PPP2CB

Summary

PPP2CB (protein phosphatase 2 catalytic subunit beta, HGNC:9300) is a protein-coding gene on chromosome 8p12, encoding Serine/threonine-protein phosphatase 2A catalytic subunit beta isoform (P62714). Catalytic subunit of protein phosphatase 2A (PP2A), a serine/threonine phosphatase involved in the regulation of a wide variety of enzymes, signal transduction pathways, and cellular events.

This gene encodes the phosphatase 2A catalytic subunit. Protein phosphatase 2A is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. This gene encodes a beta isoform of the catalytic subunit.

Source: NCBI Gene 5516 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 35 total
• Regional missense constraint (gnomAD): 1 of 4 regions constrained (≈5% of expected missense variation)
• GTEx eGene: eQTL in 19 tissues, sQTL in 6 (q < 0.05)
• Drug target: yes — 1 curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.03 (LoF-tolerant), LOEUF 0.74 (unconstrained)
• MANE Select transcript: NM_001009552

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9300
Approved symbol	PPP2CB
Name	protein phosphatase 2 catalytic subunit beta
Location	8p12
Locus type	gene with protein product
Status	Approved
Aliases	PP2Abeta
Ensembl gene	ENSG00000104695
Ensembl biotype	protein_coding
OMIM	176916
Entrez	5516

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 12 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000221138

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 3, TSL 3: 4, TSL 4: 1, TSL 5: 1

ENST00000221138, ENST00000518243, ENST00000518532, ENST00000518564, ENST00000520056, ENST00000520334, ENST00000520500, ENST00000522113, ENST00000523023, ENST00000523804, ENST00000906070, ENST00000906071, ENST00000966961, ENST00000966962, ENST00000966963, ENST00001056513, ENST00001105046, ENST00001105047, ENST00001133270

RefSeq mRNA: 1 — MANE Select: NM_001009552 NM_001009552

CCDS: CCDS6079

Canonical transcript exons

ENST00000221138 — 7 exons

Exon	Start	End
ENSE00000688018	30797581	30797754
ENSE00001483887	30812320	30812818
ENSE00001593515	30794192	30794281
ENSE00001625658	30791197	30791315
ENSE00001729232	30793917	30794078
ENSE00002094460	30785616	30786307
ENSE00003618118	30799546	30799755

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 99.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.1335 / max 271.3708, expressed in 1798 samples.

Highest expression (Bgee): pons, superior vestibular nucleus, subthalamic nucleus, cranial nerve II, dorsal plus ventral thalamus.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PPP2CB is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 19 tissues and its splicing (sQTL) in 6 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 25 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	eqtl	2.4e-86	+0.86	8:30812874:G:T
Heart Left Ventricle	sqtl	7.0e-12	+1.01	8:30792187:T:C
Muscle Skeletal	sqtl	9.3e-12	+0.83	8:30812874:G:T
Heart Atrial Appendage	sqtl	1.1e-08	+0.98	8:30774030:G:T
Testis	eqtl	1.8e-06	-0.19	8:30789727:A:C
Muscle Skeletal	eqtl	5.0e-05	-0.21	8:30954077:A:T
Artery Tibial	eqtl	1.8e-04	-0.10	8:30788444:T:C
Brain Cerebellum	eqtl	2.7e-04	+0.29	8:30808416:G:C
Esophagus Muscularis	eqtl	2.8e-04	-0.11	8:30790156:AT:A
Pituitary	eqtl	1.3e-03	-0.23	8:30833724:G:T
Thyroid	eqtl	1.4e-03	-0.09	8:30793690:A:T
Brain Cortex	eqtl	3.8e-03	+0.23	8:30808416:G:C
Skin Not Sun Exposed Suprapubic	eqtl	4.2e-03	-0.13	8:30793690:A:T
Brain Nucleus accumbens basal ganglia	sqtl	4.6e-03	+1.05	8:30774030:G:T
Skin Sun Exposed Lower leg	eqtl	5.4e-03	-0.18	8:30950540:C:T
Artery Aorta	eqtl	7.1e-03	+0.30	8:31010002:C:T
Stomach	eqtl	8.1e-03	-0.16	8:30833724:G:T
Cells Cultured fibroblasts	eqtl	1.5e-02	-0.14	8:31608180:G:A
Esophagus Gastroesophageal Junction	eqtl	1.7e-02	-0.15	8:30778624:T:C
Esophagus Mucosa	eqtl	1.8e-02	-0.16	8:30784432:T:G

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
92637	17.8412	1785
92638	1.1885	726
92636	0.7682	348
92639	0.3357	155

Top tissues by expression

showing 100 of 301 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
pons	UBERON:0000988	99.65	gold quality
superior vestibular nucleus	UBERON:0007227	99.60	gold quality
subthalamic nucleus	UBERON:0001906	99.57	gold quality
cranial nerve II	UBERON:0000941	99.55	gold quality
dorsal plus ventral thalamus	UBERON:0001897	99.55	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.55	gold quality
postcentral gyrus	UBERON:0002581	99.54	gold quality
lateral globus pallidus	UBERON:0002476	99.52	gold quality
medulla oblongata	UBERON:0001896	99.51	gold quality
adult organism	UBERON:0007023	99.45	gold quality
bronchial epithelial cell	CL:0002328	99.44	gold quality
jejunal mucosa	UBERON:0000399	99.43	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.43	gold quality
parietal lobe	UBERON:0001872	99.41	gold quality
CA1 field of hippocampus	UBERON:0003881	99.41	gold quality
substantia nigra pars compacta	UBERON:0001965	99.40	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.40	gold quality
inferior vagus X ganglion	UBERON:0005363	99.35	gold quality
lower lobe of lung	UBERON:0008949	99.34	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	99.31	gold quality
orbitofrontal cortex	UBERON:0004167	99.27	gold quality
cerebellar vermis	UBERON:0004720	99.26	gold quality
entorhinal cortex	UBERON:0002728	99.23	gold quality
colonic mucosa	UBERON:0000317	99.22	gold quality
corpus epididymis	UBERON:0004359	99.22	gold quality
trigeminal ganglion	UBERON:0001675	99.21	gold quality
palpebral conjunctiva	UBERON:0001812	99.20	gold quality
cauda epididymis	UBERON:0004360	99.20	gold quality
Brodmann (1909) area 46	UBERON:0006483	99.20	gold quality
superior frontal gyrus	UBERON:0002661	99.19	gold quality
caput epididymis	UBERON:0004358	99.18	gold quality
jejunum	UBERON:0002115	99.15	gold quality
Ammon’s horn	UBERON:0001954	99.14	gold quality
tibia	UBERON:0000979	99.10	gold quality
epithelium of bronchus	UBERON:0002031	99.10	gold quality
bronchus	UBERON:0002185	99.08	gold quality
ventral tegmental area	UBERON:0002691	99.08	gold quality
temporal lobe	UBERON:0001871	99.06	gold quality
renal medulla	UBERON:0000362	99.03	gold quality
midbrain	UBERON:0001891	99.03	gold quality
inferior olivary complex	UBERON:0002127	99.02	gold quality
substantia nigra	UBERON:0002038	99.00	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.99	gold quality
amygdala	UBERON:0001876	98.96	gold quality
olfactory bulb	UBERON:0002264	98.94	gold quality
hypothalamus	UBERON:0001898	98.90	gold quality
spinal cord	UBERON:0002240	98.89	gold quality
urethra	UBERON:0000057	98.88	gold quality
eye	UBERON:0000970	98.88	gold quality
dorsal root ganglion	UBERON:0000044	98.85	gold quality
globus pallidus	UBERON:0001875	98.84	gold quality
type B pancreatic cell	CL:0000169	98.83	gold quality
esophagus squamous epithelium	UBERON:0006920	98.83	gold quality
body of tongue	UBERON:0011876	98.82	gold quality
decidua	UBERON:0002450	98.80	gold quality
middle frontal gyrus	UBERON:0002702	98.80	gold quality
paraflocculus	UBERON:0005351	98.80	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.80	gold quality
heart right ventricle	UBERON:0002080	98.79	gold quality
ventricular zone	UBERON:0003053	98.78	gold quality
cerebral cortex	UBERON:0000956	98.77	gold quality
penis	UBERON:0000989	98.77	gold quality
telencephalon	UBERON:0001893	98.75	gold quality
metanephric glomerulus	UBERON:0004736	98.75	gold quality
renal glomerulus	UBERON:0000074	98.74	gold quality
epithelium of esophagus	UBERON:0001976	98.74	gold quality
