HGNC Approved Gene Symbol: APOD
Cytogenetic location: 3q29 Genomic coordinates (GRCh38): 3:195,568,705-195,583,940 (from NCBI)
Apolipoprotein D (ApoD) is a member of the alpha(2mu)-microglobulin superfamily of carrier proteins also known as lipocalins (e.g., lipocalin-1; 151675). It is a protein component of high-density lipoprotein in human plasma, comprising about 5% of total high-density lipoprotein (Fielding and Fielding, 1980). It is a glycoprotein of estimated molecular weight 33,000 Da. ApoD is closely associated with the enzyme lecithin:cholesterol acyltransferase (LCAT; 606967) (summary by Drayna et al., 1986).
Drayna et al. (1986) reported the amino acid sequence of apoD based on the nucleotide sequence of the coding portion of the APOD gene and on the cloned cDNA sequence. The 169-amino acid protein bore little similarity to other lipoprotein sequences but had a high degree of homology to plasma retinol-binding protein (180250, 180260, 180280, 180290), a member of the alpha(2mu)-globulin superfamily. This structural similarity may indicate some functional homology of these proteins. ApoD mRNA has been detected in many tissues. Drayna et al. (1987) described multiple RFLPs at the APOD locus. Kamboh et al. (1989) demonstrated for the first time polymorphism of apolipoprotein D by an isoelectric focusing-immunoblotting technique.
Zeng et al. (1996) identified apoD as apocrine secretion odor-binding protein-2 (ASOB2), 1 of 2 glycoproteins that bind E-3-methyl-2-hexenoic acid (E-3M2H), the most abundant axillary odor component in human males. The authors used mass spectrometry to determine the amino acid sequence and glycosylation pattern of ASOB2. The pattern of glycosylation for axillary apoD differs from that reported for plasma apoD, suggesting to Zeng et al. (1996) that there are different sites of expression for the 2 glycoproteins. In situ hybridization of an oligonucleotide probe against apoD mRNA with axillary tissue demonstrated that the message for synthesis of this protein is specific to the apocrine glands. These results suggested a remarkable similarity between human axillary secretions and nonhuman mammalian odor sources, where lipocalins have been shown to carry the odoriferous signals used in pheromonal communication.
Zeng et al. (1996) noted several studies in humans suggesting that axillary odors and secretions from both males and females are a source of chemical signals containing physiologically active components capable of altering the female menstrual cycle. These alterations include the menstrual synchrony effect first documented by McClintock (1971) in an all-female living group and later replicated by others in coeducational facilities (Graham and McGrew, 1980; Quadagno et al., 1981). In nonhuman mammals such as rodents, estrous synchrony has been shown to be mediated by airborne chemical signals (McClintock, 1978). Certain axillary components currently function as chemical signals involved in the regulation of reproductive function via alteration of the hypothalamic-pituitary-gonadal axis; chemical signals for this mode of action are termed primer pheromones. Characterization of the source of the odor in the human axillary region is not only of commercial interest but is also important biologically because axillary extracts can alter the length and timing of the female menstrual cycle. In males, the most abundant odor component is known to be E-3-methyl-2-hexenoic acid (E-3M2H), which is liberated from nonodorous apocrine secretions by axillary microorganisms. In the apocrine gland secretions, 3M2H is carried on the skin surface bound to 2 proteins, apocrine secretion odor-binding proteins 1 and 2 (ASOB1 and ASOB2) with apparent molecular masses of 45 kD and 26 kD, respectively (summary by Zeng et al., 1996).
Drayna et al. (1987) assigned the gene for APOD to 3p14.2-qter by dot blot hybridization to DNA from sorted human chromosomes and by in situ hybridization. Cellular retinol-binding proteins (180260, 180280) are coded by chromosome 3; interstitial RBP (180290) is coded by a gene on chromosome 10. Warden et al. (1992) demonstrated that the ApoD gene is located on mouse chromosome 16.
Drayna, D., Fielding, C., McLean, J., Baer, B., Castro, G., Chen, E., Comstock, L., Henzel, W., Kohr, W., Rhee, L., Wion, K., Lawn, R. Cloning and expression of human apolipoprotein D cDNA. J. Biol. Chem. 261: 16535-16539, 1986. [PubMed: 3453108]
Drayna, D., Scott, J. D., Lawn, R. Multiple RFLPs at the human apolipoprotein D (APOD) locus. Nucleic Acids Res. 15: 9617 only, 1987. [PubMed: 2891117] [Full Text: https://doi.org/10.1093/nar/15.22.9617]
Drayna, D. T., McLean, J. W., Wion, K. L., Trent, J. M., Drabkin, H. A., Lawn, R. M. Human apolipoprotein D gene: gene sequence, chromosome localization, and homology to the alpha-2mu-globulin superfamily. DNA 6: 199-204, 1987. [PubMed: 2439269] [Full Text: https://doi.org/10.1089/dna.1987.6.199]
Fielding, P. E., Fielding, C. J. A cholesteryl ester transfer complex in human plasma. Proc. Nat. Acad. Sci. 77: 3327-3330, 1980. [PubMed: 6774335] [Full Text: https://doi.org/10.1073/pnas.77.6.3327]
Graham, C. A., McGrew, W. C. Menstrual synchrony in female undergaduates living on a coeducational campus. Psychoneuroendocrinology 5: 245-252, 1980. [PubMed: 7191131] [Full Text: https://doi.org/10.1016/0306-4530(80)90028-1]
Kamboh, M. I., Albers, J. J., Majumder, P. P., Ferrell, R. E. Genetic studies of human apolipoproteins. IX. Apolipoprotein D polymorphism and its relation to serum lipoprotein lipid levels. Am. J. Hum. Genet. 45: 147-154, 1989. [PubMed: 2741945]
McClintock, M. K. Menstrual synchrony and suppression. Nature 229: 244-245, 1971. Note: Erratum: Nature 229: 643 only, 1971. [PubMed: 4994256] [Full Text: https://doi.org/10.1038/229244a0]
McClintock, M. K. Estrous synchrony and its mediation by airborn chemical communication (Rattus norvegicus). Horm. Behav. 10: 264-276, 1978. [PubMed: 568596] [Full Text: https://doi.org/10.1016/0018-506x(78)90071-5]
Quadagno, D. M., Shubeita, H. E., Deck, J., Francoeur, D. Influence of male social contacts, exercise and all-female living conditions on the menstrual cycle. Psychoneuroendocrinology 6: 239-244, 1981. [PubMed: 7291434] [Full Text: https://doi.org/10.1016/0306-4530(81)90033-0]
Warden, C. H., Diep, A., Taylor, B. A., Lusis, A. J. Localization of the gene for apolipoprotein D on mouse chromosome 16. Genomics 12: 851-852, 1992. [PubMed: 1572665] [Full Text: https://doi.org/10.1016/0888-7543(92)90325-m]
Zeng, C., Spielman, A. I., Vowels, B. R., Leyden, J. J., Biemann, K., Preti, G. A human axillary odorant is carried by apolipoprotein D. Proc. Nat. Acad. Sci. 93: 6626-6630, 1996. [PubMed: 8692868] [Full Text: https://doi.org/10.1073/pnas.93.13.6626]