CAN1_PONAB
ID CAN1_PONAB Reviewed; 714 AA.
AC Q5NVS7;
DT 24-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 04-JAN-2005, sequence version 1.
DT 03-AUG-2022, entry version 106.
DE RecName: Full=Calpain-1 catalytic subunit {ECO:0000305};
DE EC=3.4.22.52 {ECO:0000250|UniProtKB:P07384};
DE AltName: Full=Calcium-activated neutral proteinase 1 {ECO:0000250|UniProtKB:P07384};
DE Short=CANP 1 {ECO:0000250|UniProtKB:P07384};
DE AltName: Full=Calpain mu-type {ECO:0000250|UniProtKB:P07384};
DE AltName: Full=Calpain-1 large subunit;
DE AltName: Full=Micromolar-calpain {ECO:0000250|UniProtKB:P07384};
DE Short=muCANP {ECO:0000250|UniProtKB:P07384};
GN Name=CAPN1 {ECO:0000250|UniProtKB:P07384};
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Calcium-regulated non-lysosomal thiol-protease which
CC catalyzes limited proteolysis of substrates involved in cytoskeletal
CC remodeling and signal transduction. Proteolytically cleaves CTBP1.
CC {ECO:0000250|UniProtKB:P07384}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Broad endopeptidase specificity.; EC=3.4.22.52;
CC Evidence={ECO:0000250|UniProtKB:P07384};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000250|UniProtKB:P07384};
CC Note=Binds 4 Ca(2+) ions. {ECO:0000250|UniProtKB:P07384};
CC -!- ACTIVITY REGULATION: Activated by micromolar concentrations of calcium
CC and inhibited by calpastatin. {ECO:0000250|UniProtKB:P07384}.
CC -!- SUBUNIT: Forms a heterodimer with a small (regulatory) subunit CAPNS1.
CC {ECO:0000250|UniProtKB:P97571}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P07384}. Cell
CC membrane {ECO:0000250|UniProtKB:P07384}. Note=Translocates to the
CC plasma membrane upon Ca(2+) binding. {ECO:0000250|UniProtKB:P07384}.
CC -!- PTM: Undergoes calcium-induced successive autoproteolytic cleavages
CC that generate a membrane-bound 78 kDa active form and an intracellular
CC 75 kDa active form. Calpastatin reduces with high efficiency the
CC transition from 78 kDa to 75 kDa calpain forms (By similarity).
CC {ECO:0000250|UniProtKB:P07384}.
CC -!- SIMILARITY: Belongs to the peptidase C2 family. {ECO:0000305}.
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DR EMBL; CR925924; CAI29586.1; -; mRNA.
DR RefSeq; NP_001127061.1; NM_001133589.1.
DR AlphaFoldDB; Q5NVS7; -.
DR SMR; Q5NVS7; -.
DR STRING; 9601.ENSPPYP00000003556; -.
DR MEROPS; C02.001; -.
DR PRIDE; Q5NVS7; -.
DR GeneID; 100174090; -.
DR KEGG; pon:100174090; -.
DR CTD; 823; -.
DR eggNOG; KOG0045; Eukaryota.
DR InParanoid; Q5NVS7; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0004198; F:calcium-dependent cysteine-type endopeptidase activity; ISS:UniProtKB.
DR GO; GO:0008233; F:peptidase activity; ISS:UniProtKB.
DR GO; GO:0006508; P:proteolysis; ISS:UniProtKB.
DR GO; GO:0050790; P:regulation of catalytic activity; ISS:UniProtKB.
DR GO; GO:0097264; P:self proteolysis; ISS:UniProtKB.
DR CDD; cd00214; Calpain_III; 1.
DR CDD; cd00044; CysPc; 1.
DR InterPro; IPR033883; C2_III.
DR InterPro; IPR022684; Calpain_cysteine_protease.
DR InterPro; IPR022682; Calpain_domain_III.
DR InterPro; IPR022683; Calpain_III.
DR InterPro; IPR036213; Calpain_III_sf.
DR InterPro; IPR029643; CAPN1.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR000169; Pept_cys_AS.
DR InterPro; IPR001300; Peptidase_C2_calpain_cat.
DR PANTHER; PTHR10183:SF284; PTHR10183:SF284; 1.
DR Pfam; PF01067; Calpain_III; 1.
DR Pfam; PF13833; EF-hand_8; 1.
DR Pfam; PF00648; Peptidase_C2; 1.
DR PRINTS; PR00704; CALPAIN.
DR SMART; SM00720; calpain_III; 1.
DR SMART; SM00230; CysPc; 1.
DR SUPFAM; SSF47473; SSF47473; 1.
DR SUPFAM; SSF49758; SSF49758; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS50203; CALPAIN_CAT; 1.
DR PROSITE; PS00018; EF_HAND_1; 2.
DR PROSITE; PS50222; EF_HAND_2; 3.
DR PROSITE; PS00139; THIOL_PROTEASE_CYS; 1.
PE 2: Evidence at transcript level;
KW Autocatalytic cleavage; Calcium; Cell membrane; Cytoplasm; Hydrolase;
KW Membrane; Metal-binding; Phosphoprotein; Protease; Reference proteome;
KW Repeat; Thiol protease.
FT CHAIN 1..714
FT /note="Calpain-1 catalytic subunit"
FT /id="PRO_0000207698"
FT DOMAIN 55..354
FT /note="Calpain catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00239"
FT DOMAIN 541..576
FT /note="EF-hand 1"
FT /evidence="ECO:0000305"
FT DOMAIN 585..618
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 615..650
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 680..714
FT /note="EF-hand 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 355..526
FT /note="Domain III"
FT REGION 527..542
FT /note="Linker"
FT REGION 543..713
FT /note="Domain IV"
FT ACT_SITE 115
FT /evidence="ECO:0000250"
FT ACT_SITE 272
FT /evidence="ECO:0000250"
FT ACT_SITE 296
FT /evidence="ECO:0000250"
FT BINDING 109
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000305"
FT BINDING 114
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000305"
FT BINDING 316
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 318
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 323
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 598
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 600
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 602
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 604
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 609
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 628
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 630
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 632
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 634
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 639
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT SITE 15..16
FT /note="Cleavage; for 78 kDa form"
FT /evidence="ECO:0000250"
FT SITE 27..28
FT /note="Cleavage; for 75 kDa form"
FT /evidence="ECO:0000250"
FT MOD_RES 354
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P07384"
SQ SEQUENCE 714 AA; 81854 MW; 40613EBE7FBD7D3A 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 QVNYRGQMVS LIRMRNPWGE
VEWTGAWSDS SSEWNNVDPY ERDQLRVKME DGEFWMSFRD FMREFTRLEI CNLTPDALKS
RTIRKWNTTL YEGTWRRGST AGGCRNYPAT FWVNPQFKIR LDETDDPDDY GDRESGCSFV
LALMQKHRRR ERRFGRDMET IGFAVYEVPP ELAGQPAVHL KRDFFLANAS RARSEQFINL
REVSTRFRLP PGEYVVVPST FEPNKEGDFV LRFFSEKSAG TAELDDQIQA NLPDEQVLSE
EEIDENFKAL FRQLAGEDME TSVKELRTIL NRIISKHKDL RTKGFSLESC RSMVNLMDRD
GNGKLGLVEF NILWNRIRNY LSIFRKFDLD KSGSMSAYEM RMAIESAGFK LNKKLYELII
TRYSEPDLAV DFDNFVCCLV RLETMFRFFK TLDTDLDGVV TFDLFKWLQL TMFA
