Q9Y446 · PKP3_HUMAN
- ProteinPlakophilin-3
- GenePKP3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids797 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
A component of desmosome cell-cell junctions that positively regulate cellular adhesion (PubMed:24124604).
Required for the localization of DSG2, DSP and PKP2 to mature desmosome junctions (PubMed:20859650).
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).
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).
Required for the localization of DSG2, DSP and PKP2 to mature desmosome junctions (PubMed:20859650).
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).
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).
Miscellaneous
Poorly differentiated, high Gleason grade prostate adenocarcinomas show an increase in phosphorylation at Tyr-195, potentially indicating a role for SRC-driven phosphorylation of PKP3 in the dedifferentiation of prostate tumor cells.
GO annotations
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended namePlakophilin-3
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9Y446
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Peripheral membrane protein
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).
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).
Isoform PKP3a
Isoform PKP3b
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 285 | Abolishes interaction with SFN. | ||||
Sequence: S → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1,167 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000064287 | 1-797 | UniProt | Plakophilin-3 | |||
Sequence: MQDGNFLLSALQPEAGVCSLALPSDLQLDRRGAEGPEAERLRAARVQEQVRARLLQLGQQPRHNGAAEPEPEAETARGTSRGQYHTLQAGFSSRSQGLSGDKTSGFRPIAKPAYSPASWSSRSAVDLSCSRRLSSAHNGGSAFGAAGYGGAQPTPPMPTRPVSFHERGGVGSRADYDTLSLRSLRLGPGGLDDRYSLVSEQLEPAATSTYRAFAYERQASSSSSRAGGLDWPEATEVSPSRTIRAPAVRTLQRFQSSHRSRGVGGAVPGAVLEPVARAPSVRSLSLSLADSGHLPDVHGFNSYGSHRTLQRLSSGFDDIDLPSAVKYLMASDPNLQVLGAAYIQHKCYSDAAAKKQARSLQAVPRLVKLFNHANQEVQRHATGAMRNLIYDNADNKLALVEENGIFELLRTLREQDDELRKNVTGILWNLSSSDHLKDRLARDTLEQLTDLVLSPLSGAGGPPLIQQNASEAEIFYNATGFLRNLSSASQATRQKMRECHGLVDALVTSINHALDAGKCEDKSVENAVCVLRNLSYRLYDEMPPSALQRLEGRGRRDLAGAPPGEVVGCFTPQSRRLRELPLAADALTFAEVSKDPKGLEWLWSPQIVGLYNRLLQRCELNRHTTEAAAGALQNITAGDRRWAGVLSRLALEQERILNPLLDRVRTADHHQLRSLTGLIRNLSRNARNKDEMSTKVVSHLIEKLPGSVGEKSPPAEVLVNIIAVLNNLVVASPIAARDLLYFDGLRKLIFIKKKRDSPDSEKSSRAASSLLANLWQYNKLHRDFRAKGYRKEDFLGP | |||||||
Modified residue | 81 | UniProt | Omega-N-methylarginine | ||||
Sequence: R | |||||||
Modified residue (large scale data) | 84 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 86 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 92 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 95 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 114 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 115 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 118 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 123 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 123 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 134 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 148 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 159 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 163 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 176 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 178 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 180 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 180 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 183 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 183 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 195 | UniProt | Phosphotyrosine; by SRC | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 195 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 196 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 199 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 210 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 235 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 238 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 238 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 240 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 240 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 250 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 250 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 260 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 261 | UniProt | Omega-N-methylarginine | ||||
Sequence: R | |||||||
Modified residue (large scale data) | 280 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 283 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 285 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 285 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 287 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 291 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 305 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 308 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 313 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 313 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 314 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 314 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 323 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 331 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 331 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 390 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 571 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 698 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
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).
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).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in the epidermis of the skin, in squamous non-cornifying epithelial cells in the vagina, single layer epithelia of the duodenum and pancreas acini and non-epithelial dendritic reticulum cells of lymph node follicles (at protein level).
