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Q07009 (CAN2_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 144. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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-2 large subunit
Millimolar-calpain
Short name=M-calpain
Gene names
Name:Capn2
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length700 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Calcium-regulated non-lysosomal thiol-protease which catalyze limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction. Proteolytically cleaves MYOC at 'Arg-226' By similarity.

Catalytic activity

Broad endopeptidase specificity.

Cofactor

Binds 7 calcium ions.

Enzyme regulation

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

Subunit structure

Forms a heterodimer with a small (regulatory) subunit (CAPNS1). Ref.7 Ref.8

Subcellular location

Cytoplasm By similarity. Cell membrane By similarity. Note: Translocates to the plasma membrane upon Ca2+ binding By similarity.

Tissue specificity

Ubiquitous.

Sequence similarities

Belongs to the peptidase C2 family.

Contains 1 calpain catalytic domain.

Contains 3 EF-hand domains.

Ontologies

Keywords
   Cellular componentCell membrane
Cytoplasm
Membrane
   DomainRepeat
   LigandCalcium
Metal-binding
   Molecular functionHydrolase
Protease
Thiol protease
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processblastocyst development

Inferred from electronic annotation. Source: Ensembl

cellular response to amino acid stimulus

Inferred from direct assay PubMed 22711986. Source: UniProtKB

myoblast fusion

Inferred from electronic annotation. Source: Ensembl

protein autoprocessing

Inferred from direct assay PubMed 17182728. Source: RGD

proteolysis

Inferred from direct assay PubMed 22711986. Source: UniProtKB

response to hypoxia

Inferred from expression pattern PubMed 15979593. Source: RGD

   Cellular_componentchromatin

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay PubMed 22711986. Source: UniProtKB

cytosol

Inferred from sequence or structural similarity. Source: BHF-UCL

dendrite

Inferred from direct assay PubMed 22711986. Source: UniProtKB

nucleus

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Inferred from sequence or structural similarity. Source: BHF-UCL

   Molecular_functioncalcium ion binding

Inferred from direct assay PubMed 14976200PubMed 17402852. Source: RGD

calcium-dependent cysteine-type endopeptidase activity

Inferred from direct assay PubMed 22711986. Source: UniProtKB

cytoskeletal protein binding

Inferred from direct assay PubMed 17429681. Source: RGD

protein binding

Inferred from physical interaction PubMed 17543955PubMed 17889653. Source: IntAct

protein heterodimerization activity

Inferred from physical interaction PubMed 7982961. Source: RGD

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CastP273215EBI-1040438,EBI-7441624
srp-6G5EFH42EBI-1040438,EBI-1549936From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Propeptide2 – 1918Anchors to the small subunit Potential
PRO_0000026493
Chain20 – 700681Calpain-2 catalytic subunit
PRO_0000026494

Regions

Domain45 – 344300Calpain catalytic
Domain572 – 60534EF-hand 1
Domain602 – 63736EF-hand 2
Domain667 – 70034EF-hand 3
Calcium binding585 – 596121 Ref.7 Ref.8
Calcium binding615 – 626122 Ref.7 Ref.8
Region345 – 514170Domain III
Region515 – 52915Linker
Region530 – 700171Domain IV

Sites

Active site1051
Active site2621
Active site2861
Metal binding891Calcium 3; via carbonyl oxygen
Metal binding911Calcium 3; via carbonyl oxygen
Metal binding961Calcium 3
Metal binding1751Calcium 3
Metal binding2291Calcium 2
Metal binding2301Calcium 2
Metal binding2921Calcium 4
Metal binding2991Calcium 4
Metal binding3191Calcium 4; via carbonyl oxygen
Metal binding3231Calcium 4; via carbonyl oxygen
Metal binding5421Calcium 5; via carbonyl oxygen
Metal binding5451Calcium 5
Metal binding5471Calcium 5; via carbonyl oxygen
Metal binding5521Calcium 5
Metal binding5851Calcium 6
Metal binding5871Calcium 6
Metal binding5891Calcium 6; via carbonyl oxygen
Metal binding5911Calcium 6; via carbonyl oxygen
Metal binding5961Calcium 6
Metal binding6151Calcium 7
Metal binding6171Calcium 7
Metal binding6191Calcium 7; via carbonyl oxygen
Metal binding6211Calcium 7; via carbonyl oxygen
Metal binding6261Calcium 7
Metal binding6581Calcium 1
Metal binding6611Calcium 1

