PPP3CA protein phosphatase 3 catalytic subunit alpha [Homo sapiens (human)] - Gene

Summary

Official Symbol: PPP3CAprovided by HGNC
Official Full Name: protein phosphatase 3 catalytic subunit alphaprovided by HGNC
Primary source: HGNC:HGNC:9314
See related: Ensembl:ENSG00000138814 MIM:114105; AllianceGenome:HGNC:9314
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CALN; CNA1; CALNA; DEE91; IECEE; PPP2B; ACCIID; CALNA1; IECEE1
Summary: Enables several functions, including ATPase binding activity; calmodulin binding activity; and calmodulin-dependent protein phosphatase activity. Involved in several processes, including calcineurin-NFAT signaling cascade; negative regulation of angiotensin-activated signaling pathway; and peptidyl-serine dephosphorylation. Located in cytoplasm; cytoplasmic side of plasma membrane; and dendritic spine. Part of calcineurin complex. Implicated in developmental and epileptic encephalopathy 91. Biomarker of cholangiocarcinoma; focal segmental glomerulosclerosis; and schizophrenia. [provided by Alliance of Genome Resources, Jul 2025]
Expression: Broad expression in brain (RPKM 54.0), prostate (RPKM 42.7) and 24 other tissues See more
Orthologs: all
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Genomic context

Location:: 4q24

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
RS_2025_08	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (101023418..101347526, complement)
RS_2025_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (104338695..104662217, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (101944575..102268683, complement)

Chromosome 4 - NC_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Dephosphorylation of the EGFR protein by calcineurin at serine 1046/1047 enhances its stability.
Title: Dephosphorylation of the EGFR protein by calcineurin at serine 1046/1047 enhances its stability.
TRIM72 exerts antitumor effects in breast cancer and modulates lactate production and MCT4 promoter activity by interacting with PPP3CA.
Title: TRIM72 exerts antitumor effects in breast cancer and modulates lactate production and MCT4 promoter activity by interacting with PPP3CA.
Immunosuppression Affects Neutrophil Functions: Does Calcineurin-NFAT Signaling Matter?
Title: Immunosuppression Affects Neutrophil Functions: Does Calcineurin-NFAT Signaling Matter?
PPP3CA truncating variants clustered in the regulatory domain cause early-onset refractory epilepsy.
Title: PPP3CA truncating variants clustered in the regulatory domain cause early-onset refractory epilepsy.
Calcineurin regulates the stability and activity of estrogen receptor alpha.
Title: Calcineurin regulates the stability and activity of estrogen receptor α.
Calcineurin.
Title: Calcineurin.
Regulation of the Ca(2+)-activated chloride channel Anoctamin-1 (TMEM16A) by Ca(2+)-induced interaction with FKBP12 and calcineurin.
Title: Regulation of the Ca(2+)-activated chloride channel Anoctamin-1 (TMEM16A) by Ca(2+)-induced interaction with FKBP12 and calcineurin.
Differential protein expression of DARPP-32 versus Calcineurin in the prefrontal cortex and nucleus accumbens in schizophrenia and bipolar disorder.
Title: Differential protein expression of DARPP-32 versus Calcineurin in the prefrontal cortex and nucleus accumbens in schizophrenia and bipolar disorder.
Calcineurin functions as a positive and negative modulator of gene transcription.
Title: Calcineurin controls gene transcription following stimulation of a Gαq-coupled designer receptor.
Solution NMR shows that the P84A calcineurin Aalpha mutant exists in two forms, compatible with cis-trans isomers, while the P309A mutant is predominantly in the trans conformation
Title: Cis-trans proline isomers in the catalytic domain of calcineurin.

Submit: New GeneRIF Correction See all GeneRIFs (76)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Arthrogryposis, cleft palate, craniosynostosis, and impaired intellectual development MedGen: C4748872 OMIM: 618265 GeneReviews: Not available	Compare labs
Developmental and epileptic encephalopathy 91 MedGen: C4540199 OMIM: 617711 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
A genome-wide association study identifies a potential novel gene locus for keratoconus, one of the commonest causes for corneal transplantation in developed countries. EBI GWAS Catalog EBI GWAS CatalogPubMed
A genome-wide association study of anorexia nervosa. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide linkage and association scans for pulse pressure in Chinese twins. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120-induced dephosphorylation of KV2.1 is dependent on NMDA receptor-mediated activation of protein phosphatase 2B or calcineurin	PubMed
Tat	tat	Induction of TNF-alpha by HIV-1 Tat is inhibited by cyclosporin A, an inhibitor of calcineurin that acts by preventing the dephosphorylation of NF-AT, suggesting Tat activates calcineurin	PubMed

