CAPN2

Summary

CAPN2 (calpain 2, HGNC:1479) is a protein-coding gene on chromosome 1q41, encoding Calpain-2 catalytic subunit (P17655). Calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction.

The calpains, calcium-activated neutral proteases, are nonlysosomal, intracellular cysteine proteases. The mammalian calpains include ubiquitous, stomach-specific, and muscle-specific proteins. The ubiquitous enzymes consist of heterodimers with distinct large, catalytic subunits associated with a common small, regulatory subunit. This gene encodes the large subunit of the ubiquitous enzyme, calpain 2. Multiple heterogeneous transcriptional start sites in the 5’ UTR have been reported. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 824 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 163 total
• Druggable target: yes
• MANE Select transcript: NM_001748

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1479
Approved symbol	CAPN2
Name	calpain 2
Location	1q41
Locus type	gene with protein product
Status	Approved
Aliases	mCANP, CANPml, CANPL2
Ensembl gene	ENSG00000162909
Ensembl biotype	protein_coding
OMIM	114230
Entrez	824

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 13 protein_coding, 9 protein_coding_CDS_not_defined

ENST00000295006, ENST00000433674, ENST00000434648, ENST00000463997, ENST00000472601, ENST00000474026, ENST00000480581, ENST00000483579, ENST00000487223, ENST00000492565, ENST00000492664, ENST00000498027, ENST00000860586, ENST00000860587, ENST00000946743, ENST00000946744, ENST00000946745, ENST00000946746, ENST00000946747, ENST00000946748, ENST00000946749, ENST00000946750

RefSeq mRNA: 2 — MANE Select: NM_001748 NM_001146068, NM_001748

CCDS: CCDS31035, CCDS53478

Canonical transcript exons

ENST00000295006 — 21 exons

Exon	Start	End
ENSE00001069713	223749039	223749122
ENSE00001069714	223750890	223750975
ENSE00001069721	223744100	223744218
ENSE00001069725	223717762	223717831
ENSE00001069731	223746997	223747165
ENSE00001069732	223751997	223752071
ENSE00001132647	223759270	223759481
ENSE00001903247	223712539	223712877
ENSE00002364714	223745306	223745439
ENSE00002429618	223757369	223757380
ENSE00003521864	223762186	223762251
ENSE00003529178	223761581	223761617
ENSE00003547065	223771809	223771925
ENSE00003586339	223769841	223769909
ENSE00003587816	223755480	223755649
ENSE00003587965	223772181	223772239
ENSE00003596625	223766367	223766431
ENSE00003600149	223774834	223776018
ENSE00003620246	223770447	223770525
ENSE00003632276	223752796	223752956
ENSE00003649654	223764150	223764207

Expression profiles

Bgee: expression breadth ubiquitous, 303 present calls, max score 99.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 154.9938 / max 708.2937, expressed in 1810 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
8757	102.7459	1808
8760	20.4438	1731
8758	17.1071	1662
8759	6.8440	1472
8753	3.4723	666
8755	1.4544	681
8767	1.0232	551
8756	0.9290	532
8771	0.5237	269
8754	0.2859	151

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	99.65	gold quality
epithelium of bronchus	UBERON:0002031	99.60	gold quality
bronchus	UBERON:0002185	99.58	gold quality
nasal cavity epithelium	UBERON:0005384	99.57	gold quality
renal glomerulus	UBERON:0000074	99.53	gold quality
right uterine tube	UBERON:0001302	99.51	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.51	gold quality
parotid gland	UBERON:0001831	99.49	gold quality
colonic mucosa	UBERON:0000317	99.48	gold quality
metanephric glomerulus	UBERON:0004736	99.47	gold quality
parietal pleura	UBERON:0002400	99.42	gold quality
cartilage tissue	UBERON:0002418	99.39	gold quality
pleura	UBERON:0000977	99.37	gold quality
visceral pleura	UBERON:0002401	99.30	gold quality
skin of hip	UBERON:0001554	99.28	gold quality
oral cavity	UBERON:0000167	99.26	gold quality
nasal cavity mucosa	UBERON:0001826	99.26	gold quality
amniotic fluid	UBERON:0000173	99.23	gold quality
ileal mucosa	UBERON:0000331	99.23	gold quality
tongue squamous epithelium	UBERON:0006919	99.16	gold quality
germinal epithelium of ovary	UBERON:0001304	99.15	gold quality
palpebral conjunctiva	UBERON:0001812	99.14	gold quality
lower lobe of lung	UBERON:0008949	99.12	gold quality
metanephros	UBERON:0000081	99.11	gold quality
minor salivary gland	UBERON:0001830	99.05	gold quality
pharyngeal mucosa	UBERON:0000355	99.04	gold quality
epithelium of nasopharynx	UBERON:0001951	99.03	gold quality
mouth mucosa	UBERON:0003729	99.02	gold quality
nasopharynx	UBERON:0001728	99.01	gold quality
saliva-secreting gland	UBERON:0001044	99.00	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	25.79
E-GEOD-125970	yes	22.61
E-CURD-112	yes	13.30
E-GEOD-135922	yes	10.62
E-GEOD-130148	yes	7.04
E-MTAB-6386	no	1374.28
E-MTAB-7606	no	1093.90
E-MTAB-9689	no	429.78
E-CURD-89	no	313.43
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, ESR1, ESR2, TCF7L2

miRNA regulators (miRDB)

70 targeting CAPN2, 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-4692	100.00	67.32	2066
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488

Literature-anchored findings (GeneRIF, showing 40)

