CAN8_MOUSE
ID CAN8_MOUSE Reviewed; 703 AA.
AC Q91VA3; Q059W1; Q91UZ9; Q920R7;
DT 02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Calpain-8;
DE EC=3.4.22.53;
DE AltName: Full=New calpain 2;
DE Short=nCL-2;
DE AltName: Full=Stomach-specific M-type calpain;
GN Name=Capn8; Synonyms=Ncl2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), AND TISSUE
RP SPECIFICITY.
RX PubMed=11523006; DOI=10.1007/s002390010209;
RA Hata S., Nishi K., Kawamoto T., Lee H.-J., Kawahara H., Maeda T.,
RA Shintani Y., Sorimachi H., Suzuki K.;
RT "Both the conserved and the unique gene structure of stomach-specific
RT calpains reveal processes of calpain gene evolution.";
RL J. Mol. Evol. 53:191-203(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, INTERACTION WITH COPS1; COPB1; EYA2; NME2; NME4 AND TOMM70,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16476741; DOI=10.1074/jbc.m509244200;
RA Hata S., Koyama S., Kawahara H., Doi N., Maeda T., Toyama-Sorimachi N.,
RA Abe K., Suzuki K., Sorimachi H.;
RT "Stomach-specific calpain, nCL-2, localizes in mucus cells and proteolyzes
RT the beta-subunit of coatomer complex, beta-COP.";
RL J. Biol. Chem. 281:11214-11224(2006).
RN [4]
RP SUBUNIT, ACTIVITY REGULATION, DOMAIN, BIOPHYSICOCHEMICAL PROPERTIES, PTM,
RP AND MUTAGENESIS OF CYS-105.
RX PubMed=17646163; DOI=10.1074/jbc.m703168200;
RA Hata S., Doi N., Kitamura F., Sorimachi H.;
RT "Stomach-specific calpain, nCL-2/calpain 8, is active without calpain
RT regulatory subunit and oligomerizes through C2-like domains.";
RL J. Biol. Chem. 282:27847-27856(2007).
CC -!- FUNCTION: Calcium-regulated non-lysosomal thiol-protease (By
CC similarity). Involved in membrane trafficking in the gastric surface
CC mucus cells (pit cells) and may involve the membrane trafficking of
CC mucus cells via interactions with coat protein. Proteolytically cleaves
CC the beta-subunit of coatomer complex. {ECO:0000250,
CC ECO:0000269|PubMed:16476741}.
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:0000305};
CC Note=Binds 2 calcium ions. {ECO:0000305};
CC -!- ACTIVITY REGULATION: The concentration of calcium for half-maximal
CC activity is 0.3 mM. Inhibited by calpastatin and calpeptin.
CC {ECO:0000269|PubMed:17646163}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 6. {ECO:0000269|PubMed:17646163};
CC Temperature dependence:
CC Optimum temperature is 20 degrees Celsius.
CC {ECO:0000269|PubMed:17646163};
CC -!- SUBUNIT: Monomer and homooligomer. Interacts with COPS1/GPS1, COPB1,
CC EYA2, NME2, NME4 and TOMM70. {ECO:0000269|PubMed:16476741,
CC ECO:0000269|PubMed:17646163}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Golgi apparatus
CC {ECO:0000269|PubMed:16476741}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=nCL-2;
CC IsoId=Q91VA3-1; Sequence=Displayed;
CC Name=2; Synonyms=Calpain 8b, nCL-2';
CC IsoId=Q91VA3-2; Sequence=VSP_035306, VSP_035307;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in the stomach. Localizes
CC strictly to the surface mucus cells in the gastric epithelium and the
CC mucus-secreting goblet cells in the duodenum.
CC {ECO:0000269|PubMed:11523006, ECO:0000269|PubMed:16476741}.
CC -!- DOMAIN: The domain III mediates oligomerization.
CC {ECO:0000269|PubMed:17646163}.
CC -!- PTM: Undergoes autolytic cleavage between Ala-5 and Ala-6 which gives
CC rise to fragments extending from Ala-6 to the C-terminus, Ala-6 to the
CC EF-hand 2 domain and from Ala-6 to the beginning of domain III.
CC -!- SIMILARITY: Belongs to the peptidase C2 family. {ECO:0000305}.
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DR EMBL; AB050201; BAB70479.1; -; Genomic_DNA.
DR EMBL; AB050202; BAB70480.1; -; mRNA.
DR EMBL; AB050203; BAB70481.1; -; mRNA.
DR EMBL; AB061518; BAB55000.1; -; mRNA.
DR EMBL; AB061519; BAB55001.1; -; mRNA.
DR EMBL; BC125504; AAI25505.1; -; mRNA.
DR EMBL; BC125508; AAI25509.1; -; mRNA.
DR CCDS; CCDS35814.1; -. [Q91VA3-1]
DR CCDS; CCDS48477.1; -. [Q91VA3-2]
DR RefSeq; NP_001139278.1; NM_001145806.1. [Q91VA3-2]
DR RefSeq; NP_570960.2; NM_130890.2.
DR AlphaFoldDB; Q91VA3; -.
DR SMR; Q91VA3; -.
DR CORUM; Q91VA3; -.
DR STRING; 10090.ENSMUSP00000047164; -.
DR MEROPS; C02.007; -.
DR PhosphoSitePlus; Q91VA3; -.
DR EPD; Q91VA3; -.
DR jPOST; Q91VA3; -.
DR MaxQB; Q91VA3; -.
DR PaxDb; Q91VA3; -.
DR PeptideAtlas; Q91VA3; -.
DR PRIDE; Q91VA3; -.
DR ProteomicsDB; 281767; -. [Q91VA3-1]
DR ProteomicsDB; 281768; -. [Q91VA3-2]
DR Antibodypedia; 61692; 68 antibodies from 16 providers.
DR DNASU; 170725; -.
DR Ensembl; ENSMUST00000168514; ENSMUSP00000129549; ENSMUSG00000038599. [Q91VA3-2]
DR GeneID; 170725; -.
DR KEGG; mmu:170725; -.
DR UCSC; uc007dyh.2; mouse. [Q91VA3-2]
DR UCSC; uc007dyi.2; mouse. [Q91VA3-1]
DR CTD; 388743; -.
DR MGI; MGI:2181366; Capn8.
DR VEuPathDB; HostDB:ENSMUSG00000038599; -.
DR eggNOG; KOG0045; Eukaryota.
DR GeneTree; ENSGT00940000160090; -.
DR HOGENOM; CLU_010982_3_4_1; -.
DR InParanoid; Q91VA3; -.
DR OrthoDB; 704215at2759; -.
DR PhylomeDB; Q91VA3; -.
DR TreeFam; TF314748; -.
DR BRENDA; 3.4.22.B28; 3474.
DR Reactome; R-MMU-1474228; Degradation of the extracellular matrix.
DR BioGRID-ORCS; 170725; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Capn10; mouse.
DR PRO; PR:Q91VA3; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q91VA3; protein.
DR Bgee; ENSMUSG00000038599; Expressed in pyloric antrum and 21 other tissues.
DR ExpressionAtlas; Q91VA3; baseline and differential.
DR Genevisible; Q91VA3; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0004198; F:calcium-dependent cysteine-type endopeptidase activity; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; IPI:MGI.
DR GO; GO:1990092; P:calcium-dependent self proteolysis; IDA:MGI.
DR GO; GO:0007586; P:digestion; IEA:InterPro.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
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; IPR029543; CAPN8.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR000169; Pept_cys_AS.
DR InterPro; IPR001300; Peptidase_C2_calpain_cat.
DR PANTHER; PTHR10183:SF374; PTHR10183:SF374; 1.