blood vessel layer	UBERON:0004797	98.72	gold quality
pharyngeal mucosa	UBERON:0000355	98.71	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.71	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.71	gold quality
seminal vesicle	UBERON:0000998	98.69	gold quality
cardia of stomach	UBERON:0001162	98.69	gold quality
prefrontal cortex	UBERON:0000451	98.67	gold quality
mammary duct	UBERON:0001765	98.67	gold quality
synovial joint	UBERON:0002217	98.67	gold quality
medial globus pallidus	UBERON:0002477	98.66	gold quality
frontal cortex	UBERON:0001870	98.64	gold quality
myocardium	UBERON:0002349	98.64	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.64	gold quality
frontal lobe	UBERON:0016525	98.64	gold quality
neocortex	UBERON:0001950	98.62	gold quality
caudate nucleus	UBERON:0001873	98.61	gold quality
putamen	UBERON:0001874	98.61	gold quality
cingulate cortex	UBERON:0003027	98.58	gold quality
occipital lobe	UBERON:0002021	98.57	gold quality
anterior cingulate cortex	UBERON:0009835	98.57	gold quality
endothelial cell	CL:0000115	98.56	gold quality
mammalian vulva	UBERON:0000997	98.55	gold quality
parotid gland	UBERON:0001831	98.53	gold quality
forebrain	UBERON:0001890	98.53	gold quality
nucleus accumbens	UBERON:0001882	98.51	gold quality
metanephros	UBERON:0000081	98.49	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.49	gold quality
central nervous system	UBERON:0001017	98.47	gold quality
frontal pole	UBERON:0002795	98.47	gold quality
brain	UBERON:0000955	98.46	gold quality
germinal epithelium of ovary	UBERON:0001304	98.46	gold quality
skin of hip	UBERON:0001554	98.46	gold quality
visceral pleura	UBERON:0002401	98.44	gold quality
kidney epithelium	UBERON:0004819	98.44	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-100618	no	232.24
E-CURD-89	no	67.00
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Ovary	tissue	189.9	high
Hippocampus	tissue	167.2	high
Frontal cortex	tissue	154.2
Caudate putamen	tissue	141.0
Locus coeruleus	tissue	140.0
Nucleus accumbens	tissue	123.9
Kidney	tissue	123.0	high
Thyroid gland	tissue	118.6	high
Tongue	tissue	114.8
Smooth muscle	tissue	114.1	medium
Postcentral gyrus	tissue	112.0
Liver	tissue	110.7	medium
Epididymis	tissue	110.6	medium
Thalamus	tissue	107.9
Midbrain	tissue	105.7
Spinal cord	tissue	104.7
Endometrium 1	tissue	102.1	medium
Cerebral cortex	tissue	101.9	high
Somatosensory cortex	tissue	101.9
Pons	tissue	101.8
Motor cortex	tissue	97.8
Superior colliculi	tissue	96.1
Prefrontal cortex	tissue	94.6
Hippocampal formation	tissue	94.5
Medulla oblongata	tissue	94.0
Skeletal muscle	tissue	93.9	low
Occipital cortex	tissue	93.8
Substantia nigra	tissue	93.5
Corpus callosum	tissue	93.4
Entorhinal cortex	tissue	91.3
Esophagus	tissue	89.3	high
Temporal cortex	tissue	89.3
Parathyroid gland	tissue	87.6	medium
Retrosplenial and cingulate cortex	tissue	86.9
Heart muscle	tissue	85.7	low
Placenta	tissue	85.5	medium
Lung	tissue	85.3	medium
Adipose tissue	tissue	84.2	medium
Retrosplenial cortex	tissue	84.2
Choroid plexus	tissue	83.6
Putamen	tissue	82.7
Fallopian tube	tissue	82.5	medium
Seminal vesicle	tissue	82.0	medium
Small intestine	tissue	81.9	high
Periaqueductal gray	tissue	81.9
Olfactory bulb	tissue	81.8
Hypothalamus	tissue	81.5
Septum	tissue	79.8
Amygdala	tissue	79.3
Cervix	tissue	78.8	medium
Ventral forebrain	tissue	77.7
Insular cortex	tissue	77.3
Colon	tissue	74.2	high
Retina	tissue	72.1
Urinary bladder	tissue	71.7	medium
Rectum	tissue	71.4	high
Pancreas	tissue	71.4	medium
Cerebellum	tissue	71.2	high
Prostate	tissue	70.2	medium
Gallbladder	tissue	69.5	high

