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P07384 (CAN1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 170. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Calpain-1 catalytic subunit

EC=3.4.22.52
Alternative name(s):
Calcium-activated neutral proteinase 1
Short name=CANP 1
Calpain mu-type
Calpain-1 large subunit
Cell proliferation-inducing gene 30 protein
Micromolar-calpain
Short name=muCANP
Gene names
Name:CAPN1
Synonyms:CANPL1
ORF Names:PIG30
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length714 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.

Catalytic activity

Broad endopeptidase specificity.

Cofactor

Binds 4 calcium ions.

Enzyme regulation

Activated by micromolar concentrations of calcium and inhibited by calpastatin.

Subunit structure

Forms a heterodimer with a small (regulatory) subunit (CAPNS1).

Subcellular location

Cytoplasm. Cell membrane. Note: Translocates to the plasma membrane upon Ca2+ binding. Ref.7

Tissue specificity

Ubiquitous.

Post-translational modification

Undergoes calcium-induced successive autoproteolytic cleavages that generate a membrane-bound 78 kDa active form and an intracellular 75 kDa active form. Calpastatin reduces with high efficiency the transition from 78 kDa to 75 kDa calpain forms.

Sequence similarities

Belongs to the peptidase C2 family.

Contains 1 calpain catalytic domain.

Contains 4 EF-hand domains.

Ontologies

Keywords
   Cellular componentCell membrane
Cytoplasm
Membrane
   Coding sequence diversityPolymorphism
   DomainRepeat
   LigandCalcium
Metal-binding
   Molecular functionHydrolase
Protease
Thiol protease
   PTMAcetylation
Autocatalytic cleavage
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processextracellular matrix disassembly

Traceable author statement. Source: Reactome

extracellular matrix organization

Traceable author statement. Source: Reactome

positive regulation of cell proliferation

Traceable author statement PubMed 8702541. Source: ProtInc

proteolysis

Inferred from sequence or structural similarity. Source: UniProtKB

receptor catabolic process

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytoplasm

Inferred from direct assay. Source: HPA

cytosol

Inferred from direct assay PubMed 12150984PubMed 14559243. Source: BHF-UCL

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867PubMed 19199708PubMed 23376485. Source: UniProt

membrane

Inferred from direct assay PubMed 14559243. Source: BHF-UCL

plasma membrane

Inferred from direct assay PubMed 12150984. Source: BHF-UCL

   Molecular_functioncalcium ion binding

Inferred from electronic annotation. Source: InterPro

calcium-dependent cysteine-type endopeptidase activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 19712109PubMed 21988832PubMed 22805611PubMed 9407132. Source: IntAct

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.9
Chain2 – 714713Calpain-1 catalytic subunit
PRO_0000207694

Regions

Domain55 – 354300Calpain catalytic
Domain541 – 57636EF-hand 1
Domain585 – 61834EF-hand 2
Domain615 – 65036EF-hand 3
Domain680 – 71435EF-hand 4
Calcium binding99 – 10681 Ref.8 Ref.13
Calcium binding302 – 333322 Ref.8 Ref.13
Calcium binding598 – 609123 Ref.8 Ref.13
Calcium binding628 – 639124 Ref.8 Ref.13
Region355 – 526172Domain III
Region527 – 54216Linker
Region543 – 713171Domain IV

Sites

Active site1151 By similarity
Active site2721 By similarity
Active site2961 By similarity
Site15 – 162Cleavage; for 78 kDa form
Site27 – 282Cleavage; for 75 kDa form

Amino acid modifications

Modified residue21N-acetylserine Ref.9 Ref.11 Ref.12

Natural variations

Natural variant1031T → A. Ref.4
Corresponds to variant rs17885718 [ dbSNP | Ensembl ].
VAR_021085
Natural variant4331R → P. Ref.4 Ref.5
Corresponds to variant rs10895991 [ dbSNP | Ensembl ].
VAR_021086
Natural variant4921G → R. Ref.4
Corresponds to variant rs17883283 [ dbSNP | Ensembl ].
VAR_021087
Natural variant6761V → I. Ref.4
Corresponds to variant rs17884773 [ dbSNP | Ensembl ].
VAR_021088

Experimental info

Sequence conflict5481K → N in AAH08751. Ref.5

Secondary structure

........................................................... 714
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P07384 [UniParc].

