P07384 (CAN1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	CAPN1
Synonyms:	CANPL1
ORF Names:	PIG30

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	714 AA.
Sequence status	Complete.
Protein existence	Evidence 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 component	Cell membrane Cytoplasm Membrane
Coding sequence diversity	Polymorphism
Domain	Repeat
Ligand	Calcium Metal-binding
Molecular function	Hydrolase Protease Thiol protease
PTM	Autocatalytic cleavage
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	positive regulation of cell proliferation Traceable author statement PubMed 8702541. Source: ProtInc proteolysis Inferred from electronic annotation. Source: UniProtKB-KW receptor catabolic process Inferred from electronic annotation. Source: Compara
Cellular_component	cytoplasm Inferred from direct assay. Source: HPA plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: InterPro calcium-dependent cysteine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
STAT3	P40763	2	EBI-1542113,EBI-518675

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 714

714

Calpain-1 catalytic subunit

PRO_0000207694

Regions

Domain

55 – 354

300

Calpain catalytic

Domain

541 – 576

36

EF-hand 1

Domain

585 – 618

34

EF-hand 2

Domain

615 – 650

36

EF-hand 3

Domain

680 – 714

35

EF-hand 4

Calcium binding

99 – 106

8

1 Ref.8 Ref.10

Calcium binding

302 – 333

32

2 Ref.8 Ref.10

Calcium binding

598 – 609

12

3 Ref.8 Ref.10

Calcium binding

628 – 639

12

4 Ref.8 Ref.10

Region

355 – 526

172

Domain III

Region

527 – 542

16

Linker

Region

543 – 713

171

Domain IV

Sites

Active site

115

1

By similarity

Active site

272

1

By similarity

Active site

296

1

By similarity

Site

15 – 16

2

Cleavage; for 78 kDa form

Site

27 – 28

2

Cleavage; for 75 kDa form

Natural variations

Natural variant

103

1

T → A. Ref.4
Corresponds to variant rs17885718 [ dbSNP | Ensembl ].

VAR_021085

Natural variant

433

1

R → P. Ref.4 Ref.5
Corresponds to variant rs10895991 [ dbSNP | Ensembl ].

VAR_021086

Natural variant

492

1

G → R. Ref.4
Corresponds to variant rs17883283 [ dbSNP | Ensembl ].

VAR_021087

Natural variant

676

1

V → I. Ref.4
Corresponds to variant rs17884773 [ dbSNP | Ensembl ].

VAR_021088

Experimental info

Sequence conflict

548

1

K → N in AAH08751. Ref.5

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

714

Helix Strand Turn

Details...

Helix

37 – 39

3

Helix

42 – 51

10

Helix

65 – 68

4

Helix

78 – 80

3

Beta strand

84 – 86

3

Helix

88 – 91

4

Beta strand

99 – 102

4

Helix

104 – 106

3

Beta strand

111 – 113

3

Helix

115 – 124

10

Helix

128 – 134

7

Beta strand

147 – 155

9

Beta strand

158 – 166

9

Beta strand

168 – 171

4

Beta strand

174 – 177

4

Helix

187 – 198

12

Helix

203 – 205

3

Helix

210 – 216

7

Beta strand

217 – 220

4

Beta strand

221 – 226

6

Helix

227 – 229

3

Helix

234 – 244

11

Beta strand

247 – 251

5

Beta strand

256 – 258

3

Beta strand

274 – 284

11

Beta strand

287 – 295

9

Helix

312 – 316

5

Helix

319 – 325

7

Beta strand

331 – 337

7

Helix

338 – 344

7

Beta strand

347 – 352

6

Sequences

	Sequence		Length	Mass (Da)
	P07384 [UniParc]. Last modified April 1, 1988. Version 1. Checksum: 1CB6D7C56D063498	FASTA	714	81,890
	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

References

	« Hide 'large scale' referencesShow '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]	"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].
[10]	"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.

Web resources

CaBP

Calpain

Calpains homepage

NIEHS-SNPs

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.

IPI

IPI00011285.

PIR

CIHUH. A26213.

RefSeq

NP_001185797.1. NM_001198868.1.
NP_001185798.1. NM_001198869.1.
NP_005177.2. NM_005186.3.

UniGene

Hs.502842.
Hs.735492.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1ZCM	X-ray	2.00	A	33-353	[»]
2ARY	X-ray	2.40	A/B	29-360	[»]

ProteinModelPortal

P07384.

ModBase

Search...

Protein-protein interaction databases

IntAct

P07384. 6 interactions.

MINT

MINT-5004023.

STRING

9606.ENSP00000279247.

Protein family/group databases

MEROPS

C02.001.

PTM databases

PhosphoSite

P07384.

Polymorphism databases

DMDM

115574.

Proteomic databases

PaxDb

P07384.

PRIDE

P07384.

Protocols and materials databases

DNASU

823.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000279247; ENSP00000279247; ENSG00000014216.
ENST00000524773; ENSP00000434176; ENSG00000014216.
ENST00000527323; ENSP00000431984; ENSG00000014216.
ENST00000533129; ENSP00000431686; ENSG00000014216.
ENST00000533820; ENSP00000435272; ENSG00000014216.

GeneID

823.

KEGG

hsa:823.

UCSC

uc001odf.2. human.

Organism-specific databases

CTD

823.

GeneCards

GC11P064950.

HGNC

HGNC:1476. CAPN1.

HPA

HPA005992.

MIM

114220. gene.

neXtProt

NX_P07384.

PharmGKB

PA26057.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG327523.

HOGENOM

HOG000232035.

HOVERGEN

HBG012645.

InParanoid

P07384.

KO

K01367.

OMA

DFLREFS.

OrthoDB

EOG4RR6GS.

Enzyme and pathway databases

BRENDA

3.4.22.52. 2681.

Pathway_Interaction_DB

ptp1bpathway. Signaling events mediated by PTP1B.

Gene expression databases

ArrayExpress

P07384.

Bgee

P07384.

CleanEx

HS_CAPN1.

Genevestigator

P07384.

GermOnline

ENSG00000014216. Homo sapiens.

Family and domain databases

Gene3D

1.10.238.10. 1 hit.

InterPro

IPR022684. Calpain_cysteine_protease.
IPR022682. Calpain_domain_III.
IPR022683. Calpain_III.
IPR011992. EF-hand-like_dom.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR000169. Pept_cys_AS.
IPR001300. Peptidase_C2_calpain_cat.
[Graphical view]

Pfam

PF01067. Calpain_III. 1 hit.
PF13405. EF_hand_4. 1 hit.
PF00648. Peptidase_C2. 1 hit.
[Graphical view]

PRINTS

PR00704. CALPAIN.

SMART

SM00720. calpain_III. 1 hit.
SM00230. CysPc. 1 hit.
SM00054. EFh. 3 hits.
[Graphical view]

SUPFAM

SSF49758. Peptidase_C2. 1 hit.

PROSITE

PS50203. CALPAIN_CAT. 1 hit.
PS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 4 hits.
PS00640. THIOL_PROTEASE_ASN. False negative.
PS00139. THIOL_PROTEASE_CYS. 1 hit.
PS00639. THIOL_PROTEASE_HIS. False negative.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P07384.

ChEMBL

CHEMBL3891.

ChiTaRS

CAPN1. human.

EvolutionaryTrace

P07384.

GenomeRNAi

823.

NextBio

3370.

PMAP-CutDB

P07384.

SOURCE

Search...

Entry information

Entry name

CAN1_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 158 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.