Q08209 · PP2BA_HUMAN
- ProteinProtein phosphatase 3 catalytic subunit alpha
- GenePPP3CA
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids521 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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 Ca2+ levels, dephosphorylates and activates phosphatase SSH1 which results in cofilin dephosphorylation (PubMed:15671020).
In response to increased Ca2+ levels following mitochondrial depolarization, dephosphorylates DNM1L inducing DNM1L translocation to the mitochondrion (PubMed:18838687).
Positively regulates the CACNA1B/CAV2.2-mediated Ca2+ 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 Ca2+ 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).
Miscellaneous
Catalytic activity
- H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] + phosphate
Cofactor
Activity regulation
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
2.04 μM | NFATC1 | |||||
2.22 μM | DARPP32 |
Features
Showing features for binding site, active site, site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 90 | Fe cation (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 92 | Fe cation (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 118 | Fe cation (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 118 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 150 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Active site | 151 | Proton donor | ||||
Sequence: H | ||||||
Binding site | 199 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 281 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Site | 352 | Interaction with PxVP motif in substrate | ||||
Sequence: W |
GO annotations
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameProtein phosphatase 3 catalytic subunit alpha
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ08209
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Recruited to the cell membrane by scaffold protein AKAP5 following L-type Ca2+-channel activation (PubMed:22343722).
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Epileptic encephalopathy, infantile or early childhood, 1 (IECEE1)
- Note
- DescriptionA form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. IECEE1 is an autosomal dominant condition with onset of seizures between the first weeks and first years of life.
- See alsoMIM:617711
Natural variants in IECEE1
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_080348 | 92 | H>R | in IECEE1; dbSNP:rs1553925558 | |
VAR_081900 | 150 | N>I | in IECEE1 | |
VAR_081901 | 234 | D>E | in IECEE1; dbSNP:rs780035527 | |
VAR_080349 | 281 | H>Q | in IECEE1; dbSNP:rs199706529 | |
VAR_080350 | 282 | E>K | in IECEE1; dbSNP:rs1553923787 | |
VAR_085829 | 442-521 | missing | in IECEE1; results in constitutive phosphatase activity in the absence of calmodulin | |
VAR_080351 | 445-521 | missing | in IECEE1 | |
VAR_080352 | 447 | A>T | in IECEE1; uncertain significance; dbSNP:rs1553920374 |
Arthrogryposis, cleft palate, craniosynostosis, and impaired intellectual development (ACCIID)
- Note
- DescriptionAn autosomal dominant disease characterized by moderate to severe intellectual disability, craniosynostosis, cleft palate, micrognathia, arthrogryposis, and short stature. Some patients may present bone abnormalities and generalized seizures.
- See alsoMIM:618265
Natural variants in ACCIID
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_081902 | 470 | F>L | in ACCIID; dbSNP:rs1560567347 | |
VAR_081903 | 473 | A>T | in ACCIID; dbSNP:rs1560567337 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_080348 | 92 | in IECEE1; dbSNP:rs1553925558 | |||
Sequence: H → R | ||||||
Natural variant | VAR_081900 | 150 | in IECEE1 | |||
Sequence: N → I | ||||||
Natural variant | VAR_081901 | 234 | in IECEE1; dbSNP:rs780035527 | |||
Sequence: D → E | ||||||
Natural variant | VAR_080349 | 281 | in IECEE1; dbSNP:rs199706529 | |||
Sequence: H → Q | ||||||
Natural variant | VAR_080350 | 282 | in IECEE1; dbSNP:rs1553923787 | |||
Sequence: E → K | ||||||
Mutagenesis | 288 | Partial loss of Ca2+-mediated transcription factor NFAT activation; when associated with F-341. | ||||
Sequence: Y → F | ||||||
Mutagenesis | 288 | Loss of Ca2+-mediated transcription factor NFAT activation; when associated with F-341. | ||||
Sequence: Y → N or A | ||||||
