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Protein

Collagen alpha-2(VIII) chain

Gene

COL8A2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity

GO - Molecular functioni

  • extracellular matrix structural constituent Source: UniProtKB
  • protein binding, bridging Source: UniProtKB

GO - Biological processi

Keywordsi

Biological processAngiogenesis, Cell adhesion

Enzyme and pathway databases

ReactomeiR-HSA-1442490. Collagen degradation.
R-HSA-1650814. Collagen biosynthesis and modifying enzymes.
R-HSA-2022090. Assembly of collagen fibrils and other multimeric structures.
R-HSA-216083. Integrin cell surface interactions.
R-HSA-8948216. Collagen chain trimerization.

Names & Taxonomyi

Protein namesi
Recommended name:
Collagen alpha-2(VIII) chain
Alternative name(s):
Endothelial collagen
Gene namesi
Name:COL8A2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000171812.11.
HGNCiHGNC:2216. COL8A2.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Basement membrane, Extracellular matrix, Secreted

Pathology & Biotechi

Involvement in diseasei

Corneal dystrophy, Fuchs endothelial, 1 (FECD1)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:136800
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_017894155R → Q in FECD1; identified as a polymorphism in the Japanese population. 2 PublicationsCorresponds to variant dbSNP:rs75864656Ensembl.1
Natural variantiVAR_017895304R → Q in FECD1. 1 PublicationCorresponds to variant dbSNP:rs369487110Ensembl.1
Natural variantiVAR_017896357G → R in FECD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs199786966Ensembl.1
Natural variantiVAR_017897434R → H in FECD1. 1 PublicationCorresponds to variant dbSNP:rs201235688Ensembl.1
Natural variantiVAR_017898455Q → K in FECD1 and PPCD2. 1 PublicationCorresponds to variant dbSNP:rs80358191Ensembl.1
Natural variantiVAR_017899575P → L in FECD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs145553904Ensembl.1
Corneal dystrophy, posterior polymorphous, 2 (PPCD2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:609140
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_017898455Q → K in FECD1 and PPCD2. 1 PublicationCorresponds to variant dbSNP:rs80358191Ensembl.1

Keywords - Diseasei

Corneal dystrophy, Disease mutation

Organism-specific databases

DisGeNETi1296.
MalaCardsiCOL8A2.
MIMi136800. phenotype.
609140. phenotype.
OpenTargetsiENSG00000171812.
Orphaneti98974. Fuchs endothelial corneal dystrophy.
98973. Posterior polymorphous corneal dystrophy.
PharmGKBiPA26732.

Polymorphism and mutation databases

BioMutaiCOL8A2.
DMDMi45644957.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 28Sequence analysisAdd BLAST28
ChainiPRO_000000583529 – 703Collagen alpha-2(VIII) chainAdd BLAST675

Post-translational modificationi

Proteolytically cleaved by neutrophil elastase, in vitro.1 Publication
Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.

Keywords - PTMi

Hydroxylation

Proteomic databases

PaxDbiP25067.
PeptideAtlasiP25067.
PRIDEiP25067.

PTM databases

iPTMnetiP25067.
PhosphoSitePlusiP25067.

Expressioni

Tissue specificityi

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.2 Publications

Inductioni

Some up-regulation in diabetic nephropathy.1 Publication

Gene expression databases

BgeeiENSG00000171812.
CleanExiHS_COL8A2.
ExpressionAtlasiP25067. baseline and differential.
GenevisibleiP25067. HS.

Organism-specific databases

HPAiHPA049788.

Interactioni

Subunit structurei

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.1 Publication

GO - Molecular functioni

  • protein binding, bridging Source: UniProtKB

Protein-protein interaction databases

BioGridi107693. 17 interactors.
STRINGi9606.ENSP00000305913.

Structurei

3D structure databases

ProteinModelPortaliP25067.
SMRiP25067.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini570 – 703C1qPROSITE-ProRule annotationAdd BLAST134

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni29 – 76Nonhelical region (NC2)Add BLAST48
Regioni77 – 536Triple-helical regionAdd BLAST460
Regioni537 – 703Nonhelical region (NC1)Add BLAST167

Keywords - Domaini

Collagen, Repeat, Signal

Phylogenomic databases

eggNOGiENOG410IHF4. Eukaryota.
ENOG410ZRFW. LUCA.
GeneTreeiENSGT00760000118830.
HOGENOMiHOG000085653.
HOVERGENiHBG108220.
InParanoidiP25067.
OMAiKKGYMDQ.
OrthoDBiEOG091G0L3Y.
PhylomeDBiP25067.
TreeFamiTF334029.

