PKP2_HUMAN
ID PKP2_HUMAN Reviewed; 881 AA.
AC Q99959; A0AV37; B8QFA1; B8QGS6; B8QGS7; D3DUW9; Q4VC01; Q99960;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 207.
DE RecName: Full=Plakophilin-2;
GN Name=PKP2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND VARIANT PRO-366.
RX PubMed=8922383; DOI=10.1083/jcb.135.4.1009;
RA Mertens C., Kuhn C., Franke W.W.;
RT "Plakophilins 2a and 2b: constitutive proteins of dual location in the
RT karyoplasm and the desmosomal plaque.";
RL J. Cell Biol. 135:1009-1025(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANTS SER-76; ASN-112 AND
RP ILE-587.
RA Rampazzo A.;
RT "Mutations in PKP2 gene involved in ARVC.";
RL Submitted (FEB-2008) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT PRO-366.
RC TISSUE=Brain, and Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=10374264; DOI=10.1046/j.1432-0436.1999.6450277.x;
RA Mertens C., Kuhn C., Moll R., Schwetlick I., Franke W.W.;
RT "Desmosomal plakophilin 2 as a differentiation marker in normal and
RT malignant tissues.";
RL Differentiation 64:277-290(1999).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-132 AND SER-169, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-151, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-197 AND SER-329, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP INTERACTION WITH DSP, SUBCELLULAR LOCATION, AND CHARACTERIZATION OF
RP VARIANTS ARVD9 LEU-59 AND LYS-62.
RX PubMed=19533476; DOI=10.1080/15419060903009329;
RA Hall C., Li S., Li H., Creason V., Wahl J.K. III;
RT "Arrhythmogenic right ventricular cardiomyopathy plakophilin-2 mutations
RT disrupt desmosome assembly and stability.";
RL Cell Commun. Adhes. 16:15-27(2009).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-151, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-44; SER-151; SER-154;
RP SER-155; SER-251 AND SER-329, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [13]
RP INTERACTION WITH DSC2, AND VARIANT PRO-372.
RX PubMed=21062920; DOI=10.1093/cvr/cvq353;
RA Gehmlich K., Syrris P., Peskett E., Evans A., Ehler E., Asimaki A.,
RA Anastasakis A., Tsatsopoulou A., Vouliotis A.I., Stefanadis C.,
RA Saffitz J.E., Protonotarios N., McKenna W.J.;
RT "Mechanistic insights into arrhythmogenic right ventricular cardiomyopathy
RT caused by desmocollin-2 mutations.";
RL Cardiovasc. Res. 90:77-87(2011).
RN [14]
RP ALTERNATIVE SPLICING, AND VARIANT TRP-490.
RX PubMed=21378009; DOI=10.1136/hrt.2010.205880;
RA Gandjbakhch E., Charron P., Fressart V., Lorin de la Grandmaison G.,
RA Simon F., Gary F., Vite A., Hainque B., Hidden-Lucet F., Komajda M.,
RA Villard E.;
RT "Plakophilin 2A is the dominant isoform in human heart tissue: consequences
RT for the genetic screening of arrhythmogenic right ventricular
RT cardiomyopathy.";
RL Heart 97:844-849(2011).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-151; SER-154; SER-155 AND
RP SER-251, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-135; SER-151; SER-154;
RP SER-155; SER-197; SER-251; SER-294 AND SER-329, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-151; SER-155; SER-172;
RP THR-177; SER-183; SER-251 AND SER-329, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [18]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-46, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 346-620 OF VARIANT ARVD9 ARG-796,
RP VARIANT ARVD9 ARG-796, CHARACTERIZATION OF VARIANTS ARVD9 PHE-615; GLN-654
RP AND ARG-796, FUNCTION, INTERACTION WITH JUP AND DSP, SUBCELLULAR LOCATION,
RP AND TISSUE SPECIFICITY.
RX PubMed=22781308; DOI=10.1161/circgenetics.111.961854;
RA Kirchner F., Schuetz A., Boldt L.H., Martens K., Dittmar G., Haverkamp W.,
RA Thierfelder L., Heinemann U., Gerull B.;
RT "Molecular insights into arrhythmogenic right ventricular cardiomyopathy
RT caused by plakophilin-2 missense mutations.";
RL Circ. Cardiovasc. Genet. 5:400-411(2012).
RN [20]
RP VARIANTS ARVD9 PHE-615; GLN-654 AND ARG-796, AND VARIANT PHE-140.
RX PubMed=15489853; DOI=10.1038/ng1461;
RA Gerull B., Heuser A., Wichter T., Paul M., Basson C.T., McDermott D.A.,
RA Lerman B.B., Markowitz S.M., Ellinor P.T., MacRae C.A., Peters S.,
RA Grossmann K.S., Michely B., Sasse-Klaassen S., Birchmeier W., Dietz R.,
RA Breithardt G., Schulze-Bahr E., Thierfelder L.;
RT "Mutations in the desmosomal protein plakophilin-2 are common in
RT arrhythmogenic right ventricular cardiomyopathy.";
RL Nat. Genet. 36:1162-1164(2004).
RN [21]
RP VARIANTS ARVD9 SER-424 AND PHE-787, AND VARIANTS ASN-26; ILE-70; PHE-140;
RP VAL-195; SER-276; PRO-366; PRO-372; MET-526; SER-531 AND ILE-587.
RX PubMed=20031617; DOI=10.1161/circgenetics.109.858217;
RA den Haan A.D., Tan B.Y., Zikusoka M.N., Llado L.I., Jain R., Daly A.,
RA Tichnell C., James C., Amat-Alarcon N., Abraham T., Russell S.D.,
RA Bluemke D.A., Calkins H., Dalal D., Judge D.P.;
RT "Comprehensive desmosome mutation analysis in North Americans with
RT arrhythmogenic right ventricular dysplasia/cardiomyopathy.";
RL Circ. Cardiovasc. Genet. 2:428-435(2009).
RN [22]
RP VARIANTS ARVD9 LYS-62; 79-ARG--ASP-881 DEL; ARG-489 AND VAL-673, AND
RP VARIANTS ASN-26; ASP-58; ILE-70; PHE-140; ALA-338; PRO-366; SER-531 AND
RP ILE-587.
RX PubMed=19955750; DOI=10.1159/000263456;
RA Christensen A.H., Benn M., Tybjaerg-Hansen A., Haunso S., Svendsen J.H.;
RT "Missense variants in plakophilin-2 in arrhythmogenic right ventricular
RT cardiomyopathy patients -- disease-causing or innocent bystanders?";
RL Cardiology 115:148-154(2010).
RN [23]
RP VARIANTS ARVD9 LYS-137; GLY-169 AND CYS-631, AND VARIANTS ILE-70; PRO-366
RP AND ILE-587.
RX PubMed=19863551; DOI=10.1111/j.1399-0004.2009.01282.x;
RA Barahona-Dussault C., Benito B., Campuzano O., Iglesias A., Leung T.L.,
RA Robb L., Talajic M., Brugada R.;
RT "Role of genetic testing in arrhythmogenic right ventricular
RT cardiomyopathy/dysplasia.";
RL Clin. Genet. 77:37-48(2010).
CC -!- FUNCTION: May play a role in junctional plaques.
CC {ECO:0000269|PubMed:22781308}.
CC -!- SUBUNIT: Interacts with DSC2. Interacts with JUP and desmoplakin/DSP.
CC {ECO:0000269|PubMed:21062920, ECO:0000269|PubMed:22781308}.
CC -!- INTERACTION:
CC Q99959; Q5JR59: MTUS2; NbExp=5; IntAct=EBI-702235, EBI-742948;
CC Q99959; Q9GZM8: NDEL1; NbExp=4; IntAct=EBI-702235, EBI-928842;
CC Q99959; C5E526: PB1; Xeno; NbExp=2; IntAct=EBI-702235, EBI-12577179;
CC Q99959; P03431: PB1; Xeno; NbExp=8; IntAct=EBI-702235, EBI-2547514;
CC Q99959; Q1K9H5: PB1; Xeno; NbExp=3; IntAct=EBI-702235, EBI-6050669;
CC Q99959; Q5EP37: PB1; Xeno; NbExp=2; IntAct=EBI-702235, EBI-12577201;
CC Q99959-2; Q08043: ACTN3; NbExp=3; IntAct=EBI-10987518, EBI-2880652;
CC Q99959-2; Q9H257-2: CARD9; NbExp=3; IntAct=EBI-10987518, EBI-11530605;
CC Q99959-2; Q96HB5: CCDC120; NbExp=3; IntAct=EBI-10987518, EBI-744556;
CC Q99959-2; Q86Z20: CCDC125; NbExp=3; IntAct=EBI-10987518, EBI-11977221;
CC Q99959-2; Q8TD31-3: CCHCR1; NbExp=3; IntAct=EBI-10987518, EBI-10175300;
CC Q99959-2; Q13643: FHL3; NbExp=3; IntAct=EBI-10987518, EBI-741101;
CC Q99959-2; Q08379: GOLGA2; NbExp=3; IntAct=EBI-10987518, EBI-618309;
CC Q99959-2; Q4V328: GRIPAP1; NbExp=3; IntAct=EBI-10987518, EBI-717919;
CC Q99959-2; Q96ED9-2: HOOK2; NbExp=3; IntAct=EBI-10987518, EBI-10961706;
CC Q99959-2; Q15323: KRT31; NbExp=3; IntAct=EBI-10987518, EBI-948001;
CC Q99959-2; Q96A72: MAGOHB; NbExp=3; IntAct=EBI-10987518, EBI-746778;
CC Q99959-2; Q5JR59-3: MTUS2; NbExp=6; IntAct=EBI-10987518, EBI-11522433;
CC Q99959-2; Q9NZQ3-3: NCKIPSD; NbExp=3; IntAct=EBI-10987518, EBI-10963850;
CC Q99959-2; Q9GZM8: NDEL1; NbExp=3; IntAct=EBI-10987518, EBI-928842;
CC Q99959-2; Q4G0R1: PIBF1; NbExp=3; IntAct=EBI-10987518, EBI-14066006;
CC Q99959-2; Q58EX7: PLEKHG4; NbExp=3; IntAct=EBI-10987518, EBI-949255;
CC Q99959-2; Q15276: RABEP1; NbExp=3; IntAct=EBI-10987518, EBI-447043;
CC Q99959-2; Q9HAT0: ROPN1; NbExp=3; IntAct=EBI-10987518, EBI-1378139;
CC Q99959-2; P02549: SPTA1; NbExp=3; IntAct=EBI-10987518, EBI-375617;
CC Q99959-2; Q8WW24: TEKT4; NbExp=3; IntAct=EBI-10987518, EBI-750487;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:22781308}. Cell
CC junction, desmosome {ECO:0000269|PubMed:19533476,
CC ECO:0000269|PubMed:22781308}. Note=Nuclear and associated with
CC desmosomes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=2; Synonyms=B;
CC IsoId=Q99959-1; Sequence=Displayed;
CC Name=1; Synonyms=A;
CC IsoId=Q99959-2; Sequence=VSP_006736;
CC -!- TISSUE SPECIFICITY: Detected in heart right ventricle (at protein
CC level). Widely expressed. Found at desmosomal plaques in simple and
CC stratified epithelia and in non-epithelial tissues such as myocardium
CC and lymph node follicles. In most stratified epithelia found in the
CC desmosomes of the basal cell layer and seems to be absent from
CC suprabasal strata. {ECO:0000269|PubMed:10374264,
CC ECO:0000269|PubMed:22781308}.
CC -!- DISEASE: Arrhythmogenic right ventricular dysplasia, familial, 9
CC (ARVD9) [MIM:609040]: A congenital heart disease characterized by
CC infiltration of adipose and fibrous tissue into the right ventricle and
CC loss of myocardial cells, resulting in ventricular and supraventricular
CC arrhythmias. {ECO:0000269|PubMed:15489853, ECO:0000269|PubMed:19533476,
CC ECO:0000269|PubMed:19863551, ECO:0000269|PubMed:19955750,
CC ECO:0000269|PubMed:20031617, ECO:0000269|PubMed:22781308}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- MISCELLANEOUS: [Isoform 2]: Undetected in heart.
CC -!- MISCELLANEOUS: [Isoform 1]: Major isoform in heart. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the beta-catenin family. {ECO:0000305}.
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DR EMBL; X97675; CAA66264.1; -; mRNA.
DR EMBL; X97675; CAA66265.1; -; mRNA.
DR EMBL; EU492903; ACD03459.1; -; Genomic_DNA.
DR EMBL; EU520483; ACD13292.1; -; mRNA.
DR EMBL; EU520484; ACD13293.1; -; mRNA.
DR EMBL; AC087311; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC087588; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471116; EAW88511.1; -; Genomic_DNA.
DR EMBL; CH471116; EAW88514.1; -; Genomic_DNA.
DR EMBL; CH471116; EAW88515.1; -; Genomic_DNA.
DR EMBL; BC094762; AAH94762.1; -; mRNA.
DR EMBL; BC126199; AAI26200.1; -; mRNA.
DR EMBL; BC143966; AAI43967.1; -; mRNA.
DR CCDS; CCDS31771.1; -. [Q99959-2]
DR CCDS; CCDS8731.1; -. [Q99959-1]
DR RefSeq; NP_001005242.2; NM_001005242.2. [Q99959-2]
DR RefSeq; NP_004563.2; NM_004572.3. [Q99959-1]
DR PDB; 3TT9; X-ray; 1.55 A; A=346-620.
DR PDBsum; 3TT9; -.
DR AlphaFoldDB; Q99959; -.
DR SMR; Q99959; -.
DR BioGRID; 111335; 232.
DR IntAct; Q99959; 86.
DR MINT; Q99959; -.
DR STRING; 9606.ENSP00000070846; -.
DR iPTMnet; Q99959; -.
DR PhosphoSitePlus; Q99959; -.
DR SwissPalm; Q99959; -.
DR BioMuta; PKP2; -.
DR DMDM; 296452867; -.
DR EPD; Q99959; -.
DR jPOST; Q99959; -.
DR MassIVE; Q99959; -.
DR MaxQB; Q99959; -.
DR PaxDb; Q99959; -.
DR PeptideAtlas; Q99959; -.
DR PRIDE; Q99959; -.
DR ProteomicsDB; 78543; -. [Q99959-1]
DR ProteomicsDB; 78544; -. [Q99959-2]
DR Antibodypedia; 1963; 338 antibodies from 34 providers.
DR DNASU; 5318; -.
DR Ensembl; ENST00000070846.11; ENSP00000070846.6; ENSG00000057294.16. [Q99959-1]
DR Ensembl; ENST00000340811.9; ENSP00000342800.5; ENSG00000057294.16. [Q99959-2]
DR GeneID; 5318; -.
DR KEGG; hsa:5318; -.
DR MANE-Select; ENST00000340811.9; ENSP00000342800.5; NM_001005242.3; NP_001005242.2. [Q99959-2]
DR UCSC; uc001rlj.5; human. [Q99959-1]
DR CTD; 5318; -.
DR DisGeNET; 5318; -.
DR GeneCards; PKP2; -.
DR GeneReviews; PKP2; -.
DR HGNC; HGNC:9024; PKP2.
DR HPA; ENSG00000057294; Tissue enhanced (heart).
DR MalaCards; PKP2; -.
DR MIM; 602861; gene.
DR MIM; 609040; phenotype.
DR neXtProt; NX_Q99959; -.
DR OpenTargets; ENSG00000057294; -.
DR Orphanet; 130; Brugada syndrome.
DR Orphanet; 293899; Familial isolated arrhythmogenic ventricular dysplasia, biventricular form.
DR Orphanet; 293888; Familial isolated arrhythmogenic ventricular dysplasia, left dominant form.
DR Orphanet; 293910; Familial isolated arrhythmogenic ventricular dysplasia, right dominant form.
DR Orphanet; 54260; Left ventricular noncompaction.
DR PharmGKB; PA33357; -.
DR VEuPathDB; HostDB:ENSG00000057294; -.
DR eggNOG; KOG1048; Eukaryota.
DR GeneTree; ENSGT00940000158677; -.
DR HOGENOM; CLU_009111_3_0_1; -.
DR InParanoid; Q99959; -.
DR OMA; PAECGYI; -.
DR OrthoDB; 765704at2759; -.
DR PhylomeDB; Q99959; -.
DR TreeFam; TF321877; -.
DR PathwayCommons; Q99959; -.
DR Reactome; R-HSA-6805567; Keratinization.
DR Reactome; R-HSA-6809371; Formation of the cornified envelope.
DR SignaLink; Q99959; -.
DR SIGNOR; Q99959; -.
DR BioGRID-ORCS; 5318; 13 hits in 1093 CRISPR screens.
DR ChiTaRS; PKP2; human.
DR GeneWiki; PKP2; -.
DR GenomeRNAi; 5318; -.
DR Pharos; Q99959; Tbio.
DR PRO; PR:Q99959; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q99959; protein.
DR Bgee; ENSG00000057294; Expressed in heart right ventricle and 152 other tissues.
DR ExpressionAtlas; Q99959; baseline and differential.
DR Genevisible; Q99959; HS.
DR GO; GO:0005912; C:adherens junction; IBA:GO_Central.
DR GO; GO:0030054; C:cell junction; IDA:HPA.
DR GO; GO:0005911; C:cell-cell junction; ISS:BHF-UCL.
DR GO; GO:0001533; C:cornified envelope; TAS:Reactome.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0030057; C:desmosome; ISS:BHF-UCL.
DR GO; GO:0016021; C:integral component of membrane; TAS:ProtInc.
DR GO; GO:0014704; C:intercalated disc; IDA:BHF-UCL.
DR GO; GO:0005882; C:intermediate filament; ISS:BHF-UCL.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0045294; F:alpha-catenin binding; IPI:BHF-UCL.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0086083; F:cell adhesive protein binding involved in bundle of His cell-Purkinje myocyte communication; IC:BHF-UCL.
DR GO; GO:0019215; F:intermediate filament binding; IDA:BHF-UCL.
DR GO; GO:0060090; F:molecular adaptor activity; IMP:BHF-UCL.
DR GO; GO:0005080; F:protein kinase C binding; IPI:BHF-UCL.
DR GO; GO:0017080; F:sodium channel regulator activity; ISS:BHF-UCL.
DR GO; GO:0044325; F:transmembrane transporter binding; ISS:BHF-UCL.
DR GO; GO:0086073; P:bundle of His cell-Purkinje myocyte adhesion involved in cell communication; IMP:BHF-UCL.
DR GO; GO:0086002; P:cardiac muscle cell action potential involved in contraction; IMP:BHF-UCL.
DR GO; GO:0086064; P:cell communication by electrical coupling involved in cardiac conduction; ISS:BHF-UCL.
DR GO; GO:0098609; P:cell-cell adhesion; ISS:BHF-UCL.
DR GO; GO:0007043; P:cell-cell junction assembly; IBA:GO_Central.
DR GO; GO:0086019; P:cell-cell signaling involved in cardiac conduction; IMP:BHF-UCL.
DR GO; GO:0002159; P:desmosome assembly; IMP:BHF-UCL.
DR GO; GO:0002934; P:desmosome organization; IBA:GO_Central.
DR GO; GO:0007507; P:heart development; ISS:BHF-UCL.
DR GO; GO:0045110; P:intermediate filament bundle assembly; IMP:BHF-UCL.
DR GO; GO:0048496; P:maintenance of animal organ identity; IMP:BHF-UCL.
DR GO; GO:0010765; P:positive regulation of sodium ion transport; ISS:BHF-UCL.
DR GO; GO:0072659; P:protein localization to plasma membrane; IMP:BHF-UCL.