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Posterior thalamic nucleus (207.7), Inferior olive (192.4), Dorsal funiculus (white matter) (189.7), Cervical spinal cord, ventral horn (186.8), Corpus callosum, genu (white matter) (186.1).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets:

Target	Regulation
CCL2	Repression
CCL5	Repression
IL6	Repression
RELA	Repression

miRNA regulators (miRDB)

Targeting PPP2CB by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 63 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-425-5P	99.59	67.67	900
HSA-MIR-549A-3P	99.54	68.17	825
HSA-MIR-12132	99.47	68.90	1341
HSA-MIR-513A-3P	99.39	70.63	3620

Functional genomics

gnomAD constraint: pLI 0.0283, LOEUF 0.741, missense Z 2.82 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000221138 splits into 4 regions with different missense tolerance; 1 is missense-constrained (≈5% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
8:30,786,238–30,793,926	56 / 92.0	0.61	no
8:30,793,927–30,793,966	1 / 18.1	0.06	yes (p 5.8e-05)
8:30,793,967–30,799,751	110 / 244.1	0.45	no
8:30,799,752–30,812,421	59 / 42.6	1.38	no

Literature-anchored findings (GeneRIF, showing 7)

• Results describe the cell cycle expression, subcellular distribution, and metabolic stability of protein phosphatase 2Abeta in comparison with 2Aalpha. (PMID:12370081)
• Claspin may be one of the phosphoproteins through which PP2A(Aalpha/Cbeta) affects Chk1 phosphorylation when ATR is activated by human immunodeficiency virus-1 Vpr. (PMID:17210576)
• These data strongly support a recent proposal that a segment at 8p21.3 contains crucial prostate cancer tumor suppressors. (PMID:18460741)
• PP2B and PP1alpha cooperatively disrupt 7SK snRNP to release P-TEFb for transcription in response to Ca2+ signaling. (PMID:18483222)
• The GAS41-PP2Cbeta complex dephosphorylates p53 at serine 366 and regulates its stability (PMID:21317290)
• Protein phosphatase 2A in the healthy and failing heart: New insights and therapeutic opportunities. (PMID:34902541)
• Protein phosphatase 2A and complement component 4 are linked to the protective effect of APOE varepsilon2 for Alzheimer’s disease. (PMID:35142023)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ppp2cb	ENSDARG00000099241
mus_musculus	Ppp2cb	ENSMUSG00000009630
rattus_norvegicus	Ppp2cb	ENSRNOG00000015182
drosophila_melanogaster	mts	FBGN0004177

Paralogs (12): PPP5C (ENSG00000011485), PPEF1 (ENSG00000086717), PPP3CB (ENSG00000107758), PPP2CA (ENSG00000113575), PPP6C (ENSG00000119414), PPP3CC (ENSG00000120910), PPP3CA (ENSG00000138814), PPP4C (ENSG00000149923), PPEF2 (ENSG00000156194), PPP1CA (ENSG00000172531), PPP1CC (ENSG00000186298), PPP1CB (ENSG00000213639)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1321161) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 3 distinct phenotype terms.

Mouse phenotype (MP)	Records
preweaning lethality, incomplete penetrance	1
increased cornea thickness	1
decreased total retina thickness	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Oryza sativa Indica Group	A2X2G3	100.0%	Diamond
Bos taurus	A6H772	100.0%	Diamond
Sus scrofa	P11493	100.0%	Diamond
Oryctolagus cuniculus	P11611	100.0%	Diamond
Xenopus laevis	P36874	100.0%	Diamond
Gallus gallus	P62207	100.0%	Diamond
Oryza sativa Japonica Group	Q0DBD3	100.0%	Diamond
Caenorhabditis elegans	Q27497	100.0%	Diamond
Xenopus tropicalis	Q5I085	100.0%	Diamond
Pongo abelii	Q5R6K8	100.0%	Diamond
Caenorhabditis briggsae	Q61JR3	100.0%	Diamond
Canis lupus familiaris	Q8MJ47	100.0%	Diamond
Paramecium tetraurelia	A0CNL9	99.4%	Diamond
Arabidopsis thaliana	Q9LHE7	99.0%	Diamond
Aspergillus nidulans FGSC A4	P20654	98.0%	Diamond
Lathyrus oleraceus	Q8LSN3	98.0%	Diamond
Neurospora crassa OR74A	Q9UW86	98.0%	Diamond
Brassica napus	P23777	97.2%	Diamond
Nicotiana tabacum	Q9XGH7	95.7%	Diamond
Medicago sativa	Q06009	95.5%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
PURG	protein-coding	29942
TEX15	protein-coding	56154
WRN	protein-coding	7486
SMIM18	protein-coding	100507341
GSR	protein-coding	2936
GTF2E2	protein-coding	2961
UBXN8	protein-coding	7993

Protein

Protein identifiers

Serine/threonine-protein phosphatase 2A catalytic subunit beta isoform — P62714 (reviewed: P62714)

All UniProt accessions (7): A0A140VJS0, E5RFI3, E5RHC1, E5RJX4, P62714, H0YBN9, H0YC23

UniProt curated annotations — full annotation on UniProt →

Function. Catalytic subunit of protein phosphatase 2A (PP2A), a serine/threonine phosphatase involved in the regulation of a wide variety of enzymes, signal transduction pathways, and cellular events. PP2A can modulate the activity of phosphorylase B kinase, casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase. Part of the striatin-interacting phosphatase and kinase (STRIPAK) complexes. STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways including Hippo, MAPK, nuclear receptor and cytoskeleton remodeling. Different types of STRIPAK complexes are involved in a variety of biological processes such as cell growth, differentiation, apoptosis, metabolism and immune regulation.

Subunit / interactions. PP2A consists of a common heterodimeric core enzyme (composed of a 36 kDa catalytic subunit (subunit C) and a 65 kDa constant regulatory subunit (PR65) (subunit A)) that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B’’/PR72/PR130/PR59 and R5/B’/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules. Binds PPME1. May indirectly interact with SGO1, most probably through regulatory B56 subunits. Interacts with CTTNBP2NL. Interacts with PTPA. Found in a complex with at least ARL2, PPP2CB, PPP2R1A, PPP2R2A, PPP2R5E and TBCD. Interacts with TBCD. Part of the core of STRIPAK complexes composed of PP2A catalytic and scaffolding subunits, the striatins (PP2A regulatory subunits), the striatin-associated proteins MOB4, STRIP1 and STRIP2, PDCD10 and members of the STE20 kinases, such as STK24 and STK26.