Family and domain databases

Gene3Di2.60.120.40. 1 hit.
InterProiView protein in InterPro
IPR001073. C1q_dom.
IPR008160. Collagen.
IPR008983. Tumour_necrosis_fac-like_dom.
PfamiView protein in Pfam
PF00386. C1q. 1 hit.
PF01391. Collagen. 1 hit.
PRINTSiPR00007. COMPLEMNTC1Q.
SMARTiView protein in SMART
SM00110. C1Q. 1 hit.
SUPFAMiSSF49842. SSF49842. 1 hit.
PROSITEiView protein in PROSITE
PS50871. C1Q. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P25067-1 [UniParc]FASTAAdd to basket

« Hide

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

CPT
Length:703
Mass (Da):67,244
Last modified:March 15, 2004 - v2
Checksum:i84BD7CBDBDECD466
GO

Sequence cautioni

The sequence BAB84955 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti88R → W in AAA62822 (PubMed:2019595).Curated1
Sequence conflicti102M → H in AAA62822 (PubMed:2019595).Curated1
Sequence conflicti133K → N in AAA62822 (PubMed:2019595).Curated1
Sequence conflicti347E → D in AAA62822 (PubMed:2019595).Curated1
Sequence conflicti377 – 378PK → LR in AAA62822 (PubMed:2019595).Curated2
Sequence conflicti506T → R in AAA62822 (PubMed:2019595).Curated1
Sequence conflicti523P → L in AAA62822 (PubMed:2019595).Curated1
Sequence conflicti529 – 531Missing in AAA62822 (PubMed:2019595).Curated3
Sequence conflicti585F → L in AAA62822 (PubMed:2019595).Curated1
Sequence conflicti677M → I in AAA62822 (PubMed:2019595).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0178933G → R1 PublicationCorresponds to variant dbSNP:rs115156902Ensembl.1
Natural variantiVAR_017894155R → Q in FECD1; identified as a polymorphism in the Japanese population. 2 PublicationsCorresponds to variant dbSNP:rs75864656Ensembl.1
Natural variantiVAR_017895304R → Q in FECD1. 1 PublicationCorresponds to variant dbSNP:rs369487110Ensembl.1
Natural variantiVAR_017896357G → R in FECD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs199786966Ensembl.1
Natural variantiVAR_017897434R → H in FECD1. 1 PublicationCorresponds to variant dbSNP:rs201235688Ensembl.1
Natural variantiVAR_017898455Q → K in FECD1 and PPCD2. 1 PublicationCorresponds to variant dbSNP:rs80358191Ensembl.1
Natural variantiVAR_021387502T → M1 PublicationCorresponds to variant dbSNP:rs117860804Ensembl.1
Natural variantiVAR_017899575P → L in FECD1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs145553904Ensembl.1
Natural variantiVAR_017900645T → I1 PublicationCorresponds to variant dbSNP:rs200767854Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK074129 mRNA. Translation: BAB84955.1. Different initiation.
AL138787 Genomic DNA. No translation available.
CH471059 Genomic DNA. Translation: EAX07388.1.
M60832 Genomic DNA. Translation: AAA62822.1.
CCDSiCCDS403.1.
PIRiA57131.
RefSeqiNP_001281276.1. NM_001294347.1.
NP_005193.1. NM_005202.3.
UniGeneiHs.353001.

Genome annotation databases

EnsembliENST00000303143; ENSP00000305913; ENSG00000171812.
ENST00000397799; ENSP00000380901; ENSG00000171812.
GeneIDi1296.
KEGGihsa:1296.
UCSCiuc001bzv.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCO8A2_HUMAN
AccessioniPrimary (citable) accession number: P25067
Secondary accession number(s): Q5JV31, Q8TEJ5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: March 15, 2004
Last modified: September 27, 2017
This is version 164 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot