Alternative titles; symbols
HGNC Approved Gene Symbol: NUTF2
Cytogenetic location: 16q22.1 Genomic coordinates (GRCh38) : 16:67,846,933-67,872,567 (from NCBI)
Molecular trafficking between the cytoplasm and nucleus occurs through proteinaceous structures called nuclear pore complexes, which span the double membrane of the nuclear envelope and permit both passive diffusion and active transport. Proteins destined for import typically contain a nuclear localization signal (NLS), which is rich in basic residues, and interact with an NLS receptor (e.g., KPNA2; 600685) before docking to the nuclear envelope and interacting with a nucleoporin (e.g., NUP62; 605815). NUTF2 encodes a cytosolic factor for nuclear protein import that interacts with the nuclear pore complex glycoprotein NUP62 (Paschal and Gerace, 1995).
By screening a placenta cDNA library for placental protein-15 (PP15), an inhibitory molecule in the lymphocyte transformation test, Grundmann et al. (1988) isolated a cDNA encoding PP15. The deduced 127-amino acid protein contains a putative ribosome-binding site. Using biochemical purification methods and micropeptide sequencing, followed by PCR, Paschal and Gerace (1995) determined that NTF2 is encoded by the PP15 cDNA.
Stumpf (2021) mapped the NUTF2 gene to chromosome 16q22.1 based on an alignment of the NUTF2 sequence (GenBank BC002348) with the genomic sequence (GRCh38).
By functional analysis in NUP62-depleted cells, Paschal and Gerace (1995) showed that NTF2 is required for nuclear protein import after the association of the NLS ligand with the nuclear envelope. Reconstituting permeabilized cells with NTF2 and RANBP1 (601180), as well as with a 'docking fraction' that probably contained an NLS receptor, showed that these elements all perform distinct and necessary functions for nuclear protein import. Paschal and Gerace (1995) concluded that NTF2 interacts with NUP62 and acts after the docking step in the nuclear protein import pathway.
Using an in vitro nuclear import system, Ribbeck et al. (1998) found evidence that NTF2 is required for the nuclear import and reaccumulation of RAN (601179), a molecule that is depleted from the nucleus as RAN-GTP complexed with exported cargo. By mutation analysis and biochemical studies, they determined that nuclear reaccumulation of RAN is mediated by direct interaction between the 2 proteins and that RAN-GDP is the species bound and transported by NTF2.
Grundmann, U., Nerlich, C., Rein, T., Lottspeich, F., Kupper, H. A. Isolation of cDNA coding for the placental protein 15 (PP15). Nucleic Acids Res. 16: 4721 only, 1988. [PubMed: 3380696] [Full Text: https://doi.org/10.1093/nar/16.10.4721]
Paschal, B. M., Gerace, L. Identification of NTF2, a cytosolic factor for nuclear import that interacts with nuclear pore complex protein p62. J. Cell Biol. 129: 925-937, 1995. [PubMed: 7744965] [Full Text: https://doi.org/10.1083/jcb.129.4.925]
Ribbeck, K., Lipowsky, G., Kent, H. M., Stewart, M., Gorlich, D. NTF2 mediates nuclear import of Ran. EMBO J. 17: 6587-6598, 1998. [PubMed: 9822603] [Full Text: https://doi.org/10.1093/emboj/17.22.6587]
Stumpf, A. M. Personal Communication. Baltimore, Md. 08/13/2021.