PKP4 plakophilin 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PKP4provided by HGNC
Official Full Name: plakophilin 4provided by HGNC
Primary source: HGNC:HGNC:9026
See related: Ensembl:ENSG00000144283 MIM:604276; AllianceGenome:HGNC:9026
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
Also known as: p0071
Summary: Armadillo-like proteins are characterized by a series of armadillo repeats, first defined in the Drosophila 'armadillo' gene product, that are typically 42 to 45 amino acids in length. These proteins can be divided into subfamilies based on their number of repeats, their overall sequence similarity, and the dispersion of the repeats throughout their sequences. Members of the p120(ctn)/plakophilin subfamily of Armadillo-like proteins, including CTNND1, CTNND2, PKP1, PKP2, PKP4, and ARVCF. PKP4 may be a component of desmosomal plaque and other adhesion plaques and is thought to be involved in regulating junctional plaque organization and cadherin function. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2015]
Expression: Ubiquitous expression in kidney (RPKM 22.9), thyroid (RPKM 17.0) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2q24.1

Exon count:: 25

Annotation release	Status	Assembly	Chr	Location
110	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (158456952..158681429)
110	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (158913757..159138252)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (159313464..159537941)

Chromosome 2 - NC_000002.12 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?

Kir2.1 Interactome Mapping Uncovers PKP4 as a Modulator of the Kir2.1-Regulated Inward Rectifier Potassium Currents.
Title: Kir2.1 Interactome Mapping Uncovers PKP4 as a Modulator of the Kir2.1-Regulated Inward Rectifier Potassium Currents.
p0071 is required for directional vesicle movement and secretion of different KIF3-transported carriers, thereby regulating the transport of intracellular membrane vesicles along microtubules.
Title: The armadillo protein p0071 controls KIF3 motor transport.
Data show that patients with both abnormal expression of p0071 and E-cadherin had a statistically significant shorter survival than the patients without both abnormal expression.
Title: p0071 interacts with E-cadherin in the cytoplasm so as to promote the invasion and metastasis of non-small cell lung cancer.
p0071 has a key role in regulating recycling through the Rab11a-dependent perinuclear recycling compartment.
Title: The armadillo protein p0071 is involved in Rab11-dependent recycling.
This review article focuses on the functions of the p0071 protein and its closest relatives in regulating cell adhesion and cytoskeletal organization, which are critically involved in the control of cell polarity. [review]
Title: p0071/PKP4, a multifunctional protein coordinating cell adhesion with cytoskeletal organization.
Findings suggest that aspects of folliculin tumour suppressor function are linked to interaction with p0071 and the regulation of RhoA signalling.
Title: Folliculin interacts with p0071 (plakophilin-4) and deficiency is associated with disordered RhoA signalling, epithelial polarization and cytokinesis.
These data support a model in which dysregulation of the FLCN-p0071 interaction leads to alterations in cell adhesion, cell polarity, and RhoA signaling.
Title: Folliculin, the product of the Birt-Hogg-Dube tumor suppressor gene, interacts with the adherens junction protein p0071 to regulate cell-cell adhesion.
Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
The structural and functional roles of p0071 are suggested by its preferential occurrence in distinct tubule segments, and its potential use as a cytodiagnostic cell type marker in renal pathology is discussed.
Title: Protein p0071, an armadillo plaque protein of adherens junctions, is predominantly expressed in distal renal tubules.
Data indicate that p0071 and Ect2 are transported via distinct motors and identify a novel pathway implicating KIF3 in the regulation of actin organization during cytokinesis.
Title: Targeting of p0071 to the midbody depends on KIF3.

Submit: New GeneRIF Correction See all GeneRIFs (18)

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

EBI GWAS Catalog

Description
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
integrase	gag-pol	Analysis of HIV-1 proviral integration sites in antiretroviral treatment patients indicates that PKP4 gene favors HIV-1 integration for expansion and persistence of infected cells, suggesting HIV-1 IN interacts with PKP4	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-63463 (e-PCR)
- UniSTS:20228

