It additionally seems to be a key protein in sustaining the integrity of the corneal epithelium.[5] Mutations on this gene are related to each generalized atrophic benign and junctional epidermolysis bullosa,[6] in addition to recurrent corneal erosions, and expression of this gene is irregular in numerous cancers.[7] Two homotrimeric types of sort XVII collagen exist. Collagen XVII is a structural part of hemidesmosomes, multiprotein complexes on the dermal-epidermal basement membrane zone that mediate adhesion of keratinocytes to the underlying membrane. Collagen XVII is a transmembrane protein, like collagen XIII, XXIII and XXV.
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Construction[edit]
The general construction of the ectodomain is that of a versatile, rod-like triple helix[12][13] with a big thermal stability.[14][15] The membrane proximal a part of the ectodomain, inside amino acids 506-519, is chargeable for binding to alpha 6 integrin, this binding appears to be necessary for the collagen XVII integration into hemidesmosomes[citation needed]. The big C-terminal ectodomain with a molecular mass of roughly 120 kDa consists of 15 collagenous subdomains, characterised by typical collagenous G-X-Y repeat sequences, flanked by 16 brief non-collagenous stretches. The biggest collagenous area, Col15, which comprises 232 amino acids (amino acids 567-808), contributes considerably to stability of collagen XVII homotrimer.
Pathology[edit]
Entire-exome sequencing first recognized a heterozygous mutation (c.2816C>T, p.T939I) that segregated with ERED in a big Swedish pedigree courting again 200 years.(*17*) One other synonymous mutation (c.3156C>T) was proposed to introduce a cryptic donor web site, leading to aberrant splicing, a principle which subsequently was confirmed in a number of households with ERED from totally different international locations.[5][22]
Different mutations make the epithelium of the cornea within the eye brittle, which ends up in dominantly inherited recurrent corneal erosion dystrophy (ERED).
Most cancers[edit]
Expression of the COL17A1 gene is irregular in numerous cancers.[7] For instance, it was discovered irregular in 5 epithelial most cancers varieties, together with breast most cancers, cervical most cancers, head and neck most cancers and two kinds of lung most cancers. Decreased expression was noticed for breast most cancers, whereas elevated expression was noticed for the opposite cancers.[7]
Shedding[edit]
Collagen XVII is constitutively shed from the keratinocyte floor inside NC16A area by TACE (TNF-Alpha Changing Enzyme), metalloproteinase of the ADAM household.[23] The shedding is lipid raft dependent.[24] Collagen XVII is extracellularly phosphorylated by ecto-casein kinase 2 inside the NC16A area, phosphorylation negatively regulates ectodomain shedding.[25]
SPARC and osteogenesis imperfecta[edit]
The SPARC gene is totally related to homozygous mutations in collagen XVII, which in flip causes a sort of osteogenesis imperfecta.[26][27]
Interactions[edit]
Collagen, sort XVII, alpha 1 has been proven to work together with Keratin 18,[28] Actinin alpha 4,[29] Dystonin,[11][30] Actinin, alpha 1,[29] CTNND1[31] and ITGB4.[32][33]