ID PKP1_HUMAN Reviewed; 747 AA. AC Q13835; O00645; Q14CA0; Q15152; DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2002, sequence version 2. DT 27-MAR-2024, entry version 205. DE RecName: Full=Plakophilin-1; DE AltName: Full=Band 6 protein; DE Short=B6P; GN Name=PKP1; 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 1). RC TISSUE=Epidermis; RX PubMed=7527055; DOI=10.1242/jcs.107.8.2259; RA Hatzfeld M., Kristjansson G.I., Plessmann U., Weber K.; RT "Band 6 protein, a major constituent of desmosomes from stratified RT epithelia, is a novel member of the armadillo multigene family."; RL J. Cell Sci. 107:2259-2270(1994). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), SUBCELLULAR RP LOCATION, AND TISSUE SPECIFICITY. RX PubMed=9369526; DOI=10.1007/s004410050956; RA Schmidt A., Langbein L., Rode M., Praetzel S., Zimbelmann R., Franke W.W.; RT "Plakophilins 1a and 1b: widespread nuclear proteins recruited in specific RT epithelial cells as desmosomal plaque components."; RL Cell Tissue Res. 290:481-499(1997). RN [3] 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 [5] RP INVOLVEMENT IN ECTODERMAL DYSPLASIA/SKIN FRAGILITY SYNDROME, AND FUNCTION. RX PubMed=9326952; DOI=10.1038/ng1097-240; RA McGrath J.A., McMillan J.R., Shemanko C.S., Runswick S.K., Leigh I.M., RA Lane E.B., Garrod D.R., Eady R.A.J.; RT "Mutations in the plakophilin 1 gene result in ectodermal dysplasia/skin RT fragility syndrome."; RL Nat. Genet. 17:240-244(1997). RN [6] RP FUNCTION, AND INTERACTION WITH KRT5; KRT8; KRT14; KRT18; VIM; DSP AND DES. RX PubMed=10852826; DOI=10.1242/jcs.113.13.2471; RA Hofmann I., Mertens C., Brettel M., Nimmrich V., Schnoelzer M., RA Herrmann H.; RT "Interaction of plakophilins with desmoplakin and intermediate filament RT proteins: an in vitro analysis."; RL J. Cell Sci. 113:2471-2483(2000). RN [7] RP INTERACTION WITH DSP. RX PubMed=11790773; DOI=10.1074/jbc.m108765200; RA Chen X., Bonne S., Hatzfeld M., van Roy F., Green K.J.; RT "Protein binding and functional characterization of plakophilin 2. Evidence RT for its diverse roles in desmosomes and beta -catenin signaling."; RL J. Biol. Chem. 277:10512-10522(2002). RN [8] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 244-721, AND DOMAINS ARM REPEATS. RX PubMed=15663951; DOI=10.1016/j.jmb.2004.11.048; RA Choi H.-J., Weis W.I.; RT "Structure of the armadillo repeat domain of plakophilin 1."; RL J. Mol. Biol. 346:367-376(2005). CC -!- FUNCTION: Seems to play a role in junctional plaques. Contributes to CC epidermal morphogenesis (PubMed:9326952). May facilitate the formation CC of intermediate filaments (PubMed:10852826). CC {ECO:0000269|PubMed:10852826, ECO:0000269|PubMed:9326952}. CC -!- SUBUNIT: Interacts with DSP (PubMed:11790773). Interacts (via N- CC terminus) with KRT5/CK5, KRT8/CK8 (via rod domain), KRT15/CK15 and CC KRT18/CK18 (via rod domain) as part of intermediate filaments CC (PubMed:10852826). Interacts with VIM (via rod domain) CC (PubMed:10852826). Interacts with DSP (PubMed:10852826). Interacts with CC DES (PubMed:10852826). {ECO:0000269|PubMed:10852826, CC ECO:0000269|PubMed:11790773}. CC -!