collagen 17 alpha-1; bullous pemphigoid antigen 2 (COL17A1, BPAG2, BP180)

Function

• may play a role in the integrity of hemidesmosome & the attachment of basal keratinocytes to the underlying basement membrane
• the 120 kD linear IgA disease antigen is an anchoring filament component involved in dermal-epidermal cohesion
  • it is the target of linear IgA bullous dermatosis autoantibodies
  • the ectodomain is shedded from the surface of keratinocytes resulting in the soluble 120 kD linear IgA disease antigen
  • shedding is mediated by membrane-bound metalloproteases
  • cleavage is inhibited by phosophorylation at Ser-544
• the intracellular/endo domain is disulfide-linked
• Pro at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains
• interacts (via cytoplasmic region) with ITGB4 (via cytoplasmic region)
• interacts (via cytoplasmic region) with DST isoform 3 (via N-terminus)
• interacts (via N-terminus) with PLEC
• interacts (via cytoplasmic region) with DSP

Structure

• homotrimer

Compartment

• cell junction, hemidesmosome
• membrane
• single-pass type 2 membrane protein
• localized along the plasma membrane of the hemidesmosome
• 120 kD linear IgA disease antigen:
  • secreted, extracellular space, extracellular matrix, basement membrane
  • exclusively localized to anchoring filaments localized to the epidermal side of split skin
• 97 kD linear IgA disease antigen:
  • secreted, extracellular space, extracellular matrix, basement membrane
• localized in the lamina lucida beneath the hemidesmosomes

Alternative splicing

named isoforms=2

Expression

• found in stratified squamous epithelia
• found in hemidesmosomes
• expressed in cornea, oral mucosa, esophagus, intestine, renal collecting ducts, ureter, bladder, urethra & thymus
• not expressed in lung, blood vessels, skeletal muscle & nerves

Pathology

• defects in COL17A1 are a cause of generalized atrophic benign junctional epidermolysis bullosa
• mutations associated with bullous pemphigoid
• both the 120 kD linear IgA disease antigen & the 97 kD linear IgA disease antigen of COL17A1, represent major antigenic targets of autoantibodies in patients with linear IgA disease
  • the IgA autoantibodies preferentially react with 97 kD & the 120 kD forms, but not with the full-length COL17A1, suggesting that the cleavage of the ectodomain generates novel autoantigenic epitopes

More general terms

• collagen subunit
• glycoprotein
• phosphoprotein

Additional terms

• epidermolysis bullosa

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=1308
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:1308
• OMIM: https://mirror.omim.org/entry/113811
• OMIM: https://mirror.omim.org/entry/226650
• UniProt: http://www.uniprot.org/uniprot/Q9UMD9.html