PPL Gene (Protein Coding)

Periplakin

GC16M004872
GIFtS:
41
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 enve... See more...

Aliases for PPL Gene

Aliases for PPL Gene

  • Periplakin 2 3 4 5
  • 195 KDa Cornified Envelope Precursor Protein 3 4
  • 190 KDa Paraneoplastic Pemphigus Antigen 3 4
  • KIAA0568 4
  • PPL 5

External Ids for PPL Gene

Previous GeneCards Identifiers for PPL Gene

  • GC16M004955
  • GC16M004932

Summaries for PPL Gene

Entrez Gene Summary for PPL 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]

GeneCards Summary for PPL Gene

PPL (Periplakin) is a Protein Coding gene. Diseases associated with PPL include Pemphigus and Paraneoplastic Pemphigus. Among its related pathways are Cytoskeleton remodeling Neurofilaments and Butyrophilin (BTN) family interactions. Gene Ontology (GO) annotations related to this gene include structural constituent of cytoskeleton. An important paralog of this gene is EVPL.

UniProtKB/Swiss-Prot Summary for PPL Gene

  • Component of the cornified envelope of keratinocytes. May link the cornified envelope to desmosomes and intermediate filaments. May act as a localization signal in PKB/AKT-mediated signaling.

Gene Wiki entry for PPL Gene

Additional gene information for PPL Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for PPL Gene

Genomics for PPL Gene

GeneHancer (GH) Regulatory Elements Pubs

Download GeneHancer 2017 data
Promoters and enhancers for PPL Gene
GeneHancer (GH) Identifier GH Type GH
Score		 GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites		 Gene Targets
GH16J004934 Promoter/Enhancer 1.7 EPDnew Ensembl ENCODE dbSUPER 250.4 +24.1 24144 3.3 CEBPA ZNF10 ATF3 ZIC2 CHD4 YY1 MXD4 CEBPB ZNF341 ZFP64 PPL SEC14L5 SEPTIN12 ENSG00000267077 HSALNG0109297 LOC105371064 GLYR1
GH16J005032 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 10.9 -74.0 -74034 5.5 BCLAF1 SP1 MYC SIX5 SSRP1 ZNF580 ZMYM3 ATF2 KLF9 POLR2A NAGPA ALG1 lnc-NAGPA-1 NAGPA-AS1 ZNF500 C16orf89 PPL GLYR1 UBN1
GH16J004658 Promoter/Enhancer 1.7 FANTOM5 Ensembl ENCODE dbSUPER 10.5 +298.2 298188 7.3 ZNF600 CEBPA ATF3 NFIC ZIC2 YY1 MXD4 CEBPB KLF11 CHD2 MGRN1 NUDT16L1 PPL SEPTIN12 CORO7 GLYR1 NAGPA ENSG00000278700 HSALNG0109267 MIR6769A
GH16J004503 Promoter/Enhancer 1.3 Ensembl ENCODE dbSUPER 10.3 +455.6 455588 4.1 BCLAF1 SP1 ZNF600 ZNF654 CTCF REST TRIM22 FEZF1 POLR2A RAD21 NMRAL1 HMOX2 CDIP1 PPL lnc-NMRAL1-1 piR-58757 C16orf96
GH16J004911 Enhancer 1 Ensembl ENCODE dbSUPER 13.3 +48.2 48212 1.9 CEBPA CEBPB MNT MAX EP300 MAFF ZNF316 USF2 NFE2 ZNF146 PPL GLYR1 UBN1 ZNF500 ENSG00000267077 LOC105371064 HSALNG0109297 SEC14L5
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around PPL on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for PPL

Top Transcription factor binding sites by QIAGEN in the PPL gene promoter:
  • AP-1
  • ARP-1
  • c-Myb
  • E47
  • ER-alpha
  • POU2F1
  • POU2F1a
  • POU2F1b
  • POU2F1c
  • RFX1

Genomic Locations for PPL Gene

Latest Assembly
chr16:4,882,507-4,960,741
(GRCh38/hg38)
Size:
78,235 bases
Orientation:
Minus strand

Previous Assembly
chr16:4,932,508-4,987,149
(GRCh37/hg19 by Entrez Gene)
Size:
54,642 bases
Orientation:
Minus strand

chr16:4,932,508-5,010,742
(GRCh37/hg19 by Ensembl)
Size:
78,235 bases
Orientation:
Minus strand

