Q99959A0AV37B8QFA1B8QGS6B8QGS7D3DUW9Q4VC01Q99960PKP2_HUMANPlakophilin-2PKP2Homo sapiensHumanEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomoPlakophilins 2a and 2b: constitutive proteins of dual location in the karyoplasm and the desmosomal plaque.NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2)VARIANT PRO-366Mutations in PKP2 gene involved in ARVC.NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)VARIANTS SER-76; ASN-112 AND ILE-587The finished DNA sequence of human chromosome 12.NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)VARIANT PRO-366Desmosomal plakophilin 2 as a differentiation marker in normal and malignant tissues.TISSUE SPECIFICITYInteraction of plakophilins with desmoplakin and intermediate filament proteins: an in vitro analysis.INTERACTION WITH KRT5; KRT8; KRT14; KRT18 AND VIMNuclear particles containing RNA polymerase III complexes associated with the junctional plaque protein plakophilin 2.INTERACTION WITH POLR3A; POLR3F AND POLR3CSUBCELLULAR LOCATIONProtein binding and functional characterization of plakophilin 2. Evidence for its diverse roles in desmosomes and beta -catenin signaling.INTERACTION WITH DSP; JUP; DSG1; DSG2; DSG3; CTNNB1 AND CDH1SUBCELLULAR LOCATIONFunctional analysis of C-TAK1 substrate binding and identification of PKP2 as a new C-TAK1 substrate.INTERACTION WITH MARK3PHOSPHORYLATION AT SER-82MUTAGENESIS OF SER-82 AND VAL-87A unique and specific interaction between alphaT-catenin and plakophilin-2 in the area composita, the mixed-type junctional structure of cardiac intercalated discs.INTERACTION WITH CTNNA3ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage.PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-132 AND SER-169IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-151IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]A quantitative atlas of mitotic phosphorylation.PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-197 AND SER-329IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Arrhythmogenic right ventricular cardiomyopathy plakophilin-2 mutations disrupt desmosome assembly and stability.INTERACTION WITH DSPSUBCELLULAR LOCATIONCHARACTERIZATION OF VARIANTS ARVD9 LEU-59 AND LYS-62Large-scale proteomics analysis of the human kinome.PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-151IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-44; SER-151; SER-154; SER-155; SER-251 AND SER-329IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Mechanistic insights into arrhythmogenic right ventricular cardiomyopathy caused by desmocollin-2 mutations.INTERACTION WITH DSC2VARIANT PRO-372Plakophilin 2A is the dominant isoform in human heart tissue: consequences for the genetic screening of arrhythmogenic right ventricular cardiomyopathy.ALTERNATIVE SPLICINGVARIANT TRP-490System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-151; SER-154; SER-155 AND SER-251IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Toward a comprehensive characterization of a human cancer cell phosphoproteome.PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-135; SER-151; SER-154; SER-155; SER-197; SER-251; SER-294 AND SER-329IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Plakophilin 2 affects cell migration by modulating focal adhesion dynamics and integrin protein expression.FUNCTIONSUBCELLULAR LOCATIONAn enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-151; SER-155; SER-172; THR-177; SER-183; SER-251 AND SER-329IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Immunoaffinity enrichment and mass spectrometry analysis of protein methylation.METHYLATION [LARGE SCALE ANALYSIS] AT ARG-46IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Comparative influenza protein interactomes identify the role of plakophilin 2 in virus restriction.FUNCTIONINTERACTION WITH INFLUENZA A