Disease relevance of CALU

• The findings indicate that calumenin may participate in the immunological defense system and could be involved in the pathological process of amyloidosis that leads to formation of amyloid deposits seen in different types of tissues [1].
• Molecular cloning of a cDNA encoding human calumenin, expression in Escherichia coli and analysis of its Ca2+-binding activity [2].
• To define the role of macrophage-tumor cell interaction with respect to angiogenesis, human peripheral blood monocytes (PBM) were cocultured with A549 (human bronchoalveolar cell carcinoma) or Calu 6 (human anaplastic carcinoma) NSCLC cells [3].
• Our study thus indicates that calumenin may have an autocrine or a paracrine effect on the cells in its vicinity, and, therefore, may be involved in the pathophysiology of thrombosis or in wound healing [4].
• Several established cell lines derived from human lung carcinomas (SK-LU-1, Calu -1, SK-MES-1 and A-549) show a uniform pattern of cytokeratin polypeptides (nos. 7, 8, 18 and 19), similar to that found in adenocarcinomas [5].

High impact information on CALU

• Secretogranin III, cyclophilin A, and calumenin were confirmed to localize in platelets and to be released upon activation [6].
• However, in the cultured human cell lines, HaCaT keratinocytes, normal and transformed MRC-5 fibroblasts, as well as in transfected COS-1 cells, human calumenin could be demonstrated in the ER as well as in the Golgi complex [7].
• Especially in MRC-5 cells, a certain heterogeneity was observed, with some of the cells having calumenin localized solely to the ER while in other cells calumenin could be demonstrated in the ER as well as in the Golgi complex [7].
• Calumenin belongs to a family of multiple EF-hand proteins that include reticulocalbin, ERC-55, and Cab45 [7].
• Immunoelectron microscopy of placental syncytiotrophoblast cells showed that a substantial fraction of calumenin is localized in close association with the ER membrane [7].

Biological context of CALU

• Mean protein S activity was influenced by the VKORC1 3730G>A and CALU 20943T>A genotypes, after adjusting for confounding factors [8].
• Utilizing Marathon-ready cDNA library and a gene-specific primer corresponding to a partial amino acid sequence determined previously, the complete nucleotide sequence for the cDNA of crocalbin, which binds crotoxin (a phospholipase A2) and Ca2+, was obtained by polymerase chain reaction [9].
• Crocalbin: a new calcium-binding protein that is also a binding protein for crotoxin, a neurotoxic phospholipase A2 [9].
• Labeling of S-phase fibroblasts with bromo-2'deoxy-uridine indicates that calumenin added to the medium also modulates the cell cycle [4].
• Extracellularly added calumenin decreases the levels of both the N-terminal and C-terminal actin fragments, and, in addition, decreases the expression level of septin 2, which interacts with the actin cytoskeleton and is involved in cytokinesis [4].

Anatomical context of CALU

• The calumenin transcript is ubiquitously expressed in human tissue, at high levels in heart, placenta and skeletal muscle, at lower levels in lung, kidney and pancreas and at very low levels in brain and liver [2].
• Primary cultures of normal human bronchial epithelial cells (NHBE) and a cell line of human airway epithelial cells, Calu 3, were grown on Silastic membranes, and a wound was scraped across the well [10].
• Anion selectivity of apical membrane conductance of Calu 3 human airway epithelium [11].
• Proteomic profiling of fibroblasts reveals a modulating effect of extracellular calumenin on the organization of the actin cytoskeleton [4].
• Recently, it was shown that thrombin-activated thrombocytes liberate calumenin, which also is found in atherosclerotic lesions but not in normal vasculature [4].

Associations of CALU with chemical compounds

• A single patient, homozygous for G(11)A CALU mutant allele, required an exceptionally high warfarin dose (20 mg/day) and the prevalence of heterozygous (11)A allele carriers in the upper 10(th) dose percentile was significantly higher (0.27 vs. 0.18, p < 0.02) [12].
• Identification of hox genes and analysis of their transcription in the unicellular cyanobacterium Gloeocapsa alpicola CALU 743 growing under nitrate-limiting conditions [13].
• After application of a placental tissue extract we were able to elute one protein that interacts with calumenin in the presence of Ca(2+) [1].

Physical interactions of CALU

• Calumenin interacts with serum amyloid P component [1].

Analytical, diagnostic and therapeutic context of CALU

• Since its Ca2+ binding may be important for the function of the protein we have used microdialysis experiments in order to analyse for the affinity and the capacity of recombinant human (rh) calumenin [2].

References