Full text data of CAPN1
CAPN1
(CANPL1)
[Confidence: high (present in two of the MS resources)]
Calpain-1 catalytic subunit; 3.4.22.52 (Calcium-activated neutral proteinase 1; CANP 1; Calpain mu-type; Calpain-1 large subunit; Cell proliferation-inducing gene 30 protein; Micromolar-calpain; muCANP)
Calpain-1 catalytic subunit; 3.4.22.52 (Calcium-activated neutral proteinase 1; CANP 1; Calpain mu-type; Calpain-1 large subunit; Cell proliferation-inducing gene 30 protein; Micromolar-calpain; muCANP)
hRBCD
IPI00011285
IPI00011285 Calpain 1, large [catalytic] subunit calpain 5 in membrane, Broad endopeptidase specificity soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
IPI00011285 Calpain 1, large [catalytic] subunit calpain 5 in membrane, Broad endopeptidase specificity soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
UniProt
P07384
ID CAN1_HUMAN Reviewed; 714 AA.
AC P07384; Q2TTR0; Q6DHV4;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-APR-1988, sequence version 1.
DT 22-JAN-2014, entry version 164.
DE RecName: Full=Calpain-1 catalytic subunit;
DE EC=3.4.22.52;
DE AltName: Full=Calcium-activated neutral proteinase 1;
DE Short=CANP 1;
DE AltName: Full=Calpain mu-type;
DE AltName: Full=Calpain-1 large subunit;
DE AltName: Full=Cell proliferation-inducing gene 30 protein;
DE AltName: Full=Micromolar-calpain;
DE Short=muCANP;
GN Name=CAPN1; Synonyms=CANPL1; ORFNames=PIG30;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3017764; DOI=10.1016/0014-5793(86)80919-X;
RA Aoki K., Imajoh S., Ohno S., Emori Y., Koike M., Kosaki G., Suzuki K.;
RT "Complete amino acid sequence of the large subunit of the low-Ca2+-
RT requiring form of human Ca2+-activated neutral protease (muCANP)
RT deduced from its cDNA sequence.";
RL FEBS Lett. 205:313-317(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2400579;
RA Sorimachi H., Ohmi S., Emori Y., Kawasaki H., Saido T.C., Ohno S.,
RA Minami Y., Suzuki K.;
RT "A novel member of the calcium-dependent cysteine protease family.";
RL Biol. Chem. Hoppe-Seyler 371:171-176(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kim J.W.;
RT "Identification of a human cell proliferation inducing gene.";
RL Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ALA-103; PRO-433;
RP ARG-492 AND ILE-676.
RG NIEHS SNPs program;
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT PRO-433.
RC TISSUE=Kidney, Pancreas, and Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP AUTOPROTEOLYTIC PROCESSING.
RX PubMed=8954105; DOI=10.1006/bbrc.1996.1779;
RA Melloni E., Michetti M., Salamino F., Minafra R., Pontremoli S.;
RT "Modulation of the calpain autoproteolysis by calpastatin and
RT phospholipids.";
RL Biochem. Biophys. Res. Commun. 229:193-197(1996).
RN [7]
RP AUTOPROTEOLYTIC PROCESSING, AND SUBCELLULAR LOCATION.
RX PubMed=8769305; DOI=10.1016/0014-5793(96)00775-2;
RA Michetti M., Salamino F., Tedesco I., Averna M., Minafra R.,
RA Melloni E., Pontremoli S.;
RT "Autolysis of human erythrocyte calpain produces two active enzyme
RT forms with different cell localization.";
RL FEBS Lett. 392:11-15(1996).
RN [8]
RP CALCIUM-BINDING DATA.
RX PubMed=9271093;
RA Michetti M., Salamino F., Minafra R., Melloni E., Pontremoli S.;
RT "Calcium-binding properties of human erythrocyte calpain.";
RL Biochem. J. 325:721-726(1997).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 33-353 OF MUTANT ALA-213, AND
RP CALCIUM-BINDING REGIONS.
RX PubMed=16411745; DOI=10.1021/bi052077b;
RA Li Q., Hanzlik R.P., Weaver R.F., Schonbrunn E.;
RT "Molecular mode of action of a covalently inhibiting peptidomimetic on
RT the human calpain protease core.";
RL Biochemistry 45:701-708(2006).
CC -!- FUNCTION: Calcium-regulated non-lysosomal thiol-protease which
CC catalyze limited proteolysis of substrates involved in
CC cytoskeletal remodeling and signal transduction.
CC -!- CATALYTIC ACTIVITY: Broad endopeptidase specificity.
CC -!- COFACTOR: Binds 4 calcium ions.
CC -!- ENZYME REGULATION: Activated by micromolar concentrations of
CC calcium and inhibited by calpastatin.
CC -!- SUBUNIT: Forms a heterodimer with a small (regulatory) subunit
CC (CAPNS1).
CC -!- INTERACTION:
CC P15311:EZR; NbExp=2; IntAct=EBI-1542113, EBI-1056902;
CC P18031:PTPN1; NbExp=4; IntAct=EBI-1542113, EBI-968788;
CC P40763:STAT3; NbExp=2; IntAct=EBI-1542113, EBI-518675;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane. Note=Translocates
CC to the plasma membrane upon Ca(2+) binding.
