Q9QY23 · PKP3_MOUSE
- 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 (By similarity).
Required for the localization of DSG2, DSP and PKP2 to mature desmosome junctions (By similarity).
Required for the formation of DSP-containing desmosome precursors in the cytoplasm during desmosome assembly (By similarity).
Also regulates the accumulation of CDH1 to mature desmosome junctions, via cAMP-dependent signaling and its interaction with activated RAP1A (By similarity).
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:18079750).
May also regulate the protein abundance of the desmosome component PKP1 (PubMed:18079750).
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 (PubMed:18079750).
Acts as a negative regulator of the inflammatory response in hematopoietic cells of the skin and intestine, via modulation of proinflammatory cytokine production (PubMed:26173741).
Important for epithelial barrier maintenance in the intestine to reduce intestinal permeability, thereby plays a role in protection from intestinal-derived endotoxemia (PubMed:26173741).
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 (PubMed:18079750).
Promotes proliferation and cell-cycle G1/S phase transition of keratinocytes (PubMed:36689330).
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 (PubMed:36689330).
May act as a scaffold protein to facilitate MAPK phosphorylation of RPS6KA protein family members and subsequently promote downstream EGFR signaling (PubMed:36689330).
May play a role in the positive regulation of transcription of Wnt-mediated TCF-responsive target genes (By similarity).
Required for the localization of DSG2, DSP and PKP2 to mature desmosome junctions (By similarity).
Required for the formation of DSP-containing desmosome precursors in the cytoplasm during desmosome assembly (By similarity).
Also regulates the accumulation of CDH1 to mature desmosome junctions, via cAMP-dependent signaling and its interaction with activated RAP1A (By similarity).
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:18079750).
May also regulate the protein abundance of the desmosome component PKP1 (PubMed:18079750).
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 (PubMed:18079750).
Acts as a negative regulator of the inflammatory response in hematopoietic cells of the skin and intestine, via modulation of proinflammatory cytokine production (PubMed:26173741).
Important for epithelial barrier maintenance in the intestine to reduce intestinal permeability, thereby plays a role in protection from intestinal-derived endotoxemia (PubMed:26173741).
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 (PubMed:18079750).
Promotes proliferation and cell-cycle G1/S phase transition of keratinocytes (PubMed:36689330).
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 (PubMed:36689330).
May act as a scaffold protein to facilitate MAPK phosphorylation of RPS6KA protein family members and subsequently promote downstream EGFR signaling (PubMed:36689330).
May play a role in the positive regulation of transcription of Wnt-mediated TCF-responsive target genes (By similarity).
GO annotations
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended namePlakophilin-3
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ9QY23
- 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 (By similarity).
Maintains a cytoplasmic pool which can then be translocated to the desmosome, the cytoplasmic pool is maintained through PKP3 interaction with SFN (By similarity).
Aberrant increases in translocation to the desmosome result in cell junction instability and therefore decreased cell adhesion (By similarity).
Maintains a cytoplasmic pool which can then be translocated to the desmosome, the cytoplasmic pool is maintained through PKP3 interaction with SFN (By similarity).
Aberrant increases in translocation to the desmosome result in cell junction instability and therefore decreased cell adhesion (By similarity).
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Knockout mice are viable, produced at the expected Mendelian ratio and appeared normal at birth (PubMed:18079750).
Increase in protein abundance of Pkp1, Pkp2, Cdh1, Ctnna1 and Ctnnb1, and decrease in Jup protein abundance in the epidermis of newborn mice (PubMed:18079750).
Delayed hair growth at P7, as a result of misaligned anterior-posterior polarity in hair follicles that show shortened inner root sheath and hair shafts with densely packed medullas lacking normal airspaces at P8 (PubMed:18079750).
Disorganization or complete loss of desmosome cell-cell junctions in the epidermis and loss of Dsp expression in the basal layer of the outer root sheath and in the matrix cells surrounding the dermal papillae of the whisker follicles at P8 (PubMed:18079750).
Acute dermatitis and 70% of mice develop sparse coats by three weeks of age, by two months of age 90% were almost bald on their ventral side (PubMed:18079750).
