Collagen, type XVII, alpha 1

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Collagen, type XVII, alpha 1
Identifiers
Symbols COL17A1 ; BA16H23.2; BP180; BPA-2; BPAG2; LAD-1
External IDs OMIM113811 MGI88450 HomoloGene133558 GeneCards: COL17A1 Gene
RNA expression pattern
PBB GE COL17A1 204636 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 1308 12821
Ensembl ENSG00000065618 ENSMUSG00000025064
UniProt Q9UMD9 Q07563
RefSeq (mRNA) NM_000494 NM_007732
RefSeq (protein) NP_000485 NP_031758
Location (UCSC) Chr 10:
105.79 – 105.85 Mb
Chr 19:
47.65 – 47.69 Mb
PubMed search [1] [2]

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.[1]

This gene encodes the alpha chain of type XVII collagen. Collagen XVII is a transmembrane protein, like collagen XIII, XXIII and XXV. Collagen XVII is a structural component of hemidesmosomes, multiprotein complexes at the dermal-epidermal basement membrane zone that mediate adhesion of keratinocytes to the underlying membrane. Mutations in this gene are associated with both generalized atrophic benign and junctional epidermolysis bullosa. Two homotrimeric forms of type XVII collagen exist. The full length form is the transmembrane protein. A soluble form, referred to as either ectodomain or LAD-1, is generated by proteolytic processing of the full length form.[2]

Structure[edit]

Collagen XVII is a homotrimer of three alpha1(XVII)-chains [3] 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 [4][5] 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 [6][7] with a significant thermal stability.[8][9] 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. 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[edit]

Mutations in the human collagen XVII gene, COL17A1, lead to the absence or structural alterations of collagen XVII.[10] The functional consequences include diminished epidermal adhesion and skin blistering in response to minimal shearing forces . The disorder 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 acquired subepithelial blistering disorders.[11] Most immunodominant epitopes lie within the NC16A domain, and the binding of the autoantibodies perturbs adhesive functions of the collagen XVII, and this (together with inflammation-related processes) leads to epidermal-dermal separation and skin blistering.

Shedding[edit]

Collagen XVII is constitutively shed from the keratinocyte surface within NC16A domain by TACE (TNF-Alpha Converting Enzyme), metalloproteinase of the ADAM family.[12] The shedding is lipid raft dependent.[13] Collagen XVII is extracellularly phosphorylated by ecto-casein kinase 2 within the NC16A domain, phosphorylation negatively regulates ectodomain shedding.[14]

Interactions[edit]

Collagen, type XVII, alpha 1 has been shown to interact with Keratin 18,[15] Actinin alpha 4,[16] Dystonin,[5][17] Actinin, alpha 1,[16] CTNND1[18] and ITGB4.[19][20]

See also[edit]

References[edit]