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- PTM: Undergoes calcium-induced successive autoproteolytic
CC cleavages that generate a membrane-bound 78 kDa active form and an
CC intracellular 75 kDa active form. Calpastatin reduces with high
CC efficiency the transition from 78 kDa to 75 kDa calpain forms.
CC -!- SIMILARITY: Belongs to the peptidase C2 family.
CC -!- SIMILARITY: Contains 1 calpain catalytic domain.
CC -!- SIMILARITY: Contains 4 EF-hand domains.
CC -!- WEB RESOURCE: Name=CaBP; Note=Calpain;
CC URL="http://structbio.vanderbilt.edu/cabp_database/general/prot_pages/calpain.html";
CC -!- WEB RESOURCE: Name=Calpains homepage;
CC URL="http://ag.arizona.edu/calpains/";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/capn1/";
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CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
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DR EMBL; X04366; CAA27881.1; -; mRNA.
DR EMBL; AY550975; AAT52221.1; -; mRNA.
DR EMBL; AY796340; AAV41878.1; -; Genomic_DNA.
DR EMBL; BC008751; AAH08751.1; -; mRNA.
DR EMBL; BC017200; AAH17200.1; -; mRNA.
DR EMBL; BC075862; AAH75862.1; -; mRNA.
DR PIR; A26213; CIHUH.
DR RefSeq; NP_001185797.1; NM_001198868.1.
DR RefSeq; NP_001185798.1; NM_001198869.1.
DR RefSeq; NP_005177.2; NM_005186.3.
DR UniGene; Hs.502842; -.
DR UniGene; Hs.735492; -.
DR PDB; 1ZCM; X-ray; 2.00 A; A=33-353.
DR PDB; 2ARY; X-ray; 2.40 A; A/B=29-360.
DR PDBsum; 1ZCM; -.
DR PDBsum; 2ARY; -.
DR ProteinModelPortal; P07384; -.
DR SMR; P07384; 13-713.
DR IntAct; P07384; 10.
DR MINT; MINT-5004023; -.
DR STRING; 9606.ENSP00000279247; -.
DR BindingDB; P07384; -.
DR ChEMBL; CHEMBL3891; -.
DR MEROPS; C02.001; -.
DR PhosphoSite; P07384; -.
DR DMDM; 115574; -.
DR PaxDb; P07384; -.
DR PRIDE; P07384; -.
DR DNASU; 823; -.
DR Ensembl; ENST00000279247; ENSP00000279247; ENSG00000014216.
DR Ensembl; ENST00000524773; ENSP00000434176; ENSG00000014216.
DR Ensembl; ENST00000527323; ENSP00000431984; ENSG00000014216.
DR Ensembl; ENST00000533129; ENSP00000431686; ENSG00000014216.
DR Ensembl; ENST00000533820; ENSP00000435272; ENSG00000014216.
DR GeneID; 823; -.
DR KEGG; hsa:823; -.
DR UCSC; uc001odf.2; human.
DR CTD; 823; -.
DR GeneCards; GC11P064950; -.
DR HGNC; HGNC:1476; CAPN1.
DR HPA; HPA005992; -.
DR MIM; 114220; gene.
DR neXtProt; NX_P07384; -.
DR PharmGKB; PA26057; -.
DR eggNOG; NOG327523; -.
DR HOGENOM; HOG000232035; -.
DR HOVERGEN; HBG012645; -.
DR InParanoid; P07384; -.
DR KO; K01367; -.
DR OMA; PQSLGYK; -.
DR OrthoDB; EOG7RV9FM; -.
DR BRENDA; 3.4.22.52; 2681.
DR Reactome; REACT_118779; Extracellular matrix organization.
DR ChiTaRS; CAPN1; human.
DR EvolutionaryTrace; P07384; -.
DR GeneWiki; CAPN1; -.
DR GenomeRNAi; 823; -.
DR NextBio; 3370; -.
DR PMAP-CutDB; P07384; -.
DR PRO; PR:P07384; -.
DR ArrayExpress; P07384; -.
DR Bgee; P07384; -.
DR CleanEx; HS_CAPN1; -.
DR Genevestigator; P07384; -.
DR GO; GO:0005737; C:cytoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0004198; F:calcium-dependent cysteine-type endopeptidase activity; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell proliferation; TAS:ProtInc.
DR GO; GO:0006508; P:proteolysis; ISS:UniProtKB.
DR GO; GO:0032801; P:receptor catabolic process; IEA:Ensembl.
DR Gene3D; 1.10.238.10; -; 1.
DR InterPro; IPR022684; Calpain_cysteine_protease.
DR InterPro; IPR022682; Calpain_domain_III.
DR InterPro; IPR022683; Calpain_III.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR000169; Pept_cys_AS.
DR InterPro; IPR001300; Peptidase_C2_calpain_cat.
DR Pfam; PF01067; Calpain_III; 1.
DR Pfam; PF13405; EF-hand_6; 1.
DR Pfam; PF00648; Peptidase_C2; 1.
DR PRINTS; PR00704; CALPAIN.
DR SMART; SM00720; calpain_III; 1.
DR SMART; SM00230; CysPc; 1.
