CAN5_HUMAN
ID CAN5_HUMAN Reviewed; 640 AA.
AC O15484; O00263;
DT 12-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 12-FEB-2003, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Calpain-5;
DE EC=3.4.22.-;
DE AltName: Full=Calpain htra-3;
DE AltName: Full=New calpain 3;
DE Short=nCL-3;
GN Name=CAPN5; Synonyms=NCL3;
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=Brain;
RX PubMed=9367857; DOI=10.1006/bbrc.1997.7571;
RA Mugita N., Kimura Y., Ogawa M., Saya H., Nakao M.;
RT "Identification of a novel, tissue-specific calpain htra-3; a human
RT homologue of the Caenorhabditis elegans sex determination gene.";
RL Biochem. Biophys. Res. Commun. 239:845-850(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pancreas;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 1-633.
RC TISSUE=Hippocampus;
RX PubMed=9339374; DOI=10.1006/geno.1997.4870;
RA Dear T.N., Matena K., Vingron M., Boehm T.;
RT "A new subfamily of vertebrate calpains lacking a calmodulin-like domain:
RT implications for calpain regulation and evolution.";
RL Genomics 45:175-184(1997).
RN [4]
RP TISSUE SPECIFICITY, VARIANTS VRNI LEU-243 AND PRO-244, AND CHARACTERIZATION
RP OF VARIANTS VRNI LEU-243 AND PRO-244.
RX PubMed=23055945; DOI=10.1371/journal.pgen.1003001;
RA Mahajan V.B., Skeie J.M., Bassuk A.G., Fingert J.H., Braun T.A.,
RA Daggett H.T., Folk J.C., Sheffield V.C., Stone E.M.;
RT "Calpain-5 mutations cause autoimmune uveitis, retinal neovascularization,
RT and photoreceptor degeneration.";
RL PLoS Genet. 8:E1003001-E1003001(2012).
CC -!- FUNCTION: Calcium-regulated non-lysosomal thiol-protease.
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in many tissues. Strong expression in the
CC photoreceptor cells of the retina, with a punctate pattern of labeling
CC over the nuclei and inner segments with less expression along the other
CC segments and outer plexiform layer. {ECO:0000269|PubMed:23055945}.
CC -!- DISEASE: Vitreoretinopathy, neovascular inflammatory (VRNI)
CC [MIM:193235]: An autoimmune condition of the eye that sequentially
CC mimics uveitis, retinitis pigmentosa, and proliferative diabetic
CC retinopathy as it progresses to complete blindness. Patients present
CC during the second or third decade of life with posterior uveitis and
CC reduction of the electroretinogram b-wave. They become more symptomatic
CC when cataracts, cystoid macular edema, and disk edema diminish visual
CC acuity during the second stage. Severe vision loss begins during the
CC third stage when proliferative retinal neovascularization and
CC epiretinal membranes appear. There is an ongoing pigmentary retinal
CC degeneration and peripheral visual field loss during all stages. In the
CC fourth stage, proliferative vitreoretinopathy causes tractional retinal
CC detachments at the macula and vitreous base. The fifth or end-stage
CC disease is marked by phthisis. {ECO:0000269|PubMed:23055945}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the peptidase C2 family. {ECO:0000305}.
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DR EMBL; U94346; AAC51869.1; -; mRNA.
DR EMBL; BC018123; AAH18123.1; -; mRNA.
DR EMBL; Y10552; CAA71584.1; -; mRNA.
DR CCDS; CCDS8248.1; -.
DR PIR; JC5772; JC5772.
DR RefSeq; NP_004046.2; NM_004055.4.
DR RefSeq; XP_016873712.1; XM_017018223.1.
DR PDB; 6P3Q; X-ray; 2.80 A; A/B=1-343.
DR PDBsum; 6P3Q; -.
DR AlphaFoldDB; O15484; -.
DR SMR; O15484; -.
DR BioGRID; 107187; 13.
DR IntAct; O15484; 5.
DR STRING; 9606.ENSP00000278559; -.
DR MEROPS; C02.011; -.
DR iPTMnet; O15484; -.
DR PhosphoSitePlus; O15484; -.
DR SwissPalm; O15484; -.
DR BioMuta; CAPN5; -.
DR EPD; O15484; -.
DR jPOST; O15484; -.
DR MassIVE; O15484; -.
DR MaxQB; O15484; -.
DR PaxDb; O15484; -.
DR PeptideAtlas; O15484; -.
DR PRIDE; O15484; -.
DR ProteomicsDB; 48688; -.
DR Antibodypedia; 31220; 261 antibodies from 29 providers.
DR DNASU; 726; -.
DR Ensembl; ENST00000529629.5; ENSP00000432332.1; ENSG00000149260.18.
DR Ensembl; ENST00000531028.2; ENSP00000467244.2; ENSG00000149260.18.
