PPP1R2

Summary

PPP1R2 (protein phosphatase 1 regulatory inhibitor subunit 2, HGNC:9288) is a protein-coding gene on chromosome 3q29, encoding Protein phosphatase inhibitor 2 (P41236). Inhibitor of protein-phosphatase 1. It is a selective cancer dependency (DepMap: 86.6% of cell lines).

Protein phosphatase-1 (PP1) is one of the main eukaryotic serine/threonine phosphatases. The protein encoded by this gene binds to the catalytic subunit of PP1, strongly inhibiting its activity. Ten related pseudogenes have been found throughout the human genome. Several splice variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5504 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 28 total
• Cancer dependency (DepMap): dependent in 86.6% of screened cell lines
• MANE Select transcript: NM_006241

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9288
Approved symbol	PPP1R2
Name	protein phosphatase 1 regulatory inhibitor subunit 2
Location	3q29
Locus type	gene with protein product
Status	Approved
Aliases	IPP2, PPP1R2A
Ensembl gene	ENSG00000184203
Ensembl biotype	protein_coding
OMIM	601792
Entrez	5504

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron

ENST00000413183, ENST00000418939, ENST00000438848, ENST00000460437, ENST00000462906, ENST00000618156, ENST00000625807, ENST00000861021, ENST00000861022

RefSeq mRNA: 4 — MANE Select: NM_006241 NM_001291504, NM_001291505, NM_001316325, NM_006241

CCDS: CCDS3309

Canonical transcript exons

ENST00000618156 — 6 exons

Exon	Start	End
ENSE00001292604	195529794	195529901
ENSE00003513311	195519018	195519185
ENSE00003651181	195524819	195524896
ENSE00003666361	195523692	195523786
ENSE00003714138	195514428	195516942
ENSE00003731662	195542904	195543325

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 97.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 59.7384 / max 616.2442, expressed in 1825 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
46276	49.7478	1823
46277	3.7233	1565
46273	2.6353	1229
46275	2.0222	1220
46274	1.4886	868
46272	0.1212	38

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
biceps brachii	UBERON:0001507	97.52	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.16	gold quality
adult organism	UBERON:0007023	97.12	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.07	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.72	gold quality
sperm	CL:0000019	96.63	gold quality
jejunal mucosa	UBERON:0000399	96.19	gold quality
jejunum	UBERON:0002115	95.64	gold quality
gastrocnemius	UBERON:0001388	95.58	gold quality
male germ cell	CL:0000015	95.44	gold quality
muscle of leg	UBERON:0001383	95.31	gold quality
bone marrow	UBERON:0002371	94.98	gold quality
muscle organ	UBERON:0001630	94.79	gold quality
vastus lateralis	UBERON:0001379	94.76	gold quality
bone marrow cell	CL:0002092	94.72	gold quality
lymph node	UBERON:0000029	94.67	gold quality
oral cavity	UBERON:0000167	94.56	gold quality
islet of Langerhans	UBERON:0000006	94.36	gold quality
gall bladder	UBERON:0002110	94.32	gold quality
leukocyte	CL:0000738	94.20	gold quality
monocyte	CL:0000576	94.18	gold quality
blood	UBERON:0000178	94.16	gold quality
mononuclear cell	CL:0000842	94.15	gold quality
calcaneal tendon	UBERON:0003701	93.92	gold quality
left testis	UBERON:0004533	93.88	gold quality
right testis	UBERON:0004534	93.87	gold quality
buccal mucosa cell	CL:0002336	93.74	gold quality
adrenal tissue	UBERON:0018303	93.66	gold quality
quadriceps femoris	UBERON:0001377	93.28	gold quality
lower esophagus mucosa	UBERON:0035834	93.24	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	43.99
E-MTAB-6701	yes	14.99
E-HCAD-1	yes	9.76
E-HCAD-13	yes	7.43
E-GEOD-130148	yes	5.51
E-HCAD-29	no	1622.78
E-CURD-89	no	701.56
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

178 targeting PPP1R2, 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-5011-5P	100.00	83.46	5820
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-1277-5P	100.00	73.95	5056
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-1252-5P	100.00	69.80	2774
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-12136	99.98	72.81	5713
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-3148	99.97	75.06	6478

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 86.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 11)