• ionomycin-induced calpain activation promotes decrease of Bcl-2 proteins thereby triggering the intrinsic apoptotic pathway (PMID:12000759)
• Calpain activation in neurodegenerative diseases (PMID:12070670)
• colocalization with detergent-insoluble rafts on T-cells (PMID:12150984)
• localization of m-calpain within caveolae may contribute to maintenance of the enzyme in an inactive state and that m-calpain may also contribute to the regulation of calcium-sensing receptor levels. (PMID:12783889)
• activation of m-calpain during mitosis is required for cells to establish the chromosome alignment by regulating some molecules that generate polar ejection force (PMID:14688278)
• the acidic loop and the transducer region of calpain form an interconnected, extended structural unit that has the capacity to integrate and transduce Ca2+-evoked conformational changes over a long distance (PMID:14976200)
• mu-calpain and m-calpain expression may be compromised in the anterior vaginal wall of women with uterovaginal prolapse (PMID:14980313)
• calpain I and II, calpastatin, and the regulatory subunit localize to the cytosolic surface of the endoplasmic reticulum and Golgi apparatus membranes (PMID:15302874)
• nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced cell migration and invasion may occur, at least in part, through a novel mechanism involving phosphorylation of calpains that leads to their activation and secretion (PMID:15471877)
• Gas2DN can increase the activity of calpain and induce degradation of stabilized/mutated beta-catenin (PMID:15817486)
• Immunohistochemistry of fixed, permeabilized oocytes exhibit localization of calpain m isoform to the cortical region of the oocyte, as well as the cytosol. (PMID:15950654)
• mCANP degrades human aquaporin 0. (PMID:16310784)
• a novel role for PKCiota as a nicotine-activated, physiological calpain kinase that directly phosphorylates and activates calpains. (PMID:16361262)
• the ion channel TRPM7 regulates cell adhesion through m-calpain by mediating the local influx of calcium into peripheral adhesion complexes (PMID:16436382)
• Protein-protein interaction of NMTs revealed that m-calpain interacts with NMT1 while caspase-3 interacts with NMT2. (PMID:16530191)
• beside its known effect on general muscle protein degradation, calpain contributes to Duchenne muscular dystrophy pathology by specifically degrading the compensatory protein utrophin (PMID:16598790)
• cancer invasiveness is independent of intracellular calpain 2 proteolytic activity that is usually needed for turnover of integrin-linked adhesions during two-dimensional planar migration (PMID:16652152)
• Incubation of pulmonary microvascular endothelial cells with VEGF resulted in dose- and time-dependent increases in calpain activity and protein content of calpain-2. (PMID:16816119)
• These findings identify calpain 2 as a novel component of the frontness signal that promotes polarization during chemotaxis. (PMID:17192410)
• Results show an aggrecan product with the COOH terminal neoepitope VPGVA is synthesized by intracellular processing in chondrocytes; M-calpain is the major candidate of the proteinase to generate this product during intracellular aggrecan processing. (PMID:17261541)
• association between mu- and m-calpain, the specific inhibitor calpastatin, and axonal injury in post mortem brain tissue from patients who died from severe malaria (PMID:17359359)
• Physiological shear stress elicits Ca(2+) influx-sensitive activation of m-calpain and this activity is facilitated through the PI3K pathway, and is essential for subsequent focal adhesion reorganization and cell alignment under shear conditions. (PMID:17596297)
• analysis of the intracellular proteolytic cleavage of myocilin and identification of calpain II as a myocilin-processing protease (PMID:17650508)
• both calpain 1 and calpain 2 are essential for the replication of EV1 RNA. (PMID:18032503)
• Collectively, our experiments implicate a novel signaling pathway involving calpain 2, PTP1B, and Src in the regulation of invadopodia and breast cancer invasion. (PMID:18332219)
• Data support a role for calpain2/calpastatin on proteolysis in response to eccentric skeletal muscle exercise. (PMID:18340456)
• These results not only identify calpain-2 as a substrate for sumoylation but also provide an important role of sumoylation in regulating cell migration. (PMID:19422794)
• Increased calpain activity might explain, at least in part, histological alterations in dilated aorta in Marfan with aortic aneurysm (PMID:19720936)
• m-Calpain antagonizes RhoA overactivation and endothelial barrier dysfunction under disturbed shear conditions. (PMID:19752040)
• Overexpression of calpain-2 and low expression of calpastatin may involve in the pathological development of stress urinary incontinence. (PMID:19756344)
• Overactivation of Ca(2+)-calpain pathways contributes to beta cell dysfunction and apoptosis in type 2 diabetes. (PMID:19861418)
• a higher calpain/calpastatin ratio collaborates with activated ERK to promote the generation of the low molecular weight-AR (PMID:19946123)
• The calcium-calpain-caspase-12-caspase-3 cascade is altered in F508del-CFTR expressing cells. (PMID:20041182)
• excessive TRPM7 channel activity causes oxidative and nitrosative stresses, producing cell rounding mediated by p38 MAPK/JNK-dependent activation of m-calpain (PMID:20070945)
• analysis of a novel role for calpain proteolysis of FAK in regulating adhesion dynamics in motile cells (PMID:20150423)
• High m-calpain expression is associated with rhabdomyosarcoma aggressiveness. (PMID:20193680)
• Data indicate that calpains are involved in the C-terminal truncation of aggrecan and might have a minor role in arthritic diseases. (PMID:20618160)
• m-Calpain activation is regulated by its membrane localization and by its binding to phosphatidylinositol 4,5-bisphosphate. (PMID:20729206)
• Knockdown of calpain 2 expression using shRNA or chemical inhibition of calpain activity reduced glioblastoma cell invasion by 90%. (PMID:20730561)
• In brain, calpain-2 plays critical roles in developmental and adult synaptic plasticity. (PMID:20924799)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	capn2l	ENSDARG00000034211
mus_musculus	Capn2	ENSMUSG00000026509
rattus_norvegicus	Capn2	ENSRNOG00000034015
caenorhabditis_elegans		WBGENE00000542
caenorhabditis_elegans	clp-3	WBGENE00000544
caenorhabditis_elegans		WBGENE00000546
caenorhabditis_elegans		WBGENE00000547
caenorhabditis_elegans		WBGENE00006606
caenorhabditis_elegans	clp-8	WBGENE00009695
caenorhabditis_elegans	clpr-3	WBGENE00010417
caenorhabditis_elegans	clpr-1	WBGENE00012233
caenorhabditis_elegans	clpr-3	WBGENE00013184

