PKP3_HUMAN
ID PKP3_HUMAN Reviewed; 797 AA.
AC Q9Y446; F8J390; Q53EX8;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Plakophilin-3;
GN Name=PKP3;
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] (ISOFORM PKP3A).
RC TISSUE=Colon carcinoma;
RX PubMed=10374265; DOI=10.1046/j.1432-0436.1999.6450291.x;
RA Schmidt A., Langbein L., Praetzel S., Rode M., Rackwitz H.-R., Franke W.W.;
RT "Plakophilin 3 -- a novel cell-type-specific desmosomal plaque protein.";
RL Differentiation 64:291-306(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PKP3A).
RX PubMed=10381383; DOI=10.1242/jcs.112.14.2265;
RA Bonne S., van Hengel J., Nollet F., Kools P., van Roy F.;
RT "Plakophilin-3, a novel armadillo-like protein present in nuclei and
RT desmosomes of epithelial cells.";
RL J. Cell Sci. 112:2265-2276(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PKP3B), ALTERNATIVE PROMOTER USAGE, AND
RP TISSUE SPECIFICITY.
RX PubMed=24178805; DOI=10.1007/s00441-013-1736-1;
RA Muhmer M., Ditthardt D., Jakel J., Wischmann V., Moll R., Schmidt A.;
RT "An alternative promoter of the human plakophilin-3 gene controls the
RT expression of the new isoform PKP3b.";
RL Cell Tissue Res. 355:143-162(2014).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM PKP3A).
RC TISSUE=Colon;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM PKP3A).
RC TISSUE=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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-178 (ISOFORM PKP3B).
RC TISSUE=Tongue;
RX PubMed=16344560; DOI=10.1101/gr.4039406;
RA Kimura K., Wakamatsu A., Suzuki Y., Ota T., Nishikawa T., Yamashita R.,
RA Yamamoto J., Sekine M., Tsuritani K., Wakaguri H., Ishii S., Sugiyama T.,
RA Saito K., Isono Y., Irie R., Kushida N., Yoneyama T., Otsuka R., Kanda K.,
RA Yokoi T., Kondo H., Wagatsuma M., Murakawa K., Ishida S., Ishibashi T.,
RA Takahashi-Fujii A., Tanase T., Nagai K., Kikuchi H., Nakai K., Isogai T.,
RA Sugano S.;
RT "Diversification of transcriptional modulation: large-scale identification
RT and characterization of putative alternative promoters of human genes.";
RL Genome Res. 16:55-65(2006).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-238, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [8]
RP IDENTIFICATION BY 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-180; SER-238; SER-240;
RP SER-313 AND SER-314, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 IDENTIFICATION BY 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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-238; SER-313 AND SER-314, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [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 [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-314, AND IDENTIFICATION BY
RP 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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-180; SER-183; SER-238;
RP THR-250; SER-313; SER-314 AND SER-331, 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 [15]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-81 AND ARG-261, AND
RP IDENTIFICATION BY MASS 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).
CC -!- FUNCTION: May play a role in junctional plaques.
CC -!- INTERACTION:
CC Q9Y446; P14136: GFAP; NbExp=3; IntAct=EBI-2880227, EBI-744302;
CC Q9Y446; Q8NA54: IQUB; NbExp=3; IntAct=EBI-2880227, EBI-10220600;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cell junction, desmosome. Note=Nuclear
CC and associated with desmosomes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage; Named isoforms=2;
CC Name=PKP3a;
CC IsoId=Q9Y446-1; Sequence=Displayed;
CC Name=PKP3b;
CC IsoId=Q9Y446-2; Sequence=VSP_053646;
CC -!- TISSUE SPECIFICITY: Isoform PKP3a is found in desmosomes of most simple
CC and stratified epithelia. Not found in foreskin fibroblasts and various
CC sarcoma-derived cell lines. Beside dendritic reticular cells of
CC lymphatic follicles not found in non-epithelial desmosome-bearing
CC tissues. Isoform PKP3b is abundant in the desmosomes of stratified
CC epithelial cell but absent in simple epithelial cells, it is also
CC expressed in the colon and its tumors. {ECO:0000269|PubMed:24178805}.
CC -!- SIMILARITY: Belongs to the beta-catenin family. {ECO:0000305}.
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DR EMBL; Z98265; CAB44310.1; -; mRNA.
DR EMBL; AF053719; AAF23050.1; -; mRNA.