Loss of the seal between intercellular borders between the basal cells of the epidermis, potentially as a result of loss of at least half of the lateral desmosomes at two months of age (PubMed:18079750).
Increases lethality in response to lipopolysaccharide-induced systemic inflammatory response syndrome (PubMed:26173741).
Increase in mRNA expression of proinflammatory cytokines and chemokines Il6, Il1b, Tnf, Ifny, Il17a and Isyna1/iNos in the skin following PMA challenge and significant decreases in inflammatory gene expression such as Tnf and Il6 in lipopolysaccharide- or PMA-challenged neutrophils (PubMed:26173741).
Conditional knockout in intestinal epithelial cells shows no changes in survival, intestinal ulceration or cytokine production following dextran sulfate sodium (DSS)-induced colitis, however does show an increase in lethality following lipopolysaccharide-induced systemic inflammatory response syndrome (PubMed:26173741).
Conditional knockout in hematopoietic cells show earlier development of more pronounced edema, extensive hemorrhage and intraepithelial edema are evident in skin sections of the ear (PubMed:26173741).
Increase in mast cell numbers two hours post PMA challenge, followed by an increase in granulocyte numbers in the dermis and the epidermis (PubMed:26173741).
Mice show a heightened proinflammatory state in response to lipopolysaccharide-induced systemic inflammatory response syndrome (PubMed:26173741).
Following DSS-induced colitis these is an increase in weight loss, colon shortening, mucosal ulceration and macrophage infiltration (PubMed:26173741).
Colonic supernatants show higher levels of Tnf, Il1b, Il6 and Il10 mRNA during colitis (PubMed:26173741).
Increases keratinocyte proliferation in conditions that would usually result in density-dependent inhibition of growth, as a result of G1/S phase transition delay (PubMed:36689330).
Decrease in total Egfr protein abundance and its phosphorylation, as a result an increase in downstream phosphorylation of Rps6ka family members (PubMed:36689330).
Reduction in the proportion of hyperphosphorylated Rb1, an increase in the interaction between Rb1 and E2f1, resulting in an increase in nuclear Rb1 (PubMed:36689330).
Increase in protein abundance and nuclear localization of Cdkn1a and an increase in Runx3 gene transcription (PubMed:36689330).
Increase in protein abundance of Pkp1, Pkp2, Cdh1, Ctnna1 and Ctnnb1, and decrease in Jup protein abundance in the epidermis of newborn mice (PubMed:18079750).
Delayed hair growth at P7, as a result of misaligned anterior-posterior polarity in hair follicles that show shortened inner root sheath and hair shafts with densely packed medullas lacking normal airspaces at P8 (PubMed:18079750).
Disorganization or complete loss of desmosome cell-cell junctions in the epidermis and loss of Dsp expression in the basal layer of the outer root sheath and in the matrix cells surrounding the dermal papillae of the whisker follicles at P8 (PubMed:18079750).
Acute dermatitis and 70% of mice develop sparse coats by three weeks of age, by two months of age 90% were almost bald on their ventral side (PubMed:18079750).
Loss of the seal between intercellular borders between the basal cells of the epidermis, potentially as a result of loss of at least half of the lateral desmosomes at two months of age (PubMed:18079750).
Increases lethality in response to lipopolysaccharide-induced systemic inflammatory response syndrome (PubMed:26173741).
Increase in mRNA expression of proinflammatory cytokines and chemokines Il6, Il1b, Tnf, Ifny, Il17a and Isyna1/iNos in the skin following PMA challenge and significant decreases in inflammatory gene expression such as Tnf and Il6 in lipopolysaccharide- or PMA-challenged neutrophils (PubMed:26173741).
Conditional knockout in intestinal epithelial cells shows no changes in survival, intestinal ulceration or cytokine production following dextran sulfate sodium (DSS)-induced colitis, however does show an increase in lethality following lipopolysaccharide-induced systemic inflammatory response syndrome (PubMed:26173741).
