Overview
| Uniprot ID | Q08209 |
|---|
| Protein Name | Protein phosphatase 3 catalytic subunit alpha |
|---|
| Gene Name | PPP3CA |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 10 |
EPKAIDPKLSTTDRV |
| 32 |
PSHRLTAKEVFDNDG |
| 466 |
KGFSPQHKITSFEEA |
Function
Calcium-dependent, calmodulin-stimulated protein phosphatase which plays an essential role in the transduction of intracellular Ca(2+)-mediated signals (PubMed:15671020, PubMed:18838687, PubMed:19154138, PubMed:23468591, PubMed:30254215). Many of the substrates contain a PxIxIT motif and/or a LxVP motif (PubMed:17498738, PubMed:17502104, PubMed:22343722, PubMed:23468591, PubMed:27974827). In response to increased Ca(2+) levels, dephosphorylates and activates phosphatase SSH1 which results in cofilin dephosphorylation (PubMed:15671020). In response to increased Ca(2+) levels following mitochondrial depolarization, dephosphorylates DNM1L inducing DNM1L translocation to the mitochondrion (PubMed:18838687). Positively regulates the CACNA1B/CAV2.2-mediated Ca(2+) release probability at hippocampal neuronal soma and synaptic terminals (By similarity). Dephosphorylates heat shock protein HSPB1 (By similarity). Dephosphorylates and activates transcription factor NFATC1 (PubMed:19154138). In response to increased Ca(2+) levels, regulates NFAT-mediated transcription probably by dephosphorylating NFAT and promoting its nuclear translocation (PubMed:26248042). Dephosphorylates and inactivates transcription factor ELK1 (PubMed:19154138). Dephosphorylates DARPP32 (PubMed:19154138). May dephosphorylate CRTC2 at 'Ser-171' resulting in CRTC2 dissociation from 14-3-3 proteins (PubMed:30611118). Dephosphorylates transcription factor TFEB at 'Ser-211' following Coxsackievirus B3 infection, promoting nuclear translocation (PubMed:33691586). Required for postnatal development of the nephrogenic zone and superficial glomeruli in the kidneys, cell cycle homeostasis in the nephrogenic zone, and ultimately normal kidney function (By similarity). Plays a role in intracellular AQP2 processing and localization to the apical membrane in the kidney, may thereby be required for efficient kidney filtration (By similarity). Required for secretion of salivary enzymes amylase, peroxidase, lysozyme and sialic acid via formation of secretory vesicles in the submandibular glands (By similarity). Required for calcineurin activity and homosynaptic depotentiation in the hippocampus (By similarity). Required for normal differentiation and survival of keratinocytes and therefore required for epidermis superstructure formation (By similarity). Positively regulates osteoblastic bone formation, via promotion of osteoblast differentiation (By similarity). Positively regulates osteoclast differentiation, potentially via NFATC1 signaling (By similarity). May play a role in skeletal muscle fiber type specification, potentially via NFATC1 signaling (By similarity). Negatively regulates MAP3K14/NIK signaling via inhibition of nuclear translocation of the transcription factors RELA and RELB (By similarity). Required for antigen-specific T-cell proliferation response (By similarity). Dephosphorylates KLHL3, promoting the interaction between KLHL3 and WNK4 and subsequent degradation of WNK4 (PubMed:30718414). Negatively regulates SLC9A1 activity (PubMed:31375679)
Protein Sequence
10
MSEPKAIDPK
20
LSTTDRVVKA
30
VPFPPSHRLT
40
AKEVFDNDGK
50
PRVDILKAHL
60
MKEGRLEESV
70
ALRIITEGAS
80
ILRQEKNLLD
90
IDAPVTVCGD
100
IHGQFFDLMK
110
LFEVGGSPAN
120
TRYLFLGDYV
130
DRGYFSIECV
140
LYLWALKILY
150
PKTLFLLRGN
160
HECRHLTEYF
170
TFKQECKIKY
180
SERVYDACMD
190
AFDCLPLAAL
200
MNQQFLCVHG
210
GLSPEINTLD
220
DIRKLDRFKE
230
PPAYGPMCDI
240
LWSDPLEDFG
250
NEKTQEHFTH
260
NTVRGCSYFY
270
SYPAVCEFLQ
280
HNNLLSILRA
290
HEAQDAGYRM
300
YRKSQTTGFP
310
SLITIFSAPN
320
YLDVYNNKAA
330
VLKYENNVMN
340
IRQFNCSPHP
350
YWLPNFMDVF
360
TWSLPFVGEK
370
VTEMLVNVLN
380
ICSDDELGSE
390
EDGFDGATAA
400
ARKEVIRNKI
410
RAIGKMARVF
420
SVLREESESV
430
LTLKGLTPTG
440
MLPSGVLSGG
450
KQTLQSATVE
460
AIEADEAIKG
470
FSPQHKITSF
480
EEAKGLDRIN
490
ERMPPRRDAM
500
PSDANLNSIN
510
KALTSETNGT
520