DR SMART; SM00054; EFh; 3.
DR SUPFAM; SSF49758; SSF49758; 1.
DR PROSITE; PS50203; CALPAIN_CAT; 1.
DR PROSITE; PS00018; EF_HAND_1; 2.
DR PROSITE; PS50222; EF_HAND_2; 4.
DR PROSITE; PS00640; THIOL_PROTEASE_ASN; FALSE_NEG.
DR PROSITE; PS00139; THIOL_PROTEASE_CYS; 1.
DR PROSITE; PS00639; THIOL_PROTEASE_HIS; FALSE_NEG.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Autocatalytic cleavage; Calcium;
KW Cell membrane; Complete proteome; Cytoplasm; Hydrolase; Membrane;
KW Metal-binding; Polymorphism; Protease; Reference proteome; Repeat;
KW Thiol protease.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 714 Calpain-1 catalytic subunit.
FT /FTId=PRO_0000207694.
FT DOMAIN 55 354 Calpain catalytic.
FT DOMAIN 541 576 EF-hand 1.
FT DOMAIN 585 618 EF-hand 2.
FT DOMAIN 615 650 EF-hand 3.
FT DOMAIN 680 714 EF-hand 4.
FT CA_BIND 99 106 1.
FT CA_BIND 302 333 2.
FT CA_BIND 598 609 3.
FT CA_BIND 628 639 4.
FT REGION 355 526 Domain III.
FT REGION 527 542 Linker.
FT REGION 543 713 Domain IV.
FT ACT_SITE 115 115 By similarity.
FT ACT_SITE 272 272 By similarity.
FT ACT_SITE 296 296 By similarity.
FT SITE 15 16 Cleavage; for 78 kDa form.
FT SITE 27 28 Cleavage; for 75 kDa form.
FT MOD_RES 2 2 N-acetylserine.
FT VARIANT 103 103 T -> A (in dbSNP:rs17885718).
FT /FTId=VAR_021085.
FT VARIANT 433 433 R -> P (in dbSNP:rs10895991).
FT /FTId=VAR_021086.
FT VARIANT 492 492 G -> R (in dbSNP:rs17883283).
FT /FTId=VAR_021087.
FT VARIANT 676 676 V -> I (in dbSNP:rs17884773).
FT /FTId=VAR_021088.
FT CONFLICT 548 548 K -> N (in Ref. 5; AAH08751).
FT HELIX 37 39
FT HELIX 42 51
FT HELIX 65 68
FT HELIX 78 80
FT STRAND 84 86
FT HELIX 88 91
FT STRAND 99 102
FT HELIX 104 106
FT STRAND 111 113
FT HELIX 115 124
FT HELIX 128 134
FT STRAND 147 155
FT STRAND 158 166
FT STRAND 168 171
FT STRAND 174 177
FT HELIX 187 198
FT HELIX 203 205
FT HELIX 210 216
FT STRAND 217 220
FT STRAND 221 226
FT HELIX 227 229
FT HELIX 234 244
FT STRAND 247 251
FT STRAND 256 258
FT STRAND 274 284
FT STRAND 287 295
FT HELIX 312 316
FT HELIX 319 325
FT STRAND 331 337
FT HELIX 338 344
FT STRAND 347 352
SQ SEQUENCE 714 AA; 81890 MW; 1CB6D7C56D063498 CRC64;
MSEEIITPVY CTGVSAQVQK QRARELGLGR HENAIKYLGQ DYEQLRVRCL QSGTLFRDEA
FPPVPQSLGY KDLGPNSSKT YGIKWKRPTE LLSNPQFIVD GATRTDICQG ALGDCWLLAA
IASLTLNDTL LHRVVPHGQS FQNGYAGIFH FQLWQFGEWV DVVVDDLLPI KDGKLVFVHS
AEGNEFWSAL LEKAYAKVNG SYEALSGGST SEGFEDFTGG VTEWYELRKA PSDLYQIILK
ALERGSLLGC SIDISSVLDM EAITFKKLVK GHAYSVTGAK QVNYRGQVVS LIRMRNPWGE
VEWTGAWSDS SSEWNNVDPY ERDQLRVKME DGEFWMSFRD FMREFTRLEI CNLTPDALKS
RTIRKWNTTL YEGTWRRGST AGGCRNYPAT FWVNPQFKIR LDETDDPDDY GDRESGCSFV
LALMQKHRRR ERRFGRDMET IGFAVYEVPP ELVGQPAVHL KRDFFLANAS RARSEQFINL
REVSTRFRLP PGEYVVVPST FEPNKEGDFV LRFFSEKSAG TVELDDQIQA NLPDEQVLSE
EEIDENFKAL FRQLAGEDME ISVKELRTIL NRIISKHKDL RTKGFSLESC RSMVNLMDRD
GNGKLGLVEF NILWNRIRNY LSIFRKFDLD KSGSMSAYEM RMAIESAGFK LNKKLYELII
TRYSEPDLAV DFDNFVCCLV RLETMFRFFK TLDTDLDGVV TFDLFKWLQL TMFA
//
ID CAN1_HUMAN Reviewed; 714 AA.
AC P07384; Q2TTR0; Q6DHV4;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-APR-1988, sequence version 1.
