PPP3R2

Summary

PPP3R2 (protein phosphatase 3 regulatory subunit B, beta, HGNC:9318) is a protein-coding gene on chromosome 9q31.1, encoding Calcineurin subunit B type 2 (Q96LZ3). Regulatory subunit of calcineurin, a calcium-dependent, calmodulin stimulated protein phosphatase.

Enables calcium-dependent protein serine/threonine phosphatase regulator activity. Predicted to be involved in calcineurin-mediated signaling. Predicted to act upstream of or within penetration of zona pellucida. Predicted to be located in cytosol. Predicted to be part of calcineurin complex.

Source: NCBI Gene 5535 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 2 total
• MANE Select transcript: NM_147180

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9318
Approved symbol	PPP3R2
Name	protein phosphatase 3 regulatory subunit B, beta
Location	9q31.1
Locus type	gene with protein product
Status	Approved
Aliases	PPP3RL
Ensembl gene	ENSG00000188386
Ensembl biotype	protein_coding
OMIM	613821
Entrez	5535

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000374806, ENST00000636434

RefSeq mRNA: 1 — MANE Select: NM_147180 NM_147180

CCDS: CCDS6759

Canonical transcript exons

ENST00000374806 — 1 exons

Exon	Start	End
ENSE00001464705	101591604	101594969

Expression profiles

Bgee: expression breadth broad, 28 present calls, max score 96.54.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3280 / max 279.6727, expressed in 6 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
101762	0.2897	4
101763	0.0316	4
101764	0.0067	3

Top tissues by expression

205 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
adult organism	UBERON:0007023	96.54	gold quality
sperm	CL:0000019	95.64	gold quality
left testis	UBERON:0004533	95.03	gold quality
right testis	UBERON:0004534	94.06	gold quality
testis	UBERON:0000473	92.30	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.95	gold quality
tibialis anterior	UBERON:0001385	70.89	silver quality
pancreatic ductal cell	CL:0002079	66.92	silver quality
ileal mucosa	UBERON:0000331	62.64	silver quality
epithelial cell of pancreas	CL:0000083	55.49	gold quality
cerebellar vermis	UBERON:0004720	54.58	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
myocardium	UBERON:0002349	50.25	gold quality
quadriceps femoris	UBERON:0001377	48.80	gold quality
nasal cavity epithelium	UBERON:0005384	47.03	gold quality
skin of hip	UBERON:0001554	46.85	silver quality
vastus lateralis	UBERON:0001379	45.49	gold quality
thymus	UBERON:0002370	45.09	gold quality
middle temporal gyrus	UBERON:0002771	43.86	gold quality
layer of synovial tissue	UBERON:0007616	43.55	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
right coronary artery	UBERON:0001625	42.72	silver quality
sural nerve	UBERON:0015488	42.72	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
gastrocnemius	UBERON:0001388	42.36	gold quality
muscle of leg	UBERON:0001383	42.23	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

114 targeting PPP3R2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-8062	99.88	68.43	995

Literature-anchored findings (GeneRIF, showing 6)

• PPP3RL gene localizes to human chromosome 9q22 and transcripts of PPP3RL gene are specifically expressed in the testis. (PMID:15865209)
• cyclosporin and tacrolimus exert significantly different effects on calcineurin activity in renal transplant patients with stable, well-functioning grafts (PMID:16961774)
• calcineurin B potentiates the activation of procaspase-3 by accelerating its proteolytic maturation (PMID:17324936)
• Here, we report that Cabin1 has additional CN binding domain in its 701-900 amino acid residues. (PMID:17531200)
• Data suggest that calcineurin may regulate the kinase activity of CDK4 in a cell cycle-dependent manner and may be an important component of the negative regulation of CDK4. (PMID:17892862)
• Data suggest an association between polymorphisms in PPP3CA, PPP3R1 and PPP3R2 and baseline levels or trainability of endurance phenotype traits. (PMID:20107831)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ppp3r2	ENSMUSG00000028310
rattus_norvegicus	Ppp3r2	ENSRNOG00000074514
drosophila_melanogaster	CG32812	FBGN0025642
drosophila_melanogaster	Cib2	FBGN0034558
drosophila_melanogaster	elm	FBGN0037358
drosophila_melanogaster	CG14362	FBGN0038186
caenorhabditis_elegans	calm-1	WBGENE00009260
caenorhabditis_elegans		WBGENE00014109
caenorhabditis_elegans		WBGENE00019108

