CAN8_HUMAN
ID CAN8_HUMAN Reviewed; 703 AA.
AC A6NHC0; B2RXL2;
DT 02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 10-AUG-2010, sequence version 3.
DT 03-AUG-2022, entry version 114.
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 Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Leukocyte;
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 GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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).
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:0000250}. Golgi apparatus
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Stomach.
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; AC099065; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR628412; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR848842; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC157893; AAI57894.1; -; mRNA.
DR CCDS; CCDS73038.1; -.
DR RefSeq; NP_001137434.1; NM_001143962.1.
DR PDB; 2NQA; X-ray; 2.20 A; A/B=23-346.
DR PDBsum; 2NQA; -.
DR AlphaFoldDB; A6NHC0; -.
DR SMR; A6NHC0; -.
DR BioGRID; 132835; 7.
DR IntAct; A6NHC0; 4.
DR STRING; 9606.ENSP00000355837; -.
DR MEROPS; C02.007; -.
DR iPTMnet; A6NHC0; -.
DR PhosphoSitePlus; A6NHC0; -.
DR BioMuta; CAPN8; -.
DR jPOST; A6NHC0; -.
DR MassIVE; A6NHC0; -.
DR MaxQB; A6NHC0; -.
DR PeptideAtlas; A6NHC0; -.
DR PRIDE; A6NHC0; -.
DR ProteomicsDB; 1188; -.
DR Antibodypedia; 61692; 68 antibodies from 16 providers.
DR DNASU; 388743; -.
DR Ensembl; ENST00000366872.10; ENSP00000355837.6; ENSG00000203697.12.
DR GeneID; 388743; -.
DR KEGG; hsa:388743; -.
DR MANE-Select; ENST00000366872.10; ENSP00000355837.6; NM_001143962.2; NP_001137434.1.
DR UCSC; uc031vow.1; human.
DR CTD; 388743; -.
DR DisGeNET; 388743; -.
DR GeneCards; CAPN8; -.
DR HGNC; HGNC:1485; CAPN8.
DR HPA; ENSG00000203697; Tissue enriched (stomach).
DR MIM; 618777; gene.
DR neXtProt; NX_A6NHC0; -.
DR OpenTargets; ENSG00000203697; -.
DR VEuPathDB; HostDB:ENSG00000203697; -.
DR eggNOG; KOG0045; Eukaryota.
DR GeneTree; ENSGT00940000160090; -.
DR HOGENOM; CLU_010982_0_1_1; -.
DR InParanoid; A6NHC0; -.
DR OMA; IGEPCCT; -.
DR OrthoDB; 704215at2759; -.
DR PhylomeDB; A6NHC0; -.
DR TreeFam; TF314748; -.
DR BRENDA; 3.4.22.B28; 2681.
DR PathwayCommons; A6NHC0; -.
DR Reactome; R-HSA-1474228; Degradation of the extracellular matrix.
DR SignaLink; A6NHC0; -.
DR BioGRID-ORCS; 388743; 11 hits in 267 CRISPR screens.
DR ChiTaRS; CAPN8; human.
DR GenomeRNAi; 388743; -.
DR Pharos; A6NHC0; Tbio.
DR PRO; PR:A6NHC0; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; A6NHC0; protein.
DR Bgee; ENSG00000203697; Expressed in mucosa of transverse colon and 122 other tissues.
DR ExpressionAtlas; A6NHC0; baseline and differential.
DR Genevisible; A6NHC0; HS.
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; IBA:GO_Central.
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; 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: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; PS00018; EF_HAND_1; 2.
DR PROSITE; PS50222; EF_HAND_2; 3.
DR PROSITE; PS00139; THIOL_PROTEASE_CYS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Autocatalytic cleavage; Calcium; Cytoplasm; Golgi apparatus;
KW Hydrolase; Metal-binding; Protease; Reference proteome; Repeat;
KW Thiol protease.
