CALR_RABIT
ID CALR_RABIT Reviewed; 418 AA.
AC P15253;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 1.
DT 03-AUG-2022, entry version 151.
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;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Slow-twitch skeletal muscle;
RX PubMed=2600080; DOI=10.1016/s0021-9258(20)88216-7;
RA Fliegel L., Burns K., Maclennan D.H., Reithmeier R.A.F., Michalak M.;
RT "Molecular cloning of the high affinity calcium-binding protein
RT (calreticulin) of skeletal muscle sarcoplasmic reticulum.";
RL J. Biol. Chem. 264:21522-21528(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Fast-twitch skeletal muscle;
RX PubMed=2059224; DOI=10.1016/0006-291x(91)90634-j;
RA Fliegel L., Michalak M.;
RT "Fast-twitch and slow-twitch skeletal muscles express the same isoform of
RT calreticulin.";
RL Biochem. Biophys. Res. Commun. 177:979-984(1991).
RN [3]
RP PROTEIN SEQUENCE OF 18-36.
RX PubMed=2241926; DOI=10.1042/bj2710473;
RA Treves S., de Mattei M., Lanfredi M., Villa A., Green N.M., Maclennan D.H.,
RA Meldolesi J., Pozzan T.;
RT "Calreticulin is a candidate for a calsequestrin-like function in Ca2(+)-
RT storage compartments (calciosomes) of liver and brain.";
RL Biochem. J. 271:473-480(1990).
RN [4]
RP PROTEIN SEQUENCE OF 18-46.
RX PubMed=2016321; DOI=10.1016/s0021-9258(20)89624-0;
RA Milner R.E., Baksh S., Shemanko C., Carpenter M.R., Smillie L., Vance J.E.,
RA Opas M., Michalak M.;
RT "Calreticulin, and not calsequestrin, is the major calcium binding protein
RT of smooth muscle sarcoplasmic reticulum and liver endoplasmic reticulum.";
RL J. Biol. Chem. 266:7155-7165(1991).
RN [5]
RP PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Lung;
RX PubMed=1911780; DOI=10.1021/bi00105a012;
RA Guan S., Falick A.M., Williams D.E., Cashman J.R.;
RT "Evidence for complex formation between rabbit lung flavin-containing
RT monooxygenase and calreticulin.";
RL Biochemistry 30:9892-9900(1991).
RN [6]
RP FUNCTION.
RX PubMed=10581245; DOI=10.1093/emboj/18.23.6718;
RA Saito Y., Ihara Y., Leach M.R., Cohen-Doyle M.F., Williams D.B.;
RT "Calreticulin functions in vitro as a molecular chaperone for both
RT glycosylated and non-glycosylated proteins.";
RL EMBO J. 18:6718-6729(1999).
RN [7]
RP ZINC-BINDING DOMAIN.
RX PubMed=8521965; DOI=10.1016/0014-5793(95)01246-4;
RA Baksh S., Spamer C., Heilmann C., Michalak M.;
RT "Identification of the Zn2+ binding region in calreticulin.";
RL FEBS Lett. 376:53-57(1995).
RN [8]
RP MUTAGENESIS OF HIS-170.
RX PubMed=14522955; DOI=10.1074/jbc.m309497200;
RA Guo L., Groenendyk J., Papp S., Dabrowska M., Knoblach B., Kay C.,
RA Parker J.M., Opas M., Michalak M.;
RT "Identification of an N-domain histidine essential for chaperone function
RT in calreticulin.";
RL J. Biol. Chem. 278:50645-50653(2003).
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 (PubMed:10581245). This lectin interacts
CC transiently with almost all of the monoglucosylated glycoproteins that
CC are synthesized in the ER. Interacts with the DNA-binding domain of
CC NR3C1 and mediates its nuclear export (By similarity). Involved in
CC maternal gene expression regulation. May participate in oocyte
CC maturation via the regulation of calcium homeostasis (By similarity).
CC Present in the cortical granules of non-activated oocytes, is
CC exocytosed during the cortical reaction in response to oocyte
CC activation and might participate in the block to polyspermy (By
CC similarity). {ECO:0000250|UniProtKB:P27797,
CC ECO:0000250|UniProtKB:P28491, ECO:0000250|UniProtKB:Q8K3H7,
CC ECO:0000269|PubMed:10581245}.
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 CLCC1 (By similarity).
CC {ECO:0000250|UniProtKB:P14211, ECO:0000250|UniProtKB:P18418,
CC ECO:0000250|UniProtKB:P27797}.