Conditional knockout in hematopoietic cells show earlier development of more pronounced edema, extensive hemorrhage and intraepithelial edema are evident in skin sections of the ear (PubMed:26173741).
Increase in mast cell numbers two hours post PMA challenge, followed by an increase in granulocyte numbers in the dermis and the epidermis (PubMed:26173741).
Mice show a heightened proinflammatory state in response to lipopolysaccharide-induced systemic inflammatory response syndrome (PubMed:26173741).
Following DSS-induced colitis these is an increase in weight loss, colon shortening, mucosal ulceration and macrophage infiltration (PubMed:26173741).
Colonic supernatants show higher levels of Tnf, Il1b, Il6 and Il10 mRNA during colitis (PubMed:26173741).
Increases keratinocyte proliferation in conditions that would usually result in density-dependent inhibition of growth, as a result of G1/S phase transition delay (PubMed:36689330).
Decrease in total Egfr protein abundance and its phosphorylation, as a result an increase in downstream phosphorylation of Rps6ka family members (PubMed:36689330).
Reduction in the proportion of hyperphosphorylated Rb1, an increase in the interaction between Rb1 and E2f1, resulting in an increase in nuclear Rb1 (PubMed:36689330).
Increase in protein abundance and nuclear localization of Cdkn1a and an increase in Runx3 gene transcription (PubMed:36689330).
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 50 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000064288 | 1-797 | Plakophilin-3 | |||
Sequence: MQEGNFLLSALQPETGVCSLALPSDLQLDRRGAEGPEADRLRAARVQEQVRARLLQLGQQSRHNGSAELDGSAESARGMPRGQYHTMQTGFSSRSQGMSGDKTSTFRPIAKPAYSPASWSSRSAVDLTCSRRLSSAHNGGSAFGAVGYGGTQPTPPMPTRPVSFHERGGAASRADYDTLSLRSLRLGPGGLDDRYSVVSEQLEPAAASTYRAYAYERQASSGSSRAGGLDWPEATEGPPSRTIRAPAMRTLQRFQSSHRSRGGTGSVSGAGLEPVARAPSVRSLSLSLADSGHLPDVRGLDSYTGHRTLQRLSSGFDDIDLPSAVKYLMASDPNLQVLGAAYIQHRCYSDAAAKKQARSLQAVPRLVKLFNHANQEVQRHATGAMRNLIYDNVDNKLALVEENGIFELLRTLREQDDELRKNVTGILWNLSSSDHLKDRLARDTLEQLTDLVLSPLSGAGGPPLIQQNASEAEIFYNATGFLRNLSSASQATRQKMRECHGLVDALVTYINHALDVGKCEDKSVENAVCVLRNLSYRLYDEMPPSALQRLEGRGRRDMAGAPPGEMVGCFTPQSRRLRELPLTADALTFAEVSKDPKGLEWLWSPQIVGLYNRLLQRCELNRHTTEAAAGALQNITAGDRRWAGVLSRLALEQERILNPLLDRVRTADHNQLRSLTGLIRNLSRNARNKDEMSTKVVSHLIEKLPGSVGEKCPPAEVLVNIIAVLNNLVVASPIAARDLLYFDGLRKLVFIKKKRDSPDSEKSSRAASSLLANLWQYSKLHRDFRAKGYRKEDFLGP | ||||||
Modified residue | 81 | Omega-N-methylarginine | ||||
Sequence: R | ||||||
Modified residue | 123 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 180 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 183 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 195 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 240 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 250 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 261 | Omega-N-methylarginine | ||||
Sequence: R | ||||||
Modified residue | 285 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 313 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 314 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 331 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Phosphorylated at Ser-285 when localized to the cytoplasm, PKP3 at desmosome cell junctions is not phosphorylated (By similarity).
Phosphorylation at Try-195 by SRC is induced by reactive oxygen species and potentially acts as a release mechanism from desmosome cell-cell junctions (By similarity).
Phosphorylation at Try-195 by SRC is induced by reactive oxygen species and potentially acts as a release mechanism from desmosome cell-cell junctions (By similarity).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in all layers of the epidermis, but is most abundant in the basal layer (at protein level) (PubMed:18079750).
