Affinage

COL17A1

Collagen alpha-1(XVII) chain · UniProt Q9UMD9

Length
1497 aa
Mass
150.4 kDa
Annotated
2026-06-09
100 papers in source corpus 31 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

COL17A1 (BP180/BPAG2) is a type II transmembrane collagen that nucleates the keratinocyte hemidesmosome, anchoring basal epithelial cells to the underlying basement membrane (PMID:1324962, PMID:8228259). It is synthesized with an intracellular N-terminus, a single transmembrane signal-anchor, and a long C-terminal ectodomain composed of multiple collagen triple-helical domains separated by non-collagenous linkers (PMID:1846881, PMID:1324962); the secreted ectodomain assembles as a stable, highly extended homotrimer (PMID:9220968) that projects through the lamina lucida and loops back into the lamina densa, where its C-terminus lies closer to the membrane than its mid-ectodomain (PMID:9182819, PMID:9242508, PMID:11069628). The molecule bridges the cell and the matrix on both faces: its cytoplasmic domain binds beta4 and alpha6 integrin, BP230, and plectin to recruit the protein into and stabilize the hemidesmosome (PMID:7790367, PMID:9500991, PMID:10637308, PMID:12482924), while its NC16A ectodomain engages alpha6 integrin and its distal ectodomain binds laminin-332 to mediate cell-matrix adhesion (PMID:9856810, PMID:21034821). The ectodomain is constitutively shed at the cell surface as a 120-kDa fragment by ADAM9 and ADAM10, a cleavage that depends on the conformational integrity of the NC16A linker, and is further proteolyzed by neutrophil elastase during inflammation, generating neutrophil-chemotactic peptides (PMID:9545306, PMID:15047704, PMID:19574220, PMID:21979170). Beyond adhesion, COL17A1 levels gate stem cell behavior and tissue homeostasis: DNA-damage-induced proteolysis of COL17A1 drives hair follicle stem cell differentiation and aging, while EGFR-TIMP1 signaling stabilizes COL17A1 to coordinate actin and keratin networks and sustain keratinocyte stem cell motility and skin regeneration (PMID:26912707, PMID:34550317). COL17A1 also restrains keratinocyte inflammatory output, suppressing NF-kappaB-dependent IL-8 responses and limiting TSLP-driven skin inflammation independently of integrin or adaptive immunity (PMID:29866844, PMID:22775995), and acts as a p53 transcriptional target that inhibits breast cancer cell migration (PMID:28915553). Autoantibodies against the NC16A domain define its role in bullous pemphigoid, triggering IL-6/IL-8 secretion and macropinocytic internalization of BP180 and driving complement-, mast cell-, and neutrophil-dependent subepidermal blistering (PMID:11069622, PMID:18922680, PMID:23337823).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1992 High

    Established the fundamental architecture of COL17A1 as a transmembrane collagen, defining how a structural matrix protein can be membrane-anchored.

    Evidence cDNA cloning and primary structural analysis predicting a type II transmembrane topology with a collagenous ectodomain

    PMID:1324962 PMID:1846881

    Open questions at the time
    • Topology predicted from sequence required ultrastructural confirmation
    • Trimeric assembly state not yet established
  2. 1997 High

    Resolved the orientation and conformation of the protein, showing the ectodomain is an extended homotrimer projecting through the lamina lucida into the lamina densa.

    Evidence Biophysical analysis of a secreted recombinant ectodomain plus immunoelectron microscopy with domain-specific antibodies in tissue

    PMID:8228259 PMID:9182819 PMID:9220968 PMID:9242508

    Open questions at the time
    • Whether the ectodomain folds back into a loop in vivo not yet directly shown
    • Trimerization signals within the molecule not mapped
  3. 2000 Medium

    Mapped the intracellular interaction network that recruits COL17A1 into the hemidesmosome, identifying integrins, BP230, plectin, and p120ctn as cytoplasmic partners.

    Evidence Yeast two-hybrid, deletion mutagenesis, co-immunoprecipitation, and dominant-negative cell transfection assays across multiple cell lines

    PMID:10321838 PMID:10637308 PMID:7790367 PMID:9087447 PMID:9500991 PMID:9521865

    Open questions at the time
    • Most interactions mapped by yeast two-hybrid without structural validation
    • p120ctn interaction lacks cell-based functional readout
    • Stoichiometry of the assembled complex unresolved
  4. 2000 High

    Demonstrated COL17A1 acts as a bona fide cell-matrix adhesion molecule on its extracellular face, binding alpha6 integrin via NC16A and laminin-332 via its distal ectodomain.

    Evidence Peptide inhibition and recombinant interaction assays plus gain-of-function adhesion assays with siRNA and antibody blocking

    PMID:21034821 PMID:9856810

    Open questions at the time
    • Precise laminin-332 binding site on COL17A1 not mapped
    • Relative contribution of NC16A-integrin versus ectodomain-laminin adhesion in vivo unclear
  5. 2009 High

    Identified the proteases and structural requirements for constitutive ectodomain shedding, linking NC16A conformation to sheddase recognition.

    Evidence Deletion mutagenesis and shedding assays plus Adam9/Adam10 knockout keratinocytes with selective inhibitors and H2O2 stimulation

    PMID:15047704 PMID:19574220 PMID:9545306

    Open questions at the time
    • Physiological cues controlling shedding rate beyond oxidative stress not fully defined
    • Functional consequences of the released 120-kDa fragment not established
  6. 2011 High

    Established neutrophil elastase as a distinct inflammatory protease that cleaves COL17A1 to generate chemotactic peptides, connecting proteolysis to immune amplification.

