ID CALR_CRIGR Reviewed; 417 AA. AC Q8K3H7; DT 22-FEB-2003, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2002, sequence version 1. DT 27-MAR-2024, entry version 121. DE RecName: Full=Calreticulin; DE AltName: Full=CRP55; DE AltName: Full=Calregulin; DE AltName: Full=Endoplasmic reticulum resident protein 60; DE Short=ERp60; DE AltName: Full=HACBP; DE Flags: Precursor; GN Name=CALR; Synonyms=CRT {ECO:0000303|PubMed:11599052}; OS Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; OC Cricetidae; Cricetinae; Cricetulus. OX NCBI_TaxID=10029; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Chung J.Y., Lee G.M.; RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases. RN [2] RP SUBCELLULAR LOCATION, AND FUNCTION. RX PubMed=11599052; DOI=10.1002/mrd.1103; RA Munoz-Gotera R.J., Hernandez-Gonzalez E.O., Mendoza-Hernandez G., RA Contreras R.G., Mujica A.; RT "Exocytosis of a 60 kDa protein (calreticulin) from activated hamster RT oocytes."; RL Mol. Reprod. Dev. 60:405-413(2001). CC -!- FUNCTION: Calcium-binding chaperone that promotes folding, oligomeric CC assembly and quality control in the endoplasmic reticulum (ER) via the CC calreticulin/calnexin cycle. This lectin interacts transiently with CC almost all of the monoglucosylated glycoproteins that are synthesized CC in the ER. Interacts with the DNA-binding domain of NR3C1 and mediates CC its nuclear export. Involved in maternal gene expression regulation. CC May participate in oocyte maturation via the regulation of calcium CC homeostasis (By similarity). Present in the cortical granules of non- CC activated oocytes, is exocytosed during the cortical reaction in CC response to oocyte activation and might participate in the block to CC polyspermy (PubMed:11599052). {ECO:0000250|UniProtKB:P27797, CC ECO:0000250|UniProtKB:P28491, ECO:0000269|PubMed:11599052}. CC -!- SUBUNIT: Monomer. Component of an EIF2 complex at least composed of CC CELF1/CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1 and HSPA5. Interacts CC with PDIA3/ERp57 and SPACA9 (By similarity). Interacts with TRIM21. CC Interacts with NR3C1. Interacts with PPIB. Interacts (via P-domain) CC with PDIA5. Interacts with GABARAP. Interacts with CLCC1. CC {ECO:0000250|UniProtKB:P14211, ECO:0000250|UniProtKB:P18418, CC ECO:0000250|UniProtKB:P27797}. CC -!- INTERACTION: CC Q8K3H7; PRO_0000000091 [P05067]: APP; Xeno; NbExp=2; IntAct=EBI-9005068, EBI-3894543; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen CC {ECO:0000250|UniProtKB:P27797}. Cytoplasm, cytosol CC {ECO:0000250|UniProtKB:P27797}. Cytolytic granule CC {ECO:0000250|UniProtKB:P27797}. Secreted, extracellular space, CC extracellular matrix {ECO:0000250|UniProtKB:P27797}. Cell surface CC {ECO:0000250|UniProtKB:P27797}. Sarcoplasmic reticulum lumen CC {ECO:0000250|UniProtKB:P28491}. Cytoplasmic vesicle, secretory vesicle, CC Cortical granule {ECO:0000269|PubMed:11599052}. Note=Also found in cell CC surface (T cells), cytosol and extracellular matrix. During oocyte CC maturation and after parthenogenetic activation accumulates in cortical CC granules. In pronuclear and early cleaved embryos localizes weakly to CC cytoplasm around nucleus and more strongly in the region near the CC cortex (By similarity). In cortical granules of non-activated oocytes, CC is exocytosed during the cortical reaction in response to oocyte CC activation (PubMed:11599052). {ECO:0000250|UniProtKB:P27797, CC ECO:0000250|UniProtKB:P28491, ECO:0000269|PubMed:11599052}. 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 -!- DOMAIN: Associates with PDIA3 through the tip of the extended arm CC formed by the P-domain. {ECO:0000250}. 