoding the alpha-2 chain of type VIII collagen, cause two forms of corneal endothelial dystrophy." Biswas S., Munier F.L., Yardley J., Hart-Holden N., Perveen R., Cousin P., Sutphin J.E., Noble B., Batterbury M., Kielty C., Hackett A., Bonshek R., Ridgway A., McLeod D., Sheffield V.C., Stone E.M., Schorderet D.F., Black G.C.M. Hum. Mol. Genet. 10:2415-2423(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS FECD1 GLN-155; GLN-304; ARG-357; HIS-434; LYS-455 AND LEU-575, VARIANT PPCD2 LYS-455, VARIANTS ARG-3 AND ILE-645.
[10]	"Analysis of COL8A2 gene mutation in Japanese patients with Fuchs' endothelial dystrophy and posterior polymorphous dystrophy." Kobayashi A., Fujiki K., Murakami A., Kato T., Chen L.-Z., Onoe H., Nakayasu K., Sakurai M., Takahashi M., Sugiyama K., Kanai A. Jpn. J. Ophthalmol. 48:195-198(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS GLN-155 AND MET-502.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK074129 mRNA. Translation: BAB84955.1. Different initiation. AL138787 Genomic DNA. Translation: CAI22267.1. CH471059 Genomic DNA. Translation: EAX07388.1. M60832 Genomic DNA. Translation: AAA62822.1.
IPI	IPI00152756.
PIR	A57131.
RefSeq	NP_005193.1. NM_005202.2.
UniGene	Hs.353001.
3D structure databases
ProteinModelPortal	P25067.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000305913.
PTM databases
PhosphoSite	P25067.
Polymorphism databases
DMDM	45644957.
Proteomic databases
PaxDb	P25067.
PRIDE	P25067.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000303143; ENSP00000305913; ENSG00000171812. ENST00000397799; ENSP00000380901; ENSG00000171812.
GeneID	1296.
KEGG	hsa:1296.
UCSC	uc001bzv.2. human.
Organism-specific databases
CTD	1296.
GeneCards	GC01M036563.
HGNC	HGNC:2216. COL8A2.
HPA	HPA049788.
MIM	120252. gene. 136800. phenotype. 609140. phenotype.
neXtProt	NX_P25067.
Orphanet	98974. Fuchs endothelial corneal dystrophy. 98973. Posterior polymorphous corneal dystrophy.
PharmGKB	PA26732.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG114228.
HOGENOM	HOG000085653.
HOVERGEN	HBG108220.
InParanoid	P25067.
OMA	FAYHMHV.
OrthoDB	EOG4Q58PV.
PhylomeDB	P25067.
Enzyme and pathway databases
Reactome	REACT_118779. Extracellular matrix organization.
Gene expression databases
ArrayExpress	P25067.
Bgee	P25067.
CleanEx	HS_COL8A2.
Genevestigator	P25067.
GermOnline	ENSG00000171812. 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. 3 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	1296.
NextBio	5261.
SOURCE	Search...

Entry information

Entry name

CO8A2_HUMAN

Accession

Primary (citable) accession number: P25067
Secondary accession number(s): Q5JV31, Q8TEJ5

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1992
Last sequence update:	March 15, 2004
Last modified:	May 1, 2013
This is version 127 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.