Collagen α-1 (XXIII) chain is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

encoded by COL23A1

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

, which is located on chromosome 5q35 in humans, and on chromosome 11B1+2 in mice. The location of this gene was discovered by

genomic sequence A genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as ...

analysis. Collagen XXIII is a type II

transmembrane protein A transmembrane protein is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequently un ...

and the fourth in the subfamily of non-fibrillar transmembranous collagens. This kind of collagens have a single pass hydrophobic transmembrane domain. The molecule of collagen XXIII can be found either in membrane-bond form or in shed form. Type XXIII collagen is expressed in both adult tissues and developing organs. It can be found in the epidermis and other epithelia such as those in tongue, gut and lung, but also in the brain, the kidney and the cornea. It has been shown that in prostate collagen XXIII expression is associated with tumor progression. The functions of collagen XXIII are still unknown, although it is believed that they could be similar to other transmembrane proteins, such as collagen XIII.

Discovery

Collagen XXIII was first identified and isolated from rat prostate

carcinoma Carcinoma is a malignancy that develops from epithelial cells. Specifically, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that arises from cells originating in the endodermal, mesoder ...

cells by Jacqueline Banyard, Lere Bao and Bruce R. Zetter in 2003. They also identified this protein in human tissue. They concluded that at the nucleotide level, human and rat collagen XXIII alpha 1 show 76% identity. Furthermore, cellular localization of collagen XXIII was determined by

immunofluorescence Immunofluorescence (IF) is a light microscopy-based technique that allows detection and localization of a wide variety of target biomolecules within a cell or tissue at a quantitative level. The technique utilizes the binding specificity of anti ...

staining, using an

antibody An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as pathogenic bacteria, bacteria and viruses, includin ...

that recognizes the

carboxyl terminus The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When t ...

of the protein. It was demonstrated that the carboxyl terminus of collagen XXIII is present on the cell surface.

Structure

Protein structure

Human collagen α1(XXIII), which is a homotrimer, contains 540 amino acids distributed in: * A long amino-terminal non-collagenous

domain A domain is a geographic area controlled by a single person or organization. Domain may also refer to: Law and human geography * Demesne, in English common law and other Medieval European contexts, lands directly managed by their holder rather ...

(NC-1) of 120 amino acids which can be divided in three parts: a short cytoplasmic region, a transmembrane region and a short extracellular region. * A 420-amino-acid-long extracellular region organized in three collagenous (COL1, COL2 and COL3) domains which are interrupted by short non-collagenous domains (NC2, NC3 and NC4), as shown in the schematic.

Structural homology

Collagen XXIII belongs to the transmembranous subfamily of collagens. Proteins which are included in this group present an amino-terminal cytoplasmic domain followed by a membrane-spanning hydrophobic domain and at least one extracellular triple-helical collagenous domain alternated with short non-collagenous domains. Collagens

XIII XIII may refer to: * 13 (number) or XIII in Roman numerals * 13th century in Roman numerals * ''XIII'' (comics), a Belgian comic book series by Jean Van Hamme and William Vance ** ''XIII'' (2003 video game), a 2003 video game based on the comic b ...

XVII 17 (seventeen) is the natural number following 16 and preceding 18. It is a prime number. 17 was described at MIT as "the least random number", according to the Jargon File. This is supposedly because, in a study where respondents were asked to ...

, and XXV, and related proteins such as class A macrophage scavenger receptors,

ectodysplasin A Ectodysplasin A (EDA) is a protein that in humans is encoded by the EDA gene. Ectodysplasin A is a transmembrane protein of the TNF family which plays an important role in the development of ectodermal tissues such as skin in humans. It is reco ...

or the MARCO1 receptor, are also part of this group. An alternative name for this type of protein is MACITs (membrane-associated collagens with interrupted triple helices). Collagen XXIII shows structural homology with collagen XIII and collagen XXV . Apart from having the characteristic structure of transmembranous collagens, all three proteins present a high level of amino acid residue conservation in collagenous and non-collagenous domains. Collagens α1(XIII), α1(XXIII) and α1(XXV) display three collagenous domains (Col 1, Col 2, and Col 3) and four non-collagenous domains (NC1, which is also a transmembranous domain, NC2, NC3 and NC4). It has been reported that Col 1 domain of α1(XXIII) shows similarities with regions of both Col 1 and Col 2 domains of collagen types α1(XIII) and α1(XXV), whilst sequences of Col 2 and Col 3 domains of α1(XXIII) are related to the Col 3 domain of types α1(XIII)and α1(XXV). Short non-collagenous domains also exhibit similarities, especially in the NC1 and NC4 domains. Between 60 and 78% of the amino acid residues of these domains are identical in all three chains. Furthermore, possible recognition sequences for furin (a major physiological

protease A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalysis, catalyzes proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the formation of new protein products ...