• Inh2 can enhance the kinase activity of the Nek2.PP1C complex via inhibition of phosphatase activity to initiate centrosome separation (PMID:12221103)
• PP1C and Inh2 bind to KPI2 to form a regulatory complex that is localized to membranes (PMID:12393858)
• first demonstration that glycogen synthase kinase-3beta associates with PP1C/I-2 complex and phosphorylates I-2 at T72 in intact cells (PMID:12761178)
• Studies in hamster indicate that modulation of type 1 protein phosphatase (PP1) activity by inhibitor-2 (INH-2) provides a potential new treatment for heart failure without activating protein kinase A (PKA) signaling. (PMID:16627625)
• These results indicate that the protein phosphatase-1/inhibitor-2 complex differentially regulates GSK3 dephosphorylation induced by KCl and that GSK3 activity regulates SERCA2 levels. (PMID:16987514)
• Conserved together throughout eukaryotic evolution, I-2, PP1 and Aurora B function interdependently during mitosis. (PMID:18716057)
• Results suggest that phosphatase inhibitor 2 localizes to the primary cilium of human retinal epithelial cells where it affects both Ser/Thr phosphorylation and is required for full tubulin acetylation. (PMID:19036150)
• Pin1 and phosphatase inhibitor-2 are conserved among eukaryotes from yeast to humans and make an ancient partnership that provides a means for regulating Pin1 specificity and function. (PMID:21714498)
• The potential phosphosites in PPP1R2 are substituted by non-phosphorylable residues, T73P and S87R, in PPP1R2P3. (PMID:23506001)
• The results show that contrary to initial observations PPP1R2-related pseudogenes are not simple bystanders of the evolutionary process but may rather be at the origin of genes with novel functions. (PMID:24195737)
• The PP1 regulator PPP1R2 coordinately regulates AURKA and PP1 to control centrosome phosphorylation and maintain central spindle architecture. (PMID:33238888)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ppp1r2	ENSDARG00000054007
mus_musculus	Ppp1r2	ENSMUSG00000047714
mus_musculus	Ppp1r2-ps1	ENSMUSG00000094843
mus_musculus	Ppp1r2-ps6	ENSMUSG00000095869
mus_musculus	Ppp1r2-ps5	ENSMUSG00000121976
rattus_norvegicus	Ppp1r2	ENSRNOG00000001733

Paralogs (2): PPP1R2C (ENSG00000102055), PPP1R2B (ENSG00000231989)

Protein

Protein identifiers

Protein phosphatase inhibitor 2 — P41236 (reviewed: P41236)

All UniProt accessions (4): E7EMN6, E7EUI7, H7C416, P41236

UniProt curated annotations — full annotation on UniProt →

Function. Inhibitor of protein-phosphatase 1.

Subunit / interactions. Heterodimer with PP1.

Post-translational modifications. Phosphorylation on Thr-73 by GSK3 activates PP1 by dissociating the PP1-PPP1R2 complex. Phosphorylation on Ser-44 by ATM activates PP1 by dissociating the PP1-PPP1R2 complex.

Similarity. Belongs to the protein phosphatase inhibitor 2 family.

RefSeq proteins (4): NP_001278433, NP_001278434, NP_001303254, NP_006232* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007062	PPI-2	Family

Pfam: PF04979

UniProt features (24 total): modified residue 10, compositionally biased region 6, region of interest 6, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P41236-F1	68.84	0.19

Functional residue map

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

Post-translational modifications (10): 2, 44, 73, 87, 89, 92, 121, 122, 127, 130

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 184 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, HORIUCHI_WTAP_TARGETS_DN, MOOTHA_GLYCOGEN_METABOLISM, FAELT_B_CLL_WITH_VH_REARRANGEMENTS_DN, BROWNE_HCMV_INFECTION_16HR_UP, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, JIANG_TIP30_TARGETS_UP, ICHIBA_GRAFT_VERSUS_HOST_DISEASE_35D_DN, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, SCHLOSSER_SERUM_RESPONSE_DN, NADLER_HYPERGLYCEMIA_AT_OBESITY, CAIRO_HEPATOBLASTOMA_UP, PETROVA_ENDOTHELIUM_LYMPHATIC_VS_BLOOD_UP, SHAFFER_IRF4_TARGETS_IN_ACTIVATED_DENDRITIC_CELL

GO Biological Process (4): glycogen metabolic process (GO:0005977), generation of precursor metabolites and energy (GO:0006091), regulation of signal transduction (GO:0009966), intracellular signal transduction (GO:0035556)

GO Molecular Function (4): protein phosphatase inhibitor activity (GO:0004864), protein serine/threonine phosphatase inhibitor activity (GO:0004865), molecular function inhibitor activity (GO:0140678), protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signal transduction	2
energy reserve metabolic process	1
glucan metabolic process	1
metabolic process	1
regulation of cell communication	1
regulation of signaling	1
regulation of response to stimulus	1
intracellular anatomical structure	1
phosphoprotein phosphatase activity	1
phosphatase inhibitor activity	1
protein phosphatase regulator activity	1
protein serine/threonine phosphatase activity	1
protein phosphatase inhibitor activity	1
molecular function regulator activity	1
binding	1