STS-AA021522 (e-PCR)
- UniSTS:73488

D2S2505 (e-PCR)
- UniSTS:65043

DZIP1 (e-PCR)
- UniSTS:505370

RH92183 (e-PCR)
- UniSTS:89628

D2S1320 (e-PCR)
- UniSTS:71766

SHGC-144007 (e-PCR)
- UniSTS:172129

D2S1991 (e-PCR)
- UniSTS:12134

SHGC-24308 (e-PCR)
- UniSTS:12135

G20235 (e-PCR)
- UniSTS:897

A005B01 (e-PCR)
- UniSTS:898

D2S2681 (e-PCR)
- UniSTS:17026

G63204 (e-PCR)
- UniSTS:140178

A009U35 (e-PCR)
- UniSTS:81815

SHGC-85218 (e-PCR)
- UniSTS:104355

D2S1649E (e-PCR)
- UniSTS:150699

SHGC-58134 (e-PCR)
- UniSTS:64950

G32853 (e-PCR)
- UniSTS:117432

RH45241 (e-PCR)
- UniSTS:49852

SHGC-56770 (e-PCR)
- UniSTS:59068

SHGC-101671 (e-PCR)
- UniSTS:183239

D2S1986 (e-PCR)
- UniSTS:79584

SHGC-82440 (e-PCR)
- UniSTS:104417

D2S1623E (e-PCR)
- UniSTS:13547

SHGC-133038 (e-PCR)
- UniSTS:170987

SHGC-81249 (e-PCR)
- UniSTS:102382

WI-22189 (e-PCR)
- UniSTS:29431

Homology

Homologs of the PKP4 gene: The PKP4 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 401 organisms have orthologs with human gene PKP4
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cadherin binding	IBA Inferred from Biological aspect of Ancestor 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	PubMed
involved_in cell-cell junction assembly	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in cell-cell junction assembly	ISS Inferred from Sequence or Structural Similarity more info
involved_in cell-cell signaling	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of GTPase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cytokinesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of cell adhesion	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
is_active_in adherens junction	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in cell junction	IDA Inferred from Direct Assay more info
colocalizes_with cell-cell contact zone	IDA Inferred from Direct Assay more info	PubMed
located_in cell-cell junction	IDA Inferred from Direct Assay 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	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasmic side of plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in cytoskeleton	IDA Inferred from Direct Assay more info	PubMed
located_in desmosome	IDA Inferred from Direct Assay more info	PubMed
colocalizes_with midbody	IDA Inferred from Direct Assay more info	PubMed
located_in midbody	IDA Inferred from Direct Assay more info	PubMed
located_in mitotic spindle	IDA Inferred from Direct Assay more info	PubMed
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
located_in postsynaptic density	IEA Inferred from Electronic Annotation more info
located_in spindle midzone	IDA Inferred from Direct Assay more info	PubMed
located_in spindle pole	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: plakophilin-4

Names: catenin 4

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_001005476.4 → NP_001005476.1 plakophilin-4 isoform b

See identical proteins and their annotated locations for NP_001005476.1

Status: REVIEWED

Source sequence(s)

AC005042, AC008070

Consensus CDS

CCDS33306.1

UniProtKB/Swiss-Prot

Q99569

Related

ENSP00000374407.3, ENST00000389757.7

Conserved Domains (2) summary

cd00020
Location:522 → 644

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:530 → 555

ARM; armadillo repeat [structural motif]
NM_001304969.3 → NP_001291898.1 plakophilin-4 isoform c

Status: REVIEWED

Source sequence(s)

AC005042, AC008070

UniProtKB/Swiss-Prot

Q99569

Conserved Domains (5) summary

smart00185
Location:864 → 899

ARM; Armadillo/beta-catenin-like repeats

PLN03200
Location:847 → 968

PLN03200; cellulose synthase-interactive protein; Provisional

sd00043
Location:529 → 554

ARM; armadillo repeat [structural motif]

pfam00514
Location:558 → 597

Arm; Armadillo/beta-catenin-like repeat

pfam03154
Location:72 → 383

Atrophin-1; Atrophin-1 family
NM_001304970.3 → NP_001291899.1 plakophilin-4 isoform d

Status: REVIEWED

Source sequence(s)

AC005042, AC008070

UniProtKB/Swiss-Prot

Q99569

Conserved Domains (2) summary

cd00020
Location:179 → 301

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:187 → 212

ARM; armadillo repeat [structural motif]
NM_001304971.2 → NP_001291900.1 plakophilin-4 isoform e

Status: REVIEWED

Source sequence(s)

AC005042, AC008070

Conserved Domains (2) summary

cd00020
Location:522 → 644

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:530 → 555

ARM; armadillo repeat [structural motif]
NM_001377218.1 → NP_001364147.1 plakophilin-4 isoform a

Status: REVIEWED

Source sequence(s)

AC005042, AC008070

Consensus CDS

CCDS33305.1

UniProtKB/Swiss-Prot

Q86W91
NM_001377219.1 → NP_001364148.1 plakophilin-4 isoform c

Status: REVIEWED

Source sequence(s)

AC005042, AC008070

Conserved Domains (5) summary

smart00185
Location:864 → 899

ARM; Armadillo/beta-catenin-like repeats

PLN03200
Location:847 → 968

PLN03200; cellulose synthase-interactive protein; Provisional

sd00043
Location:529 → 554

ARM; armadillo repeat [structural motif]

pfam00514
Location:558 → 597

Arm; Armadillo/beta-catenin-like repeat

pfam03154
Location:72 → 383

Atrophin-1; Atrophin-1 family
NM_001377220.1 → NP_001364149.1 plakophilin-4 isoform c

