Alternative titles; symbols
HGNC Approved Gene Symbol: AFM
Cytogenetic location: 4q13.3 Genomic coordinates (GRCh38): 4:73,481,745-73,504,001 (from NCBI)
Belanger et al. (1994) identified a fourth member of the albumin gene family, alpha-albumin (ALBA), the others being albumin (ALB; 103600), alpha-fetoprotein (AFP; 104150), and vitamin D-binding protein (DBP; 139200). ALBA is selectively expressed in the liver at late stages of development. The mRNA sequence encodes a predicted secreted protein with the typical triple domain disulfide cross-linked structure.
Lichenstein et al. (1994) described the initial characterization of afamin and its cDNA and provided evidence that AFM is a novel member of the albumin family. This serum protein, with a molecular mass of 87,000 Da, was purified to homogeneity and subjected to amino acid sequence analyses. These sequences were used to design oligonucleotide primers and to isolate a full-length cDNA. The amino acid sequence encoded by the cDNA was found to share strong similarity to albumin family members, including the characteristic pattern of cys residues observed in that family.
Lichenstein et al. (1994) noted distinctions among ALB family members. Concentrations in adult serum are 50 ng/ml for AFP, 350 microg/ml for DBP, 40 mg/ml for ALB, and 30 microg/ml for AFM. ALB is not N-glycosylated, AFP and DBP each have 1 potential N-glycosylation site, and AFM has 4 potential sites. ALB expresses 1 free thiol group that has been implicated in complex formation with cysteine, glutathione, and mercurial and gold compounds. In contrast, the other 3 have an even number of cys residues, are thought not to have a free thiol, and may not bind glutathione and mercurials as does ALB.
Nishio and Dugaiczyk (1996) found that predicted ALBA protein has a 21-amino acid leader sequence followed by a 578-residue mature polypeptide.
Comparisons of coding and promoter sequences of albumin family genes suggested to Belanger et al. (1994) that ALBA could be a phylogenetic intermediate between the ALB and AFP genes. The ALB and DBP genes diverged before the emergence of amphibians 500 Myr ago, while the AFP gene evolved slowly after the amphibian/reptile separation 350 Myr ago. The fact that the 3 genes have remained closely linked in single copy per haploid genome suggests a selective advantage to their proximity, plausibly provided by shared cis-regulatory elements.
Belanger et al. (1994) noted that the developmental switch between ALBA gene activation and AFP gene repression suggested new regulatory interplays at the albumin locus and adult stage-specific ligand binding functions carried out by the ALBA gene product.
Nishio and Dugaiczyk (1996) showed that the approximately 23-kb alpha-albumin gene contains 15 exons, the last of which is untranslated. The exon structure is similar to that of the related genes for albumin, alpha-fetoprotein, and vitamin D-binding protein.
Belanger et al. (1994) located the ALBA gene 10 kb downstream from the AFP locus on chromosome 4. They found that the sequence of the 3 most closely related albumin family genes is 5-prime--ALB--AFP--ALBA--3-prime.
Lichenstein et al. (1994) also mapped the AFM gene to chromosome 4 where other members of the albumin gene family map. The mapping was performed by PCR applied to a panel of somatic cell hybrids.
Four genes in the albumin gene family, ALB, DBP, AFP, and AFM, map to the same chromosomal region in humans, mice, and rats. By refining the physical and meiotic maps of the 4q11-q13 region and creating a local PAC contig, Song et al. (1999) determined the order and transcriptional orientation of these 4 genes to be centromere--3-prime-DBP-5-prime--5-prime-ALB-3-prime--5-prime-AFP-3-prime--5-prime-AFM-3-prime--telomere. They found that the ancestral DBP gene was separated from the ALB gene by more than 1.5 Mb.
Belanger, L., Roy, S., Allard, D. New albumin gene 3-prime adjacent to the alpha-1-fetoprotein locus. J. Biol. Chem. 269: 5481-5484, 1994. [PubMed: 7509788]
Lichenstein, H. S., Lyons, D. E., Wurfel, M. M., Johnson, D. A., McGinley, M. D., Leidli, J. C., Trollinger, D. B., Mayer, J. P., Wright, S. D., Zukowski, M. M. Afamin is a new member of the albumin, alpha-fetoprotein, and vitamin D-binding protein gene family. J. Biol. Chem. 269: 18149-18154, 1994. [PubMed: 7517938]
Nishio, H., Dugaiczyk, A. Complete structure of the human alpha-albumin gene, a new member of the serum albumin multigene family. Proc. Nat. Acad. Sci. 93: 7557-7561, 1996. [PubMed: 8755513] [Full Text: https://doi.org/10.1073/pnas.93.15.7557]
Song, Y.-H., Naumova, A. K., Liebhaber, S. A., Cooke, N. E. Physical and meiotic mapping of the region of human chromosome 4q11-q13 encompassing the vitamin D binding protein DBP/Gc-globulin and albumin multigene cluster. Genome Res. 9: 581-587, 1999. [PubMed: 10400926]