(last modified February 4, 2011)
generated with the help of the Hogeschool Leiden, in particular students Daan van Luijk en Tavares Chin Sue
Plectin (PLEC) was first described by (Pytela and
Wiche 1980), as 500
KDa protein that is found in almost all mammalian cells. With 500 KDa, it is one of
largest polypeptides known. The protein is identified as a major component of intermediate filaments. It acts as a link between the actin
microfilaments, microtubules and intermediate filaments (Liu et al.
1996). Plectin plays an important role in maintaining the mechanical integrity and
visco-elastic properties of tissues.
Liu et al. (1996) first reported the cloning of the rat plectine gene by screening a placenta cDNA library with previously published human plectin probes (Wiche 1991) and probes derived from rat plectin. The deduced protein sequences for human and rat plectin are 93% identical. The human plectin gene contains 33 exons that extend over 60 Kb genomic DNA, mapped to 8q24 (Liu et al. 1996). Most of the introns reside within a region encoding the globular N-terminal domain of the molecule. The entire central-rod and C-terminal globular domains are encoded by single large exons of more than 3 kb and 6 kb, respectively.
Variants in the PLEC gene have been found in combination with several genetic diseases. Smith et al. (1996) first identified a duplication mutation in the plectin-gene, in a patient with epidermolysis bullosa simplex with muscular dystrophy (EBS-MD, OMIM 226670). Koss-Harnes et al. (2002) described a point mutation in the gene in a family with autosomal dominant epidermolysis bullosa simplex Ogna type (EBS-OG, OMIM 131950). Finally, Charlesworth et al. (2003) found point mutations and deletions in patients with epidermolysis bullosa simplex with pyloric atresia (EBS-PA, OMIM 612138).
Links to other databases:
Gene Symbol nomenclature EntrezGene OMIM Gene Map
The plectin gene (Gene symbol PLEC, aliases EBS1, PLEC1, PCN, PLTN) maps to chromosome 8q24 (Liu et al. 1996), is transcribed from telomere to centromere and is flanked by EPPK1 (centromeric) and PARP10 (telomeric), both in the same transcriptional orientation. The gene measures ~60 Kb and contains 33 exons. The gene contains 7 alternative promoters/exon 01 in intron 2, generating a range of different transcripts. Most of the introns reside within a region encoding the globular N-terminal domain of the molecule. The entire central-rod and C-terminal globular domains are encoded by single large exons of more than 3 kb and 6 kb, respectively. Overall, the organization of the human plectin gene is strikingly similar to that of human dystonin gene (bullous pemphigoid antigen-1, DST).
Lesniewicz et al. (2005) mapped the mouse Plec1 gene to chromosome 15, immediately downstream of and in a head-to-tail orientation with the Parp10 gene. The plectin gene locus in mouse has been analyzed in detail (Fuchs et al. (1999), Rezniczek et al. ), revealing a genomic exon-intron organization with well over 40 exons spanning over 62 kb and, like in human, an unusual 5' transcript complexity of plectin transcript/N-terminal isoforms. Eleven exons (1-1j) have been identified that alternatively splice directly into a common exon 2 which is the first exon to encode plectin's highly conserved actin binding domain (ABD). Three additional exons (-1, 0a, and 0) splice into an alternative first coding exon (1c), and two additional exons (2alpha and 3alpha) are optionally spliced within the exons encoding the acting binding domain (exons 2-8).
