Calreticulin

NameCalreticulin
Synonyms
  • Calregulin
  • CRP55
  • CRTC
  • Endoplasmic reticulum resident protein 60
  • ERp60
  • grp60
  • HACBP
Gene NameCALR
OrganismHuman
Amino acid sequence
>lcl|BSEQ0011528|Calreticulin
MLLSVPLLLGLLGLAVAEPAVYFKEQFLDGDGWTSRWIESKHKSDFGKFVLSSGKFYGDE
EKDKGLQTSQDARFYALSASFEPFSNKGQTLVVQFTVKHEQNIDCGGGYVKLFPNSLDQT
DMHGDSEYNIMFGPDICGPGTKKVHVIFNYKGKNVLINKDIRCKDDEFTHLYTLIVRPDN
TYEVKIDNSQVESGSLEDDWDFLPPKKIKDPDASKPEDWDERAKIDDPTDSKPEDWDKPE
HIPDPDAKKPEDWDEEMDGEWEPPVIQNPEYKGEWKPRQIDNPDYKGTWIHPEIDNPEYS
PDPSIYAYDNFGVLGLDLWQVKSGTIFDNFLITNDEAYAEEFGNETWGVTKAAEKQMKDK
QDEEQRLKEEEEDKKRKEEEEAEDKEDDEDKDEDEEDEEDKEEDEEEDVPGQAKDEL
Number of residues417
Molecular Weight48141.2
Theoretical pI4.04
GO Classification
Functions
  • unfolded protein binding
  • iron ion binding
  • zinc ion binding
  • peptide binding
  • mRNA binding
  • calcium ion binding
  • chaperone binding
  • ubiquitin protein ligase binding
  • glycoprotein binding
  • DNA binding
  • complement component C1q binding
  • androgen receptor binding
  • protein binding involved in protein folding
  • hormone binding
  • integrin binding
  • poly(A) RNA binding
  • carbohydrate binding
Processes
  • positive regulation of cell proliferation
  • protein folding in endoplasmic reticulum
  • negative regulation of intracellular steroid hormone receptor signaling pathway
  • protein export from nucleus
  • antigen processing and presentation of exogenous peptide antigen via MHC class I
  • sequestering of calcium ion
  • negative regulation of transcription, DNA-templated
  • regulation of meiotic nuclear division
  • positive regulation of phagocytosis
  • positive regulation of substrate adhesion-dependent cell spreading
  • cellular response to lithium ion
  • regulation of apoptotic process
  • chaperone-mediated protein folding
  • negative regulation of transcription from RNA polymerase II promoter
  • antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent
  • protein maturation by protein folding
  • positive regulation of DNA replication
  • antigen processing and presentation of peptide antigen via MHC class I
  • response to testosterone
  • positive regulation of cell cycle
  • regulation of transcription, DNA-templated
  • cellular calcium ion homeostasis
  • negative regulation of neuron differentiation
  • endoplasmic reticulum unfolded protein response
  • cardiac muscle cell differentiation
  • protein localization to nucleus
  • receptor-mediated endocytosis
  • negative regulation of translation
  • response to drug
  • positive regulation of gene expression
  • cellular senescence
  • response to estradiol
  • protein stabilization
  • glucocorticoid receptor signaling pathway
  • cellular protein metabolic process
  • protein folding
  • negative regulation of retinoic acid receptor signaling pathway
  • post-translational protein modification
  • cortical actin cytoskeleton organization
  • peptide antigen assembly with MHC class I protein complex
  • protein N-linked glycosylation via asparagine
  • ATF6-mediated unfolded protein response
  • cell cycle arrest
  • spermatogenesis
  • positive regulation of dendritic cell chemotaxis
Components
  • cell surface
  • Golgi apparatus
  • endocytic vesicle lumen
  • intracellular
  • acrosomal vesicle
  • smooth endoplasmic reticulum
  • cytoplasm
  • integral component of lumenal side of endoplasmic reticulum membrane
  • cytosol
  • membrane
  • MHC class I peptide loading complex
  • extracellular exosome
  • polysome
  • perinuclear region of cytoplasm
  • extracellular region
  • sarcoplasmic reticulum lumen
  • external side of plasma membrane
  • nucleus
  • focal adhesion
  • endoplasmic reticulum lumen
  • endoplasmic reticulum
  • extracellular space
  • proteinaceous extracellular matrix
General FunctionZinc ion binding
Specific FunctionCalcium-binding chaperone that promotes folding, oligomeric assembly and quality control in the endoplasmic reticulum (ER) via the calreticulin/calnexin cycle. This lectin interacts transiently with almost all of the monoglucosylated glycoproteins that are synthesized in the ER. Interacts with the DNA-binding domain of NR3C1 and mediates its nuclear export. Involved in maternal gene expression regulation. May participate in oocyte maturation via the regulation of calcium homeostasis (By similarity).