Paralogs (20): CAPN1 (ENSG00000014216), SRI (ENSG00000075142), CAPN6 (ENSG00000077274), CAPN3 (ENSG00000092529), CAPN15 (ENSG00000103326), GCA (ENSG00000115271), ADGB (ENSG00000118492), CAPNS1 (ENSG00000126247), CAPN7 (ENSG00000131375), CAPN9 (ENSG00000135773), CAPN11 (ENSG00000137225), CAPN10 (ENSG00000142330), CAPN5 (ENSG00000149260), PEF1 (ENSG00000162517), CAPN13 (ENSG00000162949), CAPN12 (ENSG00000182472), CAPN8 (ENSG00000203697), CAPN14 (ENSG00000214711), PDCD6 (ENSG00000249915), CAPNS2 (ENSG00000256812)

Protein

Protein identifiers

Calpain-2 catalytic subunit — P17655 (reviewed: P17655)

Alternative names: Calcium-activated neutral proteinase 2, Calpain M-type, Calpain large polypeptide L2, Calpain-2 large subunit, Millimolar-calpain

All UniProt accessions (2): C9JWY7, P17655

UniProt curated annotations — full annotation on UniProt →

Function. Calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction. Proteolytically cleaves MYOC at ‘Arg-226’. Proteolytically cleaves CPEB3 following neuronal stimulation which abolishes CPEB3 translational repressor activity, leading to translation of CPEB3 target mRNAs.

Subunit / interactions. Forms a heterodimer with a small (regulatory) subunit (CAPNS1). Interacts with CPEB3; this leads to cleavage of CPEB3. Interacts with PIDD1 alternative open reading frame protein altPIDD1.

Subcellular location. Cytoplasm. Cell membrane.

Tissue specificity. Ubiquitous.

Activity regulation. Activated by 200-1000 micromolar concentrations of calcium and inhibited by calpastatin.

Cofactor. Binds 7 Ca(2+) ions.

Similarity. Belongs to the peptidase C2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P17655-1	1	yes
P17655-2	2

RefSeq proteins (2): NP_001139540, NP_001739* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000169	Pept_cys_AS	Active_site
IPR001300	Peptidase_C2_calpain_cat	Domain
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR022682	Calpain_domain_III	Domain
IPR022683	Calpain_III	Domain
IPR022684	Calpain_cysteine_protease	Family
IPR033883	C2_III	Domain
IPR036213	Calpain_III_sf	Homologous_superfamily
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily
IPR042736	EFh_PEF_CAPN2	Domain

Pfam: PF00648, PF01067, PF13833

Enzyme classification (BRENDA):

• EC 3.4.22.53 — calpain-2 (BRENDA: 21 organisms, 189 substrates, 162 inhibitors, 17 Km, 12 kcat entries)

Substrate kinetics (BRENDA)

11 substrates with measured Km, best-characterized 11. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
SUCCINYL-LEU-TYR-7-AMIDO-4-METHYLCOUMARIN	0.431–3.18	4
SUCCINYL-LEU-LEU-VAL-TYR-7-AMIDO-4-METHYLCOUMARI	0.459–0.461	2
SUCCINYL-LEU-MET-7-AMIDO-4-METHYLCOUMARIN	4.66–4.68	2
T-BUTYLOXYCARBONYL-VAL-LEU-LYS-7-AMIDO-4-METHYLC	8.11–8.12	2
BOC-VAL-LEU-LYS-METHYLCOUMARIN	7.5	1
SUCCINYL-BOVINE SERUM ALBUMIN	2.2	1
SUCCINYL-CASEIN	10	1
SUCCINYL-INSULIN B	453.7	1
SUCCINYL-LEU-LEU-VAL-TYR-METHYLCOUMARIN	19.32	1
SUCCINYL-PROTAMINE	101.3	1
T-BOC-LEU-MET-METHYLCOUMARIN	5.33	1

UniProt features (127 total): strand 42, helix 27, binding site 25, turn 7, sequence variant 6, domain 4, sequence conflict 4, active site 3, region of interest 3, splice variant 2, initiator methionine 1, propeptide 1, chain 1, modified residue 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
2NQA	X-RAY DIFFRACTION	2.2
1KFU	X-RAY DIFFRACTION	2.5
1KFX	X-RAY DIFFRACTION	3.15

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P17655-F1	89.48	0.60

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 (3): 105; 262; 286

Ligand- & substrate-binding residues (25): 89; 91; 96; 175; 229; 230; 292; 299; 323; 542; 545; 547 …

Post-translational modifications (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-1474228	Degradation of the extracellular matrix
R-HSA-8862803	Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer’s disease models
R-HSA-9856530	High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells
R-HSA-9860927	Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells
R-HSA-1474244	Extracellular matrix organization
R-HSA-1643685	Disease
R-HSA-8863678	Neurodegenerative Diseases
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9645723	Diseases of programmed cell death
R-HSA-9734009	Defective Intrinsic Pathway for Apoptosis
R-HSA-9855142	Cellular responses to mechanical stimuli
R-HSA-9860931	Response of endothelial cells to shear stress

MSigDB gene sets: 483 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, MODULE_172, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, ZHAN_LATE_DIFFERENTIATION_GENES_UP, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLCHOLINE_METABOLIC_PROCESS, GOBP_BEHAVIOR, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GOBP_RESPONSE_TO_ACID_CHEMICAL, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_PHOSPHATIDYLCHOLINE_BIOSYNTHETIC_PROCESS, GOBP_RESPONSE_TO_FLUID_SHEAR_STRESS, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_CELLULAR_RESPONSE_TO_FLUID_SHEAR_STRESS

