Alternative titles; symbols
HGNC Approved Gene Symbol: CENPM
Cytogenetic location: 22q13.2 Genomic coordinates (GRCh38) : 22:41,927,196-41,947,152 (from NCBI)
The centromere is a specialized chromatin domain, present throughout the cell cycle, that acts as a platform on which the transient assembly of the kinetochore occurs during mitosis. All active centromeres are characterized by the presence of long arrays of nucleosomes in which CENPA (117139) replaces histone H3 (see 602810). CENPM is an additional factor required for centromere assembly (Foltz et al., 2006).
By searching databases for homologs of mouse Pane1, Bierie et al. (2004) identified human CENPM, which they called PANE1. The deduced protein contains 180 amino acids. In silico analysis suggested that PANE1 was expressed predominantly in cancer tissues. Dot and Northern blot analyses revealed highest expression of a 1.2-kb transcript in fetal liver, thymus, and spleen, as well as in lymphoid cells and tumor cell lines, including B- and T-cell leukemias. PANE1 was expressed in activated, but not resting, B and T lymphocytes. Immunofluorescence microscopy showed nuclear localization of PANE1 in nonconfluent culture cells, but not in confluent or dividing cells.
Brickner et al. (2006) identified a novel minor histocompatibility antigen (mHAg) recognized by a cytotoxic T-lymphocyte clone derived from a hemopoietic cell transplant recipient. By database analysis, they determined that the mHAg is encoded by 1 of 11 variants of PANE1. The variant, designated transcript K, contains a unique first exon and a second exon common to 5 of the longer PANE1 variants, including transcript C, which encodes the full-length form. Transcript K encodes a 58-amino acid protein whose 46 C-terminal amino acids are identical to those of the full-length protein. Immunogenicity of the mHAg resulted from a nonsense SNP in the unique exon 1 of transcript K. Quantitative RT-PCR analysis detected selective expression of transcript K in B-lymphoid cells, with highest expression in resting B cells and B-cell chronic lymphocytic leukemia cells. Transcript C was selectively expressed in activated B cells, suggesting a reciprocal expression pattern for transcripts K and C. Brickner et al. (2006) proposed that PANE1 is a potential therapeutic target in B-lineage chronic lymphocytic leukemia.
Bierie et al. (2004) determined that the CENPM gene contains 6 exons and spans 8.4 kb.
By immunoprecipitation of CENPA-containing complexes from HeLa cells, followed by multiple tandem affinity purifications, Foltz et al. (2006) identified CENPM as a component of a CENPA nucleosome-associated complex. Epitope-tagged CENPM bound to centromeres throughout interphase and during mitosis. CENPM, CENPN (611509), CENPT (611510), and CENPU (MLF1IP; 611511), together with CENPC (117141) and CENPH (605607), bound CENPA in a proximal nucleosome-associated complex. Small interfering RNA (siRNA)-mediated depletion of CENPM disrupted recruitment of the core complex, caused the loss of CENPN from centromeres, and increased the number of cells in mitosis.
Okada et al. (2006) found that chicken B cells expressing a conditional Cenpm deletion stopped proliferating and died following induction of the deletion. Cenpm deletion led to loss of centromeric localization of Cenph, Cenpi, Cenpk (611502), and Cenpl (611503), and while preexisting Cenpa was stable, incorporation of newly synthesized Cenpa into centromeres appeared defective in mutant cells.
By genomic sequence analysis, Brickner et al. (2006) mapped the CENPM gene to chromosome 22q13.31, about 12 kb from the TNFRSF13C gene (606269).
Bierie, B., Edwin, M., Melenhorst, J. J., Hennighausen, L. The proliferation associated nuclear element (PANE1) is conserved between mammals and fish and preferentially expressed in activated lymphoid cells. Gene Expr. Patterns 4: 389-395, 2004. [PubMed: 15183305] [Full Text: https://doi.org/10.1016/j.modgep.2004.01.008]
Brickner, A. G., Evans, A. M., Mito, J. K., Xuereb, S. M., Feng, X., Nishida, T., Fairfull, L., Ferrell, R. E., Foon, K. A., Hunt, D. F., Shabanowitz, J., Engelhard, V. H., Riddell, S. R., Warren, E. H. The PANE1 gene encodes a novel human minor histocompatibility antigen that is selectively expressed in B-lymphoid cells and B-CLL. Blood 107: 3779-3786, 2006. [PubMed: 16391015] [Full Text: https://doi.org/10.1182/blood-2005-08-3501]
Foltz, D. R., Jansen, L. E. T., Black, B. E., Bailey, A. O., Yates, J. R., III, Cleveland, D. W. The human CENP-A centromeric nucleosome-associated complex. Nature Cell Biol. 8: 458-469, 2006. [PubMed: 16622419] [Full Text: https://doi.org/10.1038/ncb1397]
Okada, M., Cheeseman, I. M., Hori, T., Okawa, K., McLeod, I. X., Yates, J. R., III, Desai, A., Fukagawa, T. The CENP-H-I complex is required for the efficient incorporation of newly synthesized CENP-A into centromeres. Nature Cell Biol. 8: 446-457, 2006. [PubMed: 16622420] [Full Text: https://doi.org/10.1038/ncb1396]