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; AY100688; AAM48568.1; -; mRNA. DR RefSeq; NP_001231051.1; NM_001244122.1. DR AlphaFoldDB; Q8K3H7; -. DR SMR; Q8K3H7; -. DR IntAct; Q8K3H7; 1. DR PaxDb; 10029-NP_001231051-1; -. DR GeneID; 100689096; -. DR KEGG; cge:100689096; -. DR CTD; 811; -. DR eggNOG; KOG0674; Eukaryota. DR OrthoDB; 5489154at2759; -. DR Proteomes; UP000694386; Unplaced. DR Proteomes; UP001108280; Chromosome 3. DR GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell. DR GO; GO:0060473; C:cortical granule; IDA:UniProtKB. DR GO; GO:0044194; C:cytolytic granule; IEA:UniProtKB-SubCell. DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW. DR GO; GO:0030496; C:midbody; IDA:UniProtKB. DR GO; GO:0033018; C:sarcoplasmic reticulum lumen; IEA:UniProtKB-SubCell. DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB. DR GO; GO:0030246; F:carbohydrate binding; IEA:UniProtKB-KW. DR GO; GO:0051082; F:unfolded protein binding; IEA:InterPro. DR GO; GO:0006457; P:protein folding; IEA:InterPro. DR GO; GO:0050821; P:protein stabilization; ISS:UniProtKB. DR Gene3D; 2.60.120.200; -; 1. DR Gene3D; 2.10.250.10; Calreticulin/calnexin, P domain; 1. DR Gene3D; 1.10.287.540; Helix hairpin bin; 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:SF16; 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. PE 1: Evidence at protein level; KW Acetylation; Calcium; Chaperone; Cytoplasm; Cytoplasmic vesicle; KW Disulfide bond; Endoplasmic reticulum; Extracellular matrix; Hydroxylation; KW Lectin; Lysosome; Metal-binding; Repeat; Sarcoplasmic reticulum; Secreted; KW Signal; Zinc. FT SIGNAL 1..17 FT /evidence="ECO:0000250" FT CHAIN 18..417 FT /note="Calreticulin" FT /id="PRO_0000004172" FT REPEAT 191..202 FT /note="1-1" FT REPEAT 210..221 FT /note="1-2" FT REPEAT 227..238 FT /note="1-3" FT REPEAT 244..255 FT /note="1-4" FT REPEAT 259..269 FT /note="2-1" FT REPEAT 273..283 FT /note="2-2" FT REPEAT 287..297 FT /note="2-3" FT REGION 18..197 FT /note="N-domain" FT REGION 191..255 FT /note="4 X approximate repeats" FT REGION 193..278 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 198..308 FT /note="P-domain" FT REGION 237..270 FT /note="Interaction with PPIB" FT /evidence="ECO:0000250" FT REGION 259..297 FT /note="3 X approximate repeats" FT REGION 309..417 FT /note="C-domain" FT REGION 350..417 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 414..417 FT /note="Prevents secretion from ER" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10138" FT COMPBIAS 199..254 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 352..381 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 382..417 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 26 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250" FT BINDING 62 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250" FT BINDING 64 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250" FT BINDING 109 FT /ligand="an alpha-D-glucoside" FT /ligand_id="ChEBI:CHEBI:22390" FT /evidence="ECO:0000250|UniProtKB:P14211" FT BINDING 111 FT /ligand="an alpha-D-glucoside" FT /ligand_id="ChEBI:CHEBI:22390" FT /evidence="ECO:0000250|UniProtKB:P14211" FT BINDING 128 FT /ligand="an alpha-D-glucoside" FT /ligand_id="ChEBI:CHEBI:22390" FT /evidence="ECO:0000250|UniProtKB:P14211" FT BINDING 135 FT /ligand="an alpha-D-glucoside" FT /ligand_id="ChEBI:CHEBI:22390" FT /evidence="ECO:0000250|UniProtKB:P14211" FT BINDING 317 FT /ligand="an alpha-D-glucoside" FT /ligand_id="ChEBI:CHEBI:22390" FT /evidence="ECO:0000250|UniProtKB:P14211" FT BINDING 328 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250" FT MOD_RES 48 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P27797" FT MOD_RES 64 FT /note="N6-(2-hydroxyisobutyryl)lysine" FT /evidence="ECO:0000250|UniProtKB:P27797" FT MOD_RES 159 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P27797" FT MOD_RES 209 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P27797" FT DISULFID 105..137 FT /evidence="ECO:0000250" SQ SEQUENCE 417 AA; 48243 MW; D617DA37D14F2D45 CRC64; MLLSVPLLLG LLGLAAAEPA VYFKEQFLDG DDWTNRWVES KHKSDFGKFV LSSGKFYGDQ EKDKGLQTSQ DARFYALSAR FEPFSNKGQT LVVQFTVKHE QNIDCGGGYV KLFPGSLDQK DMHGDSEYNI MFGPDICGPG TKKVHVIFNY KGKNVLINKD IRCKDDEFTH LYTLIVRPDN TYEVKIDNSQ VESGSLEDDW DFLPPKKIKD PDAAKPEDWD ERAKIDDPTD SKPEDWDKPE HIPDPDAKKP EDWDEEMDGE WEPPVIQNPE YKGEWKPRQI DNPDYKGTWI HPEIDNPEYS PDANIYAYDS FAVLGLDLWQ VKSGTIFDNF LITNDEAYAE EFGNETWGVT KASEKQMKDK QDEEQRLKEE EEDKKRKEEE EAEDKEDEDD RDEDEEDEDE KEEDEEDTTP GQTKDEL //