Recombinant Human Calreticulin (CALR)

1. unwanted cells such as aging neutrophils and living cancer cells are susceptible to "labeling" by secreted calreticulin (CRT) from macrophages, enabling their clearance through programmed cell removal. PMID: 30097573
2. Patients with CALR mutation had significantly higher concentration of PDGF-BB and lower concentration of SDF-1alpha than patients with JAK2V617F mutation. High concentration of PDGF-BB and low concentration of SDF-1alpha in patients with CALR(+) ET may indicate a contribution of these chemokines in disturbed Ca2+ metabolism in platelets. PMID: 29390868
3. These results implicate miR-455 regulated hydrogen sulfide protection of lung epithelial cells against hypoxia-induced apoptosis by stimulating Calr PMID: 30193773
4. Calreticulin has a dual nature, and it has been found to be up-regulated or down-regulated in several types of cancer serving as either oncogene or anti-oncogene. PMID: 30444198
5. Study propose that leukocytes infiltration via the binding of CRT to ITGAs is necessary for the onset and development of the ulcerative colitis and the inhibition of this interaction may be a novel therapeutic strategy for the treatment of inflammatory bowel diseases. PMID: 29773794
6. Triplex probe-based TaqMan qPCR is an accurate and sensitive method for screening essential thrombocythemia or primary myelofibrosis patients with type I and II mutations in CALR. PMID: 30080988
7. Comprehensive genomic characterization identified distinct genetic subgroups and provided a classification of myeloproliferative neoplasms on the basis of causal biologic mechanisms. Mutations in JAK2, CALR, or MPL being the sole abnormality in 45% of the patients. PMID: 30304655
8. The prevalence of CALR mutation in JAK2V617F-negative essential thrombocythemia in this study is 35.7%. HRM is an effective method of detecting CALR mutation and is a more advantageous method of screening for CALR mutation. PMID: 29521158
9. MPL and CALR genotypes show a similar clinical picture at essential thrombocythaemia diagnosis. In CALR genotype features of prefibrotic myelofibrosis are common. PMID: 29934356
10. explored CRT reactivity of 14 different recombinant monoclonal antibodies (mAbs) derived from CLL patients carrying BCRs from various different stereotyped subsets PMID: 28751563
11. The novel mutations occurred and changed the amino acid sequence of the C domain amino acid residues of CALR, which will interfere with the calcium-binding capacity of the molecule. The CALR mutations will improve our understanding of the pathophysiology of myeloproliferative neoplasms. PMID: 28747287
12. Our study shows that JAK2V617F leads to abnormal expression of numerous proteins at the membrane of circulating PV red blood cells, with overexpression of CALR and persistence of CANX PMID: 28385780
13. In 94.9% of PV, 85.5% ET and 85.2% PMF, authors found mutations in JAK2, MPL or CALR. 74.9% carried JAK2V617F, 12.3% CALR mutations, 2.1% MPL mutations and 10.7% were triple negative. PMID: 28990497
14. these data support the model that CALR-mutated essential thrombocythemia could be considered as a distinct disease entity from JAK2V617F-positive myeloproliferative neoplasms PMID: 29217833
15. This phenotypic diversity is further emphasized by the following report of a patient with an isolated erythrocytosis, persistent for nearly twelve years, associated with a CALR exon 9 mutation PMID: 28711709
16. CALR exon 9 mutation is associated with myeloproliferative neoplasms. PMID: 28411309
17. Absence of CALR mutations in JAK2-negative polycythemia. PMID: 27758825
18. In 136 patients with myelofibrosis and a median age of 58 years who underwent allogeneic stem cell transplantation (AHSCT) for molecular residual disease, the percentage of molecular clearance on day 100 was higher in CALR-mutated patients (92%) in comparison with MPL- (75%) and JAKV617F-mutated patients (67%). PMID: 28714945
19. Mutational subtypes of CALR correlate with different clinical features in Japanese patients with myeloproliferative neoplasms. PMID: 29464483
20. CALR mutations is associated with non-hepatosplenic extramedullary hematopoiesis(NHS-EMH) and may possibly contribute to the pathogenesis of primary myelofibrosis -associated NHS-EMH. PMID: 27315113
21. This study demonstrated that two patients had a heterozygous CALR exon9 mutation locating outside the coding region and did not alter the amino acid sequence of this protein. PMID: 28625126
22. Multivariate analysis adjusted for age, sex, follow-up period and hematological parameters confirmed that increased activated B cells were universally present in JAK2-mutated, CALR-mutated and triple-negative ET patients when compared to healthy adults. PMID: 28415571
23. these results reveal proteome alterations in MPN granulocytes depending on the phenotype and genotype of patients, highlighting new oncogenic mechanisms associated with JAK2 mutations and overexpression of calreticulin PMID: 28314843
24. CALR mutation is associated with Essential thrombocythemia. PMID: 28205126
25. the CALR-mutant stem cell would achieve clonal dominance much faster than the JAK2-mutant one and confirm the model initially proposed in which the clonal evolution of CALR-mutant MPN appears to be mainly associated with a progressive expansion of a mutant heterozygous clone that eventually becomes fully dominant in the bone marrow. PMID: 28422716
