CALR_HUMAN
ID CALR_HUMAN Reviewed; 417 AA.
AC P27797; Q6IAT4; Q9UDG2;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1992, sequence version 1.
DT 03-AUG-2022, entry version 249.
DE RecName: Full=Calreticulin {ECO:0000303|PubMed:9427624};
DE AltName: Full=CRP55;
DE AltName: Full=Calregulin;
DE AltName: Full=Endoplasmic reticulum resident protein 60;
DE Short=ERp60;
DE AltName: Full=HACBP;
DE AltName: Full=grp60;
DE Flags: Precursor;
GN Name=CALR {ECO:0000312|HGNC:HGNC:1455}; Synonyms=CRTC;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2332496; DOI=10.1172/jci114582;
RA McCauliffe D.P., Lux F.A., Lieu T.S., Sanz I., Hanke J., Newkirk M.M.,
RA Bachinski L.L., Itoh Y., Siciliano M.J., Reichlin M., Sontheimer R.D.,
RA Capra J.D.;
RT "Molecular cloning, expression, and chromosome 19 localization of a human
RT Ro/SS-A autoantigen.";
RL J. Clin. Invest. 85:1379-1391(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1919005;
RA Rokeach L.A., Haselby J.A., Meilof J.F., Smeenk R.J., Unnasch T.R.,
RA Greene B.M., Hoch S.O.;
RT "Characterization of the autoantigen calreticulin.";
RL J. Immunol. 147:3031-3039(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1733953; DOI=10.1016/s0021-9258(18)45916-9;
RA McCauliffe D.P., Yang Y.S., Wilson J., Sontheimer R.D., Capra J.D.;
RT "The 5'-flanking region of the human calreticulin gene shares homology with
RT the human GRP78, GRP94, and protein disulfide isomerase promoters.";
RL J. Biol. Chem. 267:2557-2562(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Liu J., Peng X., Yuan J., Qiang B.;
RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=19054851; DOI=10.1038/nmeth.1273;
RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y.,
RA Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A.,
RA Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y.,
RA Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T.,
RA Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y.,
RA Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S.,
RA Nomura N.;
RT "Human protein factory for converting the transcriptome into an in vitro-
RT expressed proteome.";
RL Nat. Methods 5:1011-1017(2008).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye, Pancreas, and Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP PROTEIN SEQUENCE OF 18-48; 65-92; 96-114; 168-205 AND 257-354.
RC TISSUE=Placenta;
RX PubMed=7841019; DOI=10.3891/acta.chem.scand.48-0905;
RA Houen G., Koch C.;
RT "Human placental calreticulin: purification, characterization and
RT association with other proteins.";
RL Acta Chem. Scand. 48:905-911(1994).
RN [12]
RP PROTEIN SEQUENCE OF 18-41.
RX PubMed=3260607; DOI=10.1172/jci113607;
RA Lieu T.-S., Newkirk M.M., Capra J.D., Sontheimer R.D.;
RT "Molecular characterization of human Ro/SS-A antigen. Amino terminal
RT sequence of the protein moiety of human Ro/SS-A antigen and immunological
RT activity of a corresponding synthetic peptide.";
RL J. Clin. Invest. 82:96-101(1988).
RN [13]
RP PROTEIN SEQUENCE OF 18-36.
RX PubMed=1911778; DOI=10.1021/bi00105a008;
RA Rojiani M.V., Finlay B.B., Gray V., Dedhar S.;
RT "In vitro interaction of a polypeptide homologous to human Ro/SS-A antigen
RT (calreticulin) with a highly conserved amino acid sequence in the
RT cytoplasmic domain of integrin alpha subunits.";
RL Biochemistry 30:9859-9866(1991).
RN [14]
RP PROTEIN SEQUENCE OF 18-32.
RX PubMed=2400400; DOI=10.1042/bj2700545;
RA Krause K.-H., Simmerman H.K.B., Jones L.R., Campbell K.P.;
RT "Sequence similarity of calreticulin with a Ca2(+)-binding protein that co-
RT purifies with an Ins(1,4,5)P3-sensitive Ca2+ store in HL-60 cells.";
RL Biochem. J. 270:545-548(1990).
RN [15]
RP PROTEIN SEQUENCE OF 18-28.
RC TISSUE=Liver;
RX PubMed=1286669; DOI=10.1002/elps.11501301201;
RA Hochstrasser D.F., Frutiger S., Paquet N., Bairoch A., Ravier F.,
RA Pasquali C., Sanchez J.-C., Tissot J.-D., Bjellqvist B., Vargas R.,
RA Appel R.D., Hughes G.J.;
RT "Human liver protein map: a reference database established by
RT microsequencing and gel comparison.";
RL Electrophoresis 13:992-1001(1992).
RN [16]
RP PROTEIN SEQUENCE OF 25-36; 74-111 AND 208-222, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [17]
RP PROTEIN SEQUENCE OF 25-34; 56-62; 208-221 AND 273-278.
RC TISSUE=Keratinocyte;
RX PubMed=1286667; DOI=10.1002/elps.11501301199;
RA Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E.,
RA Vandekerckhove J.;
RT "Microsequences of 145 proteins recorded in the two-dimensional gel protein
RT database of normal human epidermal keratinocytes.";
RL Electrophoresis 13:960-969(1992).
RN [18]
RP PROTEIN SEQUENCE OF 18-27, AND SUBCELLULAR LOCATION.
RX PubMed=8418194; DOI=10.1084/jem.177.1.1;
RA Dupuis M., Schaerer E., Krause K.-H., Tschopp J.;
RT "The calcium-binding protein calreticulin is a major constituent of lytic
RT granules in cytolytic T lymphocytes.";
RL J. Exp. Med. 177:1-7(1993).
