PPL
Periplakin
Also known as: PEPL_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- O60437
- Gene
- PPL
- Ensembl
- ENSG00000118898
- Chromosome
- 16
- Canonical length
- 1756 aa
- Protein class
- Plasma proteins, Predicted intracellular proteins
- Subcellular location
- Nucleoplasm,Plasma membrane,Basal body,Cytosol
- Quaternary structure
- Homodimer
OverviewNCBI Gene
The protein encoded by this gene is a component of desmosomes and of the epidermal cornified envelope in keratinocytes. The N-terminal domain of this protein interacts with the plasma membrane and its C-terminus interacts with intermediate filaments. Through its rod domain, this protein forms complexes with envoplakin. This protein may serve as a link between the cornified envelope and desmosomes as well as intermediate filaments. AKT1/PKB, a protein kinase mediating a variety of cell growth and survival signaling processes, is reported to interact with this protein, suggesting a possible role for this protein as a localization signal in AKT1-mediated signaling. [provided by RefSeq, Jul 2008]
Canonical amino-acid sequenceUniProt
1756 residues, UniProt reviewed canonical sequence.
>O60437|PPL
1 MNSLFRKRNK GKYSPTVQTR SISNKELSEL IEQLQKNADQ VEKNIVDTEA KMQSDLARLQ
61 EGRQPEHRDV TLQKVLDSEK LLYVLEADAA IAKHMKHPQG DMIAEDIRQL KERVTNLRGK
121 HKQIYRLAVK EVDPQVNWAA LVEEKLDKLN NQSFGTDLPL VDHQVEEHNI FHNEVKAIGP
181 HLAKDGDKEQ NSELRAKYQK LLAASQARQQ HLSSLQDYMQ RCTNELYWLD QQAKGRMQYD
241 WSDRNLDYPS RRRQYENFIN RNLEAKEERI NKLHSEGDQL LAAEHPGRNS IEAHMEAVHA
301 DWKEYLNLLI CEESHLKYME DYHQFHEDVK DAQELLRKVD SDLNQKYGPD FKDRYQIELL
361 LRELDDQEKV LDKYEDVVQG LQKRGQQVVP LKYRRETPLK PIPVEALCDF EGEQGLISRG
421 YSYTLQKNNG ESWELMDSAG NKLIAPAVCF VIPPTDPEAL ALADSLGSQY RSVRQKAAGS
481 KRTLQQRYEV LKTENPGDAS DLQGRQLLAG LDKVASDLDR QEKAITGILR PPLEQGRAVQ
541 DSAERAKDLK NITNELLRIE PEKTRSTAEG EAFIQALPGS GTTPLLRTRV EDTNRKYEHL
601 LQLLDLAQEK VDVANRLEKS LQQSWELLAT HENHLNQDDT VPESSRVLDS KGQELAAMAC
661 ELQAQKSLLG EVEQNLQAAK QCSSTLASRF QEHCPDLERQ EAEVHKLGQR FNNLRQQVER
721 RAQSLQSAKA AYEHFHRGHD HVLQFLVSIP SYEPQETDSL SQMETKLKNQ KNLLDEIASR
781 EQEVQKICAN SQQYQQAVKD YELEAEKLRS LLDLENGRRS HVSKRARLQS PATKVKEEEA
841 ALAAKFTEVY AINRQRLQNL EFALNLLRQQ PEVEVTHETL QRNRPDSGVE EAWKIRKELD
901 EETERRRQLE NEVKSTQEEI WTLRNQGPQE SVVRKEVLKK VPDPVLEESF QQLQRTLAEE
961 QHKNQLLQEE LEALQLQLRA LEQETRDGGQ EYVVKEVLRI EPDRAQADEV LQLREELEAL
1021 RRQKGAREAE VLLLQQRVAA LAEEKSRAQE KVTEKEVVKL QNDPQLEAEY QQLQEDHQRQ
1081 DQLREKQEEE LSFLQDKLKR LEKERAMAEG KITVKEVLKV EKDAATEREV SDLTRQYEDE
1141 AAKARASQRE KTELLRKIWA LEEENAKVVV QEKVREIVRP DPKAESEVAN LRLELVEQER
1201 KYRGAEEQLR SYQSELEALR RRGPQVEVKE VTKEVIKYKT DPEMEKELQR LREEIVDKTR
1261 LIERCDLEIY QLKKEIQALK DTKPQVQTKE VVQEILQFQE DPQTKEEVAS LRAKLSEEQK
1321 KQVDLERERA SQEEQIARKE EELSRVKERV VQQEVVRYEE EPGLRAEASA FAESIDVELR
1381 QIDKLRAELR RLQRRRTELE RQLEELERER QARREAEREV QRLQQRLAAL EQEEAEAREK
1441 VTHTQKVVLQ QDPQQAREHA LLRLQLEEEQ HRRQLLEGEL ETLRRKLAAL EKAEVKEKVV
1501 LSESVQVEKG DTEQEIQRLK SSLEEESRSK RELDVEVSRL EARLSELEFH NSKSSKELDF
1561 LREENHKLQL ERQNLQLETR RLQSEINMAA TETRDLRNMT VADSGTNHDS RLWSLERELD
1621 DLKRLSKDKD LEIDELQKRL GSVAVKREQR ENHLRRSIVV IHPDTGRELS PEEAHRAGLI
1681 DWNMFVKLRS QECDWEEISV KGPNGESSVI HDRKSGKKFS IEEALQSGRL TPAQYDRYVN
1741 KDMSIQELAV LVSGQKLocalizationUniProt · AlphaFold · HPA
Whether an antibody against PPL 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)
- 0.39
- Highest tissue expression
- 697 nTPM
Expression across tissuesHPA
Tissue
- esophagus: 697 nTPM
- vagina: 274 nTPM
- cervix: 218 nTPM
- skin: 179 nTPM
- salivary gland: 134 nTPM
- adipose tissue: 54 nTPM
Single-cell type
- esophageal apical cells: 5,894 nCPM
- esophageal suprabasal cells: 844 nCPM
- suprabasal keratinocytes: 430 nCPM
