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P25067 (CO8A2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 135. 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:
Collagen alpha-2(VIII) chain
Alternative name(s):
Endothelial collagen
Gene names
Name:COL8A2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length703 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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

Secretedextracellular spaceextracellular matrixbasement 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 processAngiogenesis
Cell adhesion
   Cellular componentBasement membrane
Extracellular matrix
Secreted
   Coding sequence diversityPolymorphism
   DiseaseCorneal dystrophy
Disease mutation
   DomainCollagen
Repeat
Signal
   PTMHydroxylation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processangiogenesis

Inferred from electronic annotation. Source: UniProtKB-KW

camera-type eye morphogenesis

Inferred from electronic annotation. Source: Ensembl

cell-cell adhesion

Non-traceable author statement Ref.4. Source: UniProtKB

collagen catabolic process

Traceable author statement. Source: Reactome

epithelial cell proliferation

Inferred from electronic annotation. Source: Ensembl

extracellular matrix disassembly

Traceable author statement. Source: Reactome

extracellular matrix organization

Non-traceable author statement Ref.4. Source: UniProtKB

   Cellular_componentbasement 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

extracellular region

Traceable author statement. Source: Reactome

proteinaceous extracellular matrix

Non-traceable author statement Ref.4. Source: UniProtKB

   Molecular_functionextracellular 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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2828 Potential
Chain29 – 703675Collagen alpha-2(VIII) chain
PRO_0000005835

Regions

Domain570 – 703134C1q
Region29 – 7648Nonhelical region (NC2)
Region77 – 536460Triple-helical region
Region537 – 703167Nonhelical region (NC1)

Natural variations

Natural variant31G → R. Ref.9
Corresponds to variant rs115156902 [ dbSNP | Ensembl ].
VAR_017893
Natural variant1551R → Q in FECD1; identified as a polymorphism in the Japanese population. Ref.9 Ref.10
Corresponds to variant rs75864656 [ dbSNP | Ensembl ].
VAR_017894
Natural variant3041R → Q in FECD1. Ref.9
VAR_017895
Natural variant3571G → R in FECD1; unknown pathological significance. Ref.9
VAR_017896
Natural variant4341R → H in FECD1. Ref.9
Corresponds to variant rs201235688 [ dbSNP | Ensembl ].
VAR_017897
Natural variant4551Q → K in FECD1 and PPCD2. Ref.9
VAR_017898
Natural variant5021T → M. Ref.10
Corresponds to variant rs117860804 [ dbSNP | Ensembl ].
VAR_021387
Natural variant5751P → L in FECD1; unknown pathological significance. Ref.9
Corresponds to variant rs145553904 [ dbSNP | Ensembl ].
VAR_017899
Natural variant6451T → I. Ref.9
Corresponds to variant rs200767854 [ dbSNP | Ensembl ].
VAR_017900

Experimental info

Sequence conflict881R → W in AAA62822. Ref.4
Sequence conflict1021M → H in AAA62822. Ref.4
Sequence conflict1331K → N in AAA62822. Ref.4
Sequence conflict3471E → D in AAA62822. Ref.4
Sequence conflict377 – 3782PK → LR in AAA62822. Ref.4
Sequence conflict5061T → R in AAA62822. Ref.4
Sequence conflict5231P → L in AAA62822. Ref.4
Sequence conflict529 – 5313Missing in AAA62822. Ref.4
Sequence conflict5851F → L in AAA62822. Ref.4
Sequence conflict6771M → I in AAA62822. Ref.4

Sequences

Sequence LengthMass (Da)Tools
P25067 [UniParc].

Last modified March 15, 2004. Version 2.
Checksum: 84BD7CBDBDECD466

FASTA70367,244
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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.
PIRA57131.
RefSeqNP_005193.1. NM_005202.2.
XP_005270535.1. XM_005270478.2.
UniGeneHs.353001.

3D structure databases

ProteinModelPortalP25067.
SMRP25067. Positions 575-702.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107693. 1 interaction.
STRING9606.ENSP00000305913.

PTM databases

PhosphoSiteP25067.

Polymorphism databases

DMDM45644957.

Proteomic databases

PaxDbP25067.
PRIDEP25067.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000303143; ENSP00000305913; ENSG00000171812.
ENST00000397799; ENSP00000380901; ENSG00000171812.
GeneID1296.
KEGGhsa:1296.
UCSCuc001bzv.2. human.

Organism-specific databases

CTD1296.
GeneCardsGC01M036563.
HGNCHGNC:2216. COL8A2.
HPAHPA049788.
MIM120252. gene.
136800. phenotype.
609140. phenotype.
neXtProtNX_P25067.
Orphanet98974. Fuchs endothelial corneal dystrophy.
98973. Posterior polymorphous corneal dystrophy.
PharmGKBPA26732.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG114228.
HOGENOMHOG000085653.
HOVERGENHBG108220.
InParanoidP25067.
OMAQYVQPMH.
OrthoDBEOG70ZZPW.
PhylomeDBP25067.
TreeFamTF334029.

Enzyme and pathway databases

ReactomeREACT_118779. Extracellular matrix organization.

Gene expression databases

ArrayExpressP25067.
BgeeP25067.
CleanExHS_COL8A2.
GenevestigatorP25067.

Family and domain databases

Gene3D2.60.120.40. 1 hit.
InterProIPR001073. C1q.
IPR008160. Collagen.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view]
PfamPF00386. C1q. 1 hit.
PF01391. Collagen. 3 hits.
[Graphical view]
PRINTSPR00007. COMPLEMNTC1Q.
SMARTSM00110. C1Q. 1 hit.
[Graphical view]
SUPFAMSSF49842. SSF49842. 1 hit.
PROSITEPS50871. C1Q. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiCOL8A2.
GenomeRNAi1296.
NextBio5261.
PROP25067.
SOURCESearch...

Entry information

Entry nameCO8A2_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 135 of the entry and version 2 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 1

Human chromosome 1: entries, gene names and cross-references to MIM