RN [19]
RP PROTEIN SEQUENCE OF 18-26.
RC TISSUE=Colon carcinoma;
RX PubMed=9150948; DOI=10.1002/elps.1150180344;
RA Ji H., Reid G.E., Moritz R.L., Eddes J.S., Burgess A.W., Simpson R.J.;
RT "A two-dimensional gel database of human colon carcinoma proteins.";
RL Electrophoresis 18:605-613(1997).
RN [20]
RP FUNCTION.
RX PubMed=7876246; DOI=10.1074/jbc.270.9.4741;
RA Nauseef W.M., McCormick S.J., Clark R.A.;
RT "Calreticulin functions as a molecular chaperone in the biosynthesis of
RT myeloperoxidase.";
RL J. Biol. Chem. 270:4741-4747(1995).
RN [21]
RP INTERACTION WITH TRIM21.
RX PubMed=8666824;
RA Cheng S.T., Nguyen T.Q., Yang Y.S., Capra J.D., Sontheimer R.D.;
RT "Calreticulin binds hYRNA and the 52-kDa polypeptide component of the
RT Ro/SS-A ribonucleoprotein autoantigen.";
RL J. Immunol. 156:4484-4491(1996).
RN [22]
RP SUBUNIT, AND INTERACTION WITH HLA-E.
RX PubMed=9427624; DOI=10.1016/s0960-9822(98)70014-4;
RA Braud V.M., Allan D.S., Wilson D., McMichael A.J.;
RT "TAP- and tapasin-dependent HLA-E surface expression correlates with the
RT binding of an MHC class I leader peptide.";
RL Curr. Biol. 8:1-10(1998).
RN [23]
RP SUBUNIT, AND INTERACTION WITH HLA-G.
RX PubMed=9640257; DOI=10.1046/j.1365-2567.1998.00439.x;
RA Wainwright S.D., Simpson K.L., Holmes C.H.;
RT "Calreticulin associates with non-HLA-A,-B class I proteins in the human
RT choriocarcinoma cell lines JEG-3 and BeWo.";
RL Immunology 93:437-445(1998).
RN [24]
RP SUBCELLULAR LOCATION.
RX PubMed=10358038; DOI=10.1074/jbc.274.24.16917;
RA Arosa F.A., de Jesus O., Porto G., Carmo A.M., de Sousa M.;
RT "Calreticulin is expressed on the cell surface of activated human
RT peripheral blood T lymphocytes in association with major histocompatibility
RT complex class I molecules.";
RL J. Biol. Chem. 274:16917-16922(1999).
RN [25]
RP SUBUNIT, AND INTERACTION WITH HLA-F.
RX PubMed=10605026; DOI=10.4049/jimmunol.164.1.319;
RA Wainwright S.D., Biro P.A., Holmes C.H.;
RT "HLA-F is a predominantly empty, intracellular, TAP-associated MHC class Ib
RT protein with a restricted expression pattern.";
RL J. Immunol. 164:319-328(2000).
RN [26]
RP FUNCTION, INTERACTION WITH NR3C1, SUBCELLULAR LOCATION, AND MASS
RP SPECTROMETRY.
RX PubMed=11149926; DOI=10.1083/jcb.152.1.127;
RA Holaska J.M., Black B.E., Love D.C., Hanover J.A., Leszyk J., Paschal B.M.;
RT "Calreticulin is a receptor for nuclear export.";
RL J. Cell Biol. 152:127-140(2001).
RN [27]
RP PARTIAL PROTEIN SEQUENCE, DISULFIDE BOND, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=Placenta;
RX PubMed=11322874; DOI=10.1046/j.1432-1327.2001.02138.x;
RA Hoejrup P., Roepstorff P., Houen G.;
RT "Human placental calreticulin characterization of domain structure and
RT post-translational modifications.";
RL Eur. J. Biochem. 268:2558-2565(2001).
RN [28]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-344.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [29]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-48; LYS-159 AND LYS-209, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [30]
RP INTERACTION WITH PPIB.
RX PubMed=20801878; DOI=10.1074/jbc.m110.160101;
RA Kozlov G., Bastos-Aristizabal S., Maattanen P., Rosenauer A., Zheng F.,
RA Killikelly A., Trempe J.F., Thomas D.Y., Gehring K.;
RT "Structural basis of cyclophilin B binding by the calnexin/calreticulin P-
RT domain.";
RL J. Biol. Chem. 285:35551-35557(2010).
RN [31]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [32]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22905912; DOI=10.1021/pr300539b;
RA Rosenow A., Noben J.P., Jocken J., Kallendrusch S., Fischer-Posovszky P.,
RA Mariman E.C., Renes J.;
RT "Resveratrol-induced changes of the human adipocyte secretion profile.";
RL J. Proteome Res. 11:4733-4743(2012).
RN [33]
RP INTERACTION WITH PDIA5.
RX PubMed=23614004; DOI=10.1371/journal.pone.0062021;
RA Vinaik R., Kozlov G., Gehring K.;
RT "Structure of the non-catalytic domain of the protein disulfide isomerase-
RT related protein (PDIR) reveals function in protein binding.";
RL PLoS ONE 8:E62021-E62021(2013).
RN [34]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [35]
RP CLEAVAGE OF SIGNAL PEPTIDE [LARGE SCALE ANALYSIS] AFTER ALA-17, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [36]
RP HYDROXYBUTYRYLATION AT LYS-64.
RX PubMed=29192674; DOI=10.1038/cr.2017.149;
RA Huang H., Luo Z., Qi S., Huang J., Xu P., Wang X., Gao L., Li F., Wang J.,
RA Zhao W., Gu W., Chen Z., Dai L., Dai J., Zhao Y.;
RT "Landscape of the regulatory elements for lysine 2-hydroxyisobutyrylation
RT pathway.";
RL Cell Res. 28:111-125(2018).