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID337487
UniProtKB IDP27797
UniProtKB Entry NameCALR_HUMAN
Cellular LocationEndoplasmic reticulum lumen
Gene sequence
>lcl|BSEQ0011529|Calreticulin (CALR)
ATGCTGCTATCCGTGCCGCTGCTGCTCGGCCTCCTCGGCCTGGCCGTCGCCGAGCCTGCC
GTCTACTTCAAGGAGCAGTTTCTGGACGGAGACGGGTGGACTTCCCGCTGGATCGAATCC
AAACACAAGTCAGATTTTGGCAAATTCGTTCTCAGTTCCGGCAAGTTCTACGGTGACGAG
GAGAAAGATAAAGGTTTGCAGACAAGCCAGGATGCACGCTTTTATGCTCTGTCGGCCAGT
TTCGAGCCTTTCAGCAACAAAGGCCAGACGCTGGTGGTGCAGTTCACGGTGAAACATGAG
CAGAACATCGACTGTGGGGGCGGCTATGTGAAGCTGTTTCCTAATAGTTTGGACCAGACA
GACATGCACGGAGACTCAGAATACAACATCATGTTTGGTCCCGACATCTGTGGCCCTGGC
ACCAAGAAGGTTCATGTCATCTTCAACTACAAGGGCAAGAACGTGCTGATCAACAAGGAC
ATCCGTTGCAAGGATGATGAGTTTACACACCTGTACACACTGATTGTGCGGCCAGACAAC
ACCTATGAGGTGAAGATTGACAACAGCCAGGTGGAGTCCGGCTCCTTGGAAGACGATTGG
GACTTCCTGCCACCCAAGAAGATAAAGGATCCTGATGCTTCAAAACCGGAAGACTGGGAT
GAGCGGGCCAAGATCGATGATCCCACAGACTCCAAGCCTGAGGACTGGGACAAGCCCGAG
CATATCCCTGACCCTGATGCTAAGAAGCCCGAGGACTGGGATGAAGAGATGGACGGAGAG
TGGGAACCCCCAGTGATTCAGAACCCTGAGTACAAGGGTGAGTGGAAGCCCCGGCAGATC
GACAACCCAGATTACAAGGGCACTTGGATCCACCCAGAAATTGACAACCCCGAGTATTCT
CCCGATCCCAGTATCTATGCCTATGATAACTTTGGCGTGCTGGGCCTGGACCTCTGGCAG
GTCAAGTCTGGCACCATCTTTGACAACTTCCTCATCACCAACGATGAGGCATACGCTGAG
GAGTTTGGCAACGAGACGTGGGGCGTAACAAAGGCAGCAGAGAAACAAATGAAGGACAAA
CAGGACGAGGAGCAGAGGCTTAAGGAGGAGGAAGAAGACAAGAAACGCAAAGAGGAGGAG
GAGGCAGAGGACAAGGAGGATGATGAGGACAAAGATGAGGATGAGGAGGATGAGGAGGAC
AAGGAGGAAGATGAGGAGGAAGATGTCCCCGGCCAGGCCAAGGACGAGCTGTAG
GenBank Gene IDM32294
GeneCard IDNot Available
GenAtlas IDCALR
HGNC IDHGNC:1455
Chromosome Location19
Locus19p13.3-p13.2
References
  1. McCauliffe DP, Lux FA, Lieu TS, Sanz I, Hanke J, Newkirk MM, Bachinski LL, Itoh Y, Siciliano MJ, Reichlin M, et al.: Molecular cloning, expression, and chromosome 19 localization of a human Ro/SS-A autoantigen. J Clin Invest. 1990 May;85(5):1379-91. 2332496
  2. Rokeach LA, Haselby JA, Meilof JF, Smeenk RJ, Unnasch TR, Greene BM, Hoch SO: Characterization of the autoantigen calreticulin. J Immunol. 1991 Nov 1;147(9):3031-9. 1919005
  3. McCauliffe DP, Yang YS, Wilson J, Sontheimer RD, Capra JD: The 5'-flanking region of the human calreticulin gene shares homology with the human GRP78, GRP94, and protein disulfide isomerase promoters. J Biol Chem. 1992 Feb 5;267(4):2557-62. 1733953
  4. Goshima N, Kawamura Y, Fukumoto A, Miura A, Honma R, Satoh R, Wakamatsu A, Yamamoto J, Kimura K, Nishikawa T, Andoh T, Iida Y, Ishikawa K, Ito E, Kagawa N, Kaminaga C, Kanehori K, Kawakami B, Kenmochi K, Kimura R, Kobayashi M, Kuroita T, Kuwayama H, Maruyama Y, Matsuo K, Minami K, Mitsubori M, Mori M, Morishita R, Murase A, Nishikawa A, Nishikawa S, Okamoto T, Sakagami N, Sakamoto Y, Sasaki Y, Seki T, Sono S, Sugiyama A, Sumiya T, Takayama T, Takayama Y, Takeda H, Togashi T, Yahata K, Yamada H, Yanagisawa Y, Endo Y, Imamoto F, Kisu Y, Tanaka S, Isogai T, Imai J, Watanabe S, Nomura N: Human protein factory for converting the transcriptome into an in vitro-expressed proteome,. Nat Methods. 2008 Dec;5(12):1011-7. 19054851
