CALR_PIG
ID CALR_PIG Reviewed; 417 AA.
AC P28491; D4N5N1;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 16-MAY-2012, sequence version 3.
DT 03-AUG-2022, entry version 147.
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 Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC TISSUE=Oocyte;
RX PubMed=20222029; DOI=10.1002/mrd.21166;
RA Zhang D.X., Li X.P., Sun S.C., Shen X.H., Cui X.S., Kim N.H.;
RT "Involvement of ER-calreticulin-Ca2+ signaling in the regulation of porcine
RT oocyte meiotic maturation and maternal gene expression.";
RL Mol. Reprod. Dev. 77:462-471(2010).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RG Porcine genome sequencing project;
RL Submitted (NOV-2009) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-105.
RC TISSUE=Small intestine;
RX PubMed=8672129; DOI=10.1007/s003359900153;
RA Winteroe A.K., Fredholm M., Davies W.;
RT "Evaluation and characterization of a porcine small intestine cDNA library:
RT analysis of 839 clones.";
RL Mamm. Genome 7:509-517(1996).
RN [4]
RP PROTEIN SEQUENCE OF 18-32, AND SUBCELLULAR LOCATION.
RC TISSUE=Uterus;
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).
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 (PubMed:20222029). 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:Q8K3H7,
CC ECO:0000269|PubMed:20222029}.
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 -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen
CC {ECO:0000269|PubMed:2016321}. Cytoplasm, cytosol
CC {ECO:0000269|PubMed:20222029}. Secreted, extracellular space,
CC extracellular matrix {ECO:0000250|UniProtKB:P27797}. Cell surface
CC {ECO:0000250|UniProtKB:P27797}. Sarcoplasmic reticulum lumen
CC {ECO:0000269|PubMed:2016321}. Cytoplasmic vesicle, secretory vesicle,
CC Cortical granule {ECO:0000305|PubMed:20222029}. 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
CC (PubMed:20222029). 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:Q8K3H7, ECO:0000269|PubMed:20222029}.
CC -!- TISSUE SPECIFICITY: In blastocyst expressed in all blastomeres (at
CC protein level). In embryos, expressed in spleen, kidney, liver, fat,
CC muscle, ovary, granulosa cells and cumulus cells.
CC {ECO:0000269|PubMed:20222029}.
CC -!- DEVELOPMENTAL STAGE: Expressed in immature GV-stage oocytes, mature
CC MII-stage oocytes, parthenogenetically activated MII-stage oocytes and
CC in pronuclear embryos (at protein level). During in vitro oocyte
CC maturation, expression initially increases after 12 hours of culture,
CC followed by a strong decline at 30 hours (MI stage) and 44 hours (MII
CC stage). Expression remains constant in MII-stage oocytes after
CC parthenogenetic activation, increasing in two- and four-cell
CC parthenotes. Not detected in blastocyst stage embryos.
CC {ECO:0000269|PubMed:20222029}.
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 -!- SIMILARITY: Belongs to the calreticulin family. {ECO:0000305}.
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DR EMBL; GQ984146; ADD52600.1; -; mRNA.
DR EMBL; CU463133; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; F14591; CAA23142.1; -; mRNA.
DR PIR; B33208; B33208.
DR RefSeq; NP_001167604.1; NM_001174133.1.
DR AlphaFoldDB; P28491; -.
DR BMRB; P28491; -.
DR SMR; P28491; -.
DR STRING; 9823.ENSSSCP00000014615; -.
DR PaxDb; P28491; -.
DR PeptideAtlas; P28491; -.
DR PRIDE; P28491; -.
DR Ensembl; ENSSSCT00000015020; ENSSSCP00000014615; ENSSSCG00000013746.
DR Ensembl; ENSSSCT00005050130; ENSSSCP00005030953; ENSSSCG00005031194.
DR Ensembl; ENSSSCT00015056716; ENSSSCP00015022723; ENSSSCG00015041073.
DR Ensembl; ENSSSCT00025083589; ENSSSCP00025036365; ENSSSCG00025060946.
DR Ensembl; ENSSSCT00030011909; ENSSSCP00030005345; ENSSSCG00030008732.
DR Ensembl; ENSSSCT00035058366; ENSSSCP00035023460; ENSSSCG00035043864.
DR Ensembl; ENSSSCT00040018461; ENSSSCP00040007553; ENSSSCG00040013848.
DR Ensembl; ENSSSCT00045041455; ENSSSCP00045028773; ENSSSCG00045024306.
DR Ensembl; ENSSSCT00050081446; ENSSSCP00050034963; ENSSSCG00050059786.
DR Ensembl; ENSSSCT00055044054; ENSSSCP00055035089; ENSSSCG00055022230.
DR Ensembl; ENSSSCT00060018212; ENSSSCP00060007287; ENSSSCG00060013787.
DR Ensembl; ENSSSCT00065025731; ENSSSCP00065010535; ENSSSCG00065019328.
DR Ensembl; ENSSSCT00070015454; ENSSSCP00070012779; ENSSSCG00070008005.
DR GeneID; 100381266; -.
DR KEGG; ssc:100381266; -.
DR CTD; 811; -.
DR VGNC; VGNC:86149; CALR.
DR eggNOG; KOG0674; Eukaryota.
DR GeneTree; ENSGT00950000182915; -.
DR HOGENOM; CLU_018224_0_2_1; -.
DR InParanoid; P28491; -.
DR OMA; MMWCKTV; -.
DR OrthoDB; 822188at2759; -.
DR TreeFam; TF338438; -.
DR Reactome; R-SSC-3000480; Scavenging by Class A Receptors.
DR Reactome; R-SSC-901042; Calnexin/calreticulin cycle.
DR Reactome; R-SSC-983170; Antigen Presentation: Folding, assembly and peptide loading of class I MHC.
DR Proteomes; UP000008227; Chromosome 2.
DR Proteomes; UP000314985; Chromosome 2.
DR Bgee; ENSSSCG00000013746; Expressed in granulosa cell and 43 other tissues.
DR ExpressionAtlas; P28491; baseline and differential.
DR Genevisible; P28491; SS.
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:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0044322; C:endoplasmic reticulum quality control compartment; IEA:Ensembl.
DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR GO; GO:0005615; C:extracellular space; IEA:Ensembl.
DR GO; GO:0042824; C:MHC class I peptide loading complex; IEA:Ensembl.
DR GO; GO:0005635; C:nuclear envelope; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0005844; C:polysome; IEA:Ensembl.
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:0005178; F:integrin binding; IEA:Ensembl.
DR GO; GO:0003729; F:mRNA binding; IEA:Ensembl.
DR GO; GO:0050681; F:nuclear androgen receptor binding; IEA:Ensembl.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IEA:Ensembl.
DR GO; GO:0051082; F:unfolded protein binding; IEA:InterPro.
DR GO; GO:0090398; P:cellular senescence; IEA:Ensembl.
DR GO; GO:0030866; P:cortical actin cytoskeleton organization; IEA:Ensembl.
DR GO; GO:0033144; P:negative regulation of intracellular steroid hormone receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; IEA:Ensembl.
DR GO; GO:0048387; P:negative regulation of retinoic acid receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0017148; P:negative regulation of translation; IEA:Ensembl.
DR GO; GO:1901164; P:negative regulation of trophoblast cell migration; IEA:Ensembl.
DR GO; GO:0002502; P:peptide antigen assembly with MHC class I protein complex; IEA:Ensembl.
DR GO; GO:0045787; P:positive regulation of cell cycle; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:2000510; P:positive regulation of dendritic cell chemotaxis; IEA:Ensembl.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IEA:Ensembl.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:0050766; P:positive regulation of phagocytosis; IEA:Ensembl.
DR GO; GO:1900026; P:positive regulation of substrate adhesion-dependent cell spreading; IEA:Ensembl.
DR GO; GO:0006611; P:protein export from nucleus; IEA:Ensembl.
DR GO; GO:0006457; P:protein folding; IBA:GO_Central.
DR GO; GO:0034504; P:protein localization to nucleus; IEA:Ensembl.
DR GO; GO:0050821; P:protein stabilization; ISS:UniProtKB.
DR GO; GO:0040020; P:regulation of meiotic nuclear division; IEA:Ensembl.
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 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 CHAIN 18..417
FT /note="Calreticulin"
FT /id="PRO_0000004175"
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..277
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 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 137..163
FT /evidence="ECO:0000250"
FT CONFLICT 15
FT /note="A -> V (in Ref. 3; CAA23142)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 417 AA; 48288 MW; 31A9E4CC95F2D54F CRC64;
MLLPVPLLLG LVGLAAAEPT IYFKEQFLDG DGWTDRWIES KHKPDFGRFV LSSGKFYGDQ
EKDKGLQTSQ DARFYALSAR FEPFSNKGQT LVVQFTVKHE QNIDCGGGYV KLFPDGLDQT
DMHGDSEYNI MFGPDICGPG TKKVHVIFNY KGKNVLINKD IRCKDDEFTH LYTLIVRPDN
TYEVKIDNSQ VESGSLEDDW DFLPPKKIKD PDAVKPEDWD ERAKIDDPTD SKPEDWDKPE
HIPDPDAKKP EDWDEEMDGE WEPPVIQNPE YKGEWKPRQI DNPDYKGTWI HPEIDNPEYS
PDSNIYAYEN FAVLGLDLWQ VKSGTIFDNF LITNDEAYAE EFGNETWGVT KAAEKQMKDK
QDEEQRLKEE EEEKKRKEEE EVDKEDEEDK DEDEEEEDEK EEEEEEDAAA GQAKDEL