    Evidence In vitro proteolysis with cleavage-site mapping by mass spectrometry, chemotaxis assays, and in vivo mouse skin injection with inhibitor

    PMID:11710917 PMID:21979170

    Open questions at the time
    • In vivo abundance of chemotactic p561 peptide in human disease not quantified
    • Crosstalk between constitutive ADAM shedding and inflammatory elastase cleavage unresolved
  7. 2013 High

    Defined COL17A1 as the autoantigen driving bullous pemphigoid, showing anti-NC16A antibodies are both signaling triggers and effectors of blistering.

    Evidence Keratinocyte cytokine assays, humanized knock-in mouse passive transfer with complement/mast cell/neutrophil depletion, and live imaging of antibody-induced internalization

    PMID:11069622 PMID:18922680 PMID:23337823

    Open questions at the time
    • Receptor/signaling pathway coupling antibody binding to IL-6/IL-8 secretion not identified
    • Link between macropinocytic internalization and complement-dependent blistering not integrated
  8. 2018 Medium

    Revealed cell-autonomous regulatory roles for COL17A1 in restraining keratinocyte inflammation independently of its structural adhesion function.

    Evidence JEB patient cells and shRNA knockdown with NF-kappaB reporter and integrin-dependency tests; DeltaNC16A mouse model dissecting TSLP, histamine, and adaptive immunity

    PMID:22775995 PMID:29866844

    Open questions at the time
    • Molecular mechanism by which COL17A1 suppresses NF-kappaB unknown
    • How a transmembrane collagen signals to control TSLP not defined
  9. 2021 High

    Connected COL17A1 stability and proteolysis to stem cell fate and tissue regeneration, positioning it as a homeostatic rheostat in epidermal and hair follicle stem cells.

    Evidence Col17a1 knockout/forced-expression mice with lineage tracing and DNA-damage analysis; live imaging, CRISPR knockout, and EGFR-TIMP1 pathway dissection with cytoskeletal readouts

    PMID:26912707 PMID:34550317

    Open questions at the time
    • Protease responsible for DNA-damage-induced COL17A1 cleavage in HFSCs not identified
    • Mechanism linking COL17A1 to coordinated actin/keratin dynamics unresolved
  10. 2021 Medium

    Extended COL17A1 function to cancer, implicating it in p53-dependent migration suppression and in metabolic resistance to ferroptosis in transformed epithelia.

    Evidence ChIP and reporter assays with migration/invasion readouts; plasma membrane screening, CRISPR knockout, and metabolome/ROS/ferroptosis assays with CD44

    PMID:28915553 PMID:34087104

    Open questions at the time
    • How a hemidesmosomal collagen influences mitochondrial metabolism mechanistically unclear
    • Whether the p53-COL17A1 axis and CD44-COL17A1 axis are connected unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The signaling mechanism by which COL17A1 transduces extracellular cues into intracellular outcomes (NF-kappaB suppression, TSLP control, stem cell fate, mitochondrial metabolism) remains undefined.
  • No receptor or adaptor coupling COL17A1 status to intracellular signaling identified
  • Protease specificity governing context-dependent COL17A1 cleavage outcomes not resolved
  • Structural basis of the trimeric ectodomain loop and its partner-binding surfaces unsolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 2 GO:0060089 molecular transducer activity 2 GO:0098631 cell adhesion mediator activity 2
Localization
GO:0005829 cytosol 3 GO:0005886 plasma membrane 3 GO:0031012 extracellular matrix 3
Pathway
R-HSA-1500931 Cell-Cell communication 4 R-HSA-168256 Immune System 4 R-HSA-1474244 Extracellular matrix organization 3 R-HSA-1266738 Developmental Biology 2
Partners
CTNND1DSTITGA6ITGB4LAMA3PLEC
Complex memberships
hemidesmosome