- INTERACTION: CC Q13835; Q02413: DSG1; NbExp=2; IntAct=EBI-2513407, EBI-1045757; CC Q13835; Q9UHL9: GTF2IRD1; NbExp=2; IntAct=EBI-2513407, EBI-372530; CC Q13835; Q63HR2: TNS2; NbExp=3; IntAct=EBI-2513407, EBI-949753; CC Q13835-2; A1A5D9: BICDL2; NbExp=3; IntAct=EBI-9087684, EBI-10171799; CC Q13835-2; Q9BWT7: CARD10; NbExp=3; IntAct=EBI-9087684, EBI-3866279; CC Q13835-2; Q8TAP6: CEP76; NbExp=3; IntAct=EBI-9087684, EBI-742887; CC Q13835-2; P15924: DSP; NbExp=2; IntAct=EBI-9087684, EBI-355041; CC Q13835-2; Q08379: GOLGA2; NbExp=3; IntAct=EBI-9087684, EBI-618309; CC Q13835-2; Q96ED9-2: HOOK2; NbExp=3; IntAct=EBI-9087684, EBI-10961706; CC Q13835-2; O75031: HSF2BP; NbExp=3; IntAct=EBI-9087684, EBI-7116203; CC Q13835-2; P02533: KRT14; NbExp=2; IntAct=EBI-9087684, EBI-702178; CC Q13835-2; P05783: KRT18; NbExp=4; IntAct=EBI-9087684, EBI-297888; CC Q13835-2; P13647: KRT5; NbExp=2; IntAct=EBI-9087684, EBI-702187; CC Q13835-2; P05787: KRT8; NbExp=3; IntAct=EBI-9087684, EBI-297852; CC Q13835-2; Q8NI38: NFKBID; NbExp=3; IntAct=EBI-9087684, EBI-10271199; CC Q13835-2; P08670: VIM; NbExp=3; IntAct=EBI-9087684, EBI-353844; CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell junction, desmosome CC {ECO:0000269|PubMed:9369526}. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Nucleus CC {ECO:0000269|PubMed:9369526}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11790773}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=2; Synonyms=1b {ECO:0000303|PubMed:9369526}; CC IsoId=Q13835-1; Sequence=Displayed; CC Name=1; Synonyms=1a {ECO:0000303|PubMed:9369526}; CC IsoId=Q13835-2; Sequence=VSP_006735; CC -!- TISSUE SPECIFICITY: [Isoform 1]: Expressed in stratified squamous, CC complex, glandular duct and bladder epithelia (at protein level). CC {ECO:0000269|PubMed:9369526}. CC -!- TISSUE SPECIFICITY: [Isoform 2]: Widely expressed (at protein level). CC {ECO:0000269|PubMed:9369526}. CC -!- DISEASE: Ectodermal dysplasia-skin fragility syndrome (EDSFS) CC [MIM:604536]: A form of ectodermal dysplasia, a heterogeneous group of CC disorders due to abnormal development of two or more ectodermal CC structures. Characterized by features of both cutaneous fragility and CC congenital ectodermal dysplasia affecting skin, hair and nails. There CC is no evidence of significant abnormalities in other epithelia or CC tissues. Desmosomes in the skin are small and poorly formed with CC widening of keratinocyte intercellular spaces and perturbed CC desmosome/keratin intermediate filament interactions. Note=The disease CC is caused by variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the beta-catenin family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X79293; CAA55881.1; -; mRNA. DR