RN [37]
RP INTERACTION WITH CLCC1.
RX PubMed=30157172; DOI=10.1371/journal.pgen.1007504;
RA Li L., Jiao X., D'Atri I., Ono F., Nelson R., Chan C.C., Nakaya N., Ma Z.,
RA Ma Y., Cai X., Zhang L., Lin S., Hameed A., Chioza B.A., Hardy H., Arno G.,
RA Hull S., Khan M.I., Fasham J., Harlalka G.V., Michaelides M., Moore A.T.,
RA Coban Akdemir Z.H., Jhangiani S., Lupski J.R., Cremers F.P.M., Qamar R.,
RA Salman A., Chilton J., Self J., Ayyagari R., Kabir F., Naeem M.A., Ali M.,
RA Akram J., Sieving P.A., Riazuddin S., Baple E.L., Riazuddin S.A.,
RA Crosby A.H., Hejtmancik J.F.;
RT "Mutation in the intracellular chloride channel CLCC1 associated with
RT autosomal recessive retinitis pigmentosa.";
RL PLoS Genet. 14:E1007504-E1007504(2018).
RN [38]
RP INVOLVEMENT IN MYELOPROLIFERATIVE NEOPLASMS.
RX PubMed=24325356; DOI=10.1056/nejmoa1311347;
RA Klampfl T., Gisslinger H., Harutyunyan A.S., Nivarthi H., Rumi E.,
RA Milosevic J.D., Them N.C., Berg T., Gisslinger B., Pietra D., Chen D.,
RA Vladimer G.I., Bagienski K., Milanesi C., Casetti I.C., Sant'Antonio E.,
RA Ferretti V., Elena C., Schischlik F., Cleary C., Six M., Schalling M.,
RA Schoenegger A., Bock C., Malcovati L., Pascutto C., Superti-Furga G.,
RA Cazzola M., Kralovics R.;
RT "Somatic mutations of calreticulin in myeloproliferative neoplasms.";
RL N. Engl. J. Med. 369:2379-2390(2013).
RN [39]
RP INVOLVEMENT IN MYELOPROLIFERATIVE NEOPLASMS.
RX PubMed=24325359; DOI=10.1056/nejmoa1312542;
RA Nangalia J., Massie C.E., Baxter E.J., Nice F.L., Gundem G., Wedge D.C.,
RA Avezov E., Li J., Kollmann K., Kent D.G., Aziz A., Godfrey A.L., Hinton J.,
RA Martincorena I., Van Loo P., Jones A.V., Guglielmelli P., Tarpey P.,
RA Harding H.P., Fitzpatrick J.D., Goudie C.T., Ortmann C.A., Loughran S.J.,
RA Raine K., Jones D.R., Butler A.P., Teague J.W., O'Meara S., McLaren S.,
RA Bianchi M., Silber Y., Dimitropoulou D., Bloxham D., Mudie L., Maddison M.,
RA Robinson B., Keohane C., Maclean C., Hill K., Orchard K., Tauro S.,
RA Du M.Q., Greaves M., Bowen D., Huntly B.J.P., Harrison C.N., Cross N.C.P.,
RA Ron D., Vannucchi A.M., Papaemmanuil E., Campbell P.J., Green A.R.;
RT "Somatic CALR mutations in myeloproliferative neoplasms with nonmutated
RT JAK2.";
RL N. Engl. J. Med. 369:2391-2405(2013).
RN [40]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 195-205 IN COMPLEX WITH GABARAP,
RP AND INTERACTION WITH GABARAP.
RX PubMed=19154346; DOI=10.1111/j.1742-4658.2008.06857.x;
RA Thielmann Y., Weiergraber O.H., Mohrluder J., Willbold D.;
RT "Structural framework of the GABARAP-calreticulin interface -- implications
RT for substrate binding to endoplasmic reticulum chaperones.";
RL FEBS J. 276:1140-1152(2009).
RN [41]
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 18-368 IN COMPLEX WITH CALCIUM
RP IONS, AND DISULFIDE BOND.
RX PubMed=21423620; DOI=10.1371/journal.pone.0017886;
RA Chouquet A., Paidassi H., Ling W.L., Frachet P., Houen G., Arlaud G.J.,
RA Gaboriaud C.;
RT "X-ray structure of the human calreticulin globular domain reveals a
RT peptide-binding area and suggests a multi-molecular mechanism.";
RL PLoS ONE 6:E17886-E17886(2011).
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 (PubMed:7876246). Interacts with the DNA-binding domain of
CC NR3C1 and mediates its nuclear export (PubMed:11149926). 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:P28491,
CC ECO:0000250|UniProtKB:Q8K3H7, ECO:0000269|PubMed:11149926,
CC ECO:0000269|PubMed:7876246}.
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 (PubMed:8666824). Interacts with NR3C1 (PubMed:11149926). Interacts
CC with PPIB (PubMed:20801878). Interacts (via P-domain) with PDIA5
CC (PubMed:23614004). Interacts with GABARAP (PubMed:19154346). Interacts
CC with HLA-E-B2M and HLA-G-B2M complexes (PubMed:9427624,
CC PubMed:9640257). Interacts with HLA-F (PubMed:10605026). Interacts with
CC CLCC1 (PubMed:30157172). {ECO:0000250|UniProtKB:P14211,
CC ECO:0000250|UniProtKB:P18418, ECO:0000269|PubMed:10605026,
CC ECO:0000269|PubMed:11149926, ECO:0000269|PubMed:19154346,
CC ECO:0000269|PubMed:20801878, ECO:0000269|PubMed:23614004,
CC ECO:0000269|PubMed:30157172, ECO:0000269|PubMed:8666824,
CC ECO:0000269|PubMed:9427624, ECO:0000269|PubMed:9640257}.