DR EMBL; FN421477; CAZ65731.1; -; mRNA.
DR EMBL; AK223511; BAD97231.1; -; mRNA.
DR EMBL; BC000081; AAH00081.1; -; mRNA.
DR EMBL; DA439471; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS7695.1; -. [Q9Y446-1]
DR RefSeq; NP_001289958.1; NM_001303029.1. [Q9Y446-2]
DR RefSeq; NP_009114.1; NM_007183.3. [Q9Y446-1]
DR AlphaFoldDB; Q9Y446; -.
DR SMR; Q9Y446; -.
DR BioGRID; 116357; 139.
DR IntAct; Q9Y446; 49.
DR MINT; Q9Y446; -.
DR STRING; 9606.ENSP00000331678; -.
DR GlyGen; Q9Y446; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9Y446; -.
DR PhosphoSitePlus; Q9Y446; -.
DR SwissPalm; Q9Y446; -.
DR BioMuta; PKP3; -.
DR DMDM; 20139301; -.
DR CPTAC; CPTAC-990; -.
DR EPD; Q9Y446; -.
DR jPOST; Q9Y446; -.
DR MassIVE; Q9Y446; -.
DR MaxQB; Q9Y446; -.
DR PaxDb; Q9Y446; -.
DR PeptideAtlas; Q9Y446; -.
DR PRIDE; Q9Y446; -.
DR ProteomicsDB; 86098; -. [Q9Y446-1]
DR Antibodypedia; 4571; 294 antibodies from 33 providers.
DR DNASU; 11187; -.
DR Ensembl; ENST00000331563.7; ENSP00000331678.2; ENSG00000184363.10. [Q9Y446-1]
DR GeneID; 11187; -.
DR KEGG; hsa:11187; -.
DR MANE-Select; ENST00000331563.7; ENSP00000331678.2; NM_007183.4; NP_009114.1.
DR UCSC; uc001lpc.3; human. [Q9Y446-1]
DR CTD; 11187; -.
DR DisGeNET; 11187; -.
DR GeneCards; PKP3; -.
DR HGNC; HGNC:9025; PKP3.
DR HPA; ENSG00000184363; Tissue enhanced (esophagus, skin, vagina).
DR MIM; 605561; gene.
DR neXtProt; NX_Q9Y446; -.
DR OpenTargets; ENSG00000184363; -.
DR PharmGKB; PA33358; -.
DR VEuPathDB; HostDB:ENSG00000184363; -.
DR eggNOG; KOG1048; Eukaryota.
DR GeneTree; ENSGT00940000159515; -.
DR HOGENOM; CLU_009111_2_0_1; -.
DR InParanoid; Q9Y446; -.
DR OMA; LDWPEAS; -.
DR OrthoDB; 233858at2759; -.
DR PhylomeDB; Q9Y446; -.
DR TreeFam; TF321877; -.
DR PathwayCommons; Q9Y446; -.
DR Reactome; R-HSA-6805567; Keratinization.
DR Reactome; R-HSA-6809371; Formation of the cornified envelope.
DR SignaLink; Q9Y446; -.
DR BioGRID-ORCS; 11187; 8 hits in 1079 CRISPR screens.
DR ChiTaRS; PKP3; human.
DR GeneWiki; PKP3; -.
DR GenomeRNAi; 11187; -.
DR Pharos; Q9Y446; Tbio.
DR PRO; PR:Q9Y446; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9Y446; protein.
DR Bgee; ENSG00000184363; Expressed in lower esophagus mucosa and 156 other tissues.
DR ExpressionAtlas; Q9Y446; baseline and differential.
DR Genevisible; Q9Y446; HS.
DR GO; GO:0005912; C:adherens junction; HDA:BHF-UCL.
DR GO; GO:0030054; C:cell junction; IDA:HPA.
DR GO; GO:0005911; C:cell-cell junction; TAS:ProtInc.
DR GO; GO:0001533; C:cornified envelope; TAS:Reactome.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0030057; C:desmosome; IEA:UniProtKB-SubCell.
DR GO; GO:1990124; C:messenger ribonucleoprotein complex; IDA:CAFA.
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; IBA:GO_Central.
DR GO; GO:0098641; F:cadherin binding involved in cell-cell adhesion; HDA:BHF-UCL.
DR GO; GO:0050839; F:cell adhesion molecule binding; IPI:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; IPI:CAFA.
DR GO; GO:0098609; P:cell-cell adhesion; IBA:GO_Central.