EMBL; Z34974; CAA84426.1; -; mRNA. DR EMBL; Z73677; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; Z73678; CAA98022.1; -; Genomic_DNA. DR EMBL; CH471067; EAW91350.1; -; Genomic_DNA. DR EMBL; BC114571; AAI14572.1; -; mRNA. DR CCDS; CCDS30966.1; -. [Q13835-1] DR CCDS; CCDS30967.1; -. [Q13835-2] DR PIR; S60712; S60712. DR RefSeq; NP_000290.2; NM_000299.3. [Q13835-1] DR RefSeq; NP_001005337.1; NM_001005337.2. [Q13835-2] DR PDB; 1XM9; X-ray; 2.80 A; A=244-721. DR PDBsum; 1XM9; -. DR AlphaFoldDB; Q13835; -. DR SMR; Q13835; -. DR BioGRID; 111334; 192. DR CORUM; Q13835; -. DR IntAct; Q13835; 42. DR MINT; Q13835; -. DR STRING; 9606.ENSP00000263946; -. DR ChEMBL; CHEMBL4295817; -. DR GlyGen; Q13835; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q13835; -. DR PhosphoSitePlus; Q13835; -. DR SwissPalm; Q13835; -. DR BioMuta; PKP1; -. DR DMDM; 20138951; -. DR EPD; Q13835; -. DR jPOST; Q13835; -. DR MassIVE; Q13835; -. DR MaxQB; Q13835; -. DR PaxDb; 9606-ENSP00000263946; -. DR PeptideAtlas; Q13835; -. DR PRIDE; Q13835; -. DR ProteomicsDB; 59699; -. [Q13835-1] DR ProteomicsDB; 59700; -. [Q13835-2] DR Antibodypedia; 20641; 235 antibodies from 20 providers. DR DNASU; 5317; -. DR Ensembl; ENST00000263946.7; ENSP00000263946.3; ENSG00000081277.13. [Q13835-1] DR Ensembl; ENST00000352845.3; ENSP00000295597.3; ENSG00000081277.13. [Q13835-1] DR Ensembl; ENST00000367324.8; ENSP00000356293.4; ENSG00000081277.13. [Q13835-2] DR GeneID; 5317; -. DR KEGG; hsa:5317; -. DR MANE-Select; ENST00000367324.8; ENSP00000356293.4; NM_001005337.3; NP_001005337.1. [Q13835-2] DR UCSC; uc001gwd.3; human. [Q13835-1] DR AGR; HGNC:9023; -. DR CTD; 5317; -. DR DisGeNET; 5317; -. DR GeneCards; PKP1; -. DR HGNC; HGNC:9023; PKP1. DR HPA; ENSG00000081277; Group enriched (esophagus, skin, vagina). DR MalaCards; PKP1; -. DR MIM; 601975; gene. DR MIM; 604536; phenotype. DR neXtProt; NX_Q13835; -. DR OpenTargets; ENSG00000081277; -. DR Orphanet; 158668; Ectodermal dysplasia-skin fragility syndrome. DR PharmGKB; PA33356; -. DR VEuPathDB; HostDB:ENSG00000081277; -. DR eggNOG; KOG1048; Eukaryota. DR GeneTree; ENSGT00940000156735; -. DR HOGENOM; CLU_009111_3_1_1; -. DR InParanoid; Q13835; -. DR OMA; NSSWGYP; -. DR OrthoDB; 5473239at2759; -. DR PhylomeDB; Q13835; -. DR TreeFam; TF321877; -. DR PathwayCommons; Q13835; -. DR Reactome; R-HSA-351906; Apoptotic cleavage of cell adhesion proteins. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR Reactome; R-HSA-6805567; Keratinization. DR Reactome; R-HSA-6809371; Formation of the cornified envelope. DR SignaLink; Q13835; -. DR SIGNOR; Q13835; -. DR BioGRID-ORCS; 5317; 7 hits in 1157 CRISPR screens. DR ChiTaRS; PKP1; human. DR EvolutionaryTrace; Q13835; -. DR GeneWiki; PKP1; -. DR GenomeRNAi; 5317; -. DR Pharos; Q13835; Tbio. DR PRO; PR:Q13835; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q13835; Protein. DR Bgee; ENSG00000081277; Expressed in upper arm skin and 114 other cell types or tissues. DR ExpressionAtlas; Q13835; baseline and differential. DR GO; GO:0005912; C:adherens junction; IBA:GO_Central. DR GO; GO:0001533; C:cornified envelope; TAS:Reactome. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0030057; C:desmosome; NAS:UniProtKB. DR GO; GO:0101003; C:ficolin-1-rich granule membrane; TAS:Reactome. DR GO; GO:0005882; C:intermediate filament; TAS:ProtInc. 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:HPA. DR GO; GO:0045296; F:cadherin binding; IBA:GO_Central. DR GO; GO:0019215; F:intermediate filament binding; NAS:UniProtKB. DR GO; GO:0005521; F:lamin binding; IDA:BHF-UCL. DR GO; GO:0030280; F:structural constituent of skin epidermis; NAS:UniProtKB. DR GO; GO:0007155; P:cell adhesion; NAS:UniProtKB. 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:0045110; P:intermediate filament bundle assembly; IDA:BHF-UCL. 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:0007165; P:signal transduction; NAS:UniProtKB. DR Gene3D; 1.25.10.10; Leucine-rich Repeat Variant; 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:SF3; PLAKOPHILIN-1; 1. DR PANTHER; PTHR10372; PLAKOPHILLIN-RELATED; 1. DR Pfam; PF00514; Arm; 1. DR SMART; SM00185; ARM; 6. DR SUPFAM; SSF48371; ARM repeat; 1. DR PROSITE; PS50176; ARM_REPEAT; 3. DR Genevisible; Q13835; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell adhesion; Cell junction; KW Developmental protein; Ectodermal dysplasia; Nucleus; Phosphoprotein; KW Reference proteome; Repeat. FT CHAIN 1..747 FT /note="Plakophilin-1" FT /id="PRO_0000064284" FT REPEAT 243..274 FT /note="ARM 1" FT REPEAT 275..316 FT /note="ARM 2" FT REPEAT 317..359 FT /note="ARM 3" FT REPEAT 360..415 FT /note="ARM 4" FT REPEAT 416..463 FT /note="ARM 5" FT REPEAT 525..556 FT /note="ARM 6" FT REPEAT 557..603 FT /note="ARM 7" FT REPEAT 604..649 FT /note="ARM 8" FT REPEAT 650..713 FT /note="ARM 9" FT REGION 48..68 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 121 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P97350" FT MOD_RES 142 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P97350" FT VAR_SEQ 412..432 FT /note="Missing (in isoform 1)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:7527055, ECO:0000303|PubMed:9369526" FT /id="VSP_006735" FT VARIANT 116 FT /note="R -> H (in dbSNP:rs34626929)" FT /id="VAR_033526" FT VARIANT 161 FT /note="C -> Y (in dbSNP:rs34704938)" FT /id="VAR_033527" FT VARIANT 196 FT /note="I -> V (in dbSNP:rs35507614)" FT /id="VAR_033528" FT VARIANT 415 FT /note="G -> D (in dbSNP:rs1626370)" FT /id="VAR_053811" FT VARIANT 463 FT /note="A -> V (in dbSNP:rs10920171)" FT /id="VAR_062171" FT CONFLICT 154 FT /note="R -> G (in Ref. 1; CAA55881)" FT /evidence="ECO:0000305" FT CONFLICT 216..222 FT /note="PPISCNK -> RHLLQQ (in Ref. 1; CAA55881)" FT /evidence="ECO:0000305" FT CONFLICT 462 FT /note="V -> E (in Ref. 1; CAA55881)" FT /evidence="ECO:0000305" FT CONFLICT 496 FT /note="Q -> K (in