Localization of the human gene for 230-kDal bullous pemphigoid autoantigen (BPAG1) to chromosome 6pter→q15

“…In the fly, the spectraplakin shot emerged from genetic screens aimed at identifying genes required for integrin-mediated adhesion (Prout et al, 1997;Gregory and Brown, 1998;Strumpf and Volk, 1998) or axon extension (Van Vactor et al, 1993;Lee et al, 2000). The vertebrate spectraplakin BPAG1/dystonin was identified as a protein targeted by the autoimmune disease bullous pemphigoid in humans (Minoshima et al, 1991) and as the gene affected in the disease dystonia musculorum in mice (Brown et al, 1995a;Guo et al, 1995). …”

mentioning

confidence: 99%

The `Spectraplakins': cytoskeletal giants with characteristics of both spectrin and plakin families

Röper

Gregory

Brown

2002

Journal of Cell Science

153

169

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IntroductionA recently discovered family of cytoskeletal proteins belongs within both the spectrin and plakin superfamilies. These superfamilies consist of proteins that contribute to the linkage between the plasma membrane and the cytoskeleton. Spectrin superfamily members bind and crosslink actin filaments and attach these to membrane receptors. Members of the plakin superfamily were first identified as components of desmosomes and hemidesmosomes, connecting the adhesion receptors to intermediate filaments, but they also can crosslink different cytoskeletal elements. At present we know of two mammalian genes that encode related members of the new family, BPAG1 and MACF1, and a single Drosophila gene, short stop (shot) (Figs 1 and 2). Each of these is also known by other names, which reflects their independent discovery by different groups: MACF1 is known as ACF7, MACF, MACF7, macrophin, trabeculin α and ABP620; BPAG1 is known as dystonin and MACF2; shot is known as kakapo, kopupu and groovin (Brown et al., 1995a;Bernier et al., 1996;Becker et al., 1997;Prout et al., 1997;Gregory and Brown, 1998;Strumpf and Volk, 1998;Walsh and Brown, 1998;Leung et al., 1999b; Okuda et al., 1999;Sun et al., 1999;Yang et al., 1999;Lee et al., 2000;Leung et al., 2001b;Sun et al., 2001). A single Caenorhabditis elegans gene can also be identified in the genomic sequence; this is currently annotated as three genes: ZK1151.1, ZK1151.2 and ZK1151.3 (C. elegans Sequencing Consortium, 1998). Because the proteins encoded by these genes share features with both spectrin and plakin superfamily members and may represent the evolutionary precursor of the plakins (see below), we refer to them as spectraplakins to highlight their dual nature. Here we discuss the possible functions of spectraplakins indicated by their sequences and by biochemical and genetic studies, extrapolating from the functions of homologous cytoskeletal proteins.Spectraplakins in various species were identified independently in quite different contexts. In the fly, the spectraplakin shot emerged from genetic screens aimed at identifying genes required for integrin-mediated adhesion (Prout et al., 1997;Gregory and Brown, 1998;Strumpf and Volk, 1998) or axon extension (Van Vactor et al., 1993;Lee et al., 2000). The vertebrate spectraplakin BPAG1/dystonin was identified as a protein targeted by the autoimmune disease bullous pemphigoid in humans (Minoshima et al., 1991) and as the gene affected in the disease dystonia musculorum in mice (Brown et al., 1995a;Guo et al., 1995). Diverse motifs within spectraplakin isoformsThe full complexity of the genes producing spectraplakins has gradually emerged. The first spectraplakin product characterised, BPAG1e, is a substantial protein of 2649 residues encoded by an 8.7 kb mRNA; yet this appears to be the smallest and simplest of the spectraplakin products (Fig. 3). The previous lack of awareness of the larger spectraplakins is likely to have led to erroneous conclusions being drawn in the older literature about the functions of th...

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“…The results indicated that the human BPAGl gene resides at locus 6pl 1-6p 12, and this conclu sion was supported by hybridizations with a panel of hu man x rodent hybrid cell DNA, which indicated concor dance with the human chromosome 6 [13,16). Different genes of the human basement membrane zone components have been previously mapped to different loci, and for 30 Tamai/Sawamura/Choi Do/Li/Uitto Human BPAGl Gene …”

Section: Chromosomal Mapping Of the Bpag1 Genementioning

confidence: 77%

“…21) without interruption, while the most upstream of the 3 sub domains was encoded by 3 separate exons (No. [15][16][17]. The region corresponding to the amino-terminal globular domain consisted of 15 exons varying from 78 to 591 bp in size ( fig.…”

Section: Determination Of the Exon-lntron Organization Of The Bpag1 Genementioning

confidence: 99%

Molecular Biology of the 230-kD Bullous Pemphigoid Antigen

Tamai¹,

Sawamura²,

Choi³

et al. 1994

Dermatology

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The 230-kD bullous pemphigoid antigen is a hemidesmosomal protein of the cutaneous basement membrane zone. We have previously cloned overlapping cDNAs corresponding to the human 230-kD bullous pemphigoid antigen gene (BPAG1), located at the human chromosomal locus 6p11–12. Utilizing the cDNA clones, a genomic DNA λFIX II phage library was screened. Seven overlapping genomic clones, spanning ∼20 kb, were isolated. These clones were shown to contain the entire ∼ 9-kb coding sequence of BPAG1 and it consisted of 22 separate exons which varied from 78 to 2,810 bp in size. Elucidation of 2.6 kb of 5′-flanking DNA was found to contain several putative transcriptional response elements, and development of promoter chloramphenicol acetyltransferase (CAT) reporter gene constructs allowed identification of putative cis-elements which confer keratinocyte-specific expression to the gene. In particular, a putative AP2-binding sequence (KRE2) in the position ––(1,786––1,778) was shown to be responsible for marked enhancement of the endogenous promoter, as well as of a heterologous thymidine kinase/CAT construct, activity in normal human keratinocytes. Normal human keratinocyte nuclear extracts contained a protein, designated as KTP1, which complexed with the KRE2 oligomer by gel mobility shift assays. UV cross-linking and Southwestern analysis suggested that KTP1 is a DNA-binding protein clearly distinct from AP2, and this protein may be responsible for the basal keratinocyte-specific expression of the BPAG1 gene.

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Localization of the human gene for 230-kDal bullous pemphigoid autoantigen (BPAG1) to chromosome 6pter→q15

Cited by 13 publications

References 16 publications

Report of the committee on the genetic constitution of chromosome 6

Report of the committee on the genetic constitution of chromosome 6

The `Spectraplakins': cytoskeletal giants with characteristics of both spectrin and plakin families

Molecular Biology of the 230-kD Bullous Pemphigoid Antigen

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