PKP3
entrez
11187
canonical
uniprot
Q9Y446
canonical
ensembl
ENSG00000184363
resolver
ensp
ENSP00000331678
resolver
ensp
ENSP00000434517
resolver
genesymbol
PKP3
resolver
hgnc
HGNC:9025
resolver
uniprot
F8J390
resolver
uniprot
Q53EX8
resolver
uniprot_entry
PKP3_HUMAN
resolver
uniprot_sec
F8J390
resolver
uniprot_sec
Q53EX8
resolver
amino_acid_sequence
MQDGNFLLSALQPEAGVCSLALPSDLQLDRRGAEGPEAERLRAARVQEQVRARLLQLGQQPRHNGAAEPEPEAETARGTSRGQYHTLQAGFSSRSQGLSGDKTSGFRPIAKPAYSPASWSSRSAVDLSCSRRLSSAHNGGSAFGAAGYGGAQPTPPMPTRPVSFHERGGVGSRADYDTLSLRSLRLGPGGLDDRYSLVSEQLEPAATSTYRAFAYERQASSSSSRAGGLDWPEATEVSPSRTIRAPAVRTLQRFQSSHRSRGVGGAVPGAVLEPVARAPSVRSLSLSLADSGHLPDVHGFNSYGSHRTLQRLSSGFDDIDLPSAVKYLMASDPNLQVLGAAYIQHKCYSDAAAKKQARSLQAVPRLVKLFNHANQEVQRHATGAMRNLIYDNADNKLALVEENGIFELLRTLREQDDELRKNVTGILWNLSSSDHLKDRLARDTLEQLTDLVLSPLSGAGGPPLIQQNASEAEIFYNATGFLRNLSSASQATRQKMRECHGLVDALVTSINHALDAGKCEDKSVENAVCVLRNLSYRLYDEMPPSALQRLEGRGRRDLAGAPPGEVVGCFTPQSRRLRELPLAADALTFAEVSKDPKGLEWLWSPQIVGLYNRLLQRCELNRHTTEAAAGALQNITAGDRRWAGVLSRLALEQERILNPLLDRVRTADHHQLRSLTGLIRNLSRNARNKDEMSTKVVSHLIEKLPGSVGEKSPPAEVLVNIIAVLNNLVVASPIAARDLLYFDGLRKLIFIKKKRDSPDSEKSSRAASSLLANLWQYNKLHRDFRAKGYRKEDFLGP
uniprot
proteins
function
FUNCTION: A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:24124604). Required for the localization of DSG2, DSP and PKP2 to mature desmosome junctions (PubMed:20859650). May also play a role in the maintenance of DSG3 protein abundance in keratinocytes (By similarity). Required for the formation of DSP-containing desmosome precursors in the cytoplasm during desmosome assembly (PubMed:25208567). Also regulates the accumulation of CDH1 to mature desmosome junctions, via cAMP-dependent signaling and its interaction with activated RAP1A (PubMed:25208567). Positively regulates the stabilization of PKP2 mRNA and therefore protein abundance, via its interaction with FXR1, may also regulate the protein abundance of DSP via the same mechanism (PubMed:25225333). May also regulate the protein abundance of the desmosome component PKP1 (By similarity). Required for the organization of desmosome junctions at intercellular borders between basal keratinocytes of the epidermis, as a result plays a role in maintenance of the dermal barrier and regulation of the dermal inflammatory response (By similarity). Required during epidermal keratinocyte differentiation for cell adherence at tricellular cell-cell contacts, via regulation of the timely formation of adherens junctions and desmosomes in a calcium-dependent manner, and may also play a role in the organization of the intracellular actin fiber belt (By similarity). Acts as a negative regulator of the inflammatory response in hematopoietic cells of the skin and intestine, via modulation of proinflammatory cytokine production (By similarity). Important for epithelial barrier maintenance in the intestine to reduce intestinal permeability, thereby plays a role in protection from intestinal-derived endotoxemia (By similarity). Required for the development of hair follicles, via a role in the regulation of inner root sheaf length, correct alignment and anterior-posterior polarity of hair follicles (By similarity). Promotes proliferation and cell-cycle G1/S phase transition of keratinocytes (By similarity). Promotes E2F1-driven transcription of G1/S phase promoting genes by acting to release E2F1 from its inhibitory interaction with RB1, via sequestering RB1 and CDKN1A to the cytoplasm and thereby increasing CDK4- and CDK6-driven phosphorylation of RB1 (By similarity). May act as a scaffold protein to facilitate MAPK phosphorylation of RPS6KA protein family members and subsequently promote downstream EGFR signaling (By similarity). May play a role in the positive regulation of transcription of Wnt-mediated TCF-responsive target genes (PubMed:34058472). {ECO:0000250|UniProtKB:Q9QY23, ECO:0000269|PubMed:20859650, ECO:0000269|PubMed:24124604, ECO:0000269|PubMed:25208567, ECO:0000269|PubMed:25225333, ECO:0000269|PubMed:34058472}.