26. The present study detected expression of CRT in patients with osteosarcoma , in the non-metastasis group compared with the metastasis group, and in the chemotherapy group compared with the non-chemotherapy group. CONCLUSIONS: These results could indicate a brand-new biological marker which may be applied to estimate the features and prognosis of osteosarcoma. PMID: 28106543
27. in molecularly annotated ET patients at diagnosis, JAK2-V617F patients have more circulating microparticles and higher MP-associated procoagulant activities than CALR-mutated and TN ET patients. PMID: 27247323
28. results suggest that CALR exon 9 mutations hold promise as targets for cancer immune therapies; for example as targets for vaccines or adoptive cell therapies. In order to formally establish that the CALR mutations act as tumor antigens for immunotherapy, we are currently working to establish specific T-cell clones to show that such clones recognize target cells that endogenously express mutated CALR PMID: 27560107
29. Report PCR clamping technique for detection of type 1 and type 2 mutations in CALR gene in myeloproliferative neoplasms. PMID: 28031530
30. Late-stage inhibition of autophagy enhances calreticulin surface exposure in colonic tumor cells. PMID: 27825129
31. JAK2 and CALR mutations have roles in patients with essential thrombocythemia PMID: 27486987
32. Clinical features of JAK2V617F- or CALR-mutated essential thrombocythemia and primary myelofibrosis. PMID: 26994960
33. Studies indicate there are two main types of calreticulin gene (CALR) mutants, type 1 and type 2, and there is evidence about their distinct clinical/prognostic implications. PMID: 27384487
34. our data suggest the involvement of autoimmune reactivity to CRT in a subset of patients suffering from DCM or HCM. PMID: 27689957
35. Endoplasmic reticulum chaperone CRT plays a regulatory role in the invasion of EVTs, suggesting the importance of CRT expression in placental development during early pregnancy. PMID: 28938427
36. findings demonstrate the potency of CALR mutants to drive expression of megakaryocytic differentiation markers such as NF-E2 and CD41 as well as Mpl. Furthermore, CALR mutants undergo accelerated protein degradation that involves the secretory pathway and/or protein glycosylation. PMID: 27177927
37. Essential Thrombocythemia and Primary Myelofibrosis patients with CALR mutations are at high risk for Thrombotic Events. PMID: 28766534
38. These findings showed that mutant CALR activates jak-stat signaling through an mpl-dependent mechanism to mediate pathogenic thrombopoiesis in zebrafish, and illustrated that the signaling machinery related to mutant CALR tumorigenesis are conserved between human and zebrafish. PMID: 27716741
39. The present work suggests that Ca(2+)-dependent regulation is caused by different conformations of a long proline-rich loop that changes the accessibility to the peptide/lectin-binding site. Our results indicate that the binding of Ca(2+) to calreticulin may thus not only just be a question of Ca(2+) storage but is likely to have an impact on the chaperone activity. PMID: 27195812
40. CRT regulates TGF-beta1-induced-EMT through modulating Smad signaling PMID: 28778674
41. Our results showed that a wide range of different CALR mutations are associated with a distinct ET clinical phenotype that is associated with the male gender, younger age at diagnosis, higher platelet and lower leukocyte and erythrocyte counts and lower hemoglobin level, and a milder clinical course. PMID: 27521277
42. alpha-Integrin expression and function modulates presentation of cell surface calreticulin. PMID: 27310876
43. Although CALR mutations resulted in protein instability and proteosomal degradation, mutant CALR was able to enhance megakaryopoiesis and pro-platelet production from human CD34(+) progenitors. PMID: 27740635
44. Studies show that all CALR mutations generate frameshift mutation in the exon 9, which encodes the C-terminus end conferring a common mutant-specific sequence in all mutants. Mutant CALR constitutively activates MPL to induce cellular transformation. The interaction between the mutant CALR and MPL is achieved by the conformational change in the C-terminal allowing N-domain binding to MPL. [review] PMID: 28741795
45. C-CALR in response to Ca2+ undergoes conformational changes that trigger its function to export GR from the nucleus, resetting the stress response of normal erythroid cells. Impairment of this function in JAK2V617F-positive erythroid cells maintains EPO-R signaling in proliferation mode, contributing to erythrocytosis in PV. PMID: 28232234
46. Mannan-binding lectin (MBL) bound to T cells through interaction between the collagen-like region of MBL and calreticulin (CRT) expressed on the T-cell surface. PMID: 28209773
47. CRT exposure represents a novel powerful prognostic biomarker for patients with acute myeloid leukemia. PMID: 27802968
48. In absence of CALR, immature MPO protein precursors are degraded in the proteasome. PMID: 27013444
49. In patients with HD, a panel using calretinin and peripherin with or without MAP-2 may be most helpful in identifying transition zones PMID: 26469323
50. Coexisting mutations of the JAK2, CALR, and MPL genes in myeloproliferative neoplasms suggest that CALR and MPL should be analyzed not only in JAK2-negative patients but also in low V617F mutation patients. PMID: 27855276

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HGNC: 1455

OMIM: 109091

KEGG: hsa:811

STRING: 9606.ENSP00000320866

UniGene: Hs.515162