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 BP180/COL17A1 contains two collagen triple-helical domains (242 and 30 amino acids) separated by a non-collagen stretch; collagenase digestion of the encoded fusion protein generated a peptide fragment consistent with predicted cleavage sites, establishing the collagenous nature of these domains. cDNA sequence analysis, collagenase digestion of recombinant fusion protein The Journal of Clinical Investigation Medium 1846881
1992 BP180/COL17A1 is a type II transmembrane protein with an intracellular N-terminus and a long C-terminal extracellular collagenous domain consisting of 15 collagen domains separated by non-collagenous sequences; a transmembrane domain located 76 amino acids upstream of the collagenous region acts as a signal-anchor directing the C-terminal collagenous segment to the cell exterior. cDNA cloning and primary structural analysis, open reading frame prediction The Journal of Investigative Dermatology High 1324962
1993 BP180/BPAG2 autoantibody-reactive region (NC16A, non-collagenous domain) is localized extracellularly to the epidermal basal lamina immediately adjacent to the hemidesmosome, confirming type II transmembrane orientation with the C-terminal collagenous domain projecting into the basal lamina. Bacterial fusion protein expression, immunoblotting, immunoadsorption, immunofluorescence with affinity-purified antiserum Journal of Immunology High 8228259
1997 The BP180 ectodomain exists as an elongated, flexible homotrimeric structure; a recombinant secreted form (sec180e) assembles as a stable homotrimer prior to secretion, with a Stokes radius of 13.6 nm, sedimentation coefficient of 6.5 S, and frictional ratio of 3.01, indicating highly extended conformation; native BP180 from human epidermis also exists in a heat-labile, SDS-stable high-molecular-mass complex. Gel filtration, sedimentation analysis, pulse-chase, chemical cross-linking, COS-1 cell expression Biochemistry High 9220968
1995 BP180/COL17A1 cytoplasmic domain interacts with the alpha6 integrin subunit; a deletion mutant lacking the extracellular collagenous domains (D1) co-precipitates with alpha6 integrin in HT1080 transfectants, and a 36-amino-acid N-terminal cytoplasmic deletion (D1-36N) disrupts polarization, while deletion of the 27-aa non-collagenous extracellular juxtamembrane domain (D1-27C) prevents co-distribution with hemidesmosomal components. Transfection of deletion mutants into 804G, FG, and HT1080 cells; co-immunoprecipitation; immunofluorescence localization The Journal of Cell Biology Medium 7790367
1998 BP180 interacts with alpha6 integrin via the non-collagenous NC16A extracellular domain (residues 506-519); this interaction is necessary for hemidesmosome assembly, as a 14-mer peptide spanning this region inhibits the BP180/alpha6 interaction in yeast two-hybrid and recombinant assays and blocks hemidesmosome assembly in 804G cells. Yeast two-hybrid, recombinant protein interaction assay, peptide inhibition, cell culture hemidesmosome assembly assay The Journal of Investigative Dermatology High 9856810
1998 The intracellular domain of BP180 (amino acids 13–89, including a predicted N-terminal beta-sheet) directly interacts with the beta4 integrin subunit intracellular domain (requiring the connecting segment, second pair of FNIII repeats, and tail region of beta4) as established by yeast two-hybrid analysis. Yeast two-hybrid system with serial deletion constructs Biochemical and Biophysical Research Communications Medium 9500991
1997 BP180 cytoplasmic domain contains sufficient information for recruitment into hemidesmosomes; a 265-amino-acid segment spanning the central and N-terminal portions of the cytoplasmic domain mediates hemidesmosomal localization; co-localization with alpha6beta4 requires sequences within the cytoplasmic tail of beta4 (specifically the C-terminal half and the tyrosine activation motif). Transfection of wild-type and deletion mutant cDNA constructs into 804G and COS-7 cells; immunofluorescence localization The Journal of Cell Biology Medium 9087447
2000 The N-terminal domain of BP180 directly binds the N-terminal domain of BP230; expression of the BP230 N-terminus in 804G cells disrupts BP180 distribution at hemidesmosome sites, competing with endogenous BP230 for BP180 binding, thereby demonstrating that this interaction is required for BP180 incorporation into the hemidesmosome. Yeast two-hybrid, recombinant protein binding, cell transfection with dominant-negative fragment Molecular Biology of the Cell Medium 10637308
2003 BP180 binds both BP230 and plectin via the Y subdomain of their N-terminal plakin domains interacting with residues 145–230 of the BP180 cytoplasmic domain; different but overlapping sequences on BP180 mediate binding to beta4 integrin (which associates via its third FNIII repeat); BP230 localization into hemidesmosome-like structures depends on its Z-Y subdomains and requires available BP180. Yeast two-hybrid, cell transfection assays, domain mapping Journal of Cell Science Medium 12482924
1998 BP180 is constitutively cleaved on the cell surface to release a 120-kDa collagenous extracellular fragment (LAD-1); the cleavage product lacks the globular head present in intact BP180 and is detectable in culture medium and in vivo in bovine skin basement membrane; it is recognized by a monoclonal antibody (1337) that binds an epitope exposed only upon cleavage. Immunofluorescence microscopy, immunoprecipitation, rotary shadow electron microscopy, immunoblotting The Journal of Biological Chemistry High 9545306