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

G42352 (e-PCR)
- UniSTS:94211

PPP3CA (e-PCR)
- UniSTS:519172

STS-N27154 (e-PCR)
- UniSTS:13832

SHGC-50332 (e-PCR)
- UniSTS:82707

SHGC-67753 (e-PCR)
- UniSTS:65299

SHGC-19097 (e-PCR)
- UniSTS:82708

RH98934 (e-PCR)
- UniSTS:84762

G66787 (e-PCR)
- UniSTS:166694

SHGC4-996 (e-PCR)
- UniSTS:54320

D4S1591 (e-PCR)
- UniSTS:54321

G62618 (e-PCR)
- UniSTS:139598

WI-18296 (e-PCR)
- UniSTS:72271

RH25535 (e-PCR)
- UniSTS:90708

WI-18743 (e-PCR)
- UniSTS:50264

SHGC-142728 (e-PCR)
- UniSTS:171614

G59661 (e-PCR)
- UniSTS:136815

EST26A4-T (e-PCR)
- UniSTS:263284

SHGC-106455 (e-PCR)
- UniSTS:169860

SHGC-106093 (e-PCR)
- UniSTS:169622

PPP3CA (e-PCR)
- UniSTS:503449

WI-16419 (e-PCR)
- UniSTS:61859

SHGC-67693 (e-PCR)
- UniSTS:30634

WI-20975 (e-PCR)
- UniSTS:30635

J05479 (e-PCR)
- UniSTS:124858

SHGC-67255 (e-PCR)
- UniSTS:14011

RH66646 (e-PCR)
- UniSTS:56514

G62859 (e-PCR)
- UniSTS:139984

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATPase binding	IPI Inferred from Physical Interaction more info	PubMed
enables calcium ion binding	NAS Non-traceable Author Statement more info	PubMed
enables calmodulin binding	EXP Inferred from Experiment more info	PubMed
enables calmodulin binding	IBA Inferred from Biological aspect of Ancestor more info
enables calmodulin binding	IDA Inferred from Direct Assay more info	PubMed
enables calmodulin binding	IEA Inferred from Electronic Annotation more info
enables calmodulin binding	IPI Inferred from Physical Interaction more info	PubMed
enables calmodulin binding	NAS Non-traceable Author Statement more info	PubMed
enables calmodulin-dependent protein phosphatase activity	IBA Inferred from Biological aspect of Ancestor more info
enables calmodulin-dependent protein phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
enables calmodulin-dependent protein phosphatase activity	IEA Inferred from Electronic Annotation more info
enables calmodulin-dependent protein phosphatase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables calmodulin-dependent protein phosphatase activity	TAS Traceable Author Statement more info	PubMed
enables enzyme binding	IDA Inferred from Direct Assay more info	PubMed
enables hydrolase activity	IEA Inferred from Electronic Annotation more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables phosphoprotein phosphatase activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein dimerization activity	IPI Inferred from Physical Interaction more info	PubMed
enables protein serine/threonine phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein serine/threonine phosphatase activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine phosphatase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables protein serine/threonine phosphatase activity	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in T cell activation	TAS Traceable Author Statement more info	PubMed
involved_in calcineurin-NFAT signaling cascade	IBA Inferred from Biological aspect of Ancestor more info
involved_in calcineurin-NFAT signaling cascade	IDA Inferred from Direct Assay more info	PubMed
involved_in calcineurin-NFAT signaling cascade	IEA Inferred from Electronic Annotation more info
involved_in calcineurin-NFAT signaling cascade	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in calcineurin-mediated signaling	IEA Inferred from Electronic Annotation more info
involved_in calcineurin-mediated signaling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in dephosphorylation	TAS Traceable Author Statement more info	PubMed
involved_in epidermis development	IEA Inferred from Electronic Annotation more info
involved_in epidermis development	ISS Inferred from Sequence or Structural Similarity more info
involved_in keratinocyte differentiation	IEA Inferred from Electronic Annotation more info
involved_in keratinocyte differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in modulation of chemical synaptic transmission	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of angiotensin-activated signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of calcium ion import across plasma membrane	NAS Non-traceable Author Statement more info	PubMed
involved_in negative regulation of gene expression	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of signaling	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of signaling	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of activated T cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of activated T cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of calcineurin-NFAT signaling cascade	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of calcium ion import across plasma membrane	NAS Non-traceable Author Statement more info	PubMed
acts_upstream_of_or_within positive regulation of calcium ion-dependent exocytosis of neurotransmitter	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of cardiac muscle hypertrophy	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cardiac muscle hypertrophy in response to stress	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cell adhesion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of connective tissue replacement	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of endocytosis	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of gene expression	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of glomerulus development	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of glomerulus development	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of osteoblast differentiation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of osteoblast differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of osteoclast differentiation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of osteoclast differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of saliva secretion	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of saliva secretion	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in postsynaptic modulation of chemical synaptic transmission	IEA Inferred from Electronic Annotation more info
involved_in protein dephosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein dephosphorylation	NAS Non-traceable Author Statement more info	PubMed
involved_in regulation of cell proliferation involved in kidney morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in regulation of cell proliferation involved in kidney morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in renal filtration	IEA Inferred from Electronic Annotation more info
involved_in renal filtration	ISS Inferred from Sequence or Structural Similarity more info
involved_in response to calcium ion	IDA Inferred from Direct Assay more info	PubMed
involved_in skeletal muscle fiber development	ISS Inferred from Sequence or Structural Similarity more info
involved_in skeletal muscle tissue regeneration	TAS Traceable Author Statement more info	PubMed
involved_in wound healing	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
is_active_in Schaffer collateral - CA1 synapse	IEA Inferred from Electronic Annotation more info
located_in Z disc	IEA Inferred from Electronic Annotation more info
part_of calcineurin complex	IBA Inferred from Biological aspect of Ancestor more info
part_of calcineurin complex	IDA Inferred from Direct Assay more info	PubMed
part_of calcineurin complex	IEA Inferred from Electronic Annotation more info
part_of calcineurin complex	NAS Non-traceable Author Statement more info	PubMed
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
colocalizes_with cytoplasmic side of plasma membrane	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	IEA Inferred from Electronic Annotation more info
located_in cytosol	NAS Non-traceable Author Statement more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in dendritic spine	IDA Inferred from Direct Assay more info	PubMed
located_in dendritic spine	IEA Inferred from Electronic Annotation more info
located_in extrinsic component of plasma membrane	IC Inferred by Curator more info	PubMed
is_active_in glutamatergic synapse	IEA Inferred from Electronic Annotation more info
located_in mitochondrion	IEA Inferred from Electronic Annotation more info
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IEA Inferred from Electronic Annotation more info
located_in sarcolemma	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: protein phosphatase 3 catalytic subunit alpha