Paralogs (8): TESC (ENSG00000088992), CIB2 (ENSG00000136425), CIB3 (ENSG00000141977), CIB4 (ENSG00000157884), CHP2 (ENSG00000166869), CIB1 (ENSG00000185043), CHP1 (ENSG00000187446), PPP3R1 (ENSG00000221823)

Protein

Protein identifiers

Calcineurin subunit B type 2 — Q96LZ3 (reviewed: Q96LZ3)

Alternative names: Calcineurin B-like protein, Calcineurin BII, PPP3R1-like, Protein phosphatase 2B regulatory subunit 2, Protein phosphatase 3 regulatory subunit B beta isoform

All UniProt accessions (2): A0A1B0GUC7, Q96LZ3

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit of calcineurin, a calcium-dependent, calmodulin stimulated protein phosphatase. Confers calcium sensitivity.

Subunit / interactions. 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). 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). Interacts with SPATA33 (via PQIIIT motif).

Subcellular location. Mitochondrion.

Tissue specificity. Testis-specific.

Miscellaneous. This protein has four functional calcium-binding sites.

Similarity. Belongs to the calcineurin regulatory subunit family.

RefSeq proteins (1): NP_671709* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR018247	EF_Hand_1_Ca_BS	Binding_site

Pfam: PF13499

Enzyme classification (BRENDA):

• EC 3.1.3.16 — protein-serine/threonine phosphatase (BRENDA: 92 organisms, 641 substrates, 468 inhibitors, 127 Km, 67 kcat entries)

Substrate kinetics (BRENDA)

59 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
6,8-DIFLUORO-4-METHYLUMBELLIFERYL PHOSPHATE	0.023–0.862	22
4-NITROPHENYL PHOSPHATE	0.0028–12.7	13
P-NITROPHENYL PHOSPHATE	3–200	11
RRAPTVA	0.058–1.954	4
PHOSPHOCASEIN	0.0001–0.002	3
PHOSPHOHISTONE	0.0023–0.0723	3
PHOSPHORYLATED MYOSIN LIGHT CHAIN PEPTIDE	0.01–0.11	3
PHOSPHOSERINE-MYELIN BASIC PROTEIN	0.0004–0.022	3
DLDVPIPGRFDRRVSVAAE	0.0006–0.0138	2
DLDVPIPGRFDRRVY(P)VAAE	0.0025–0.023	2
PHOSPHORYLASE A	0.004–0.021	2
RRA(PT)VA	0.0536–0.308	2
80S-RIBOSOME	0.0027	1
AAAPTVA	0.206	1
AGPALSPVPPV	0.357	1

UniProt features (31 total): binding site 20, domain 4, site 2, initiator methionine 1, chain 1, lipid moiety-binding region 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96LZ3-F1	91.96	0.77

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 118 (interaction with pxvp motif in substrates of the catalytic subunit); 122 (interaction with pxvp motif in substrates of the catalytic subunit)

Ligand- & substrate-binding residues (20): 37; 42; 63; 65; 67; 69; 74; 100; 102; 104; 106; 111 …

Post-translational modifications (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 136 (showing top): GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, GOBP_SINGLE_FERTILIZATION, GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_REGULATION_OF_CALCIUM_MEDIATED_SIGNALING, KEGG_MAPK_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_CALCIUM_MEDIATED_SIGNALING, GOBP_NEGATIVE_REGULATION_OF_TRANSPORT, GOBP_REGULATION_OF_CALCIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_CALCIUM_ION_IMPORT, GOBP_NEGATIVE_REGULATION_OF_CALCIUM_ION_IMPORT, GOBP_POSITIVE_REGULATION_OF_MONOATOMIC_ION_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_REGULATION_OF_CALCIUM_ION_IMPORT

GO Biological Process (5): penetration of zona pellucida (GO:0007341), positive regulation of calcineurin-NFAT signaling cascade (GO:0070886), calcineurin-mediated signaling (GO:0097720), positive regulation of calcium ion import across plasma membrane (GO:1905665), negative regulation of calcium ion import across plasma membrane (GO:1905949)

