PKP3 plakophilin 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PKP3provided by HGNC
Official Full Name: plakophilin 3provided by HGNC
Primary source: HGNC:HGNC:9025
See related: Ensembl:ENSG00000184363 MIM:605561; AllianceGenome:HGNC:9025
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Summary: This gene encodes a member of the arm-repeat (armadillo) and plakophilin gene families. Plakophilin proteins contain numerous armadillo repeats, localize to cell desmosomes and nuclei, and participate in linking cadherins to intermediate filaments in the cytoskeleton. This protein may act in cellular desmosome-dependent adhesion and signaling pathways. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2014]
Expression: Biased expression in skin (RPKM 51.4), esophagus (RPKM 46.7) and 11 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 11p15.5

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (392596..404908)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (437907..450273)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (392596..404908)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Role and function of plakophilin 3 in cancer progression and skin disease.
Title: Role and function of plakophilin 3 in cancer progression and skin disease.
Disease-related blood-based differential methylation in cystic fibrosis and its representation in lung cancer revealed a regulatory locus in PKP3 in lung epithelial cells.
Title: Disease-related blood-based differential methylation in cystic fibrosis and its representation in lung cancer revealed a regulatory locus in PKP3 in lung epithelial cells.
Plakophilin 3 and Par3 facilitate desmosomes' association with the apical junctional complex.
Title: Plakophilin 3 and Par3 facilitate desmosomes' association with the apical junctional complex.
A catenin of the plakophilin-subfamily, Pkp3, responds to canonical-Wnt pathway components and signals.
Title: A catenin of the plakophilin-subfamily, Pkp3, responds to canonical-Wnt pathway components and signals.
14-3-3sigma (also known as stratifin, encoded by SFN) interacted preferentially with S285-phosphorylated PKP3 to promote its accumulation at tricellular contact sites, leading to stable desmosomes.
Title: 14-3-3 proteins regulate desmosomal adhesion via plakophilins.
PKP3 loss leads to an increase in invasion, tumor formation and metastasis and these phenotypes were dependent on the increase in LCN2 expression.
Title: Plakophilin3 loss leads to an increase in lipocalin2 expression, which is required for tumour formation.
The result of this study PKP3 as the oncogene candidate and a potential target for the treatment of ovarian cancer.
Title: PKP3 interactions with MAPK-JNK-ERK1/2-mTOR pathway regulates autophagy and invasion in ovarian cancer.
Nasopharyngeal carcinoma (NPC) tissues display a significant high miR-149 and low PKP3 expressions indicating that both play an important role in NPC metastasis. Downregulation of miR-149 resulting in the increment of PKP3 expression. Also, N,N'-dinitrosopiperazine (DNP)-mediated PKP3 decrease was eliminated by miR-149 in NPC cells. This suggests that DNP may reduce PKP3 expression through upregulating miR-149.
Title: Dinitrosopiperazine-decreased PKP3 through upregulating miR-149 participates in nasopharyngeal carcinoma metastasis.
plakophilin 3 appears to be involved in tumor invasion in malignant mesothelioma
Title: Expression of plakophilin 3 in diffuse malignant pleural mesothelioma.
PKP3 overexpression increases the stability of other desmosomal proteins independently of the increase in DSC2 levels and regulates desmosome formation and stability by a multimodal mechanism affecting transcription, protein stability and cell border localization of desmosomal proteins.
Title: Plakophilin3 increases desmosome assembly, size and stability by increasing expression of desmocollin2.

Submit: New GeneRIF Correction See all GeneRIFs (33)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables alpha-catenin binding	IPI Inferred from Physical Interaction more info	PubMed
enables cadherin binding	IBA Inferred from Biological aspect of Ancestor more info
enables cadherin binding involved in cell-cell adhesion	HDA more info	PubMed
enables cell adhesion molecule binding	IPI Inferred from Physical Interaction more info	PubMed
enables enzyme binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in cell-cell adhesion	IBA Inferred from Biological aspect of Ancestor more info
involved_in desmosome assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of mRNA catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein localization to plasma membrane	IMP Inferred from Mutant Phenotype more info	PubMed
NOT involved_in regulation of translation	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in adherens junction	HDA more info	PubMed
is_active_in adherens junction	IBA Inferred from Biological aspect of Ancestor more info
located_in cell junction	IDA Inferred from Direct Assay more info
located_in cell-cell junction	TAS Traceable Author Statement more info	PubMed
located_in cornified envelope	TAS Traceable Author Statement more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in desmosome	IEA Inferred from Electronic Annotation more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: plakophilin-3

Names: plakophilin 3b

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001303029.2 → NP_001289958.1 plakophilin-3 isoform PKP3b

See identical proteins and their annotated locations for NP_001289958.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) encodes the longer isoform (PKP3b).

Source sequence(s)

AC138230, AK025067, BC000081, CA947983, FN421477

UniProtKB/Swiss-Prot

Q9Y446

Conserved Domains (2) summary

cd00020
Location:336 → 447

ARM; Armadillo/beta-catenin-like repeats. An approximately 40 amino acid long tandemly repeated sequence motif first identified in the Drosophila segment polarity gene armadillo; these repeats were also found in the mammalian armadillo homolog beta-catenin, ...

sd00043
Location:336 → 361

ARM; armadillo repeat [structural motif]
NM_007183.4 → NP_009114.1 plakophilin-3 isoform PKP3a

See identical proteins and their annotated locations for NP_009114.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) uses an alternate 5' exon structure and differs in the 5' UTR and coding region, compared to variant 2. The resulting isoform (PKP3a) has a shorter and distinct N-terminus compared to isoform PKP3b.

Source sequence(s)

AK025067, BC000081, CA947983, DB139782, FN421477

Consensus CDS

CCDS7695.1

UniProtKB/Swiss-Prot

F8J390, Q53EX8, Q9Y446

Related

ENSP00000331678.2, ENST00000331563.7

Conserved Domains (2) summary

smart00185
Location:350 → 390

ARM; Armadillo/beta-catenin-like repeats

sd00043
Location:321 → 346

ARM; armadillo repeat [structural motif]