Protein interactions and networks

STRING

562 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPP1R2	PPP1R1A	Q13522	887
PPP1R2	PPP1CA	P08129	808
PPP1R2	PPP1CB	P37140	777
PPP1R2	PPP1CC	P36873	776
PPP1R2	LMTK2	Q8IWU2	749
PPP1R2	PPP2CA	P05323	630
PPP1R2	PPP1R3A	Q16821	608
PPP1R2	PPP1R7	Q15435	581
PPP1R2	PPP1R11	O60927	556
PPP1R2	PPP1R12A	O14974	537
PPP1R2	GYS1	P13807	497
PPP1R2	WDR82	Q6UXN9	490
PPP1R2	PPP3CB	P16298	477
PPP1R2	EPS15	P42566	463
PPP1R2	PPP3CA	Q08209	456

IntAct

66 interactions, top by confidence:

A	B	Type	Score
GSK3B	AXIN1	psi-mi:“MI:0914”(association)	0.980
PPP1CA	PPP1R2	psi-mi:“MI:0407”(direct interaction)	0.950
PPP1CA	PPP1R2	psi-mi:“MI:0915”(physical association)	0.950
PPP1R2	PPP1CA	psi-mi:“MI:0915”(physical association)	0.950
PPP1R2	PPP1CC	psi-mi:“MI:0407”(direct interaction)	0.900
PPP1R2	PPP1CC	psi-mi:“MI:0914”(association)	0.900
PPP1CC	PPP1R2	psi-mi:“MI:0914”(association)	0.900
GSK3A	AXIN1	psi-mi:“MI:0914”(association)	0.800
PPP1CB	CCDC85C	psi-mi:“MI:0914”(association)	0.750
PPP1CB	CCDC85C	psi-mi:“MI:2364”(proximity)	0.750
PPP1CC	CCDC85C	psi-mi:“MI:0914”(association)	0.740
PPP1CC	CCDC85C	psi-mi:“MI:2364”(proximity)	0.740
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PPP1R2	LMTK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.680
PPP1R2	LMTK2	psi-mi:“MI:0915”(physical association)	0.680
PPP1CA	CCDC85C	psi-mi:“MI:0914”(association)	0.670

BioGRID (108): PPP1R2 (Affinity Capture-MS), PPP1R2 (Affinity Capture-MS), PPP1R2 (Affinity Capture-MS), PPP1R2 (Affinity Capture-MS), PPP1R11 (Co-fractionation), PPP1R2 (Co-fractionation), PPP1R2 (Co-fractionation), PPP1R2 (Co-fractionation), PPP1R2 (Co-fractionation), PPP1R2 (Co-fractionation), PPP1R2 (Co-fractionation), PPP1R2 (Co-fractionation), PPP1R2 (Co-fractionation), SULT1C3 (Co-fractionation), PPP1R2 (Proximity Label-MS)

ESM2 similar proteins: A2VDK6, B5X3I1, O08585, O43290, O88271, P04973, P04975, P08081, P08082, P09496, P09497, P09741, P13805, P41236, P50751, P50753, Q02614, Q0VFP5, Q2QY04, Q3U155, Q40554, Q5BK07, Q5EA95, Q5I0B5, Q5PQS7, Q5RGJ6, Q5XIW8, Q5ZIH9, Q5ZK95, Q6INR1, Q6IRU5, Q6NUB2, Q6NXS1, Q6PII3, Q75QI0, Q75UQ2, Q7SXU0, Q8BH43, Q8LDQ4, Q8R1N0

Diamond homologs: O14990, P11845, P41236, P50411, Q3SZX2, Q4R615, Q6NXS1, Q96PQ5, Q9DCL8

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
ATM	down-regulates	PPP1R2	phosphorylation
PPP1R2	down-regulates	PPP1CA	binding
PPP1R2	down-regulates	PP1	binding
CSNK2A1	up-regulates	PPP1R2	phosphorylation
CDK5	unknown	PPP1R2	phosphorylation
CSNK2A1	“up-regulates activity”	PPP1R2	phosphorylation
CSNK2A2	“up-regulates activity”	PPP1R2	phosphorylation
GSK3B	“up-regulates activity”	PPP1R2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 39 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.