Isoform PKP3a
Expressed in the oral cavity mucosa, epidermis and small intestine epithelium (at protein level).
Isoform PKP3b
Expressed in the oral cavity mucosa and epithelial cells of the crypts and villi in the small intestine (at protein level) (PubMed:24178805).
Expressed in the epidermis with more abundant expression found in the basal and low spinous cells (at protein level) (PubMed:24178805).
Expressed in the epidermis with more abundant expression found in the basal and low spinous cells (at protein level) (PubMed:24178805).
Gene expression databases
Organism-specific databases
Interaction
Subunit
Found in a complex composed of CDH1, RAP1A and PKP3; PKP3 acts as a scaffold protein within the complex, the complex is required for CDH1 localization to mature desmosome cell junctions (PubMed:25208567).
Interacts with FXR1; the interaction facilitates the binding of PKP3 to PKP2 mRNA (PubMed:25225333).
Interacts (via ARM repeats) with GSK3B; the interaction may be involved in PKP3 protein degradation (PubMed:34058472).
Interacts with hyperphosphorylated and hypophosphorylated RB1; the interaction inhibits RB1 interaction with and repression of the transcription factor E2F1, potentially via sequestering RB1 to the cytoplasm (By similarity).
Interacts with CDKN1A; the interaction sequesters CDKN1A to the cytoplasm thereby repressing its role as an inhibitor of CDK4- and CDK6-driven RB1 phosphorylation (By similarity).
Interacts (via N-terminus) with SFN; the interaction maintains the cytoplasmic pool of PKP3 and restricts PKP3 localization to existing desmosome cell junctions (PubMed:24124604).
Interacts (via N-terminus) with JUP; the interaction is required for PKP3 localization to desmosome cell-cell junctions (PubMed:20859650).
Interacts with FXR1; the interaction facilitates the binding of PKP3 to PKP2 mRNA (PubMed:25225333).
Interacts (via ARM repeats) with GSK3B; the interaction may be involved in PKP3 protein degradation (PubMed:34058472).
Interacts with hyperphosphorylated and hypophosphorylated RB1; the interaction inhibits RB1 interaction with and repression of the transcription factor E2F1, potentially via sequestering RB1 to the cytoplasm (By similarity).
Interacts with CDKN1A; the interaction sequesters CDKN1A to the cytoplasm thereby repressing its role as an inhibitor of CDK4- and CDK6-driven RB1 phosphorylation (By similarity).
Interacts (via N-terminus) with SFN; the interaction maintains the cytoplasmic pool of PKP3 and restricts PKP3 localization to existing desmosome cell junctions (PubMed:24124604).
Interacts (via N-terminus) with JUP; the interaction is required for PKP3 localization to desmosome cell-cell junctions (PubMed:20859650).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9Y446 | GFAP P14136 | 3 | EBI-2880227, EBI-744302 | |
BINARY | Q9Y446 | IQUB Q8NA54 | 3 | EBI-2880227, EBI-10220600 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, repeat.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 56-82 | Disordered | ||||