  1. ^ Franzke, C. W.; Bruckner, P.; Bruckner-Tuderman, L. (2005). "Collagenous transmembrane proteins: recent insights into biology and pathology". J Biol. Chem. 280: 4005–4008. doi:10.1074/jbc.R400034200. 
  2. ^ "Entrez Gene: COL17A1 collagen, type XVII, alpha 1". 
  3. ^ 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): 13739–13745. doi:10.1074/jbc.271.23.13739. PMID 8662839. 
  4. ^ Hopkinson, S. B.; Findlay, K.; Jones, J. C.; Jones, JC (1998). "Interaction of BP180 (type XVII collagen) and alpha 6 integrin is necessary for stabilization of hemidesmosome structure". J.Invest Dermatol 111 (6): 1015–1022. doi:10.1046/j.1523-1747.1998.00452.x. PMID 9856810. 
  5. ^ a b Hopkinson, S B; Jones J C (January 2000). "The N terminus of the transmembrane protein BP180 interacts with the N-terminal domain of BP230, thereby mediating keratin cytoskeleton anchorage to the cell surface at the site of the hemidesmosome". Mol. Biol. Cell (UNITED STATES) 11 (1): 277–86. doi:10.1091/mbc.11.1.277. ISSN 1059-1524. PMC 14774. PMID 10637308. 
  6. ^ 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): 13739–13745. doi:10.1074/jbc.271.23.13739. PMID 8662839. 
  7. ^ Hirako, Y.; Usukura, J.; Uematsu, J.; Hashimoto, T.; Kitajima, Y.; Owaribe, K. (1998). "Cleavage of BP180, a 180-kDa bullous pemphigoid antigen, yields a 120-kDa collagenous extracellular polypeptide". J Biol. Chem. 273: 9711–9717. doi:10.1074/jbc.273.16.9711. 
  8. ^ Schacke, H.; Schumann, H.; Hammami-Hauasli, N.; Raghunath, M.; Bruckner-Tuderman, L. (1998). "Two forms of collagen XVII in keratinocytes. A full-length transmembrane protein and a soluble ectodomain". J Biol. Chem. 273 (40): 25937–25943. doi:10.1074/jbc.273.40.25937. PMID 9748270. 
  9. ^ Areida, S. K.; Reinhardt, D. P.; Muller, P. K.; Fietzek, P. P.; Kowitz, J.; Marinkovich, M. P.; Notbohm, H. (2001). "Properties of the collagen type XVII ectodomain. Evidence for n- to c-terminal triple helix folding". J Biol. Chem. 276: 1594–1601. doi:10.1074/jbc.M008709200. 
  10. ^ Zillikens, D.; Giudice, G. J. (1999). "BP180/type XVII collagen: its role in acquired and inherited disorders or the dermal-epidermal junction". Arch Dermatol. Res 291 (4): 187–194. doi:10.1007/s004030050392. PMID 10335914. 
  11. ^ Zillikens, D. (1999). "Acquired skin disease of hemidesmosomes". J.Dermatol. Sci. 20 (2): 134–154. doi:10.1016/S0923-1811(99)00019-5. PMID 10379705. 
  12. ^ Franzke, C. W.; Tasanen, K.; Borradori, L.; Huotari, V.; Bruckner-Tuderman, L. (2004). "Shedding of collagen XVII/BP180: structural motifs influence cleavage from cell surface". J Biol. Chem. 279: 24521–24529. doi:10.1074/jbc.M308835200. 
  13. ^ Zimina, EP, Bruckner-Tuderman, L, Franzke, CW. (2005). "Shedding of collagen XVII ectodomain depends on plasma membrane microenvironment". J Biol Chem 280 (40): 34019–24. doi:10.1074/jbc.M503751200. PMID 16020548. 
  14. ^ Zimina, EP, Fritsch, A, Schermer, B, Bakulina, AY, Bashkurov, M, Benzing, T, Bruckner-Tuderman, L. (2007). "Extracellular phosphorylation of collagen XVII by ecto-casein kinase 2 inhibits ectodomain shedding". J Biol Chem 282 (31): 22737–46. doi:10.1074/jbc.M701937200. PMID 17545155. 
  15. ^ Aho, S; Uitto J (March 1999). "180-kD bullous pemphigoid antigen/type XVII collagen: tissue-specific expression and molecular interactions with keratin 18". J. Cell. Biochem. (UNITED STATES) 72 (3): 356–67. doi:10.1002/(SICI)1097-4644(19990301)72:3<356::AID-JCB5>3.0.CO;2-M. ISSN 0730-2312. PMID 10022517. 
  16. ^ a b Gonzalez, A M; Otey C; Edlund M; Jones J C (December 2001). "Interactions of a hemidesmosome component and actinin family members". J. Cell. Sci. (England) 114 (Pt 23): 4197–206. ISSN 0021-9533. PMID 11739652. 
  17. ^ Koster, January; Geerts Dirk; Favre Bertrand; Borradori Luca; Sonnenberg Arnoud (January 2003). "Analysis of the interactions between BP180, BP230, plectin and the integrin alpha6beta4 important for hemidesmosome assembly". J. Cell. Sci. (England) 116 (Pt 2): 387–99. doi:10.1242/jcs.00241. ISSN 0021-9533. PMID 12482924. 
  18. ^ Aho, S; Rothenberger K; Uitto J (June 1999). "Human p120ctn catenin: tissue-specific expression of isoforms and molecular interactions with BP180/type XVII collagen". J. Cell. Biochem. (UNITED STATES) 73 (3): 390–9. doi:10.1002/(SICI)1097-4644(19990601)73:3<390::AID-JCB10>3.0.CO;2-1. ISSN 0730-2312. PMID 10321838. 
  19. ^ Aho, S; Uitto J (February 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. (UNITED STATES) 243 (3): 694–9. doi:10.1006/bbrc.1998.8162. ISSN 0006-291X. PMID 9500991. 
  20. ^ Schaapveld, R Q; Borradori L; Geerts D; van Leusden M R; Kuikman I; Nievers M G; Niessen C M; Steenbergen R D; Snijders P J; Sonnenberg A (July 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. (UNITED STATES) 142 (1): 271–84. doi:10.1083/jcb.142.1.271. ISSN 0021-9525. PMC 2133016. PMID 9660880. 

Further reading[edit]