Last modified April 1, 1988. Version 1.
Checksum: 1CB6D7C56D063498

FASTA71481,890
        10         20         30         40         50         60 
MSEEIITPVY CTGVSAQVQK QRARELGLGR HENAIKYLGQ DYEQLRVRCL QSGTLFRDEA 

        70         80         90        100        110        120 
FPPVPQSLGY KDLGPNSSKT YGIKWKRPTE LLSNPQFIVD GATRTDICQG ALGDCWLLAA 

       130        140        150        160        170        180 
IASLTLNDTL LHRVVPHGQS FQNGYAGIFH FQLWQFGEWV DVVVDDLLPI KDGKLVFVHS 

       190        200        210        220        230        240 
AEGNEFWSAL LEKAYAKVNG SYEALSGGST SEGFEDFTGG VTEWYELRKA PSDLYQIILK 

       250        260        270        280        290        300 
ALERGSLLGC SIDISSVLDM EAITFKKLVK GHAYSVTGAK QVNYRGQVVS LIRMRNPWGE 

       310        320        330        340        350        360 
VEWTGAWSDS SSEWNNVDPY ERDQLRVKME DGEFWMSFRD FMREFTRLEI CNLTPDALKS 

       370        380        390        400        410        420 
RTIRKWNTTL YEGTWRRGST AGGCRNYPAT FWVNPQFKIR LDETDDPDDY GDRESGCSFV 

       430        440        450        460        470        480 
LALMQKHRRR ERRFGRDMET IGFAVYEVPP ELVGQPAVHL KRDFFLANAS RARSEQFINL 

       490        500        510        520        530        540 
REVSTRFRLP PGEYVVVPST FEPNKEGDFV LRFFSEKSAG TVELDDQIQA NLPDEQVLSE 

       550        560        570        580        590        600 
EEIDENFKAL FRQLAGEDME ISVKELRTIL NRIISKHKDL RTKGFSLESC RSMVNLMDRD 

       610        620        630        640        650        660 
GNGKLGLVEF NILWNRIRNY LSIFRKFDLD KSGSMSAYEM RMAIESAGFK LNKKLYELII 

       670        680        690        700        710 
TRYSEPDLAV DFDNFVCCLV RLETMFRFFK TLDTDLDGVV TFDLFKWLQL TMFA 

« Hide

References

« Hide 'large scale' references
[1]"Complete amino acid sequence of the large subunit of the low-Ca2+-requiring form of human Ca2+-activated neutral protease (muCANP) deduced from its cDNA sequence."
Aoki K., Imajoh S., Ohno S., Emori Y., Koike M., Kosaki G., Suzuki K.
FEBS Lett. 205:313-317(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"A novel member of the calcium-dependent cysteine protease family."
Sorimachi H., Ohmi S., Emori Y., Kawasaki H., Saido T.C., Ohno S., Minami Y., Suzuki K.
Biol. Chem. Hoppe-Seyler 371:171-176(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Identification of a human cell proliferation inducing gene."
Kim J.W.
Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]NIEHS SNPs program
Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ALA-103; PRO-433; ARG-492 AND ILE-676.
[5]"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], VARIANT PRO-433.
Tissue: Kidney, Pancreas and Placenta.
[6]"Modulation of the calpain autoproteolysis by calpastatin and phospholipids."
Melloni E., Michetti M., Salamino F., Minafra R., Pontremoli S.
Biochem. Biophys. Res. Commun. 229:193-197(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: AUTOPROTEOLYTIC PROCESSING.
[7]"Autolysis of human erythrocyte calpain produces two active enzyme forms with different cell localization."
Michetti M., Salamino F., Tedesco I., Averna M., Minafra R., Melloni E., Pontremoli S.
FEBS Lett. 392:11-15(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: AUTOPROTEOLYTIC PROCESSING, SUBCELLULAR LOCATION.
[8]"Calcium-binding properties of human erythrocyte calpain."
Michetti M., Salamino F., Minafra R., Melloni E., Pontremoli S.
Biochem. J. 325:721-726(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: CALCIUM-BINDING DATA.
[9]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[10]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"Molecular mode of action of a covalently inhibiting peptidomimetic on the human calpain protease core."
Li Q., Hanzlik R.P., Weaver R.F., Schonbrunn E.
Biochemistry 45:701-708(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 33-353 OF MUTANT ALA-213, CALCIUM-BINDING REGIONS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X04366 mRNA. Translation: CAA27881.1.
AY550975 mRNA. Translation: AAT52221.1.
AY796340 Genomic DNA. Translation: AAV41878.1.
BC008751 mRNA. Translation: AAH08751.1.
BC017200 mRNA. Translation: AAH17200.1.
BC075862 mRNA. Translation: AAH75862.1.
CCDSCCDS44644.1.
PIRCIHUH. A26213.
RefSeqNP_001185797.1. NM_001198868.1.
NP_001185798.1. NM_001198869.1.
NP_005177.2. NM_005186.3.
XP_006718761.1. XM_006718698.1.
UniGeneHs.502842.
Hs.735492.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1ZCMX-ray2.00A33-353[»]
2ARYX-ray2.40A/B29-360[»]
ProteinModelPortalP07384.
SMRP07384. Positions 13-713.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107273. 68 interactions.
IntActP07384. 10 interactions.
MINTMINT-5004023.
STRING9606.ENSP00000279247.