uniprot
proteins
mass_dalton
87082
uniprot
proteins
mutagenesis
MUTAGEN 285; /note="S->A: Abolishes interaction with SFN."; /evidence="ECO:0000269|PubMed:24124604, ECO:0000269|PubMed:29678907
uniprot
proteins
post_translational_modification
PTM: Phosphorylated at Ser-285 when localized to the cytoplasm, PKP3 at desmosome cell junctions is not phosphorylated (PubMed:24124604). Phosphorylation at Try-195 by SRC is induced by reactive oxygen species and potentially acts as a release mechanism from desmosome cell-cell junctions (PubMed:25501895). {ECO:0000269|PubMed:24124604, ECO:0000269|PubMed:25501895}.
uniprot
proteins
protein_family
Beta-catenin family
uniprot
proteins
pubmed
10374265
uniprot
proteins
pubmed
10381383
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16344560
uniprot
proteins
pubmed
16964243
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20613778
uniprot
proteins
pubmed
20859650
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24124604
uniprot
proteins
pubmed
24129315
uniprot
proteins
pubmed
24178805
uniprot
proteins
pubmed
25208567
uniprot
proteins
pubmed
25225333
uniprot
proteins
pubmed
25501895
uniprot
proteins
pubmed
29678907
uniprot
proteins
pubmed
30949721
uniprot
proteins
pubmed
34058472
uniprot
proteins
sequence_length
797
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:24124604, ECO:0000269|PubMed:34058472}. Cell junction, desmosome {ECO:0000269|PubMed:10374265, ECO:0000269|PubMed:20613778, ECO:0000269|PubMed:20859650, ECO:0000269|PubMed:24124604, ECO:0000269|PubMed:25501895}. Cytoplasm {ECO:0000269|PubMed:24124604, ECO:0000269|PubMed:25501895, ECO:0000269|PubMed:34058472}. Cell membrane {ECO:0000269|PubMed:25501895, ECO:0000269|PubMed:30949721}; Peripheral membrane protein {ECO:0000305}. Cell junction, adherens junction {ECO:0000250|UniProtKB:Q9QY23}. Note=Translocates to the nucleus following canonical WNT signaling activation by WNT3A (PubMed:34058472). Maintains a cytoplasmic pool which can then be translocated to the desmosome, the cytoplasmic pool is maintained through PKP3 interaction with SFN (PubMed:24124604). Aberrant increases in translocation to the desmosome result in cell junction instability and therefore decreased cell adhesion (PubMed:24124604). Partially colocalizes at cell junctions in a zipper-like pattern with DSP, CDH1, CTNNB1 and CTNND1 in the early stages of keratinocyte differentiation (By similarity). Moves to cell junctions at tricellular contacts as differentiation progresses and as epithelial sheet formation completes (By similarity). {ECO:0000250|UniProtKB:Q9QY23, ECO:0000269|PubMed:24124604, ECO:0000269|PubMed:34058472}.; SUBCELLULAR LOCATION: [Isoform PKP3a]: Cell junction, desmosome {ECO:0000269|PubMed:24178805}. Cytoplasm {ECO:0000269|PubMed:24178805}.; SUBCELLULAR LOCATION: [Isoform PKP3b]: Cell junction, desmosome {ECO:0000269|PubMed:24178805}. Cytoplasm {ECO:0000269|PubMed:24178805}.
uniprot
proteins