GO Biological Process (23): response to hypoxia (GO:0001666), blastocyst development (GO:0001824), proteolysis (GO:0006508), myoblast fusion (GO:0007520), female pregnancy (GO:0007565), response to mechanical stimulus (GO:0009612), positive regulation of cardiac muscle cell apoptotic process (GO:0010666), protein autoprocessing (GO:0016540), regulation of interleukin-6 production (GO:0032675), cellular response to interferon-beta (GO:0035458), response to hydrogen peroxide (GO:0042542), behavioral response to pain (GO:0048266), synaptic vesicle endocytosis (GO:0048488), regulation of cytoskeleton organization (GO:0051493), obsolete proteolysis involved in protein catabolic process (GO:0051603), cellular response to lipopolysaccharide (GO:0071222), cellular response to amino acid stimulus (GO:0071230), vascular endothelial cell response to laminar fluid shear stress (GO:0097700), vascular endothelial cell response to oscillatory fluid shear stress (GO:0097706), protein catabolic process at postsynapse (GO:0140249), positive regulation of myoblast fusion (GO:1901741), positive regulation of phosphatidylcholine biosynthetic process (GO:2001247), protein catabolic process (GO:0030163)

GO Molecular Function (10): calcium-dependent cysteine-type endopeptidase activity (GO:0004198), calcium ion binding (GO:0005509), cytoskeletal protein binding (GO:0008092), cysteine-type peptidase activity (GO:0008234), enzyme binding (GO:0019899), protein-containing complex binding (GO:0044877), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (25): chromatin (GO:0000785), nucleus (GO:0005634), cytoplasm (GO:0005737), lysosome (GO:0005764), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), focal adhesion (GO:0005925), external side of plasma membrane (GO:0009897), dendrite (GO:0030425), cortical actin cytoskeleton (GO:0030864), pseudopodium (GO:0031143), neuronal cell body (GO:0043025), membrane raft (GO:0045121), extracellular exosome (GO:0070062), perinuclear endoplasmic reticulum (GO:0097038), sperm midpiece (GO:0097225), sperm principal piece (GO:0097228), presynapse (GO:0098793), postsynapse (GO:0098794), calpain complex (GO:0110158), sperm head-tail coupling apparatus (GO:0120212), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Response of endothelial cells to shear stress	2
Extracellular matrix organization	1
Neurodegenerative Diseases	1
Defective Intrinsic Pathway for Apoptosis	1
Disease	1
Diseases of programmed cell death	1
Cellular responses to stimuli	1
Cellular responses to mechanical stimuli	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
intracellular membrane-bounded organelle	3
cytoplasm	3
vascular endothelial cell response to fluid shear stress	2
protein binding	2
binding	2
endomembrane system	2
sperm flagellum	2
response to stress	1
response to decreased oxygen levels	1
in utero embryonic development	1
anatomical structure development	1
protein metabolic process	1
syncytium formation by cell-cell fusion	1
myotube differentiation	1
multi-organism reproductive process	1
multi-multicellular organism process	1
response to external stimulus	1
response to abiotic stimulus	1
cardiac muscle cell apoptotic process	1
positive regulation of striated muscle cell apoptotic process	1
regulation of cardiac muscle cell apoptotic process	1
protein processing	1
regulation of cytokine production	1
interleukin-6 production	1
response to interferon-beta	1
cellular response to cytokine stimulus	1
response to reactive oxygen species	1
behavior	1
response to pain	1
synaptic vesicle recycling	1
presynaptic endocytosis	1
cytoskeleton organization	1
regulation of organelle organization	1
response to lipopolysaccharide	1
cellular response to molecule of bacterial origin	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
response to amino acid	1
cellular response to acid chemical	1

Protein interactions and networks

STRING

1806 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CAPN2	CAST	P20810	993
CAPN2	CAPNS1	P04632	981
CAPN2	SPTAN1	Q13813	757
CAPN2	TLN1	Q9Y490	704
CAPN2	SRC	P12931	694
CAPN2	PRELID1	Q9Y255	684
CAPN2	CAPN1	P07384	645
CAPN2	PTK2	Q05397	577
CAPN2	TNS2	Q63HR2	545
CAPN2	TLN2	Q9Y4G6	509
CAPN2	CASP3	P42574	485
CAPN2	GRIA1	P42261	473
CAPN2	PTGDR2	Q9Y5Y4	470
CAPN2	PLAU	P00749	469
CAPN2	MSN	P26038	469

IntAct

103 interactions, top by confidence:

A	B	Type	Score
CAPN1	CAPNS1	psi-mi:“MI:0914”(association)	0.840
CAPNS1	CAPN2	psi-mi:“MI:0407”(direct interaction)	0.810
CAPN2	CAPNS1	psi-mi:“MI:0915”(physical association)	0.810
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
FAM9C	NDC80	psi-mi:“MI:0914”(association)	0.670
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
PIDD1	CAPN2	psi-mi:“MI:0915”(physical association)	0.580
CASP6	CAPN2	psi-mi:“MI:0915”(physical association)	0.560
LAMP2	CAPN2	psi-mi:“MI:0915”(physical association)	0.560
P4HB	CAPN2	psi-mi:“MI:0915”(physical association)	0.560
PLP1	CAPN2	psi-mi:“MI:0915”(physical association)	0.560
RAN	CAPN2	psi-mi:“MI:0915”(physical association)	0.560
ST13	CAPN2	psi-mi:“MI:0915”(physical association)	0.560
NUPR1	CAPN2	psi-mi:“MI:0915”(physical association)	0.560
PRPF40A	CAPN2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (228): UBE2I (Affinity Capture-Western), CAPN2 (Two-hybrid), CAPN2 (Affinity Capture-Western), ATG5 (Biochemical Activity), CAPN2 (Affinity Capture-MS), CAPN2 (Affinity Capture-MS), CAPN2 (Affinity Capture-MS), CAPN2 (Co-fractionation), CAPN2 (Affinity Capture-MS), CAPN2 (Affinity Capture-MS), CAPN2 (Affinity Capture-MS), ATXN3 (Biochemical Activity), CAPN2 (Affinity Capture-MS), CAPN2 (Affinity Capture-MS), CAPN2 (Affinity Capture-MS)