DT 22-JAN-2014, entry version 164.
DE RecName: Full=Calpain-1 catalytic subunit;
DE EC=3.4.22.52;
DE AltName: Full=Calcium-activated neutral proteinase 1;
DE Short=CANP 1;
DE AltName: Full=Calpain mu-type;
DE AltName: Full=Calpain-1 large subunit;
DE AltName: Full=Cell proliferation-inducing gene 30 protein;
DE AltName: Full=Micromolar-calpain;
DE Short=muCANP;
GN Name=CAPN1; Synonyms=CANPL1; ORFNames=PIG30;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3017764; DOI=10.1016/0014-5793(86)80919-X;
RA Aoki K., Imajoh S., Ohno S., Emori Y., Koike M., Kosaki G., Suzuki K.;
RT "Complete amino acid sequence of the large subunit of the low-Ca2+-
RT requiring form of human Ca2+-activated neutral protease (muCANP)
RT deduced from its cDNA sequence.";
RL FEBS Lett. 205:313-317(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2400579;
RA Sorimachi H., Ohmi S., Emori Y., Kawasaki H., Saido T.C., Ohno S.,
RA Minami Y., Suzuki K.;
RT "A novel member of the calcium-dependent cysteine protease family.";
RL Biol. Chem. Hoppe-Seyler 371:171-176(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kim J.W.;
RT "Identification of a human cell proliferation inducing gene.";
RL Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ALA-103; PRO-433;
RP ARG-492 AND ILE-676.
RG NIEHS SNPs program;
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT PRO-433.
RC TISSUE=Kidney, Pancreas, and Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP AUTOPROTEOLYTIC PROCESSING.
RX PubMed=8954105; DOI=10.1006/bbrc.1996.1779;
RA Melloni E., Michetti M., Salamino F., Minafra R., Pontremoli S.;
RT "Modulation of the calpain autoproteolysis by calpastatin and
RT phospholipids.";
RL Biochem. Biophys. Res. Commun. 229:193-197(1996).
RN [7]
RP AUTOPROTEOLYTIC PROCESSING, AND SUBCELLULAR LOCATION.
RX PubMed=8769305; DOI=10.1016/0014-5793(96)00775-2;
RA Michetti M., Salamino F., Tedesco I., Averna M., Minafra R.,
RA Melloni E., Pontremoli S.;
RT "Autolysis of human erythrocyte calpain produces two active enzyme
RT forms with different cell localization.";
RL FEBS Lett. 392:11-15(1996).
RN [8]
RP CALCIUM-BINDING DATA.
RX PubMed=9271093;
RA Michetti M., Salamino F., Minafra R., Melloni E., Pontremoli S.;
RT "Calcium-binding properties of human erythrocyte calpain.";
RL Biochem. J. 325:721-726(1997).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 33-353 OF MUTANT ALA-213, AND
RP CALCIUM-BINDING REGIONS.
RX PubMed=16411745; DOI=10.1021/bi052077b;
RA Li Q., Hanzlik R.P., Weaver R.F., Schonbrunn E.;
RT "Molecular mode of action of a covalently inhibiting peptidomimetic on
RT the human calpain protease core.";
RL Biochemistry 45:701-708(2006).
CC -!- FUNCTION: Calcium-regulated non-lysosomal thiol-protease which
CC catalyze limited proteolysis of substrates involved in
CC cytoskeletal remodeling and signal transduction.
CC -!- CATALYTIC ACTIVITY: Broad endopeptidase specificity.
CC -!- COFACTOR: Binds 4 calcium ions.
CC -!- ENZYME REGULATION: Activated by micromolar concentrations of
CC calcium and inhibited by calpastatin.
CC -!- SUBUNIT: Forms a heterodimer with a small (regulatory) subunit
CC (CAPNS1).
CC -!- INTERACTION:
CC P15311:EZR; NbExp=2; IntAct=EBI-1542113, EBI-1056902;
CC P18031:PTPN1; NbExp=4; IntAct=EBI-1542113, EBI-968788;
CC P40763:STAT3; NbExp=2; IntAct=EBI-1542113, EBI-518675;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane. Note=Translocates
CC to the plasma membrane upon Ca(2+) binding.
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- PTM: Undergoes calcium-induced successive autoproteolytic
CC cleavages that generate a membrane-bound 78 kDa active form and an
CC intracellular 75 kDa active form. Calpastatin reduces with high
CC efficiency the transition from 78 kDa to 75 kDa calpain forms.
CC -!- SIMILARITY: Belongs to the peptidase C2 family.
CC -!- SIMILARITY: Contains 1 calpain catalytic domain.
CC -!- SIMILARITY: Contains 4 EF-hand domains.
CC -!- WEB RESOURCE: Name=CaBP; Note=Calpain;
CC URL="http://structbio.vanderbilt.edu/cabp_database/general/prot_pages/calpain.html";
CC -!- WEB RESOURCE: Name=Calpains homepage;
CC URL="http://ag.arizona.edu/calpains/";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/capn1/";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; X04366; CAA27881.1; -; mRNA.
DR EMBL; AY550975; AAT52221.1; -; mRNA.
