PKP1
entrez
5317
canonical
uniprot
Q13835
canonical
ensembl
ENSG00000081277
resolver
ensp
ENSP00000263946
resolver
ensp
ENSP00000356293
resolver
genesymbol
PKP1
resolver
hgnc
HGNC:9023
resolver
uniprot
O00645
resolver
uniprot
Q14CA0
resolver
uniprot
Q15152
resolver
uniprot_entry
PKP1_HUMAN
resolver
uniprot_sec
O00645
resolver
uniprot_sec
Q14CA0
resolver
uniprot_sec
Q15152
resolver
amino_acid_sequence
MNHSPLKTALAYECFQDQDNSTLALPSDQKMKTGTSGRQRVQEQVMMTVKRQKSKSSQSSTLSHSNRGSMYDGLADNYNYGTTSRSSYYSKFQAGNGSWGYPIYNGTLKREPDNRRFSSYSQMENWSRHYPRGSCNTTGAGSDICFMQKIKASRSEPDLYCDPRGTLRKGTLGSKGQKTTQNRYSFYSTCSGQKAIKKCPVRPPSCASKQDPVYIPPISCNKDLSFGHSRASSKICSEDIECSGLTIPKAVQYLSSQDEKYQAIGAYYIQHTCFQDESAKQQVYQLGGICKLVDLLRSPNQNVQQAAAGALRNLVFRSTTNKLETRRQNGIREAVSLLRRTGNAEIQKQLTGLLWNLSSTDELKEELIADALPVLADRVIIPFSGWCDGNSNMSREVVDPEVFFNATGCLRKRLGMRELLALVPQRATSSRVNLSSADAGRQTMRNYSGLIDSLMAYVQNCVAASRCDDKSVENCMCVLHNLSYRLDAEVPTRYRQLEYNARNAYTEKSSTGCFSNKSDKMMNNNYDCPLPEEETNPKGSGWLYHSDAIRTYLNLMGKSKKDATLEACAGALQNLTASKGLMSSGMSQLIGLKEKGLPQIARLLQSGNSDVVRSGASLLSNMSRHPLLHRVMGNQVFPEVTRLLTSHTGNTSNSEDILSSACYTVRNLMASQPQLAKQYFSSSMLNNIINLCRSSASPKAAEAARLLLSDMWSSKELQGVLRQQGFDRNMLGTLAGANSLRNFTSRF
uniprot
proteins
disease_involvement
DISEASE: Ectodermal dysplasia-skin fragility syndrome (EDSFS) [MIM:604536]: A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. Characterized by features of both cutaneous fragility and congenital ectodermal dysplasia affecting skin, hair and nails. There is no evidence of significant abnormalities in other epithelia or tissues. Desmosomes in the skin are small and poorly formed with widening of keratinocyte intercellular spaces and perturbed desmosome/keratin intermediate filament interactions. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:23444369). Plays a role in desmosome protein expression regulation and localization to the desmosomal plaque, thereby maintaining cell sheet integrity and anchorage of desmosomes to intermediate filaments (PubMed:10852826, PubMed:23444369). Required for localization of DSG3 and YAP1 to the cell membrane in keratinocytes in response to mechanical strain, via the formation of an interaction complex composed of DSG3, YAP1, PKP1 and YWHAG (PubMed:31835537). Positively regulates differentiation of keratinocytes, potentially via promoting localization of DSG1 at desmosome cell junctions (By similarity). Required for calcium-independent development and maturation of desmosome plaques specifically at lateral cell-cell contacts in differentiating keratinocytes (By similarity). Plays a role in the maintenance of DSG3 protein abundance, DSG3 clustering and localization of these clusters to the cell membrane in keratinocytes (By similarity). May also promote keratinocyte proliferation and morphogenesis during postnatal development (PubMed:9326952). Required for tight junction inside-out transepidermal barrier function of the skin (By similarity). Promotes Wnt-mediated proliferation and differentiation of ameloblasts, via facilitating TJP1/ZO-1 localization to tight junctions (By similarity). Binds single-stranded DNA (ssDNA), and may thereby play a role in sensing DNA damage and promoting cell survival (PubMed:20613778). Positively regulates cap-dependent translation and as a result cell proliferation, via recruitment of EIF4A1 to the initiation complex and promotion of EIF4A1 ATPase activity (PubMed:20156963, PubMed:23444369). Regulates the mRNA stability and protein abundance of desmosome components PKP2, PKP3, DSC2 and DSP, potentially via its interaction with FXR1 (PubMed:25225333). {ECO:0000250|UniProtKB:P97350, ECO:0000269|PubMed:10852826, ECO:0000269|PubMed:20156963, ECO:0000269|PubMed:20613778, ECO:0000269|PubMed:23444369, ECO:0000269|PubMed:25225333, ECO:0000269|PubMed:31835537, ECO:0000269|PubMed:9326952}.
