ID   CALR_BOVIN              Reviewed;         417 AA.
AC   P52193; P28489; P42918; Q8SQ53;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   22-FEB-2003, sequence version 2.
DT   02-SEP-2026, entry version 156.
DE   RecName: Full=Calreticulin;
DE   AltName: Full=CRP55;
DE   AltName: Full=Calregulin;
DE   AltName: Full=HACBP;
DE   Flags: Precursor;
GN   Name=CALR; Synonyms=CRT;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Brain;
RX   PubMed=8373827; DOI=10.1016/0167-4838(93)90064-x;
RA   Liu N., Fine R.E., Johnson R.J.;
RT   "Comparison of cDNAs from bovine brain coding for two isoforms of
RT   calreticulin.";
RL   Biochim. Biophys. Acta 1202:70-76(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Brain;
RA   Hossain M.A., Takuwa K., Minakata H., Nakajima T.;
RT   "Bovine brain calreticulin.";
RL   Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   PROTEIN SEQUENCE OF 18-417.
RC   TISSUE=Brain;
RX   PubMed=8135753; DOI=10.1042/bj2980435;
RA   Matsuoka K., Seta K., Yamakawa Y., Okuyama T., Shinoda T., Isobe T.;
RT   "Covalent structure of bovine brain calreticulin.";
RL   Biochem. J. 298:435-442(1994).
RN   [4]
RP   PROTEIN SEQUENCE OF 18-30.
RC   TISSUE=Liver;
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, AND SUBCELLULAR LOCATION.
RX   PubMed=12782144; DOI=10.1016/s0945-053x(02)00117-8;
RA   Somogyi E., Petersson U., Hultenby K., Wendel M.;
RT   "Calreticulin -- an endoplasmic reticulum protein with calcium-binding
RT   activity is also found in the extracellular matrix.";
RL   Matrix Biol. 22:179-191(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. 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 (By similarity). Involved in maternal gene
CC       expression regulation. May participate in oocyte maturation via the
CC       regulation of calcium homeostasis (By similarity). Present in the
CC       cortical granules of non-activated oocytes, is exocytosed during the
CC       cortical reaction in response to oocyte activation and might
CC       participate in the block to polyspermy (By similarity).
CC       {ECO:0000250|UniProtKB:P27797, ECO:0000250|UniProtKB:P28491,
CC       ECO:0000250|UniProtKB:Q8K3H7}.
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 (By
CC       similarity). {ECO:0000250|UniProtKB:P14211,
CC       ECO:0000250|UniProtKB:P18418, ECO:0000250|UniProtKB:P27797}.
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       {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}.
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DR   EMBL; L13462; AAC37307.1; -; mRNA.
DR   EMBL; AB067687; BAB86913.1; -; mRNA.
DR   PIR; A33208; A33208.
DR   PIR; S36799; S36799.
DR   PIR; S43376; S43376.
DR   RefSeq; NP_776425.1; NM_174000.2.
DR   AlphaFoldDB; P52193; -.
DR   SMR; P52193; -.
DR   FunCoup; P52193; 3250.
DR   IntAct; P52193; 2.
DR   STRING; 9913.ENSBTAP00000020111; -.
DR   GlyCosmos; P52193; 1 site, No reported glycans.
DR   GlyGen; P52193; 1 site.
DR   PaxDb; 9913-ENSBTAP00000020111; -.
DR   PeptideAtlas; P52193; -.
DR   Ensembl; ENSBTAT00085048673; ENSBTAP00085042716; ENSBTAG00085037741.
DR   Ensembl; ENSBTAT00090067112; ENSBTAP00090036679; ENSBTAG00090031698.
DR   GeneID; 281036; -.
DR   KEGG; bta:281036; -.
DR   CTD; 811; -.
DR   eggNOG; KOG0674; Eukaryota.
DR   InParanoid; P52193; -.
DR   OrthoDB; 1938156at2759; -.
