PLEC

Protein identityUniProt · HPA

UniProt accession

Q15149

Gene

PLEC

Ensembl

ENSG00000178209

Chromosome

8

Canonical length

4684 aa

Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins

Subcellular location

Intermediate filaments,Focal adhesion sites,Cytosol

Quaternary structure

Homotetramer

OverviewNCBI Gene

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 These names were superseded by plectin.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]

Canonical amino-acid sequenceUniProt

4684 residues, UniProt reviewed canonical sequence.

>Q15149|PLEC
     1  MVAGMLMPRD QLRAIYEVLF REGVMVAKKD RRPRSLHPHV PGVTNLQVMR AMASLRARGL
    61  VRETFAWCHF YWYLTNEGIA HLRQYLHLPP EIVPASLQRV RRPVAMVMPA RRTPHVQAVQ
   121  GPLGSPPKRG PLPTEEQRVY RRKELEEVSP ETPVVPATTQ RTLARPGPEP APATDERDRV
   181  QKKTFTKWVN KHLIKAQRHI SDLYEDLRDG HNLISLLEVL SGDSLPREKG RMRFHKLQNV
   241  QIALDYLRHR QVKLVNIRND DIADGNPKLT LGLIWTIILH FQISDIQVSG QSEDMTAKEK
   301  LLLWSQRMVE GYQGLRCDNF TSSWRDGRLF NAIIHRHKPL LIDMNKVYRQ TNLENLDQAF
   361  SVAERDLGVT RLLDPEDVDV PQPDEKSIIT YVSSLYDAMP RVPDVQDGVR ANELQLRWQE
   421  YRELVLLLLQ WMRHHTAAFE ERRFPSSFEE IEILWSQFLK FKEMELPAKE ADKNRSKGIY
   481  QSLEGAVQAG QLKVPPGYHP LDVEKEWGKL HVAILEREKQ LRSEFERLEC LQRIVTKLQM
   541  EAGLCEEQLN QADALLQSDV RLLAAGKVPQ RAGEVERDLD KADSMIRLLF NDVQTLKDGR
   601  HPQGEQMYRR VYRLHERLVA IRTEYNLRLK AGVAAPATQV AQVTLQSVQR RPELEDSTLR
   661  YLQDLLAWVE ENQHRVDGAE WGVDLPSVEA QLGSHRGLHQ SIEEFRAKIE RARSDEGQLS
   721  PATRGAYRDC LGRLDLQYAK LLNSSKARLR SLESLHSFVA AATKELMWLN EKEEEEVGFD
   781  WSDRNTNMTA KKESYSALMR ELELKEKKIK ELQNAGDRLL REDHPARPTV ESFQAALQTQ
   841  WSWMLQLCCC IEAHLKENAA YFQFFSDVRE AEGQLQKLQE ALRRKYSCDR SATVTRLEDL
   901  LQDAQDEKEQ LNEYKGHLSG LAKRAKAVVQ LKPRHPAHPM RGRLPLLAVC DYKQVEVTVH
   961  KGDECQLVGP AQPSHWKVLS SSGSEAAVPS VCFLVPPPNQ EAQEAVTRLE AQHQALVTLW
  1021  HQLHVDMKSL LAWQSLRRDV QLIRSWSLAT FRTLKPEEQR QALHSLELHY QAFLRDSQDA
  1081  GGFGPEDRLM AEREYGSCSH HYQQLLQSLE QGAQEESRCQ RCISELKDIR LQLEACETRT
  1141  VHRLRLPLDK EPARECAQRI AEQQKAQAEV EGLGKGVARL SAEAEKVLAL PEPSPAAPTL
  1201  RSELELTLGK LEQVRSLSAI YLEKLKTISL VIRGTQGAEE VLRAHEEQLK EAQAVPATLP