Chemistry

BindingDBP07384.
ChEMBLCHEMBL3038466.

Protein family/group databases

MEROPSC02.001.

PTM databases

PhosphoSiteP07384.

Polymorphism databases

DMDM115574.

Proteomic databases

MaxQBP07384.
PaxDbP07384.
PRIDEP07384.

Protocols and materials databases

DNASU823.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000279247; ENSP00000279247; ENSG00000014216.
ENST00000524773; ENSP00000434176; ENSG00000014216.
ENST00000527323; ENSP00000431984; ENSG00000014216.
ENST00000533129; ENSP00000431686; ENSG00000014216.
ENST00000533820; ENSP00000435272; ENSG00000014216.
GeneID823.
KEGGhsa:823.
UCSCuc001odf.2. human.

Organism-specific databases

CTD823.
GeneCardsGC11P064950.
HGNCHGNC:1476. CAPN1.
HPAHPA005992.
MIM114220. gene.
neXtProtNX_P07384.
PharmGKBPA26057.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG327523.
HOGENOMHOG000232035.
HOVERGENHBG012645.
InParanoidP07384.
KOK01367.
OMAPQSLGYK.
OrthoDBEOG7RV9FM.
PhylomeDBP07384.
TreeFamTF314748.

Enzyme and pathway databases

BRENDA3.4.22.52. 2681.
ReactomeREACT_118779. Extracellular matrix organization.

Gene expression databases

ArrayExpressP07384.
BgeeP07384.
CleanExHS_CAPN1.
GenevestigatorP07384.

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.
PF13405. EF-hand_6. 1 hit.
PF00648. Peptidase_C2. 1 hit.
[Graphical view]
PRINTSPR00704. CALPAIN.
SMARTSM00720. calpain_III. 1 hit.
SM00230. CysPc. 1 hit.
SM00054. EFh. 3 hits.
[Graphical view]
SUPFAMSSF49758. SSF49758. 1 hit.
PROSITEPS50203. CALPAIN_CAT. 1 hit.
PS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 4 hits.
PS00139. THIOL_PROTEASE_CYS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCAPN1. human.
EvolutionaryTraceP07384.
GeneWikiCAPN1.
GenomeRNAi823.
NextBio3370.
PMAP-CutDBP07384.
PROP07384.
SOURCESearch...

Entry information

Entry nameCAN1_HUMAN
AccessionPrimary (citable) accession number: P07384
Secondary accession number(s): Q2TTR0, Q6DHV4
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1988
Last sequence update: April 1, 1988
Last modified: July 9, 2014
This is version 170 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

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

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM