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Gene Review

C21orf2  -  chromosome 21 open reading frame 2

Homo sapiens

Synonyms: A2, C21orf-HUMF09G8.5, LRRC76, Protein C21orf2, YF5, ...
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Disease relevance of C21orf2


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


Biological context of C21orf2


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


  1. Reduction of chromatin assembly factor 1 p60 and C21orf2 protein, encoded on chromosome 21, in Down syndrome brain. Shim, K.S., Bergelson, J.M., Furuse, M., Ovod, V., Krude, T., Lubec, G. J. Neural Transm. Suppl. (2003) [Pubmed]
  2. Developmental gene expression in Leishmania donovani: differential cloning and analysis of an amastigote-stage-specific gene. Charest, H., Matlashewski, G. Mol. Cell. Biol. (1994) [Pubmed]
  3. Autoantibodies against the fibrinolytic receptor, annexin 2, in antiphospholipid syndrome. Cesarman-Maus, G., Ríos-Luna, N.P., Deora, A.B., Huang, B., Villa, R., Cravioto, M.d.e.l. .C., Alarcón-Segovia, D., Sánchez-Guerrero, J., Hajjar, K.A. Blood (2006) [Pubmed]
  4. Lack of genetic association between the phospholipase A2 gene and bipolar mood disorder in a European multicentre case-control study. Dikeos, D.G., Papadimitriou, G.N., Souery, D., Del-Favero, J., Massat, I., Blackwood, D., Cichon, S., Daskalopoulou, E., Ivezic, S., Kaneva, R., Karadima, G., Lorenzi, C., Milanova, V., Muir, W., Nöthen, M., Oruc, L., Rietschel, M., Serretti, A., Van Broeckhoven, C., Soldatos, C.R., Stefanis, C.N., Mendlewicz, J. Psychiatr. Genet. (2006) [Pubmed]
  5. Association study of bipolar disorder at the phospholipase A2 gene (PLA2A) in the Darier's disease (DAR) region of chromosome 12q23-q24.1. Jacobsen, N., Daniels, J., Moorhead, S., Harrison, D., Feldman, E., McGuffin, P., Owen, M.J., Craddock, N. Psychiatr. Genet. (1996) [Pubmed]
  6. Identification of a developmental timer regulating the stability of embryonic cyclin A and a new somatic A-type cyclin at gastrulation. Howe, J.A., Howell, M., Hunt, T., Newport, J.W. Genes Dev. (1995) [Pubmed]
  7. Spatial codes in dendritic BC1 RNA. Muslimov, I.A., Iacoangeli, A., Brosius, J., Tiedge, H. J. Cell Biol. (2006) [Pubmed]
  8. Accelerated evolution in the protein-coding regions is universal in crotalinae snake venom gland phospholipase A2 isozyme genes. Nakashima, K., Nobuhisa, I., Deshimaru, M., Nakai, M., Ogawa, T., Shimohigashi, Y., Fukumaki, Y., Hattori, M., Sakaki, Y., Hattori, S. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  9. Possible role of mammalian secretory group II phospholipase A2 in T-lymphocyte activation: implication in propagation of inflammatory reaction. Asaoka, Y., Yoshida, K., Sasaki, Y., Nishizuka, Y., Murakami, M., Kudo, I., Inoue, K. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  10. Multiple components of blood group A and B antigens in human erythrocyte membranes and their difference between A1 and A2 status. Fujii, H., Yoshida, A. Proc. Natl. Acad. Sci. U.S.A. (1980) [Pubmed]
  11. Human Fab fragments specific for the Haemophilus influenzae b polysaccharide isolated from a bacteriophage combinatorial library use variable region gene combinations and express an idiotype that mirrors in vivo expression. Reason, D.C., Wagner, T.C., Lucas, A.H. Infect. Immun. (1997) [Pubmed]