  1261  ELEATKASLK KLRAQAEAQQ PTFDALRDEL RGAQEVGERL QQRHGERDVE VERWRERVAQ
  1321  LLERWQAVLA QTDVRQRELE QLGRQLRYYR ESADPLGAWL QDARRRQEQI QAMPLADSQA
  1381  VREQLRQEQA LLEEIERHGE KVEECQRFAK QYINAIKDYE LQLVTYKAQL EPVASPAKKP
  1441  KVQSGSESVI QEYVDLRTHY SELTTLTSQY IKFISETLRR MEEEERLAEQ QRAEERERLA
  1501  EVEAALEKQR QLAEAHAQAK AQAEREAKEL QQRMQEEVVR REEAAVDAQQ QKRSIQEELQ
  1561  QLRQSSEAEI QAKARQAEAA ERSRLRIEEE IRVVRLQLEA TERQRGGAEG ELQALRARAE
  1621  EAEAQKRQAQ EEAERLRRQV QDESQRKRQA EVELASRVKA EAEAAREKQR ALQALEELRL
  1681  QAEEAERRLR QAEVERARQV QVALETAQRS AEAELQSKRA SFAEKTAQLE RSLQEEHVAV
  1741  AQLREEAERR AQQQAEAERA REEAERELER WQLKANEALR LRLQAEEVAQ QKSLAQAEAE
  1801  KQKEEAEREA RRRGKAEEQA VRQRELAEQE LEKQRQLAEG TAQQRLAAEQ ELIRLRAETE
  1861  QGEQQRQLLE EELARLQREA AAATQKRQEL EAELAKVRAE MEVLLASKAR AEEESRSTSE
  1921  KSKQRLEAEA GRFRELAEEA ARLRALAEEA KRQRQLAEED AARQRAEAER VLAEKLAAIG
  1981  EATRLKTEAE IALKEKEAEN ERLRRLAEDE AFQRRRLEEQ AAQHKADIEE RLAQLRKASD
  2041  SELERQKGLV EDTLRQRRQV EEEILALKAS FEKAAAGKAE LELELGRIRS NAEDTLRSKE
  2101  QAELEAARQR QLAAEEERRR REAEERVQKS LAAEEEAARQ RKAALEEVER LKAKVEEARR
  2161  LRERAEQESA RQLQLAQEAA QKRLQAEEKA HAFAVQQKEQ ELQQTLQQEQ SVLDQLRGEA
  2221  EAARRAAEEA EEARVQAERE AAQSRRQVEE AERLKQSAEE QAQARAQAQA AAEKLRKEAE
  2281  QEAARRAQAE QAALRQKQAA DAEMEKHKKF AEQTLRQKAQ VEQELTTLRL QLEETDHQKN
  2341  LLDEELQRLK AEATEAARQR SQVEEELFSV RVQMEELSKL KARIEAENRA LILRDKDNTQ
  2401  RFLQEEAEKM KQVAEEAARL SVAAQEAARL RQLAEEDLAQ QRALAEKMLK EKMQAVQEAT
  2461  RLKAEAELLQ QQKELAQEQA RRLQEDKEQM AQQLAEETQG FQRTLEAERQ RQLEMSAEAE
  2521  RLKLRVAEMS RAQARAEEDA QRFRKQAEEI GEKLHRTELA TQEKVTLVQT LEIQRQQSDH
  2581  DAERLREAIA ELEREKEKLQ QEAKLLQLKS EEMQTVQQEQ LLQETQALQQ SFLSEKDSLL
  2641  QRERFIEQEK AKLEQLFQDE VAKAQQLREE QQRQQQQMEQ ERQRLVASME EARRRQHEAE
  2701  EGVRRKQEEL QQLEQQRRQQ EELLAEENQR LREQLQLLEE QHRAALAHSE EVTASQVAAT
  2761  KTLPNGRDAL DGPAAEAEPE HSFDGLRRKV SAQRLQEAGI LSAEELQRLA QGHTTVDELA
  2821  RREDVRHYLQ GRSSIAGLLL KATNEKLSVY AALQRQLLSP GTALILLEAQ AASGFLLDPV
  2881  RNRRLTVNEA VKEGVVGPEL HHKLLSAERA VTGYKDPYTG QQISLFQAMQ KGLIVREHGI
  2941  RLLEAQIATG GVIDPVHSHR VPVDVAYRRG YFDEEMNRVL ADPSDDTKGF FDPNTHENLT
  3001  YLQLLERCVE DPETGLCLLP LTDKAAKGGE LVYTDSEARD VFEKATVSAP FGKFQGKTVT