CC -!- INTERACTION:
CC P27797; P05067: APP; NbExp=5; IntAct=EBI-1049597, EBI-77613;
CC P27797; Q8N1W1-4: ARHGEF28; NbExp=3; IntAct=EBI-1049597, EBI-13062134;
CC P27797; Q8TAB5: C1orf216; NbExp=3; IntAct=EBI-1049597, EBI-747505;
CC P27797; O94983-5: CAMTA2; NbExp=3; IntAct=EBI-1049597, EBI-10176008;
CC P27797; O75175: CNOT3; NbExp=3; IntAct=EBI-1049597, EBI-743073;
CC P27797; Q6UXH1-2: CRELD2; NbExp=3; IntAct=EBI-1049597, EBI-21670927;
CC P27797; P49184: DNASE1L1; NbExp=3; IntAct=EBI-1049597, EBI-20894690;
CC P27797; Q8IY82: DRC7; NbExp=3; IntAct=EBI-1049597, EBI-10262896;
CC P27797; Q99944: EGFL8; NbExp=3; IntAct=EBI-1049597, EBI-3924130;
CC P27797; P16422: EPCAM; NbExp=3; IntAct=EBI-1049597, EBI-1171184;
CC P27797; Q9NVM1: EVA1B; NbExp=3; IntAct=EBI-1049597, EBI-10314666;
CC P27797; Q96GK7: FAHD2A; NbExp=3; IntAct=EBI-1049597, EBI-21647872;
CC P27797; Q10981: FUT2; NbExp=3; IntAct=EBI-1049597, EBI-9090702;
CC P27797; O95166: GABARAP; NbExp=4; IntAct=EBI-1049597, EBI-712001;
CC P27797; P36382: GJA5; NbExp=3; IntAct=EBI-1049597, EBI-750433;
CC P27797; P09471: GNAO1; NbExp=3; IntAct=EBI-1049597, EBI-715087;
CC P27797; O15499: GSC2; NbExp=3; IntAct=EBI-1049597, EBI-19954058;
CC P27797; P79483: HLA-DRB3; NbExp=3; IntAct=EBI-1049597, EBI-3910269;
CC P27797; P14060: HSD3B1; NbExp=3; IntAct=EBI-1049597, EBI-17426018;
CC P27797; P04792: HSPB1; NbExp=2; IntAct=EBI-1049597, EBI-352682;
CC P27797; Q7Z6Z7-2: HUWE1; NbExp=3; IntAct=EBI-1049597, EBI-10975491;
CC P27797; O75874: IDH1; NbExp=3; IntAct=EBI-1049597, EBI-715695;
CC P27797; Q9ULR0: ISY1; NbExp=3; IntAct=EBI-1049597, EBI-2557660;
CC P27797; A0JP07: KIAA1683; NbExp=3; IntAct=EBI-1049597, EBI-10171456;
CC P27797; P26715: KLRC1; NbExp=3; IntAct=EBI-1049597, EBI-9018187;
CC P27797; Q6P5S2: LEG1; NbExp=3; IntAct=EBI-1049597, EBI-11750531;
CC P27797; P09382: LGALS1; NbExp=3; IntAct=EBI-1049597, EBI-1048875;
CC P27797; O00214-2: LGALS8; NbExp=3; IntAct=EBI-1049597, EBI-12069522;
CC P27797; P43356: MAGEA2B; NbExp=3; IntAct=EBI-1049597, EBI-5650739;
CC P27797; Q7Z434: MAVS; NbExp=3; IntAct=EBI-1049597, EBI-995373;
CC P27797; P11226: MBL2; NbExp=6; IntAct=EBI-1049597, EBI-5325353;
CC P27797; Q8NCR3: MFI; NbExp=3; IntAct=EBI-1049597, EBI-744790;
CC P27797; Q8TB02: MGC39372; NbExp=3; IntAct=EBI-1049597, EBI-25834188;
CC P27797; Q96EY8: MMAB; NbExp=3; IntAct=EBI-1049597, EBI-7825413;
CC P27797; P48039: MTNR1A; NbExp=3; IntAct=EBI-1049597, EBI-1188238;
CC P27797; A2RUH7: MYBPHL; NbExp=3; IntAct=EBI-1049597, EBI-9088235;
CC P27797; Q9NPC7: MYNN; NbExp=3; IntAct=EBI-1049597, EBI-3446748;
CC P27797; Q9HC98-4: NEK6; NbExp=3; IntAct=EBI-1049597, EBI-11750983;
CC P27797; Q8NCF5-2: NFATC2IP; NbExp=3; IntAct=EBI-1049597, EBI-12305293;
CC P27797; Q96P20: NLRP3; NbExp=3; IntAct=EBI-1049597, EBI-6253230;
CC P27797; Q8N323: NXPE1; NbExp=3; IntAct=EBI-1049597, EBI-25834085;
CC P27797; Q6P4D5-2: PABIR3; NbExp=3; IntAct=EBI-1049597, EBI-9091052;
CC P27797; Q8N2W9: PIAS4; NbExp=3; IntAct=EBI-1049597, EBI-473160;
CC P27797; Q8NBT0: POC1A; NbExp=3; IntAct=EBI-1049597, EBI-2557132;
CC P27797; O14829: PPEF1; NbExp=3; IntAct=EBI-1049597, EBI-2931238;
CC P27797; Q96QH2: PRAM1; NbExp=3; IntAct=EBI-1049597, EBI-2860740;
CC P27797; Q9Y617: PSAT1; NbExp=3; IntAct=EBI-1049597, EBI-709652;
CC P27797; P43686: PSMC4; NbExp=3; IntAct=EBI-1049597, EBI-743997;
CC P27797; Q13200: PSMD2; NbExp=3; IntAct=EBI-1049597, EBI-357648;
CC P27797; Q9Y3Y4: PYGO1; NbExp=3; IntAct=EBI-1049597, EBI-3397474;
CC P27797; Q13636: RAB31; NbExp=3; IntAct=EBI-1049597, EBI-725987;
CC P27797; Q96E17: RAB3C; NbExp=3; IntAct=EBI-1049597, EBI-4287022;
CC P27797; P61224: RAP1B; NbExp=3; IntAct=EBI-1049597, EBI-358143;
CC P27797; P50749: RASSF2; NbExp=3; IntAct=EBI-1049597, EBI-960081;