DR EMBL; AY796340; AAV41878.1; -; Genomic_DNA.
DR EMBL; BC008751; AAH08751.1; -; mRNA.
DR EMBL; BC017200; AAH17200.1; -; mRNA.
DR EMBL; BC075862; AAH75862.1; -; mRNA.
DR PIR; A26213; CIHUH.
DR RefSeq; NP_001185797.1; NM_001198868.1.
DR RefSeq; NP_001185798.1; NM_001198869.1.
DR RefSeq; NP_005177.2; NM_005186.3.
DR UniGene; Hs.502842; -.
DR UniGene; Hs.735492; -.
DR PDB; 1ZCM; X-ray; 2.00 A; A=33-353.
DR PDB; 2ARY; X-ray; 2.40 A; A/B=29-360.
DR PDBsum; 1ZCM; -.
DR PDBsum; 2ARY; -.
DR ProteinModelPortal; P07384; -.
DR SMR; P07384; 13-713.
DR IntAct; P07384; 10.
DR MINT; MINT-5004023; -.
DR STRING; 9606.ENSP00000279247; -.
DR BindingDB; P07384; -.
DR ChEMBL; CHEMBL3891; -.
DR MEROPS; C02.001; -.
DR PhosphoSite; P07384; -.
DR DMDM; 115574; -.
DR PaxDb; P07384; -.
DR PRIDE; P07384; -.
DR DNASU; 823; -.
DR Ensembl; ENST00000279247; ENSP00000279247; ENSG00000014216.
DR Ensembl; ENST00000524773; ENSP00000434176; ENSG00000014216.
DR Ensembl; ENST00000527323; ENSP00000431984; ENSG00000014216.
DR Ensembl; ENST00000533129; ENSP00000431686; ENSG00000014216.
DR Ensembl; ENST00000533820; ENSP00000435272; ENSG00000014216.
DR GeneID; 823; -.
DR KEGG; hsa:823; -.
DR UCSC; uc001odf.2; human.
DR CTD; 823; -.
DR GeneCards; GC11P064950; -.
DR HGNC; HGNC:1476; CAPN1.
DR HPA; HPA005992; -.
DR MIM; 114220; gene.
DR neXtProt; NX_P07384; -.
DR PharmGKB; PA26057; -.
DR eggNOG; NOG327523; -.
DR HOGENOM; HOG000232035; -.
DR HOVERGEN; HBG012645; -.
DR InParanoid; P07384; -.
DR KO; K01367; -.
DR OMA; PQSLGYK; -.
DR OrthoDB; EOG7RV9FM; -.
DR BRENDA; 3.4.22.52; 2681.
DR Reactome; REACT_118779; Extracellular matrix organization.
DR ChiTaRS; CAPN1; human.
DR EvolutionaryTrace; P07384; -.
DR GeneWiki; CAPN1; -.
DR GenomeRNAi; 823; -.
DR NextBio; 3370; -.
DR PMAP-CutDB; P07384; -.
DR PRO; PR:P07384; -.
DR ArrayExpress; P07384; -.
DR Bgee; P07384; -.
DR CleanEx; HS_CAPN1; -.
DR Genevestigator; P07384; -.
DR GO; GO:0005737; C:cytoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0004198; F:calcium-dependent cysteine-type endopeptidase activity; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell proliferation; TAS:ProtInc.
DR GO; GO:0006508; P:proteolysis; ISS:UniProtKB.
DR GO; GO:0032801; P:receptor catabolic process; IEA:Ensembl.
DR Gene3D; 1.10.238.10; -; 1.
DR InterPro; IPR022684; Calpain_cysteine_protease.
DR InterPro; IPR022682; Calpain_domain_III.
DR InterPro; IPR022683; Calpain_III.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR000169; Pept_cys_AS.
DR InterPro; IPR001300; Peptidase_C2_calpain_cat.
DR Pfam; PF01067; Calpain_III; 1.
DR Pfam; PF13405; EF-hand_6; 1.
DR Pfam; PF00648; Peptidase_C2; 1.
DR PRINTS; PR00704; CALPAIN.
DR SMART; SM00720; calpain_III; 1.
DR SMART; SM00230; CysPc; 1.
DR SMART; SM00054; EFh; 3.
DR SUPFAM; SSF49758; SSF49758; 1.
DR PROSITE; PS50203; CALPAIN_CAT; 1.
DR PROSITE; PS00018; EF_HAND_1; 2.
DR PROSITE; PS50222; EF_HAND_2; 4.
DR PROSITE; PS00640; THIOL_PROTEASE_ASN; FALSE_NEG.
DR PROSITE; PS00139; THIOL_PROTEASE_CYS; 1.
DR PROSITE; PS00639; THIOL_PROTEASE_HIS; FALSE_NEG.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Autocatalytic cleavage; Calcium;
KW Cell membrane; Complete proteome; Cytoplasm; Hydrolase; Membrane;
KW Metal-binding; Polymorphism; Protease; Reference proteome; Repeat;
KW Thiol protease.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 714 Calpain-1 catalytic subunit.
FT /FTId=PRO_0000207694.
FT DOMAIN 55 354 Calpain catalytic.
FT DOMAIN 541 576 EF-hand 1.