Sequence: QLGQQPRHNGAAEPEPEAETARGTSRG | ||||||
Region | 283-288 | Required for interaction with SFN | ||||
Sequence: SLSLSL | ||||||
Region | 294-724 | Required for interaction with GSK3B | ||||
Sequence: LPDVHGFNSYGSHRTLQRLSSGFDDIDLPSAVKYLMASDPNLQVLGAAYIQHKCYSDAAAKKQARSLQAVPRLVKLFNHANQEVQRHATGAMRNLIYDNADNKLALVEENGIFELLRTLREQDDELRKNVTGILWNLSSSDHLKDRLARDTLEQLTDLVLSPLSGAGGPPLIQQNASEAEIFYNATGFLRNLSSASQATRQKMRECHGLVDALVTSINHALDAGKCEDKSVENAVCVLRNLSYRLYDEMPPSALQRLEGRGRRDLAGAPPGEVVGCFTPQSRRLRELPLAADALTFAEVSKDPKGLEWLWSPQIVGLYNRLLQRCELNRHTTEAAAGALQNITAGDRRWAGVLSRLALEQERILNPLLDRVRTADHHQLRSLTGLIRNLSRNARNKDEMSTKVVSHLIEKLPGSVGEKSPPAEVLVNIIAV | ||||||
Repeat | 305-348 | ARM 1 | ||||
Sequence: SHRTLQRLSSGFDDIDLPSAVKYLMASDPNLQVLGAAYIQHKCY | ||||||
Repeat | 351-390 | ARM 2 | ||||
Sequence: AAAKKQARSLQAVPRLVKLFNHANQEVQRHATGAMRNLIY | ||||||
Repeat | 393-432 | ARM 3 | ||||
Sequence: ADNKLALVEENGIFELLRTLREQDDELRKNVTGILWNLSS | ||||||
Repeat | 449-487 | ARM 4 | ||||
Sequence: TDLVLSPLSGAGGPPLIQQNASEAEIFYNATGFLRNLSS | ||||||
Repeat | 491-536 | ARM 5 | ||||
Sequence: ATRQKMRECHGLVDALVTSINHALDAGKCEDKSVENAVCVLRNLSY | ||||||
Region | 516-797 | Required for binding to PKP2 mRNA | ||||
Sequence: AGKCEDKSVENAVCVLRNLSYRLYDEMPPSALQRLEGRGRRDLAGAPPGEVVGCFTPQSRRLRELPLAADALTFAEVSKDPKGLEWLWSPQIVGLYNRLLQRCELNRHTTEAAAGALQNITAGDRRWAGVLSRLALEQERILNPLLDRVRTADHHQLRSLTGLIRNLSRNARNKDEMSTKVVSHLIEKLPGSVGEKSPPAEVLVNIIAVLNNLVVASPIAARDLLYFDGLRKLIFIKKKRDSPDSEKSSRAASSLLANLWQYNKLHRDFRAKGYRKEDFLGP | ||||||
Repeat | 596-637 | ARM 6 | ||||
Sequence: PKGLEWLWSPQIVGLYNRLLQRCELNRHTTEAAAGALQNITA | ||||||
Repeat | 645-684 | ARM 7 | ||||
Sequence: VLSRLALEQERILNPLLDRVRTADHHQLRSLTGLIRNLSR | ||||||
Repeat | 689-730 | ARM 8 | ||||
Sequence: KDEMSTKVVSHLIEKLPGSVGEKSPPAEVLVNIIAVLNNLVV |
Sequence similarities
Belongs to the beta-catenin family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative promoter usage.
Q9Y446-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- NamePKP3a
- Length797
- Mass (Da)87,082
- Last updated1999-11-01 v1
- ChecksumD43C7E77FA805E7E
Q9Y446-2
- NamePKP3b
- Differences from canonical
- 1-12: MQDGNFLLSALQ → MESWTPRPSAVASGMSWEAGGIRTTSR
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_053646 | 1-12 | in isoform PKP3b | |||
Sequence: MQDGNFLLSALQ → MESWTPRPSAVASGMSWEAGGIRTTSR | ||||||
Sequence conflict | 719 | in Ref. 4; BAD97231 | ||||
Sequence: V → A | ||||||
Sequence conflict | 730 | in Ref. 4; BAD97231 | ||||
Sequence: V → G |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
Z98265 EMBL· GenBank· DDBJ | CAB44310.1 EMBL· GenBank· DDBJ | mRNA | ||
AF053719 EMBL· GenBank· DDBJ | AAF23050.1 EMBL· GenBank· DDBJ | mRNA | ||
FN421477 EMBL· GenBank· DDBJ | CAZ65731.1 EMBL· GenBank· DDBJ | mRNA | ||
AK223511 EMBL· GenBank· DDBJ | BAD97231.1 EMBL· GenBank· DDBJ | mRNA | ||
BC000081 EMBL· GenBank· DDBJ | AAH00081.1 EMBL· GenBank· DDBJ | mRNA | ||
DA439471 EMBL· GenBank· DDBJ | - | mRNA | No translation available. |