Status: REVIEWED

Source sequence(s)

AC005042, AC008070

Conserved Domains (5) summary

smart00185
Location:864 → 899

ARM; Armadillo/beta-catenin-like repeats

PLN03200
Location:847 → 968

PLN03200; cellulose synthase-interactive protein; Provisional

sd00043
Location:529 → 554

ARM; armadillo repeat [structural motif]

pfam00514
Location:558 → 597

Arm; Armadillo/beta-catenin-like repeat

pfam03154
Location:72 → 383

Atrophin-1; Atrophin-1 family
NM_001377221.1 → NP_001364150.1 plakophilin-4 isoform c

Status: REVIEWED

Source sequence(s)

AC005042, AC008070

Conserved Domains (5) summary

smart00185
Location:864 → 899

ARM; Armadillo/beta-catenin-like repeats

PLN03200
Location:847 → 968

PLN03200; cellulose synthase-interactive protein; Provisional

sd00043
Location:529 → 554

ARM; armadillo repeat [structural motif]

pfam00514
Location:558 → 597

Arm; Armadillo/beta-catenin-like repeat

pfam03154
Location:72 → 383

Atrophin-1; Atrophin-1 family
NM_001377222.1 → NP_001364151.1 plakophilin-4 isoform f

Status: REVIEWED

Source sequence(s)

AC005042, AC008070

Conserved Domains (5) summary

smart00185
Location:601 → 642

ARM; Armadillo/beta-catenin-like repeats

PLN03200
Location:846 → 967

PLN03200; cellulose synthase-interactive protein; Provisional

sd00043
Location:528 → 553

ARM; armadillo repeat [structural motif]

pfam00514
Location:557 → 596

Arm; Armadillo/beta-catenin-like repeat

pfam03154
Location:72 → 381

Atrophin-1; Atrophin-1 family
NM_001377223.1 → NP_001364152.1 plakophilin-4 isoform f

Status: REVIEWED

Source sequence(s)

AC005042, AC008070

Conserved Domains (5) summary

smart00185
Location:601 → 642

ARM; Armadillo/beta-catenin-like repeats

PLN03200
Location:846 → 967

PLN03200; cellulose synthase-interactive protein; Provisional

sd00043
Location:528 → 553

ARM; armadillo repeat [structural motif]

pfam00514
Location:557 → 596

Arm; Armadillo/beta-catenin-like repeat

pfam03154
Location:72 → 381

Atrophin-1; Atrophin-1 family
NM_001377224.1 → NP_001364153.1 plakophilin-4 isoform g

Status: REVIEWED

Source sequence(s)

AC005042, AC008070

Conserved Domains (5) summary

smart00185
Location:600 → 641

ARM; Armadillo/beta-catenin-like repeats

PLN03200
Location:845 → 966

PLN03200; cellulose synthase-interactive protein; Provisional

sd00043
Location:527 → 552

ARM; armadillo repeat [structural motif]

pfam00514
Location:556 → 595

Arm; Armadillo/beta-catenin-like repeat

pfam03154
Location:72 → 381

Atrophin-1; Atrophin-1 family
NM_001377225.1 → NP_001364154.1 plakophilin-4 isoform b

Status: REVIEWED

Source sequence(s)

AC005042, AC008070

Consensus CDS

CCDS33306.1
NM_001377226.1 → NP_001364155.1 plakophilin-4 isoform h

Status: REVIEWED

Source sequence(s)

AC005042, AC008070

Conserved Domains (5) summary

smart00185
Location:864 → 899

ARM; Armadillo/beta-catenin-like repeats

PLN03200
Location:847 → 968

PLN03200; cellulose synthase-interactive protein; Provisional

sd00043
Location:529 → 554

ARM; armadillo repeat [structural motif]

pfam00514
Location:558 → 597

Arm; Armadillo/beta-catenin-like repeat

pfam03154
Location:72 → 383

Atrophin-1; Atrophin-1 family
NM_003628.6 → NP_003619.2 plakophilin-4 isoform a

See identical proteins and their annotated locations for NP_003619.2

Status: REVIEWED

Source sequence(s)

AC005042, AC008070

Consensus CDS

CCDS33305.1

UniProtKB/Swiss-Prot

Q86W91, Q99569

Related

ENSP00000374409.3, ENST00000389759.8

Conserved Domains (2) summary

cd00020
Location:522 → 644

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:530 → 555

ARM; armadillo repeat [structural motif]