DR Ensembl; ENST00000648180.1; ENSP00000498132.1; ENSG00000149260.18.
DR GeneID; 726; -.
DR KEGG; hsa:726; -.
DR MANE-Select; ENST00000648180.1; ENSP00000498132.1; NM_004055.5; NP_004046.2.
DR UCSC; uc001oxx.4; human.
DR CTD; 726; -.
DR DisGeNET; 726; -.
DR GeneCards; CAPN5; -.
DR HGNC; HGNC:1482; CAPN5.
DR HPA; ENSG00000149260; Tissue enhanced (intestine).
DR MalaCards; CAPN5; -.
DR MIM; 193235; phenotype.
DR MIM; 602537; gene.
DR neXtProt; NX_O15484; -.
DR OpenTargets; ENSG00000149260; -.
DR Orphanet; 329211; Autosomal dominant neovascular inflammatory vitreoretinopathy.
DR PharmGKB; PA26062; -.
DR VEuPathDB; HostDB:ENSG00000149260; -.
DR eggNOG; KOG0045; Eukaryota.
DR GeneTree; ENSGT00940000156536; -.
DR HOGENOM; CLU_010982_3_2_1; -.
DR InParanoid; O15484; -.
DR OrthoDB; 704215at2759; -.
DR PhylomeDB; O15484; -.
DR TreeFam; TF314748; -.
DR BRENDA; 3.4.22.B25; 2681.
DR PathwayCommons; O15484; -.
DR Reactome; R-HSA-1474228; Degradation of the extracellular matrix.
DR SignaLink; O15484; -.
DR BioGRID-ORCS; 726; 14 hits in 1073 CRISPR screens.
DR ChiTaRS; CAPN5; human.
DR GeneWiki; CAPN5; -.
DR GenomeRNAi; 726; -.
DR Pharos; O15484; Tbio.
DR PRO; PR:O15484; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; O15484; protein.
DR Bgee; ENSG00000149260; Expressed in mucosa of transverse colon and 146 other tissues.
DR ExpressionAtlas; O15484; baseline and differential.
DR Genevisible; O15484; HS.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0045202; C:synapse; IEA:Ensembl.
DR GO; GO:0004198; F:calcium-dependent cysteine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR CDD; cd04046; C2_Calpain; 1.
DR CDD; cd00214; Calpain_III; 1.
DR CDD; cd00044; CysPc; 1.
DR Gene3D; 2.60.40.150; -; 1.
DR InterPro; IPR033884; C2_Calpain.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
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; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR000169; Pept_cys_AS.
DR InterPro; IPR001300; Peptidase_C2_calpain_cat.
DR Pfam; PF00168; C2; 1.
DR Pfam; PF01067; Calpain_III; 1.
DR Pfam; PF00648; Peptidase_C2; 1.
DR PRINTS; PR00704; CALPAIN.
DR SMART; SM00239; C2; 1.
DR SMART; SM00720; calpain_III; 1.
DR SMART; SM00230; CysPc; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF49758; SSF49758; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS50203; CALPAIN_CAT; 1.
DR PROSITE; PS00139; THIOL_PROTEASE_CYS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disease variant; Hydrolase; Protease; Reference proteome;
KW Thiol protease.
FT CHAIN 1..640
FT /note="Calpain-5"
FT /id="PRO_0000207713"
FT DOMAIN 26..343
FT /note="Calpain catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00239"
FT DOMAIN 499..614
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 344..496
FT /note="Domain III"
FT ACT_SITE 81
FT /evidence="ECO:0000250"
FT ACT_SITE 252
FT /evidence="ECO:0000250"
FT ACT_SITE 284
FT /evidence="ECO:0000250"
FT VARIANT 243
FT /note="R -> L (in VRNI; largely mislocalized to the
FT cytoplasm whereas the wild-type protein is localized near
FT the cell surface; dbSNP:rs397514601)"
FT /evidence="ECO:0000269|PubMed:23055945"
FT /id="VAR_069277"
FT VARIANT 244
