Collagen, type XVII, alpha 1
| COL17A1 | |||
|---|---|---|---|
| Identifiers | |||
Gene ontology | |||
| Molecular function | |||
| Cellular component | |||
| Biological process | |||
| Sources:Amigo / QuickGO | |||
Ensembl |
| ||||||||
|---|---|---|---|---|---|---|---|---|---|
| UniProt |
| ||||||||
| RefSeq (mRNA) |
| ||||||||
| RefSeq (protein) |
| ||||||||
| Location (UCSC) | Chr 10: 104.03 – 104.09 Mb | n/a | |||||||
| PubMed search | [2] | n/a | |||||||
| View/Edit Human | |||
Collagen XVII, previously called BP180, is a transmembrane protein which plays a critical role in maintaining the linkage between the intracellular and the extracellular structural elements involved in epidermal adhesion, identified by Diaz and colleagues in 1990.[3][4]
COL17A1 is the official name of the gene. It encodes the alpha chain of type XVII collagen. Collagen XVII is a transmembrane protein, like
Structure
Collagen XVII is a homotrimer of three alpha1(XVII)-chains [9] and a transmembrane protein in type II orientation. Each 180 kD a-chain contains a globular intracellular domain of approximately 70 kDa, which interacts with beta4-integrin, plectin, and BP230 [10][11] and is necessary for the stable attachment of hemidesmosomes to keratin intermediate filaments. The large C-terminal ectodomain with a molecular mass of approximately 120 kDa consists of 15 collagenous subdomains, characterized by typical collagenous G-X-Y repeat sequences, flanked by 16 short non-collagenous stretches. The overall structure of the ectodomain is that of a flexible, rod-like triple helix[12][13] with a significant thermal stability.[14][15] The membrane proximal part of the ectodomain, within amino acids 506-519, is responsible for binding to alpha 6 integrin, this binding seems to be important for the collagen XVII integration into hemidesmosomes [citation needed]. The largest collagenous domain, Col15, which contains 232 amino acids (amino acids 567-808), contributes significantly to stability of collagen XVII homotrimer. The C-terminus of collagen XVII binds to laminin 5, and correct integration of laminin 5 into the matrix requires collagen XVII.
Pathology
Mutations in the human collagen XVII gene, COL17A1, lead to the absence or structural alterations and mutations of collagen XVII.[16] The functional consequences include diminished epidermal adhesion and skin blistering in response to minimal shearing forces. The disorder caused by biallelic COL17A1 mutations and is called junctional epidermolysis bullosa, an autosomal recessive skin disease with variable clinical phenotypes. Morphological characteristics of junctional epidermolysis bullosa are rudimentary hemidesmosomes and subepidermal tissue separation. Clinical hallmarks, in addition to blisters and erosions of the skin and mucous membranes, include nail dystrophy, loss of hair, and dental anomalies.
Collagen XVII also plays a role as an autoantigen in
Other mutations make the epithelium of the cornea in the eye brittle, which results in dominantly inherited
Cancer
Expression of the COL17A1 gene is abnormal in various cancers.[7] For example, it was found abnormal in five epithelial cancer types, including breast cancer, cervical cancer, head and neck cancer and two types of lung cancer. Decreased expression was observed for breast cancer, while increased expression was observed for the other cancers.[7]
Shedding
Collagen XVII is constitutively shed from the keratinocyte surface within NC16A domain by TACE (TNF-Alpha Converting Enzyme), metalloproteinase of the ADAM family.[23] The shedding is lipid raft dependent.[24] Collagen XVII is extracellularly phosphorylated by ecto-casein kinase 2 within the NC16A domain, phosphorylation negatively regulates ectodomain shedding.[25]
SPARC and osteogenesis imperfecta
The SPARC gene is completely associated with
Interactions
Collagen, type XVII, alpha 1 has been shown to
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000065618 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 15561712.
- PMID 1698819.
- ^ PMID 26786512.
- S2CID 221861310.
- ^ PMID 27891193
- ^ "Entrez Gene: COL17A1 collagen, type XVII, alpha 1".
- PMID 8662839.
- PMID 9856810.
- ^ PMID 10637308.
- PMID 8662839.
- PMID 9545306.
- PMID 9748270.
- PMID 11042218.
- S2CID 27592712.
- PMID 10379705.
- PMID 1698819.
- PMID 8228259.
- PMID 7693763.
- S2CID 13562400.
- PMID 27309958.
- PMID 15047704.
- PMID 16020548.
- PMID 17545155.
- ^ Reference GH. "SPARC gene". Genetics Home Reference.
- ^ "OMIM Entry - # 616507 - OSTEOGENESIS IMPERFECTA, TYPE XVII; OI17". omim.org.
- S2CID 30404639.
- ^ PMID 11739652.
- S2CID 16745491.
- S2CID 43899550.
- PMID 9500991.
- PMID 9660880.
Further reading
- Giudice GJ, Emery DJ, Diaz LA (1992). "Cloning and primary structural analysis of the bullous pemphigoid autoantigen BP180". J. Invest. Dermatol. 99 (3): 243–50. PMID 1324962.
- Li KH, Sawamura D, Giudice GJ, et al. (1992). "Genomic organization of collagenous domains and chromosomal assignment of human 180-kDa bullous pemphigoid antigen-2, a novel collagen of stratified squamous epithelium". J. Biol. Chem. 266 (35): 24064–9. PMID 1748679.