Subcellular location. Cytoplasm. Nucleus. Chromosome. Centromere. Cytoskeleton. Spindle pole.

Post-translational modifications. Reversibly methyl esterified on Leu-309 by leucine carboxyl methyltransferase 1 (LCMT1) and protein phosphatase methylesterase 1 (PPME1). Carboxyl methylation influences the affinity of the catalytic subunit for the different regulatory subunits, thereby modulating the PP2A holoenzyme’s substrate specificity, enzyme activity and cellular localization. Phosphorylation of either threonine (by autophosphorylation-activated protein kinase) or tyrosine results in inactivation of the phosphatase. Auto-dephosphorylation has been suggested as a mechanism for reactivation. May be monoubiquitinated by NOSIP.

Cofactor. Binds 2 manganese ions per subunit.

Similarity. Belongs to the PPP phosphatase family. PP-1 subfamily.

RefSeq proteins (1): NP_001009552* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004843	Calcineurin-like_PHP	Domain
IPR006186	Ser/Thr-sp_prot-phosphatase	Domain
IPR029052	Metallo-depent_PP-like	Homologous_superfamily
IPR047129	PPA2-like	Family

Pfam: PF00149

Catalyzed reactions (Rhea)

• O-phospho-L-seryl-[protein] + H2O = L-seryl-[protein] + phosphate (RHEA:20629)
• O-phospho-L-threonyl-[protein] + H2O = L-threonyl-[protein] + phosphate (RHEA:47004)

UniProt features (14 total): binding site 7, modified residue 2, mutagenesis site 2, chain 1, active site 1, sequence conflict 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P62714-F1	95.08	0.93

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IH approved · IF supported

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 (1)

Position	Role
118	proton donor

Ligand- & substrate-binding residues (7)

Position	Role
57	Mn(2+)
59	Mn(2+)
85	Mn(2+)
117	Mn(2+)
167	Mn(2+)
241	Mn(2+)

Post-translational modifications (2)

Type	Positions
Leucine methyl ester	309
Phosphotyrosine	307

Mutagenesis-validated functional residues (2)

Position	Phenotype
59	catalytically inactive. no effect on interaction with ppme1.
118	catalytically inactive. no effect on interaction with ppme1.

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 126; 15 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

showing 60 of 126 pathways:

ID	Pathway	Evidence
R-HSA-9833482	PKR-mediated signaling	curated
R-HSA-5467337	APC truncation mutants have impaired AXIN binding ⚕	—
R-HSA-5467340	AXIN missense mutants destabilize the destruction complex ⚕	—
R-HSA-5358747	CTNNB1 S33 mutants aren’t phosphorylated ⚕	—
R-HSA-5358749	CTNNB1 S37 mutants aren’t phosphorylated ⚕	—
R-HSA-5358751	CTNNB1 S45 mutants aren’t phosphorylated ⚕	—
R-HSA-5358752	CTNNB1 T41 mutants aren’t phosphorylated ⚕	—
R-HSA-1643685	Disease ⚕	—
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers ⚕	—
R-HSA-4839748	Signaling by AMER1 mutants ⚕	—
R-HSA-4839744	Signaling by APC mutants ⚕	—
R-HSA-4839735	Signaling by AXIN mutants ⚕	—
R-HSA-4839743	Signaling by CTNNB1 phospho-site mutants ⚕	—
R-HSA-5339716	Signaling by GSK3beta mutants ⚕	—
R-HSA-4791275	Signaling by WNT in cancer ⚕	—
R-HSA-5467348	Truncations of AMER1 destabilize the destruction complex ⚕	—
R-HSA-1280218	Adaptive Immune System	—
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	—
R-HSA-141424	Amplification of signal from the kinetochores	—
R-HSA-1169410	Antimicrobial mechanism of IFN-stimulated genes	—
R-HSA-196299	Beta-catenin phosphorylation cascade	—
R-HSA-1640170	Cell Cycle	—
R-HSA-69620	Cell Cycle Checkpoints	—
R-HSA-69278	Cell Cycle, Mitotic	—
R-HSA-389513	Co-inhibition by CTLA4	—
R-HSA-389356	Co-stimulation by CD28	—
R-HSA-69273	Cyclin A/B1/B2 associated events during G2/M transition	—
R-HSA-69231	Cyclin D associated events in G1	—
R-HSA-1280215	Cytokine Signaling in Immune system	—
R-HSA-180024	DARPP-32 events	—
R-HSA-195253	Degradation of beta-catenin by the destruction complex	—
R-HSA-4641262	Disassembly of the destruction complex and recruitment of AXIN to the membrane	—
R-HSA-113510	E2F mediated regulation of DNA replication	—
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation	—
R-HSA-198753	ERK/MAPK targets	—
R-HSA-202670	ERKs are inactivated	—
R-HSA-418594	G alpha (i) signalling events	—
R-HSA-69236	G1 Phase	—
R-HSA-69206	G1/S Transition	—
R-HSA-69275	G2/M Transition	—
R-HSA-388396	GPCR downstream signalling	—
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-212436	Generic Transcription Pathway	—
R-HSA-70326	Glucose metabolism	—
R-HSA-70171	Glycolysis	—
R-HSA-109582	Hemostasis	—
R-HSA-168256	Immune System	—
R-HSA-113501	Inhibition of replication initiation of damaged DNA by RB1/E2F1	—
R-HSA-168249	Innate Immune System	—
R-HSA-163685	Integration of energy metabolism	—
R-HSA-913531	Interferon Signaling	—
R-HSA-448424	Interleukin-17 signaling	—
R-HSA-9006925	Intracellular signaling by second messengers	—
R-HSA-68886	M Phase	—
R-HSA-450294	MAP kinase activation	—
R-HSA-5683057	MAPK family signaling cascades	—
R-HSA-450282	MAPK targets/ Nuclear events mediated by MAP kinases	—
R-HSA-5684996	MAPK1/MAPK3 signaling	—
R-HSA-2465910	MASTL Facilitates Mitotic Progression	—
R-HSA-1430728	Metabolism	—