  3061  IWEIINSEYF TAEQRRDLLR QFRTGRITVE KIIKIIITVV EEQEQKGRLC FEGLRSLVPA
  3121  AELLESRVID RELYQQLQRG ERSVRDVAEV DTVRRALRGA NVIAGVWLEE AGQKLSIYNA
  3181  LKKDLLPSDM AVALLEAQAG TGHIIDPATS ARLTVDEAVR AGLVGPEFHE KLLSAEKAVT
  3241  GYRDPYTGQS VSLFQALKKG LIPREQGLRL LDAQLSTGGI VDPSKSHRVP LDVACARGCL
  3301  DEETSRALSA PRADAKAYSD PSTGEPATYG ELQQRCRPDQ LTGLSLLPLS EKAARARQEE
  3361  LYSELQARET FEKTPVEVPV GGFKGRTVTV WELISSEYFT AEQRQELLRQ FRTGKVTVEK
  3421  VIKILITIVE EVETLRQERL SFSGLRAPVP ASELLASGVL SRAQFEQLKD GKTTVKDLSE
  3481  LGSVRTLLQG SGCLAGIYLE DTKEKVSIYE AMRRGLLRAT TAALLLEAQA ATGFLVDPVR
  3541  NQRLYVHEAV KAGVVGPELH EQLLSAEKAV TGYRDPYSGS TISLFQAMQK GLVLRQHGIR
  3601  LLEAQIATGG IIDPVHSHRV PVDVAYQRGY FSEEMNRVLA DPSDDTKGFF DPNTHENLTY
  3661  RQLLERCVED PETGLRLLPL KGAEKAEVVE TTQVYTEEET RRAFEETQID IPGGGSHGGS
  3721  TMSLWEVMQS DLIPEEQRAQ LMADFQAGRV TKERMIIIII EIIEKTEIIR QQGLASYDYV
  3781  RRRLTAEDLF EARIISLETY NLLREGTRSL REALEAESAW CYLYGTGSVA GVYLPGSRQT
  3841  LSIYQALKKG LLSAEVARLL LEAQAATGFL LDPVKGERLT VDEAVRKGLV GPELHDRLLS
  3901  AERAVTGYRD PYTEQTISLF QAMKKELIPT EEALRLLDAQ LATGGIVDPR LGFHLPLEVA
  3961  YQRGYLNKDT HDQLSEPSEV RSYVDPSTDE RLSYTQLLRR CRRDDGTGQL LLPLSDARKL
  4021  TFRGLRKQIT MEELVRSQVM DEATALQLRE GLTSIEEVTK NLQKFLEGTS CIAGVFVDAT
  4081  KERLSVYQAM KKGIIRPGTA FELLEAQAAT GYVIDPIKGL KLTVEEAVRM GIVGPEFKDK
  4141  LLSAERAVTG YKDPYSGKLI SLFQAMKKGL ILKDHGIRLL EAQIATGGII DPEESHRLPV
  4201  EVAYKRGLFD EEMNEILTDP SDDTKGFFDP NTEENLTYLQ LMERCITDPQ TGLCLLPLKE
  4261  KKRERKTSSK SSVRKRRVVI VDPETGKEMS VYEAYRKGLI DHQTYLELSE QECEWEEITI
  4321  SSSDGVVKSM IIDRRSGRQY DIDDAIAKNL IDRSALDQYR AGTLSITEFA DMLSGNAGGF
  4381  RSRSSSVGSS SSYPISPAVS RTQLASWSDP TEETGPVAGI LDTETLEKVS ITEAMHRNLV
  4441  DNITGQRLLE AQACTGGIID PSTGERFPVT DAVNKGLVDK IMVDRINLAQ KAFCGFEDPR
  4501  TKTKMSAAQA LKKGWLYYEA GQRFLEVQYL TGGLIEPDTP GRVPLDEALQ RGTVDARTAQ
  4561  KLRDVGAYSK YLTCPKTKLK ISYKDALDRS MVEEGTGLRL LEAAAQSTKG YYSPYSVSGS
  4621  GSTAGSRTGS RTGSRAGSRR GSFDATGSGF SMTFSSSSYS SSGYGRRYAS GSSASLGGPE
  4681  SAVA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PLEC can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0