FT /note="L -> P (in VRNI; largely mislocalized to the
FT cytoplasm whereas the wild-type protein is localized near
FT the cell surface; dbSNP:rs397514602)"
FT /evidence="ECO:0000269|PubMed:23055945"
FT /id="VAR_069278"
FT CONFLICT 18
FT /note="R -> Q (in Ref. 1; AAC51869)"
FT /evidence="ECO:0000305"
FT CONFLICT 51
FT /note="W -> R (in Ref. 3; CAA71584)"
FT /evidence="ECO:0000305"
FT CONFLICT 112..115
FT /note="EKPN -> RKAQ (in Ref. 1; AAC51869)"
FT /evidence="ECO:0000305"
FT CONFLICT 128..131
FT /note="FGEW -> LGM (in Ref. 1; AAC51869)"
FT /evidence="ECO:0000305"
FT CONFLICT 138
FT /note="D -> E (in Ref. 1; AAC51869)"
FT /evidence="ECO:0000305"
FT CONFLICT 502
FT /note="E -> K (in Ref. 1; AAC51869)"
FT /evidence="ECO:0000305"
FT HELIX 8..10
FT /evidence="ECO:0007829|PDB:6P3Q"
FT HELIX 13..23
FT /evidence="ECO:0007829|PDB:6P3Q"
FT STRAND 30..32
FT /evidence="ECO:0007829|PDB:6P3Q"
FT TURN 36..39
FT /evidence="ECO:0007829|PDB:6P3Q"
FT HELIX 54..57
FT /evidence="ECO:0007829|PDB:6P3Q"
FT STRAND 58..60
FT /evidence="ECO:0007829|PDB:6P3Q"
FT HELIX 81..92
FT /evidence="ECO:0007829|PDB:6P3Q"
FT HELIX 94..100
FT /evidence="ECO:0007829|PDB:6P3Q"
FT HELIX 104..107
FT /evidence="ECO:0007829|PDB:6P3Q"
FT STRAND 111..113
FT /evidence="ECO:0007829|PDB:6P3Q"
FT HELIX 114..116
FT /evidence="ECO:0007829|PDB:6P3Q"
FT STRAND 119..127
FT /evidence="ECO:0007829|PDB:6P3Q"
FT STRAND 130..137
FT /evidence="ECO:0007829|PDB:6P3Q"
FT STRAND 142..154
FT /evidence="ECO:0007829|PDB:6P3Q"
FT HELIX 159..171
FT /evidence="ECO:0007829|PDB:6P3Q"
FT HELIX 174..179
FT /evidence="ECO:0007829|PDB:6P3Q"
FT HELIX 182..190
FT /evidence="ECO:0007829|PDB:6P3Q"
FT STRAND 191..198
FT /evidence="ECO:0007829|PDB:6P3Q"
FT HELIX 199..202
FT /evidence="ECO:0007829|PDB:6P3Q"
FT HELIX 204..206
FT /evidence="ECO:0007829|PDB:6P3Q"
FT HELIX 209..223
FT /evidence="ECO:0007829|PDB:6P3Q"
FT STRAND 227..231
FT /evidence="ECO:0007829|PDB:6P3Q"
FT HELIX 237..239
FT /evidence="ECO:0007829|PDB:6P3Q"
FT STRAND 253..263
FT /evidence="ECO:0007829|PDB:6P3Q"
FT HELIX 269..272
FT /evidence="ECO:0007829|PDB:6P3Q"
FT STRAND 275..283
FT /evidence="ECO:0007829|PDB:6P3Q"
FT HELIX 300..303
FT /evidence="ECO:0007829|PDB:6P3Q"
FT HELIX 307..313
FT /evidence="ECO:0007829|PDB:6P3Q"
FT STRAND 322..326
FT /evidence="ECO:0007829|PDB:6P3Q"
FT HELIX 327..333
FT /evidence="ECO:0007829|PDB:6P3Q"
FT STRAND 335..341
FT /evidence="ECO:0007829|PDB:6P3Q"
SQ SEQUENCE 640 AA; 73169 MW; 7A3A9A1A920410BC CRC64;
MFSCVKPYED QNYSALRRDC RRRKVLFEDP LFPATDDSLY YKGTPGPAVR WKRPKGICED
PRLFVDGISS HDLHQGQVGN CWFVAACSSL ASRESLWQKV IPDWKEQEWD PEKPNAYAGI
FHFHFWRFGE WVDVVIDDRL PTVNNQLIYC HSNSRNEFWC ALVEKAYAKL AGCYQALDGG
NTADALVDFT GGVSEPIDLT EGDFANDETK RNQLFERMLK VHSRGGLISA SIKAVTAADM
EARLACGLVK GHAYAVTDVR KVRLGHGLLA FFKSEKLDMI RLRNPWGERE WNGPWSDTSE
EWQKVSKSER EKMGVTVQDD GEFWMTFEDV CRYFTDIIKC RVINTSHLSI HKTWEEARLH
GAWTLHEDPR QNRGGGCINH KDTFFQNPQY IFEVKKPEDE VLICIQQRPK RSTRREGKGE
NLAIGFDIYK VEENRQYRMH SLQHKAASSI YINSRSVFLR TDQPEGRYVI IPTTFEPGHT
GEFLLRVFTD VPSNCRELRL DEPPHTCWSS LCGYPQLVTQ VHVLGAAGLK DSPTGANSYV
IIKCEGDKVR SAVQKGTSTP EYNVKGIFYR KKLSQPITVQ VWNHRVLKDE FLGQVHLKAD
PDNLQALHTL HLRDRNSRQP SNLPGTVAVH ILSSTSLMAV