DR GO; GO:0007043; P:cell-cell junction assembly; IBA:GO_Central.
DR GO; GO:0002159; P:desmosome assembly; IMP:UniProtKB.
DR GO; GO:1902373; P:negative regulation of mRNA catabolic process; IMP:CAFA.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:CAFA.
DR GO; GO:0072659; P:protein localization to plasma membrane; IMP:UniProtKB.
DR Gene3D; 1.25.10.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR000225; Armadillo.
DR InterPro; IPR028434; Plakophilin-3.
DR InterPro; IPR028435; Plakophilin/d_Catenin.
DR PANTHER; PTHR10372; PTHR10372; 1.
DR PANTHER; PTHR10372:SF1; PTHR10372:SF1; 1.
DR Pfam; PF00514; Arm; 2.
DR SMART; SM00185; ARM; 4.
DR SUPFAM; SSF48371; SSF48371; 1.
DR PROSITE; PS50176; ARM_REPEAT; 1.
PE 1: Evidence at protein level;
KW Alternative promoter usage; Cell adhesion; Cell junction; Methylation;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..797
FT /note="Plakophilin-3"
FT /id="PRO_0000064287"
FT REPEAT 305..348
FT /note="ARM 1"
FT REPEAT 351..390
FT /note="ARM 2"
FT REPEAT 393..432
FT /note="ARM 3"
FT REPEAT 449..487
FT /note="ARM 4"
FT REPEAT 491..536
FT /note="ARM 5"
FT REPEAT 596..637
FT /note="ARM 6"
FT REPEAT 645..684
FT /note="ARM 7"
FT REPEAT 689..730
FT /note="ARM 8"
FT REGION 56..82
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 81
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 123
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9QY23"
FT MOD_RES 180
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 183
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 238
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 240
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 250
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 261
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 313
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 314
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 331
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..12
FT /note="MQDGNFLLSALQ -> MESWTPRPSAVASGMSWEAGGIRTTSR (in
FT isoform PKP3b)"
FT /evidence="ECO:0000303|PubMed:16344560,
FT ECO:0000303|PubMed:24178805"
FT /id="VSP_053646"
FT CONFLICT 719
FT /note="V -> A (in Ref. 4; BAD97231)"
FT /evidence="ECO:0000305"
FT CONFLICT 730
FT /note="V -> G (in Ref. 4; BAD97231)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 797 AA; 87082 MW; D43C7E77FA805E7E CRC64;
MQDGNFLLSA LQPEAGVCSL ALPSDLQLDR RGAEGPEAER LRAARVQEQV RARLLQLGQQ
PRHNGAAEPE PEAETARGTS RGQYHTLQAG FSSRSQGLSG DKTSGFRPIA KPAYSPASWS
SRSAVDLSCS RRLSSAHNGG SAFGAAGYGG AQPTPPMPTR PVSFHERGGV GSRADYDTLS
LRSLRLGPGG LDDRYSLVSE QLEPAATSTY RAFAYERQAS SSSSRAGGLD WPEATEVSPS
RTIRAPAVRT LQRFQSSHRS RGVGGAVPGA VLEPVARAPS VRSLSLSLAD SGHLPDVHGF
NSYGSHRTLQ RLSSGFDDID LPSAVKYLMA SDPNLQVLGA AYIQHKCYSD AAAKKQARSL
QAVPRLVKLF NHANQEVQRH ATGAMRNLIY DNADNKLALV EENGIFELLR TLREQDDELR
KNVTGILWNL SSSDHLKDRL ARDTLEQLTD LVLSPLSGAG GPPLIQQNAS EAEIFYNATG
FLRNLSSASQ ATRQKMRECH GLVDALVTSI NHALDAGKCE DKSVENAVCV LRNLSYRLYD
EMPPSALQRL EGRGRRDLAG APPGEVVGCF TPQSRRLREL PLAADALTFA EVSKDPKGLE
WLWSPQIVGL YNRLLQRCEL NRHTTEAAAG ALQNITAGDR RWAGVLSRLA LEQERILNPL
LDRVRTADHH QLRSLTGLIR NLSRNARNKD EMSTKVVSHL IEKLPGSVGE KSPPAEVLVN
IIAVLNNLVV ASPIAARDLL YFDGLRKLIF IKKKRDSPDS EKSSRAASSL LANLWQYNKL
HRDFRAKGYR KEDFLGP
