Disease relevance of C21orf2

• Reduction of chromatin assembly factor 1 p60 and C21orf2 protein, encoded on chromosome 21, in Down syndrome brain [1].
• Using immunoblotting we determined Coxsackievirus and adenovirus receptor (CAR), Claudin-8, C21orf2, Chromatin assembly factor 1 p60 subunit (CAF-1 p60) in frontal cortex from DS, AD and control patients [1].
• The recombinant A2 protein produced in Escherichia coli cells was specifically recognized by immune serum from a patient with visceral leishmaniasis [2].
• Anti-A2 antibodies (titer > 3 SDs) were significantly more prevalent in patients with APS (22.6%; venous, 17.5%; arterial, 34.3%; and mixed thrombosis, 40.4%) than in healthy individuals (2.1%, P < .001), patients with nonautoimmune thrombosis (0%, P = .017), or patients with lupus without thrombosis (6.3%, P < .001) [3].
• We propose that anti-A2 antibodies contribute to the prothrombotic diathesis in antiphospholipid syndrome [3].

Psychiatry related information on C21orf2

• The possible association between phospholipase A2 gene and bipolar mood disorder was examined in 557 bipolar patients and 725 controls (all personally interviewed), recruited from seven countries (Belgium, Bulgaria, Croatia, Germany, Greece, Italy, and UK) [4].
• Association study of bipolar disorder at the phospholipase A2 gene (PLA2A) in the Darier's disease (DAR) region of chromosome 12q23-q24.1 [5].

High impact information on C21orf2

• At gastrulation, however, both A1 and A2 proteins turn over rapidly during interphase of the cell cycle [6].
• It specifically interacts with heterogeneous nuclear ribonucleoprotein A2, a trans-acting targeting factor that has previously been implicated in the transport of MBP mRNA in oligodendrocytes and neurons [7].
• Accelerated evolution in the protein-coding regions is universal in crotalinae snake venom gland phospholipase A2 isozyme genes [8].
• Diacylglycerol and ionomycin were essential for this cellular response, and phospholipase A2 alone showed no effect [9].
• These results indicate the heterogeneity of blood group components in erythrocytes membranes and the qualitative difference between A1 and A2 antigens on these membranes [10].

Chemical compound and disease context of C21orf2

• Usage of V(H)26 in combination with A2 V regions containing a junctional arginine is a predominant configuration of naturally occurring Hib PS-specific Abs [11].
• The protein activity was assessed by the inhibition of pancreatic phospholipase A2 on [3H]oleic acid-labelled Escherichia coli membranes as substrate and on the prostaglandin E2 production of cultured thyroid cells [12].
• Human cytomegalovirus stimulates arachidonic acid metabolism through pathways that are affected by inhibitors of phospholipase A2 and protein kinase C [13].
• To elucidate the postreceptor signal transduction mechanism involved in respiratory burst stimulation various inhibitors were used as follows: neomycin (for phospholipase C enzyme), mepacrine (for phospholipase A2 enzyme) and pertussis toxin (for GTP binding regulatory protein) [14].

Biological context of C21orf2

• Hybridization of the EST clones to a cosmid contig in chromosome 21q22.3 mapped C21orf2 just distal to PFKL, a critical mapping region for several genetic diseases [15].
• Mutation analysis using sequencing of RT-PCR and genomic DNA-derived PCR products, SSCP, and Southern and Northern blot analyses in APECED patients excluded C21orf2 as the gene for APECED [15].
• Characterization of a novel gene, C21orf2, on human chromosome 21q22.3 and its exclusion as the APECED gene by mutation analysis [15].
• The decrease of C21orf2 may represent mitochondrial dysfunction that has been reported repeatedly and also data on CAR and claudin-8 are not supporting the gene-dosage hypothesis at the protein level [1].
• Synaptojanin-1 and C21orf2 were increased in DS, but others were comparable between DS and controls, suggesting that the DS phenotype cannot be simply explained by gene dosage effects [16].

Anatomical context of C21orf2

• Annexin 2 (A2) is a profibrinolytic endothelial cell surface receptor that binds plasminogen, its tissue activator (tPA), and beta(2)-glycoprotein I (beta2GPI), the main antigen for antiphospholipid antibodies [3].
• Five of these were closely related (A2 series) and recognized, by Northern (RNA) blot analyses, a 3.5-kb transcript in amastigotes and in amastigote-infected macrophages [2].
• In four different human cell lines, an interfering oligonucleotide carrying A1/A2 binding sites also shifted the alternative splicing of the Bcl-x pre-mRNA more efficiently than oligonucleotides acting through duplex formation only [17].
• These findings suggest that phospholipase A2 activation in response to MSUC requires an intact microtubule structure, and that phospholipase A2 and PLAP may be important modulators of at least a portion of the gouty inflammatory response [18].
• Phospholipase A2 gene expression and activity in histologically normal ileal mucosa and in Crohn's ileitis [19].

Associations of C21orf2 with chemical compounds

• Thus, the potentiation of arachidonic acid release by PMA appeared to be due to phospholipase A2 activity [20].
• A further mobilization of cytosolic Ca2+ interrupts the phosphatidylinositol cycle by inhibiting conversion of phosphatidic acid to phosphatidylinositol and also activates phospholipases of the A2 type [21].
• Two distinct enzymes are produced: the A1 enzyme, a serine beta-lactamase behaving as a group 1 cephalosporinase, and the A2 enzyme, a metallo beta-lactamase which hydrolyses a wide range of beta-lactam agents including the carbapenems [22].
• The novel heterodimeric glycoprotein hormone thyrostimulin consists of two unique subunits, A2 and B5 [23].
• All these proteins inhibit phospholipase A2 activity in vitro and the three smaller ones inhibit the [3H]arachidonic acid release from prelabelled monocytes induced by the calcium ionophore A23187 in a dose-dependent manner [24].

Other interactions of C21orf2

• As aberrant expression of the four proteins was not found in brains of patients with AD, decreased CAF and C21orf2 can be considered specific for DS [1].

Analytical, diagnostic and therapeutic context of C21orf2

• Northern blot analysis of this gene, termed C21orf2 (chromosome 21 open reading frame 2), revealed two ubiquitously expressed mRNAs of 2.2 and 1.2 kb produced by use of alternative polyadenylation sites [15].
• Serum samples from 434 individuals (206 patients with systemic lupus erythematosus without thrombosis, 62 with APS, 21 with nonautoimmune thrombosis, and 145 healthy individuals) were analyzed by enzyme-linked immunosorbent assay (ELISA) and immunoblot for antiphospholipid and A2 antibodies [3].
• The sequence and conformation of human pancreatic procarboxypeptidase A2. cDNA cloning, sequence analysis, and three-dimensional model [25].
• RESULTS: The CTL responses in A2/Kb transgenic mice were induced with vaccination using identified epitope peptides restricted to HLA-A*0201 [26].
• Thus, the effects of HR on ATP depletion, phospholipase A2 activation and neutrophil adherence were investigated in hypoxia-activated human umbilical vein endothelial cells in primary cell culture [27].

References