CC P27797; Q96I25: RBM17; NbExp=3; IntAct=EBI-1049597, EBI-740272;
CC P27797; P52756: RBM5; NbExp=3; IntAct=EBI-1049597, EBI-714003;
CC P27797; Q96EQ0: SGTB; NbExp=3; IntAct=EBI-1049597, EBI-744081;
CC P27797; Q02978: SLC25A11; NbExp=3; IntAct=EBI-1049597, EBI-359174;
CC P27797; Q12824: SMARCB1; NbExp=5; IntAct=EBI-1049597, EBI-358419;
CC P27797; Q3SY56: SP6; NbExp=3; IntAct=EBI-1049597, EBI-11175533;
CC P27797; Q96L03: SPATA17; NbExp=3; IntAct=EBI-1049597, EBI-13322423;
CC P27797; Q7Z698: SPRED2; NbExp=3; IntAct=EBI-1049597, EBI-7082156;
CC P27797; Q53T94: TAF1B; NbExp=3; IntAct=EBI-1049597, EBI-1560239;
CC P27797; Q03518: TAP1; NbExp=2; IntAct=EBI-1049597, EBI-747259;
CC P27797; F6Y2X3: TAZ; NbExp=3; IntAct=EBI-1049597, EBI-25833693;
CC P27797; P48775: TDO2; NbExp=3; IntAct=EBI-1049597, EBI-743494;
CC P27797; Q9BQ29: THAP4; NbExp=3; IntAct=EBI-1049597, EBI-22013570;
CC P27797; Q9BT49: THAP7; NbExp=3; IntAct=EBI-1049597, EBI-741350;
CC P27797; P49746: THBS3; NbExp=3; IntAct=EBI-1049597, EBI-2530931;
CC P27797; Q96JJ7-2: TMX3; NbExp=3; IntAct=EBI-1049597, EBI-25833898;
CC P27797; Q9H2S6-2: TNMD; NbExp=3; IntAct=EBI-1049597, EBI-12003398;
CC P27797; Q68CL5-3: TPGS2; NbExp=3; IntAct=EBI-1049597, EBI-9091010;
CC P27797; Q9ULW0: TPX2; NbExp=3; IntAct=EBI-1049597, EBI-1037322;
CC P27797; Q9NX07: TRNAU1AP; NbExp=3; IntAct=EBI-1049597, EBI-12581310;
CC P27797; P07437: TUBB; NbExp=3; IntAct=EBI-1049597, EBI-350864;
CC P27797; Q7Z780: U2AF1; NbExp=3; IntAct=EBI-1049597, EBI-25833730;
CC P27797; O75317: USP12; NbExp=3; IntAct=EBI-1049597, EBI-2511507;
CC P27797; Q96EF9: ZHX1-C8orf76; NbExp=3; IntAct=EBI-1049597, EBI-25830993;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen
CC {ECO:0000269|PubMed:10358038, ECO:0000269|PubMed:11149926}. Cytoplasm,
CC cytosol {ECO:0000269|PubMed:11149926}. Secreted, extracellular space,
CC extracellular matrix {ECO:0000305}. Cell surface
CC {ECO:0000269|PubMed:10358038}. Sarcoplasmic reticulum lumen
CC {ECO:0000250|UniProtKB:P28491}. Cytoplasmic vesicle, secretory vesicle,
CC Cortical granule {ECO:0000250|UniProtKB:Q8K3H7}. Cytolytic granule
CC {ECO:0000269|PubMed:8418194}. Note=Also found in cell surface (T
CC cells), cytosol and extracellular matrix (PubMed:10358038). During
CC oocyte maturation and after parthenogenetic activation accumulates in
CC cortical granules. In pronuclear and early cleaved embryos localizes
CC weakly to cytoplasm around nucleus and more strongly in the region near
CC the cortex (By similarity). In cortical granules of non-activated
CC oocytes, is exocytosed during the cortical reaction in response to
CC oocyte activation (By similarity). {ECO:0000250|UniProtKB:P28491,
CC ECO:0000250|UniProtKB:Q8K3H7, ECO:0000269|PubMed:8418194}.
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.
CC -!- DOMAIN: The interaction with glycans occurs through a binding site in
CC the globular lectin domain.
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.
CC -!- MASS SPECTROMETRY: Mass=46879; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:11149926};
CC -!- DISEASE: Note=CALR somatic mutations are frequently found in
CC myeloproliferative neoplasms lacking JAK2 or MPL mutations.
CC Myeloproliferative neoplasms are chronic myeloid cancers characterized
CC by overproduction of mature blood cells, and may evolve into acute
CC myeloid leukemia. In addition to chronic myeloid leukemia with the BCR-
CC ABL fusion gene, the three most common myeloproliferative neoplasms are
CC essential thrombocythemia, polycythemia vera, and myelofibrosis.
CC {ECO:0000269|PubMed:24325356, ECO:0000269|PubMed:24325359}.
CC -!- SIMILARITY: Belongs to the calreticulin family. {ECO:0000305}.
