ID CALR_CAEEL Reviewed; 395 AA. AC P27798; DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1992, sequence version 1. DT 27-MAR-2024, entry version 189. DE RecName: Full=Calreticulin; DE Flags: Precursor; GN Name=crt-1; ORFNames=Y38A10A.5; OS Caenorhabditis elegans. OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida; OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae; OC Caenorhabditis. OX NCBI_TaxID=6239; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=Bristol N2; RX PubMed=1627827; DOI=10.3109/10425179209020808; RA Smith M.J.; RT "A C. elegans gene encodes a protein homologous to mammalian RT calreticulin."; RL DNA Seq. 2:235-240(1992). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Bristol N2; RX PubMed=9851916; DOI=10.1126/science.282.5396.2012; RG The C. elegans sequencing consortium; RT "Genome sequence of the nematode C. elegans: a platform for investigating RT biology."; RL Science 282:2012-2018(1998). RN [3] RP PROTEOLYTIC CLEAVAGE, AND MUTAGENESIS OF ASP-182; ASP-225 AND ASP-253. RX PubMed=17371877; DOI=10.1074/jbc.m611051200; RA Taylor R.C., Brumatti G., Ito S., Hengartner M.O., Derry W.B., Martin S.J.; RT "Establishing a blueprint for CED-3-dependent killing through RT identification of multiple substrates for this protease."; RL J. Biol. Chem. 282:15011-15021(2007). RN [4] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=20153198; DOI=10.1016/j.cub.2009.12.061; RA Zahreddine H., Zhang H., Diogon M., Nagamatsu Y., Labouesse M.; RT "CRT-1/calreticulin and the E3 ligase EEL-1/HUWE1 control hemidesmosome RT maturation in C. elegans development."; RL Curr. Biol. 20:322-327(2010). RN [5] RP FUNCTION, AND INDUCTION BY ER STRESS. RX PubMed=24933177; DOI=10.1016/j.biocel.2014.06.005; RA Lim Y., Lee D., Kalichamy K., Hong S.E., Michalak M., Ahnn J., Kim D.H., RA Lee S.K.; RT "Sumoylation regulates ER stress response by modulating calreticulin gene RT expression in XBP-1-dependent mode in Caenorhabditis elegans."; RL Int. J. Biochem. Cell Biol. 53:399-408(2014). RN [6] RP FUNCTION. RX PubMed=29346364; DOI=10.1371/journal.pgen.1007106; RA Offenburger S.L., Jongsma E., Gartner A.; RT "Mutations in Caenorhabditis elegans neuroligin-like glit-1, the apoptosis RT pathway and the calcium chaperone crt-1 increase dopaminergic RT neurodegeneration after 6-OHDA treatment."; RL PLoS Genet. 14:E1007106-E1007106(2018). RN [7] RP FUNCTION, INDUCTION, AND MUTAGENESIS OF 28-TRP--LEU-395. RX PubMed=32905769; DOI=10.1016/j.celrep.2020.108125; RA Burkewitz K., Feng G., Dutta S., Kelley C.A., Steinbaugh M., Cram E.J., RA Mair W.B.; RT "Atf-6 Regulates Lifespan through ER-Mitochondrial Calcium Homeostasis."; RL Cell Rep. 32:108125-108125(2020). CC -!- FUNCTION: Molecular calcium-binding chaperone promoting folding, CC oligomeric assembly and quality control in the endoplasmic reticulum CC (ER) via the calreticulin/calnexin cycle (By similarity). This lectin CC may interact transiently with almost all of the monoglucosylated CC glycoproteins that are synthesized in the ER (By similarity). Probably CC by controlling the folding of extracellular matrix protein unc- CC 52/Perlecan, may play a role in the formation of fibrous organelles, a CC hemidesmosome-like structure attaching muscles to the epidermis CC (PubMed:20153198). Protects dopaminergic neurons against oxidative CC stress-induced neurodegeneration (PubMed:29346364). May play a role in CC protection against ER stress (PubMed:24933177). Plays a role in CC modulating lifespan, acting by influencing ER calcium homeostasis CC (PubMed:32905769). {ECO:0000250|UniProtKB:P14211, CC ECO:0000269|PubMed:20153198, ECO:0000269|PubMed:24933177, CC ECO:0000269|PubMed:29346364}. CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen. CC -!