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Protein

Calpain-2 catalytic subunit

Gene

CAPN2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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' (PubMed:17650508). Proteolytically cleaves CPEB3 following neuronal stimulation which abolishes CPEB3 translational repressor activity, leading to translation of CPEB3 target mRNAs (By similarity).By similarity1 Publication

Catalytic activityi

Broad endopeptidase specificity.

Cofactori

Ca2+By similarityNote: Binds 7 Ca2+ ions.By similarity

Activity regulationi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi89Calcium 3; via carbonyl oxygenBy similarity1
Metal bindingi91Calcium 3; via carbonyl oxygenBy similarity1
Metal bindingi96Calcium 3By similarity1
Active sitei105By similarity1
Metal bindingi175Calcium 3By similarity1
Metal bindingi229Calcium 2By similarity1
Metal bindingi230Calcium 2By similarity1
Active sitei262By similarity1
Active sitei286By similarity1
Metal bindingi292Calcium 4By similarity1
Metal bindingi299Calcium 4By similarity1
Metal bindingi323Calcium 4; via carbonyl oxygenBy similarity1
Metal bindingi542Calcium 5; via carbonyl oxygenBy similarity1
Metal bindingi545Calcium 5By similarity1
Metal bindingi547Calcium 5; via carbonyl oxygenBy similarity1
Metal bindingi552Calcium 5By similarity1
Metal bindingi585Calcium 6By similarity1
Metal bindingi587Calcium 6By similarity1
Metal bindingi589Calcium 6; via carbonyl oxygenBy similarity1
Metal bindingi591Calcium 6; via carbonyl oxygenBy similarity1
Metal bindingi596Calcium 6By similarity1
Metal bindingi615Calcium 7By similarity1
Metal bindingi617Calcium 7By similarity1
Metal bindingi619Calcium 7; via carbonyl oxygenBy similarity1
Metal bindingi621Calcium 7; via carbonyl oxygenBy similarity1
Metal bindingi626Calcium 7By similarity1
Metal bindingi658Calcium 1By similarity1
Metal bindingi661Calcium 1By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi585 – 5961Add BLAST12
Calcium bindingi615 – 6262Add BLAST12

GO - Molecular functioni

  • calcium-dependent cysteine-type endopeptidase activity Source: BHF-UCL
  • calcium ion binding Source: Ensembl
  • cysteine-type peptidase activity Source: ProtInc
  • cytoskeletal protein binding Source: BHF-UCL
  • enzyme binding Source: Ensembl
  • protein heterodimerization activity Source: Ensembl

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease, Thiol protease
LigandCalcium, Metal-binding

Enzyme and pathway databases

BRENDAi3.4.22.53 2681
ReactomeiR-HSA-1474228 Degradation of the extracellular matrix
R-HSA-8862803 Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models
SIGNORiP17655

Protein family/group databases

MEROPSiC02.002

Names & Taxonomyi

Protein namesi
Recommended name:
Calpain-2 catalytic subunit (EC:3.4.22.53)
Alternative name(s):
Calcium-activated neutral proteinase 2
Short name:
CANP 2
Calpain M-type
Calpain large polypeptide L2
Calpain-2 large subunit
Millimolar-calpain
Short name:
M-calpain
Gene namesi
Name:CAPN2
Synonyms:CANPL2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000162909.17
HGNCiHGNC:1479 CAPN2
MIMi114230 gene
neXtProtiNX_P17655

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi824
OpenTargetsiENSG00000162909
PharmGKBiPA26060

Chemistry databases

ChEMBLiCHEMBL2382
GuidetoPHARMACOLOGYi2337

Polymorphism and mutation databases

BioMutaiCAPN2
DMDMi317373596

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
PropeptideiPRO_00000264872 – 19Anchors to the small subunitSequence analysisAdd BLAST18
ChainiPRO_000002648820 – 700Calpain-2 catalytic subunitAdd BLAST681

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiP17655
MaxQBiP17655
PaxDbiP17655
PeptideAtlasiP17655
PRIDEiP17655
ProteomicsDBi53499
53500 [P17655-2]

PTM databases

iPTMnetiP17655
PhosphoSitePlusiP17655
SwissPalmiP17655

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

BgeeiENSG00000162909 Expressed in 233 organ(s), highest expression level in nasal cavity epithelium
CleanExiHS_CAPN2
ExpressionAtlasiP17655 baseline and differential
GenevisibleiP17655 HS

