COL18A1

Function

Probably plays a major role in determining the retinal structure as well as in the closure of the neural tube.

Non-collagenous domain 1

May regulate extracellular matrix-dependent motility and morphogenesis of endothelial and non-endothelial cells; the function requires homotrimerization and implicates MAPK signaling.

Endostatin

Potently inhibits endothelial cell proliferation and angiogenesis (PubMed:9459295). May inhibit angiogenesis by binding to the heparan sulfate proteoglycans involved in growth factor signaling (By similarity). Inhibits VEGFA-induced endothelial cell proliferation and migration. Seems to inhibit VEGFA-mediated signaling by blocking the interaction of VEGFA to its receptor KDR/VEGFR2. Modulates endothelial cell migration in an integrin-dependent manner implicating integrin ITGA5:ITGB1 and to a lesser extent ITGAV:ITGB3 and ITGAV:ITGB5 (By similarity). May negatively regulate the activity of homotrimeric non-collagenous domain 1 (PubMed:11257123).

Involvement in disease

Knobloch syndrome 1

KNO1

A developmental disorder primarily characterized by typical eye abnormalities, including high myopia, cataracts, dislocated lens, vitreoretinal degeneration, and retinal detachment, with occipital skull defects, which can range from occipital encephalocele to occult cutis aplasia.

None

The disease is caused by variants affecting the gene represented in this entry.

Glaucoma, primary closed-angle

GLCC

An autosomal dominant form of primary glaucoma, an ocular disease characterized by a marked increase of intraocular pressure causing damage to eye structures and function. GLCC is characterized by elevated intraocular pressure due to iridocorneal angle closure with retention of the aqueous humor in the anterior chamber. Iridocorneal angle changes are apparent in the fourth to fifth decade of life, and patients manifest age-related variation in the severity of glaucomatous damage.

None

The disease may be caused by variants affecting the gene represented in this entry.

Post-translational modifications

Prolines at the third position of the tripeptide repeating unit (G-X-Y) of the triple-helical regions are hydroxylated.

Circulating endostatins are found as sialoglycoprotein and asialoglycoprotein structures.

Undergoes proteolytic processing by CTSL/cathepsin-L and elastase-like proteases to generate both non-collagenous domain 1 trimers and endostatin monomers (PubMed:10626789). In tissue extracts (brain, skeletal muscle, heart, kidney, testis and liver) predominantly bands of approximately 38 kDa are detected; recombinant non-collagenous domain 1 shows similar mobility. In vitro, several proteolytic cleavage sites in the non-collagenous domain 1 hinge region generating different endostatin-like peptides are reported (By similarity).

Sequence Similarities

Belongs to the multiplexin collagen family.

Tissue Specificity

Detected in placenta (at protein level) (PubMed:32337544). Present in multiple organs with highest levels in liver, lung and kidney.

Cellular localization

• Secreted
• Extracellular space
• Extracellular matrix
• Secreted
• Extracellular space
• Extracellular matrix
• Basement membrane
• Non-collagenous domain 1
• Secreted
• Extracellular space
• Extracellular matrix
• Basement membrane
• Secreted
• Endostatin
• Secreted
• Secreted
• Extracellular space
• Extracellular matrix
• Basement membrane

Alternative names

Collagen alpha-1(XVIII) chain, COL18A1

Database links

swissprot:P39060 omim:120328 entrezGene:1306 entrezGene:80781 swissprot:P39059