Names: CAM-PRP catalytic subunit; CNA alpha; calcineurin A alpha; protein phosphatase 3 catalytic subunit alpha isozyme

NP_000935.1

EC 3.1.3.16

NP_001124163.1

EC 3.1.3.16

NP_001124164.1

EC 3.1.3.16

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_000944.5 → NP_000935.1 protein phosphatase 3 catalytic subunit alpha isoform 1

See identical proteins and their annotated locations for NP_000935.1

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AL353950, AP001816, AP001870, AW973358, EU192652

Consensus CDS

CCDS34037.1

UniProtKB/Swiss-Prot

A1A441, A8K3B7, A8W6Z7, A8W6Z8, B5BUA2, Q08209, Q8TAW9

UniProtKB/TrEMBL

A0A0S2Z4C6

Related

ENSP00000378323.3, ENST00000394854.8

Conserved Domains (1) summary

cd07416
Location:41 → 345

MPP_PP2B; PP2B, metallophosphatase domain
NM_001130691.2 → NP_001124163.1 protein phosphatase 3 catalytic subunit alpha isoform 2

See identical proteins and their annotated locations for NP_001124163.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) lacks an in-frame exon in the 3' coding region, compared to variant 1, and encodes a shorter protein (isoform 2), compared to isoform 1.

Source sequence(s)

AP001816, AP001870, AW973358, BC025714, EU192652

Consensus CDS

CCDS47114.1

UniProtKB/TrEMBL

A0A0S2Z4B5

Related

ENSP00000378322.4, ENST00000394853.8

Conserved Domains (1) summary

cd07416
Location:41 → 345

MPP_PP2B; PP2B, metallophosphatase domain
NM_001130692.2 → NP_001124164.1 protein phosphatase 3 catalytic subunit alpha isoform 3

See identical proteins and their annotated locations for NP_001124164.1

Status: VALIDATED

Description

Transcript Variant: This variant (3) lacks multiple in-frame exons in the 3' coding region, compared to variant 1, and encodes a shorter protein (isoform 3), compared to isoform 1.

Source sequence(s)

AP001816, AP001870, AW973358, EU192652

Consensus CDS

CCDS47113.1

UniProtKB/Swiss-Prot

Q08209

Related

ENSP00000320580.6, ENST00000323055.10

Conserved Domains (1) summary

cd07416
Location:41 → 329

MPP_PP2B; PP2B, metallophosphatase domain