uniprot
proteins
mass_dalton
82861
uniprot
proteins
mutagenesis
MUTAGEN 54; /note="S->A: No effect on interaction with YWHAG."; /evidence="ECO:0000269|PubMed:29678907"; MUTAGEN 118; /note="S->A: Reduces the interaction with YWHAG."; /evidence="ECO:0000269|PubMed:29678907"; MUTAGEN 119; /note="S->A: Reduces the interaction with YWHAG."; /evidence="ECO:0000269|PubMed:29678907"; MUTAGEN 155; /note="S->A: Abolishes interaction with YWHAG."; /evidence="ECO:0000269|PubMed:29678907"; MUTAGEN 171; /note="T->A: No effect on interaction with YWHAG."; /evidence="ECO:0000269|PubMed:29678907
uniprot
proteins
post_translational_modification
PTM: Phosphorylated by AKT2; required for interaction with YWHAG and subsequent localization away from desmosomes to the cytoplasm (By similarity). Phosphorylation of Ser-118 by AKT2 promotes PKP1-driven cap-dependent mRNA translation and decreases intercellular adhesion, phosphorylation is promoted by insulin (PubMed:23444369). Phosphorylation by RIPK4 at the N-terminus is required for its role in differentiation of keratinocytes and DSG1 localization at cell junctions (By similarity). {ECO:0000250|UniProtKB:P97350, ECO:0000269|PubMed:23444369}.
uniprot
proteins
protein_family
Beta-catenin family
uniprot
proteins
pubmed
10852826
uniprot
proteins
pubmed
11790773
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15663951
uniprot
proteins
pubmed
19136012
uniprot
proteins
pubmed
20156963
uniprot
proteins
pubmed
20613778
uniprot
proteins
pubmed
21756917
uniprot
proteins
pubmed
23444369
uniprot
proteins
pubmed
25225333
uniprot
proteins
pubmed
29678907
uniprot
proteins
pubmed
30949721
uniprot
proteins
pubmed
31835537
uniprot
proteins
pubmed
7527055
uniprot
proteins
pubmed
9326952
uniprot
proteins
pubmed
9369526
uniprot
proteins
sequence_length
747
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Isoform 1]: Cell junction, desmosome {ECO:0000269|PubMed:9369526}.; SUBCELLULAR LOCATION: [Isoform 2]: Nucleus {ECO:0000269|PubMed:9369526}.; SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11790773, ECO:0000269|PubMed:20613778}. Cytoplasm, perinuclear region {ECO:0000269|PubMed:20156963}. Cytoplasm {ECO:0000269|PubMed:20613778, ECO:0000269|PubMed:23444369}. Cell junction, desmosome {ECO:0000269|PubMed:20613778, ECO:0000269|PubMed:23444369}. Cell membrane {ECO:0000269|PubMed:20156963, ECO:0000269|PubMed:30949721}. Cytoplasm, Stress granule {ECO:0000269|PubMed:20156963}. Note=Colocalizes with EIF4A1 in stress granules following arsenate or hydrogen peroxide treatment (PubMed:20156963). Localizes to nucleoli following DNA damage (PubMed:20613778). Located in the cytoplasm during early tooth development, however localizes to the cell membrane in ameloblasts during molar growth (By similarity). Ca(2+)-mediated localization to the cell membrane in dental epithelial cells is inhibited via WNT3A (By similarity). Localizes to the cytoplasm when the phosphorylated form interacts with YWHAG (By similarity). Initially localized to the cytoplasm however as keratinocyte differentiation proceeds becomes localized to cell junctions as early cell-cell contacts become linear as part of membrane sealing (By similarity). Localized to lateral cell contacts in colocalization with DSP as epithelial sheet formation completes (By similarity). Protein stability is increased and localizes to the cytoplasm when phosphorylated at the N-terminus by AKT2 (PubMed:23444369). The unphosphorylated form is preferentially localized to desmosomes (PubMed:23444369). {ECO:0000250|UniProtKB:P97350, ECO:0000269|PubMed:20156963, ECO:0000269|PubMed:20613778, ECO:0000269|PubMed:23444369}.
uniprot
proteins