Summary: Plectin is a prominent member of an important family of structurally and in part functionally related proteins, termed plakins or cytolinkers, that are capable of interlinking different elements of the cytoskeleton. Plakins, with their multi-domain structure and enormous size, not only play crucial roles in maintaining cell and tissue integrity and orchestrating dynamic changes in cytoarchitecture and cell shape, but also serve as scaffolding platforms for the assembly, positioning, and regulation of signaling complexes (reviewed in PMID: 9701547, 11854008, and 17499243). Plectin is expressed as several protein isoforms in a wide range of cell types and tissues from a single gene located on chromosome 8 in humans (PMID: 8633055, 8698233). Until 2010, this locus was named plectin 1 (symbol PLEC1 in human; Plec1 in mouse and rat) and the gene product had been referred to as 'hemidesmosomal protein 1' or 'plectin 1, intermediate filament binding 500kDa'. These names were superseded by plectin. The plectin gene locus in mouse on chromosome 15 has been analyzed in detail (PMID: 10556294, 14559777), revealing a genomic exon-intron organization with well over 40 exons spanning over 62 kb and an unusual 5' transcript complexity of plectin 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). Analysis of the human locus has identified eight of the eleven alternative 5' exons found in mouse and rat (PMID: 14672974); exons 1i, 1j and 1h have not been confirmed in human. Furthermore, 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 direct the targeting of the various isoforms to distinct subcellular locations (PMID: 14559777). As the expression of specific plectin isoforms was found to be dependent on cell type (tissue) and stage of development (PMID: 10556294, 12542521, 17389230) it appears that each cell type (tissue) contains a unique set (proportion and composition) of plectin isoforms, as if custom-made for specific requirements of the particular cells. Concordantly, individual isoforms were found to carry out distinct and specific functions (PMID: 14559777, 12542521, 18541706). In 1996, a number of groups reported that patients suffering from epidermolysis bullosa simplex with muscular dystrophy (EBS-MD) lacked plectin expression in skin and muscle tissues due to defects in the plectin gene (PMID: 8698233, 8941634, 8636409, 8894687, 8696340). Two other subtypes of plectin-related EBS have been described: EBS-pyloric atresia (PA) and EBS-Ogna. For reviews of plectin-related diseases see PMID: 15810881, 19945614. Mutations in the plectin gene related to human diseases should be named based on the position in NM_000445 (variant 1, isoform 1c), unless the mutation is located within one of the other alternative first exons, in which case the position in the respective Reference Sequence should be used. [provided by RefSeq, Aug 2011].


GO terms in PLEC

Term TypeEvidence TypeGO Term IDGO Des.
MFHDAGO:0003723RNA binding
MFIEAGO:0003779actin binding
MFIBAGO:0005198structural molecule activity
MFIBAGO:0005200structural constituent of cytoskeleton
MFIPIGO:0005515protein binding
MFIBAGO:0008307structural constituent of muscle
MFTASGO:0008307structural constituent of muscle
MFIBAGO:0030506ankyrin binding
MFIPIGO:0030506ankyrin binding
MFHDAGO:0045296cadherin binding
MFIBAGO:0045296cadherin binding
CCIBAGO:0005882intermediate filament
CCNASGO:0005886plasma membrane
CCIEAGO:0005903brush border
CCHDAGO:0005925focal adhesion
CCIBAGO:0005925focal adhesion
CCIDAGO:0005925focal adhesion
CCIDAGO:0045111intermediate filament cytoskeleton
CCIBAGO:0048471perinuclear region of cytoplasm
CCHDAGO:0070062extracellular exosome
BPIBAGO:0031581hemidesmosome assembly
BPIDAGO:0031581hemidesmosome assembly
BPTASGO:0031581hemidesmosome assembly
BPIBAGO:0042060wound healing
BPIBAGO:0045104intermediate filament cytoskeleton organization

Gene expression in normal tissue: PLEC

Gene-model tissue-cancer distribution: Bubble Plot

Gene-drug pathway distribution

Pathways in PLEC

DatabasePathway IDPathway Des.
reactomeR-HSA-111465Apoptotic cleavage of cellular proteins
reactomeR-HSA-1474244Extracellular matrix organization
reactomeR-HSA-1474290Collagen formation
reactomeR-HSA-1500931Cell-Cell communication
reactomeR-HSA-2022090Assembly of collagen fibrils and other multimeric structures
reactomeR-HSA-264870Caspase-mediated cleavage of cytoskeletal proteins
reactomeR-HSA-446107Type I hemidesmosome assembly
reactomeR-HSA-446728Cell junction organization
reactomeR-HSA-5357801Programmed Cell Death
reactomeR-HSA-75153Apoptotic execution phase

Gene-Drug: Aster Plot

Drug IDDrug NameModel Num.

Gene in drug-gene network: Network Plot

Gene-drug targets distribution

Gene Structure: PDB

Models in PLEC