MSigDB gene sets: 329 (showing top): REACTOME_INHIBITION_OF_REPLICATION_INITIATION_OF_DAMAGED_DNA_BY_RB1_E2F1, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, REACTOME_SIGNALING_BY_FGFR, CHUANG_OXIDATIVE_STRESS_RESPONSE_UP, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, KEGG_TIGHT_JUNCTION

GO Biological Process (9): mitotic cell cycle (GO:0000278), protein dephosphorylation (GO:0006470), response to lead ion (GO:0010288), negative regulation of gene expression (GO:0010629), negative regulation of tumor necrosis factor-mediated signaling pathway (GO:0010804), regulation of microtubule polymerization (GO:0031113), negative regulation of canonical NF-kappaB signal transduction (GO:0043124), negative regulation of Ras protein signal transduction (GO:0046580), regulation of neurofibrillary tangle assembly (GO:1902996)

GO Molecular Function (7): protein serine/threonine phosphatase activity (GO:0004722), transmembrane transporter binding (GO:0044325), metal ion binding (GO:0046872), tau protein binding (GO:0048156), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (8): protein phosphatase type 2A complex (GO:0000159), chromosome, centromeric region (GO:0000775), spindle pole (GO:0000922), nucleoplasm (GO:0005654), cytosol (GO:0005829), FAR/SIP/STRIPAK complex (GO:0090443), nucleus (GO:0005634), cytoplasm (GO:0005737)

Reactome top-level categories

21 top-level categories:

Category	Pathways
Signaling by CTNNB1 phospho-site mutants	3
Regulation of T cell activation by CD28 family	2
E2F mediated regulation of DNA replication	1
Negative regulation of FGFR1 signaling	1
Negative regulation of FGFR2 signaling	1
Negative regulation of FGFR3 signaling	1
Negative regulation of FGFR4 signaling	1
Amplification of signal from the kinetochores	1
Integration of energy metabolism	1
Opioid Signalling	1
Signaling by WNT	1
Degradation of beta-catenin by the destruction complex	1
Nuclear Events (kinase and transcription factor activation)	1
MAPK targets/ Nuclear events mediated by MAP kinases	1
ERK/MAPK targets	1
Mitotic Prophase	1
Mitotic Anaphase	1
Mitotic Prometaphase	1
Platelet homeostasis	1
TCF dependent signaling in response to WNT	1
Signaling by WNT in cancer	1

GO top-level categories

40 GO namespaces:

Category	Terms
cellular anatomical structure	4
cell cycle	1
mitotic nuclear division	1
dephosphorylation	1
protein modification process	1
response to metal ion	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
negative regulation of cytokine-mediated signaling pathway	1
regulation of tumor necrosis factor-mediated signaling pathway	1
tumor necrosis factor-mediated signaling pathway	1
regulation of microtubule polymerization or depolymerization	1
regulation of protein polymerization	1
microtubule polymerization	1
regulation of supramolecular fiber organization	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
negative regulation of intracellular signal transduction	1
Ras protein signal transduction	1
regulation of Ras protein signal transduction	1
negative regulation of small GTPase mediated signal transduction	1
regulation of inclusion body assembly	1
neurofibrillary tangle assembly	1
phosphoprotein phosphatase activity	1
protein binding	1
cation binding	1
cytoskeletal protein binding	1
phosphatase activity	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
protein serine/threonine phosphatase complex	1
chromosomal region	1
spindle	1
nuclear lumen	1
cytoplasm	1
protein-containing complex	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 5 of 24 annotations. The rest are phylogenetic / computational / electronic (IEA).