- INDUCTION: By ER stress in an xbp-1-dependent manner (PubMed:24933177). CC By aging (PubMed:32905769). {ECO:0000269|PubMed:24933177, CC ECO:0000269|PubMed:32905769}. CC -!- DOMAIN: Can be divided into a N-terminal globular domain, a proline- CC rich P-domain forming an elongated arm-like structure and a C-terminal CC acidic domain. The P-domain binds one molecule of calcium with high CC affinity, whereas the acidic C-domain binds multiple calcium ions with CC low affinity (By similarity). {ECO:0000250}. CC -!- DOMAIN: The interaction with glycans occurs through a binding site in CC the globular lectin domain. {ECO:0000250}. CC -!- DOMAIN: The zinc binding sites are localized to the N-domain. CC {ECO:0000250}. CC -!- PTM: Cleaved by caspase ced-3 in vitro. {ECO:0000269|PubMed:17371877}. CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown in a vab-10(e698) mutant CC background causes 45 percent embryonic lethality. In the surviving CC animals, causes a 14 percent larval lethality associated with the CC detachment of muscles from the epidermis. CC {ECO:0000269|PubMed:20153198}. CC -!- SIMILARITY: Belongs to the calreticulin 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; X59589; CAA42159.1; -; Genomic_DNA. DR EMBL; BX284605; CCD69629.1; -; Genomic_DNA. DR PIR; S25851; S25851. DR RefSeq; NP_504575.1; NM_072174.3. DR AlphaFoldDB; P27798; -. DR SMR; P27798; -. DR BioGRID; 44045; 26. DR DIP; DIP-25701N; -. DR IntAct; P27798; 4. DR MINT; P27798; -. DR STRING; 6239.Y38A10A.5.2; -. DR EPD; P27798; -. DR PaxDb; 6239-Y38A10A-5-1; -. DR PeptideAtlas; P27798; -. DR EnsemblMetazoa; Y38A10A.5.1; Y38A10A.5.1; WBGene00000802. DR GeneID; 178997; -. DR KEGG; cel:CELE_Y38A10A.5; -. DR UCSC; Y38A10A.5.1; c. elegans. DR AGR; WB:WBGene00000802; -. DR WormBase; Y38A10A.5; CE21562; WBGene00000802; crt-1. DR eggNOG; KOG0674; Eukaryota. DR GeneTree; ENSGT00950000182915; -. DR HOGENOM; CLU_018224_0_2_1; -. DR InParanoid; P27798; -. DR OMA; ESPYHIM; -. DR OrthoDB; 5489154at2759; -. DR PhylomeDB; P27798; -. DR Reactome; R-CEL-901042; Calnexin/calreticulin cycle. DR PRO; PR:P27798; -. DR Proteomes; UP000001940; Chromosome V. DR Bgee; WBGene00000802; Expressed in embryo and 5 other cell types or tissues. DR GO; GO:0005737; C:cytoplasm; IDA:WormBase. DR GO; GO:0005788; C:endoplasmic reticulum lumen; IEA:UniProtKB-SubCell. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central. DR GO; GO:0005509; F:calcium ion binding; IDA:WormBase. DR GO; GO:0030246; F:carbohydrate binding; IEA:UniProtKB-KW. DR GO; GO:0051082; F:unfolded protein binding; IEA:InterPro. DR GO; GO:0030421; P:defecation; IGI:WormBase. DR GO; GO:0008340; P:determination of adult lifespan; IMP:UniProtKB. DR GO; GO:0032469; P:endoplasmic reticulum calcium ion homeostasis; IMP:UniProtKB. DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IMP:WormBase. DR GO; GO:0031581; P:hemidesmosome assembly; IGI:WormBase. DR GO; GO:0048609; P:multicellular organismal reproductive process; IGI:WormBase. DR GO; GO:0012501; P:programmed cell death; IGI:WormBase. DR GO; GO:0006457; P:protein folding; IBA:GO_Central. DR GO; GO:0010468; P:regulation of gene expression; IMP:WormBase. DR GO; GO:0045471; P:response to ethanol; IEP:WormBase. DR GO; GO:0009408; P:response to heat; IMP:WormBase. DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; IBA:GO_Central. DR Gene3D; 2.60.120.200; -; 1. DR Gene3D; 2.10.250.10; Calreticulin/calnexin, P domain; 1. DR InterPro; IPR001580; Calret/calnex. DR InterPro; IPR018124; Calret/calnex_CS. DR