FT DOMAIN 585 618 EF-hand 2.
FT DOMAIN 615 650 EF-hand 3.
FT DOMAIN 680 714 EF-hand 4.
FT CA_BIND 99 106 1.
FT CA_BIND 302 333 2.
FT CA_BIND 598 609 3.
FT CA_BIND 628 639 4.
FT REGION 355 526 Domain III.
FT REGION 527 542 Linker.
FT REGION 543 713 Domain IV.
FT ACT_SITE 115 115 By similarity.
FT ACT_SITE 272 272 By similarity.
FT ACT_SITE 296 296 By similarity.
FT SITE 15 16 Cleavage; for 78 kDa form.
FT SITE 27 28 Cleavage; for 75 kDa form.
FT MOD_RES 2 2 N-acetylserine.
FT VARIANT 103 103 T -> A (in dbSNP:rs17885718).
FT /FTId=VAR_021085.
FT VARIANT 433 433 R -> P (in dbSNP:rs10895991).
FT /FTId=VAR_021086.
FT VARIANT 492 492 G -> R (in dbSNP:rs17883283).
FT /FTId=VAR_021087.
FT VARIANT 676 676 V -> I (in dbSNP:rs17884773).
FT /FTId=VAR_021088.
FT CONFLICT 548 548 K -> N (in Ref. 5; AAH08751).
FT HELIX 37 39
FT HELIX 42 51
FT HELIX 65 68
FT HELIX 78 80
FT STRAND 84 86
FT HELIX 88 91
FT STRAND 99 102
FT HELIX 104 106
FT STRAND 111 113
FT HELIX 115 124
FT HELIX 128 134
FT STRAND 147 155
FT STRAND 158 166
FT STRAND 168 171
FT STRAND 174 177
FT HELIX 187 198
FT HELIX 203 205
FT HELIX 210 216
FT STRAND 217 220
FT STRAND 221 226
FT HELIX 227 229
FT HELIX 234 244
FT STRAND 247 251
FT STRAND 256 258
FT STRAND 274 284
FT STRAND 287 295
FT HELIX 312 316
FT HELIX 319 325
FT STRAND 331 337
FT HELIX 338 344
FT STRAND 347 352
SQ SEQUENCE 714 AA; 81890 MW; 1CB6D7C56D063498 CRC64;
MSEEIITPVY CTGVSAQVQK QRARELGLGR HENAIKYLGQ DYEQLRVRCL QSGTLFRDEA
FPPVPQSLGY KDLGPNSSKT YGIKWKRPTE LLSNPQFIVD GATRTDICQG ALGDCWLLAA
IASLTLNDTL LHRVVPHGQS FQNGYAGIFH FQLWQFGEWV DVVVDDLLPI KDGKLVFVHS
AEGNEFWSAL LEKAYAKVNG SYEALSGGST SEGFEDFTGG VTEWYELRKA PSDLYQIILK
ALERGSLLGC SIDISSVLDM EAITFKKLVK GHAYSVTGAK QVNYRGQVVS LIRMRNPWGE
VEWTGAWSDS SSEWNNVDPY ERDQLRVKME DGEFWMSFRD FMREFTRLEI CNLTPDALKS
RTIRKWNTTL YEGTWRRGST AGGCRNYPAT FWVNPQFKIR LDETDDPDDY GDRESGCSFV
LALMQKHRRR ERRFGRDMET IGFAVYEVPP ELVGQPAVHL KRDFFLANAS RARSEQFINL
REVSTRFRLP PGEYVVVPST FEPNKEGDFV LRFFSEKSAG TVELDDQIQA NLPDEQVLSE
EEIDENFKAL FRQLAGEDME ISVKELRTIL NRIISKHKDL RTKGFSLESC RSMVNLMDRD
GNGKLGLVEF NILWNRIRNY LSIFRKFDLD KSGSMSAYEM RMAIESAGFK LNKKLYELII
TRYSEPDLAV DFDNFVCCLV RLETMFRFFK TLDTDLDGVV TFDLFKWLQL TMFA
//
MIM
114220
*RECORD*
*FIELD* NO
114220
*FIELD* TI
*114220 CALPAIN 1; CAPN1
;;CALPAIN, LARGE POLYPEPTIDE L1;;
CALPAIN I, LARGE SUBUNIT; CANPL1;;
read moreCALCIUM-ACTIVATED NEUTRAL PROTEASE 1, CATALYTIC SUBUNIT; CANP1
*FIELD* TX
DESCRIPTION
Calpain (calcium-dependent protease; EC 3.4.22.17) is an intracellular
protease that requires calcium for its catalytic activity. Two isozymes,
calpain I (mu-calpain) and calpain II (m-calpain), with different
calcium requirements, have been identified. Both are heterodimers
composed of L (large, catalytic, 80 kD) and S (small, regulatory, 30 kD)
subunits. The isozymes share an identical S subunit (CAPNS1; 114170),
with the differences arising from the L subunits, L1 (CAPN1) and L2
(CAPN2; 114230) (summary by Ohno et al., 1990).
