Target Information

Target General Information

Target ID

T92517

Target Name

Calpain-1 (CAPN1)

Synonyms

muCANP; PIG30; Micromolar-calpain; Cell proliferation-inducing gene 30 protein; Calpain-1 large subunit; Calpain-1 catalytic subunit; Calpain mu-type; Calcium-activated neutral proteinase 1; CANPL1; CANP 1

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Gene Name

CAPN1

Target Type

Patented-recorded target

[1]

Function

Calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction.

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BioChemical Class

Peptidase

UniProt ID

CAN1_HUMAN

EC Number

EC 3.4.22.52

Sequence

MSEEIITPVYCTGVSAQVQKQRARELGLGRHENAIKYLGQDYEQLRVRCLQSGTLFRDEA
FPPVPQSLGYKDLGPNSSKTYGIKWKRPTELLSNPQFIVDGATRTDICQGALGDCWLLAA
IASLTLNDTLLHRVVPHGQSFQNGYAGIFHFQLWQFGEWVDVVVDDLLPIKDGKLVFVHS
AEGNEFWSALLEKAYAKVNGSYEALSGGSTSEGFEDFTGGVTEWYELRKAPSDLYQIILK
ALERGSLLGCSIDISSVLDMEAITFKKLVKGHAYSVTGAKQVNYRGQVVSLIRMRNPWGE
VEWTGAWSDSSSEWNNVDPYERDQLRVKMEDGEFWMSFRDFMREFTRLEICNLTPDALKS
RTIRKWNTTLYEGTWRRGSTAGGCRNYPATFWVNPQFKIRLDETDDPDDYGDRESGCSFV
LALMQKHRRRERRFGRDMETIGFAVYEVPPELVGQPAVHLKRDFFLANASRARSEQFINL
REVSTRFRLPPGEYVVVPSTFEPNKEGDFVLRFFSEKSAGTVELDDQIQANLPDEQVLSE
EEIDENFKALFRQLAGEDMEISVKELRTILNRIISKHKDLRTKGFSLESCRSMVNLMDRD
GNGKLGLVEFNILWNRIRNYLSIFRKFDLDKSGSMSAYEMRMAIESAGFKLNKKLYELII
TRYSEPDLAVDFDNFVCCLVRLETMFRFFKTLDTDLDGVVTFDLFKWLQLTMFA

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3D Structure

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AlphaFold

HIT2.0 ID

T26TBJ

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Drug Binding Sites of Target

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Ligand Name: N-[(Benzyloxy)carbonyl]leucyl-N~1~-[3-Fluoro-1-(4-Hydroxybenzyl)-2-Oxopropyl]leucinamide

Ligand Info

Structure Description

Human calpain protease core inhibited by ZLLYCH2F

PDB:1ZCM

Method

X-ray diffraction

Resolution

2.00 Å

Mutation

Yes

[2]

PDB Sequence

NAIKYLGQDY

⁴²

EQLRVRCLQS

⁵²

GTLFRDEAFP

⁶²

PVPQSLGYKD

⁷²

LGPNSSKTYG

⁸²

IKWKRPTELL

⁹²

SNPQFIVDGA

¹⁰²

TRTDICQGAL

¹¹²

GDCWLLAAIA

¹²²

SLTLNDTLLH

¹³²

RVVPHGQSFQ

¹⁴²

NGYAGIFHFQ

¹⁵²

LWQFGEWVDV

¹⁶²

VVDDLLPIKD

¹⁷²

GKLVFVHSAE

¹⁸²

GNEFWSALLE

¹⁹²

KAYAKVNGSY

²⁰²

EALSGGSTSE

²¹²

AFEDFTGGVT

²²²

EWYELRKAPS

²³²

DLYQIILKAL

²⁴²

ERGSLLGCSI

²⁵²

DISSVLDMEA

²⁶²

ITFKKLVKGH

²⁷²

AYSVTGAKQV

²⁸²

NYRGQVVSLI

²⁹²

RMRNPWGEVE

³⁰²

WTGAWSDSSS

³¹²

EWNNVDPYER

³²²

DQLRVKMEDG

³³²

EFWMSFRDFM

³⁴²

REFTRLEICN

³⁵²

Residue

Distance (Å)

GLN109

3.017

LEU112

4.193

GLY113

3.073

ASP114

3.587

CYS115

1.674

TRP116

3.325

SER206

3.354

GLY207

3.351

GLY208

2.935

Residue

Distance (Å)

SER209

4.632

THR210

3.557

SER251

4.148

MET260

4.277

GLU261

3.600

GLY271

3.505

HIS272

3.203

ALA273

3.885

GLU349

4.931

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Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues. The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021). Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function. Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006). Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database. The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017). Human Similarity Proteins Human Tissue Distribution Human Pathway Affiliation Biological Network Descriptors

Different Human System Profiles of Target

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Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.

The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021).

Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.

Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006).

Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.

The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017).

Human Similarity Proteins

Human Tissue Distribution

Human Pathway Affiliation

Biological Network Descriptors

Protein Name	Pfam ID	Percentage of Identity (%)	E value
Calpain small subunit 1 (CAPNS1)		50.000 (88/176)	1.13E-56
Peflin (PEF1)	PF13405 ; PF13499	26.144 (40/153)	2.10E-16
Programmed cell death protein 6 (PDCD6)	PF13202 ; PF13499	24.031 (31/129)	8.04E-13
Calmodulin-like protein 3 (CALML3)	PF13499	28.289 (43/152)	1.03E-05
Calmodulin-3 (CALM3)	PF13499	28.289 (43/152)	1.04E-05
Calmodulin-2 (CALM2)	PF13499	28.289 (43/152)	1.04E-05
Calmodulin-1 (CALM1)	PF13499	28.289 (43/152)	1.04E-05
Calmodulin-like protein 5 (CALML5)	PF13499	25.962 (27/104)	1.00E-03
Calcium-binding protein 4 (CABP4)	PF00036 ; PF13499	33.803 (24/71)	5.00E-03
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Note: If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.

KEGG Pathway	Pathway ID	Affiliated Target
Protein processing in endoplasmic reticulum	hsa04141	Affiliated Target
Class: Genetic Information Processing => Folding, sorting and degradation	Pathway Hierarchy
Apoptosis	hsa04210	Affiliated Target
Class: Cellular Processes => Cell growth and death	Pathway Hierarchy
Necroptosis	hsa04217	Affiliated Target
Class: Cellular Processes => Cell growth and death	Pathway Hierarchy
Cellular senescence	hsa04218	Affiliated Target
Class: Cellular Processes => Cell growth and death	Pathway Hierarchy

Degree	4	Degree centrality	4.30E-04	Betweenness centrality	8.58E-05
Closeness centrality	2.01E-01	Radiality	1.35E+01	Clustering coefficient	1.67E-01
Neighborhood connectivity	1.08E+01	Topological coefficient	2.70E-01	Eccentricity	13
Download	Click to Download the Full PPI Network of This Target