Calreticulin (CALR)
The protein contains 417 amino acids for an estimated molecular weight of 48142 Da.
Calcium-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 (PubMed:7876246). Interacts with the DNA-binding domain of NR3C1 and mediates its nuclear export (PubMed:11149926). Involved in maternal gene expression regulation. May participate in oocyte maturation via the regulation of calcium homeostasis (By similarity). Present in the cortical granules of non-activated oocytes, is exocytosed during the cortical reaction in response to oocyte activation and might participate in the block to polyspermy (By similarity). (updated: April 7, 2021)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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Biological Process
Antigen processing and presentation of exogenous peptide antigen via MHC class I
Antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent
Antigen processing and presentation of peptide antigen via MHC class I
ATF6-mediated unfolded protein response
Cardiac muscle cell differentiation
Cell cycle arrest
Cellular calcium ion homeostasis
Cellular protein metabolic process
Cellular response to lithium ion
Cellular senescence
Chaperone-mediated protein folding
Cortical actin cytoskeleton organization
Endoplasmic reticulum unfolded protein response
Glucocorticoid receptor signaling pathway
Negative regulation of cell cycle arrest
Negative regulation of intracellular steroid hormone receptor signaling pathway
Negative regulation of neuron differentiation
Negative regulation of retinoic acid receptor signaling pathway
Negative regulation of transcription by RNA polymerase II
Negative regulation of transcription, DNA-templated
Negative regulation of translation
Negative regulation of trophoblast cell migration
Obsolete activation of signaling protein activity involved in unfolded protein response
Peptide antigen assembly with MHC class I protein complex
Positive regulation of cell cycle
Positive regulation of cell population proliferation
Positive regulation of dendritic cell chemotaxis
Positive regulation of DNA replication
Positive regulation of endothelial cell migration
Positive regulation of gene expression
Positive regulation of NIK/NF-kappaB signaling
Positive regulation of phagocytosis
Positive regulation of substrate adhesion-dependent cell spreading
Post-translational protein modification
Protein export from nucleus
Protein folding
Protein folding in endoplasmic reticulum
Protein localization to nucleus
Protein maturation by protein folding
Protein N-linked glycosylation via asparagine
Protein stabilization
Receptor-mediated endocytosis
Regulation of apoptotic process
Regulation of meiotic nuclear division
Regulation of transcription, DNA-templated
Response to drug
Response to estradiol
Response to testosterone
Sequestering of calcium ion
Spermatogenesis
Vesicle fusion with endoplasmic reticulum-Golgi intermediate compartment (ERGIC) membrane
Cellular Component
Acrosomal vesicle
Cell surface
Collagen-containing extracellular matrix
Cortical granule
Cytoplasm
Cytosol
Endocytic vesicle lumen
Endoplasmic reticulum
Endoplasmic reticulum lumen
Endoplasmic reticulum membrane
Endoplasmic reticulum quality control compartment
Endoplasmic reticulum-Golgi intermediate compartment membrane
External side of plasma membrane
Extracellular exosome
Extracellular matrix
Extracellular region
Extracellular space
Focal adhesion
Golgi apparatus
Integral component of lumenal side of endoplasmic reticulum membrane
Intracellular anatomical structure
Membrane
MHC class I peptide loading complex
Nuclear envelope
Nucleus
Obsolete cell
Perinuclear region of cytoplasm
Phagocytic vesicle membrane
Polysome
Proteinaceous extracellular matrix
Sarcoplasmic reticulum lumen
Smooth endoplasmic reticulum
Transport vesicle
Molecular Function
Androgen receptor binding
Calcium ion binding
Carbohydrate binding
Chaperone binding
Complement component C1q complex binding
DNA binding
Glycoprotein binding
Hormone binding
Integrin binding
Iron ion binding
MRNA binding
Peptide binding
Poly(A) RNA binding
Protein folding chaperone
RNA binding
Ubiquitin protein ligase binding
Unfolded protein binding
Zinc ion binding
The reference OMIM entry for this protein is 109091
Calreticulin; calr
Crt
Autoantigen ro; ro
Complement component c1q receptor; cc1qr
DESCRIPTION
Calreticulin is a multifunctional protein that acts as a major Ca(2+)-binding (storage) protein in the lumen of the endoplasmic reticulum. It is also found in the nucleus, suggesting that it may have a role in transcription regulation (Burns et al., 1994).CLONING
Calreticulin binds to the synthetic peptide KLGFFKR, which is almost identical to an amino acid sequence in the DNA-binding domain of the superfamily of nuclear receptors. McCauliffe et al. (1990) showed that calreticulin binds to antibodies in certain sera of systemic lupus and Sjogren patients which contain anti-Ro/SSA antibodies, that it is highly conserved among species, and that it is located in the endoplasmic and sarcoplasmic reticulum where it may bind calcium. With synthetic oligonucleotides corresponding to the amino acid sequence, McCauliffe et al. (1990) isolated full-length CALR cDNA that encodes a human Ro ribonucleoprotein autoantigen. The deduced 417-amino acid protein has a predicted molecular mass of 48 kD. Southern filter hybridization analysis showed that the CALR gene is not highly polymorphic and exists in single copy in the human genome. Frank (1994) pointed out that the CALR gene mapped to chromosome 19p encodes the 48-kD calreticulin, a protein with Ro/SSA properties. Itoh et al. (1991) showed that the 52-kD and the 60-kD forms of Ro/SSA ribonucleoproteins are encoded by separate genes mapping to chromosome 11 (TRIM21; 109092) and chromosome 1 (TROVE2; 600063), respectively. By Northern blot analysis of human tissues, Persson et al. (2002) found ubiquitous expression of a 1.9-kb CALR transcript.GENE FUNCTION
Burns et al. (1994) reported that the amino terminus of calreticulin interacts with the DNA-binding domain of the glucocorticoid receptor and prevents the receptor from binding to its specific glucocorticoid response element. Dedhar et al. (1994) showed that calreticulin can inhibit the binding of androgen receptor to its hormone-responsive DNA element and can inhibit androgen receptor and retinoic acid receptor transcriptional activities in vivo, as well as retinoic acid-induced neuronal differentiation. Thus, calreticulin can act as an important modulator of the regulation of gene transcription by nuclear hormone receptors. Boehm et al. (1994) showed that SLE is associated with increased autoantibody titers against calreticulin but that calreticulin is not a Ro/SS-A antigen. Orth et al. (1996) found increased autoantibody titers against human calreticulin in infants with complete congenital heart block (234700) of both the IgG and IgM classes. THBS1 (188060) or a peptide of the 19-amino acid active site in its heparin-binding domain signals focal adhesion disassembly through interaction with a cell surface form of CRT. Using bovine aortic endothelial cells and wildtype and low density lipoprotein receptor-related protein (LRP, or LRP1; 107770) -/- mouse fibroblasts, Orr et al. (2003) showed that Lrp interacted with Crt and was required to mediate focal adhesion disassembly and downstream signaling for reorganization of focal adhesions. Binding of the LRP ligand RAP (LRPAP1; 104225) to purified human LRP inhibited interaction between recombinant human CRT and LRP. Gardai et al. (2005) stated that calreticulin on the surface of apoptotic cells serves as a recognition and clearance ligand by activating the internalization receptor LRP1 (107770) on the responding phagocyte cell surface. Using mouse and hu ... More on the omim web site
April 10, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 109091 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed