Alternative titles; symbols
HGNC Approved Gene Symbol: AKAP8L
Cytogenetic location: 19p13.12 Genomic coordinates (GRCh38) : 19:15,380,050-15,418,988 (from NCBI)
By searching for sequences similar to AKAP95 (AKAP8; 604692), followed by 5-prime RACE of a skeletal muscle cDNA library and screening an amnion cell cDNA library, Orstavik et al. (2000) cloned AKAP8L, which they designated HA95. The deduced 646-amino acid protein shares 61% homology with AKAP95. Northern blot analysis showed ubiquitous and uniform expression of a 5.0-kb HA95 transcript. The N-terminal half of HA95 localized to the nucleus during interphase in a transfected human lymphoma cell line.
Seki et al. (2000) cloned AKAP8L, which they designated NAKAP95, from a fetal brain cDNA library. The deduced 646-amino acid protein shares 30% identity with AKAP95. Both contain 2 C2H2-type zinc finger motifs at similar positions and a nuclear localization signal, but NAKAP95 lacks the protein kinase A (PKA; see 176911)-binding motif found in AKAP95. PCR analysis detected NAPAK95 in all tissues examined.
Using the C-terminal domain of RNA helicase A (RHA, or DDX9; 603115) as bait in a yeast 2-hybrid screen of a leukocyte cDNA library, followed by screening a T-cell lymphoma cell line, Westberg et al. (2000) cloned AKAP8L, which they designated HAP95. The predicted protein has a calculated molecular mass of 72 kD, but SDS-PAGE showed an apparent molecular mass of about 100 kD. The N terminus of HAP95 contains both tandem and nontandem YG dipeptide repeats, followed by 3 FG repeats and a central nuclear localization signal. The C-terminal half contains 2 zinc finger motifs and 2 proline-rich SH3-binding domains. Northern blot analysis detected transcripts of 2.0 and 4.0 kb in all cell lines examined. Fluorescence-tagged HAP95 primarily localized to the nucleus of transfected HeLa cells, with exclusion from nucleoli. Heterokaryon assays indicated that HAP95 shuttles between the nucleus and cytoplasm.
By immunoprecipitation of epitope-tagged proteins, Orstavik et al. (2000) found that HA95 interacted with itself, but not with AKAP95.
By coimmunoprecipitation of transfected HeLa cells, Westberg et al. (2000) confirmed that HAP95 interacts with the C-terminal domain of RHA. HAP95 also interacted with the type D retrovirus constitutive transport element (CTE), which mediates nuclear export of unspliced viral transcripts, in transfected human embryonic kidney cells. CTE RNA immunoprecipitated with HAP95 and with TAP (NXF1; 602647). HAP95 overexpression upregulated CTE-dependent gene expression, but it had no effect on general gene expression or expression mediated by the Rev/Rev response element of human immunodeficiency virus-1.
Using a yeast 2-hybrid screen, Sayer et al. (2005) found that mouse Hypa (PRPF40A; 612941) interacted with human NAKAP. Deletion mapping indicated that the binding occurred via a proline-rich domain of NAKAP and the WW domain of Hypa. In human embryonic kidney cells, NAKAP and HYPA localized within the nucleus and copurified with the nuclear matrix. NAKAP associated with HYPA in normal human brain, and both proteins copurified with a portion of huntingtin (613004) protein in Huntington disease (143100) brain.
Orstavik et al. (2000) determined that the coding region of the AKAP8L gene contains 14 exons and spans about 37 kb.
By genomic sequence analysis, Orstavik et al. (2000) mapped the AKAP8L gene maps to chromosome 19p13.1 immediately upstream of the AKAP95 gene. The 2 genes are oriented in tandem on the same DNA strand and lie about 280 bp apart.
By somatic cell hybrid and radiation hybrid analyses, Seki et al. (2000) mapped the AKAP8L gene to chromosome 19p13.12-p13.11.
Orstavik, S., Eide, T., Collas, P., Han, I., Tasken, K., Kieff, E., Jahnsen, T., Skalhegg, B. S. Identification, cloning and characterization of a novel nuclear protein, HA95, homologous to A-kinase anchoring protein 95. Biol. Cell 92: 27-37, 2000. [PubMed: 10761695] [Full Text: https://doi.org/10.1016/s0248-4900(00)88761-4]
Sayer, J. A., Manczak, M., Akileswaran, L., Reddy, P. H., Coghlan, V. M. Interaction of the nuclear matrix protein NAKAP with HypA and huntingtin: implications for nuclear toxicity in Huntington's disease pathogenesis. Neuromolec. Med. 7: 297-310, 2005. [PubMed: 16391387] [Full Text: https://doi.org/10.1385/NMM:7:4:297]
Seki, N., Ueki, N., Yano, K., Saito, T., Masuho, Y., Muramatsu, M. cDNA cloning of a novel human gene NAKAP95, neighbor of A-kinase anchoring protein 95 (AKAP95) on chromosome 19p13.11-p13.12 region. J. Hum. Genet. 45: 31-37, 2000. [PubMed: 10697960] [Full Text: https://doi.org/10.1007/s100380070040]
Westberg, C., Yang, J.-P., Tang, H., Reddy, T. R., Wong-Staal, F. A novel shuttle protein binds to RNA helicase A and activates the retroviral constitutive transport element. J. Biol. Chem. 275: 21396-21401, 2000. [PubMed: 10748171] [Full Text: https://doi.org/10.1074/jbc.M909887199]