Organism-specific databases

HPAiHPA024470

Interactioni

Subunit structurei

Forms a heterodimer with a small (regulatory) subunit (CAPNS1). Interacts with CPEB3; this leads to cleavage of CPEB3.By similarity

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107274, 54 interactors
IntActiP17655, 13 interactors
MINTiP17655
STRINGi9606.ENSP00000295006

Chemistry databases

BindingDBiP17655

Structurei

Secondary structure

1700
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP17655
SMRiP17655
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP17655

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini45 – 344Calpain catalyticPROSITE-ProRule annotationAdd BLAST300
Domaini572 – 605EF-hand 1PROSITE-ProRule annotationAdd BLAST34
Domaini602 – 637EF-hand 2PROSITE-ProRule annotationAdd BLAST36
Domaini667 – 700EF-hand 3PROSITE-ProRule annotationAdd BLAST34

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni345 – 514Domain IIIAdd BLAST170
Regioni515 – 529LinkerAdd BLAST15
Regioni530 – 700Domain IVAdd BLAST171

Sequence similaritiesi

Belongs to the peptidase C2 family.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0045 Eukaryota
ENOG410XP0B LUCA
GeneTreeiENSGT00760000118971
HOVERGENiHBG012645
InParanoidiP17655
KOiK03853
OMAiTNIHLGK
OrthoDBiEOG091G049E
PhylomeDBiP17655
TreeFamiTF314748

Family and domain databases

CDDicd00214 Calpain_III, 1 hit
cd00044 CysPc, 1 hit
InterProiView protein in InterPro
IPR033883 C2_III
IPR022684 Calpain_cysteine_protease
IPR022682 Calpain_domain_III
IPR022683 Calpain_III
IPR036213 Calpain_III_sf
IPR029539 CAPN2
IPR011992 EF-hand-dom_pair
IPR018247 EF_Hand_1_Ca_BS
IPR002048 EF_hand_dom
IPR038765 Papain_like_cys_pep_sf
IPR000169 Pept_cys_AS
IPR001300 Peptidase_C2_calpain_cat
PANTHERiPTHR10183:SF268 PTHR10183:SF268, 1 hit
PfamiView protein in Pfam
PF01067 Calpain_III, 1 hit
PF13833 EF-hand_8, 1 hit
PF00648 Peptidase_C2, 1 hit
PRINTSiPR00704 CALPAIN
SMARTiView protein in SMART
SM00720 calpain_III, 1 hit
SM00230 CysPc, 1 hit
SUPFAMiSSF47473 SSF47473, 1 hit
SSF49758 SSF49758, 1 hit
SSF54001 SSF54001, 1 hit
PROSITEiView protein in PROSITE
PS50203 CALPAIN_CAT, 1 hit
PS00018 EF_HAND_1, 2 hits
PS50222 EF_HAND_2, 3 hits
PS00139 THIOL_PROTEASE_CYS, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: P17655-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MAGIAAKLAK DREAAEGLGS HDRAIKYLNQ DYEALRNECL EAGTLFQDPS
60 70 80 90 100
FPAIPSALGF KELGPYSSKT RGIEWKRPTE ICADPQFIIG GATRTDICQG
110 120 130 140 150
ALGDCWLLAA IASLTLNEEI LARVVPLNQS FQENYAGIFH FQFWQYGEWV
160 170 180 190 200
EVVVDDRLPT KDGELLFVHS AEGSEFWSAL LEKAYAKING CYEALSGGAT
210 220 230 240 250
TEGFEDFTGG IAEWYELKKP PPNLFKIIQK ALQKGSLLGC SIDITSAADS
260 270 280 290 300
EAITFQKLVK GHAYSVTGAE EVESNGSLQK LIRIRNPWGE VEWTGRWNDN
310 320 330 340 350
CPSWNTIDPE ERERLTRRHE DGEFWMSFSD FLRHYSRLEI CNLTPDTLTS
360 370 380 390 400
DTYKKWKLTK MDGNWRRGST AGGCRNYPNT FWMNPQYLIK LEEEDEDEED
410 420 430 440 450
GESGCTFLVG LIQKHRRRQR KMGEDMHTIG FGIYEVPEEL SGQTNIHLSK
460 470 480 490 500
NFFLTNRARE RSDTFINLRE VLNRFKLPPG EYILVPSTFE PNKDGDFCIR
510 520 530 540 550
VFSEKKADYQ AVDDEIEANL EEFDISEDDI DDGFRRLFAQ LAGEDAEISA
560 570 580 590 600
FELQTILRRV LAKRQDIKSD GFSIETCKIM VDMLDSDGSG KLGLKEFYIL
610 620 630 640 650
WTKIQKYQKI YREIDVDRSG TMNSYEMRKA LEEAGFKMPC QLHQVIVARF
660 670 680 690 700
ADDQLIIDFD NFVRCLVRLE TLFKIFKQLD PENTGTIELD LISWLCFSVL
Length:700
Mass (Da):79,995
Last modified:January 11, 2011 - v6
Checksum:i8CF8294351A024E3
GO
Isoform 2 (identifier: P17655-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-78: Missing.
     79-79: T → M

Note: No experimental confirmation available.
Show »
Length:622
Mass (Da):71,476
Checksum:i60ED3A3498F6DD5D
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9JWY7C9JWY7_HUMAN
Calpain-2 catalytic subunit
CAPN2
131Annotation score:

Sequence cautioni

The sequence AAH07686 differs from that shown. Contaminating sequence. Potential poly-A sequence.Curated
The sequence AAH11828 differs from that shown. Contaminating sequence. Potential poly-A sequence.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti73 – 74IE → MR in AAA35645 (PubMed:2852952).Curated2
Sequence conflicti256Q → K in AAF99682 (PubMed:10944468).Curated1
Sequence conflicti300N → S in AAF99682 (PubMed:10944468).Curated1
Sequence conflicti534F → V in AAA35645 (PubMed:2852952).Curated1
Sequence conflicti534F → V in AAF99682 (PubMed:10944468).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01443522D → ECombined sources5 PublicationsCorresponds to variant dbSNP:rs25655Ensembl.1
Natural variantiVAR_02140468S → G2 PublicationsCorresponds to variant dbSNP:rs2230083Ensembl.1
Natural variantiVAR_021405476K → R1 PublicationCorresponds to variant dbSNP:rs9804140Ensembl.1
Natural variantiVAR_021406521E → Q1 PublicationCorresponds to variant dbSNP:rs28370127Ensembl.1
Natural variantiVAR_014436568K → Q1 PublicationCorresponds to variant dbSNP:rs17599Ensembl.1
Natural variantiVAR_021407677K → Q1 PublicationCorresponds to variant dbSNP:rs2230082Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0430271 – 78Missing in isoform 2. 1 PublicationAdd BLAST78
Alternative sequenceiVSP_04302879T → M in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M23254 mRNA Translation: AAA35645.1
AF261089 mRNA Translation: AAF99682.1
AK316211 mRNA Translation: BAH14582.1
AY835586 Genomic DNA Translation: AAV80421.1
AC096542 Genomic DNA No translation available.
AC099065 Genomic DNA No translation available.
BC007686 mRNA Translation: AAH07686.1 Sequence problems.
BC011828 mRNA Translation: AAH11828.1 Sequence problems.
BC021303 mRNA Translation: AAH21303.1
J04700 Genomic DNA Translation: AAA52760.1
CCDSiCCDS31035.1 [P17655-1]
CCDS53478.1 [P17655-2]
PIRiS10590 CIHUH2
RefSeqiNP_001139540.1, NM_001146068.1 [P17655-2]
NP_001739.2, NM_001748.4
UniGeneiHs.350899

Genome annotation databases

EnsembliENST00000295006; ENSP00000295006; ENSG00000162909 [P17655-1]
ENST00000433674; ENSP00000413158; ENSG00000162909 [P17655-2]
GeneIDi824
KEGGihsa:824
UCSCiuc001hob.5 human [P17655-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M23254 mRNA Translation: AAA35645.1
AF261089 mRNA Translation: AAF99682.1
AK316211 mRNA Translation: BAH14582.1
AY835586 Genomic DNA Translation: AAV80421.1
AC096542 Genomic DNA No translation available.
AC099065 Genomic DNA No translation available.
BC007686 mRNA Translation: AAH07686.1 Sequence problems.
BC011828 mRNA Translation: AAH11828.1 Sequence problems.
BC021303 mRNA Translation: AAH21303.1
J04700 Genomic DNA Translation: AAA52760.1
CCDSiCCDS31035.1 [P17655-1]
CCDS53478.1 [P17655-2]
PIRiS10590 CIHUH2
RefSeqiNP_001139540.1, NM_001146068.1 [P17655-2]
NP_001739.2, NM_001748.4
UniGeneiHs.350899