DR Pfam; PF01067; Calpain_III; 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; PS00139; THIOL_PROTEASE_CYS; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Autocatalytic cleavage; Calcium; Cytoplasm;
KW Golgi apparatus; Hydrolase; Metal-binding; Protease; Reference proteome;
KW Repeat; Thiol protease.
FT CHAIN 1..703
FT /note="Calpain-8"
FT /id="PRO_0000349281"
FT DOMAIN 45..344
FT /note="Calpain catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00239"
FT DOMAIN 531..566
FT /note="EF-hand 1"
FT DOMAIN 575..610
FT /note="EF-hand 2"
FT DOMAIN 605..640
FT /note="EF-hand 3"
FT DOMAIN 670..703
FT /note="EF-hand 4"
FT REGION 355..512
FT /note="Domain III"
FT REGION 513..531
FT /note="Linker"
FT /evidence="ECO:0000250"
FT REGION 532..703
FT /note="Domain IV"
FT /evidence="ECO:0000250"
FT ACT_SITE 105
FT /evidence="ECO:0000250"
FT ACT_SITE 262
FT /evidence="ECO:0000250"
FT ACT_SITE 286
FT /evidence="ECO:0000250"
FT BINDING 588
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255"
FT BINDING 590
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255"
FT BINDING 592
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255"
FT BINDING 594
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255"
FT BINDING 599
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255"
FT BINDING 618
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255"
FT BINDING 620
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255"
FT BINDING 624
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255"
FT BINDING 629
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255"
FT VAR_SEQ 379..381
FT /note="ATY -> GSF (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11523006"
FT /id="VSP_035306"
FT VAR_SEQ 382..703
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11523006"
FT /id="VSP_035307"
FT MUTAGEN 105
FT /note="C->S: Loss of activity."
FT /evidence="ECO:0000269|PubMed:17646163"
FT CONFLICT 354
FT /note="H -> Q (in Ref. 1; BAB70479)"
FT /evidence="ECO:0000305"
FT CONFLICT 519
FT /note="P -> A (in Ref. 2; AAI25505/AAI25509)"
FT /evidence="ECO:0000305"
FT CONFLICT 700
FT /note="R -> C (in Ref. 2; AAI25505/AAI25509)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 703 AA; 79335 MW; 50F2F9CCF2192FB6 CRC64;
MAALAAGISK QRAAAQGLGS NQNAVKYLGQ DFETLRKQCL NSGVLFKDPE FPACPSALGY
RDLGPGSAET QGIIWKRPTE LCSNPQFIVG GATRTDIRQG GLGDCWLLAA IASLTLNEKL
LYRVVPRDQS FQKNYAGIFH FQFWQYGEWV EVVIDDRLPT KNGQLLFLHS EEGNEFWSAL
LEKAYAKLNG SYEALAGGST IEGFEDFTGG ISEFYDLRKP PGNLYYTIQK ALRKGSLLGC
SIDVSNAAEA EATTRQKLVK GHAYSVTGVE EVDFRGLPEK LIRLRNPWGE VEWTGAWSDS
APEWNYIDPQ KKGELDKRAE DGEFWMSFSD FLKQFSRLEI CNLSPDSLSS EEIHKWNLVL
FNGRWTRGST AGGCQNYPAT YWTNPQFKIH LDEVDEDQEE GTSEPCCTVL LGLMQKNRRR
QRRIGQGMLS IGYAVYQIPK ELENHTDEHL GRDFFQGRQP STCSSTYMNL REVSSRVQLP
PGQYLVVPST FEPFKDGDFC LRVFSEKKAQ ALEIGDAVPG DPHEPHPRDM DGEDEHFWSL
SEEFADKDSE ISAHQLKRVL NGLLSKRTDM KFDGFNINTC REMISLLDGD GTGSLRPVEF
KTLWLKICKY LEIYQEMDHS RAGTIDAHEM RTALKKAGFT LNNQVQQTIA TRYACSKLGV
DFDGFVACMI RLEILFKLFR LLDKDQNGIV QLSLAEWLCR ALV