InterPro; IPR009169; Calreticulin. DR InterPro; IPR009033; Calreticulin/calnexin_P_dom_sf. DR InterPro; IPR013320; ConA-like_dom_sf. DR PANTHER; PTHR11073:SF45; CALRETICULIN; 1. DR PANTHER; PTHR11073; CALRETICULIN AND CALNEXIN; 1. DR Pfam; PF00262; Calreticulin; 2. DR PIRSF; PIRSF002356; Calreticulin; 1. DR PRINTS; PR00626; CALRETICULIN. DR SUPFAM; SSF49899; Concanavalin A-like lectins/glucanases; 1. DR SUPFAM; SSF63887; P-domain of calnexin/calreticulin; 1. DR PROSITE; PS00803; CALRETICULIN_1; 1. DR PROSITE; PS00804; CALRETICULIN_2; 1. DR PROSITE; PS00805; CALRETICULIN_REPEAT; 3. DR PROSITE; PS00014; ER_TARGET; 1. DR World-2DPAGE; 0020:P27798; -. PE 1: Evidence at protein level; KW Calcium; Chaperone; Disulfide bond; Endoplasmic reticulum; Lectin; KW Metal-binding; Reference proteome; Repeat; Signal; Zinc. FT SIGNAL 1..15 FT /evidence="ECO:0000255" FT CHAIN 16..395 FT /note="Calreticulin" FT /id="PRO_0000004180" FT REPEAT 186..197 FT /note="1-1" FT REPEAT 205..216 FT /note="1-2" FT REPEAT 222..233 FT /note="1-3" FT REPEAT 239..250 FT /note="1-4" FT REPEAT 254..264 FT /note="2-1" FT REPEAT 268..278 FT /note="2-2" FT REPEAT 282..292 FT /note="2-3" FT REGION 186..250 FT /note="4 X approximate repeats" FT REGION ?..192 FT /note="N-domain" FT REGION 193..301 FT /note="P-domain" FT REGION 202..255 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 254..292 FT /note="3 X approximate repeats" FT REGION 302..395 FT /note="C-domain" FT REGION 340..395 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 392..395 FT /note="Prevents secretion from ER" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10138" FT COMPBIAS 202..216 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 224..249 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 340..377 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 378..395 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 105 FT /ligand="an alpha-D-glucoside" FT /ligand_id="ChEBI:CHEBI:22390" FT /evidence="ECO:0000250|UniProtKB:P14211" FT BINDING 107 FT /ligand="an alpha-D-glucoside" FT /ligand_id="ChEBI:CHEBI:22390" FT /evidence="ECO:0000250|UniProtKB:P14211" FT BINDING 124 FT /ligand="an alpha-D-glucoside" FT /ligand_id="ChEBI:CHEBI:22390" FT /evidence="ECO:0000250|UniProtKB:P14211" FT BINDING 131 FT /ligand="an alpha-D-glucoside" FT /ligand_id="ChEBI:CHEBI:22390" FT /evidence="ECO:0000250|UniProtKB:P14211" FT BINDING 312 FT /ligand="an alpha-D-glucoside" FT /ligand_id="ChEBI:CHEBI:22390" FT /evidence="ECO:0000250|UniProtKB:P14211" FT DISULFID 101..133 FT /evidence="ECO:0000250" FT MUTAGEN 28..395 FT /note="Missing: In bz29; extended lifespan." FT /evidence="ECO:0000269|PubMed:32905769" FT MUTAGEN 182 FT /note="D->E: Partial reduction in ced-3-mediated cleavage; FT when associated with E-225 and E-253." FT /evidence="ECO:0000269|PubMed:17371877" FT MUTAGEN 225 FT /note="D->E: Partial reduction in ced-3-mediated cleavage; FT when associated with E-182 and E-253." FT /evidence="ECO:0000269|PubMed:17371877" FT MUTAGEN 253 FT /note="D->E: Partial reduction in ced-3-mediated cleavage; FT when associated with E-182 and E-225." FT /evidence="ECO:0000269|PubMed:17371877" SQ SEQUENCE 395 AA; 45616 MW; 35CA7D2EC1D56B03 CRC64; MKSLCLLAIV AVVSAEVYFK EEFNDASWEK RWVQSKHKDD FGAFKLSAGK FFDVESRDQG IQTSQDAKFY SRAAKFDKDF SNKGKTLVIQ YTVKHEQGID CGGGYVKVMR ADADLGDFHG ETPYNVMFGP DICGPTRRVH VILNYKGENK LIKKEITCKS DELTHLYTLI LNSDNTYEVK IDGESAQTGS LEEDWDLLPA KKIKDPDAKK PEDWDEREYI DDAEDAKPED WEKPEHIPDP DAKKPEDWDD EMDGEWEPPM IDNPEYKGEW KPKQIKNPAY KGKWIHPEIE NPEYTPDDEL YSYESWGAIG FDLWQVKSGT IFDNIIITDS VEEAEAHAAE TFDKLKTVEK EKKEKADEET RKAEEEARKK AEEEKEAKKD DDEEEKEEEE GHDEL //