UniProt:P48454 PPP3CC

chain
  • chain:1-512
checksum 1C3AA7996660D575
comment
  • FUNCTION Calcium-dependent, calmodulin-stimulated protein phosphatase which plays an essential role in the transduction of intracellular Ca(2+)-mediated signals. Dephosphorylates and activates transcription factor NFATC1. Dephosphorylates and inactivates transcription factor ELK1. Dephosphorylates DARPP32.CATALYTIC ACTIVITY O-phospho-L-seryl-[protein] + H2O = L-seryl-[protein] + phosphateCATALYTIC ACTIVITY O-phospho-L-threonyl-[protein] + H2O = L-threonyl-[protein] + phosphateCOFACTOR Binds 1 Fe(3+) ion per subunit.COFACTOR Binds 1 zinc ion per subunit.ACTIVITY REGULATION Activated by Ca(2+)-bound calmodulin following an increase in intracellular Ca(2+). At low Ca(2+) concentrations, the catalytic subunit (also known as calcineurin A) is inactive and is bound to the regulatory subunit (also known as calcineurin B) in which only two high-affinity binding sites are occupied by Ca(2+). In response to elevated calcium levels, the occupancy of the low-affinity sites on calcineurin B by Ca(2+) causes a conformational change of the C-terminal regulatory domain of calcineurin A, resulting in the exposure of the calmodulin-binding domain and in the partial activation of calcineurin A. The subsequent binding of Ca(2+)-bound calmodulin leads to the displacement of the autoinhibitory domain from the active site and possibly of the autoinhibitory segment from the substrate binding site which fully activates calcineurin A.BIOPHYSICOCHEMICAL PROPERTIES Forms a complex composed of a calmodulin-dependent catalytic subunit (also known as calcineurin A) and a regulatory Ca(2+)-binding subunit (also known as calcineurin B) (PubMed:19154138). 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 Ca(2+) intracellular levels, forms a complex composed of PPP3CC/calcineurin A, calcineurin B and calmodulin (By similarity). Interacts (via calmodulin-binding domain) with calmodulin; the interaction depends on calmodulin binding to Ca(2+) (By similarity). Interacts with UNC119 (By similarity). Interacts with SPATA33 (via PQIIIT motif) (PubMed:34446558). Interacts with VDAC2 in a SPATA33-dependent manner (By similarity).INTERACTION Localizes in the mitochondria in a SPATA33-dependent manner.ALTERNATIVE PRODUCTS Testis.DOMAIN The autoinhibitory domain prevents access to the catalytic site.DOMAIN The autoinhibitory segment prevents access to the substrate binding site.DOMAIN Possible isomerization of Pro-305 within the SAPNY motif triggers a conformation switch which affects the organization and thus accessibility of the active site and the substrate binding region (PxIxIF motif). The trans- to cis-transition may favor calcineurin A activation and substrate binding. The reverse cis- to trans-transition may be enhanced by peptidyl-prolyl isomerases such as PPIA.SIMILARITY Belongs to the PPP phosphatase family. PP-2B subfamily.
crossReference
databaseName UniProt
dbId 61114
description
  • recommendedName: Serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform ecNumber evidence="6"3.1.3.16 alternativeName: CAM-PRP catalytic subunit alternativeName: Calcineurin, testis-specific catalytic subunit alternativeName: Calmodulin-dependent calcineurin A subunit gamma isoform
displayName UniProt:P48454 PPP3CC
geneName
  • PPP3CC
  • CALNA3
  • CNA3
identifier P48454
isSequenceChanged false
keyword
  • 3D-structure
  • Alternative splicing
  • Calmodulin-binding
  • Hydrolase
  • Iron
  • Metal-binding
  • Mitochondrion
  • Phosphoprotein
  • Protein phosphatase
  • Proteomics identification
  • Reference proteome
  • Zinc
modified [InstanceEdit:9939033] Weiser, Joel, 2025-02-21
moleculeType Protein
name
  • PPP3CC
otherIdentifier
  • 11722420_a_at
  • 17066627
  • 207000_PM_s_at
  • 207000_s_at
  • 3089402
  • 3089403
  • 3089404
  • 3089408
  • 3089409
  • 3089410
  • 3089411
  • 3089427
  • 3089428
  • 3089429
  • 3089430
  • 3089431
  • 3089433
  • 3089434
  • 3089436
  • 3089437
  • 3089438
  • 3089439
  • 3089440
  • 3089443
  • 3089444
  • 3089445
  • 3089448
  • 3089449
  • 3089450
  • 3089458
  • 3089461
  • 3089462
  • 3089463
  • 32541_PM_at
  • 32541_at
  • 5533
  • 8145136
  • A_14_P119710
  • A_23_P157495
  • GE58778
  • GO:0003824
  • GO:0004721
  • GO:0004722
  • GO:0004723
  • GO:0005515
  • GO:0005516
  • GO:0005737
  • GO:0005739
  • GO:0005829
  • GO:0005955
  • GO:0006470
  • GO:0008287
  • GO:0016787
  • GO:0033173
  • GO:0033192
  • GO:0046872
  • GO:0070886
  • GO:0097720
  • GO:0098793
  • GO:0098978
  • GO:0140096
  • GO:1900242
  • GO:1900244
  • GO:1905665
  • GO:1905949
  • HMNXSV003014039
  • HMNXSV003045682
  • ILMN_1690546
  • PH_hs_0004287
  • S46622_at
  • TC08000172.hg
  • g5031988_3p_s_at
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
referenceTranscript
schemaClass ReferenceGeneProduct
secondaryIdentifier
  • PP2BC_HUMAN
  • B4DRT5
  • Q9BSS6
  • Q9H4M5
sequenceLength 512
species [Species:48887] Homo sapiens
stId uniprot:P48454
url http://purl.uniprot.org/uniprot/P48454
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