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Protein

Calpain-1 catalytic subunit

Gene

CAPN1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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

Catalytic activityi

Broad endopeptidase specificity.

Cofactori

Ca2+Note: Binds 4 Ca2+ ions.

Enzyme regulationi

Activated by micromolar concentrations of calcium and inhibited by calpastatin.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei115By similarity1
Active sitei272By similarity1
Active sitei296By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi99 – 10618
Calcium bindingi302 – 3332Add BLAST32
Calcium bindingi598 – 6093Add BLAST12
Calcium bindingi628 – 6394Add BLAST12

GO - Molecular functioni

GO - Biological processi

  • extracellular matrix disassembly Source: Reactome
  • mammary gland involution Source: Ensembl
  • positive regulation of cell proliferation Source: ProtInc
  • proteolysis Source: UniProtKB
  • receptor catabolic process Source: Ensembl
  • regulation of macroautophagy Source: ParkinsonsUK-UCL
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Ligandi

Calcium, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:HS00359-MONOMER.
BRENDAi3.4.22.52. 2681.
3.4.22.53. 2681.
ReactomeiR-HSA-1474228. Degradation of the extracellular matrix.
R-HSA-6798695. Neutrophil degranulation.
R-HSA-6809371. Formation of the cornified envelope.

Protein family/group databases

MEROPSiC02.001.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:CAPN1
Synonyms:CANPL1
ORF Names:PIG30
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:1476. CAPN1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: HPA
  • cytosol Source: BHF-UCL
  • extracellular exosome Source: UniProtKB
  • focal adhesion Source: UniProtKB
  • lysosome Source: Ensembl
  • membrane Source: BHF-UCL
  • mitochondrion Source: Ensembl
  • plasma membrane Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi823.
OpenTargetsiENSG00000014216.
PharmGKBiPA26057.

Chemistry databases

ChEMBLiCHEMBL3891.

Polymorphism and mutation databases

BioMutaiCAPN1.
DMDMi115574.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00002076942 – 714Calpain-1 catalytic subunitAdd BLAST713

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1
Modified residuei354PhosphothreonineCombined sources1

Post-translational modificationi

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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei15 – 16Cleavage; for 78 kDa form2
Sitei27 – 28Cleavage; for 75 kDa form2

Keywords - PTMi

Acetylation, Autocatalytic cleavage, Phosphoprotein

Proteomic databases

EPDiP07384.
MaxQBiP07384.
PaxDbiP07384.
PeptideAtlasiP07384.
PRIDEiP07384.

PTM databases

iPTMnetiP07384.
PhosphoSitePlusiP07384.
SwissPalmiP07384.

Miscellaneous databases

PMAP-CutDBP07384.

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

BgeeiENSG00000014216.
CleanExiHS_CAPN1.
ExpressionAtlasiP07384. baseline and differential.
GenevisibleiP07384. HS.

Organism-specific databases

HPAiHPA005992.

Interactioni

Subunit structurei

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

Binary interactionsi

WithEntry#Exp.IntActNotes
EZRP153112EBI-1542113,EBI-1056902
PTPN1P180314EBI-1542113,EBI-968788
STAT3P407632EBI-1542113,EBI-518675

Protein-protein interaction databases

BioGridi107273. 107 interactors.
IntActiP07384. 21 interactors.
MINTiMINT-5004023.
STRINGi9606.ENSP00000279247.

Chemistry databases

BindingDBiP07384.

Structurei

Secondary structure

1714
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi37 – 39Combined sources3
Helixi42 – 51Combined sources10
Helixi65 – 68Combined sources4
Helixi78 – 80Combined sources3
Beta strandi84 – 86Combined sources3
Helixi88 – 91Combined sources4
Beta strandi99 – 102Combined sources4
Helixi104 – 106Combined sources3
Beta strandi111 – 113Combined sources3
Helixi115 – 124Combined sources10
Helixi128 – 134Combined sources7
Beta strandi147 – 155Combined sources9
Beta strandi158 – 166Combined sources9
Beta strandi168 – 171Combined sources4
Beta strandi174 – 177Combined sources4
Helixi187 – 198Combined sources12
Helixi203 – 205Combined sources3
Helixi210 – 216Combined sources7
Beta strandi217 – 220Combined sources4
Beta strandi221 – 226Combined sources6
Helixi227 – 229Combined sources3
Helixi234 – 244Combined sources11
Beta strandi247 – 251Combined sources5
Beta strandi256 – 258Combined sources3
Beta strandi274 – 284Combined sources11
Beta strandi287 – 295Combined sources9
Helixi312 – 316Combined sources5
Helixi319 – 325Combined sources7
Beta strandi331 – 337Combined sources7
Helixi338 – 344Combined sources7
Beta strandi347 – 352Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1ZCMX-ray2.00A33-353[»]
2ARYX-ray2.40A/B29-360[»]
ProteinModelPortaliP07384.
SMRiP07384.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP07384.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini55 – 354Calpain catalyticPROSITE-ProRule annotationAdd BLAST300
Domaini541 – 576EF-hand 1PROSITE-ProRule annotationAdd BLAST36
Domaini585 – 618EF-hand 2PROSITE-ProRule annotationAdd BLAST34
Domaini615 – 650EF-hand 3PROSITE-ProRule annotationAdd BLAST36
Domaini680 – 714EF-hand 4PROSITE-ProRule annotationAdd BLAST35

