Seroatlas · Human Serome Atlas

PKP2

Plakophilin-2

Also known as: PKP2_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q99959
Gene: PKP2
Ensembl: ENSG00000057294
Chromosome: 12
Canonical length: 881 aa
Protein class: Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins
Subcellular location: Nucleoplasm,Cell Junctions

OverviewNCBI Gene

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 gene may regulate the signaling activity of beta-catenin and is required to maintain transcription of genes that control intracellular calcium cycling including ryanodine receptor 2, ankyrin-B, triadin, and calcium channel, voltage-dependent, L type, alpha 1C. Mutations in this gene are associated with different inherited cardiac conditions including Arrythmogenic Cardiomyopathy, Brugada Syndrome, and Idiopathic Ventricular Fibrillation. A processed pseudogene with high similarity to this gene has been mapped to chromosome 12p13. [provided by RefSeq, May 2022]

Canonical amino-acid sequenceUniProt

881 residues, UniProt reviewed canonical sequence.

>Q99959|PKP2
     1  MAAPGAPAEY GYIRTVLGQQ ILGQLDSSSL ALPSEAKLKL AGSSGRGGQT VKSLRIQEQV
    61  QQTLARKGRS SVGNGNLHRT SSVPEYVYNL HLVENDFVGG RSPVPKTYDM LKAGTTATYE
   121  GRWGRGTAQY SSQKSVEERS LRHPLRRLEI SPDSSPERAH YTHSDYQYSQ RSQAGHTLHH
   181  QESRRAALLV PPRYARSEIV GVSRAGTTSR QRHFDTYHRQ YQHGSVSDTV FDSIPANPAL
   241  LTYPRPGTSR SMGNLLEKEN YLTAGLTVGQ VRPLVPLQPV TQNRASRSSW HQSSFHSTRT
   301  LREAGPSVAV DSSGRRAHLT VGQAAAGGSG NLLTERSTFT DSQLGNADME MTLERAVSML
   361  EADHMLPSRI SAAATFIQHE CFQKSEARKR VNQLRGILKL LQLLKVQNED VQRAVCGALR
   421  NLVFEDNDNK LEVAELNGVP RLLQVLKQTR DLETKKQITD HTVNLRSRNG WPGAVAHACN
   481  PSTLGGQGGR ITRSGVRDQP DQHGLLWNLS SNDKLKNLMI TEALLTLTEN IIIPFSGWPE
   541  GDYPKANGLL DFDIFYNVTG CLRNMSSAGA DGRKAMRRCD GLIDSLVHYV RGTIADYQPD
   601  DKATENCVCI LHNLSYQLEA ELPEKYSQNI YIQNRNIQTD NNKSIGCFGS RSRKVKEQYQ
   661  DVPMPEEKSN PKGVEWLWHS IVIRMYLSLI AKSVRNYTQE ASLGALQNLT AGSGPMPTSV
   721  AQTVVQKESG LQHTRKMLHV GDPSVKKTAI SLLRNLSRNL SLQNEIAKET LPDLVSIIPD
   781  TVPSTDLLIE TTASACYTLN NIIQNSYQNA RDLLNTGGIQ KIMAISAGDA YASNKASKAA
   841  SVLLYSLWAH TELHHAYKKA QFKKTDFVNS RTAKAYHSLK D

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PKP2 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): 0.45
Highest tissue expression: 185 nTPM

Expression across tissuesHPA

Tissue

heart muscle: 185 nTPM
fallopian tube: 69 nTPM
salivary gland: 55 nTPM
colon: 51 nTPM
rectum: 46 nTPM
parathyroid gland: 35 nTPM

Single-cell type

cardiomyocytes: 661 nCPM
salivary ionocytes: 619 nCPM
lacrimal acinar cells: 489 nCPM
extravillous trophoblasts: 408 nCPM
fallopian tube ciliated cells: 346 nCPM
salivary acinar cells: 278 nCPM

Immune cell

eosinophil: 6.9 nTPM
basophil: 5.6 nTPM
myeloid DC: 2.7 nTPM
non-classical monocyte: 1.2 nTPM
intermediate monocyte: 1.1 nTPM
NK-cell: 0.9 nTPM

Brain region

hippocampal formation: 17 nTPM
choroid plexus: 16 nTPM
cerebral cortex: 8.6 nTPM
cerebellum: 7.3 nTPM
basal ganglia: 5.8 nTPM
amygdala: 5 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PKP2.

Disease | AllUniProt

Conditions PKP2 is implicated in, by any mechanism.

Arrhythmogenic right ventricular dysplasia, familial, 9 (ARVD9) MIM:609040

Disease | GeneticClinVar

354 pathogenic / likely-pathogenic of 2,327 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Arrhythmogenic right ventricular dysplasia 9
Cardiovascular phenotype
Arrhythmogenic right ventricular cardiomyopathy
Cardiomyopathy
Familial isolated arrhythmogenic right ventricular dysplasia

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): 1.06
gnomAD pLI: 0
gnomAD missense Z: -0.21
DepMap mean gene effect: -0.04
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

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of PKP2 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 PKP2 as an antibody target. Whether an autoantibody or antibody against PKP2 could matter depends on whether native PKP2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

PKP2 is annotated at the cell surface, where native PKP2 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 PKP2 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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