Amino acid modifications

Modified residue21N-acetylalanine By similarity

Experimental info

Mutagenesis1051C → S: Loss of activity. Ref.5
Mutagenesis2261K → S: 12% decrease in activity.
Mutagenesis2301K → E: 84% decrease in activity. Ref.4
Mutagenesis2301K → S: No effect. Ref.4
Mutagenesis2341K → E: 85% decrease in activity. Ref.4
Mutagenesis2341K → S: 20% decrease in activity. Ref.4
Mutagenesis2621H → A: Loss of activity. Ref.5
Mutagenesis2861N → A: Loss of activity. Ref.5
Mutagenesis2881W → Y: 95% decrease in activity. Ref.5
Mutagenesis4171R → A: Decreases catalytic activity. Ref.7
Mutagenesis4201R → A: Decreases catalytic activity. Ref.7
Mutagenesis4691R → A: Decreases catalytic activity. Ref.7
Mutagenesis5041E → S: 10% decrease in activity. Ref.4

Secondary structure

................................................................................................................................... 700
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q07009 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 296B0DC3BEEF5B90

FASTA70079,919
        10         20         30         40         50         60 
MAGIAMKLAK DREAAEGLGS HERAIKYLNQ DYETLRNECL EAGALFQDPS FPALPSSLGF 

        70         80         90        100        110        120 
KELGPYSSKT RGIEWKRPTE ICADPQFIIG GATRTDICQG ALGDCWLLAA IASLTLNEEI 

       130        140        150        160        170        180 
LARVVPLDQS FQENYAGIFH FQFWQYGEWV EVVVDDRLPT KDGELLFVHS AEGSEFWSAL 

       190        200        210        220        230        240 
LEKAYAKING CYEALSGGAT TEGFEDFTGG IAEWYELRKP PPNLFKIIQK ALEKGSLLGC 

       250        260        270        280        290        300 
SIDITSAADS EAVTYQKLVK GHAYSVTGAE EVESSGSLQK LIRIRNPWGQ VEWTGKWNDN 

       310        320        330        340        350        360 
CPSWNTVDPE VRANLTERQE DGEFWMSFSD FLRHYSRLEI CNLTPDTLTC DSYKKWKLTK 

       370        380        390        400        410        420 
MDGNWRRGST AGGCRNYPNT FWMNPQYLIK LEEEDEDDED GERGCTFLVG LIQKHRRRQR 

       430        440        450        460        470        480 
KMGEDMHTIG FGIYEVPEEL TGQTNIHLSK NFFLTTRARE RSDTFINLRE VLNRFKLPPG 

       490        500        510        520        530        540 
EYVLVPSTFE PHKNGDFCIR VFSEKKADYQ TVDDEIEANI EEIEANEEDI GDGFRRLFAQ 

       550        560        570        580        590        600 
LAGEDAEISA FELQTILRRV LAKREDIKSD GFSIETCKIM VDMLDEDGSG KLGLKEFYIL 

       610        620        630        640        650        660 
WTKIQKYQKI YREIDVDRSG TMNSYEMRKA LEEAGFKLPC QLHQVIVARF ADDELIIDFD 