  12. Purification and characterization of phospholipase A2 inhibitory proteins from pig thyroid gland. Antonicelli, F., Rothhut, B., Martiny, L., Aguie-Aguie, G., Lambert, B., Bellon, G., Russo-Marie, F., Jacquemin, C., Haye, B. FEBS Lett. (1988) [Pubmed]
  13. Human cytomegalovirus stimulates arachidonic acid metabolism through pathways that are affected by inhibitors of phospholipase A2 and protein kinase C. AbuBakar, S., Boldogh, I., Albrecht, T. Biochem. Biophys. Res. Commun. (1990) [Pubmed]
  14. Studies on opsonized zymozan, FMLP, carbachol, PMA and A23187 stimulated respiratory burst of human PMNLs. Fülöp, T., Varga, Z., Nagy, J.T., Fóris, G. Biochem. Int. (1988) [Pubmed]
  15. Characterization of a novel gene, C21orf2, on human chromosome 21q22.3 and its exclusion as the APECED gene by mutation analysis. Scott, H.S., Kyriakou, D.S., Peterson, P., Heino, M., Tähtinen, M., Krohn, K., Chen, H., Rossier, C., Lalioti, M.D., Antonarakis, S.E. Genomics (1998) [Pubmed]
  16. Protein levels of genes encoded on chromosome 21 in fetal Down syndrome brain: challenging the gene dosage effect hypothesis (Part III). Cheon, M.S., Kim, S.H., Ovod, V., Kopitar Jerala, N., Morgan, J.I., Hatefi, Y., Ijuin, T., Takenawa, T., Lubec, G. Amino Acids (2003) [Pubmed]
  17. Reprogramming alternative pre-messenger RNA splicing through the use of protein-binding antisense oligonucleotides. Villemaire, J., Dion, I., Elela, S.A., Chabot, B. J. Biol. Chem. (2003) [Pubmed]
  18. Monosodium urate crystals stimulate phospholipase A2 enzyme activities and the synthesis of a phospholipase A2-activating protein. Bomalaski, J.S., Baker, D.G., Brophy, L.M., Clark, M.A. J. Immunol. (1990) [Pubmed]
  19. Phospholipase A2 gene expression and activity in histologically normal ileal mucosa and in Crohn's ileitis. Lilja, I., Smedh, K., Olaison, G., Sjödahl, R., Tagesson, C., Gustafson-Svärd, C. Gut (1995) [Pubmed]
  20. Phorbol esters and oleoyl acetoyl glycerol enhance release of arachidonic acid in platelets stimulated by Ca2+ ionophore A23187. Halenda, S.P., Zavoico, G.B., Feinstein, M.B. J. Biol. Chem. (1985) [Pubmed]
  21. Evidence for multiple metabolic pools of phosphatidylinositol in stimulated platelets. Billah, M.M., Lapetina, E.G. J. Biol. Chem. (1982) [Pubmed]
  22. Aeromonas infections and their treatment. Jones, B.L., Wilcox, M.H. J. Antimicrob. Chemother. (1995) [Pubmed]
  23. Promoter cloning and characterisation of the transcriptional regulation of the human thyrostimulin A2 subunit. Breous, E., Wenzel, A., Loos, U. Mol. Cell. Endocrinol. (2005) [Pubmed]
  24. Identification and characterization of phospholipase A2 inhibitory proteins in human mononuclear cells. Coméra, C., Rothhut, B., Russo-Marie, F. Eur. J. Biochem. (1990) [Pubmed]
  25. The sequence and conformation of human pancreatic procarboxypeptidase A2. cDNA cloning, sequence analysis, and three-dimensional model. Catasús, L., Vendrell, J., Avilés, F.X., Carreira, S., Puigserver, A., Billeter, M. J. Biol. Chem. (1995) [Pubmed]
  26. Inhibition of tumor growth with antiangiogenic cancer vaccine using epitope peptides derived from human vascular endothelial growth factor receptor 1. Ishizaki, H., Tsunoda, T., Wada, S., Yamauchi, M., Shibuya, M., Tahara, H. Clin. Cancer Res. (2006) [Pubmed]
  27. Effects of hydroxyethylrutosides on hypoxia-induced activation of human endothelial cells in vitro. Janssens, D., Michiels, C., Arnould, T., Remacle, J. Br. J. Pharmacol. (1996) [Pubmed]
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