DR GO; GO:0086091; P:regulation of heart rate by cardiac conduction; IMP:BHF-UCL.
DR GO; GO:0098911; P:regulation of ventricular cardiac muscle cell action potential; IMP:BHF-UCL.
DR GO; GO:0086005; P:ventricular cardiac muscle cell action potential; IMP:BHF-UCL.
DR GO; GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; IMP:BHF-UCL.
DR Gene3D; 1.25.10.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR000225; Armadillo.
DR InterPro; IPR028435; Plakophilin/d_Catenin.
DR PANTHER; PTHR10372; PTHR10372; 1.
DR Pfam; PF00514; Arm; 1.
DR SMART; SM00185; ARM; 5.
DR SUPFAM; SSF48371; SSF48371; 1.
DR PROSITE; PS50176; ARM_REPEAT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cardiomyopathy; Cell adhesion;
KW Cell junction; Disease variant; Methylation; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat.
FT CHAIN 1..881
FT /note="Plakophilin-2"
FT /id="PRO_0000064286"
FT REPEAT 341..383
FT /note="ARM 1"
FT REPEAT 385..424
FT /note="ARM 2"
FT REPEAT 427..467
FT /note="ARM 3"
FT REPEAT 571..616
FT /note="ARM 4"
FT REPEAT 671..711
FT /note="ARM 5"
FT REPEAT 719..758
FT /note="ARM 6"
FT REPEAT 763..804
FT /note="ARM 7"
FT REPEAT 807..849
FT /note="ARM 8"
FT REGION 282..314
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 282..301
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 44
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 46
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 132
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332"
FT MOD_RES 135
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 151
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 154
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 155
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 169
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332"
FT MOD_RES 172
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 177
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 183
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 197
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 251
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 294
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 329
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT VAR_SEQ 460..503
FT /note="Missing (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:8922383"
FT /id="VSP_006736"
FT VARIANT 26
FT /note="D -> N (may be associated with increased
FT susceptibility to arrhythmogenic right ventricular
FT cardiomyopathy; dbSNP:rs143004808)"
FT /evidence="ECO:0000269|PubMed:19955750,
FT ECO:0000269|PubMed:20031617"
FT /id="VAR_065701"
FT VARIANT 58
FT /note="E -> D (in dbSNP:rs146708884)"
FT /evidence="ECO:0000269|PubMed:19955750"
FT /id="VAR_065702"
FT VARIANT 59
FT /note="Q -> L (in ARVD9; unknown pathological significance;
FT decreased interaction with DSP; dbSNP:rs730880179)"
FT /evidence="ECO:0000269|PubMed:19533476"
FT /id="VAR_080397"
FT VARIANT 62
FT /note="Q -> K (in ARVD9; unknown pathological significance;