CC -!- INTERACTION:
CC P15253; P05067: APP; Xeno; NbExp=3; IntAct=EBI-9005200, EBI-77613;
CC P15253; PRO_0000000092 [P05067]: APP; Xeno; NbExp=2; IntAct=EBI-9005200, EBI-821758;
CC P15253; PRO_0000000093 [P05067]: APP; Xeno; NbExp=2; IntAct=EBI-9005200, EBI-2431589;
CC P15253; P12023: App; Xeno; NbExp=2; IntAct=EBI-9005200, EBI-78814;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen
CC {ECO:0000250|UniProtKB:P27797}. Cytoplasm, cytosol
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:0000250|UniProtKB:Q8K3H7}. Cytolytic granule
CC {ECO:0000250|UniProtKB:P27797}. Note=Also found in cell surface (T
CC cells), cytosol and extracellular matrix. During oocyte maturation and
CC after parthenogenetic activation accumulates in cortical granules. In
CC pronuclear and early cleaved embryos localizes weakly to cytoplasm
CC around nucleus and more strongly in the region near the cortex (By
CC similarity). In cortical granules of non-activated oocytes, is
CC exocytosed during the cortical reaction in response to oocyte
CC activation (By similarity). {ECO:0000250|UniProtKB:P27797,
CC ECO:0000250|UniProtKB:P28491, ECO:0000250|UniProtKB:Q8K3H7}.
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 -!- 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}.
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DR EMBL; J05138; AAA31188.1; -; mRNA.
DR PIR; A34154; A34154.
DR PIR; C33208; C33208.
DR PIR; D33208; D33208.
DR PIR; S13046; S13046.
DR RefSeq; NP_001075704.1; NM_001082235.1.
DR AlphaFoldDB; P15253; -.
DR BMRB; P15253; -.
DR SMR; P15253; -.
DR BioGRID; 1172073; 1.
DR CORUM; P15253; -.
DR IntAct; P15253; 4.
DR PRIDE; P15253; -.
DR GeneID; 100009050; -.
DR KEGG; ocu:100009050; -.
DR CTD; 811; -.
DR InParanoid; P15253; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell.
DR GO; GO:0060473; C:cortical granule; ISS: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:0016529; C:sarcoplasmic reticulum; IDA:CAFA.
DR GO; GO:0033018; C:sarcoplasmic reticulum lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; IDA:CAFA.
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; 2.10.250.10; -; 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 Acetylation; Calcium; Chaperone; Cytoplasm; Cytoplasmic vesicle;
KW Direct protein sequencing; Disulfide bond; Endoplasmic reticulum;
KW Extracellular matrix; Hydroxylation; Lectin; Lysosome; Metal-binding;
KW Reference proteome; Repeat; Sarcoplasmic reticulum; Secreted; Signal; Zinc.
FT SIGNAL 1..17
FT /evidence="ECO:0000269|PubMed:2016321,
FT ECO:0000269|PubMed:2241926"
FT CHAIN 18..418
FT /note="Calreticulin"
FT /id="PRO_0000004176"
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..418
FT /note="C-domain"
FT REGION 349..418
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 415..418
FT /note="Prevents secretion from ER"
FT COMPBIAS 199..254
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 352..375
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 376..418
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"
FT VARIANT 35
FT /note="E -> D"
FT MUTAGEN 170
FT /note="H->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:14522955"
FT CONFLICT 90
FT /note="P -> T (in Ref. 5; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 418 AA; 48275 MW; B6082B689DC763A6 CRC64;
MLLPVPLLLG LLGLAAAEPV VYFKEQFLDG DGWTERWIES KHKSDFGKFV LSSGKFYGDQ
EKDKGLQTSQ DARFYALSAR FEPFSNKGQP LVVQFTVKHE QNIDCGGGYV KLFPAGLDQK
DMHGDSEYNI MFGPDICGPG TKKVHVIFNY KGKNVLINKD IRCKDDEFTH LYTLIVRPDN
TYEVKIDNSQ VESGSLEDDW DFLPPKKIKD PDASKPEDWD ERAKIDDPTD SKPEDWDKPE
HIPDPDAKKP EDWDEEMDGE WEPPVIQNPE YKGEWKPRQI DNPDYKGTWI HPEIDNPEYS
PDANIYAYDS FAVLGLDLWQ VKSGTIFDNF LITNDEAYAE EFGNETWGVT KTAEKQMKDK
QDEEQRLKEE EEEKKRKEEE EAEEDEEDKD DKEDEDEDEE DKDEEEEEAA AGQAKDEL