GO Molecular Function (5): calcium ion binding (GO:0005509), calcium-dependent protein serine/threonine phosphatase regulator activity (GO:0008597), phosphatase binding (GO:0019902), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (7): mitochondrion (GO:0005739), cytosol (GO:0005829), calcineurin complex (GO:0005955), protein serine/threonine phosphatase complex (GO:0008287), sperm mitochondrial sheath (GO:0097226), sperm flagellum (GO:0036126), sperm midpiece (GO:0097225)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
calcium ion import across plasma membrane	2
regulation of calcium ion import across plasma membrane	2
cytoplasm	2
single fertilization	1
multi-multicellular organism process	1
multicellular organismal reproductive process	1
calcineurin-NFAT signaling cascade	1
regulation of calcineurin-NFAT signaling cascade	1
positive regulation of calcineurin-mediated signaling	1
calcium-mediated signaling	1
positive regulation of calcium ion import	1
positive regulation of calcium ion transmembrane transport	1
negative regulation of calcium ion import	1
negative regulation of calcium ion transmembrane transport	1
metal ion binding	1
calcium-dependent protein serine/threonine phosphatase activity	1
protein phosphatase regulator activity	1
enzyme binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
protein serine/threonine phosphatase complex	1
intracellular protein-containing complex	1
phosphatase complex	1
sperm midpiece	1
9+2 motile cilium	1
sperm flagellum	1

Protein interactions and networks

STRING

1719 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPP3R2	PPP3CC	P48454	795
PPP3R2	PPP3CB	P16298	739
PPP3R2	PPP3CA	Q08209	685
PPP3R2	SOS2	Q07890	577
PPP3R2	CALML6	Q8TD86	496
PPP3R2	CALML4	Q96GE6	496
PPP3R2	SNRK	Q9NRH2	479
PPP3R2	ZBTB25	P24278	433
PPP3R2	STK25	O00506	431
PPP3R2	STK11	Q15831	391
PPP3R2	AURKA	O14965	383
PPP3R2	PPP3R1	P06705	376
PPP3R2	PIK3C2A	O00443	352
PPP3R2	SFRP4	Q6FHJ7	348
PPP3R2	ZNF346	Q9UL40	326

IntAct

20 interactions, top by confidence:

A	B	Type	Score
VPS25	VPS36	psi-mi:“MI:0914”(association)	0.800
TFCP2	PPP3R2	psi-mi:“MI:0915”(physical association)	0.560
CD14	PPP3R2	psi-mi:“MI:0915”(physical association)	0.370
PPP3R2	APC	psi-mi:“MI:0915”(physical association)	0.370
AURKA	PPP3R2	psi-mi:“MI:0915”(physical association)	0.370
PPP3R2	BUB1	psi-mi:“MI:0915”(physical association)	0.370
PPP3R2	CCND1	psi-mi:“MI:0915”(physical association)	0.370
DLC1	PPP3R2	psi-mi:“MI:0915”(physical association)	0.370
PPP3R2	FBXW7	psi-mi:“MI:0915”(physical association)	0.370
MLH3	PPP3R2	psi-mi:“MI:0915”(physical association)	0.370
MSH2	PPP3R2	psi-mi:“MI:0915”(physical association)	0.370
PPP3R2	PDGFRL	psi-mi:“MI:0915”(physical association)	0.370
PTPN12	PPP3R2	psi-mi:“MI:0915”(physical association)	0.370
PTPRJ	PPP3R2	psi-mi:“MI:0915”(physical association)	0.370
SMAD4	PPP3R2	psi-mi:“MI:0915”(physical association)	0.370
PPP3R2	ANKRD33B	psi-mi:“MI:0914”(association)	0.350
PPP3R2	MAP2K7	psi-mi:“MI:0914”(association)	0.350

BioGRID (32): TFCP2 (Two-hybrid), PPP3R2 (Two-hybrid), PPP3R2 (Two-hybrid), PPP3R2 (Two-hybrid), PPP3R2 (Two-hybrid), PPP3R2 (Two-hybrid), PPP3R2 (Two-hybrid), PPP3R2 (Two-hybrid), PPP3R2 (Two-hybrid), PPP3R2 (Two-hybrid), PPP3R2 (Two-hybrid), PPP3R2 (Two-hybrid), PPP3R2 (Two-hybrid), PPP3R2 (Two-hybrid), PPP3R2 (Two-hybrid)

ESM2 similar proteins: G5EDN6, O73761, P0CM54, P0CM55, P21457, P22728, P25296, P28470, P29104, P34057, P35243, P35332, P42322, P43080, P43081, P46065, P48451, P61022, P61023, P62760, P62761, P62762, P62763, P62764, P63098, P63099, P63100, P79880, P87072, Q24214, Q2TBI5, Q4R5F7, Q54MF3, Q55G87, Q5R6S5, Q5R7F0, Q5RD22, Q63810, Q63811, Q6BWS8