GENE FUNCTION
By quantitative RT-PCR, Ueyama et al. (1998) found that expression of
calpain-1 and calpain-2 mRNA was significantly increased in muscle
biopsy samples derived from 5 men with progressive muscular dystrophy
(e.g., DMD; 310200) and 2 men and 3 women with amyotrophic lateral
sclerosis (ALS; 105400) compared with controls.
Using cell biologic, pharmacologic, and genetic methods,
Chandramohanadas et al. (2009) found that the apicomplexan parasites
Plasmodium falciparum and Toxoplasma gondii, the causative agents of
malaria and toxoplasmosis, respectively, used host cell calpains to
facilitate parasite egress. Immunodepletion and inhibition experiments
showed that calpain-1 was required for escape of P. falciparum from
human erythrocytes. Similarly, elimination of both calpain-1 and
calpain-2 via small interfering RNA against the common regulatory
subunit CAPNS1 in human osteosarcoma cells or deletion of Capns1 in
mouse embryonic fibroblasts blocked egress of T. gondii.
Chandramohanadas et al. (2009) concluded that P. falciparum and T.
gondii both exploit host cell calpains to facilitate escape from
intracellular parasitophorous vacuoles and/or the host plasma membrane,
a process required for parasite proliferation.
MAPPING
Using cDNA clones as probes, Ohno et al. (1989, 1990) mapped the CANPL1
and CANPL2 genes as well as the CANPS gene and a gene for another
protein, L3 (CAPN3; 114240), that is homologous to the other 2 L
subunits. They used a combination of spot-blot hybridization with sorted
chromosomes and Southern hybridization with human-mouse cell hybrid
DNAs. In this way they were able to assign CANPL1 to chromosome 11,
CANPL2 to chromosome 1, CANPL3 to chromosome 15, and CANPS to chromosome
19.
Courseaux et al. (1996) used a combination of methods to refine maps of
an approximately 5-Mb region of 11q13. They mapped the CAPN1 gene within
this region, telomeric to the FAU gene (134690) and centromeric to the
MLK3 (MAP3K11; 600050) and RELA (164014) genes.
*FIELD* RF
1. Chandramohanadas, R.; Davis, P. H.; Beiting, D. P.; Harbut, M.
B.; Darling, C.; Velmourougane, G.; Lee, M. Y.; Greer, P. A.; Roos,
D. S.; Greenbaum, D. C.: Apicomplexan parasites co-opt host calpains
to facilitate their escape from infected cells. Science 324: 794-797,
2009.
2. Courseaux, A.; Grosgeorge, J.; Gaudray, P.; Pannett, A. A. J.;
Forbes, S. A.; Williamson, C.; Bassett, D.; Thakker, R. V.; Teh, B.
T.; Farnebo, F.; Shepherd, J.; Skogseid, B.; Larsson, C.; Giraud,
S.; Zhang, C. X.; Salandre, J.; Calender, A.: Definition of the minimal
MEN1 candidate area based on a 5-Mb integrated map of proximal 11q13. Genomics 37:
354-365, 1996.
3. Ohno, S.; Minoshima, S.; Kudoh, J.; Fukuyama, R.; Ohmi-Imajoh,
S.; Suzuki, K.; Shimizu, Y.; Shimizu, N.: Four genes for the calpain
family locate on four distinct human chromosomes. (Abstract) Cytogenet.
Cell Genet. 51: 1054-1055, 1989.
4. Ohno, S.; Minoshima, S.; Kudoh, J.; Fukuyama, R.; Shimizu, Y.;
Ohmi-Imajoh, S.; Shimizu, N.; Suzuki, K.: Four genes for the calpain
family locate on four distinct human chromosomes. Cytogenet. Cell
Genet. 53: 225-229, 1990.
5. Ueyama, H.; Kumamoto, T.; Fujimoto, S.; Murakami, T.; Tsuda, T.
: Expression of three calpain isoform genes in human skeletal muscles. J.
Neurol. Sci. 155: 163-169, 1998.
*FIELD* CN
Paul J. Converse - updated: 7/2/2009
Ada Hamosh - updated: 3/11/2009
Patricia A. Hartz - updated: 11/22/2005
Alan F. Scott - updated: 8/5/1997
*FIELD* CD
Victor A. McKusick: 6/5/1989
*FIELD* ED
carol: 06/22/2011
carol: 2/9/2011
mgross: 7/7/2009
terry: 7/2/2009
alopez: 3/16/2009
terry: 3/11/2009
mgross: 12/2/2005
terry: 11/22/2005
psherman: 4/10/2000
carol: 8/18/1998
joanna: 8/6/1997
terry: 8/5/1997
supermim: 3/16/1992
carol: 4/29/1991
supermim: 3/20/1990
carol: 12/19/1989
ddp: 10/27/1989
*RECORD*
*FIELD* NO
114220
*FIELD* TI
*114220 CALPAIN 1; CAPN1
;;CALPAIN, LARGE POLYPEPTIDE L1;;
CALPAIN I, LARGE SUBUNIT; CANPL1;;
read moreCALCIUM-ACTIVATED NEUTRAL PROTEASE 1, CATALYTIC SUBUNIT; CANP1
*FIELD* TX
DESCRIPTION
Calpain (calcium-dependent protease; EC 3.4.22.17) is an intracellular
protease that requires calcium for its catalytic activity. Two isozymes,
calpain I (mu-calpain) and calpain II (m-calpain), with different
calcium requirements, have been identified. Both are heterodimers
composed of L (large, catalytic, 80 kD) and S (small, regulatory, 30 kD)
subunits. The isozymes share an identical S subunit (CAPNS1; 114170),
with the differences arising from the L subunits, L1 (CAPN1) and L2
(CAPN2; 114230) (summary by Ohno et al., 1990).