Mutagenesis | 328-332 | Loss of Ca2+-mediated transcription factor NFAT activation; when associated with F-341. | ||||
Sequence: Missing | ||||||
Mutagenesis | 341 | Resistant to cyclosporin A-mediated inhibition. Loss of Ca2+-mediated transcription factor NFAT activation; when associated with N-288, A-228 or 328-V--R-332 DEL. Partial loss in Ca2+-mediated transcription factor NFAT activation; when associated with F-288. | ||||
Sequence: Y → F | ||||||
Natural variant | VAR_085829 | 442-521 | in IECEE1; results in constitutive phosphatase activity in the absence of calmodulin | |||
Sequence: Missing | ||||||
Natural variant | VAR_080351 | 445-521 | in IECEE1 | |||
Sequence: Missing | ||||||
Natural variant | VAR_080352 | 447 | in IECEE1; uncertain significance; dbSNP:rs1553920374 | |||
Sequence: A → T | ||||||
Natural variant | VAR_081902 | 470 | in ACCIID; dbSNP:rs1560567347 | |||
Sequence: F → L | ||||||
Natural variant | VAR_081903 | 473 | in ACCIID; dbSNP:rs1560567337 | |||
Sequence: A → T |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 418 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Initiator methionine | 1 | UniProt | Removed | ||||
Sequence: M | |||||||
Modified residue | 2 | UniProt | N-acetylserine | ||||
Sequence: S | |||||||
Chain | PRO_0000058822 | 2-521 | UniProt | Protein phosphatase 3 catalytic subunit alpha | |||
Sequence: SEPKAIDPKLSTTDRVVKAVPFPPSHRLTAKEVFDNDGKPRVDILKAHLMKEGRLEESVALRIITEGASILRQEKNLLDIDAPVTVCGDIHGQFFDLMKLFEVGGSPANTRYLFLGDYVDRGYFSIECVLYLWALKILYPKTLFLLRGNHECRHLTEYFTFKQECKIKYSERVYDACMDAFDCLPLAALMNQQFLCVHGGLSPEINTLDDIRKLDRFKEPPAYGPMCDILWSDPLEDFGNEKTQEHFTHNTVRGCSYFYSYPAVCEFLQHNNLLSILRAHEAQDAGYRMYRKSQTTGFPSLITIFSAPNYLDVYNNKAAVLKYENNVMNIRQFNCSPHPYWLPNFMDVFTWSLPFVGEKVTEMLVNVLNICSDDELGSEEDGFDGATAAARKEVIRNKIRAIGKMARVFSVLREESESVLTLKGLTPTGMLPSGVLSGGKQTLQSATVEAIEADEAIKGFSPQHKITSFEEAKGLDRINERMPPRRDAMPSDANLNSINKALTSETNGTDSNGSNSSNIQ | |||||||
Modified residue (large scale data) | 107 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 224 | UniProt | 3'-nitrotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 373 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 411 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 427 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 438 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 469 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 469 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 492 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 492 | PRIDE | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
There are three catalytic subunits, each encoded by a separate gene (PPP3CA, PPP3CB, and PPP3CC) and two regulatory subunits which are also encoded by separate genes (PPP3R1 and PPP3R2). In response to an increase in Ca2+ intracellular levels, forms a complex composed of PPP3CA/calcineurin A, calcineurin B and calmodulin (By similarity).
Interacts (via calcineurin B binding domain) with regulatory subunit PPP3R1/calcineurin B (PubMed:12218175, PubMed:12357034, PubMed:17498738, PubMed:22343722, PubMed:23468591, PubMed:27974827, PubMed:8524402).
Interacts (via calmodulin-binding domain) with CALM1/calmodulin; the interaction depends on calmodulin binding to Ca2+ (PubMed:18384083, PubMed:19404396, PubMed:25144868, Ref.34). Forms a complex composed of MYOZ2 and ACTN1 (By similarity).
Within the complex interacts with MYOZ2 (PubMed:11114196).
Interacts with MYOZ1 (PubMed:11114196).
Interacts with MYOZ3 (PubMed:11842093).
Interacts with CIB1; the interaction increases upon cardiomyocyte hypertrophy (By similarity).
Interacts with CHP1 and CHP2 (By similarity).
Interacts with CRTC1 (PubMed:30611118).
Interacts with CRTC2 (PubMed:15454081, PubMed:30611118).
Interacts with DNM1L; the interaction dephosphorylates DNM1L and promotes its translocation to mitochondria (PubMed:18838687).
Interacts with CMYA5; this interaction represses calcineurin activity in muscle (By similarity).
Interacts (constitutively active form) with SYNPO2 (PubMed:17923693).
Interacts with scaffold protein AKAP5 (via IAIIIT motif); the interaction recruits PPP3CA to the plasma membrane following L-type Ca2+-channel activation (PubMed:22343722).
Interacts with NFATC2 (PubMed:26248042).
Interacts with RCAN3 (PubMed:26248042).
Interacts with PPIA (PubMed:12218175, PubMed:12357034).
Interacts with RCAN1 (PubMed:12809556).
Interacts with UNC119 (By similarity).