Ref. 1; CAA55881)" FT /evidence="ECO:0000305" FT CONFLICT 506 FT /note="T -> P (in Ref. 1; CAA55881)" FT /evidence="ECO:0000305" FT CONFLICT 553 FT /note="L -> S (in Ref. 1; CAA55881)" FT /evidence="ECO:0000305" FT HELIX 247..255 FT /evidence="ECO:0007829|PDB:1XM9" FT HELIX 260..272 FT /evidence="ECO:0007829|PDB:1XM9" FT HELIX 279..285 FT /evidence="ECO:0007829|PDB:1XM9" FT HELIX 288..295 FT /evidence="ECO:0007829|PDB:1XM9" FT HELIX 301..315 FT /evidence="ECO:0007829|PDB:1XM9" FT HELIX 319..327 FT /evidence="ECO:0007829|PDB:1XM9" FT HELIX 331..338 FT /evidence="ECO:0007829|PDB:1XM9" FT HELIX 344..358 FT /evidence="ECO:0007829|PDB:1XM9" FT STRAND 360..362 FT /evidence="ECO:0007829|PDB:1XM9" FT HELIX 364..378 FT /evidence="ECO:0007829|PDB:1XM9" FT HELIX 381..384 FT /evidence="ECO:0007829|PDB:1XM9" FT HELIX 400..411 FT /evidence="ECO:0007829|PDB:1XM9" FT HELIX 438..444 FT /evidence="ECO:0007829|PDB:1XM9" FT HELIX 450..464 FT /evidence="ECO:0007829|PDB:1XM9" FT HELIX 472..482 FT /evidence="ECO:0007829|PDB:1XM9" FT TURN 483..485 FT /evidence="ECO:0007829|PDB:1XM9" FT HELIX 486..489 FT /evidence="ECO:0007829|PDB:1XM9" FT HELIX 493..499 FT /evidence="ECO:0007829|PDB:1XM9" FT HELIX 539..544 FT /evidence="ECO:0007829|PDB:1XM9" FT HELIX 546..558 FT /evidence="ECO:0007829|PDB:1XM9" FT HELIX 562..575 FT /evidence="ECO:0007829|PDB:1XM9" FT STRAND 579..581 FT /evidence="ECO:0007829|PDB:1XM9" FT HELIX 582..591 FT /evidence="ECO:0007829|PDB:1XM9" FT HELIX 597..603 FT /evidence="ECO:0007829|PDB:1XM9" FT HELIX 609..623 FT /evidence="ECO:0007829|PDB:1XM9" FT HELIX 626..628 FT /evidence="ECO:0007829|PDB:1XM9" FT HELIX 629..635 FT /evidence="ECO:0007829|PDB:1XM9" FT HELIX 637..642 FT /evidence="ECO:0007829|PDB:1XM9" FT HELIX 654..669 FT /evidence="ECO:0007829|PDB:1XM9" FT HELIX 674..679 FT /evidence="ECO:0007829|PDB:1XM9" FT HELIX 682..686 FT /evidence="ECO:0007829|PDB:1XM9" FT HELIX 689..693 FT /evidence="ECO:0007829|PDB:1XM9" FT HELIX 698..709 FT /evidence="ECO:0007829|PDB:1XM9" FT STRAND 712..714 FT /evidence="ECO:0007829|PDB:1XM9" SQ SEQUENCE 747 AA; 82861 MW; 60C1BCCC50AB4E6F CRC64; MNHSPLKTAL AYECFQDQDN STLALPSDQK MKTGTSGRQR VQEQVMMTVK RQKSKSSQSS TLSHSNRGSM YDGLADNYNY GTTSRSSYYS KFQAGNGSWG YPIYNGTLKR EPDNRRFSSY SQMENWSRHY PRGSCNTTGA GSDICFMQKI KASRSEPDLY CDPRGTLRKG TLGSKGQKTT QNRYSFYSTC SGQKAIKKCP VRPPSCASKQ DPVYIPPISC NKDLSFGHSR ASSKICSEDI ECSGLTIPKA VQYLSSQDEK YQAIGAYYIQ HTCFQDESAK QQVYQLGGIC KLVDLLRSPN QNVQQAAAGA LRNLVFRSTT NKLETRRQNG IREAVSLLRR TGNAEIQKQL TGLLWNLSST DELKEELIAD ALPVLADRVI IPFSGWCDGN SNMSREVVDP EVFFNATGCL RKRLGMRELL ALVPQRATSS RVNLSSADAG RQTMRNYSGL IDSLMAYVQN CVAASRCDDK SVENCMCVLH NLSYRLDAEV PTRYRQLEYN ARNAYTEKSS TGCFSNKSDK MMNNNYDCPL PEEETNPKGS GWLYHSDAIR TYLNLMGKSK KDATLEACAG ALQNLTASKG LMSSGMSQLI GLKEKGLPQI ARLLQSGNSD VVRSGASLLS NMSRHPLLHR VMGNQVFPEV TRLLTSHTGN TSNSEDILSS ACYTVRNLMA SQPQLAKQYF SSSMLNNIIN LCRSSASPKA AEAARLLLSD MWSSKELQGV LRQQGFDRNM LGTLAGANSL RNFTSRF //