Overview
| Uniprot ID | Q99959 |
|---|
| Protein Name | Plakophilin-2 |
|---|
| Gene Name | PKP2 |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 692 |
MYLSLIAKSVRNYTQ |
Function
A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:25208567). Regulates focal adhesion turnover resulting in changes in focal adhesion size, cell adhesion and cell spreading, potentially via transcriptional modulation of beta-integrins (PubMed:23884246). Required to maintain gingival epithelial barrier function (PubMed:34368962). Important component of the desmosome that is also required for localization of desmosome component proteins such as DSC2, DSG2 and JUP to the desmosome cell-cell junction (PubMed:22781308, PubMed:25208567). Required for the formation of desmosome cell junctions in cardiomyocytes, thereby required for the correct formation of the heart, specifically trabeculation and formation of the atria walls (By similarity). Loss of desmosome cell junctions leads to mis-localization of DSP and DSG2 resulting in disruption of cell-cell adhesion and disordered intermediate filaments (By similarity). Modulates profibrotic gene expression in cardiomyocytes via regulation of DSP expression and subsequent activation of downstream TGFB1 and MAPK14/p38 MAPK signaling (By similarity). Required for cardiac sodium current propagation and electrical synchrony in cardiac myocytes, via ANK3 stabilization and modulation of SCN5A/Nav1.5 localization to cell-cell junctions (By similarity). Required for mitochondrial function, nuclear envelope integrity and positive regulation of SIRT3 transcription via maintaining DES localization at its nuclear envelope and cell tip anchoring points, and thereby preserving regulation of the transcriptional program (PubMed:35959657). Maintenance of nuclear envelope integrity protects against DNA damage and transcriptional dysregulation of genes, especially those involved in the electron transport chain, thereby preserving mitochondrial function and protecting against superoxide radical anion generation (PubMed:35959657). Binds single-stranded DNA (ssDNA) (PubMed:20613778). May regulate the localization of GJA1 to gap junctions in intercalated disks of the heart (PubMed:18662195). Involved in the inhibition of viral infection by influenza A viruses (IAV) (PubMed:28169297). Acts as a host restriction factor for IAV viral propagation, potentially via disrupting the interaction of IAV polymerase complex proteins (PubMed:28169297)
Protein Sequence
10
MAAPGAPAEY
20
GYIRTVLGQQ
30
ILGQLDSSSL
40
ALPSEAKLKL
50
AGSSGRGGQT
60
VKSLRIQEQV
70
QQTLARKGRS
80
SVGNGNLHRT
90
SSVPEYVYNL
100
HLVENDFVGG
110
RSPVPKTYDM
120
LKAGTTATYE
130
GRWGRGTAQY
140
SSQKSVEERS
150
LRHPLRRLEI
160
SPDSSPERAH
170
YTHSDYQYSQ
180
RSQAGHTLHH
190
QESRRAALLV
200
PPRYARSEIV
210
GVSRAGTTSR
220
QRHFDTYHRQ
230
YQHGSVSDTV
240
FDSIPANPAL
250
LTYPRPGTSR
260
SMGNLLEKEN
270
YLTAGLTVGQ
280
VRPLVPLQPV
290
TQNRASRSSW
300
HQSSFHSTRT
310
LREAGPSVAV
320
DSSGRRAHLT
330
VGQAAAGGSG
340
NLLTERSTFT
350
DSQLGNADME
360
MTLERAVSML
370
EADHMLPSRI
380
SAAATFIQHE
390
CFQKSEARKR
400
VNQLRGILKL
410
LQLLKVQNED
420
VQRAVCGALR
430
NLVFEDNDNK
440
LEVAELNGVP
450
RLLQVLKQTR
460
DLETKKQITD
470
HTVNLRSRNG
480
WPGAVAHACN
490
PSTLGGQGGR
500
ITRSGVRDQP
510
DQHGLLWNLS
520
SNDKLKNLMI
530
TEALLTLTEN
540
IIIPFSGWPE
550
GDYPKANGLL
560
DFDIFYNVTG
570
CLRNMSSAGA
580
DGRKAMRRCD
590
GLIDSLVHYV
600