5 experimentally-supported GO terms:

GO term	NS	Evidence
negative regulation of canonical NF-kappaB signal transduction	BP	genetic interaction
negative regulation of gene expression	BP	mutant phenotype
negative regulation of tumor necrosis factor-mediated signaling pathway	BP	genetic interaction
FAR/SIP/STRIPAK complex	CC	direct assay
nucleoplasm	CC	direct assay

Protein interactions and networks

IntAct

Human interaction partners of PPP2CB in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 56 partners by confidence:

Partner	Interaction type	MIscore	Records
PPP2R1A	direct interaction	0.940	2
IGBP1	physical association	0.880	1
STRIP1	physical association	0.870	2
STRN	association	0.790	4
CEP43	association	0.730	1
AXIN2	physical association	0.650	4
TIPRL	direct interaction	0.590	1
FMR1	physical association	0.560	3
SMP1	physical association	0.560	3
IFT81	physical association	0.400	1
STRIP2	physical association	0.400	1
ACP5	physical association	0.370	1
AURKA	physical association	0.370	1
BUB1	physical association	0.370	1
C22orf39	physical association	0.370	1
DOCK7	physical association	0.370	1
DYNLT2B	physical association	0.370	1
EGFR	physical association	0.370	1
GSTA1	physical association	0.370	1
HK3	physical association	0.370	1
KRAS	physical association	0.370	1
MAK	physical association	0.370	1
MLH1	physical association	0.370	1
MLH3	physical association	0.370	1
NRAS	physical association	0.370	1
PDGFRL	physical association	0.370	1
PLXNA3	physical association	0.370	1
PMS2	physical association	0.370	1
PTPRJ	physical association	0.370	1
RAF1	physical association	0.370	1

BioGRID (554 interactions; top human partners by supporting records): PPP2R1A (Affinity Capture-MS; 22 records), PPP2R2A (Affinity Capture-MS; 12 records), PPP2R1B (Affinity Capture-MS; 10 records), PPP2R2D (Affinity Capture-MS; 10 records), PPP2R5D (Affinity Capture-MS; 10 records), STRN3 (Affinity Capture-MS; 9 records), IGBP1 (Co-fractionation; 8 records), PPME1 (Affinity Capture-MS; 8 records), PPP2CA (Co-fractionation; 8 records), STRIP1 (Affinity Capture-MS; 8 records), STRN (Affinity Capture-MS; 8 records), ANKLE2 (Affinity Capture-MS; 7 records), CTTNBP2NL (Affinity Capture-MS; 7 records), FGFR1OP (Affinity Capture-MS; 7 records), MOB4 (Affinity Capture-MS; 7 records)

SIGNOR signaling

showing 35 of 51 signaling interactions:

A	Effect	B	Mechanism
PPP2R1A	up-regulates	PPP2CB	binding
PPP2CB	down-regulates	MYC	dephosphorylation
PLAAT3	down-regulates	PPP2CB
PPP2CB	down-regulates	RALA	dephosphorylation
SET	down-regulates	PPP2CB	binding
TLX1	“down-regulates activity”	PPP2CB	binding
PPP2CB	“down-regulates activity”	CHEK1	dephosphorylation
PPP2CB	“down-regulates activity”	IKBKB	dephosphorylation
PPP2CB	“up-regulates activity”	CHEK2	dephosphorylation
PPP2CB	“up-regulates quantity by stabilization”	TP53	dephosphorylation
PPP2CB	unknown	KRT8	dephosphorylation
PPP2CB	“up-regulates activity”	BCL2	dephosphorylation
PPP2CB	“down-regulates activity”	ELF1	dephosphorylation
PPP2CB	“down-regulates activity”	SNCA	dephosphorylation
PPP2CB	“down-regulates activity”	ATM	dephosphorylation
PPP2CB	“up-regulates activity”	HDAC7	dephosphorylation
PPP2CB	“down-regulates activity”	CARD11	dephosphorylation
PPP2CB	“down-regulates activity”	AKT3	dephosphorylation
PPP2CB	“down-regulates activity”	AKT	dephosphorylation
PPP2CB	down-regulates	AKT1	dephosphorylation
AMBRA1	“up-regulates activity”	PPP2CB	binding
PPP2CB	down-regulates	AKT	dephosphorylation
PPP2CB	down-regulates	AKT2	dephosphorylation
PPP2CB	up-regulates	MDM2	dephosphorylation
PPP2CB	“up-regulates activity”	MDM2	dephosphorylation
PPP2CB	“down-regulates activity”	PRKCD	dephosphorylation
PPP2CB	“down-regulates activity”	TRAF2	dephosphorylation
STRN4	“up-regulates activity”	PPP2CB	binding
STRN	“up-regulates activity”	PPP2CB	binding
PPP2CB	“down-regulates activity”	PRKCB	dephosphorylation
PPP2CB	“down-regulates activity”	MAPK1	dephosphorylation
PPP2CB	“down-regulates activity”	PAK1	dephosphorylation
PPP2CB	unknown	PPP1R1A	dephosphorylation
PPME1	“down-regulates activity”	PPP2CB	demethylation
LCMT1	“up-regulates activity”	PPP2CB	methylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 56 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
RAF activation	6	46.9×	1e-06
Signaling by high-kinase activity BRAF mutants	5	36.9×	4e-05
MAP2K and MAPK activation	5	33.2×	4e-05
Signaling by RAF1 mutants	5	32.4×	4e-05
Negative regulation of MAPK pathway	5	30.9×	4e-05
Signaling by moderate kinase activity BRAF mutants	5	29.5×	4e-05
Paradoxical activation of RAF signaling by kinase inactive BRAF	5	29.5×	4e-05
Signaling downstream of RAS mutants	5	29.5×	4e-05