) cleavage sites have been found in both amino-terminal NC1 domain and carboxyl-terminal NC4 domain of each one of these collagens. The activity of this protease is vital to explain the origin of the two forms that collagen types XIII, XXIII and XXV can adopt.

Shedding

A common feature of transmembrane collagens is the presence of two forms of the molecule: a full-length membrane-bound form and an ectodomain shed form. This characteristic can be also applicable to collagen XXIII. The distribution of both collagen XXIII forms is tissue-specific, since there are organs such as the brain where the shed form is predominant, whereas in the lungs the molecule is generally found as the full-length form. It has been reported that the cell is able to regulate the amounts of collagen XXIII in the membrane-bound form and in the secreted shed form, influencing the production of one form or the other when it is needed. For that reason, the shedding process of collagen XXIII has been described as a selective

proteolysis Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Protein degradation is a major regulatory mechanism of gene expression and contributes substantially to shaping mammalian proteomes. Uncatalysed, the hydrolysis o ...

, carried out principally by furin, although there are other enzymes, like serine and cysteine proteases, which are able to shed the molecule too. When collagen XXIII is inside the

Golgi apparatus The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic Cell (biology), cells. Part of the endomembrane system in the cytoplasm, it protein targeting, packages proteins ...

, furin proteases act, cleaving the protein and originating the shed form of the molecule, which will be released to the

extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix (ICM), is a network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structural and bio ...

by means of

exocytosis Exocytosis is a term for the active transport process that transports large molecules from cell to the extracellular area. Hormones, proteins and neurotransmitters are examples of large molecules that can be transported out of the cell. Exocytosis ...

. There is also the possibility that the full-length form of the molecule reaches the cell surface before furin cleaves it. When this happens, the full molecule of collagen is introduced in the plasmatic membrane and is stabilized by its non-collagenous transmembranous domains, leaving the collagenous domains outside the cell. Full-length molecules of collagen XXIII are usually found in

lipid rafts The plasma membranes of cells contain combinations of glycosphingolipids, cholesterol and protein receptors organized in glycolipoprotein lipid microdomains termed lipid rafts. Their existence in cellular membranes remains controversial. Indee ...

, which are cholesterol-rich and sphingolipid-rich, tightly-packed microdomains of the cell membrane. Furin proteases are not able to reach collagen XXIII molecules when they are inside

, therefore, collagen XXIII molecules can conserve their full-length form. In case that these molecules lose the lipid raft protection (i.e. when membrane cholesterol levels decrease) furin proteases can act, cleaving the protein right outside the cell, releasing the shed form of collagen XXIII directly to the

Interaction with integrin α2β1

Cellular receptors for collagens belong to the family of β1 integrins. Collagen XXIII interacts in an ion-and conformation-dependent manner with

integrin α2β1 Integrins are transmembrane receptors that help cell–cell and cell–extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, or ...

. Integrin α2β1 is a collagen-binding integrin present at the epidermis, therefore this is the location where the interaction takes place. Both proteins co-localize on basal

keratinocytes Keratinocytes are the primary type of cell found in the epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells. Basal cells in the basal layer (''stratum basale'') of the skin are sometimes refer ...

surface.

Clinical significance

Collagen XXIII plays a role as a

biomarker In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, ...

for detection and recurrence of NCLSC cells (non-small cell lung carcinoma) and the reappearance of prostate cancer. Some experiments suggest that collagen XXIII influences cellular adhesion and stimulates

metastasis Metastasis is a pathogenic agent's spreading from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, ...

development by facilitating cancer cells growth and survival when they are rounded and not able to spread. It has been shown that loss of collagen XXIII may complicate cellular adhesion and reduce lung cancer cell retention.

References

External links

UniProtKB

NCBI: The National Center for Biotechnology Information

NextProt

IHC/ICC: Collagen XXIII alpha 1 image

ExPASy
{{Fibrous proteins Collagens