Expressed in the anagen non-keratinized inner root sheath cuticle and hair cuticle (at protein level) (PubMed:18079750).
Also expressed in the matrix, precursors of the inner root sheath and hair shaft lineages (at protein level) (PubMed:18079750).
Expressed at apical membranes in the outer hair root sheath and basal layer keratinocytes (at protein level) (PubMed:18079750).
Expressed in intestinal epithelial cells and lamina propria of the ileum (at protein level) (PubMed:26173741).
Expressed in keratinocytes (at protein level) (PubMed:36689330).
Expressed in the anagen non-keratinized inner root sheath cuticle and hair cuticle (at protein level) (PubMed:18079750).
Also expressed in the matrix, precursors of the inner root sheath and hair shaft lineages (at protein level) (PubMed:18079750).
Expressed at apical membranes in the outer hair root sheath and basal layer keratinocytes (at protein level) (PubMed:18079750).
Expressed in intestinal epithelial cells and lamina propria of the ileum (at protein level) (PubMed:26173741).
Expressed in keratinocytes (at protein level) (PubMed:36689330).
Induction
Induced by bacterial lipopolysaccharide and phorbol myristate acetate in neutrophils.
Gene expression 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 (By similarity).
Interacts with FXR1; the interaction facilitates the binding of PKP3 to PKP2 mRNA (By similarity).
Interacts (via ARM repeats) with GSK3B; the interaction may be involved in PKP3 protein degradation (By similarity).
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 (PubMed:36689330).
Interacts with CDKN1A; the interaction sequesters CDKN1A to the cytoplasm thereby repressing its role as an inhibitor of CDK4- and CDK6-driven RB1 phosphorylation (PubMed:36689330).
Interacts (via N-terminus) with SFN; the interaction maintains the cytoplasmic pool of PKP3 and restricts PKP3 localization to existing desmosome cell junctions (By similarity).
Interacts (via N-terminus) with JUP; the interaction is required for PKP3 localization to desmosome cell-cell junctions (By similarity).
Interacts with FXR1; the interaction facilitates the binding of PKP3 to PKP2 mRNA (By similarity).
Interacts (via ARM repeats) with GSK3B; the interaction may be involved in PKP3 protein degradation (By similarity).
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 (PubMed:36689330).
Interacts with CDKN1A; the interaction sequesters CDKN1A to the cytoplasm thereby repressing its role as an inhibitor of CDK4- and CDK6-driven RB1 phosphorylation (PubMed:36689330).
Interacts (via N-terminus) with SFN; the interaction maintains the cytoplasmic pool of PKP3 and restricts PKP3 localization to existing desmosome cell junctions (By similarity).
Interacts (via N-terminus) with JUP; the interaction is required for PKP3 localization to desmosome cell-cell junctions (By similarity).