GENE FUNCTION
By quantitative RT-PCR, Ueyama et al. (1998) found that expression of
calpain-1 and calpain-2 mRNA was significantly increased in muscle
biopsy samples derived from 5 men with progressive muscular dystrophy
(e.g., DMD; 310200) and 2 men and 3 women with amyotrophic lateral
sclerosis (ALS; 105400) compared with controls.
Using cell biologic, pharmacologic, and genetic methods,
Chandramohanadas et al. (2009) found that the apicomplexan parasites
Plasmodium falciparum and Toxoplasma gondii, the causative agents of
malaria and toxoplasmosis, respectively, used host cell calpains to
facilitate parasite egress. Immunodepletion and inhibition experiments
showed that calpain-1 was required for escape of P. falciparum from
human erythrocytes. Similarly, elimination of both calpain-1 and
calpain-2 via small interfering RNA against the common regulatory
subunit CAPNS1 in human osteosarcoma cells or deletion of Capns1 in
mouse embryonic fibroblasts blocked egress of T. gondii.
Chandramohanadas et al. (2009) concluded that P. falciparum and T.
gondii both exploit host cell calpains to facilitate escape from
intracellular parasitophorous vacuoles and/or the host plasma membrane,
a process required for parasite proliferation.
MAPPING
Using cDNA clones as probes, Ohno et al. (1989, 1990) mapped the CANPL1
and CANPL2 genes as well as the CANPS gene and a gene for another
protein, L3 (CAPN3; 114240), that is homologous to the other 2 L
subunits. They used a combination of spot-blot hybridization with sorted
chromosomes and Southern hybridization with human-mouse cell hybrid
DNAs. In this way they were able to assign CANPL1 to chromosome 11,
CANPL2 to chromosome 1, CANPL3 to chromosome 15, and CANPS to chromosome
19.
Courseaux et al. (1996) used a combination of methods to refine maps of
an approximately 5-Mb region of 11q13. They mapped the CAPN1 gene within
this region, telomeric to the FAU gene (134690) and centromeric to the
MLK3 (MAP3K11; 600050) and RELA (164014) genes.
*FIELD* RF
1. Chandramohanadas, R.; Davis, P. H.; Beiting, D. P.; Harbut, M.
B.; Darling, C.; Velmourougane, G.; Lee, M. Y.; Greer, P. A.; Roos,
D. S.; Greenbaum, D. C.: Apicomplexan parasites co-opt host calpains
to facilitate their escape from infected cells. Science 324: 794-797,
2009.
2. Courseaux, A.; Grosgeorge, J.; Gaudray, P.; Pannett, A. A. J.;
Forbes, S. A.; Williamson, C.; Bassett, D.; Thakker, R. V.; Teh, B.
T.; Farnebo, F.; Shepherd, J.; Skogseid, B.; Larsson, C.; Giraud,
S.; Zhang, C. X.; Salandre, J.; Calender, A.: Definition of the minimal
MEN1 candidate area based on a 5-Mb integrated map of proximal 11q13. Genomics 37:
354-365, 1996.
3. Ohno, S.; Minoshima, S.; Kudoh, J.; Fukuyama, R.; Ohmi-Imajoh,
S.; Suzuki, K.; Shimizu, Y.; Shimizu, N.: Four genes for the calpain
family locate on four distinct human chromosomes. (Abstract) Cytogenet.
Cell Genet. 51: 1054-1055, 1989.
4. Ohno, S.; Minoshima, S.; Kudoh, J.; Fukuyama, R.; Shimizu, Y.;
Ohmi-Imajoh, S.; Shimizu, N.; Suzuki, K.: Four genes for the calpain
family locate on four distinct human chromosomes. Cytogenet. Cell
Genet. 53: 225-229, 1990.
5. Ueyama, H.; Kumamoto, T.; Fujimoto, S.; Murakami, T.; Tsuda, T.
: Expression of three calpain isoform genes in human skeletal muscles. J.
Neurol. Sci. 155: 163-169, 1998.
*FIELD* CN
Paul J. Converse - updated: 7/2/2009
Ada Hamosh - updated: 3/11/2009
Patricia A. Hartz - updated: 11/22/2005
Alan F. Scott - updated: 8/5/1997
*FIELD* CD
Victor A. McKusick: 6/5/1989
*FIELD* ED
carol: 06/22/2011
carol: 2/9/2011
mgross: 7/7/2009
terry: 7/2/2009
alopez: 3/16/2009
terry: 3/11/2009
mgross: 12/2/2005
terry: 11/22/2005
psherman: 4/10/2000
carol: 8/18/1998
joanna: 8/6/1997
terry: 8/5/1997
supermim: 3/16/1992
carol: 4/29/1991
supermim: 3/20/1990
carol: 12/19/1989
ddp: 10/27/1989