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Link to original content: https://omim.org/entry/606907
Alternative titles; symbols
HGNC Approved Gene Symbol: APOM
Cytogenetic location: 6p21.33 Genomic coordinates (GRCh38) : 6:31,652,404-31,658,210 (from NCBI)
Xu and Dahlback (1999) identified APOM through N-terminal sequencing of proteins associated with triglyceride-rich lipoproteins (TGRLP). By searching 2 liver cDNA libraries with probes designed from an EST containing the sequence, they cloned human APOM. The deduced 188-amino acid protein has a calculated molecular mass of about 21 kD. It contains a potential N-glycosylation site, 2 possible disulfide bridges, and a hydrophobic alpha-helical signal peptide that is retained in the mature protein. Sequence analysis revealed 79% identity between the human and mouse proteins. Northern blot analysis by Xu and Dahlback (1999) detected restricted expression of a 750-bp transcript in liver and kidney. Northern blot analysis of several cell lines by Albertella et al. (1996) detected a 1.1-kb transcript in HepG2 liver cells but not in human fibroblast, leukocyte, or monocytic cell lines. By Western blot analysis, Xu and Dahlback (1999) found that APOM is a minor component of high and low density lipoproteins as well as TGRLP. In vitro translation in the presence of microsomes resulted in a protein of 26 kD, suggesting that APOM is translocated through the membrane and glycosylated.
By Southern blot analysis, Albertella et al. (1996) determined that APOM is present in single copy in the genome.
By homology with the corresponding mouse gene, Ng20, which maps to chromosome 17, and by sequence analysis, Xu and Dahlback (1999) mapped the human APOM gene to chromosome 6p21.3, between the BAT3 (142590) and BAT4 (142610) genes.
Blaho et al. (2015) demonstrated that ApoM-sphingosine-1-phosphate (S1P) is dispensable for lymphocyte trafficking yet restrains lymphopoiesis by activating the S1P1 receptor (601974) on bone marrow lymphocyte progenitors. Mice that lacked ApoM (Apom -/-) had increased proliferation of lineage-negative/Sca1+/cKit+ hematopoietic progenitor cells (LSKs) and common lymphoid progenitors (CLPs) in bone marrow. Pharmacologic activation or genetic overexpression of S1P1 suppressed this progenitor cell proliferation in vivo. ApoM was stably associated with bone marrow CLPs, which showed active S1P1 signaling in vivo. Moreover, ApoM-bound S1P, but not albumin (103600)-bound S1P, inhibited lymphopoiesis in vitro. Upon immune stimulation, Apom -/- mice developed more severe experimental autoimmune encephalomyelitis, characterized by increased lymphocytes in the central nervous system and breakdown of the blood-brain barrier. Thus, Blaho et al. (2015) concluded that the ApoM-S1P-S1P1 signaling axis restrains the lymphocyte compartment and, subsequently, adaptive immune responses.
Wolfrum et al. (2005) demonstrated that mice deficient in Apom accumulated cholesterol in large HDL particles while the conversion of HDL to pre-beta-HDL was impaired, leading to a markedly reduced cholesterol efflux from macrophages to Apom-deficient HDL compared to normal HDL in vitro. Overexpression of Apom in low density lipoprotein receptor (LDLR; 606945)-null mice protected against atherosclerosis when the mice were challenged with a cholesterol-enriched diet. Wolfrum et al. (2005) concluded that APOM is important for the formation of pre-beta-HDL and cholesterol efflux to HDL, and thereby inhibits formation of atherosclerotic lesions.
Wolfrum et al. (2008) observed a 4-fold decrease in plasma mRNA and protein levels of Apom, but not other apolipoproteins, in hyperinsulinemic and obese mice compared with nonobese wildtype mice. Analysis of hepatocytes from these mice showed that decreased Apom levels were dependent on increased insulin levels and were associated with localization of Foxa2 (600288) to cytosol. Further analysis showed that Foxa2 also regulated plasma high density lipoprotein (HDL) levels and that insulin and Pik3ca (171834) transcriptionally regulated Apom via Foxa2. Haploinsufficient Foxa2 +/- mice exhibited decreased hepatic Apom expression and plasma pre-beta-HDL and HDL levels. Apom -/- mice did not show increased plasma HDL levels, even with expression of constitutively active Foxa2. Wolfrum et al. (2008) concluded that their findings revealed a mechanism by which insulin regulates plasma HDL levels in physiologic and insulin-resistant states.
Albertella, M. R., Jones, H., Thomson, W., Olavesen, M. G., Campbell, R. D. Localization of eight additional genes in the human major histocompatibility complex, including the gene encoding the casein kinase II beta subunit (CSNK2B). Genomics 36: 240-251, 1996. [PubMed: 8812450] [Full Text: https://doi.org/10.1006/geno.1996.0459]
Blaho, V. A., Galvani, S., Engelbrecht, E., Liu, C., Swendeman, S. L., Kono, M., Proia, R. L., Steinman, L., Han, M. H., Hla, T. HDL-bound sphingosine-1-phosphate restrains lymphopoiesis and neuroinflammation. Nature 523: 342-346, 2015. [PubMed: 26053123] [Full Text: https://doi.org/10.1038/nature14462]
Wolfrum, C., Howell, J. J., Ndungo, E., Stoffel, M. Foxa2 activity increases plasma high density lipoprotein levels by regulating apolipoprotein M. J. Biol. Chem. 283: 16940-16949, 2008. [PubMed: 18381283] [Full Text: https://doi.org/10.1074/jbc.M801930200]
Wolfrum, C., Poy, M. N., Stoffel, M. Apolipoprotein M is required for pre-beta-HDL formation and cholesterol efflux to HDL and protects against atherosclerosis. Nature Med. 11: 418-422, 2005. [PubMed: 15793583] [Full Text: https://doi.org/10.1038/nm1211]
Xu, N., Dahlback, B. A novel human apolipoprotein (apoM). J. Biol. Chem. 274: 31286-31290, 1999. [PubMed: 10531326] [Full Text: https://doi.org/10.1074/jbc.274.44.31286]