GO biological processes:

GO term	Partners	Fold	FDR
glycogen metabolic process	6	92.9×	2e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

743 predictions. Top by Δscore:

Variant	Effect	Δscore
3:195516939:GATCC:G	acceptor_loss	1.0000
3:195516941:TC:T	acceptor_gain	1.0000
3:195516941:TCC:T	acceptor_loss	1.0000
3:195516942:CC:C	acceptor_gain	1.0000
3:195516942:CCT:C	acceptor_loss	1.0000
3:195516943:C:CC	acceptor_gain	1.0000
3:195519014:TAA:T	donor_loss	1.0000
3:195519016:A:T	donor_loss	1.0000
3:195519017:CCTTG:C	donor_loss	1.0000
3:195519032:T:TA	donor_gain	1.0000
3:195519182:TTTT:T	acceptor_gain	1.0000
3:195519184:TTC:T	acceptor_loss	1.0000
3:195519185:TC:T	acceptor_loss	1.0000
3:195519186:C:CC	acceptor_gain	1.0000
3:195519186:C:T	acceptor_loss	1.0000
3:195523782:CTAAT:C	acceptor_gain	1.0000
3:195523787:C:CC	acceptor_gain	1.0000
3:195523789:A:C	acceptor_gain	1.0000
3:195523799:C:CT	acceptor_gain	1.0000
3:195523800:A:AC	acceptor_gain	1.0000
3:195523800:A:C	acceptor_gain	1.0000
3:195524817:A:AC	donor_gain	1.0000
3:195524817:ACTT:A	donor_gain	1.0000
3:195524818:C:CC	donor_gain	1.0000
3:195524818:CTTC:C	donor_gain	1.0000
3:195524820:T:TA	donor_gain	1.0000
3:195524892:TCATA:T	acceptor_gain	1.0000
3:195524893:CATAC:C	acceptor_gain	1.0000
3:195524895:TA:T	acceptor_gain	1.0000
3:195524897:C:CC	acceptor_gain	1.0000

AlphaMissense

1370 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:195519157:C:A	R144S	1.000
3:195519157:C:G	R144S	1.000
3:195519158:C:G	R144T	1.000
3:195529883:C:A	W47C	1.000
3:195529883:C:G	W47C	1.000
3:195529885:A:G	W47R	1.000
3:195529885:A:T	W47R	1.000
3:195519150:G:C	H147D	0.999
3:195519158:C:A	R144M	0.999
3:195519169:A:C	F140L	0.999
3:195519169:A:T	F140L	0.999
3:195519171:A:G	F140L	0.999
3:195529841:T:A	K61N	0.999
3:195529841:T:G	K61N	0.999
3:195529842:T:A	K61I	0.999
3:195529855:G:C	H57D	0.999
3:195529869:A:C	I52S	0.999
3:195529869:A:G	I52T	0.999
3:195529869:A:T	I52N	0.999
3:195529871:G:C	N51K	0.999
3:195529871:G:T	N51K	0.999
3:195529884:C:A	W47L	0.999
3:195529884:C:G	W47S	0.999
3:195542985:A:G	I14T	0.999
3:195519119:G:T	A157D	0.998
3:195519148:G:C	H147Q	0.998
3:195519148:G:T	H147Q	0.998
3:195519150:G:T	H147N	0.998
3:195529864:C:G	A54P	0.998
3:195542982:A:G	L15S	0.998

dbSNP variants (sampled 300 via entrez): RS1000005546 (3:195534291 G>A), RS1000068595 (3:195537145 T>C), RS1000124958 (3:195534261 C>G,T), RS1000154657 (3:195540260 C>A,T), RS1000239918 (3:195517180 T>C,G), RS1000266053 (3:195540313 G>A), RS1000323691 (3:195521151 T>C), RS1000494464 (3:195532599 C>A), RS1000590414 (3:195516744 A>G,T), RS1000635108 (3:195515233 C>T), RS1000672431 (3:195538691 T>G), RS1000801124 (3:195544349 G>A,T), RS1000931553 (3:195534676 C>G), RS1000964374 (3:195515527 A>C), RS1001068538 (3:195521809 C>G,T)

Disease associations

OMIM: gene MIM:601792 | 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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases methylation	6
sodium arsenite	affects expression, affects cotreatment, increases abundance, increases expression	3
Fluorouracil	decreases expression	2
Nickel	increases expression	2
Cyclosporine	increases expression	2
GSK-J4	increases expression	1
bisphenol F	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
coumarin	affects phosphorylation	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
mesotrione	affects methylation, increases abundance	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	decreases expression	1
Resveratrol	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Aspirin	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Caffeine	affects phosphorylation	1
Coumestrol	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	increases expression	1
Estradiol	affects cotreatment, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2BV	Abcam HeLa PPP1R2 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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