ESM2 similar proteins: A2YQ56, A3QRX8, A6NHC0, O08529, O14815, O35350, O35920, P00789, P07384, P17569, P17655, P20807, P35750, P36776, P39866, P93648, P93655, P97571, Q07009, Q07093, Q11002, Q27970, Q27971, Q4KM30, Q59HJ6, Q5NVS7, Q5PQ09, Q5R456, Q5XIT6, Q5ZIV7, Q641Z6, Q69UZ3, Q6DC39, Q6GLM5, Q6ICB0, Q78EJ9, Q8CGK3, Q8X1T0, Q91VA3, Q92178

Diamond homologs: A6NHC0, A8MX76, G3V7W1, O08529, O08688, O14815, O15484, O23184, O35350, O35646, O35920, O75808, O88456, O88501, P00789, P04574, P04632, P05044, P06813, P06814, P06815, P07384, P13135, P16259, P17655, P20807, P27398, P27730, P28676, P30626, P34308, P35750, P43367, P43368, P51186, P97571, Q07009, Q11002, Q22036, Q27970

SIGNOR signaling

15 interactions.

A	Effect	B	Mechanism
PRKACA	down-regulates	CAPN2	phosphorylation
MAPK1	up-regulates	CAPN2	phosphorylation
MAPK3	up-regulates	CAPN2	phosphorylation
CAPN2	“up-regulates activity”	CDK5/CDK5R1	cleavage
CAST	“down-regulates activity”	CAPN2	binding
CAPN2	“up-regulates activity”	CDK5R1	cleavage
CAPN2	“down-regulates activity”	MAPT	cleavage
CAPN2	“up-regulates activity”	GSK3A	cleavage
CAPN2	“up-regulates activity”	GSK3B	cleavage
Gbeta	up-regulates	CAPN2	phosphorylation
ERK1/2	up-regulates	CAPN2	phosphorylation
CAPN2	“down-regulates activity”	F2RL1	cleavage
SRC	“up-regulates activity”	CAPN2	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	122
Likely benign	5
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

3003 predictions. Top by Δscore:

Variant	Effect	Δscore
1:223744094:TCACA:T	acceptor_loss	1.0000
1:223744095:CACA:C	acceptor_loss	1.0000
1:223744097:CA:C	acceptor_loss	1.0000
1:223744098:A:AG	acceptor_gain	1.0000
1:223744099:G:GG	acceptor_gain	1.0000
1:223744099:G:GT	acceptor_loss	1.0000
1:223744214:TCCAG:T	donor_loss	1.0000
1:223744216:CAGG:C	donor_loss	1.0000
1:223744217:AGGT:A	donor_loss	1.0000
1:223744218:GG:G	donor_loss	1.0000
1:223744219:G:A	donor_loss	1.0000
1:223744220:T:A	donor_loss	1.0000
1:223745301:TGCAG:T	acceptor_loss	1.0000
1:223745302:GCA:G	acceptor_loss	1.0000
1:223745304:A:AG	acceptor_gain	1.0000
1:223745304:AGTTC:A	acceptor_loss	1.0000
1:223745305:G:GA	acceptor_gain	1.0000
1:223745305:GT:G	acceptor_gain	1.0000
1:223745305:GTTCT:G	acceptor_gain	1.0000
1:223745435:GCCAA:G	donor_gain	1.0000
1:223745436:CCAA:C	donor_gain	1.0000
1:223745437:CAA:C	donor_gain	1.0000
1:223745437:CAAG:C	donor_loss	1.0000
1:223745438:AA:A	donor_gain	1.0000
1:223745438:AAG:A	donor_loss	1.0000
1:223745439:AGT:A	donor_loss	1.0000
1:223745440:G:C	donor_loss	1.0000
1:223745440:G:GG	donor_gain	1.0000
1:223745441:T:A	donor_loss	1.0000
1:223747161:TCGAC:T	donor_gain	1.0000

AlphaMissense

4642 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:223712863:T:A	W75R	1.000
1:223712863:T:C	W75R	1.000
1:223744105:T:C	C105R	1.000
1:223744106:G:A	C105Y	1.000
1:223744107:C:G	C105W	1.000
1:223744108:T:A	W106R	1.000
1:223744108:T:C	W106R	1.000
1:223745408:T:A	W177R	1.000
1:223745408:T:C	W177R	1.000
1:223749095:C:A	H262Q	1.000
1:223749095:C:G	H262Q	1.000
1:223749099:T:C	Y264H	1.000
1:223749106:T:A	V266D	1.000
1:223750934:T:A	N286K	1.000
1:223750934:T:G	N286K	1.000
1:223750938:T:A	W288R	1.000
1:223750938:T:C	W288R	1.000
1:223750953:T:A	W293R	1.000
1:223750953:T:C	W293R	1.000
1:223752067:T:C	F324L	1.000
1:223752069:C:A	F324L	1.000
1:223752069:C:G	F324L	1.000
1:223752844:T:G	C341W	1.000
1:223752914:T:A	W365R	1.000
1:223752914:T:C	W365R	1.000
1:223752916:G:C	W365C	1.000
1:223752916:G:T	W365C	1.000
1:223752936:G:A	G372E	1.000
1:223752938:G:C	G373R	1.000
1:223752939:G:A	G373D	1.000

dbSNP variants (sampled 300 via entrez): RS1000002729 (1:223737921 C>A,G), RS1000032679 (1:223772387 C>A,T), RS1000058332 (1:223729584 G>T), RS1000092672 (1:223723701 C>T), RS1000114478 (1:223700729 C>T), RS1000150250 (1:223753576 T>G), RS1000164672 (1:223736308 C>T), RS1000254938 (1:223724018 G>A), RS1000298306 (1:223742722 T>C), RS1000325818 (1:223742436 A>G), RS1000348717 (1:223750315 C>T), RS1000390569 (1:223731437 C>T), RS1000412975 (1:223713850 G>C), RS1000446299 (1:223772128 G>A), RS1000555017 (1:223706464 G>A,C)

