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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
Related
epidermolysis bullosa
General
collagen subunit
glycoprotein
phosphoprotein
Properties
SIZE: entity length = 1497 aa
MW = 150 kD
COMPARTMENT: cellular membrane
MOTIF: Nonhelical region (NC16) {1-566}
MOTIF: Tyr phosphorylation site {Y40}
Tyr phosphorylation site {Y64}
Ser phosphorylation site {S85}
Ser phosphorylation site {S93}
DST interaction {145-230}
Ser phosphorylation site {S148}
Tyr phosphorylation site {Y396}
Ser phosphorylation site {S400}
transmembrane domain {468-488}
Ser phosphorylation site {S544}
Triple-helical region {567-1482}
MOTIF: N-glycosylation site {N1421}
Nonhelical region (NC1) {1483-1497}
Database Correlations
OMIM correlations
UniProt Q9UMD9
Pfam PF01391
Entrez Gene 1308
Kegg hsa:1308
References
- UniProt :accession Q9UMD9
- GeneReviews
http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/COL17A1