1997 The BP180 extracellular domain projects through the lamina lucida to the lamina densa; immuno-electron microscopy with antibodies to the NC16A (membrane-proximal) domain localizes to the upper lamina lucida, whereas antibodies to the C-terminal region localize to the lower lamina lucida/lamina densa interface, co-localizing with anchoring filaments and laminin-5. Immunoelectron microscopy, immunogold localization, immunoadsorption The Journal of Investigative Dermatology High 9182819
1997 The C-terminus (distal ectodomain) of BPAG2/COL17A1 localizes within the lamina densa, 41 nm beneath the plasma membrane of basal keratinocytes, and the extracellular domain runs along anchoring filaments; this was established using anti-BV4 IgG raised against a baculovirus-expressed C-terminal recombinant of BPAG2. Baculovirus expression, affinity purification, immunogold electron microscopy (pre- and post-embedding) The Journal of Investigative Dermatology High 9242508
2000 In vivo, the extracellular domain of BPAG2 has at least one loop structure in the lamina densa; immunogold EM with antibodies to intracellular head (20 nm from membrane), mid-extracellular portion (~amino acids 1000–1320, 65 nm from membrane), and C-terminal end (~amino acids 1320–1500, 39 nm from membrane) demonstrates that the C-terminal end is closer to the plasma membrane than the mid-extracellular region, implying a loop. Low temperature post-embedding immunoelectron microscopy with three domain-specific monoclonal antibodies The Journal of Investigative Dermatology Medium 11069628
2001 Neutrophil elastase (NE) directly cleaves the extracellular collagenous domain of BP180 in human bullous pemphigoid lesions and blister fluid; NE but not proMMP-9 (which remains inactive in blister fluid, where TIMP-1 levels are high) is responsible for direct BP180 proteolysis during blister formation. In vitro proteolysis of recombinant BP180 with recombinant MMP-9, NE, and blister fluid; inhibition with chloromethylketone (elastase inhibitor) or batimastat (MMP inhibitor); lesional skin and blister fluid analysis The Journal of Investigative Dermatology High 11710917
2004 Shedding of collagen XVII/BP180 ectodomain requires the conformational integrity of the NC16A linker domain; the stretch of amino acids 528–547 within NC16A is critical for sheddase recognition and cleavage; furin does not directly cleave collagen XVII but activates ADAMs; large NC16A deletions preventing shedding also result in lower triple-helix thermal stability. Deletion mutagenesis of NC16A domain, expression in COS-7 cells, shedding assay, secondary structure prediction, triple-helix folding thermal stability assay The Journal of Biological Chemistry High 15047704
2009 ADAM10 and ADAM9 are the major sheddases for collagen XVII/BP180 in primary keratinocytes; constitutive shedding is strongly reduced in Adam10−/− cells and is sensitive to the ADAM10-selective inhibitor GI254023X; Adam9−/− keratinocytes show 55% reduction in constitutive shedding; H2O2 enhances ADAM9 expression and stimulates collagen XVII shedding, an effect absent in Adam9−/− mice; ADAM17 only indirectly affects collagen XVII shedding (phorbol ester stimulation does not increase shedding). Adam10−/− and Adam9−/− knockout keratinocytes, selective ADAM inhibitor GI254023X, H2O2 stimulation, in vivo mouse skin experiments The Journal of Biological Chemistry High 19574220
2011 Neutrophil elastase (NE) cleaves murine BP180 within the extracellular immunodominant domain at amino acid positions 506 and 561, generating peptide p561 which is chemotactic for neutrophils in vitro and in vivo; NE also directly cleaves native human BP180 trimer; NE injection in mouse skin recruits neutrophils, blocked by alpha-1 proteinase inhibitor. In vitro proteolysis with recombinant NE, mass spectrometry identification of cleavage sites, neutrophil chemotaxis assays, in vivo mouse skin injection, NE inhibitor experiment Matrix Biology High 21979170
2000 Anti-BP180 autoantibodies trigger a signal transduction event in keratinocytes that leads to production and secretion of IL-6 and IL-8 (but not IL-1alpha, IL-1beta, TNF-alpha, IL-10, or MCP-1); this effect is BP180-dependent, as it requires reactivity to the NC16A domain and does not occur in BP180-deficient keratinocytes from a GABEB patient. Treatment of cultured human keratinocytes with BP IgG, cytokine ELISA, mRNA analysis, antibody depletion experiments, BP180-deficient keratinocytes as negative control The Journal of Investigative Dermatology High 11069622
2008 Human anti-BP180NC16A autoantibodies induce BP-like subepidermal blistering in humanized mice (NC16A+/+); F(ab')2 fragments that cannot activate complement are not pathogenic; complement depletion, mast cell activation blockade, or neutrophil depletion prevent blister formation, establishing that the humoral anti-BP180 response depends on complement, mast cells, and neutrophils. Humanized knock-in mouse model (murine NC14A replaced with human NC16A), passive transfer of IgG and F(ab')2, complement depletion, mast cell inhibition, neutrophil depletion Journal of Autoimmunity High 18922680