FT decreased protein stability; decreased interaction with
FT DSP; does not affect subcellular location to the
FT desmosomes; dbSNP:rs199601548)"
FT /evidence="ECO:0000269|PubMed:19533476,
FT ECO:0000269|PubMed:19955750"
FT /id="VAR_065703"
FT VARIANT 70
FT /note="S -> I (in dbSNP:rs75909145)"
FT /evidence="ECO:0000269|PubMed:19863551,
FT ECO:0000269|PubMed:19955750, ECO:0000269|PubMed:20031617"
FT /id="VAR_065704"
FT VARIANT 76
FT /note="N -> S (in dbSNP:rs1201224837)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_070276"
FT VARIANT 79..881
FT /note="Missing (in ARVD9)"
FT /evidence="ECO:0000269|PubMed:19955750"
FT /id="VAR_080398"
FT VARIANT 112
FT /note="K -> N"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_070277"
FT VARIANT 137
FT /note="E -> K (in ARVD9; dbSNP:rs781739949)"
FT /evidence="ECO:0000269|PubMed:19863551"
FT /id="VAR_065705"
FT VARIANT 140
FT /note="S -> F (in dbSNP:rs150821281)"
FT /evidence="ECO:0000269|PubMed:15489853,
FT ECO:0000269|PubMed:19955750, ECO:0000269|PubMed:20031617"
FT /id="VAR_021148"
FT VARIANT 169
FT /note="S -> G (in ARVD9; dbSNP:rs139139859)"
FT /evidence="ECO:0000269|PubMed:19863551"
FT /id="VAR_065706"
FT VARIANT 195
FT /note="A -> V (in dbSNP:rs1041783952)"
FT /evidence="ECO:0000269|PubMed:20031617"
FT /id="VAR_065707"
FT VARIANT 276
FT /note="P -> S (in dbSNP:rs201944276)"
FT /evidence="ECO:0000269|PubMed:20031617"
FT /id="VAR_065708"
FT VARIANT 338
FT /note="T -> A (in dbSNP:rs139851304)"
FT /evidence="ECO:0000269|PubMed:19955750"
FT /id="VAR_065709"
FT VARIANT 366
FT /note="L -> P (in dbSNP:rs1046116)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:19863551, ECO:0000269|PubMed:19955750,
FT ECO:0000269|PubMed:20031617, ECO:0000269|PubMed:8922383"
FT /id="VAR_063108"
FT VARIANT 372
FT /note="A -> P (in dbSNP:rs200586695)"
FT /evidence="ECO:0000269|PubMed:20031617,
FT ECO:0000269|PubMed:21062920"
FT /id="VAR_065710"
FT VARIANT 424
FT /note="F -> S (in ARVD9; dbSNP:rs397516990)"
FT /evidence="ECO:0000269|PubMed:20031617"
FT /id="VAR_065711"
FT VARIANT 489
FT /note="G -> R (in ARVD9; unknown pathological significance;
FT dbSNP:rs111450489)"
FT /evidence="ECO:0000269|PubMed:19955750"
FT /id="VAR_065712"
FT VARIANT 490
FT /note="R -> W (in dbSNP:rs149930872)"
FT /evidence="ECO:0000269|PubMed:21378009"
FT /id="VAR_070037"
FT VARIANT 526
FT /note="T -> M (in dbSNP:rs146882581)"
FT /evidence="ECO:0000269|PubMed:20031617"
FT /id="VAR_065713"
FT VARIANT 531
FT /note="I -> S (in dbSNP:rs147240502)"
FT /evidence="ECO:0000269|PubMed:19955750,
FT ECO:0000269|PubMed:20031617"
FT /id="VAR_065714"
FT VARIANT 587
FT /note="V -> I (may be associated with increased
FT susceptibility to arrhythmogenic right ventricular
FT cardiomyopathy; dbSNP:rs146102241)"
FT /evidence="ECO:0000269|PubMed:19863551,
FT ECO:0000269|PubMed:19955750, ECO:0000269|PubMed:20031617,
FT ECO:0000269|Ref.2"
FT /id="VAR_065715"
FT VARIANT 615