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, repeat.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 58-81 | Disordered | ||||
Sequence: GQQSRHNGSAELDGSAESARGMPR | ||||||
Region | 219-241 | Disordered | ||||
Sequence: ASSGSSRAGGLDWPEATEGPPSR | ||||||
Region | 253-274 | Disordered | ||||
Sequence: RFQSSHRSRGGTGSVSGAGLEP | ||||||
Region | 283-288 | Required for interaction with SFN | ||||
Sequence: SLSLSL | ||||||
Region | 294-724 | Required for interaction with GSK3B | ||||
Sequence: LPDVRGLDSYTGHRTLQRLSSGFDDIDLPSAVKYLMASDPNLQVLGAAYIQHRCYSDAAAKKQARSLQAVPRLVKLFNHANQEVQRHATGAMRNLIYDNVDNKLALVEENGIFELLRTLREQDDELRKNVTGILWNLSSSDHLKDRLARDTLEQLTDLVLSPLSGAGGPPLIQQNASEAEIFYNATGFLRNLSSASQATRQKMRECHGLVDALVTYINHALDVGKCEDKSVENAVCVLRNLSYRLYDEMPPSALQRLEGRGRRDMAGAPPGEMVGCFTPQSRRLRELPLTADALTFAEVSKDPKGLEWLWSPQIVGLYNRLLQRCELNRHTTEAAAGALQNITAGDRRWAGVLSRLALEQERILNPLLDRVRTADHNQLRSLTGLIRNLSRNARNKDEMSTKVVSHLIEKLPGSVGEKCPPAEVLVNIIAV | ||||||
Repeat | 305-348 | ARM 1 | ||||
Sequence: GHRTLQRLSSGFDDIDLPSAVKYLMASDPNLQVLGAAYIQHRCY | ||||||
Repeat | 351-390 | ARM 2 | ||||
Sequence: AAAKKQARSLQAVPRLVKLFNHANQEVQRHATGAMRNLIY | ||||||
Repeat | 393-432 | ARM 3 | ||||
Sequence: VDNKLALVEENGIFELLRTLREQDDELRKNVTGILWNLSS | ||||||
Repeat | 449-487 | ARM 4 | ||||
Sequence: TDLVLSPLSGAGGPPLIQQNASEAEIFYNATGFLRNLSS | ||||||
Repeat | 491-536 | ARM 5 | ||||
Sequence: ATRQKMRECHGLVDALVTYINHALDVGKCEDKSVENAVCVLRNLSY | ||||||
Region | 516-797 | Required for binding to PKP2 mRNA | ||||
Sequence: VGKCEDKSVENAVCVLRNLSYRLYDEMPPSALQRLEGRGRRDMAGAPPGEMVGCFTPQSRRLRELPLTADALTFAEVSKDPKGLEWLWSPQIVGLYNRLLQRCELNRHTTEAAAGALQNITAGDRRWAGVLSRLALEQERILNPLLDRVRTADHNQLRSLTGLIRNLSRNARNKDEMSTKVVSHLIEKLPGSVGEKCPPAEVLVNIIAVLNNLVVASPIAARDLLYFDGLRKLVFIKKKRDSPDSEKSSRAASSLLANLWQYSKLHRDFRAKGYRKEDFLGP | ||||||
Repeat | 596-637 | ARM 6 | ||||
Sequence: PKGLEWLWSPQIVGLYNRLLQRCELNRHTTEAAAGALQNITA | ||||||
Repeat | 645-684 | ARM 7 | ||||
Sequence: VLSRLALEQERILNPLLDRVRTADHNQLRSLTGLIRNLSR | ||||||
Repeat | 689-730 | ARM 8 | ||||
Sequence: KDEMSTKVVSHLIEKLPGSVGEKCPPAEVLVNIIAVLNNLVV |
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 splicing.
Q9QY23-1
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.
- Name1
- Length797
- Mass (Da)87,333
- Last updated2007-06-12 v2
- ChecksumC2ECF73BDE7323B1
Q9QY23-2
- Name2
- Differences from canonical
- 1-12: MQEGNFLLSALQ → MEPTAGSRTRMEPRRNCPTAGTSRMSQGASGGQTSGK
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_026139 | 1-12 | in isoform 2 | |||
Sequence: MQEGNFLLSALQ → MEPTAGSRTRMEPRRNCPTAGTSRMSQGASGGQTSGK | ||||||
Sequence conflict | 182 | in Ref. 1; AAD55892 | ||||
Sequence: R → P | ||||||
Sequence conflict | 216 | in Ref. 1; AAD55892 | ||||
Sequence: E → K | ||||||
Sequence conflict | 459 | in Ref. 1; AAD55892 | ||||
Sequence: A → P |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF136719 EMBL· GenBank· DDBJ | AAD55892.1 EMBL· GenBank· DDBJ | mRNA | ||
BC090668 EMBL· GenBank· DDBJ | AAH90668.1 EMBL· GenBank· DDBJ | mRNA | ||
BC106141 EMBL· GenBank· DDBJ | AAI06142.1 EMBL· GenBank· DDBJ | mRNA | ||
BC139775 EMBL· GenBank· DDBJ | AAI39776.1 EMBL· GenBank· DDBJ | mRNA |