FT CHAIN 1..703
FT /note="Calpain-8"
FT /id="PRO_0000349280"
FT DOMAIN 45..344
FT /note="Calpain catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00239"
FT DOMAIN 575..610
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 618..640
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 670..703
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 356..379
FT /note="Domain III"
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:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 620
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 622
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 624
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 629
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT CONFLICT 245
FT /note="S -> Y (in Ref. 3; AAI57894)"
FT /evidence="ECO:0000305"
FT CONFLICT 592
FT /note="T -> M (in Ref. 3; AAI57894)"
FT /evidence="ECO:0000305"
FT HELIX 27..29
FT /evidence="ECO:0007829|PDB:2NQA"
FT HELIX 32..42
FT /evidence="ECO:0007829|PDB:2NQA"
FT HELIX 55..58
FT /evidence="ECO:0007829|PDB:2NQA"
FT TURN 69..72
FT /evidence="ECO:0007829|PDB:2NQA"
FT STRAND 74..76
FT /evidence="ECO:0007829|PDB:2NQA"
FT HELIX 78..81
FT /evidence="ECO:0007829|PDB:2NQA"
FT HELIX 94..96
FT /evidence="ECO:0007829|PDB:2NQA"
FT HELIX 105..114
FT /evidence="ECO:0007829|PDB:2NQA"
FT HELIX 118..124
FT /evidence="ECO:0007829|PDB:2NQA"
FT STRAND 136..145
FT /evidence="ECO:0007829|PDB:2NQA"
FT STRAND 148..155
FT /evidence="ECO:0007829|PDB:2NQA"
FT STRAND 158..161
FT /evidence="ECO:0007829|PDB:2NQA"
FT STRAND 164..167
FT /evidence="ECO:0007829|PDB:2NQA"
FT HELIX 177..188
FT /evidence="ECO:0007829|PDB:2NQA"
FT STRAND 190..192
FT /evidence="ECO:0007829|PDB:2NQA"
FT HELIX 193..195
FT /evidence="ECO:0007829|PDB:2NQA"
FT HELIX 207..209
FT /evidence="ECO:0007829|PDB:2NQA"
FT STRAND 213..216
FT /evidence="ECO:0007829|PDB:2NQA"
FT HELIX 224..234
FT /evidence="ECO:0007829|PDB:2NQA"
FT STRAND 237..241
FT /evidence="ECO:0007829|PDB:2NQA"
FT HELIX 247..249
FT /evidence="ECO:0007829|PDB:2NQA"
FT STRAND 259..261
FT /evidence="ECO:0007829|PDB:2NQA"
FT STRAND 264..274
FT /evidence="ECO:0007829|PDB:2NQA"
FT STRAND 277..285
FT /evidence="ECO:0007829|PDB:2NQA"
FT HELIX 302..306
FT /evidence="ECO:0007829|PDB:2NQA"
FT HELIX 309..315
FT /evidence="ECO:0007829|PDB:2NQA"
FT STRAND 321..327
FT /evidence="ECO:0007829|PDB:2NQA"
FT HELIX 328..334
FT /evidence="ECO:0007829|PDB:2NQA"
FT STRAND 337..341
FT /evidence="ECO:0007829|PDB:2NQA"
SQ SEQUENCE 703 AA; 79144 MW; 2A6DFFC0814894A8 CRC64;
MAAQAAGVSR QRAATQGLGS NQNALKYLGQ DFKTLRQQCL DSGVLFKDPE FPACPSALGY
KDLGPGSPQT QGIIWKRPTE LCPSPQFIVG GATRTDICQG GLGDCWLLAA IASLTLNEEL
LYRVVPRDQD FQENYAGIFH FQFWQYGEWV EVVIDDRLPT KNGQLLFLHS EQGNEFWSAL
LEKAYAKLNG CYEALAGGST VEGFEDFTGG ISEFYDLKKP PANLYQIIRK ALCAGSLLGC
SIDVSSAAEA EAITSQKLVK SHAYSVTGVE EVNFQGHPEK LIRLRNPWGE VEWSGAWSDD
APEWNHIDPR RKEELDKKVE DGEFWMSLSD FVRQFSRLEI CNLSPDSLSS EEVHKWNLVL
FNGHWTRGST AGGCQNYPAT YWTNPQFKIR LDEVDEDQEE SIGEPCCTVL LGLMQKNRRW
RKRIGQGMLS IGYAVYQVPK ELESHTDAHL GRDFFLAYQP SARTSTYVNL REVSGRARLP
PGEYLVVPST FEPFKDGEFC LRVFSEKKAQ ALEIGDVVAG NPYEPHPSEV DQEDDQFRRL
FEKLAGKDSE ITANALKILL NEAFSKRTDI KFDGFNINTC REMISLLDSN GTGTLGAVEF
KTLWLKIQKY LEIYWETDYN HSGTIDAHEM RTALRKAGFT LNSQVQQTIA LRYACSKLGI
NFDSFVACMI RLETLFKLFS LLDEDKDGMV QLSLAEWLCC VLV