2010 COL17A1 (collagen XVII) functions as a cell-matrix adhesion molecule by binding to laminin 332; COL17-expressing SK-MEL1 and K562 cells preferentially adhere to laminin 332 substrate with >7-fold greater adhesive force than COL17-negative cells; adhesion is abolished by siRNA knockdown of COL17 or blocking antibodies to COL17 or laminin 332. Ectopic expression of COL17 in adherence-incompetent cell lines, quantitative cell adhesion assay, siRNA knockdown, antibody blocking Matrix Biology Medium 21034821
1998 BP180 is required for correct BP230 localization into hemidesmosome-like structures; reexpression of BP180 in BP180-deficient GABEB keratinocytes causes BP230 to redistribute from diffuse cytoplasmic distribution to HD-like structures; a 36-amino-acid N-terminal cytoplasmic deletion of BP180 abolishes this effect; BP180 deletion mutant lacking the collagenous extracellular domain still promotes BP230 relocalization. Immortalized GABEB keratinocytes, transfection of wild-type and deletion mutant BP180, immunofluorescence Experimental Cell Research Medium 9521865
2016 DNA damage response in hair follicle stem cells (HFSCs) causes proteolysis of COL17A1, triggering HFSC aging characterized by loss of stemness and epidermal commitment; HFSCs are cyclically eliminated through terminal epidermal differentiation causing hair follicle miniaturization; Col17a1 deficiency recapitulates aging and forced maintenance of COL17A1 prevents it. In vivo fate analysis, Col17a1 knockout mice, COL17A1 forced expression, DNA damage response analysis, immunofluorescence, lineage tracing Science High 26912707
2013 BP-IgG induces internalization of BP180 via a macropinocytic pathway in epithelial cells; BP-IgG treatment decreases adhesive strength of cells to substrate, and a macropinocytosis inhibitor rescues BP-IgG-induced reduction in adhesive strength; BP180-GFP co-internalizes with early endosomal antigen-1 after antibody clustering. GFP-tagged BP180 live imaging, endocytosis inhibitors, fluid-uptake assay, adhesion assay in 804G cells and human keratinocytes The American Journal of Pathology Medium 23337823
2018 BP180 dysfunction (ΔNC16A mice lacking functional BP180) causes spontaneous skin inflammatory disease with severe itch, defective skin barrier, infiltrating immune cells, elevated serum IgE, and increased TSLP expression; itch is independent of adaptive immunity and histamine but dependent on TSLP produced by keratinocytes; COL17A1 thus regulates skin inflammation via TSLP independently of adaptive immunity. BP180-dysfunctional (ΔNC16A) knock-in mouse model, adaptive immunity-deficient cross, histamine pathway analysis, TSLP measurement, keratinocyte TSLP expression PNAS High 29866844
2021 EGFR activation drives keratinocyte stem cell motility by inhibiting COL17A1 proteolysis through secretion of TIMP1; COL17A1 directly regulates keratinocyte stem cell motility and collective cell migration by coordinating actin and keratin filament networks; age-associated decline of EGFR signaling reduces COL17A1 levels and impairs skin regeneration. Live-imaging, receptor tyrosine kinase array, EGFR activation/inhibition culture experiments, TIMP1 measurement, CRISPR COL17A1 knockout, computer simulation, actin/keratin cytoskeletal analysis The Journal of Cell Biology High 34550317
1999 BP180 N-terminal intracellular domain (amino acids 13–25) interacts with p120ctn catenin isoforms 1–3 (but not isoform 4) via a domain encoded by exons 5–6 of p120ctn; confirmed by yeast two-hybrid and in vitro protein-protein interaction assay. Yeast two-hybrid system, in vitro protein-protein interaction assay Journal of Cellular Biochemistry Medium 10321838
2012 COL17A1 modulates keratinocyte IL-8 proinflammatory response via NF-kappaB; COL17-deficient EK (from JEB patient or shRNA knockdown) show abnormally high IL-8 after LPS, UV-B, or TNF treatment; restoration of COL17 normalizes LPS-induced IL-8; NF-kappaB inhibition normalizes IL-8 in COL17-negative cells; the effect is not dependent on alpha6beta4 integrin. JEB patient keratinocytes, shRNA knockdown, COL17 re-expression, NF-kappaB reporter assay, siRNA knockdown of alpha6/beta4 integrin subunits Experimental Dermatology Medium 22775995
2017 COL17A1 is a novel transcriptional target of p53; p53-binding sequences were identified in the COL17A1 intron by reporter assay and ChIP; COL17A1 expression increases in a p53-dependent manner; overexpression of COL17A1 in MDA-MB-231 cells reduces migration and invasion in vitro. ChIP assay, reporter assay, cDNA microarray, ectopic COL17A1 overexpression, migration/invasion assay Oncotarget Medium 28915553
2021 COL17A1 and CD44 co-accumulate in RasV12-, Src-, or ErbB2-transformed epithelial cells; COL17A1 and CD44 suppress mitochondrial membrane potential and ROS production, promoting resistance to ferroptosis upon cell extrusion and thereby supporting multilayered transformed epithelial structures; COL17A1 regulates the metabolic pathway from the GABA shunt to mitochondrial complex I via succinate; CD44 regulates membrane accumulation of COL17A1. Plasma membrane protein screening, CRISPR-knockout, metabolome analysis, ROS measurement, cell extrusion assay, ferroptosis assay Current Biology Medium 34087104
1992 TGF-beta1 and TGF-beta2 (10 ng/ml) up-regulate BPAG2/COL17A1 mRNA levels (up to 4.6-fold) in normal keratinocytes, with greater effect in low-calcium conditions; transformed cell lines show extremely low baseline BPAG2 expression. Northern hybridization, in situ hybridization, TGF-beta treatment of normal and transformed keratinocytes The Journal of Investigative Dermatology Low 1401998

