CALR

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. 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. Calreticulin binds to antibodies in certain sera of systemic lupus and Sjogren patients which contain anti-Ro/SSA antibodies, it is highly conserved among species, and it is located in the endoplasmic and sarcoplasmic reticulum where it may bind calcium. 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. 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. Systemic lupus erythematosus is associated with increased autoantibody titers against calreticulin but calreticulin is not a Ro/SS-A antigen. Earlier papers referred to calreticulin as an Ro/SS-A antigen but this was later disproven. Increased autoantibody titer against human calreticulin is found in infants with complete congenital heart block of both the IgG and IgM classes. [provided by RefSeq, Jul 2008]

Calreticulin

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).

Antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent Source: Reactome
Antigen processing and presentation of peptide antigen via MHC class I Source: Reactome
ATF6-mediated unfolded protein response Source: Reactome
Cardiac muscle cell differentiation Source: Ensembl
Cellular calcium ion homeostasis Source: UniProtKB
Cellular response to lithium ion Source: Ensembl
Cellular senescence Source: BHF-UCL
Cortical actin cytoskeleton organization Source: Ensembl
Endoplasmic reticulum unfolded protein response Source: GO_Central
Glucocorticoid receptor signaling pathway Source: BHF-UCL
Negative regulation of cell cycle arrest Source: BHF-UCL
Negative regulation of intracellular steroid hormone receptor signaling pathway Source: BHF-UCL
Negative regulation of neuron differentiation Source: BHF-UCL
Negative regulation of retinoic acid receptor signaling pathway Source: BHF-UCL
Negative regulation of transcription, DNA-templated Source: BHF-UCL
Negative regulation of transcription by RNA polymerase II Source: BHF-UCL
Negative regulation of translation Source: BHF-UCL
Negative regulation of trophoblast cell migration Source: CAFA
Peptide antigen assembly with MHC class I protein complex Source: BHF-UCL
Positive regulation of cell cycle Source: BHF-UCL
Positive regulation of cell population proliferation Source: BHF-UCL
Positive regulation of dendritic cell chemotaxis Source: UniProtKB
Positive regulation of endothelial cell migration Source: CAFA
Positive regulation of gene expression Source: Ensembl
Positive regulation of NIK/NF-kappaB signaling Source: Ensembl
Positive regulation of phagocytosis Source: BHF-UCL
Positive regulation of substrate adhesion-dependent cell spreading Source: UniProtKB
Protein export from nucleus Source: UniProtKB
Protein folding Source: GO_Central
Protein folding in endoplasmic reticulum Source: ParkinsonsUK-UCL
Protein localization to nucleus Source: UniProtKB
Protein maturation by protein folding Source: BHF-UCL
Protein stabilization Source: UniProtKB
Receptor-mediated endocytosis Source: Reactome
Regulation of apoptotic process Source: UniProtKB
Regulation of meiotic nuclear division Source: Ensembl
Regulation of transcription, DNA-templated Source: ProtInc
Response to drug Source: Ensembl
Response to estradiol Source: Ensembl
Response to testosterone Source: Ensembl
Sequestering of calcium ion Source: BHF-UCL
Spermatogenesis Source: Ensembl
Vesicle fusion with endoplasmic reticulum-Golgi intermediate compartment (ERGIC) membrane Source: Reactome

Extracellular matrix; Cytolytic granule; Endoplasmic reticulum lumen; Cytosol; Cell surface; Sarcoplasmic reticulum lumen; Cortical granule. Also found in cell surface (T cells), cytosol and extracellular matrix (PubMed:10358038). During oocyte maturation and after parthenogenetic activation accumulates in cortical granules. In pronuclear and early cleaved embryos localizes weakly to cytoplasm around nucleus and more strongly in the region near the cortex (By similarity). In cortical granules of non-activated oocytes, is exocytosed during the cortical reaction in response to oocyte activation (By similarity).

CARL somatic mutations are frequently found in myeloproliferative neoplasms lacking JAK2 or MPL mutations. Myeloproliferative neoplasms are chronic myeloid cancers characterized by overproduction of mature blood cells, and may evolve into acute myeloid leukemia. In addition to chronic myeloid leukemia with the BCR-ABL fusion gene, the three most common myeloproliferative neoplasms are essential thrombocythemia, polycythemia vera, and myelofibrosis.