VIRUS PB1 (MICROBIAL INFECTION)SUBCELLULAR LOCATIONTISSUE SPECIFICITYTISSUE SPECIFICITY (MICROBIAL INFECTION)Impaired function of epithelial plakophilin-2 is associated with periodontal disease.FUNCTIONSUBCELLULAR LOCATIONTISSUE SPECIFICITYINDUCTION BY P.GINGIVALIS INFECTION (MICROBIAL INFECTION)Loss of Nuclear Envelope Integrity and Increased Oxidant Production Cause DNA Damage in Adult Hearts Deficient in PKP2: A Molecular Substrate of ARVC.FUNCTIONINVOLVEMENT IN ARVD9Molecular insights into arrhythmogenic right ventricular cardiomyopathy caused by plakophilin-2 missense mutations.X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 346-620 OF VARIANT ARVD9 ARG-796VARIANT ARVD9 ARG-796CHARACTERIZATION OF VARIANTS ARVD9 PHE-615; GLN-654 AND ARG-796FUNCTIONINTERACTION WITH JUP AND DSPSUBCELLULAR LOCATIONTISSUE SPECIFICITYMutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy.VARIANTS ARVD9 PHE-615; GLN-654 AND ARG-796VARIANT PHE-140Comprehensive desmosome mutation analysis in North Americans with arrhythmogenic right ventricular dysplasia/cardiomyopathy.VARIANTS ARVD9 SER-424 AND PHE-787VARIANTS ASN-26; ILE-70; PHE-140; VAL-195; SER-276; PRO-366; PRO-372; MET-526; SER-531 AND ILE-587Missense variants in plakophilin-2 in arrhythmogenic right ventricular cardiomyopathy patients -- disease-causing or innocent bystanders?VARIANTS ARVD9 LYS-62; 79-ARG--ASP-881 DEL; ARG-489 AND VAL-673VARIANTS ASN-26; ASP-58; ILE-70; PHE-140; ALA-338; PRO-366; SER-531 AND ILE-587Role of genetic testing in arrhythmogenic right ventricular cardiomyopathy/dysplasia.VARIANTS ARVD9 LYS-137; GLY-169 AND CYS-631VARIANTS ILE-70; PRO-366 AND ILE-587Regulates focal adhesion turnover resulting in changes in focal adhesion size, cell adhesion and cell spreading, potentially via transcriptional modulation of beta-integrins (PubMed:23884246). Required to maintain gingival epithelial barrier function (PubMed:34368962). Required for cardiac sodium current propagation and electrical synchrony in cardiac myocytes, via ANK3 stabilization and modulation of SCN5A/Nav1.5 localization to cell-cell junctions (By similarity). Required for the formation of desmosome cell junctions in cardiomyocytes, thereby required for the correct formation of the heart, specifically trabeculation and formation of the atria walls (By similarity). Loss of desmosome cell junctions leads to mis-localization of DSP and DSG2 resulting in disruption of cell-cell adhesion and disordered intermediate filaments (By similarity). Modulates profibrotic gene expression in cardiomyocytes via regulation of DSP expression and subsequent activation of downstream TGFB1 and MAPK14/p38 MAPK signaling (By similarity). Required for mitochondrial function, nuclear envelope integrity and positive regulation of SIRT3 transcription via maintaining DES localization at its nuclear envelope and cell tip anchoring points, and thereby preserving regulation of the transcriptional program (PubMed:35959657). Maintenance of nuclear envelope integrity protects against DNA damage and transcriptional dysregulation of genes, especially those involved in the electron transport chain, thereby preserving mitochondrial function and protecting against superoxide radical anion generation (PubMed:35959657). May play a role in junctional plaques (PubMed:22781308). Involved in the inhibition of viral infection by influenza A viruses (IAV) (PubMed:28169297). Acts as a host restriction factor for IAV viral propagation, potentially via disrupting the interaction of IAV polymerase complex proteins (PubMed:28169297).Interacts with DSC2 (PubMed:21062920). Interacts with JUP (PubMed:22781308, PubMed:11790773). Interacts with KRT5/CK5, KRT8/CK8, KRT14/CK14, KRT18/CK18 and VIM (PubMed:10852826). Interacts (via N-terminus) with MARK3/C-TAK1 (PubMed:12941695). Interacts with DSP (PubMed:11790773, PubMed:22781308). Interacts with DSG1, DSG2 and DSG3 (PubMed:11790773). Interacts (via N-terminus) with CTNNB1 (PubMed:11790773). Interacts with CDH1 (PubMed:11790773). Interacts with the RNA polymerase III (Pol III) complex proteins POLR3A/RPC155, POLR3F/RPC39 and POLR3C/RPC82 (PubMed:11416169). Interacts with CTNNA3 (PubMed:17535849). Interacts (via N-terminus) with SCN5A/Nav1.5 (By similarity). Interacts with ANK3/ANKG and GJA1/CX43 (By similarity).(Microbial infection) Interacts (via N-terminus) with influenza A virus RNA polymerase subunit PB1 (via C-terminus); the interaction competitively inhibits the interaction between the subunits PB1 and PB2.Q99959Q5JR59false5Q99959Q9GZM8false4Q99959P31947false5Q99959P62258false4Q99959C5E526true2Q99959P03431true8Q99959Q1K9H5true3Q99959Q5EP37true2Q99959PRO_0000449619true3Q99959-2Q08043false3Q99959-2Q9H257-2false3Q99959-2Q96HB5false3Q99959-2Q86Z20false3Q99959-2Q8TD31-3false3Q99959-2Q13643false3Q99959-2Q08379false3Q99959-2Q4V328false3Q99959-2Q96ED9-2false3Q99959-2Q15323false3Q99959-2Q96A72false3Q99959-2Q5JR59-3false6Q99959-2Q9NZQ3-3false3Q99959-2Q9GZM8false3Q99959-2Q4G0R1false3Q99959-2Q58EX7false3Q99959-2Q15276false3Q99959-2Q9HAT0false3Q99959-2P02549false3Q99959-2Q8WW24false3NucleusCell junctionDesmosomeCell junctionCytoplasmColocalizes with CTNNA3 and SCN5A/Nav1.5 at intercalated disks in the heart.Q99959-12BQ99959-21ADetected in heart right ventricle (at protein level). Expressed in gingival epithelial, endothelial and fibroblast cells (at protein level) (PubMed:34368962). Faintly expressed in tracheal epithelial cells (at protein level) (PubMed:28169297). Widely expressed. Found at desmosomal plaques in simple and stratified epithelia and in non-epithelial tissues such as myocardium and lymph node follicles. In most stratified epithelia found in the desmosomes of the basal cell layer and seems to be absent from suprabasal strata.(Microbial infection) Abundantly expressed in tracheal epithelial cells following influenza A virus infection (at protein level).(Microbial infection) mRNA levels increase in response to P.gingivalis challenge while protein expression decreases, suggesting proteasomal degradation in response to P.gingivalis infection of gingival epithelial cells.Arrhythmogenic right ventricular dysplasia, familial, 9
ARVD9
A congenital heart disease characterized by infiltration of adipose and fibrous tissue into the right ventricle and loss of myocardial cells, resulting in ventricular and supraventricular arrhythmias.The disease is caused by variants affecting the gene represented in this entry.Isoform 2Undetected in heart.Isoform 1Major isoform in heart.Belongs to the beta-catenin family.3D-structureAlternative splicingCardiomyopathyCell adhesionCell junctionCytoplasmDisease variantMethylationNucleusPhosphoproteinReference proteomeRepeatDNEDQLQKSINSKNEKSFSGAVPSTALPAPFSGRRWTMISVISFYCKQGVLFCRSAVAMAAPGAPAEYGYIRTVLGQQILGQLDSSSLALPSEAKLKLAGSSGRGGQTVKSLRIQEQVQQTLARKGRSSVGNGNLHRTSSVPEYVYNLHLVENDFVGGRSPVPKTYDMLKAGTTATYEGRWGRGTAQYSSQKSVEERSLRHPLRRLEISPDSSPERAHYTHSDYQYSQRSQAGHTLHHQESRRAALLVPPRYARSEIVGVSRAGTTSRQRHFDTYHRQYQHGSVSDTVFDSIPANPALLTYPRPGTSRSMGNLLEKENYLTAGLTVGQVRPLVPLQPVTQNRASRSSWHQSSFHSTRTLREAGPSVAVDSSGRRAHLTVGQAAAGGSGNLLTERSTFTDSQLGNADMEMTLERAVSMLEADHMLPSRISAAATFIQHECFQKSEARKRVNQLRGILKLLQLLKVQNEDVQRAVCGALRNLVFEDNDNKLEVAELNGVPRLLQVLKQTRDLETKKQITDHTVNLRSRNGWPGAVAHACNPSTLGGQGGRITRSGVRDQPDQHGLLWNLSSNDKLKNLMITEALLTLTENIIIPFSGWPEGDYPKANGLLDFDIFYNVTGCLRNMSSAGADGRKAMRRCDGLIDSLVHYVRGTIADYQPDDKATENCVCILHNLSYQLEAELPEKYSQNIYIQNRNIQTDNNKSIGCFGSRSRKVKEQYQDVPMPEEKSNPKGVEWLWHSIVIRMYLSLIAKSVRNYTQEASLGALQNLTAGSGPMPTSVAQTVVQKESGLQHTRKMLHVGDPSVKKTAISLLRNLSRNLSLQNEIAKETLPDLVSIIPDTVPSTDLLIETTASACYTLNNIIQNSYQNARDLLNTGGIQKIMAISAGDAYASNKASKAASVLLYSLWAHTELHHAYKKAQFKKTDFVNSRTAKAYHSLKD
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