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1992 Cloning and primary structural analysis of the bullous pemphigoid autoantigen BP180. The Journal of investigative dermatology 467 1324962
2016 Hair follicle aging is driven by transepidermal elimination of stem cells via COL17A1 proteolysis. Science (New York, N.Y.) 314 26912707
1993 Bullous pemphigoid and herpes gestationis autoantibodies recognize a common non-collagenous site on the BP180 ectodomain. Journal of immunology (Baltimore, Md. : 1950) 301 8228259
1995 Mutations in the 180-kD bullous pemphigoid antigen (BPAG2), a hemidesmosomal transmembrane collagen (COL17A1), in generalized atrophic benign epidermolysis bullosa. Nature genetics 300 7550320
2000 Serum levels of autoantibodies to BP180 correlate with disease activity in patients with bullous pemphigoid. Archives of dermatology 264 10677092
1997 Tight clustering of extracellular BP180 epitopes recognized by bullous pemphigoid autoantibodies. The Journal of investigative dermatology 250 9326393
1996 Cicatricial pemphigoid autoantibodies react with multiple sites on the BP180 extracellular domain. The Journal of investigative dermatology 207 8592065
2002 BP180 ELISA using bacterial recombinant NC16a protein as a diagnostic and monitoring tool for bullous pemphigoid. Journal of dermatological science 184 12443845
2003 Analysis of the interactions between BP180, BP230, plectin and the integrin alpha6beta4 important for hemidesmosome assembly. Journal of cell science 175 12482924
1998 The 97 kDa linear IgA bullous disease antigen is identical to a portion of the extracellular domain of the 180 kDa bullous pemphigoid antigen, BPAg2. The Journal of investigative dermatology 175 9506436
1993 Cloning of type XVII collagen. Complementary and genomic DNA sequences of mouse 180-kilodalton bullous pemphigoid antigen (BPAG2) predict an interrupted collagenous domain, a transmembrane segment, and unusual features in the 5'-end of the gene and the 3'-untranslated region of the mRNA. The Journal of biological chemistry 167 8473327
2002 Severity and phenotype of bullous pemphigoid relate to autoantibody profile against the NH2- and COOH-terminal regions of the BP180 ectodomain. The Journal of investigative dermatology 146 12445194
2000 IgG4 and IgE are the major immunoglobulins targeting the NC16A domain of BP180 in Bullous pemphigoid: serum levels of these immunoglobulins reflect disease activity. Journal of the American Academy of Dermatology 142 10727301
1995 180-kD bullous pemphigoid antigen (BP180) is deficient in generalized atrophic benign epidermolysis bullosa. The Journal of clinical investigation 142 7883981
1997 Bullous pemphigoid and cicatricial pemphigoid autoantibodies react with ultrastructurally separable epitopes on the BP180 ectodomain: evidence that BP180 spans the lamina lucida. The Journal of investigative dermatology 122 9182819
2017 Correlation of Serum Levels of IgE Autoantibodies Against BP180 With Bullous Pemphigoid Disease Activity. JAMA dermatology 120 27829102
1995 Molecular genetic studies of a human epidermal autoantigen (the 180-kD bullous pemphigoid antigen/BP180): identification of functionally important sequences within the BP180 molecule and evidence for an interaction between BP180 and alpha 6 integrin. The Journal of cell biology 118 7790367
1991 Identification of two collagen domains within the bullous pemphigoid autoantigen, BP180. The Journal of clinical investigation 118 1846881
2007 Enzyme-linked immunosorbent assay using multimers of the 16th non-collagenous domain of the BP180 antigen for sensitive and specific detection of pemphigoid autoantibodies. Experimental dermatology 110 17697150
1998 Cleavage of BP180, a 180-kDa bullous pemphigoid antigen, yields a 120-kDa collagenous extracellular polypeptide. The Journal of biological chemistry 110 9545306
2008 Subepidermal blistering induced by human autoantibodies to BP180 requires innate immune players in a humanized bullous pemphigoid mouse model. Journal of autoimmunity 109 18922680
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. The Journal of cell biology 109 9087447
2000 Autoantibodies to BP180 associated with bullous pemphigoid release interleukin-6 and interleukin-8 from cultured human keratinocytes. The Journal of investigative dermatology 107 11069622
2008 Correlation of IgE autoantibody to BP180 with a severe form of bullous pemphigoid. Archives of dermatology 104 18209167
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 102 9012408
1997 The extracellular domain of BPAG2 localizes to anchoring filaments and its carboxyl terminus extends to the lamina densa of normal human epidermal basement membrane. The Journal of investigative dermatology 100 9242508
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. Molecular biology of the cell 97 10637308
2006 Autoreactive T and B cells from bullous pemphigoid (BP) patients recognize epitopes clustered in distinct regions of BP180 and BP230. Journal of immunology (Baltimore, Md. : 1950) 92 16424234
2004 Correlation of clinical severity and ELISA indices for the NC16A domain of BP180 measured using BP180 ELISA kit in bullous pemphigoid. Journal of dermatological science 91 15734283
2001 Respective contribution of neutrophil elastase and matrix metalloproteinase 9 in the degradation of BP180 (type XVII collagen) in human bullous pemphigoid. The Journal of investigative dermatology 90 11710917
2000 IgG, IgA and IgE autoantibodies against the ectodomain of BP180 in patients with bullous and cicatricial pemphigoid and linear IgA bullous dermatosis. The British journal of dermatology 87 10951144
1994 Development of an ELISA to detect anti-BP180 autoantibodies in bullous pemphigoid and herpes gestationis. The Journal of investigative dermatology 86 7516396
