PKP1_HUMAN
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 03-AUG-2022, entry version 196.
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).
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 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. {ECO:0000269|PubMed:9326952}.
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]: Nucleus. Cell junction, desmosome.
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=2; Synonyms=1b;
CC IsoId=Q13835-1; Sequence=Displayed;
CC Name=1; Synonyms=1a;
CC IsoId=Q13835-2; Sequence=VSP_006735;
CC -!- TISSUE SPECIFICITY: Isoform 2 is widely expressed. Isoform 1 is
CC expressed in stratified squamous, complex, glandular duct and bladder
CC epithelia.
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}.
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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; 177.
DR CORUM; Q13835; -.
DR IntAct; Q13835; 38.
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; Q13835; -.
DR PeptideAtlas; Q13835; -.
DR PRIDE; Q13835; -.
DR ProteomicsDB; 59699; -. [Q13835-1]
DR ProteomicsDB; 59700; -. [Q13835-2]
DR Antibodypedia; 20641; 211 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 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; SYYTKTQ; -.
DR OrthoDB; 765704at2759; -.
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 BioGRID-ORCS; 5317; 7 hits in 1079 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 113 other tissues.
DR ExpressionAtlas; Q13835; baseline and differential.
DR Genevisible; Q13835; HS.
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; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR000225; Armadillo.
DR InterPro; IPR028432; Plakophilin-1.
DR InterPro; IPR028435; Plakophilin/d_Catenin.
DR PANTHER; PTHR10372; PTHR10372; 1.
DR PANTHER; PTHR10372:SF3; PTHR10372:SF3; 1.
DR Pfam; PF00514; Arm; 1.
DR SMART; SM00185; ARM; 6.
DR SUPFAM; SSF48371; SSF48371; 1.
DR PROSITE; PS50176; ARM_REPEAT; 3.
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