Disease associations

OMIM: gene MIM:114230 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002674_3	Febrile seizures (MMR vaccine-related)	6.000000e-06
GCST003938_3	Carotenoid levels (alpha-carotene)	4.000000e-08
GCST006585_2655	Blood protein levels	3.000000e-07
GCST008145_1	Waist circumference	8.000000e-06
GCST90007005_6	Gut microbiota relative abundance (Eubacterium belonging to family Erysipelotrichaceae)	2.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006519	MMR-related febrile seizures
EFO:0007893	alpha-carotene measurement
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2382 (SINGLE PROTEIN), CHEMBL3038466 (PROTEIN FAMILY)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — C2: Calpain

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
compound 19 [PMID: 8831774]	Inhibition	7.82	pIC50
compound 5a [PMID: 20690647]	Inhibition	7.17	pKi

Binding affinities (BindingDB)

2 measured of 16 human assays (16 total across all organisms); most potent 2 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
benzyl N-[(1S)-2-methyl-1-[(1-oxo-3-phenylpropan-2-yl)carbamoyl]propyl]carbamate	IC50	100 nM
benzyl N-[1-[(4-fluoro-3-oxo-1-phenylbutan-2-yl)amino]-1-oxo-3-phenylpropan-2-yl]carbamate	IC50	397 nM

ChEMBL bioactivities

181 potent at pChembl≥5 of 185 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.30	Ki	5	nM	CHEMBL315636
8.30	Ki	5	nM	CHEMBL91991
8.24	Ki	5.7	nM	CHEMBL117023
8.15	Ki	7	nM	CHEMBL92114
8.15	Ki	7	nM	CHEMBL89766
8.05	Ki	9	nM	CHEMBL89008
7.96	Ki	11	nM	CHEMBL88895
7.89	Ki	13	nM	CHEMBL88646
7.82	Ki	15	nM	CHEMBL130506
7.77	Ki	17	nM	CHEMBL89100
7.77	Ki	17	nM	CHEMBL130114
7.72	Ki	19	nM	CHEMBL325401
7.72	Ki	19	nM	CHEMBL325223
7.66	Ki	22	nM	CHEMBL117336
7.66	Ki	22	nM	CHEMBL335293
7.66	Ki	22	nM	CHEMBL118908
7.66	Ki	22	nM	CHEMBL118025
7.64	Ki	23	nM	CHEMBL134283
7.62	Ki	24	nM	CHEMBL331850
7.55	Ki	28	nM	CHEMBL432443
7.52	IC50	30	nM	CHEMBL1921830
7.48	Ki	33	nM	CHEMBL424074
7.46	Ki	35	nM	CHEMBL98777
7.41	Ki	39	nM	CHEMBL420872
7.39	Ki	41	nM	CHEMBL134002
7.39	Ki	41	nM	CHEMBL5723370
7.38	Ki	42	nM	CHEMBL419898
7.37	Ki	43	nM	CHEMBL119622
7.36	Ki	44	nM	CHEMBL117888
7.34	Ki	46	nM	CHEMBL134173
7.34	Ki	46	nM	CHEMBL419590
7.30	Ki	50	nM	CHEMBL116477
7.30	Ki	50	nM	CHEMBL134179
7.30	Ki	50	nM	CHEMBL131540
7.30	Ki	50	nM	CHEMBL444594
7.29	Ki	51	nM	CHEMBL133106
7.29	Ki	51	nM	CHEMBL98777
7.23	Ki	59	nM	CHEMBL116256
7.22	Ki	60	nM	CHEMBL130753
7.20	Ki	63	nM	CHEMBL326290
7.19	Ki	65	nM	CHEMBL441280
7.18	Ki	66	nM	CHEMBL131319
7.17	Ki	67	nM	CHEMBL116429
7.17	Ki	68	nM	CHEMBL133634
7.16	Ki	69	nM	CHEMBL131781
7.14	Ki	73	nM	CHEMBL419898
7.13	Ki	74	nM	CHEMBL132587
7.12	Ki	76	nM	CHEMBL132773
7.11	Ki	78	nM	CHEMBL134121
7.11	Kd	76.84	nM	CHEMBL5653589