- salivary duct cells: 264 nCPM
- ocular epithelial cells: 261 nCPM
- alveolar cells type 1: 205 nCPM
Immune cell
- neutrophil: 0.2 nTPM
- basophil: 0 nTPM
- classical monocyte: 0 nTPM
- eosinophil: 0 nTPM
- gdT-cell: 0 nTPM
- intermediate monocyte: 0 nTPM
Brain region
- cerebral cortex: 18 nTPM
- hippocampal formation: 17 nTPM
- choroid plexus: 17 nTPM
- basal ganglia: 16 nTPM
- midbrain: 15 nTPM
- amygdala: 12 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about PPL.
Disease | ImmuneIEDB
Conditions an epitope on PPL was assayed in.
- pemphigus B cell
Disease | AutoantibodyPubMed
Conditions in which antibodies against PPL are reported. Each links to that disease's full target list.
Showing 1 of 2 — disease pages carrying at least 10 antigens.
ReferencesPubMed · IEDB
Publications for PPL 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.
Reference: AutoantibodyPubMed
11 publications
- Identification of periplakin as a new target for autoreactivity in idiopathic pulmonary fibrosis.
2011 · Am J Respir Crit Care Med · RCR 2.6 · 99 citations - Clinical and immunopathological spectrum of paraneoplastic pemphigus.
2010 · J Dtsch Dermatol Ges · RCR 2.5 · 65 citations - Detection of anti-envoplakin and anti-periplakin autoantibodies by ELISA in patients with paraneoplastic pemphigus.
2009 · Arch Dermatol Res · RCR 1 · 29 citations - Mucosal dominant pemphigus vulgaris with anti-desmoplakin autoantibodies.
2004 · J Am Acad Dermatol · RCR 0.9 · 30 citations - Pemphigus vegetans Neumann type with anti-desmoglein and anti-periplakin autoantibodies.
2007 · Eur J Dermatol · RCR 0.8 · 22 citations
Show 6 more
- Role of autoantibodies against the linker subdomains of envoplakin and periplakin in the pathogenesis of paraneoplastic pemphigus.
2009 · Chin Med J (Engl) · RCR 0.5 · 14 citations - Sera from patients with toxic epidermal necrolysis contain autoantibodies to periplakin.
2006 · Br J Dermatol · RCR 0.5 · 14 citations - Detection of autoantibodies to periplakin and envoplakin in paraneoplastic pemphigus but not idiopathic pulmonary fibrosis using full-length recombinant proteins.
2014 · Clin Chim Acta · RCR 0.5 · 11 citations - Perip7lakin is a target for autoimmunity in asthma.
2016 · Respir Res · RCR 0.4 · 11 citations - Detection of anti-periplakin auto-antibodies during idiopathic pulmonary fibrosis.
2014 · Clin Chim Acta · RCR 0.1 · 4 citations - Author's reply to "detection of anti-periplakin autoantibodies during idiopathic pulmonary fibrosis" by Taillé et al.
2014 · Clin Chim Acta · RCR 0 · 1 citations
Reference: B cellIEDB
1 publication
- Epitopes in the linker subdomain region of envoplakin recognized by autoantibodies in paraneoplastic pemphigus patients.
2006 · J Invest Dermatol · RCR 1.2 · 34 citations
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)
- 1.03
- gnomAD pLI
- 0
- gnomAD missense Z
- -3.66
- DepMap mean gene effect
- -0.18
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- intermediate filament cytoskeleton organization
- keratinization
- response to mechanical stimulus
- wound healing
Molecular functions
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of PPL in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads PPL as an antibody target. Whether an autoantibody or antibody against PPL could matter depends on whether native PPL is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
PPL is annotated at the cell surface, where native PPL is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Annotation status
The present source text does not explicitly label PPL as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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