Other entities represented in this entry:
HGNC Approved Gene Symbol: GABPB1
Cytogenetic location: 15q21.2 Genomic coordinates (GRCh38): 15:50,275,389-50,355,198 (from NCBI)
The GA-binding protein (GABP) transcription factor, also referred to as nuclear respiratory factor-2 (NRF2) and adenovirus E4 gene transcription factor-1 (E4TF1), was initially identified through its role in the expression of the adenovirus E4 gene. The GABP complex, which consists of an alpha subunit (GABPA) and a beta subunit, contributes to the transcriptional regulation of a number of subunits of mitochondrial enzymes, including cytochrome c oxidase (CO; see 516030). The GABPB gene encodes at least 4 beta subunit isoforms that were originally thought to be encoded by 2 separate genes, GABPB1 and GABPB2.
Watanabe et al. (1993) cloned HeLA cell cDNAs encoding 3 subunits of E4TF1: a 60-kD subunit (GABPA; 600609), a 53-kD subunit (GABPB1), and a 47-kD subunit (GABPB2). The predicted GABPB1 and GABPB2 subunits contain 383 and 347 amino acids, respectively, and are highly homologous. The N-terminal 332 amino acids of GABPB1 and GABPB2, including 4 tandemly repeated Notch motifs, are identical; the proteins differ at their C termini. Watanabe et al. (1993) stated that all 3 E4TF1 proteins show high homology with the corresponding rat GA-binding proteins.
By PCR of a HeLa cell library using degenerate primers designed from the amino acid sequences of purified GABP proteins, Gugneja et al. (1995) cloned NRF2-beta-1 and -beta-2 and NRF2-gamma-1 and -gamma-2. These variants were originally thought to represent splice variants of 2 separate genes (GABPB1, or NRF2-beta, and GABPB2, or NRF2-gamma, respectively). However, it was later determined that all 4 variants are encoded by a single gene, GABPB (Rosmarin, 2003).
Watanabe et al. (1993) determined that GABPB1 and GABPB2 do not bind DNA, but both associate with the DNA-binding GABPA subunit.
Gugneja et al. (1995) verified DNA-binding activity in the alpha subunit of NRF2. They found that the NRF2-beta or -gamma subunit variants were required for transcriptional activation and that the alpha subunit was transcriptionally inactive. The 4 NRF2-beta and -gamma variants were equally proficient in activating transcription in transfected cells when fused to a GAL4 (602518) DNA-binding domain.
Suzuki et al. (1998) reported that the GABPB variant containing a C-terminal leucine zipper motif, which they called GABP-beta, can homodimerize and form a transcriptionally active heterotetrameric complex with GABPA. The variant lacking this motif, which they called GABP-gamma, can form heterodimers but cannot form transcriptionally active heterotetramers with GABPA. Suzuki et al. (1998) determined that the GABP-beta and GABP-gamma isoforms both stabilize the DNA-binding affinity of GABPA by imparting a slower dissociation rate. Northern and Western blot analyses showed that GABP-beta and GABP-gamma are coexpressed at different ratios in several tissues and established cell lines. The 2 forms bound GABPA competitively in vitro, and cotransfection assays revealed that the ratio of GABP-beta to GABP-gamma affected transcription from a GABP-activated promoter.
Stumpf (2024) mapped the GABPB gene to chromosome 15q21.2 based on an alignment of the GABPB sequence (GenBank AK303901) with the genomic sequence (GRCh38).
Sawada et al. (1995) originally mapped the E4TF1B gene to chromosome 7q11.21 by fluorescence in situ hybridization. However, this region contains a GABPA pseudogene rather than the GABPB gene (Luo et al., 1999; Rosmarin, 2003).
Gugneja, S., Virbasius, J. V., Scarpulla, R. C. Four structurally distinct, non-DNA-binding subunits of human nuclear respiratory factor 2 share a conserved transcriptional activation domain. Molec. Cell. Biol. 15: 102-111, 1995. [PubMed: 7799916] [Full Text: https://doi.org/10.1128/MCB.15.1.102]
Luo, M., Shang, J., Yang, Z., Simkevich, C. P., Jackson, C. L., King, T. C., Rosmarin, A. G. Characterization and localization to chromosome 7 of psi-hGABP-alpha, a human processed pseudogene related to the ets transcription factor, hGABP-alpha. Gene 234: 119-126, 1999. [PubMed: 10393246] [Full Text: https://doi.org/10.1016/s0378-1119(99)00167-5]
Rosmarin, A. G. Personal Communication. Baltimore, Md. 7/11/2003.
Sawada, J., Goto, M., Watanabe, H., Handa, H., Yoshida, M. C. Regional mapping of two subunits of transcription factor E4TF1 to human chromosome. Jpn. J. Cancer Res. 86: 10-12, 1995. [PubMed: 7737900] [Full Text: https://doi.org/10.1111/j.1349-7006.1995.tb02981.x]
Stumpf, A. M. Personal Communication. Baltimore, Md. 04/05/2024.
Suzuki, F., Goto, M., Sawa, C., Ito, S., Watanabe, H., Sawada, J., Handa, H. Functional interactions of transcription factor human GA-binding protein subunits. J. Biol. Chem. 273: 29302-29308, 1998. [PubMed: 9792629] [Full Text: https://doi.org/10.1074/jbc.273.45.29302]
Watanabe, H., Sawada, J., Yano, K.-I., Yamaguchi, K., Goto, M., Handa, H. cDNA cloning of transcription factor E4TF1 subunits with Ets and notch motifs. Molec. Cell. Biol. 13: 1385-1391, 1993. [PubMed: 8441384] [Full Text: https://doi.org/10.1128/mcb.13.3.1385-1391.1993]