Genomic View for PPL Gene

Genes around PPL on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PPL Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for PPL Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for PPL Gene

Proteins for PPL Gene

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  • Protein details for PPL Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O60437-PEPL_HUMAN
    Recommended name:
    Periplakin
    Protein Accession:
    O60437
    Secondary Accessions:
    • O60314
    • O60454
    • Q14C98

    Protein attributes for PPL Gene

    Size:
    1756 amino acids
    Molecular mass:
    204747 Da
    Quaternary structure:
    • Homodimer or a heterodimer with EVPL (PubMed:9412476). Found in a complex composed of PPL (via C-terminal linker domain), BFSP1 and BFSP2 in the retinal lens (By similarity). Within the complex interacts (via C-terminal linker domain) with BFSP2 (By similarity). Interacts with VIM (By similarity). Binds to the PH domain of AKT1 (PubMed:12244133). Interacts with FCGR1A (PubMed:15229321). May interact with PPHLN1 (PubMed:12853457).

    Three dimensional structures from OCA and Proteopedia for PPL Gene

neXtProt entry for PPL Gene

Protein Expression for PPL Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for PPL Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for PPL Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibodies for research

No data available for DME Specific Peptides for PPL Gene

Domains & Families for PPL Gene

Gene Families for PPL Gene

HGNC:
Human Protein Atlas (HPA):
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for PPL Gene

InterPro:
Blocks:
  • Plectin repeat

Suggested Antigen Peptide Sequences for PPL Gene

GenScript: Design optimal peptide antigens:
  • 195 kDa cornified envelope precursor protein (PEPL_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O60437

UniProtKB/Swiss-Prot:

PEPL_HUMAN :
  • Belongs to the plakin or cytolinker family.
Family:
  • Belongs to the plakin or cytolinker family.
genes like me logo Genes that share domains with PPL: view

Function for PPL Gene

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  6. Cell Lines for research

Molecular function for PPL Gene

UniProtKB/Swiss-Prot Function:
Component of the cornified envelope of keratinocytes. May link the cornified envelope to desmosomes and intermediate filaments. May act as a localization signal in PKB/AKT-mediated signaling.
UniProtKB/Swiss-Prot Induction:
During differentiation of epidermal keratinocytes.
GENATLAS Biochemistry:
periplakin,expressed in specialized epithelia (keratinocytes),plakin family of cell junction proteins,with multiple repeats,acting as an autoantigen in the malignant autoimmune blistering disease,paraneoplastic pemphigus

Phenotypes From GWAS Catalog for PPL Gene

Gene Ontology (GO) - Molecular Function for PPL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005198 structural molecule activity IBA 21873635
GO:0005200 structural constituent of cytoskeleton TAS 9521878
GO:0005515 protein binding IEA,IPI 12244133
GO:0045296 cadherin binding HDA 25468996
genes like me logo Genes that share ontologies with PPL: view
genes like me logo Genes that share phenotypes with PPL: view

Animal Models for PPL Gene

MGI Knock Outs for PPL:
  • Ppl Ppl<tm1Aho>
  • Ppl Ppl<tm1b(KOMP)Wtsi>

Animal Models for research

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PPL

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for PPL Gene

Localization for PPL Gene

Subcellular locations from UniProtKB/Swiss-Prot for PPL Gene

Cell junction, desmosome. Cytoplasm, cytoskeleton. Cell membrane. Cytoplasm.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for PPL gene
Compartment Confidence
cytosol 5
plasma membrane 4
extracellular 4
cytoskeleton 4
nucleus 3
mitochondrion 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Plasma membrane (3)
  • Cytosol (2)
  • Nucleoplasm (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for PPL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001533 cornified envelope TAS --
GO:0005737 cytoplasm IEA,ISS --
GO:0005829 cytosol TAS --
GO:0005856 cytoskeleton IEA,TAS 9521878
GO:0005882 colocalizes_with intermediate filament IBA 21873635
genes like me logo Genes that share ontologies with PPL: view

