Alternative titles; symbols
HGNC Approved Gene Symbol: MAN2A2
Cytogenetic location: 15q26.1 Genomic coordinates (GRCh38): 15:90,902,382-90,922,585 (from NCBI)
Golgi alpha-mannosidase II (154582) is an enzyme involved in the processing of N-linked glycans. Using a previously isolated murine cDNA clone as a probe, Misago et al. (1995) isolated cDNA clones encompassing the human MANA2 cDNA open reading frame. During the isolation of genomic clones, genes related to that encoding alpha-mannosidase II were isolated. One such gene was found to encode an isozyme, which they designated alpha-mannosidase II(x). A 5-kb cDNA clone of the MANA2X gene was then isolated from a human melanoma cDNA library. Comparison between the MANA2X and MANA2 cDNAs suggested that the cloned cDNA encodes a truncated polypeptide with 796 amino acid residues, while the product of the MANA2 gene consists of 1144 amino acid residues. However, further studies indicated that alternative splicing of the MANA2X transcript can result in an additional transcript encoding an 1139-amino acid polypeptide. Northern analysis showed transcription of MANA2X in various tissues, suggesting that it is a housekeeping gene. COS cells transfected with MANA2X cDNA containing the full-length open reading frame showed an increase in alpha-mannosidase activity.
By isotopic in situ hybridization, Misago et al. (1995) mapped the MANA2X gene to human chromosome 15q25; the MANA2 gene was mapped to 5q21-q22.
Akama et al. (2002) generated mice deficient for the Man2a2 gene, which encodes alpha-mannosidase-IIX, an enzyme that forms intermediate asparagine-linked carbohydrates (N-glycans). Male mice lacking Man2a2 are largely infertile. The Man2a2-null spermatogenic cells fail to adhere to Sertoli cells and are prematurely released from the testis to the epididymis. Akama et al. (2002) identified an N-glycan structure that plays a key role in germ cell-Sertoli cell adhesion and identified a specific carbohydrate that is required for spermatogenesis. This carbohydrate is designated 310.11 and is an N-acetylglucosamine-terminated tri-antennary and fucosylated N-glycan structure.
Akama et al. (2006) produced Man2a1 and Man2a2 double-knockout mice. Some double-null mice died between embryonic days 15.5 and 18.5, but most survived until shortly after birth and died of respiratory failure. Recombinant mouse Man2a1 and Man2a2 showed identical substrate specificities toward N-glycan substrates, suggesting that either can biochemically compensate for deficiency of the other in vivo.
Akama, T. O., Nakagawa, H., Sugihara, K., Narisawa, S., Ohyama, C., Nishimura, S.-I., O'Brien, D. A., Moremen, K. W., Millan, J. L., Fukuda, M. N. Germ cell survival through carbohydrate-mediated interaction with Sertoli cells. Science 295: 124-127, 2002. [PubMed: 11778047] [Full Text: https://doi.org/10.1126/science.1065570]
Akama, T. O., Nakagawa, H., Wong, N. K., Sutton-Smith, M., Dell, A., Morris, H. R., Nakayama, J., Nishimura, S.-I., Pai, A., Moremen, K. W., Marth, J. D., Fukuda, M. N. Essential and mutually compensatory roles of alpha-mannosidase II and alpha-mannosidase IIx in N-glycan processing in vivo in mice. Proc. Nat. Acad. Sci. 103: 8983-8988, 2006. [PubMed: 16754854] [Full Text: https://doi.org/10.1073/pnas.0603248103]
Misago, M., Liao, Y.-F., Kudo, S., Eto, S., Mattei, M.-G., Moremen, K. W., Fukuda, M. N. Molecular cloning and expression of cDNAs encoding human alpha-mannosidase II and a previously unrecognized alpha-mannosidase II(X) isozyme. Proc. Nat. Acad. Sci. 92: 11766-11770, 1995. [PubMed: 8524845] [Full Text: https://doi.org/10.1073/pnas.92.25.11766]