2011 Usefulness of BP230 and BP180-NC16a enzyme-linked immunosorbent assays in the initial diagnosis of bullous pemphigoid: a retrospective study of 138 patients. Archives of dermatology 82 21422334
2009 Shedding of collagen XVII/BP180 in skin depends on both ADAM10 and ADAM9. The Journal of biological chemistry 78 19574220
2017 Detection of IgE autoantibodies to BP180 and BP230 and their relationship to clinical features in bullous pemphigoid. The British journal of dermatology 77 27716903
2009 A novel ELISA reveals high frequencies of BP180-specific IgE production in bullous pemphigoid. Journal of immunological methods 76 19422829
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 71 9199555
2000 Patients with bullous pemphigoid and linear IgA disease show a dual IgA and IgG autoimmune response to BP180. Journal of autoimmunity 68 11040070
1998 Immunoreactivity of bullous pemphigoid (BP) autoantibodies against the NC16A and C-terminal domains of the 180 kDa BP antigen (BP180): immunoblot analysis and enzyme-linked immunosorbent assay using BP180 recombinant proteins. The British journal of dermatology 67 9767278
1999 Digenic junctional epidermolysis bullosa: mutations in COL17A1 and LAMB3 genes. American journal of human genetics 66 10577906
2016 In epithelial cancers, aberrant COL17A1 promoter methylation predicts its misexpression and increased invasion. Clinical epigenetics 63 27891193
2005 Multiple correcting COL17A1 mutations in patients with revertant mosaicism of epidermolysis bullosa. American journal of human genetics 62 16252234
2004 Development of a novel ELISA system for detection of anti-BP180 IgG and characterization of autoantibody profile in bullous pemphigoid patients. The British journal of dermatology 62 15541078
2004 Shedding of collagen XVII/BP180: structural motifs influence cleavage from cell surface. The Journal of biological chemistry 61 15047704
1999 BP180 gene delivery in junctional epidermolysis bullosa. Gene therapy 61 10341874
2005 Collagen XVII/BP180: a collagenous transmembrane protein and component of the dermoepidermal anchoring complex. Clinical and experimental dermatology 60 16197389
2004 Evaluation of a BP180-NC16a enzyme-linked immunosorbent assay in the initial diagnosis of bullous pemphigoid. The British journal of dermatology 60 15270881
1998 Interaction of BP180 (type XVII collagen) and alpha6 integrin is necessary for stabilization of hemidesmosome structure. The Journal of investigative dermatology 59 9856810
1997 A recombinant form of the human BP180 ectodomain forms a collagen-like homotrimeric complex. Biochemistry 59 9220968
2011 Neutrophil elastase cleaves the murine hemidesmosomal protein BP180/type XVII collagen and generates degradation products that modulate experimental bullous pemphigoid. Matrix biology : journal of the International Society for Matrix Biology 58 21979170
1999 Revertant mosaicism: partial correction of a germ-line mutation in COL17A1 by a frame-restoring mutation. The Journal of clinical investigation 58 10330419
1996 A homozygous deletion mutation in the gene encoding the 180-kDa bullous pemphigoid antigen (BPAG2) in a family with generalized atrophic benign epidermolysis bullosa. The Journal of investigative dermatology 57 8618019
2005 Usefulness of BP180 NC16a enzyme-linked immunosorbent assay in the serodiagnosis of pemphigoid gestationis and in differentiating between pemphigoid gestationis and pruritic urticarial papules and plaques of pregnancy. Archives of dermatology 55 15967916
1998 Direct interaction between the intracellular domains of bullous pemphigoid antigen 2 (BP180) and beta 4 integrin, hemidesmosomal components of basal keratinocytes. Biochemical and biophysical research communications 55 9500991
2021 EGFR-mediated epidermal stem cell motility drives skin regeneration through COL17A1 proteolysis. The Journal of cell biology 54 34550317
1998 Role of the bullous pemphigoid antigen 180 (BP180) in the assembly of hemidesmosomes and cell adhesion--reexpression of BP180 in generalized atrophic benign epidermolysis bullosa keratinocytes. Experimental cell research 52 9521865
2013 Bullous pemphigoid IgG induces BP180 internalization via a macropinocytic pathway. The American journal of pathology 51 23337823
2012 Natural gene therapy may occur in all patients with generalized non-Herlitz junctional epidermolysis bullosa with COL17A1 mutations. The Journal of investigative dermatology 50 22318390
2014 BP180- and BP230-specific IgG autoantibodies in pruritic disorders of the elderly: a preclinical stage of bullous pemphigoid? The British journal of dermatology 47 24601973
2008 Serum levels of autoantibodies to BP180 correlate with disease activity in patients with bullous pemphigoid. International journal of dermatology 47 18289320
2010 Type XVII collagen (BP180) can function as a cell-matrix adhesion molecule via binding to laminin 332. Matrix biology : journal of the International Society for Matrix Biology 46 21034821
1999 BP180/type XVII collagen: its role in acquired and inherited disorders or the dermal-epidermal junction. Archives of dermatological research 44 10335914
2009 T cells reactive with the NC16A domain of BP180 are present in vulval lichen sclerosus and lichen planus. Journal of the European Academy of Dermatology and Venereology : JEADV 43 19686329
2015 Mutations in collagen, type XVII, alpha 1 (COL17A1) cause epithelial recurrent erosion dystrophy (ERED). Human mutation 41 25676728
2018 BP180 dysfunction triggers spontaneous skin inflammation in mice. Proceedings of the National Academy of Sciences of the United States of America 40 29866844
2012 Usefulness of Enzyme-linked Immunosorbent Assay Using Recombinant BP180 and BP230 for Serodiagnosis and Monitoring Disease Activity of Bullous Pemphigoid. Annals of dermatology 40 22363155