- Sawamura D, Li KH, Nomura K, et al. (1991). "Bullous pemphigoid antigen: cDNA cloning, cellular expression, and evidence for polymorphism of the human gene". J. Invest. Dermatol. 96 (6): 908–15. PMID 2045679.
- McGrath JA, Gatalica B, Christiano AM, et al. (1995). "Mutations in the 180-kD bullous pemphigoid antigen (BPAG2), a hemidesmosomal transmembrane collagen (COL17A1), in generalized atrophic benign epidermolysis bullosa". Nat. Genet. 11 (1): 83–6. S2CID 23732185.
- Myers JC, Sun MJ, D'Ippolito JA, et al. (1993). "Human cDNA clones transcribed from an unusually high-molecular-weight RNA encode a new collagen chain". Gene. 123 (2): 211–7. PMID 7916703.
- Hirako Y, Usukura J, Nishizawa Y, Owaribe K (1996). "Demonstration of the molecular shape of BP180, a 180-kDa bullous pemphigoid antigen and its potential for trimer formation". J. Biol. Chem. 271 (23): 13739–45. PMID 8662839.
- McGrath JA, Gatalica B, Li K, et al. (1996). "Compound heterozygosity for a dominant glycine substitution and a recessive internal duplication mutation in the type XVII collagen gene results in junctional epidermolysis bullosa and abnormal dentition". Am. J. Pathol. 148 (6): 1787–96. PMID 8669466.
- Gatalica B, Pulkkinen L, Li K, et al. (1997). "Cloning of the human type XVII collagen gene (COL17A1), and detection of novel mutations in generalized atrophic benign epidermolysis bullosa". American Journal of Human Genetics. 60 (2): 352–65. PMID 9012408.
- Jonkman MF, Scheffer H, Stulp R, et al. (1997). "Revertant mosaicism in epidermolysis bullosa caused by mitotic gene conversion". Cell. 88 (4): 543–51. S2CID 18970859.
- Borradori L, Koch PJ, Niessen CM, et al. (1997). "The localization of bullous pemphigoid antigen 180 (BP180) in hemidesmosomes is mediated by its cytoplasmic domain and seems to be regulated by the beta4 integrin subunit". J. Cell Biol. 136 (6): 1333–47. PMID 9087447.
- Schumann H, Hammami-Hauasli N, Pulkkinen L, et al. (1997). "Three novel homozygous point mutations and a new polymorphism in the COL17A1 gene: relation to biological and clinical phenotypes of junctional epidermolysis bullosa". American Journal of Human Genetics. 60 (6): 1344–53. PMID 9199555.
- Chavanas S, Gache Y, Tadini G, et al. (1997). "A homozygous in-frame deletion in the collagenous domain of bullous pemphigoid antigen BP180 (type XVII collagen) causes generalized atrophic benign epidermolysis bullosa". J. Invest. Dermatol. 109 (1): 74–8. PMID 9204958.
- Darling TN, Yee C, Koh B, et al. (1998). "Cycloheximide facilitates the identification of aberrant transcripts resulting from a novel splice-site mutation in COL17A1 in a patient with generalized atrophic benign epidermolysis bullosa". J. Invest. Dermatol. 110 (2): 165–9. PMID 9457913.
- Aho S, Uitto J (1998). "Direct interaction between the intracellular domains of bullous pemphigoid antigen 2 (BP180) and beta 4 integrin, hemidesmosomal components of basal keratinocytes". Biochem. Biophys. Res. Commun. 243 (3): 694–9. PMID 9500991.
- Aho S, McLean WH, Li K, Uitto J (1998). "cDNA cloning, mRNA expression, and chromosomal mapping of human and mouse periplakin genes". Genomics. 48 (2): 242–7. PMID 9521878.
- Schaapveld RQ, Borradori L, Geerts D, et al. (1998). "Hemidesmosome formation is initiated by the beta4 integrin subunit, requires complex formation of beta4 and HD1/plectin, and involves a direct interaction between beta4 and the bullous pemphigoid antigen 180". J. Cell Biol. 142 (1): 271–84. PMID 9660880.
- Ishiko A, Shimizu H, Masunaga T, et al. (1998). "97 kDa linear IgA bullous dermatosis antigen localizes in the lamina lucida between the NC16A and carboxyl terminal domains of the 180 kDa bullous pemphigoid antigen". J. Invest. Dermatol. 111 (1): 93–6. PMID 9665393.
- Floeth M, Fiedorowicz J, Schäcke H, et al. (1998). "Novel homozygous and compound heterozygous COL17A1 mutations associated with junctional epidermolysis bullosa". J. Invest. Dermatol. 111 (3): 528–33. PMID 9740252.
- Schäcke H, Schumann H, Hammami-Hauasli N, et al. (1998). "Two forms of collagen XVII in keratinocytes. A full-length transmembrane protein and a soluble ectodomain". J. Biol. Chem. 273 (40): 25937–43. PMID 9748270.
- Aho S, Uitto J (1999). "180-kD bullous pemphigoid antigen/type XVII collagen: tissue-specific expression and molecular interactions with keratin 18". J. Cell. Biochem. 72 (3): 356–67. S2CID 30404639.