CAN2_RABIT
ID CAN2_RABIT Reviewed; 422 AA.
AC P06814;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1988, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Calpain-2 catalytic subunit;
DE EC=3.4.22.53;
DE AltName: Full=Calcium-activated neutral proteinase 2;
DE Short=CANP 2;
DE AltName: Full=Calpain M-type;
DE AltName: Full=Calpain-2 large subunit;
DE AltName: Full=Millimolar-calpain;
DE Short=M-calpain;
DE Flags: Fragment;
GN Name=CAPN2;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2424911; DOI=10.1016/s0021-9258(18)67679-3;
RA Emori Y., Kawasaki H., Sugihara H., Imajoh S., Kawashima S., Suzuki K.;
RT "Isolation and sequence analyses of cDNA clones for the large subunits of
RT two isozymes of rabbit calcium-dependent protease.";
RL J. Biol. Chem. 261:9465-9471(1986).
RN [2]
RP CALCIUM-BINDING DATA.
RX PubMed=3038855; DOI=10.1093/oxfordjournals.jbchem.a121956;
RA Minami Y., Emori Y., Kawasaki H., Suzuki K.;
RT "E-F hand structure-domain of calcium-activated neutral protease (CANP) can
RT bind Ca2+ ions.";
RL J. Biochem. 101:889-895(1987).
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 MYOC at
CC 'Arg-226'. Proteolytically cleaves CPEB3 following neuronal stimulation
CC which abolishes CPEB3 translational repressor activity, leading to
CC translation of CPEB3 target mRNAs. {ECO:0000250|UniProtKB:O08529,
CC ECO:0000250|UniProtKB:P17655}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Broad endopeptidase specificity.; EC=3.4.22.53;
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250};
CC Note=Binds 7 Ca(2+) ions. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Activated by 200-1000 micromolar concentrations of
CC calcium and inhibited by calpastatin.
CC -!- SUBUNIT: Forms a heterodimer with a small (regulatory) subunit
CC (CAPNS1). Interacts with CPEB3; this leads to cleavage of CPEB3.
CC {ECO:0000250|UniProtKB:O08529, ECO:0000250|UniProtKB:Q07009}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane. Note=Translocates to
CC the plasma membrane upon Ca(2+) binding.
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- SIMILARITY: Belongs to the peptidase C2 family. {ECO:0000305}.
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DR EMBL; M13797; AAA31455.1; -; mRNA.
DR PIR; B24815; B24815.
DR AlphaFoldDB; P06814; -.
DR SMR; P06814; -.
DR STRING; 9986.ENSOCUP00000017627; -.
DR MEROPS; C02.972; -.
DR eggNOG; KOG0045; Eukaryota.
DR InParanoid; P06814; -.
DR BRENDA; 3.4.22.53; 1749.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
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:0071230; P:cellular response to amino acid stimulus; ISS:UniProtKB.
DR GO; GO:0006508; P:proteolysis; ISS:UniProtKB.
DR GO; GO:0051493; P:regulation of cytoskeleton organization; IEA:InterPro.
DR CDD; cd00214; Calpain_III; 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; IPR029539; CAPN2.
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; IPR001300; Peptidase_C2_calpain_cat.
DR PANTHER; PTHR10183:SF268; PTHR10183:SF268; 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; SM00054; EFh; 3.
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.
PE 1: Evidence at protein level;
KW Calcium; Cell membrane; Cytoplasm; Hydrolase; Membrane; Metal-binding;
KW Protease; Reference proteome; Repeat; Thiol protease.
FT CHAIN <1..422
FT /note="Calpain-2 catalytic subunit"
FT /id="PRO_0000207704"
FT DOMAIN <1..66
FT /note="Calpain catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00239"
FT DOMAIN 294..327
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 324..359
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 389..422
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 67..236
FT /note="Domain III"
FT REGION 237..251
FT /note="Linker"
FT REGION 252..422
FT /note="Domain IV"
FT ACT_SITE 8
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00239,
FT ECO:0000255|PROSITE-ProRule:PRU10088, ECO:0000255|PROSITE-
FT ProRule:PRU10089, ECO:0000255|PROSITE-ProRule:PRU10090"
FT BINDING 14
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 21
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 45
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 264
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250"
FT BINDING 267
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250"
FT BINDING 269
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250"
FT BINDING 274
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250"
FT BINDING 307
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:3038855"
FT BINDING 309
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:3038855"
FT BINDING 311
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:3038855"
FT BINDING 313
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:3038855"
FT BINDING 318
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:3038855"
FT BINDING 337
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:3038855"
FT BINDING 339
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:3038855"
FT BINDING 341
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:3038855"
FT BINDING 343
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:3038855"
FT BINDING 348
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:3038855"
FT BINDING 380
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 383
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT NON_TER 1
SQ SEQUENCE 422 AA; 49494 MW; AE4FA3C48A333C41 CRC64;
QKLIRIRNPW GEVEWTGRWN DNCPNWNTVD PEVRERLAER HEDGEFWMSF SDFLRHYSRL
EICNLTPDTL TSDTYKKWKL TKMDGNWRRG STAGGCRNYP NTFWMNPQYV IKLEEEDEDQ
EDGESGCTFL VGLIQKHRRR QRKMGEDMHT IGFGIYEVPE ELRGQTNIHL GKNFFLTTRA
RERSDTFINL REVLNRFKLP PGEYILVPST FEPNKNGDFC VRVFSEKKAD YQAVDDEIEA
DLEEADVSED DIDDGFRRLF AQLAGEDAEI SAFELQNILR RVLAKRQDIK TDGLSIETCK
IMVDMLDSDG TGKLGLKEFY VLWTKIQKYQ KIYREIDVDR SGTMNSYEMR KALEEAGFKL
PCQLHEVIVA RFADDQLIID FDNFVRCLVR LETLFKIFKQ LDPDNTGMIQ LDLISWLCFS
VL
