Tbio PLEC Plectin

Protein Summary

Description

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. 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 These names were superseded by plectin.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]

Uniprot Accession IDs

• Q15149
• Q15148
• Q16640
• Q6S376
• Q6S377
• Q6S378
• Q6S379
• Q6S380
• Q6S381
• Q6S382
• Q6S383
• PCN

Gene Name

• PLEC

Ensembl ID

• ENST00000322810
• ENSP00000323856
• ENSG00000178209
• ENST00000345136
• ENSP00000344848
• ENST00000354589
• ENSP00000346602
• ENST00000354958
• ENSP00000347044
• ENST00000356346
• ENSP00000348702
• ENST00000357649
• ENSP00000350277
• ENST00000398774
• ENSP00000381756
• ENST00000436759
• ENSP00000388180
• ENST00000527096
• ENSP00000434583

Symbol

• PLEC1
• HD1
• PCN
• EBS1
• EBSO
• PLTN
• EBSMD
• EBSND
• EBSOG
• EBSPA
• PLEC1
• LGMD2Q
• PLEC1b
• LGMDR17

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
hub protein	1
ligand (protein) perturbation	0.99
drug perturbation	0.96
transcription factor binding site profile	0.96
transcription factor perturbation	0.91

Protein Classes

PANTHER Classes

Protein / Cytoskeletal Protein / Intermediate Filament / Intermediate Filament Binding Protein / Plectin

DTO Classes

Protein / Cellular Structure / Intermediate Filament / Intermediate Filament Binding Protein / Plectin

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 480.03   (req: < 5)

Gene RIFs: 50   (req: <= 3)

Antibodies: 180   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 480.03   (req: >= 5)

Gene RIFs: 50   (req: > 3)

Antibodies: 180   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 10

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Expression Data (0 Tissues)

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No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (4)

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (0)

No active ligands found

Protein-Protein Interactions (381)

Explore Interacting Targets

1 – 10 of 381

• See Interactions on String-DB

C6orf141

Tdark

Novelty:  1.46022784

p_int:  0.999985129

p_ni:  0.000014871

Data Source:  BioPlex

GSDME

Tbio

Novelty:  0.01231123

p_int:  0.994392417

p_ni:  0.005607583

Score:  0.167

Data Source:  BioPlex,STRINGDB

CCDC68

Tbio

Novelty:  0.1262502

p_int:  0.992687381

p_ni:  0.007312619

Score:  0.201

Data Source:  BioPlex,STRINGDB

NEFM

Tbio

Novelty:  0.00239134

p_int:  0.991598474

p_ni:  0.008401526

Score:  0.305

Data Source:  BioPlex,STRINGDB

RAPGEF5

Tbio

Novelty:  0.02449802

p_int:  0.985649193

p_ni:  0.014350807

Data Source:  BioPlex

GFOD1

Tdark

Family:  Enzyme

Novelty:  0.35031766

p_int:  0.957384589

p_ni:  0.042615411

Score:  0.166

Data Source:  BioPlex,STRINGDB

FAM24B

Tdark

Novelty:  1.04675689

p_int:  0.93225298

p_ni:  0.06774702

Data Source:  BioPlex

SOCS6

Tbio

Novelty:  0.00993375

p_int:  0.887467941

p_ni:  0.112532058

Score:  0.193

Data Source:  BioPlex,STRINGDB

TFDP3

Tbio

Family:  TF

Novelty:  0.00223003

p_int:  0.879869728

p_ni:  0.120130272

Score:  0.195

Data Source:  BioPlex,STRINGDB

PRUNE1

Tchem

Novelty:  0.02136836

p_int:  0.867573742

p_ni:  0.132426258

Data Source:  BioPlex

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (18)

Reactome (11)

PathwayCommons (2)

WikiPathways (5)

Apoptosis (R-HSA-109581)

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1 – 5 of 11

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Apoptosis	177 targets	R-HSA-109581
Reactome	Apoptotic cleavage of cellular proteins	38 targets	R-HSA-111465
Reactome	Apoptotic execution phase	52 targets	R-HSA-75153
Reactome	Assembly of collagen fibrils and other multimeric structures	57 targets	R-HSA-2022090
Reactome	Caspase-mediated cleavage of cytoskeletal proteins	12 targets	R-HSA-264870

Name	Explore in Pharos	Explore in Source
Apoptosis	177 targets	R-HSA-109581
Apoptotic cleavage of cellular proteins	38 targets	R-HSA-111465
Apoptotic execution phase	52 targets	R-HSA-75153
Assembly of collagen fibrils and other multimeric structures	57 targets	R-HSA-2022090
Caspase-mediated cleavage of cytoskeletal proteins	12 targets	R-HSA-264870

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (23)

Functions (7)

Components (13)

Processes (3)

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Items per page:

10

1 – 7 of 7

GO Term	Evidence	Assigned by
ankyrin binding	Inferred from Physical Interaction (IPI)	BHF-UCL
structural constituent of muscle	Inferred from Mutant Phenotype (IMP)	UniProtKB
cadherin binding	Inferred from High Throughput Direct Assay (HDA)	BHF-UCL
RNA binding	Inferred from High Throughput Direct Assay (HDA)	UniProtKB
structural constituent of cytoskeleton	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
structural molecule activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
actin binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Disease Associations (null)

No disease associations found

GWAS Traits (24)

• Explore on Target Illumination GWAS Analytics (TIGA)

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1 – 5 of 24

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
low density lipoprotein cholesterol measurement	EFO_0004611	9	8	11		96.6
platelet count	EFO_0004309	3	2	2	2.3	94.5
mean corpuscular volume	EFO_0004526	2	2	2		90.4
total cholesterol measurement	EFO_0004574	4	4	4		89.4
apolipoprotein B measurement	EFO_0004615	2	2	2		87.4

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 24

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
low density lipoprotein cholesterol measurement	EFO_0004611	11		96.6
platelet count	EFO_0004309	2	2.3	94.5
mean corpuscular volume	EFO_0004526	2		90.4
total cholesterol measurement	EFO_0004574	4		89.4
apolipoprotein B measurement	EFO_0004615	2		87.4

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Acetylation
Actin-binding
Alternative splicing
Cell junction
Coiled coil
Complete proteome
Cytoplasm
Cytoskeleton
Direct protein sequencing

GWAS Trait Find Similar Targets

No Header	No Header
apolipoprotein B measurement
bipolar I disorder
body height
creatinine measurement
diastolic blood pressure
electrocardiography
fibrinogen measurement
glomerular filtration rate
hip circumference
HMG CoA reductase inhibitor use measurement

MGI Phenotype Find Similar Targets

No Header	No Header
behavior/neurological phenotype
cardiovascular system phenotype
cellular phenotype
growth/size/body region phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype
integument phenotype
mortality/aging
muscle phenotype

IDG Resources

No IDG generated resources found

Orthologs (10)

1 – 5 of 10

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	plectin	VGNC:821	464454
Macaque	plectin		699517
Mouse	plectin	MGI:1277961	18810
Rat	plectin	RGD:621649	64204
Dog	plectin	VGNC:44665	482083

Species	Name	OMA	EggNOG	Inparanoid
Chimp	plectin
Macaque	plectin
Mouse	plectin
Rat	plectin
Dog	plectin

Publication Statistics

PubMed Score 480.03

PubMed score by year

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PubTator Score 262.31

PubTator score by year

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Related Publications

Text Mined References (114)

GeneRif Annotations (50)

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PMID	Year	Title