PLEC1

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 (for reviews see 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 (PMID: 8633055, 8698233). 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). Furthermore, isoforms lacking the central rod domain encoded by exon 31 have been detected in mouse and rat (PMID:10556294, 9177781), and as judged by molecular size, have also been detected in human on the protein level (PMID: 11441066, 10780662). It has been shown that 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

plectin 1, intermediate filament binding protein 500kDa

Interlinks intermediate filaments with microtubules and microfilaments and anchors intermediate filaments to desmosomes or hemidesmosomes. Could also bind muscle proteins such as actin to membrane complexes in muscle. May be involved not only in the filaments network, but also in the regulation of their dynamics. Structural component of muscle. Isoform 9 plays a major role in the maintenance of myofiber integrity.

Actin cytoskeleton reorganizationIEA:Ensembl
Actomyosin contractile ring assembly actin filament organizationIEA:Ensembl
Adherens junction organizationIEA:Ensembl
Cardiac muscle cell developmentIEA:Ensembl
Cell morphogenesisIEA:Ensembl
Cellular response to extracellular stimulusIEA:Ensembl
Cellular response to fluid shear stressIEA:Ensembl
Cellular response to hydrostatic pressureIEA:Ensembl
Cellular response to mechanical stimulusIEA:Ensembl
Establishment of skin barrierIEA:Ensembl
Fibroblast migrationIEA:Ensembl
Gene expressionIEA:Ensembl
Hemidesmosome assemblyManual Assertion Based On ExperimentIDA:UniProtKB
Intermediate filament cytoskeleton organizationManual Assertion Based On ExperimentIBA:GO_Central
Intermediate filament organizationIEA:Ensembl
Keratinocyte developmentIEA:Ensembl
Leukocyte migration involved in immune responseIEA:Ensembl
Mitochondrion morphogenesisIEA:Ensembl
Multicellular organism growthIEA:Ensembl
Myoblast differentiationIEA:Ensembl
Negative regulation of protein kinase activityIEA:Ensembl
Nucleus organizationIEA:Ensembl
Peripheral nervous system myelin maintenanceIEA:Ensembl
Protein localizationIEA:Ensembl
Protein-containing complex organizationIEA:Ensembl
Regulation of ATP citrate synthase activityIEA:Ensembl
Regulation of vascular permeabilityIEA:Ensembl
Respiratory electron transport chainIEA:Ensembl
Response to foodIEA:Ensembl
Sarcomere organizationIEA:Ensembl
Skeletal muscle fiber developmentIEA:Ensembl
Skeletal myofibril assemblyIEA:Ensembl
T cell chemotaxisIEA:Ensembl
Tight junction organizationIEA:Ensembl
Transmission of nerve impulseIEA:Ensembl
Wound healingManual Assertion Based On ExperimentIBA:GO_Central

Cytoplasm, cytoskeleton
Cell junction, hemidesmosome

Epidermolysis bullosa simplex with pyloric atresia (EBS-PA):
Autosomal recessive genodermatosis characterized by severe skin blistering at birth and congenital pyloric atresia. Death usually occurs in infancy. This disorder is allelic to MD-EBS.
Epidermolysis bullosa simplex, with muscular dystrophy (MD-EBS):
A form of epidermolysis bullosa characterized by the association of blister formation at the level of the hemidesmosome with late-onset muscular dystrophy.
Epidermolysis bullosa simplex, Ogna type (O-EBS):
A form of intraepidermal epidermolysis bullosa characterized by generalized skin bruising, skin fragility with non-scarring blistering and small hemorrhagic blisters on hands. At the ultrastructural level, it is differentiated from classical cases of K-EBS, WC-EBS and DM-EBS, by the occurrence of blisters originating in basal cells above hemidesmosomes, and abnormal hemidesmosome intracellular attachment plates.
Muscular dystrophy, limb-girdle, autosomal recessive 17 (LGMDR17):
A form of limb-girdle muscular dystrophy characterized by early childhood onset of proximal muscle weakness. Limb-girdle muscular dystrophies are characterized by proximal weakness, weakness of the hip and shoulder girdles and prominent asymmetrical quadriceps femoris and biceps brachii atrophy.
Epidermolysis bullosa simplex with nail dystrophy (EBSND):
A form of epidermolysis bullosa, a dermatologic disorder characterized by skin blistering. EBSND patients also manifest nail dystrophy.

Phosphorylated by CDK1; regulates dissociation from intermediate filaments during mitosis.