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of MAPK cascade	6	9.1×	9e-03

Disease & clinical

Genetic variants

Variant evidence for PPP2CB: 35 ClinVar records (0 pathogenic / likely pathogenic); 2 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	26
Likely benign	2
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 46 predictions of 540):

Position(s)	Effect	Δscore	Sites
8:30791316–30791317	acceptor_loss	1.0000	5
8:30793915–30793916	donor_loss	1.0000	4
8:30794079–30794080	acceptor_loss	1.0000	6
8:30794084–30794085	acceptor_gain	1.0000	2
8:30797579–30797580	donor_loss	1.0000	5
8:30797755–30797756	acceptor_loss	1.0000	4
8:30799544–30799545	donor_loss	1.0000	5
8:30799756–30799757	acceptor_loss	1.0000	6
8:30812318–30812319	donor_loss	1.0000	4
8:30791195–30791196	donor_loss	0.9900	5

AlphaMissense

1,443 missense substitutions predicted likely pathogenic (of 2,021 scored), across 279 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M245	9	0.896	0.987
D88	8	1.000	1.000
H118	8	1.000	1.000
D57	8	0.999	1.000
H59	8	0.999	1.000
D64	8	0.999	0.999
D85	8	0.999	1.000
D202	8	0.999	1.000
H241	8	0.999	1.000
N117	8	0.998	1.000
H167	8	0.998	1.000
N271	8	0.998	1.000
D197	8	0.997	1.000
F260	8	0.996	1.000
F129	8	0.994	1.000
F82	8	0.992	0.999
D151	8	0.992	0.998
D131	8	0.991	0.999
F150	8	0.991	0.999
F308	8	0.990	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	3.75e-09
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.000162

Disease associations

OMIM: gene MIM:176916 | disease phenotypes:

GWAS associations

2 associations:

Study	Trait	p-value
GCST012489_87	Heel bone mineral density x serum urate levels interaction	1e-9
GCST003518_15	Daytime sleep phenotypes	2e-6

EFO canonical traits (from GWAS)

3 canonical traits:

EFO ID	Trait name
EFO:0007828	daytime rest measurement
EFO:0004531	urate measurement
EFO:0009270	heel bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2435 (SINGLE PROTEIN)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the PPP2CB protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

1 curated-mechanism drugs:

Drug	Modality	Max phase
LB-100	Small molecule	2

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

63 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression, affects reaction, decreases phosphorylation (+2 more)	5
Tobacco Smoke Pollution	affects expression, increases expression	3
bisphenol A	affects expression, decreases expression	2
Arsenic Trioxide	increases expression	2
Air Pollutants	increases expression, decreases expression, increases abundance	2
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
Smoke	decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
echimidine	increases expression, increases metabolic processing	1
lasiocarpine	increases expression, increases metabolic processing	1
pirinixic acid	affects binding, decreases expression, increases activity	1
riddelliine	increases expression, increases metabolic processing	1
tetrahydropalmatine	decreases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	increases expression	1
bufalin	decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
potassium chromate(VI)	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	increases expression	1
obeticholic acid	increases expression	1
morroniside	affects binding, decreases activity, decreases methylation, decreases reaction, increases phosphorylation (+1 more)	1
bisphenol B	increases expression	1
abrine	increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Air Pollutants, Occupational	decreases expression	1
Atrazine	increases expression	1
Chelating Agents	affects binding, increases expression	1
Cocaine	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4119016	Binding	Binding affinity to PPP2CB in human NCI-H358 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — *Bioorg Med Chem*

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D1PZ	Abcam K-562 PPP2CB KO	Cancer cell line	Female
CVCL_D2LL	Abcam Raji PPP2CB KO	Cancer cell line	Male
CVCL_TF90	HAP1 PPP2CB (-) 1	Cancer cell line	Male
CVCL_TF91	HAP1 PPP2CB (-) 2	Cancer cell line	Male
CVCL_TF92	HAP1 PPP2CB (-) 3	Cancer cell line	Male
CVCL_WQ36	Abcam Jurkat PPP2CB KO	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.