2012 Missing the target: characterization of bullous pemphigoid patients who are negative using the BP180 enzyme-linked immunosorbant assay. Journal of the American Academy of Dermatology 40 23083837
1995 Diminished expression of the extracellular domain of bullous pemphigoid antigen 2 (BPAG2) in the epidermal basement membrane of patients with generalized atrophic benign epidermolysis bullosa. Experimental dermatology 39 8535614
2021 The CD44/COL17A1 pathway promotes the formation of multilayered, transformed epithelia. Current biology : CB 38 34087104
1999 Bullous pemphigoid sera that contain antibodies to BPAg2 also contain antibodies to LABD97 that recognize epitopes distal to the NC16A domain. The Journal of investigative dermatology 38 9989788
1997 A homozygous in-frame deletion in the collagenous domain of bullous pemphigoid antigen BP180 (type XVII collagen) causes generalized atrophic benign epidermolysis bullosa. The Journal of investigative dermatology 37 9204958
2003 Cicatricial pemphigoid sera specifically react with the most C-terminal portion of BP180. Journal of dermatological science 36 12788530
2017 Identification of a novel p53 target, COL17A1, that inhibits breast cancer cell migration and invasion. Oncotarget 35 28915553
2013 A role for anti-BP180 autoantibodies in chronic rhinosinusitis. The Laryngoscope 35 24167818
1992 Cloning of partial cDNA for mouse 180-kDa bullous pemphigoid antigen (BPAG2), a highly conserved collagenous protein of the cutaneous basement membrane zone. The Journal of investigative dermatology 35 1512460
2000 Bullous pemphigoid of childhood: autoantibodies target the same epitopes within the NC16A domain of BP180 as autoantibodies in bullous pemphigoid of adulthood. Archives of dermatology 34 10768652
2016 Clinical and Immunological Studies of 332 Japanese Patients Tentatively Diagnosed as Anti-BP180-type Mucous Membrane Pemphigoid: A Novel BP180 C-terminal Domain Enzyme-linked Immunosorbent Assay. Acta dermato-venereologica 33 26984589
2007 Localized and generalized forms of blistering in junctional epidermolysis bullosa due to COL17A1 mutations in the Netherlands. The British journal of dermatology 33 17263807
2003 BP180 (type XVII collagen) and its role in cutaneous biology and disease. Advances in dermatology 33 14626817
2016 A COL17A1 Splice-Altering Mutation Is Prevalent in Inherited Recurrent Corneal Erosions. Ophthalmology 31 26786512
2001 A homozygous nonsense mutation in type XVII collagen gene (COL17A1) uncovers an alternatively spliced mRNA accounting for an unusually mild form of non-Herlitz junctional epidermolysis bullosa. The Journal of investigative dermatology 31 11168815
2018 Prospective study in bullous pemphigoid: association of high serum anti-BP180 IgG levels with increased mortality and reduced Karnofsky score. The British journal of dermatology 30 29607480
2018 Next generation sequencing identifies double homozygous mutations in two distinct genes (EXPH5 and COL17A1) in a patient with concomitant simplex and junctional epidermolysis bullosa. Human mutation 28 30016581
2012 Collagen XVII (BP180) modulates keratinocyte expression of the proinflammatory chemokine, IL-8. Experimental dermatology 27 22775995
2021 BP180/Collagen XVII: A Molecular View. International journal of molecular sciences 26 34830116
2010 Childhood vulval lichen sclerosus: autoimmunity to the basement membrane zone protein BP180 and its relationship to autoimmunity. Clinical and experimental dermatology 26 20456392
2002 BP180 as the common autoantigen in blistering diseases with different clinical phenotypes. The Keio journal of medicine 26 11951375
2000 The extracellular domain of BPAG2 has a loop structure in the carboxy terminal flexible tail in vivo. The Journal of investigative dermatology 26 11069628
1998 Novel homozygous and compound heterozygous COL17A1 mutations associated with junctional epidermolysis bullosa. The Journal of investigative dermatology 26 9740252
1993 Chromosomal localization of mouse bullous pemphigoid antigens. BPAG1 and BPAG2: identification of a new region of homology between mouse and human chromosomes. Genomics 26 8432531
1998 Hemidesmosomes and their unique transmembrane protein BP180. Microscopy research and technique 25 9840798
2013 Detection of IgG and IgE reactivity to BP180 using the ISAC® microarray system. The British journal of dermatology 24 23252883
1999 Human p120ctn catenin: tissue-specific expression of isoforms and molecular interactions with BP180/type XVII collagen. Journal of cellular biochemistry 24 10321838
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. The Journal of investigative dermatology 23 9457913
2018 BP180 Autoantibodies Target Different Epitopes in Multiple Sclerosis or Alzheimer's Disease than in Bullous Pemphigoid. The Journal of investigative dermatology 22 30315782
2008 Autoantibodies to basement membrane proteins BP180 and BP230 are commonly detected in normal subjects by immunoblotting. The Australasian journal of dermatology 22 18638220
2007 Bullous pemphigoid positive for anti-BP180 and anti-laminin 5 antibodies in a patient with graft-vs-host disease. Journal of the American Academy of Dermatology 22 17434049
2018 Clinical and Immunological Profiles of 14 Patients With Bullous Pemphigoid Without IgG Autoantibodies to the BP180 NC16A Domain. JAMA dermatology 21 29299596
1992 Transforming growth factor-beta up-regulates the expression of the genes for beta 4 integrin and bullous pemphigoid antigens (BPAG1 and BPAG2) in normal and transformed human keratinocytes. The Journal of investigative dermatology 21 1401998
2022 Paired nicking-mediated COL17A1 reframing for junctional epidermolysis bullosa. Molecular therapy : the journal of the American Society of Gene Therapy 20 35490295

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