  5. Grimwood J, Gordon LA, Olsen A, Terry A, Schmutz J, Lamerdin J, Hellsten U, Goodstein D, Couronne O, Tran-Gyamfi M, Aerts A, Altherr M, Ashworth L, Bajorek E, Black S, Branscomb E, Caenepeel S, Carrano A, Caoile C, Chan YM, Christensen M, Cleland CA, Copeland A, Dalin E, Dehal P, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Garcia C, Georgescu AM, Glavina T, Gomez M, Gonzales E, Groza M, Hammon N, Hawkins T, Haydu L, Ho I, Huang W, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Larionov V, Leem SH, Lopez F, Lou Y, Lowry S, Malfatti S, Martinez D, McCready P, Medina C, Morgan J, Nelson K, Nolan M, Ovcharenko I, Pitluck S, Pollard M, Popkie AP, Predki P, Quan G, Ramirez L, Rash S, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, She X, Smith D, Slezak T, Solovyev V, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wagner M, Wheeler J, Wu K, Xie G, Yang J, Dubchak I, Furey TS, DeJong P, Dickson M, Gordon D, Eichler EE, Pennacchio LA, Richardson P, Stubbs L, Rokhsar DS, Myers RM, Rubin EM, Lucas SM: The DNA sequence and biology of human chromosome 19. Nature. 2004 Apr 1;428(6982):529-35. 15057824
  6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  7. Houen G, Koch C: Human placental calreticulin: purification, characterization and association with other proteins. Acta Chem Scand. 1994 Nov;48(11):905-11. 7841019
  8. Lieu TS, Newkirk MM, Capra JD, Sontheimer RD: Molecular characterization of human Ro/SS-A antigen. Amino terminal sequence of the protein moiety of human Ro/SS-A antigen and immunological activity of a corresponding synthetic peptide. J Clin Invest. 1988 Jul;82(1):96-101. 3260607
  9. Rojiani MV, Finlay BB, Gray V, Dedhar S: In vitro interaction of a polypeptide homologous to human Ro/SS-A antigen (calreticulin) with a highly conserved amino acid sequence in the cytoplasmic domain of integrin alpha subunits. Biochemistry. 1991 Oct 15;30(41):9859-66. 1911778
  10. Krause KH, Simmerman HK, Jones LR, Campbell KP: Sequence similarity of calreticulin with a Ca2(+)-binding protein that co-purifies with an Ins(1,4,5)P3-sensitive Ca2+ store in HL-60 cells. Biochem J. 1990 Sep 1;270(2):545-8. 2400400
  11. Hochstrasser DF, Frutiger S, Paquet N, Bairoch A, Ravier F, Pasquali C, Sanchez JC, Tissot JD, Bjellqvist B, Vargas R, et al.: Human liver protein map: a reference database established by microsequencing and gel comparison. Electrophoresis. 1992 Dec;13(12):992-1001. 1286669
  12. Rasmussen HH, van Damme J, Puype M, Gesser B, Celis JE, Vandekerckhove J: Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes. Electrophoresis. 1992 Dec;13(12):960-9. 1286667
  13. Dupuis M, Schaerer E, Krause KH, Tschopp J: The calcium-binding protein calreticulin is a major constituent of lytic granules in cytolytic T lymphocytes. J Exp Med. 1993 Jan 1;177(1):1-7. 8418194