CC -!- CAUTION: Was originally thought to be the 52 kDa Ro autoantigen.
CC {ECO:0000305|PubMed:2332496}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Calreticulin entry;
CC URL="https://en.wikipedia.org/wiki/Calreticulin";
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - Glycan Binding;
CC Note=Calreticulin;
CC URL="http://www.functionalglycomics.org/glycomics/GBPServlet?&operationType=view&cbpId=cbp_hum_other_405";
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DR EMBL; M32294; AAA36582.1; -; mRNA.
DR EMBL; M84739; AAA51916.1; -; mRNA.
DR EMBL; AY047586; AAL13126.1; -; mRNA.
DR EMBL; AB451408; BAG70222.1; -; mRNA.
DR EMBL; BT007448; AAP36116.1; -; mRNA.
DR EMBL; CR457070; CAG33351.1; -; mRNA.
DR EMBL; AD000092; AAB51176.1; -; Genomic_DNA.
DR EMBL; CH471106; EAW84331.1; -; Genomic_DNA.
DR EMBL; BC002500; AAH02500.1; -; mRNA.
DR EMBL; BC007911; AAH07911.1; -; mRNA.
DR EMBL; BC020493; AAH20493.1; -; mRNA.
DR CCDS; CCDS12288.1; -.
DR PIR; A42330; A37047.
DR RefSeq; NP_004334.1; NM_004343.3.
DR PDB; 2CLR; X-ray; 2.00 A; C/F=1-10.
DR PDB; 3DOW; X-ray; 2.30 A; B=195-205.
DR PDB; 3POS; X-ray; 1.65 A; A/B/C=18-204, A/B/C=302-368.
DR PDB; 3POW; X-ray; 1.55 A; A=18-204, A=302-368.
DR PDB; 5LK5; X-ray; 2.30 A; A/B/C/D/E/F/G/H/I/J=18-204, A/B/C/D/E/F/G/H/I/J=303-368.
DR PDB; 5V90; X-ray; 3.25 A; B/D=238-273.
DR PDB; 6ENY; EM; 5.80 A; G=18-417.
DR PDBsum; 2CLR; -.
DR PDBsum; 3DOW; -.
DR PDBsum; 3POS; -.
DR PDBsum; 3POW; -.
DR PDBsum; 5LK5; -.
DR PDBsum; 5V90; -.
DR PDBsum; 6ENY; -.
DR AlphaFoldDB; P27797; -.
DR BMRB; P27797; -.
DR SMR; P27797; -.
DR BioGRID; 107262; 367.
DR CORUM; P27797; -.
DR DIP; DIP-104N; -.
DR IntAct; P27797; 164.
DR MINT; P27797; -.
DR STRING; 9606.ENSP00000320866; -.
DR DrugBank; DB00025; Antihemophilic factor, human recombinant.
DR DrugBank; DB11093; Calcium citrate.
DR DrugBank; DB11348; Calcium Phosphate.
DR DrugBank; DB14481; Calcium phosphate dihydrate.
DR DrugBank; DB09130; Copper.
DR DrugBank; DB13949; Ferric cation.
DR DrugBank; DB06245; Lanoteplase.
DR DrugBank; DB13998; Lonoctocog alfa.
DR DrugBank; DB01065; Melatonin.
DR DrugBank; DB13999; Moroctocog alfa.
DR DrugBank; DB00031; Tenecteplase.
DR DrugBank; DB14520; Tetraferric tricitrate decahydrate.
DR MoonProt; P27797; -.
DR UniLectin; P27797; -.
DR GlyConnect; 1060; 10 N-Linked glycans (1 site).
DR GlyGen; P27797; 2 sites, 10 N-linked glycans (1 site), 1 O-linked glycan (1 site).
DR iPTMnet; P27797; -.
DR MetOSite; P27797; -.
DR PhosphoSitePlus; P27797; -.
DR SwissPalm; P27797; -.
DR BioMuta; CALR; -.
DR DMDM; 117501; -.
DR DOSAC-COBS-2DPAGE; P27797; -.
DR OGP; P27797; -.
DR REPRODUCTION-2DPAGE; IPI00020599; -.
DR SWISS-2DPAGE; P27797; -.
DR UCD-2DPAGE; P27797; -.
DR CPTAC; CPTAC-33; -.
DR CPTAC; CPTAC-34; -.
DR CPTAC; CPTAC-698; -.
DR EPD; P27797; -.
DR jPOST; P27797; -.
DR MassIVE; P27797; -.
DR PaxDb; P27797; -.
DR PeptideAtlas; P27797; -.
DR PRIDE; P27797; -.
DR ProteomicsDB; 54410; -.
DR TopDownProteomics; P27797; -.
DR ABCD; P27797; 3 sequenced antibodies.
DR Antibodypedia; 1028; 1147 antibodies from 47 providers.
DR CPTC; P27797; 1 antibody.
DR DNASU; 811; -.
DR Ensembl; ENST00000316448.10; ENSP00000320866.4; ENSG00000179218.15.
DR Ensembl; ENST00000586967.2; ENSP00000466037.2; ENSG00000179218.15.
DR GeneID; 811; -.
DR KEGG; hsa:811; -.
DR MANE-Select; ENST00000316448.10; ENSP00000320866.4; NM_004343.4; NP_004334.1.
DR CTD; 811; -.
DR DisGeNET; 811; -.
DR GeneCards; CALR; -.
DR HGNC; HGNC:1455; CALR.
DR HPA; ENSG00000179218; Low tissue specificity.
DR MalaCards; CALR; -.
DR MIM; 109091; gene.
DR neXtProt; NX_P27797; -.
DR OpenTargets; ENSG00000179218; -.
DR Orphanet; 131; Budd-Chiari syndrome.
DR Orphanet; 3318; Essential thrombocythemia.