DR   Proteomes; UP000009136; Unplaced.
DR   GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR   GO; GO:0060473; C:cortical granule; ISS:UniProtKB.
DR   GO; GO:0044194; C:cytolytic granule; ISS:UniProtKB.
DR   GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR   GO; GO:0005788; C:endoplasmic reticulum lumen; ISS:UniProtKB.
DR   GO; GO:0033018; C:sarcoplasmic reticulum lumen; ISS:UniProtKB.
DR   GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR   GO; GO:0036503; P:ERAD pathway; IBA:GO_Central.
DR   GO; GO:0006457; P:protein folding; IBA:GO_Central.
DR   GO; GO:0050821; P:protein stabilization; ISS:UniProtKB.
DR   FunFam; 2.10.250.10:FF:000002; Calreticulin; 1.
DR   FunFam; 2.60.120.200:FF:000113; Calreticulin 3; 1.
DR   FunFam; 2.60.120.200:FF:000122; Calreticulin 3; 1.
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: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   Direct protein sequencing; Disulfide bond; Endoplasmic reticulum;
KW   Extracellular matrix; Glycoprotein; Hydroxylation; Lectin; Lysosome;
KW   Metal-binding; Reference proteome; Repeat; Sarcoplasmic reticulum;
KW   Secreted; Signal; Zinc.
FT   SIGNAL          1..17
FT                   /evidence="ECO:0000269|PubMed:2016321,
FT                   ECO:0000269|PubMed:8135753"
FT   CHAIN           18..417
FT                   /note="Calreticulin"
FT                   /id="PRO_0000004170"
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..270
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        207..251
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        252..261
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        352..378
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        379..408
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   CARBOHYD        179
FT                   /note="N-linked (GlcNAc...) asparagine"
FT   DISULFID        137..163
FT   CONFLICT        1..99
FT                   /note="MLLPVPLLLGLLGLAAADPTVYFKEQFLDGDGWTERWIESKHKPDFGKFVLS
FT                   SGKFYGDQEKDKGLQTSQDARFYALSARFEPFSNKGQTLVVQFTVKH -> MCLNHFLL
FT                   SLVLSIVLLFHFVFYICLHHIVTFLREETVFFSEQFLTLDLKYKASKLSSIREALSMSK
FT                   VGIIENFCFSEISFLQESIKSHGRRTLVGCSPWGHE (in Ref. 1; AAC37307)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        18..21
FT                   /note="DPTV -> EPAI (in Ref. 4; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        111..112
FT                   /note="KL -> NV (in Ref. 1; AAC37307)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        265
FT                   /note="V -> L (in Ref. 1; AAC37307)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        383
FT                   /note="D -> E (in Ref. 1; AAC37307)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        411
FT                   /note="G -> A (in Ref. 1; AAC37307)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   417 AA;  48039 MW;  7BF812C7B5417BE9 CRC64;
     MLLPVPLLLG LLGLAAADPT VYFKEQFLDG DGWTERWIES KHKPDFGKFV LSSGKFYGDQ
     EKDKGLQTSQ DARFYALSAR FEPFSNKGQT LVVQFTVKHE QNIDCGGGYV KLFPAGLDQT
     DMHGDSEYNI MFGPDICGPG TKKVHVIFNY KGKNVLINKD IRCKDDEFTH LYTLIVRPNN
     TYEVKIDNSQ VESGSLEDDW DFLPPKKIKD PDAAKPEDWD DRAKIDDPTD SKPEDWDKPE
     HIPDPDAKKP EDWDEEMDGE WEPPVIQNPE YKGEWKPRQI DNPEYKGIWI HPEIDNPEYS
     PDSNIYAYEN FAVLGLDLWQ VKSGTIFDNF LITNDEAYAE EFGNETWGVT KAAEKQMKDK
     QDEEQRLHEE EEEKKGKEEE EADKDDDEDK DEDEEDEDEK EEEEEEDAAA GQAKDEL
//