PubChem BioAssay actives

173 with measured affinity, of 210 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2R)-2-(methanesulfonamido)-N-[(2S)-1-oxo-3-(4-phenylmethoxyphenyl)propan-2-yl]-3-phenylmethoxypropanamide	46728: Inhibitory activity against Calpain-II receptor in porcine kidney	ki	0.0050	uM
(2R)-2-(methanesulfonamido)-N-[(2S)-1-oxo-3-phenylpropan-2-yl]-3-phenylmethoxypropanamide	46728: Inhibitory activity against Calpain-II receptor in porcine kidney	ki	0.0050	uM
3-[[4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]-2-oxo-4-phenylbutanoic acid	46711: Inhibitory activity of alpha-keto esters towards calpain 2 at pH 8.0	ki	0.0057	uM
(2S)-3-benzylsulfanyl-2-(methanesulfonamido)-N-[(2S)-1-oxo-3-phenylpropan-2-yl]propanamide	46728: Inhibitory activity against Calpain-II receptor in porcine kidney	ki	0.0070	uM
(2R)-2-(methanesulfonamido)-N-[(2S)-1-oxo-3-phenylpropan-2-yl]-3-phenylmethoxybutanamide	46728: Inhibitory activity against Calpain-II receptor in porcine kidney	ki	0.0070	uM
(2R)-2-(ethylsulfonylamino)-N-[(2S)-1-oxo-3-phenylpropan-2-yl]-3-phenylmethoxypropanamide	46728: Inhibitory activity against Calpain-II receptor in porcine kidney	ki	0.0090	uM
(2R)-2-(methanesulfonamido)-N-[(2S)-1-oxo-3-phenylpropan-2-yl]-3-thiophen-2-ylpropanamide	46728: Inhibitory activity against Calpain-II receptor in porcine kidney	ki	0.0110	uM
(2R)-2-(methanesulfonamido)-N-[(2S)-1-oxo-3-phenylpropan-2-yl]-3-phenylpropanamide	46728: Inhibitory activity against Calpain-II receptor in porcine kidney	ki	0.0130	uM
benzyl N-[1-[[1-[(2-hydroxy-2-phenylethyl)amino]-1,2-dioxopentan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46710: Compound was evaluated for the inhibition of Cysteine protease Calpain 2	ki	0.0150	uM
benzyl N-[1-[[1,2-dioxo-1-(pyridin-2-ylmethylamino)pentan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46710: Compound was evaluated for the inhibition of Cysteine protease Calpain 2	ki	0.0170	uM
(2R)-N-[(2S)-6-(benzenesulfonamido)-1-oxohexan-2-yl]-2-(methanesulfonamido)-3-phenylmethoxypropanamide	46728: Inhibitory activity against Calpain-II receptor in porcine kidney	ki	0.0170	uM
benzyl N-[1-[(1-amino-1,2-dioxopentan-3-yl)amino]-4-methyl-1-oxopentan-2-yl]carbamate	46711: Inhibitory activity of alpha-keto esters towards calpain 2 at pH 8.0	ki	0.0190	uM
benzyl N-[4-methyl-1-[[1-(octylamino)-1,2-dioxopentan-3-yl]amino]-1-oxopentan-2-yl]carbamate	46711: Inhibitory activity of alpha-keto esters towards calpain 2 at pH 8.0	ki	0.0190	uM
benzyl N-[1-[[1,2-dioxo-1-(2-phenylethylamino)pentan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46710: Compound was evaluated for the inhibition of Cysteine protease Calpain 2	ki	0.0220	uM
3-[[4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]-2-oxopentanoic acid	46711: Inhibitory activity of alpha-keto esters towards calpain 2 at pH 8.0	ki	0.0220	uM
benzyl N-[1-[[1-(benzylamino)-1,2-dioxopentan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46711: Inhibitory activity of alpha-keto esters towards calpain 2 at pH 8.0	ki	0.0220	uM
benzyl N-[1-[[1-[(3,5-dimethoxyphenyl)methylamino]-1,2-dioxopentan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46710: Compound was evaluated for the inhibition of Cysteine protease Calpain 2	ki	0.0220	uM
benzyl N-[1-[[3,4-dioxo-1-phenyl-4-(quinolin-2-ylmethylamino)butan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46710: Compound was evaluated for the inhibition of Cysteine protease Calpain 2	ki	0.0230	uM
benzyl N-[1-[[3,4-dioxo-1-phenyl-4-(2-phenylethylamino)butan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46710: Compound was evaluated for the inhibition of Cysteine protease Calpain 2	ki	0.0240	uM
benzyl N-[1-[[4-(butylamino)-3,4-dioxo-1-phenylbutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46711: Inhibitory activity of alpha-keto esters towards calpain 2 at pH 8.0	ki	0.0280	uM
benzyl N-[(7S,10S,13S)-7-formyl-10-(2-methylpropyl)-9,12-dioxo-2-oxa-8,11-diazabicyclo[13.2.2]nonadeca-1(17),15,18-trien-13-yl]carbamate	1575191: Inhibition of calpain-2 (unknown origin)	ic50	0.0300	uM
benzyl N-[1-[[1-(furan-2-ylmethylamino)-1,2-dioxopentan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46710: Compound was evaluated for the inhibition of Cysteine protease Calpain 2	ki	0.0330	uM
benzyl N-[(2S)-1-[[1-(ethylamino)-1-oxo-3-phenylpropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46704: Tested for inhibitory activity on human calpain 2 from placenta	ki	0.0350	uM
benzyl N-[1-[[4-(ethylamino)-3,4-dioxo-1-phenylbutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46710: Compound was evaluated for the inhibition of Cysteine protease Calpain 2	ki	0.0390	uM
benzyl N-[4-methyl-1-[[1-(3-morpholin-4-ylpropylamino)-1,2-dioxopentan-3-yl]amino]-1-oxopentan-2-yl]carbamate	46710: Compound was evaluated for the inhibition of Cysteine protease Calpain 2	ki	0.0410	uM
benzyl N-[(2S)-1-[[1-(ethylamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46709: Tested for inhibitory activity on porcine calpain 2 from kidney	ki	0.0420	uM
benzyl N-[1-[[1,2-dioxo-1-(3-phenylpropylamino)pentan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46710: Compound was evaluated for the inhibition of Cysteine protease Calpain 2	ki	0.0430	uM
benzyl N-[1-[[1-(cyclohexylmethylamino)-1,2-dioxopentan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46710: Compound was evaluated for the inhibition of Cysteine protease Calpain 2	ki	0.0440	uM
benzyl N-[1-[[4-(benzylamino)-3,4-dioxo-1-phenylbutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46710: Compound was evaluated for the inhibition of Cysteine protease Calpain 2	ki	0.0460	uM
benzyl N-[1-[[1-[2-(4-methoxyphenyl)ethylamino]-1,2-dioxopentan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46710: Compound was evaluated for the inhibition of Cysteine protease Calpain 2	ki	0.0460	uM
benzyl N-[1-[[3,4-dioxo-1-phenyl-4-(propylamino)butan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46710: Compound was evaluated for the inhibition of Cysteine protease Calpain 2	ki	0.0500	uM