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni355 – 526Domain IIIAdd BLAST172
Regioni527 – 542LinkerAdd BLAST16
Regioni543 – 713Domain IVAdd BLAST171

Sequence similaritiesi

Belongs to the peptidase C2 family.Curated
Contains 1 calpain catalytic domain.PROSITE-ProRule annotation
Contains 4 EF-hand domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0045. Eukaryota.
ENOG410XP0B. LUCA.
GeneTreeiENSGT00760000118971.
HOGENOMiHOG000232035.
HOVERGENiHBG012645.
InParanoidiP07384.
KOiK01367.
OMAiNYQGQMV.
OrthoDBiEOG091G049E.
PhylomeDBiP07384.
TreeFamiTF314748.

Family and domain databases

CDDicd00214. Calpain_III. 1 hit.
cd00044. CysPc. 1 hit.
cd00051. EFh. 1 hit.
Gene3Di1.10.238.10. 1 hit.
InterProiIPR033883. C2_III.
IPR022684. Calpain_cysteine_protease.
IPR022682. Calpain_domain_III.
IPR022683. Calpain_III.
IPR029643. CAPN1.
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]
PANTHERiPTHR10183:SF284. PTHR10183:SF284. 1 hit.
PfamiPF01067. Calpain_III. 1 hit.
PF13833. EF-hand_8. 1 hit.
PF00648. Peptidase_C2. 1 hit.
[Graphical view]
PRINTSiPR00704. CALPAIN.
SMARTiSM00720. calpain_III. 1 hit.
SM00230. CysPc. 1 hit.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
SSF49758. SSF49758. 1 hit.
PROSITEiPS50203. CALPAIN_CAT. 1 hit.
PS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 4 hits.
PS00139. THIOL_PROTEASE_CYS. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

P07384-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSEEIITPVY CTGVSAQVQK QRARELGLGR HENAIKYLGQ DYEQLRVRCL
60 70 80 90 100
QSGTLFRDEA FPPVPQSLGY KDLGPNSSKT YGIKWKRPTE LLSNPQFIVD
110 120 130 140 150
GATRTDICQG ALGDCWLLAA IASLTLNDTL LHRVVPHGQS FQNGYAGIFH
160 170 180 190 200
FQLWQFGEWV DVVVDDLLPI KDGKLVFVHS AEGNEFWSAL LEKAYAKVNG
210 220 230 240 250
SYEALSGGST SEGFEDFTGG VTEWYELRKA PSDLYQIILK ALERGSLLGC
260 270 280 290 300
SIDISSVLDM EAITFKKLVK GHAYSVTGAK QVNYRGQVVS LIRMRNPWGE
310 320 330 340 350
VEWTGAWSDS SSEWNNVDPY ERDQLRVKME DGEFWMSFRD FMREFTRLEI
360 370 380 390 400
CNLTPDALKS RTIRKWNTTL YEGTWRRGST AGGCRNYPAT FWVNPQFKIR
410 420 430 440 450
LDETDDPDDY GDRESGCSFV LALMQKHRRR ERRFGRDMET IGFAVYEVPP
460 470 480 490 500
ELVGQPAVHL KRDFFLANAS RARSEQFINL REVSTRFRLP PGEYVVVPST
510 520 530 540 550
FEPNKEGDFV LRFFSEKSAG TVELDDQIQA NLPDEQVLSE EEIDENFKAL
560 570 580 590 600
FRQLAGEDME ISVKELRTIL NRIISKHKDL RTKGFSLESC RSMVNLMDRD
610 620 630 640 650
GNGKLGLVEF NILWNRIRNY LSIFRKFDLD KSGSMSAYEM RMAIESAGFK
660 670 680 690 700
LNKKLYELII TRYSEPDLAV DFDNFVCCLV RLETMFRFFK TLDTDLDGVV
710
TFDLFKWLQL TMFA
Length:714
Mass (Da):81,890
Last modified:April 1, 1988 - v1
Checksum:i1CB6D7C56D063498
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti548K → N in AAH08751 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_021085103T → A.1 PublicationCorresponds to variant rs17885718dbSNPEnsembl.1
Natural variantiVAR_021086433R → P.2 PublicationsCorresponds to variant rs10895991dbSNPEnsembl.1
Natural variantiVAR_021087492G → R.1 PublicationCorresponds to variant rs17883283dbSNPEnsembl.1
Natural variantiVAR_021088676V → I.1 PublicationCorresponds to variant rs17884773dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS44644.1.
PIRiA26213. CIHUH.
RefSeqiNP_001185797.1. NM_001198868.1.
NP_001185798.1. NM_001198869.1.
NP_005177.2. NM_005186.3.
XP_006718761.1. XM_006718698.1.
XP_011543594.1. XM_011545292.1.
UniGeneiHs.502842.
Hs.735492.

