CAN8_RAT
ID CAN8_RAT Reviewed; 703 AA.
AC Q78EJ9; Q64698; Q78EJ8; Q8K407;
DT 02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Calpain-8;
DE EC=3.4.22.53;
DE AltName: Full=Calpain large subunit 4;
DE AltName: Full=New calpain 2;
DE Short=nCL-2;
DE AltName: Full=Stomach-specific M-type calpain;
GN Name=Capn8; Synonyms=Cls4, Ncl2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Gastric mucosa;
RX PubMed=7690035; DOI=10.1016/s0021-9258(19)36540-8;
RA Sorimachi H., Ishiura S., Suzuki K.;
RT "A novel tissue-specific calpain species expressed predominantly in the
RT stomach comprises two alternative splicing products with and without
RT Ca(2+)-binding domain.";
RL J. Biol. Chem. 268:19476-19482(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-17, AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley;
RX PubMed=12150941; DOI=10.1016/s0006-291x(02)00655-1;
RA Duan W.R., Ito M., Lee E.J., Chien P.-Y., Jameson J.L.;
RT "Estrogen regulates a tissue-specific calpain in the anterior pituitary.";
RL Biochem. Biophys. Res. Commun. 295:261-266(2002).
CC -!- FUNCTION: Calcium-regulated non-lysosomal thiol-protease. Involved in
CC membrane trafficking in the gastric surface mucus cells (pit cells) and
CC may involve the membrane trafficking of mucus cells via interactions
CC with coat protein. Proteolytically cleaves the beta-subunit of coatomer
CC complex (By similarity). {ECO:0000250}.
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 -!- SUBUNIT: Monomer and homooligomer. Interacts with COPS1/GPS1, COPB1,
CC EYA2, NME2, NME4 and TOMM70 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:7690035}. Golgi
CC apparatus {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=nCL-2;
CC IsoId=Q78EJ9-1; Sequence=Displayed;
CC Name=2; Synonyms=Calpain 8b, nCL-2';
CC IsoId=Q78EJ9-2; Sequence=VSP_035308, VSP_035309;
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. Detected in the pituitary
CC after estrogen stimulation. {ECO:0000269|PubMed:12150941,
CC ECO:0000269|PubMed:7690035}.
CC -!- DOMAIN: The domain III mediates oligomerization. {ECO:0000250}.
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 {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the peptidase C2 family. {ECO:0000305}.
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DR EMBL; D14478; BAA03369.1; -; Transcribed_RNA.
DR EMBL; D14479; BAA03370.1; -; mRNA.
DR EMBL; D14480; BAA03371.1; -; mRNA.
DR EMBL; AF514419; AAM94284.1; -; Genomic_DNA.
DR PIR; A48764; A48764.
DR RefSeq; NP_579843.2; NM_133309.2. [Q78EJ9-1]
DR AlphaFoldDB; Q78EJ9; -.
DR SMR; Q78EJ9; -.
DR STRING; 10116.ENSRNOP00000062898; -.
DR MEROPS; C02.007; -.
DR iPTMnet; Q78EJ9; -.
DR PhosphoSitePlus; Q78EJ9; -.
DR PaxDb; Q78EJ9; -.
DR Ensembl; ENSRNOT00000004649; ENSRNOP00000004649; ENSRNOG00000003468. [Q78EJ9-2]
DR Ensembl; ENSRNOT00000067005; ENSRNOP00000062898; ENSRNOG00000003468. [Q78EJ9-1]
DR GeneID; 170808; -.
DR KEGG; rno:170808; -.
DR UCSC; RGD:620085; rat. [Q78EJ9-1]
DR CTD; 388743; -.
DR RGD; 620085; Capn8.
DR eggNOG; KOG0045; Eukaryota.
DR GeneTree; ENSGT00940000160090; -.
DR HOGENOM; CLU_010982_0_1_1; -.
DR InParanoid; Q78EJ9; -.
DR OMA; IGEPCCT; -.
DR OrthoDB; 704215at2759; -.
DR PhylomeDB; Q78EJ9; -.
DR TreeFam; TF314748; -.
DR Reactome; R-RNO-1474228; Degradation of the extracellular matrix.
DR PRO; PR:Q78EJ9; -.
DR Proteomes; UP000002494; Chromosome 13.
DR Bgee; ENSRNOG00000003468; Expressed in stomach and 8 other tissues.
DR Genevisible; Q78EJ9; RN.
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; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:1990092; P:calcium-dependent self proteolysis; ISO:RGD.
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; 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: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 SMART; SM00054; EFh; 2.
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; 1.
DR PROSITE; PS50222; EF_HAND_2; 4.
DR PROSITE; PS00139; THIOL_PROTEASE_CYS; 1.
PE 2: Evidence at transcript 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_0000349282"
FT DOMAIN 45..344
FT /note="Calpain catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00239"
FT DOMAIN 532..566
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 575..608
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 605..640
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 670..703
FT /note="EF-hand 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
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|PROSITE-ProRule:PRU00448"
FT BINDING 590
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 592
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 594
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 599
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 618
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 620
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 624
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 629
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT VAR_SEQ 380..381
FT /note="TY -> SS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:7690035"
FT /id="VSP_035308"
FT VAR_SEQ 382..703
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:7690035"
FT /id="VSP_035309"
FT CONFLICT 103
FT /note="G -> V (in Ref. 1; BAA03369)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 703 AA; 79555 MW; C0688B055FC0D6EC CRC64;
MAALAAGVSK QRAVAEGLGS NQNAVKYLGQ DFETLRKQCL NSGVLFKDPE FPACPSALGY
KDLGPGSPDT QGIVWKRPTE LCPNPQFIVG GATRTDIRQG GLGDCWLLAA IASLTLNEKL
LYRVLPRDQS FQKDYAGIFH FQFWQYGEWV EVVIDDRLPT KNGQLLFLHS EEGNEFWSAL
LEKAYAKLNG SYEALVGGST IEGFEDFTGG ISEFYDLKKP PENLYYIIQK ALRKGSLLGC
SIDVSTAAEA EATTRQKLVK GHAYSVTGVE EVNFHGRPEK LIRLRNPWGE VEWSGAWSDN
APEWNYIDPR RKEELDKKAE DGEFWMSFSD FLKQYSRLEI CNLSPDSLSS EEIHKWNLVL
FNGRWTRGST AGGCLNYPGT YWTNPQFKIH LDEVDEDQEE GTSEPCCTVL LGLMQKNRRR
QKRIGQGMLS IGYAVYQIPK ELESHTDAHL GRDFFLGRQP STCSSTYMNL REVSSRVRLP
PGQYLVVPST FEPFKDGDFC LRVFSEKKAK ALEIGDTVSG HPHEPHPRDM DEEDEHVRSL
FEEFVGKDSE ISANQLKRVL NEVLSKRTDM KFDGFNINTC REMISLLDSD GTGSLGPMEF
KTLWLKIRTY LEIFQEMDHN HVGTIEAHEM RTALKKAGFT LNNQVQQTIA MRYACSKLGV
DFNGFVACMI RLETLFKLFR LLDKDQNGIV QLSLAEWLCC VLV