Interacts with C16orf74 (via PxIxIT motif, when phosphorylated on 'Thr-44') (PubMed:28881575).
Interacts (via N-terminus) with MAP3K14/NIK (via C-terminus and kinase domain) (By similarity).
Interacts with TRAF3 (By similarity).
Interacts with SPATA33 (via PQIIIT motif) (PubMed:34446558).
Binary interactions
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, motif, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 56-340 | Catalytic | ||||
Sequence: LEESVALRIITEGASILRQEKNLLDIDAPVTVCGDIHGQFFDLMKLFEVGGSPANTRYLFLGDYVDRGYFSIECVLYLWALKILYPKTLFLLRGNHECRHLTEYFTFKQECKIKYSERVYDACMDAFDCLPLAALMNQQFLCVHGGLSPEINTLDDIRKLDRFKEPPAYGPMCDILWSDPLEDFGNEKTQEHFTHNTVRGCSYFYSYPAVCEFLQHNNLLSILRAHEAQDAGYRMYRKSQTTGFPSLITIFSAPNYLDVYNNKAAVLKYENNVMNIRQFNCSPHP | ||||||
Motif | 307-311 | SAPNY motif | ||||
Sequence: SAPNY | ||||||
Region | 327-336 | Interaction with PxIxIF motif in substrate | ||||
Sequence: NVMNIRQFNC | ||||||
Region | 341-369 | Calcineurin B binding | ||||
Sequence: YWLPNFMDVFTWSLPFVGEKVTEMLVNVL | ||||||
Region | 392-406 | Calmodulin-binding | ||||
Sequence: RKEVIRNKIRAIGKM | ||||||
Region | 407-414 | Autoinhibitory segment | ||||
Sequence: ARVFSVLR | ||||||
Region | 465-487 | Autoinhibitory domain | ||||
Sequence: HKITSFEEAKGLDRINERMPPRR | ||||||
Region | 475-521 | Disordered | ||||
Sequence: GLDRINERMPPRRDAMPSDANLNSINKALTSETNGTDSNGSNSSNIQ | ||||||
Compositional bias | 493-521 | Polar residues | ||||
Sequence: DANLNSINKALTSETNGTDSNGSNSSNIQ |
Domain
Sequence similarities
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 5 isoforms produced by Alternative splicing.
Q08209-1
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
- Length521
- Mass (Da)58,688
- Last updated1996-02-01 v1
- Checksum16480D62DDBF1F40
Q08209-2
- Name2
- Differences from canonical
- 448-457: Missing
Q08209-3
- Name3
Q08209-4
- Name4
- Differences from canonical
- 87-318: Missing
Q08209-5
- Name5
- Differences from canonical
- 20-86: Missing
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Features
Showing features for alternative sequence, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_054467 | 20-86 | in isoform 5 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_047755 | 87-318 | in isoform 4 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_043378 | 318-359 | in isoform 3 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_018562 | 448-457 | in isoform 2 and isoform 3 | |||
Sequence: Missing | ||||||
Compositional bias | 493-521 | Polar residues | ||||
Sequence: DANLNSINKALTSETNGTDSNGSNSSNIQ |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
L14778 EMBL· GenBank· DDBJ | AAA02631.1 EMBL· GenBank· DDBJ | mRNA | ||
EU192652 EMBL· GenBank· DDBJ | ABW74484.1 EMBL· GenBank· DDBJ | mRNA | ||
EU192653 EMBL· GenBank· DDBJ | ABW74485.1 EMBL· GenBank· DDBJ | mRNA | ||
AY904364 EMBL· GenBank· DDBJ | AAY17314.1 EMBL· GenBank· DDBJ | mRNA | ||
AK290532 EMBL· GenBank· DDBJ | BAF83221.1 EMBL· GenBank· DDBJ | mRNA | ||
AL353950 EMBL· GenBank· DDBJ | CAB89253.1 EMBL· GenBank· DDBJ | mRNA | ||
AB451338 EMBL· GenBank· DDBJ | BAG70152.1 EMBL· GenBank· DDBJ | mRNA | ||
AB451487 EMBL· GenBank· DDBJ | BAG70301.1 EMBL· GenBank· DDBJ | mRNA | ||
AC092671 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AP001816 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AP001870 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AP001939 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471057 EMBL· GenBank· DDBJ | EAX06125.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471057 EMBL· GenBank· DDBJ | EAX06124.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC025714 EMBL· GenBank· DDBJ | AAH25714.1 EMBL· GenBank· DDBJ | mRNA |