       670        680        690        700 
NFVRCLVRLE ILFKIFKQLD PENTGTIQLD LISWLSFSVL 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning and bacterial expression of cDNA for rat calpain II 80 kDa subunit."
Deluca C.I., Davies P.L., Samis J.A., Elce J.S.
Biochim. Biophys. Acta 1216:81-93(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Prostate.
[3]"Ca(2+)-induced structural changes in rat m-calpain revealed by partial proteolysis."
Moldoveanu T., Hosfield C.M., Jia Z., Elce J.S., Davies P.L.
Biochim. Biophys. Acta 1545:245-254(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL PROTEIN SEQUENCE.
[4]"Calpain mutants with increased Ca2+ sensitivity and implications for the role of the C(2)-like domain."
Hosfield C.M., Moldoveanu T., Davies P.L., Elce J.S., Jia Z.
J. Biol. Chem. 276:7404-7407(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF LYS-230; LYS-234 AND GLU-504.
[5]"Active site residues in m-calpain: identification by site-directed mutagenesis."
Arthur J.S., Gauthier S., Elce J.S.
FEBS Lett. 368:397-400(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF CYS-105; HIS-262; ASN-286 AND TRP-288.
[6]"Crystal structure of calpain reveals the structural basis for Ca(2+)-dependent protease activity and a novel mode of enzyme activation."
Hosfield C.M., Elce J.S., Davies P.L., Jia Z.
EMBO J. 18:6880-6889(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS).
[7]"Concerted multi-pronged attack by calpastatin to occlude the catalytic cleft of heterodimeric calpains."
Moldoveanu T., Gehring K., Green D.R.
Nature 456:404-408(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.95 ANGSTROMS) IN COMPLEX WITH CAPNS1 AND CALPASTATIN, CALCIUM-BINDING SITES, SUBUNIT, MUTAGENESIS OF ARG-417; ARG-420 AND ARG-469.
[8]"Calcium-bound structure of calpain and its mechanism of inhibition by calpastatin."
Hanna R.A., Campbell R.L., Davies P.L.
Nature 456:409-412(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF MUTANT SER-105 IN COMPLEX WITH CAPNS1 AND CALPASTATIN, CALCIUM-BINDING SITES, SUBUNIT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L09120 mRNA. Translation: AAA16327.1.
BC065306 mRNA. Translation: AAH65306.1.
PIRS38361.
RefSeqNP_058812.1. NM_017116.2.
UniGeneRn.6822.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1DF0X-ray2.60A1-700[»]
1MDWX-ray1.95A/B19-346[»]
1QXPX-ray2.80A/B1-700[»]
1U5IX-ray2.86A1-700[»]
3BOWX-ray2.40A1-700[»]
3DF0X-ray2.95A1-700[»]
ProteinModelPortalQ07009.
SMRQ07009. Positions 2-700.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-6139N.
IntActQ07009. 4 interactions.
MINTMINT-112911.
STRING10116.ENSRNOP00000046509.

Protein family/group databases

MEROPSC02.002.

Proteomic databases

PaxDbQ07009.
PRIDEQ07009.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000045326; ENSRNOP00000046509; ENSRNOG00000034015.
GeneID29154.
KEGGrno:29154.
UCSCRGD:2268. rat.

Organism-specific databases

CTD824.
RGD2268. Capn2.

Phylogenomic databases

eggNOGNOG327523.
GeneTreeENSGT00750000117643.
HOGENOMHOG000232035.
HOVERGENHBG012645.
InParanoidQ07009.
KOK03853.
OMADTYKKWK.
OrthoDBEOG7RV9FM.
PhylomeDBQ07009.
TreeFamTF314748.

Enzyme and pathway databases

BRENDA3.4.22.53. 5301.

Gene expression databases

GenevestigatorQ07009.

Family and domain databases

Gene3D1.10.238.10. 1 hit.
InterProIPR022684. Calpain_cysteine_protease.
IPR022682. Calpain_domain_III.
IPR022683. Calpain_III.
IPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR000169. Pept_cys_AS.
IPR001300. Peptidase_C2_calpain_cat.
[Graphical view]
PfamPF01067. Calpain_III. 1 hit.
PF00648. Peptidase_C2. 1 hit.
[Graphical view]
PRINTSPR00704. CALPAIN.
SMARTSM00720. calpain_III. 1 hit.
SM00230. CysPc. 1 hit.
SM00054. EFh. 2 hits.
[Graphical view]
SUPFAMSSF49758. SSF49758. 1 hit.
PROSITEPS50203. CALPAIN_CAT. 1 hit.
PS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 3 hits.
PS00139. THIOL_PROTEASE_CYS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ07009.
NextBio608171.
PROQ07009.

Entry information

Entry nameCAN2_RAT
AccessionPrimary (citable) accession number: Q07009
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: January 23, 2007
Last modified: June 11, 2014
This is version 144 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references