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 24-JAN-2024, entry version 138. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 10116-ENSRNOP00000062898; -. DR Ensembl; ENSRNOT00000004649.7; ENSRNOP00000004649.6; ENSRNOG00000003468.9. [Q78EJ9-2] DR Ensembl; ENSRNOT00000067005.5; ENSRNOP00000062898.3; ENSRNOG00000003468.9. [Q78EJ9-1] DR Ensembl; ENSRNOT00055021606; ENSRNOP00055017520; ENSRNOG00055012655. [Q78EJ9-1] DR Ensembl; ENSRNOT00060012817; ENSRNOP00060009702; ENSRNOG00060007746. [Q78EJ9-1] DR Ensembl; ENSRNOT00065029852; ENSRNOP00065023699; ENSRNOG00065017838. [Q78EJ9-1] DR GeneID; 170808; -. DR KEGG; rno:170808; -. DR UCSC; RGD:620085; rat. [Q78EJ9-1] DR AGR; RGD:620085; -. 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 OrthoDB; 142935at2759; -. 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 cell types or tissues. 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:0006508; P:proteolysis; IBA:GO_Central. DR CDD; cd00214; Calpain_III; 1. DR CDD; cd00044; CysPc; 1. DR Gene3D; 2.60.120.380; -; 1. DR Gene3D; 3.90.70.10; Cysteine proteinases; 1. DR Gene3D; 1.10.238.10; EF-hand; 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; 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; CALPAIN; 1. DR PANTHER; PTHR10183:SF374; CALPAIN-8; 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; SSF49758; Calpain large subunit, middle domain (domain III); 1. DR SUPFAM; SSF54001; Cysteine proteinases; 1. DR SUPFAM; SSF47473; EF-hand; 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. DR Genevisible; Q78EJ9; RN. 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 //