Diamond homologs: A0A2I0BVG8, A6H742, A7E3Q8, O23184, O50064, O59945, O88818, P13796, P13797, P19179, P28470, P32599, P48451, P54680, P62343, P62344, P87072, Q0DJ94, Q14651, Q24214, Q25088, Q338P8, Q3E9C0, Q3V0K9, Q61233, Q63598, Q63811, Q6DG81, Q6P698, Q6Z2M9, Q7F0J0, Q7G188, Q7XHW4, Q84UL5, Q8C5W0, Q96LZ3, Q99K51, Q9FI19, Q9FJ70, Q9FKI0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

2 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	2
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

26 predictions. Top by Δscore:

Variant	Effect	Δscore
9:101594310:T:TA	donor_gain	0.9100
9:101594413:A:AC	donor_gain	0.7900
9:101594414:C:CC	donor_gain	0.7900
9:101594415:G:C	donor_gain	0.7500
9:101594311:C:A	donor_gain	0.6400
9:101594429:T:TA	donor_gain	0.6200
9:101594417:TGAGG:T	donor_gain	0.5200
9:101594957:C:CT	acceptor_gain	0.5100
9:101594451:G:T	donor_gain	0.4900
9:101594483:T:TA	donor_gain	0.4900
9:101593331:T:TA	donor_gain	0.4800
9:101594409:T:TA	donor_gain	0.4800
9:101594411:A:T	donor_gain	0.4000
9:101594949:C:CT	acceptor_gain	0.3600
9:101594484:C:A	donor_gain	0.3400
9:101594958:G:T	acceptor_gain	0.3200
9:101594494:T:TA	donor_gain	0.3100
9:101594950:A:T	acceptor_gain	0.3100
9:101594949:C:G	acceptor_gain	0.2600
9:101594467:T:TA	donor_gain	0.2500
9:101594701:T:TA	donor_gain	0.2400
9:101594590:TCCCC:T	acceptor_gain	0.2300
9:101594168:T:TA	donor_gain	0.2200
9:101594351:CT:C	acceptor_gain	0.2100
9:101594352:TT:T	acceptor_gain	0.2100
9:101594412:T:C	donor_gain	0.2000

AlphaMissense

1152 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:101594634:G:C	F96L	0.996
9:101594634:G:T	F96L	0.996
9:101594636:A:G	F96L	0.996
9:101594463:G:C	F153L	0.993
9:101594463:G:T	F153L	0.993
9:101594465:A:G	F153L	0.993
9:101594841:A:C	F27L	0.992
9:101594841:A:T	F27L	0.992
9:101594843:A:G	F27L	0.992
9:101594602:A:T	I107N	0.991
9:101594524:A:T	V133D	0.990
9:101594842:A:G	F27S	0.988
9:101594635:A:G	F96S	0.987
9:101594575:A:G	L116P	0.986
9:101594698:A:G	F75S	0.986
9:101594536:A:G	L129P	0.985
9:101594602:A:C	I107S	0.985
9:101594464:A:G	F153S	0.984
9:101594527:A:G	L132P	0.984
9:101594623:T:G	D100A	0.983
9:101594587:A:G	L112P	0.982
9:101594624:C:G	D100H	0.982
9:101594479:A:T	I148K	0.980
9:101594525:C:A	V133F	0.979
9:101594636:A:T	F96I	0.979
9:101594697:G:C	F75L	0.978
9:101594697:G:T	F75L	0.978
9:101594699:A:G	F75L	0.978
9:101594602:A:G	I107T	0.977
9:101594622:G:C	D100E	0.977

dbSNP variants (sampled 300 via entrez): RS1000027248 (9:101591544 C>A), RS1000044664 (9:101595713 G>T), RS1000079271 (9:101592007 C>G,T), RS1000566431 (9:101593447 T>C), RS1000618850 (9:101593210 G>A,T), RS1002362338 (9:101593090 G>C), RS1002414761 (9:101592710 G>T), RS1003032138 (9:101595989 T>G), RS1003493574 (9:101591131 C>T), RS1003547641 (9:101591482 C>T), RS1003780109 (9:101591413 G>A), RS1004164122 (9:101593658 T>C), RS1004285448 (9:101593404 A>T), RS1004316984 (9:101592665 T>C), RS1004338148 (9:101592432 C>T)

Disease associations

OMIM: gene MIM:613821 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, decreases expression	2
Benzo(a)pyrene	affects methylation	1
Carbamazepine	affects expression	1
Copper	affects cotreatment, decreases expression	1
Formaldehyde	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Copper Sulfate	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.