CALR_CAEEL
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 03-AUG-2022, entry version 180.
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}.
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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; 24.
DR DIP; DIP-25701N; -.
DR IntAct; P27798; 4.
DR MINT; P27798; -.
DR STRING; 6239.Y38A10A.5.1; -.
DR World-2DPAGE; 0020:P27798; -.
DR EPD; P27798; -.
DR PaxDb; P27798; -.
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 CTD; 178997; -.
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; DYKDDPY; -.
DR OrthoDB; 822188at2759; -.
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 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: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:1903204; P:negative regulation of oxidative stress-induced neuron death; IMP:UniProtKB.
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; 2.10.250.10; -; 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; PTHR11073; 1.
DR Pfam; PF00262; Calreticulin; 2.
DR PIRSF; PIRSF002356; Calreticulin; 1.
DR PRINTS; PR00626; CALRETICULIN.
DR SUPFAM; SSF49899; SSF49899; 1.
DR SUPFAM; SSF63887; SSF63887; 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.
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