Pathways & Interactions for PPL Gene

genes like me logo Genes that share pathways with PPL: view

Pathways by source for PPL Gene

1 GeneGo (Thomson Reuters) pathway for PPL Gene
  • Cytoskeleton remodeling Keratin filaments

Gene Ontology (GO) - Biological Process for PPL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0009612 response to mechanical stimulus IEP 19211270
GO:0031424 keratinization IEA --
GO:0042060 wound healing IBA 21873635
GO:0045104 intermediate filament cytoskeleton organization IEA,IBA 21873635
GO:0070268 cornification TAS --
genes like me logo Genes that share ontologies with PPL: view

No data available for SIGNOR curated interactions for PPL Gene

Drugs & Compounds for PPL Gene

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(2) Additional Compounds for PPL Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with PPL: view

Transcripts for PPL Gene

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mRNA/cDNA for PPL Gene

1 REFSEQ mRNAs :
7 NCBI additional mRNA sequence :
6 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PPL

Alternative Splicing Database (ASD) splice patterns (SP) for PPL Gene

No ASD Table

Relevant External Links for PPL Gene

GeneLoc Exon Structure for
PPL

Expression for PPL Gene

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  1. Primer products for research
  2. Gene Expression Assays for research

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for PPL Gene

mRNA expression in normal human tissues for PPL Gene
mRNA expression by GTEx for PPL GenemRNA expression by BioGPS for PPL Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for PPL Gene

This gene is overexpressed in Esophagus - Mucosa (x18.6), Vagina (x6.0), Skin - Sun Exposed (Lower leg) (x4.4), and Cervix - Ectocervix (x4.2).

Protein differential expression in normal tissues from HIPED for PPL Gene

This gene is overexpressed in Nasal epithelium (36.6) and Saliva (6.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for PPL Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for PPL

SOURCE GeneReport for Unigene cluster for PPL Gene:

Hs.192233

mRNA Expression by UniProt/SwissProt for PPL Gene:

O60437-PEPL_HUMAN
Tissue specificity: Expressed in stratified squamous epithelia and in some other epithelia.

Evidence on tissue expression from TISSUES for PPL Gene

  • Liver(4.7)
  • Lung(4.7)
  • Skin(4.6)
  • Nervous system(4.4)
  • Pancreas(3.4)
  • Heart(2.4)
  • Muscle(2.4)
  • Intestine(2.2)
  • Blood(2.1)
  • Kidney(2.1)
genes like me logo Genes that share expression patterns with PPL: view

Primer products for research

No data available for Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for PPL Gene

Orthologs for PPL Gene

This gene was present in the common ancestor of animals.

Orthologs for PPL Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
 Mammalia PPL 29 30
  • 96.84 (n)
 OneToOne
Dog
(Canis familiaris)
 Mammalia PPL 29 30
  • 86.86 (n)
 OneToOne
Cow
(Bos Taurus)
 Mammalia PPL 29 30
  • 85.37 (n)
 OneToOne
Mouse
(Mus musculus)
 Mammalia Ppl 29 16 30
  • 84.78 (n)
 OneToOne
Rat
(Rattus norvegicus)
 Mammalia Ppl 29
  • 84.51 (n)
Oppossum
(Monodelphis domestica)
 Mammalia PPL 30
  • 82 (a)
 OneToOne
Platypus
(Ornithorhynchus anatinus)
 Mammalia PPL 30
  • 62 (a)
 OneToOne
Chicken
(Gallus gallus)
 Aves PPL 29 30
  • 72.18 (n)
 OneToOne
Lizard
(Anolis carolinensis)
 Reptilia PPL 30
  • 69 (a)
 OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
 Amphibia ppl 29
  • 65.87 (n)
Str.10922 29
African clawed frog
(Xenopus laevis)
 Amphibia Xl.13246 29
Zebrafish
(Danio rerio)
 Actinopterygii ppl 29 30
  • 60.51 (n)
 OneToOne
sbcb180 29
Fruit Fly
(Drosophila melanogaster)
 Insecta shot 30
  • 4 (a)
 OneToMany
Worm
(Caenorhabditis elegans)
 Secernentea vab-10 30
  • 6 (a)
 OneToMany
Sea Squirt
(Ciona savignyi)
 Ascidiacea -- 30
OneToMany
Species where no ortholog for PPL was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for PPL Gene

ENSEMBL:
Gene Tree for PPL (if available)
TreeFam:
Gene Tree for PPL (if available)
Aminode:
Evolutionary constrained regions (ECRs) for PPL: view image
Alliance of Genome Resources:
Additional Orthologs for PPL