DR Orphanet; 824; Primary myelofibrosis.
DR PharmGKB; PA26046; -.
DR VEuPathDB; HostDB:ENSG00000179218; -.
DR eggNOG; KOG0674; Eukaryota.
DR GeneTree; ENSGT00950000182915; -.
DR HOGENOM; CLU_018224_0_2_1; -.
DR InParanoid; P27797; -.
DR OMA; MMWCKTV; -.
DR OrthoDB; 822188at2759; -.
DR PhylomeDB; P27797; -.
DR TreeFam; TF338438; -.
DR PathwayCommons; P27797; -.
DR Reactome; R-HSA-1236974; ER-Phagosome pathway.
DR Reactome; R-HSA-168316; Assembly of Viral Components at the Budding Site.
DR Reactome; R-HSA-3000480; Scavenging by Class A Receptors.
DR Reactome; R-HSA-3000484; Scavenging by Class F Receptors.
DR Reactome; R-HSA-381183; ATF6 (ATF6-alpha) activates chaperone genes.
DR Reactome; R-HSA-901042; Calnexin/calreticulin cycle.
DR Reactome; R-HSA-983170; Antigen Presentation: Folding, assembly and peptide loading of class I MHC.
DR SignaLink; P27797; -.
DR BioGRID-ORCS; 811; 28 hits in 1097 CRISPR screens.
DR ChiTaRS; CALR; human.
DR EvolutionaryTrace; P27797; -.
DR GeneWiki; Calreticulin; -.
DR GenomeRNAi; 811; -.
DR Pharos; P27797; Tbio.
DR PRO; PR:P27797; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P27797; protein.
DR Bgee; ENSG00000179218; Expressed in stromal cell of endometrium and 203 other tissues.
DR ExpressionAtlas; P27797; baseline and differential.
DR Genevisible; P27797; HS.
DR GO; GO:0001669; C:acrosomal vesicle; IEA:Ensembl.
DR GO; GO:0009986; C:cell surface; TAS:BHF-UCL.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IEA:Ensembl.
DR GO; GO:0060473; C:cortical granule; ISS:UniProtKB.
DR GO; GO:0044194; C:cytolytic granule; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0071682; C:endocytic vesicle lumen; TAS:Reactome.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IDA:UniProtKB.
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:0033116; C:endoplasmic reticulum-Golgi intermediate compartment membrane; TAS:Reactome.
DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IMP:CAFA.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl.
DR GO; GO:0071556; C:integral component of lumenal side of endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0042824; C:MHC class I peptide loading complex; IDA:UniProtKB.
DR GO; GO:0005635; C:nuclear envelope; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:BHF-UCL.
DR GO; GO:0030670; C:phagocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0005844; C:polysome; IDA:BHF-UCL.
DR GO; GO:0033018; C:sarcoplasmic reticulum lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0005790; C:smooth endoplasmic reticulum; IEA:Ensembl.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0030246; F:carbohydrate binding; TAS:BHF-UCL.
DR GO; GO:0051087; F:chaperone binding; TAS:BHF-UCL.
DR GO; GO:0001849; F:complement component C1q complex binding; TAS:BHF-UCL.
DR GO; GO:0003677; F:DNA binding; NAS:UniProtKB.
DR GO; GO:0042562; F:hormone binding; IEA:Ensembl.
DR GO; GO:0005178; F:integrin binding; IPI:BHF-UCL.
DR GO; GO:0005506; F:iron ion binding; IEA:Ensembl.
DR GO; GO:0003729; F:mRNA binding; IDA:BHF-UCL.
DR GO; GO:0050681; F:nuclear androgen receptor binding; IDA:BHF-UCL.
DR GO; GO:0042277; F:peptide binding; IEA:Ensembl.
DR GO; GO:0044183; F:protein folding chaperone; TAS:BHF-UCL.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0051082; F:unfolded protein binding; TAS:BHF-UCL.
DR GO; GO:0008270; F:zinc ion binding; TAS:BHF-UCL.
DR GO; GO:0055007; P:cardiac muscle cell differentiation; IEA:Ensembl.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; TAS:UniProtKB.
DR GO; GO:0071257; P:cellular response to electrical stimulus; IEA:Ensembl.
DR GO; GO:0071285; P:cellular response to lithium ion; IEA:Ensembl.
DR GO; GO:0098586; P:cellular response to virus; IEA:Ensembl.
DR GO; GO:0090398; P:cellular senescence; IGI:BHF-UCL.
DR GO; GO:0030866; P:cortical actin cytoskeleton organization; IEA:Ensembl.
DR GO; GO:0042921; P:glucocorticoid receptor signaling pathway; TAS:BHF-UCL.
DR GO; GO:0033144; P:negative regulation of intracellular steroid hormone receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; IDA:BHF-UCL.
DR GO; GO:0048387; P:negative regulation of retinoic acid receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:BHF-UCL.
DR GO; GO:0017148; P:negative regulation of translation; IDA:BHF-UCL.
DR GO; GO:1901164; P:negative regulation of trophoblast cell migration; IMP:CAFA.
DR GO; GO:0002502; P:peptide antigen assembly with MHC class I protein complex; ISS:BHF-UCL.
DR GO; GO:0045787; P:positive regulation of cell cycle; IGI:BHF-UCL.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IGI:BHF-UCL.
DR GO; GO:2000510; P:positive regulation of dendritic cell chemotaxis; IMP:UniProtKB.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IMP:CAFA.
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; ISS:BHF-UCL.
DR GO; GO:1900026; P:positive regulation of substrate adhesion-dependent cell spreading; IMP:UniProtKB.
DR GO; GO:0006611; P:protein export from nucleus; IDA:UniProtKB.