DSNGSNSSNI
Q
Gene Ontology
| Classification |
GO ID |
Description |
| Biological Process |
GO:0030216 |
keratinocyte differentiation |
| Cellular Component |
GO:0005955 |
calcineurin complex |
| Cellular Component |
GO:0005737 |
cytoplasm |
| Cellular Component |
GO:0005829 |
cytosol |
| Cellular Component |
GO:0043197 |
dendritic spine |
| Cellular Component |
GO:0019897 |
extrinsic component of plasma membrane |
| Cellular Component |
GO:0098978 |
glutamatergic synapse |
| Cellular Component |
GO:0005739 |
mitochondrion |
| Cellular Component |
GO:0005654 |
nucleoplasm |
| Cellular Component |
GO:0005886 |
plasma membrane |
| Cellular Component |
GO:0042383 |
sarcolemma |
| Cellular Component |
GO:0098685 |
Schaffer collateral - CA1 synapse |
| Cellular Component |
GO:0030018 |
Z disc |
| Molecular Function |
GO:0051117 |
ATPase binding |
| Molecular Function |
GO:0005509 |
calcium ion binding |
| Molecular Function |
GO:0005516 |
calmodulin binding |
| Molecular Function |
GO:0033192 |
calmodulin-dependent protein phosphatase activity |
| Molecular Function |
GO:0019899 |
enzyme binding |
| Molecular Function |
GO:0046983 |
protein dimerization activity |
| Molecular Function |
GO:0004722 |
protein serine/threonine phosphatase activity |
| Biological Process |
GO:0097720 |
calcineurin-mediated signaling |
| Biological Process |
GO:0033173 |
calcineurin-NFAT signaling cascade |
| Biological Process |
GO:0016311 |
dephosphorylation |
| Biological Process |
GO:0008544 |
epidermis development |
| Biological Process |
GO:0050804 |
modulation of chemical synaptic transmission |
| Biological Process |
GO:0110062 |
negative regulation of angiotensin-activated signaling pathway |
| Biological Process |
GO:1905949 |
negative regulation of calcium ion import across plasma membrane |
| Biological Process |
GO:0010629 |
negative regulation of gene expression |
| Biological Process |
GO:0023057 |
negative regulation of signaling |
| Biological Process |
GO:0042104 |
positive regulation of activated T cell proliferation |
| Biological Process |
GO:0070886 |
positive regulation of calcineurin-NFAT signaling cascade |
| Biological Process |
GO:1905665 |
positive regulation of calcium ion import across plasma membrane |
| Biological Process |
GO:1903235 |
positive regulation of calcium ion-dependent exocytosis of neurotransmitter |
| Biological Process |
GO:1903244 |
positive regulation of cardiac muscle hypertrophy in response to stress |
| Biological Process |
GO:0045785 |
positive regulation of cell adhesion |
| Biological Process |
GO:0030335 |
positive regulation of cell migration |
| Biological Process |
GO:1905205 |
positive regulation of connective tissue replacement |
| Biological Process |
GO:0045807 |
positive regulation of endocytosis |
| Biological Process |
GO:0010628 |
positive regulation of gene expression |
| Biological Process |
GO:0090193 |
positive regulation of glomerulus development |
| Biological Process |
GO:0045669 |
positive regulation of osteoblast differentiation |
| Biological Process |
GO:0045672 |
positive regulation of osteoclast differentiation |
| Biological Process |
GO:0046878 |
positive regulation of saliva secretion |
| Biological Process |
GO:0045944 |
positive regulation of transcription by RNA polymerase II |
| Biological Process |
GO:0099170 |
postsynaptic modulation of chemical synaptic transmission |
| Biological Process |
GO:0006470 |
protein dephosphorylation |
| Biological Process |
GO:0061006 |
regulation of cell proliferation involved in kidney morphogenesis |
| Biological Process |
GO:0097205 |
renal filtration |
| Biological Process |
GO:0051592 |
response to calcium ion |
| Biological Process |
GO:0048741 |
skeletal muscle fiber development |
| Biological Process |
GO:0043403 |
skeletal muscle tissue regeneration |
| Biological Process |
GO:0042110 |
T cell activation |
| Biological Process |
GO:0042060 |
wound healing |
Reference
[1] Shi CM, Wang QC, Li XL, Yang YH, Tang XY et al.. Global Profiling of Protein Lactylation in Human Hippocampi.. Proteomics Clin Appl 19(2):e202400061. 2025 Mar. PMID: 39610256.