Paralogs for PPL Gene

Paralogs for PPL Gene

(1) SIMAP similar genes for PPL Gene using alignment to 3 proteins:

  • PEPL_HUMAN
  • K7EKI8_HUMAN
  • K7EQ71_HUMAN
genes like me logo Genes that share paralogs with PPL: view

Variants for PPL Gene

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  1. SNP Genotyping and Copy Number Assays for research

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for PPL Gene

SNP ID Clinical significance and condition Chr 16 pos Variation AA Info Type
780180 Benign: not provided 4,888,159(-) T/.
NM_002705.5(PPL):c.2457= (p.Arg819=) 		NO_SEQUENCE_ALTERATION
rs111499322 Benign: not provided 4,890,179(-) C/G
NM_002705.5(PPL):c.2313+5G>C 		INTRON
rs115478590 Benign: not provided 4,902,510(-) C/T
NM_002705.5(PPL):c.334G>A (p.Glu112Lys) 		MISSENSE
rs117997908 Likely Benign: not provided 4,884,062(-) G/A
NM_002705.5(PPL):c.4593C>T (p.Arg1531=) 		SYNONYMOUS
rs11863749 Benign: not provided 4,885,277(-) G/T
NM_002705.5(PPL):c.3378C>A (p.Thr1126=) 		SYNONYMOUS

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for PPL Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for PPL Gene

Variant ID Type Subtype PubMed ID
esv2422516 CNV deletion 17116639
esv25186 CNV gain 19812545
esv2659199 CNV deletion 23128226
esv2750430 CNV deletion 23290073
esv2760069 CNV gain+loss 17122850
esv3637710 CNV loss 21293372
esv3637711 CNV loss 21293372
esv3637712 CNV loss 21293372
nsv1039730 CNV loss 25217958
nsv1046986 CNV gain 25217958
nsv1720 CNV deletion 18451855
nsv510674 CNV deletion 20534489
nsv827530 CNV gain 20364138

Variation tolerance for PPL Gene

Residual Variation Intolerance Score: 99.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 21.51; 99.29% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for PPL Gene

Human Gene Mutation Database (HGMD)
PPL
SNPedia medical, phenotypic, and genealogical associations of SNPs for
PPL
Leiden Open Variation Database (LOVD)
PPL

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for PPL Gene

Disorders for PPL Gene

MalaCards: The human disease database

(19) MalaCards diseases for PPL Gene - From: COP and GCD

Disorder Aliases PubMed IDs
pemphigus
paraneoplastic pemphigus
pemphigus foliaceus
  • pf
pemphigus vulgaris, familial
  • pemphigus vulgaris
bullous pemphigoid
  • benign pemphigus
- elite association - COSMIC cancer census association via MalaCards
Search PPL in MalaCards View complete list of genes associated with diseases

Additional Disease Information for PPL

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with PPL: view

No data available for UniProtKB/Swiss-Prot and Genatlas for PPL Gene

Publications for PPL Gene

  1. cDNA cloning, mRNA expression, and chromosomal mapping of human and mouse periplakin genes. (PMID: 9521878) Aho S … Uitto J (Genomics 1998) 2 3 4 22
  2. Direct interaction between FcgammaRI (CD64) and periplakin controls receptor endocytosis and ligand binding capacity. (PMID: 15229321) Beekman JM … Leusen JH (Proceedings of the National Academy of Sciences of the United States of America 2004) 3 4 22
  3. Binding of protein kinase B to the plakin family member periplakin. (PMID: 12244133) van den Heuvel AP … Burgering BM (Journal of cell science 2002) 3 4 22
  4. Human periplakin: genomic organization in a clonally unstable region of chromosome 16p with an abundance of repetitive sequence elements. (PMID: 10051401) Aho S … Uitto J (Genomics 1999) 3 4 22
  5. Periplakin, a novel component of cornified envelopes and desmosomes that belongs to the plakin family and forms complexes with envoplakin. (PMID: 9412476) Ruhrberg C … Watt FM (The Journal of cell biology 1997) 3 4 22

ExternalLinks

View latest publications for PPL gene in Mastermind

Products for PPL Gene

Sources for PPL Gene