Gene Symbol

CALR

Aliases

CRT, HEL-S-99n, RO, SSA, cC1qR

Entrez Gene ID

811

Gene Name

Calreticulin

Chromosomal Location

19p13.13

HGNC ID

HGNC:1455

Summary

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]

Function

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. 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).

P27797

PDB

2CLR, 6ENY, 3DOW, 3POS, 3POW, 5LK5, 5V90

STRING	MINT	IntAct
ENSP00000432660	P23528	P23528

PMID: 19141487

Gene expression microarray profiles of cumulus cells in lean and overweight-obese polycystic ovary syndrome patients. Kenigsberg Shlomit, Bentov Yaakov, Chalifa-Caspi Vered, Potashnik Gad, Ofir Rivka, Birk Ohad S The Morris Kahn Laboratory of Human Genetics, National Institute for Biotechnology in the Negev, Ben-Gurion University, Beer-Sheva, Israel. Mol Hum Reprod. 2009 Feb;15(2):89-103. doi: 10.1093/molehr/gan082. Epub 2009 Jan Abstract The aim of this work was to study gene expression patterns of cultured cumulus cells from lean and overweight-obese polycystic ovary syndrome (PCOS) patients using genome-wide oligonucleotide microarray. The study included 25 patients undergoing in vitro fertilization and intra-cytoplasmic sperm injection: 12 diagnosed with PCOS and 13 matching controls. Each of the groups was subdivided into lean (body mass index (BMI) < 24) and overweight (BMI > 27) subgroups. The following comparisons of gene expression data were made: lean PCOS versus lean controls, lean PCOS versus overweight PCOS, all PCOS versus all controls, overweight PCOS versus overweight controls, overweight controls versus lean controls and all overweight versus all lean. The largest number of differentially expressed genes (DEGs), with fold change (FC)

PMID: 22959458

Proteomic biomarkers for ovarian cancer risk in women with polycystic ovary syndrome: a systematic review and biomarker database integration. Galazis Nicolas, Olaleye Olalekan, Haoula Zeina, Layfield Robert, Atiomo William Division of Human Development, School of Clinical Sciences, University of Nottingham, Queen's Medical Centre Campus, Nottingham University Hospitals, Nottingham, United Kingdom. ngalazis@gmail.com Fertil Steril. 2012 Dec;98(6):1590-601.e1. doi: 10.1016/j.fertnstert.2012.08.002. Abstract OBJECTIVE: To review and identify possible biomarkers for ovarian cancer (OC) in women with polycystic ovary syndrome (PCOS). DESIGN: Systematic literature searches of MEDLINE, EMBASE, and Cochrane using the search terms "proteomics," "proteomic," and "ovarian cancer" or "ovarian carcinoma." Proteomic biomarkers for OC were then integrated with an updated previously published database of all proteomic biomarkers identified to date in patients with PCOS. SETTING: Academic department of obstetrics and gynecology in the United Kingdom. PATIENT(S): A total of 180 women identified in the six studies. INTERVENTION(S): Tissue samples from women with OC vs. tissue samples from women without OC. MAIN OUTCOME MEASURE(S): Proteomic biomarkers, proteomic technique used, and methodologic quality score. RESULT(S): A panel of six biomarkers was overexpressed both in women with OC and in women with PCOS. These biomarkers include calreticulin, fibrinogen-gamma, superoxide dismutase, vimentin, malate dehydrogenase, and lamin B2. CONCLUSION(S): These biomarkers could help improve our understanding of the links between PCOS and OC and could potentially be used to identify subgroups of women with PCOS at increased risk of OC. More studies are required to further evaluate the role these biomarkers play in women with PCOS and OC.