Col18a1

What is COL18A1 protein?

COL18A1 (collagen type XVIII alpha 1 chain) gene is a protein coding gene which situated on the long arm of chromosome 21 at locus 21q22. This gene encodes the alpha chain of type XVIII collagen. This collagen is one of the multiplexins, extracellular matrix proteins that contain multiple triple-helix domains (collagenous domains) interrupted by non-collagenous domains. The proteolytically produced C-terminal fragment of type XVIII collagen is endostatin, a potent antiangiogenic protein. The COL18A1 protein is consisted of 1754 amino acids and its molecular mass is approximately 178.2 kDa.

What is the function of COL18A1 protein?

It functions as an anti-angiogenic cytokine that is expressed in various organs with the highest levels in liver, lung and kidney. COL18A1 inhibits angiogenesis by blocking the pro-angiogenic activities of VEGF and FGF basic. It also probably plays a major role in determining the retinal structure as well as in the closure of the neural tube and may negatively regulate the activity of homotrimeric non-collagenous domain 1.

Fig1. The possible mechanism of synergic effect of anti-PD-1 and endostar on LLC.

COL18A1 Related Signaling Pathway

COL18A1 is mainly involved in angiogenesis and cell proliferation. COL18A1 can specifically inhibit the proliferation and angiogenesis of endothelial cells, affect angiogenesis, and then affect the occurrence and development of tumors. COL18A1 can regulate the transmission process of TGF-β signal by binding to TGF-β receptor, and then affect the synthesis and level of extracellular matrix. Specifically related signaling pathways such as TGF-β signaling pathway, PI3K/AKT signaling pathway, Wnt/β-catenin signaling pathway, etc.

COL18A1 Related Diseases

COL18A1 is mainly found in tissues such as eyes, skin, lungs and kidneys. It is associated with abnormalities in bone and joint diseases (Marfan syndrome), eye diseases (keratoconus and macular degeneration), skin elastofibrosis and kidney diseases.

Bioapplications of COL18A1

The functional properties of COL18A1 in the extracellular matrix make it promising to be a special biomaterial for the development of drugs as a target in the treatment of anticancer and related diseases.

Case study 1: K A Spivey, 2012

Collagen XXIII is a transmembrane collagen previously shown to be upregulated in metastatic prostate cancer that has been used as a tissue and fluid biomarker for non-small cell lung cancer and prostate cancer. To determine whether collagen XXIII facilitates cancer cell metastasis in vivo and to establish a function for collagen XXIII in cancer progression, collagen XXIII knockdown cells were examined for alterations in in vivo metastasis as well as in vitro cell adhesion.

Loss of collagen XXIII in H460 cells also impaired cell adhesion, anchorage-independent growth and cell seeding to the lung, but did not affect cell proliferation. Corroborating a role for collagen XXIII in cell adhesion, overexpression of collagen XXIII in H1299 cells, which do not express endogenous collagen XXIII, enhanced cell adhesion. This study suggests a potential role for collagen XXIII in mediating metastasis by facilitating cell-cell and cell-matrix adhesion as well as anchorage-independent cell growth.

Fig1. To assess the role of collagen XXIII in cell proliferation, control and knockdown cell lines were seeded in triplicate and grown in complete media for 24, 48, 72, or 96 hours.

Fig2. shRNA-mediated silencing of collagen XXIII alters the expression of proteins involved in cell adhesion and structure.

Case study 2: Chun-Hong Ma, 2004

To explore a safe and efficient strategy of tumor therapy using anti-angiogenetic agents. Endostatin gene with a signal sequence of human IgGgamma chain was amplified by PCR and cloned into pVAX1 plasmid which was the only vector authorized by FDA in clinical trial to construct a recombinant plasmid named as pVAX-sEN. The recombinant plasmid was detected with EcoRI/KpnI and DNA sequencing. To compare the efficiency of gene transfection, expression of endostatin at the treated tumor site was assayed with ELISA.

DNA sequencing showed the endostatin gene with the signal peptide was correctly cloned. In situ gene expression assay indicated that both the ratio of DNA and liposome and the dose of DNA could affect the gene transfection efficiency. Interestingly, naked pVAX-sEN had a similar in situ endostatin expression to pVAX-sEN with liposome. Naked endostatin plasmid intratumoral injection can get a similar gene transfection efficiency to liposome-DNA complex when used in situ.

Fig3. Inhibitory effect of recombinant secretive endostatin on mouse hepatoma cells.

Fig4. In vivo endostatin expression in peripheral blood of treated mice.

Col18a1 has several biochemical functions, for example, identical protein binding,metal ion binding,protein binding. Some of the functions are cooperated with other proteins, some of the functions could acted by Col18a1 itself. We selected most functions Col18a1 had, and list some proteins which have the same functions with Col18a1. You can find most of the proteins on our site.

Col18a1 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with Col18a1 here. Most of them are supplied by our site. Hope this information will be useful for your research of Col18a1.

TECPR1;PYHIN1;AHI1