DR GO; GO:0006457; P:protein folding; IBA:GO_Central.
DR GO; GO:0034975; P:protein folding in endoplasmic reticulum; TAS:ParkinsonsUK-UCL.
DR GO; GO:0034504; P:protein localization to nucleus; IDA:UniProtKB.
DR GO; GO:0022417; P:protein maturation by protein folding; TAS:BHF-UCL.
DR GO; GO:0050821; P:protein stabilization; ISS:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; TAS:UniProtKB.
DR GO; GO:0040020; P:regulation of meiotic nuclear division; IEA:Ensembl.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; TAS:ProtInc.
DR GO; GO:0032355; P:response to estradiol; IEA:Ensembl.
DR GO; GO:1903416; P:response to glycoside; IEA:Ensembl.
DR GO; GO:0033574; P:response to testosterone; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0051208; P:sequestering of calcium ion; TAS:BHF-UCL.
DR GO; GO:0007283; P:spermatogenesis; 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 3D-structure; Acetylation; Calcium; Chaperone; Cytoplasm;
KW Cytoplasmic vesicle; Direct protein sequencing; Disulfide bond;
KW Endoplasmic reticulum; Extracellular matrix; Glycoprotein; Hydroxylation;
KW Lectin; Lysosome; Metal-binding; Reference proteome; Repeat;
KW Sarcoplasmic reticulum; Secreted; Signal; Zinc.
FT SIGNAL 1..17
FT /evidence="ECO:0000269|PubMed:1286669,
FT ECO:0000269|PubMed:1911778, ECO:0000269|PubMed:2400400,
FT ECO:0000269|PubMed:3260607, ECO:0000269|PubMed:7841019,
FT ECO:0000269|PubMed:8418194, ECO:0000269|PubMed:9150948,
FT ECO:0007744|PubMed:25944712"
FT CHAIN 18..417
FT /note="Calreticulin"
FT /id="PRO_0000004173"
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 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 BINDING 62
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT BINDING 64
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
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 MOD_RES 48
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 64
FT /note="N6-(2-hydroxyisobutyryl)lysine"
FT /evidence="ECO:0000269|PubMed:29192674"
FT MOD_RES 159
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 209
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT CARBOHYD 344
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT DISULFID 105..137
FT /evidence="ECO:0000269|PubMed:11322874,
FT ECO:0000269|PubMed:21423620"
FT STRAND 20..25
FT /evidence="ECO:0007829|PDB:3POW"
FT HELIX 30..35
FT /evidence="ECO:0007829|PDB:3POW"
FT STRAND 37..39
FT /evidence="ECO:0007829|PDB:3POW"
FT STRAND 42..44
FT /evidence="ECO:0007829|PDB:3POW"
FT STRAND 49..52
FT /evidence="ECO:0007829|PDB:3POW"
FT TURN 60..63
FT /evidence="ECO:0007829|PDB:3POW"
FT STRAND 65..68
FT /evidence="ECO:0007829|PDB:3POW"
FT STRAND 70..84
FT /evidence="ECO:0007829|PDB:3POW"
FT STRAND 91..98
FT /evidence="ECO:0007829|PDB:3POW"
FT STRAND 104..107
FT /evidence="ECO:0007829|PDB:3POW"
FT STRAND 110..113
FT /evidence="ECO:0007829|PDB:3POW"
FT HELIX 119..121
FT /evidence="ECO:0007829|PDB:3POW"
FT STRAND 129..138
FT /evidence="ECO:0007829|PDB:3POW"
FT STRAND 142..150
FT /evidence="ECO:0007829|PDB:3POW"
FT STRAND 153..156
FT /evidence="ECO:0007829|PDB:3POW"
FT STRAND 166..176
FT /evidence="ECO:0007829|PDB:3POW"
FT STRAND 180..186
FT /evidence="ECO:0007829|PDB:3POW"
FT STRAND 189..195
FT /evidence="ECO:0007829|PDB:3POW"
FT HELIX 196..199
FT /evidence="ECO:0007829|PDB:3POW"
FT STRAND 201..203
FT /evidence="ECO:0007829|PDB:3DOW"
FT TURN 255..257
FT /evidence="ECO:0007829|PDB:5V90"
FT TURN 303..306
FT /evidence="ECO:0007829|PDB:5LK5"
FT STRAND 311..322
FT /evidence="ECO:0007829|PDB:3POW"
FT STRAND 326..334
FT /evidence="ECO:0007829|PDB:3POW"
FT HELIX 336..345
FT /evidence="ECO:0007829|PDB:3POW"
FT HELIX 347..366
FT /evidence="ECO:0007829|PDB:3POW"
SQ SEQUENCE 417 AA; 48142 MW; BC37C3C0F1054FB2 CRC64;
MLLSVPLLLG LLGLAVAEPA VYFKEQFLDG DGWTSRWIES KHKSDFGKFV LSSGKFYGDE
EKDKGLQTSQ DARFYALSAS FEPFSNKGQT LVVQFTVKHE QNIDCGGGYV KLFPNSLDQT
DMHGDSEYNI MFGPDICGPG TKKVHVIFNY KGKNVLINKD IRCKDDEFTH LYTLIVRPDN
TYEVKIDNSQ VESGSLEDDW DFLPPKKIKD PDASKPEDWD ERAKIDDPTD SKPEDWDKPE
HIPDPDAKKP EDWDEEMDGE WEPPVIQNPE YKGEWKPRQI DNPDYKGTWI HPEIDNPEYS
PDPSIYAYDN FGVLGLDLWQ VKSGTIFDNF LITNDEAYAE EFGNETWGVT KAAEKQMKDK
QDEEQRLKEE EEDKKRKEEE EAEDKEDDED KDEDEEDEED KEEDEEEDVP GQAKDEL