|5' cDNA position (in bp)||Splice
|2||199||36484||-6||1||5' UTR, alternative translation initiation site GNE isoforms 3, translation initiation site GNE isoforms 1|
|01h||alternative promoters/first exon 01h, 5' UTR, alternative translation initiation site|
|01g||alternative promoters/first exon 01g, 5' UTR, alternative translation initiation site|
|01f||alternative promoters/first exon 01f, 5' UTR, alternative translation initiation site|
|01e||alternative promoters/first exon 01e, 5' UTR, alternative translation initiation site|
|01d||alternative promoters/first exon 01d, 5' UTR, alternative translation initiation site|
|01c||alternative promoters/first exon 01c, 5' UTR, alternative translation initiation site|
|01b||alternative promoters/first exon 01b, 5' UTR, alternative translation initiation site|
|33||7243||-||7507||-||translation stop codon, 3'UTR|
Exon: numbering of exons with the first base of the Met-codon counted as position 1 (see coding DNA Reference Sequence). Exon size: size of exon indicated in basepairs (bp). Intron size: size of intron indicated in basepairs. 5' cDNA position: first base of the exon. Splice after: splicing occurs in between of two coding triplets (0), after the first (1) or the second (2) base of a triplet. Remarks: 5'UTR = 5' untranslated region, 3'UTR = 3' untranslated region.
Links to other databases: UniGene: Hs.434248 RefSeq: NM_000445.3
Due to the use of 8 different promoter/first exons, 7 located in intron 2, the PLEC generates a range of transcript variants (see coding DNA Reference Sequence). Transcripts lacking exon 31 have been detected in mouse (PMID:10556294), rat (PMID: 9177781), and human (PMID: 11441066, 10780662, 20052759).
By RT-PCR Kazerounian et al. (2002) found that plectin was expressed in all adult and fetal tissues examined, except leukocytes. Only a weak band was obtained from adult brain and thymus.
Links to other databases: RefSeq: NP_000436.2 UniProt: Q15149
The plectin protein is one of the largest proteins known. Consisting of between 4515 and 4684 amino acids it has a predicted weight of 518-kD. At the N-terminus the protein contains an actin-binding domain homologous to that of the dystrophin family. At its C-terminus plectin shows homology to intermediate filament-associated protein desmoplakin (DSP).
Isoforms lacking the central rod domain encoded by exon 31 have been detected in mouse (PMID:10556294), rat (PMID: 9177781), and human (PMID: 11441066, 10780662, 20052759). The short alternative amino-terminal sequences encoded by the different first exons have been shown to direct the targeting of the protein isoforms to distinct subcellular locations (Rezniczek et al. 2003).
Natsuga et al. (2010) determined that human fibroblasts express 2 different plectin isoforms; a 500-kD full-length protein and a 390-kD protein lacking the rod domain. Immunoblot assays found that the quantitative ratio of full-length : rodless plectin was 14.2:1 in fibroblasts, 21.3:1 in keratinocytes and 1.37:1 in skeletal muscle.
Multiple protein sequence alignment for PLEC
Links to other databases: OMIM: 226670, 131950 and 612138
Disease-causing variants in the PLEC gene have been identified in patients with various types of the epidermolysis bullosa simplex (EBS). The three types of EBS were plectin plays a role are; EBS with Muscular Dystrophy (EBS-MD), EBS Ogna Type (EBS-OG) and EBS with Pyloric Atresia (EBS-PA).
Smith et al. (1996) were the first to describe pathogenic changes in the plectin gene. In a patient with epidermolysis bullosa simplex with muscular dystrophy (EBS-MD, OMIM 226670) they found a homozygous 8-bp duplication mutation (insertion of the sequence GTGGAGGA) leading to a frame shift on protein level.
In the original Norwegian family with autosomal dominant epidermolysis bullosa simplex Ogna type (EBS-OG, OMIM 131950) reported by Gedde-Dahl (1971), Koss-Harnes et al. (2002) reported a heterozygous C-to-T substiturion in exon 31 of the PLEC1 gene predicted to result in an Arg2110Trp change.
In 3 sisters with epidermolysis bullosa simplex with pyloric atresia, Charlesworth et al. (2003) identified a homozygous 14-bp deletion at nucleotide 2727 in the PLEC gene.
Andra et al. (1997) iinactivated the plectin gene in mice, revealing an essential function in maintaining the integrity of skin, muscle, and heart cytro-architecture. Targeted mutations result in neanatal death, skin blistering, impaired myofibril integrity, reduced hemidesmosome number and disintegrateion of intercalated disks in the heart. Mice lacking isoform- 1 are viable with no skin blistering but leukocyte recruitment to wounds is impaired.
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