Alternative titles; symbols
HGNC Approved Gene Symbol: MOAP1
Cytogenetic location: 14q32.12 Genomic coordinates (GRCh38) : 14:93,182,199-93,184,897 (from NCBI)
Using amino acids 1 to 171 of mouse Bax (600040) in a yeast 2-hybrid screen of a human brain cDNA library, followed by screening of a cerebellum cDNA library, Tan et al. (2001) cloned MAP1. The deduced 351-amino acid protein has a calculated molecular mass of 39 kD. MAP1 contains a central BH3-like motif that is similar to the BH3-B domain of BID (601997). Northern blot analysis detected a 2.8-kb MAP1 transcript in all tissues examined, with highest expression in heart and brain.
Tan et al. (2001) found that overexpression of MAP1 in a breast carcinoma cell line induced apoptosis, which was abrogated by inclusion of a broad-spectrum caspase (see 147678) inhibitor. MAP1 formed homodimers, and it associated with BAX, BCL2 (151430), and BCLXL (BCL2L1; 600039) in vitro and in transfected human embryonic kidney cells. MAP1 did not bind other members of the BCL2 family. Mutation analysis indicated that the BH3-like domain of MAP1 was required to mediate apoptosis and for binding of MAP1 to BAX, but not to BCLXL. All 3 BH domains of BAX were required for binding with MAP1.
Baksh et al. (2005) found that MAP1 interacted with RASSF1A (605082) following TNF-alpha (191160) stimulation. Mutation analysis determined that a basic stretch in MAP1 mediated the interaction with RASSF1A, and the BH3-like domain of MAP1 was dispensable for RASSF1A/MAP1 interaction. In the absence of RASSF1A, MAP1 appeared to exist in an inactive closed conformation in which the BH3-like domain was unavailable for interaction with BAX. RASSF1A binding relieved the inhibitory interaction, allowing MAP1 to bind BAX. RASSF1A/MAP1 interaction was required for conformational change in BAX, mitochondrial membrane insertion, and maximal apoptosis in response to death receptor stimulation. RASSF1A and MAP1 were recruited to both the TNF-alpha and TRAIL (603598) receptor complexes in response to their respective cognate ligands.
Gross (2014) mapped the MOAP1 gene to chromosome 14q32.12 based on an alignment of the MOAP1 sequence (GenBank AF305550) with the genomic sequence (GRCh37).
Baksh, S., Tommasi, S., Fenton, S., Yu, V. C., Martins, L. M., Pfeifer, G. P., Latif, F., Downward, J., Neel, B. G. The tumor suppressor RASSF1A and MAP-1 link death receptor signaling to Bax conformational change and cell death. Molec. Cell 18: 637-650, 2005. [PubMed: 15949439] [Full Text: https://doi.org/10.1016/j.molcel.2005.05.010]
Gross, M. B. Personal Communication. Baltimore, Md. 2/27/2014.
Tan, K. O., Tan, K. M. L., Chan, S.-L., Yee, K. S. Y., Bevort, M., Ang, K. C., Yu, V. C. MAP-1, a novel proapoptotic protein containing a BH3-like motif that associates with Bax through its Bcl-2 homology domains. J. Biol. Chem. 276: 2802-2807, 2001. [PubMed: 11060313] [Full Text: https://doi.org/10.1074/jbc.M008955200]