FT /note="S -> F (in ARVD9; impairs protein stability;
FT dbSNP:rs1060501186)"
FT /evidence="ECO:0000269|PubMed:15489853,
FT ECO:0000269|PubMed:22781308"
FT /id="VAR_021149"
FT VARIANT 631
FT /note="Y -> C (in ARVD9; dbSNP:rs1060501183)"
FT /evidence="ECO:0000269|PubMed:19863551"
FT /id="VAR_065716"
FT VARIANT 654
FT /note="K -> Q (in ARVD9; impairs protein stability;
FT dbSNP:rs1319690519)"
FT /evidence="ECO:0000269|PubMed:15489853,
FT ECO:0000269|PubMed:22781308"
FT /id="VAR_021150"
FT VARIANT 673
FT /note="G -> V (in ARVD9; unknown pathological significance;
FT dbSNP:rs1426480515)"
FT /evidence="ECO:0000269|PubMed:19955750"
FT /id="VAR_065717"
FT VARIANT 787
FT /note="L -> F (in ARVD9; dbSNP:rs1462688980)"
FT /evidence="ECO:0000269|PubMed:20031617"
FT /id="VAR_065718"
FT VARIANT 796
FT /note="C -> R (in ARVD9; impairs protein stability;
FT dbSNP:rs794729098)"
FT /evidence="ECO:0000269|PubMed:15489853,
FT ECO:0000269|PubMed:22781308"
FT /id="VAR_021151"
FT HELIX 353..358
FT /evidence="ECO:0007829|PDB:3TT9"
FT HELIX 367..381
FT /evidence="ECO:0007829|PDB:3TT9"
FT HELIX 385..393
FT /evidence="ECO:0007829|PDB:3TT9"
FT HELIX 396..402
FT /evidence="ECO:0007829|PDB:3TT9"
FT HELIX 403..405
FT /evidence="ECO:0007829|PDB:3TT9"
FT HELIX 409..423
FT /evidence="ECO:0007829|PDB:3TT9"
FT HELIX 427..435
FT /evidence="ECO:0007829|PDB:3TT9"
FT HELIX 438..448
FT /evidence="ECO:0007829|PDB:3TT9"
FT HELIX 452..459
FT /evidence="ECO:0007829|PDB:3TT9"
FT HELIX 504..510
FT /evidence="ECO:0007829|PDB:3TT9"
FT HELIX 513..515
FT /evidence="ECO:0007829|PDB:3TT9"
FT HELIX 516..530
FT /evidence="ECO:0007829|PDB:3TT9"
FT HELIX 532..536
FT /evidence="ECO:0007829|PDB:3TT9"
FT HELIX 540..542
FT /evidence="ECO:0007829|PDB:3TT9"
FT HELIX 552..565
FT /evidence="ECO:0007829|PDB:3TT9"
FT HELIX 570..577
FT /evidence="ECO:0007829|PDB:3TT9"
FT HELIX 582..595
FT /evidence="ECO:0007829|PDB:3TT9"
FT HELIX 602..614
FT /evidence="ECO:0007829|PDB:3TT9"
SQ SEQUENCE 881 AA; 97415 MW; 947838B0C8275D5D CRC64;
MAAPGAPAEY GYIRTVLGQQ ILGQLDSSSL ALPSEAKLKL AGSSGRGGQT VKSLRIQEQV
QQTLARKGRS SVGNGNLHRT SSVPEYVYNL HLVENDFVGG RSPVPKTYDM LKAGTTATYE
GRWGRGTAQY SSQKSVEERS LRHPLRRLEI SPDSSPERAH YTHSDYQYSQ RSQAGHTLHH
QESRRAALLV PPRYARSEIV GVSRAGTTSR QRHFDTYHRQ YQHGSVSDTV FDSIPANPAL
LTYPRPGTSR SMGNLLEKEN YLTAGLTVGQ VRPLVPLQPV TQNRASRSSW HQSSFHSTRT
LREAGPSVAV DSSGRRAHLT VGQAAAGGSG NLLTERSTFT DSQLGNADME MTLERAVSML
EADHMLPSRI SAAATFIQHE CFQKSEARKR VNQLRGILKL LQLLKVQNED VQRAVCGALR
NLVFEDNDNK LEVAELNGVP RLLQVLKQTR DLETKKQITD HTVNLRSRNG WPGAVAHACN
PSTLGGQGGR ITRSGVRDQP DQHGLLWNLS SNDKLKNLMI TEALLTLTEN IIIPFSGWPE
GDYPKANGLL DFDIFYNVTG CLRNMSSAGA DGRKAMRRCD GLIDSLVHYV RGTIADYQPD
DKATENCVCI LHNLSYQLEA ELPEKYSQNI YIQNRNIQTD NNKSIGCFGS RSRKVKEQYQ
DVPMPEEKSN PKGVEWLWHS IVIRMYLSLI AKSVRNYTQE ASLGALQNLT AGSGPMPTSV
AQTVVQKESG LQHTRKMLHV GDPSVKKTAI SLLRNLSRNL SLQNEIAKET LPDLVSIIPD
TVPSTDLLIE TTASACYTLN NIIQNSYQNA RDLLNTGGIQ KIMAISAGDA YASNKASKAA
SVLLYSLWAH TELHHAYKKA QFKKTDFVNS RTAKAYHSLK D