  14. Ji H, Reid GE, Moritz RL, Eddes JS, Burgess AW, Simpson RJ: A two-dimensional gel database of human colon carcinoma proteins. Electrophoresis. 1997 Mar-Apr;18(3-4):605-13. 9150948
  15. Nauseef WM, McCormick SJ, Clark RA: Calreticulin functions as a molecular chaperone in the biosynthesis of myeloperoxidase. J Biol Chem. 1995 Mar 3;270(9):4741-7. 7876246
  16. Cheng ST, Nguyen TQ, Yang YS, Capra JD, Sontheimer RD: Calreticulin binds hYRNA and the 52-kDa polypeptide component of the Ro/SS-A ribonucleoprotein autoantigen. J Immunol. 1996 Jun 1;156(11):4484-91. 8666824
  17. Arosa FA, de Jesus O, Porto G, Carmo AM, de Sousa M: Calreticulin is expressed on the cell surface of activated human peripheral blood T lymphocytes in association with major histocompatibility complex class I molecules. J Biol Chem. 1999 Jun 11;274(24):16917-22. 10358038
  18. Holaska JM, Black BE, Love DC, Hanover JA, Leszyk J, Paschal BM: Calreticulin Is a receptor for nuclear export. J Cell Biol. 2001 Jan 8;152(1):127-40. 11149926
  19. Hojrup P, Roepstorff P, Houen G: Human placental calreticulin characterization of domain structure and post-translational modifications. Eur J Biochem. 2001 May;268(9):2558-65. 11322874
  20. Chen R, Jiang X, Sun D, Han G, Wang F, Ye M, Wang L, Zou H: Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry. J Proteome Res. 2009 Feb;8(2):651-61. doi: 10.1021/pr8008012. 19159218
  21. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. 19608861
  22. Kozlov G, Bastos-Aristizabal S, Maattanen P, Rosenauer A, Zheng F, Killikelly A, Trempe JF, Thomas DY, Gehring K: Structural basis of cyclophilin B binding by the calnexin/calreticulin P-domain. J Biol Chem. 2010 Nov 12;285(46):35551-7. doi: 10.1074/jbc.M110.160101. Epub 2010 Aug 27. 20801878
  23. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. 21269460
  24. Rosenow A, Noben JP, Jocken J, Kallendrusch S, Fischer-Posovszky P, Mariman EC, Renes J: Resveratrol-induced changes of the human adipocyte secretion profile. J Proteome Res. 2012 Sep 7;11(9):4733-43. doi: 10.1021/pr300539b. Epub 2012 Aug 27. 22905912
  25. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. 24275569
  26. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. 25944712
  27. Thielmann Y, Weiergraber OH, Mohrluder J, Willbold D: Structural framework of the GABARAP-calreticulin interface--implications for substrate binding to endoplasmic reticulum chaperones. FEBS J. 2009 Feb;276(4):1140-52. doi: 10.1111/j.1742-4658.2008.06857.x. Epub 2009 Jan 16. 19154346
  28. Chouquet A, Paidassi H, Ling WL, Frachet P, Houen G, Arlaud GJ, Gaboriaud C: X-ray structure of the human calreticulin globular domain reveals a peptide-binding area and suggests a multi-molecular mechanism. PLoS One. 2011 Mar 15;6(3):e17886. doi: 10.1371/journal.pone.0017886. 21423620