GANP: is a member of the SAC3 family of nuclear export factors. In combination with ENY2, PCID2 and centrins, forms the TREX-2 complex that links transcription/ processing with nuclear mRNA export. GANP, required to recruit ENY2 to nuclear pore complexes (NPCs), requires both its CID and MCM3AP domains, together with nucleoporin Nup153, for recruitment to NPCs. The MCM3AP domain, corresponding to the carboxy-terminal 721 amino acids of GANP, shows homology with the Gcn5-related N acetyltransferase superfamily. The protein MCM3AP is encoded entirely within the 3¿ region of the GANP gene. MCM3AP transcription begins within intron 16 of GANP immediately upstream of the first MCM3AP exon, where NF-IL6, AP-1, NF-¿B, and p53 consensus transcription factor binding sites are located. In contrast, the GANP promoter region contains consensus transcription factor binding sites for E2F, E-box, BSAP, and PU.1. MCM3AP interacts with MCM3, which it can acetylate weakly in vivo. GANP is required for efficient mRNA nuclear export: GANP depletion results in the nuclear accumulation of poly(A)+RNA. It interacts via its N-terminal FG repeat domain with the mRNA export factor NXF1. GANP plays a role in the immune response: antibodies from mice deficient for GANP have reduced affinities against T-cell dependent antigens and a lower frequency of variable region somatic mutation. GANP expression is markedly decreased in malignant glioma (MG) with a poor prognosis, consistently lower than that observed in anaplastic astrocytomas. Significant decreases in GANP expression are associated with hyperploidy and chromosomal instability
Protein type: Karyopherin; Acetyltransferase
Chromosomal Location of Human Ortholog: 21q22.3
Cellular Component: nucleoplasm; nuclear membrane; cytoplasm; nuclear pore; nucleus; cytosol
Molecular Function: DNA binding; transferase activity, transferring acyl groups
Biological Process: mRNA transport; protein import into nucleus; immune system process; DNA replication
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