benzyl N-[1-[[1-(butylamino)-1,2-dioxopentan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46711: Inhibitory activity of alpha-keto esters towards calpain 2 at pH 8.0	ki	0.0500	uM
benzyl N-[1-[[4-[(2-hydroxy-2-phenylethyl)amino]-3,4-dioxo-1-phenylbutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46710: Compound was evaluated for the inhibition of Cysteine protease Calpain 2	ki	0.0500	uM
benzyl N-[1-[[1-[2-(1H-indol-3-yl)ethylamino]-1,2-dioxopentan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46710: Compound was evaluated for the inhibition of Cysteine protease Calpain 2	ki	0.0500	uM
benzyl N-[1-[[1-(5-hydroxypentylamino)-1,2-dioxopentan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46710: Compound was evaluated for the inhibition of Cysteine protease Calpain 2	ki	0.0510	uM
benzyl N-[1-[[1,2-dioxo-1-(2-phenylpropylamino)pentan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46711: Inhibitory activity of alpha-keto esters towards calpain 2 at pH 8.0	ki	0.0590	uM
benzyl N-[1-[[1-[2-(4-hydroxyphenyl)ethylamino]-1,2-dioxopentan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46710: Compound was evaluated for the inhibition of Cysteine protease Calpain 2	ki	0.0600	uM
benzyl N-[1-[[1-(2,2-diphenylethylamino)-1,2-dioxopentan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46711: Inhibitory activity of alpha-keto esters towards calpain 2 at pH 8.0	ki	0.0630	uM
benzyl N-[4-methyl-1-[[4-(2-methylpropylamino)-3,4-dioxo-1-phenylbutan-2-yl]amino]-1-oxopentan-2-yl]carbamate	46711: Inhibitory activity of alpha-keto esters towards calpain 2 at pH 8.0	ki	0.0650	uM
benzyl N-[1-[[1,2-dioxo-1-(oxolan-2-ylmethylamino)pentan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46710: Compound was evaluated for the inhibition of Cysteine protease Calpain 2	ki	0.0660	uM
benzyl N-[1-[[1-(heptylamino)-1,2-dioxopentan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46711: Inhibitory activity of alpha-keto esters towards calpain 2 at pH 8.0	ki	0.0670	uM
benzyl N-[1-[[1-(3-imidazol-1-ylpropylamino)-1,2-dioxopentan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46710: Compound was evaluated for the inhibition of Cysteine protease Calpain 2	ki	0.0680	uM
benzyl N-[1-[[1-[(5-hydroxy-1,3,3-trimethylcyclohexyl)methylamino]-1,2-dioxopentan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46710: Compound was evaluated for the inhibition of Cysteine protease Calpain 2	ki	0.0690	uM
2-[(2,2-diphenylacetyl)amino]-4-methyl-N-[4-(3-morpholin-4-ylpropylamino)-3,4-dioxo-1-phenylbutan-2-yl]pentanamide	46710: Compound was evaluated for the inhibition of Cysteine protease Calpain 2	ki	0.0740	uM
benzyl N-[4-methyl-1-[[1-[2-(1-methylpyrrol-2-yl)ethylamino]-1,2-dioxopentan-3-yl]amino]-1-oxopentan-2-yl]carbamate	46710: Compound was evaluated for the inhibition of Cysteine protease Calpain 2	ki	0.0760	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147992: Binding affinity to human CAPN2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0768	uM
benzyl N-[1-[(1-amino-1,2-dioxohexan-3-yl)amino]-4-methyl-1-oxopentan-2-yl]carbamate	46711: Inhibitory activity of alpha-keto esters towards calpain 2 at pH 8.0	ki	0.0780	uM
benzyl N-[1-[[1-(2-hydroxyethylamino)-1,2-dioxopentan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46710: Compound was evaluated for the inhibition of Cysteine protease Calpain 2	ki	0.0780	uM
benzyl N-[4-methyl-1-[[1-(methylamino)-1,2-dioxopentan-3-yl]amino]-1-oxopentan-2-yl]carbamate	46710: Compound was evaluated for the inhibition of Cysteine protease Calpain 2	ki	0.0830	uM
benzyl N-[(7S,10S,13S)-7-formyl-9,12-dioxo-10-propan-2-yl-2-oxa-8,11-diazabicyclo[13.2.2]nonadeca-1(17),15,18-trien-13-yl]carbamate	631287: Inhibition of CAPN2 using BODIPY-labeled casein substrate by fluorometric analysis	ic50	0.0850	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, increases expression, decreases expression, decreases methylation, affects cotreatment	6
Benzo(a)pyrene	affects cotreatment, increases expression, increases methylation	6
Aflatoxin B1	increases expression, affects expression, decreases methylation	5
Estradiol	increases expression, affects cotreatment, decreases expression	3
Cyclosporine	increases expression	3
sodium arsenite	increases expression, increases reaction, decreases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
(+)-JQ1 compound	decreases expression	2
Arsenic Trioxide	increases expression	2
Acetaminophen	decreases expression, increases expression	2
Cannabidiol	decreases expression, affects cotreatment	2
Cisplatin	affects reaction, increases cleavage, increases reaction, decreases expression, increases activity (+3 more)	2
Hydrogen Peroxide	affects expression, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
tert-Butylhydroperoxide	affects expression, decreases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
testosterone enanthate	affects expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
honokiol	decreases activity, decreases expression, increases reaction, decreases reaction, increases expression	1
surfactin peptide	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
antibiotic G 418	increases cleavage	1
pyrazolo(3,4-d)pyrimidine	affects expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction	1

ChEMBL screening assays

32 unique, capped per target: 28 binding, 4 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1012294	Binding	Inhibition of human CAPN2	Synthesis, biological evaluation and molecular modelling of N-heterocyclic dipeptide aldehydes as selective calpain inhibitors. — Bioorg Med Chem
CHEMBL5723080	Functional	Affinity Biochemical interaction: (enzymatic assay (fluorogenic substrate cleavage)) EUB0002134a CAPN2	Affinity Biochemical Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

4 cell lines: 2 cancer cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A9AZ	MDA-MB-231 CAPN2 KO	Cancer cell line	Female
CVCL_B2TG	Abcam HEK293T CAPN2 KO	Transformed cell line	Female
CVCL_D9AZ	Ubigene HEK293 CAPN2 KO	Transformed cell line	Female
CVCL_XM44	HAP1 CAPN2 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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