RGTIADYQPD
610
DKATENCVCI
620
LHNLSYQLEA
630
ELPEKYSQNI
640
YIQNRNIQTD
650
NNKSIGCFGS
660
RSRKVKEQYQ
670
DVPMPEEKSN
680
PKGVEWLWHS
690
IVIRMYLSLI
700
AKSVRNYTQE
710
ASLGALQNLT
720
AGSGPMPTSV
730
AQTVVQKESG
740
LQHTRKMLHV
750
GDPSVKKTAI
760
SLLRNLSRNL
770
SLQNEIAKET
780
LPDLVSIIPD
790
TVPSTDLLIE
800
TTASACYTLN
810
NIIQNSYQNA
820
RDLLNTGGIQ
830
KIMAISAGDA
840
YASNKASKAA
850
SVLLYSLWAH
860
TELHHAYKKA
870
QFKKTDFVNS
880
RTAKAYHSLK
D
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005912 |
adherens junction |
| Cellular Component |
GO:0030054 |
cell junction |
| Cellular Component |
GO:0051286 |
cell tip |
| Cellular Component |
GO:0005911 |
cell-cell junction |
| Cellular Component |
GO:0001533 |
cornified envelope |
| Cellular Component |
GO:0005737 |
cytoplasm |
| Cellular Component |
GO:0030057 |
desmosome |
| Cellular Component |
GO:0014704 |
intercalated disc |
| Cellular Component |
GO:0005882 |
intermediate filament |
| Cellular Component |
GO:0016020 |
membrane |
| Cellular Component |
GO:0005654 |
nucleoplasm |
| Cellular Component |
GO:0005634 |
nucleus |
| Cellular Component |
GO:0005886 |
plasma membrane |
| Molecular Function |
GO:0045294 |
alpha-catenin binding |
| Molecular Function |
GO:0045296 |
cadherin binding |
| Molecular Function |
GO:0086083 |
cell adhesive protein binding involved in bundle of His cell-Purkinje myocyte communication |
| Molecular Function |
GO:0003677 |
DNA binding |
| Molecular Function |
GO:0019215 |
intermediate filament binding |
| Molecular Function |
GO:0060090 |
molecular adaptor activity |
| Molecular Function |
GO:0005080 |
protein kinase C binding |
| Molecular Function |
GO:0017080 |
sodium channel regulator activity |
| Molecular Function |
GO:0044325 |
transmembrane transporter binding |
| Biological Process |
GO:0086073 |
bundle of His cell-Purkinje myocyte adhesion involved in cell communication |
| Biological Process |
GO:0086002 |
cardiac muscle cell action potential involved in contraction |
| Biological Process |
GO:0086064 |
cell communication by electrical coupling involved in cardiac conduction |
| Biological Process |
GO:0098609 |
cell-cell adhesion |
| Biological Process |
GO:0007267 |
cell-cell signaling |
| Biological Process |
GO:0002159 |
desmosome assembly |
| Biological Process |
GO:0002934 |
desmosome organization |
| Biological Process |
GO:0007507 |
heart development |
| Biological Process |
GO:0045110 |
intermediate filament bundle assembly |
| Biological Process |
GO:0048496 |
maintenance of animal organ identity |
| Biological Process |
GO:0099017 |
maintenance of protein localization at cell tip |
| Biological Process |
GO:0010765 |
positive regulation of sodium ion transport |
| Biological Process |
GO:0072659 |
protein localization to plasma membrane |
| Biological Process |
GO:0010810 |
regulation of cell-substrate adhesion |
| Biological Process |
GO:0086091 |
regulation of heart rate by cardiac conduction |
| Biological Process |
GO:1900024 |
regulation of substrate adhesion-dependent cell spreading |
| Biological Process |
GO:0098911 |
regulation of ventricular cardiac muscle cell action potential |
| Biological Process |
GO:0086005 |
ventricular cardiac muscle cell action potential |
| Biological Process |
GO:0055010 |
ventricular cardiac muscle tissue morphogenesis |
Reference
[1] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.