Highest tissue expression

230 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PLEC.

Disease | AllUniProt

Conditions PLEC is implicated in, by any mechanism.

• Epidermolysis bullosa simplex 5C, with pyloric atresia (EBS5C) MIM:612138
• Epidermolysis bullosa simplex 5B, with muscular dystrophy (EBS5B) MIM:226670
• Epidermolysis bullosa simplex 5A, Ogna type (EBS5A) MIM:131950
• Muscular dystrophy, limb-girdle, autosomal recessive 17 (LGMDR17) MIM:613723
• Epidermolysis bullosa simplex 5D, generalized intermediate, autosomal recessive (EBS5D) MIM:616487

Disease | GeneticClinVar

156 pathogenic / likely-pathogenic of 6,684 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Epidermolysis bullosa simplex 5B, with muscular dystrophy
• Epidermolysis bullosa simplex with nail dystrophy
• Epidermolysis bullosa simplex 5C, with pyloric atresia
• Autosomal recessive limb-girdle muscular dystrophy type 2Q
• Epidermolysis bullosa simplex, Ogna type

Disease | ImmuneIEDB

Conditions an epitope on PLEC was assayed in.

• invasive ductal carcinoma T cell

Disease | AutoantibodyPubMed

Conditions in which antibodies against PLEC are reported. Each links to that disease's full target list.

• Pemphigoid, Bullous 4

ReferencesPubMed · IEDB

Publications for PLEC from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.39

gnomAD pLI

0

gnomAD missense Z

-2.57

DepMap mean gene effect

-0.12

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 10% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adherens junction organization
• cardiac muscle cell development
• cell morphogenesis
• cellular response to fluid shear stress
• cellular response to hydrostatic pressure
• cellular response to mechanical stimulus
• establishment of skin barrier
• fibroblast migration
• gene expression
• hemidesmosome assembly
• intermediate filament cytoskeleton organization
• intermediate filament organization
• intracellular protein localization
• keratinocyte development
• leukocyte migration involved in immune response
• mitochondrion organization
• multicellular organism growth
• myoblast differentiation
• nucleus organization
• peripheral nervous system myelin maintenance
• regulation of vascular permeability
• respiratory electron transport chain
• response to food
• sarcomere organization
• skeletal muscle fiber development
• skeletal myofibril assembly
• T cell chemotaxis
• tight junction organization
• transmission of nerve impulse
• wound healing
• actomyosin contractile ring assembly actin filament organization
• protein-containing complex organization

Molecular functions

• actin filament binding
• ankyrin binding
• cadherin binding
• dystroglycan binding
• identical protein binding
• RNA binding
• structural constituent of cytoskeleton
• structural constituent of muscle

Cellular components

• axon
• brush border
• costamere
• cytoplasm
• cytosol
• dendrite
• extracellular exosome
• focal adhesion
• hemidesmosome
• intermediate filament cytoskeleton
• mitochondrial outer membrane
• myelin sheath
• perinuclear region of cytoplasm
• plasma membrane
• podosome
• sarcolemma
• sarcoplasm
• Z disc

Protein domainsUniProt · Pfam · InterPro

• Plectin repeat
• SH3 domain
• Actinin-type actin-binding domain, conserved site
• Calponin homology domain
• Plectin/eS10, N-terminal
• Spectrin/alpha-actinin
• Plakin repeat superfamily
• Winged helix-like DNA-binding domain superfamily
• CH domain superfamily
• Desmoplakin, spectrin-like domain
• Desmoplakin, SH3 domain
• Plakin
• Plectin-like, spectrin-like repeat
• Calponin homology (CH) domain
• Plectin repeat
• Plectin/S10 domain
• SH3 domain
• Spectrin like domain
• Spectrin-like repeat
• Spectrin-like repeat
• Spectrin repeat

KeywordsUniProt

• Acetylation
• Actin-binding
• Cell junction
• Cell projection
• Coiled coil
• Cytoplasm
• Cytoskeleton
• Epidermolysis bullosa
• Limb-girdle muscular dystrophy
• Methylation
• Phosphoprotein
• Repeat
• SH3 domain

InteractionsUniProt · HPA

Protein binding partners of PLEC in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ANK3
• COL17A1
• DES
• FER
• KRT10
• KRT14
• KRT15
• KRT18
• TOR1A
• VIM
• SYNE3
• WNK1