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1KFUX-ray2.50L2-700[»]
1KFXX-ray3.15L2-700[»]
2NQAX-ray2.20A/B48-346[»]
ProteinModelPortaliP17655
SMRiP17655
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107274, 54 interactors
IntActiP17655, 13 interactors
MINTiP17655
STRINGi9606.ENSP00000295006

Chemistry databases

BindingDBiP17655
ChEMBLiCHEMBL2382
GuidetoPHARMACOLOGYi2337

Protein family/group databases

MEROPSiC02.002

PTM databases

iPTMnetiP17655
PhosphoSitePlusiP17655
SwissPalmiP17655

Polymorphism and mutation databases

BioMutaiCAPN2
DMDMi317373596

Proteomic databases

EPDiP17655
MaxQBiP17655
PaxDbiP17655
PeptideAtlasiP17655
PRIDEiP17655
ProteomicsDBi53499
53500 [P17655-2]

Protocols and materials databases

DNASUi824
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000295006; ENSP00000295006; ENSG00000162909 [P17655-1]
ENST00000433674; ENSP00000413158; ENSG00000162909 [P17655-2]
GeneIDi824
KEGGihsa:824
UCSCiuc001hob.5 human [P17655-1]

Organism-specific databases

CTDi824
DisGeNETi824
EuPathDBiHostDB:ENSG00000162909.17
GeneCardsiCAPN2
HGNCiHGNC:1479 CAPN2
HPAiHPA024470
MIMi114230 gene
neXtProtiNX_P17655
OpenTargetsiENSG00000162909
PharmGKBiPA26060
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0045 Eukaryota
ENOG410XP0B LUCA
GeneTreeiENSGT00760000118971
HOVERGENiHBG012645
InParanoidiP17655
KOiK03853
OMAiTNIHLGK
OrthoDBiEOG091G049E
PhylomeDBiP17655
TreeFamiTF314748

Enzyme and pathway databases

BRENDAi3.4.22.53 2681
ReactomeiR-HSA-1474228 Degradation of the extracellular matrix
R-HSA-8862803 Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models
SIGNORiP17655

Miscellaneous databases

ChiTaRSiCAPN2 human
EvolutionaryTraceiP17655
GeneWikiiCAPN2
GenomeRNAii824
PROiPR:P17655
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000162909 Expressed in 233 organ(s), highest expression level in nasal cavity epithelium
CleanExiHS_CAPN2
ExpressionAtlasiP17655 baseline and differential
GenevisibleiP17655 HS

Family and domain databases

CDDicd00214 Calpain_III, 1 hit
cd00044 CysPc, 1 hit
InterProiView protein in InterPro
IPR033883 C2_III
IPR022684 Calpain_cysteine_protease
IPR022682 Calpain_domain_III
IPR022683 Calpain_III
IPR036213 Calpain_III_sf
IPR029539 CAPN2
IPR011992 EF-hand-dom_pair
IPR018247 EF_Hand_1_Ca_BS
IPR002048 EF_hand_dom
IPR038765 Papain_like_cys_pep_sf
IPR000169 Pept_cys_AS
IPR001300 Peptidase_C2_calpain_cat
PANTHERiPTHR10183:SF268 PTHR10183:SF268, 1 hit
PfamiView protein in Pfam
PF01067 Calpain_III, 1 hit
PF13833 EF-hand_8, 1 hit
PF00648 Peptidase_C2, 1 hit
PRINTSiPR00704 CALPAIN
SMARTiView protein in SMART
SM00720 calpain_III, 1 hit
SM00230 CysPc, 1 hit
SUPFAMiSSF47473 SSF47473, 1 hit
SSF49758 SSF49758, 1 hit
SSF54001 SSF54001, 1 hit
PROSITEiView protein in PROSITE
PS50203 CALPAIN_CAT, 1 hit
PS00018 EF_HAND_1, 2 hits
PS50222 EF_HAND_2, 3 hits
PS00139 THIOL_PROTEASE_CYS, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCAN2_HUMAN
AccessioniPrimary (citable) accession number: P17655
Secondary accession number(s): A6NDG7
, B7ZA96, E7ES58, Q16738, Q6PJT3, Q8WU26, Q9HBB1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: January 11, 2011
Last modified: November 7, 2018
This is version 219 of the entry and version 6 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Peptidase families
    Classification of peptidase families and list of entries
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  7. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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