Genome annotation databases

EnsembliENST00000279247; ENSP00000279247; ENSG00000014216.
ENST00000524773; ENSP00000434176; ENSG00000014216.
ENST00000527323; ENSP00000431984; ENSG00000014216.
ENST00000533129; ENSP00000431686; ENSG00000014216.
ENST00000533820; ENSP00000435272; ENSG00000014216.
GeneIDi823.
KEGGihsa:823.
UCSCiuc001odf.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

CaBP

Calpain

Calpains homepage
NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS44644.1.
PIRiA26213. CIHUH.
RefSeqiNP_001185797.1. NM_001198868.1.
NP_001185798.1. NM_001198869.1.
NP_005177.2. NM_005186.3.
XP_006718761.1. XM_006718698.1.
XP_011543594.1. XM_011545292.1.
UniGeneiHs.502842.
Hs.735492.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1ZCMX-ray2.00A33-353[»]
2ARYX-ray2.40A/B29-360[»]
ProteinModelPortaliP07384.
SMRiP07384.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107273. 107 interactors.
IntActiP07384. 21 interactors.
MINTiMINT-5004023.
STRINGi9606.ENSP00000279247.

Chemistry databases

BindingDBiP07384.
ChEMBLiCHEMBL3891.

Protein family/group databases

MEROPSiC02.001.

PTM databases

iPTMnetiP07384.
PhosphoSitePlusiP07384.
SwissPalmiP07384.

Polymorphism and mutation databases

BioMutaiCAPN1.
DMDMi115574.

Proteomic databases

EPDiP07384.
MaxQBiP07384.
PaxDbiP07384.
PeptideAtlasiP07384.
PRIDEiP07384.

Protocols and materials databases

DNASUi823.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000279247; ENSP00000279247; ENSG00000014216.
ENST00000524773; ENSP00000434176; ENSG00000014216.
ENST00000527323; ENSP00000431984; ENSG00000014216.
ENST00000533129; ENSP00000431686; ENSG00000014216.
ENST00000533820; ENSP00000435272; ENSG00000014216.
GeneIDi823.
KEGGihsa:823.
UCSCiuc001odf.3. human.

Organism-specific databases

CTDi823.
DisGeNETi823.
GeneCardsiCAPN1.
HGNCiHGNC:1476. CAPN1.
HPAiHPA005992.
MIMi114220. gene.
neXtProtiNX_P07384.
OpenTargetsiENSG00000014216.
PharmGKBiPA26057.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0045. Eukaryota.
ENOG410XP0B. LUCA.
GeneTreeiENSGT00760000118971.
HOGENOMiHOG000232035.
HOVERGENiHBG012645.
InParanoidiP07384.
KOiK01367.
OMAiNYQGQMV.
OrthoDBiEOG091G049E.
PhylomeDBiP07384.
TreeFamiTF314748.

Enzyme and pathway databases

BioCyciZFISH:HS00359-MONOMER.
BRENDAi3.4.22.52. 2681.
3.4.22.53. 2681.
ReactomeiR-HSA-1474228. Degradation of the extracellular matrix.
R-HSA-6798695. Neutrophil degranulation.
R-HSA-6809371. Formation of the cornified envelope.

Miscellaneous databases

ChiTaRSiCAPN1. human.
EvolutionaryTraceiP07384.
GeneWikiiCAPN1.
GenomeRNAii823.
PMAP-CutDBP07384.
PROiP07384.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000014216.
CleanExiHS_CAPN1.
ExpressionAtlasiP07384. baseline and differential.
GenevisibleiP07384. HS.

Family and domain databases

CDDicd00214. Calpain_III. 1 hit.
cd00044. CysPc. 1 hit.
cd00051. EFh. 1 hit.
Gene3Di1.10.238.10. 1 hit.
InterProiIPR033883. C2_III.
IPR022684. Calpain_cysteine_protease.
IPR022682. Calpain_domain_III.
IPR022683. Calpain_III.
IPR029643. CAPN1.
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]
PANTHERiPTHR10183:SF284. PTHR10183:SF284. 1 hit.
PfamiPF01067. Calpain_III. 1 hit.
PF13833. EF-hand_8. 1 hit.
PF00648. Peptidase_C2. 1 hit.
[Graphical view]
PRINTSiPR00704. CALPAIN.
SMARTiSM00720. calpain_III. 1 hit.
SM00230. CysPc. 1 hit.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
SSF49758. SSF49758. 1 hit.
PROSITEiPS50203. CALPAIN_CAT. 1 hit.
PS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 4 hits.
PS00139. THIOL_PROTEASE_CYS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCAN1_HUMAN
AccessioniPrimary (citable) accession number: P07384
Secondary accession number(s): Q2TTR0, Q6DHV4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1988
Last sequence update: April 1, 1988
Last modified: November 30, 2016
This is version 196 of the entry and version 1 of the sequence. [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, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.