Alternative titles; symbols
HGNC Approved Gene Symbol: NUP205
Cytogenetic location: 7q33 Genomic coordinates (GRCh38): 7:135,557,917-135,648,753 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 7q33 | ?Nephrotic syndrome, type 13 | 616893 | Autosomal recessive | 3 |
NUP205 is a subunit of the 120-million-Da nuclear pore complex, which functions in active transport of molecules between the nucleus and cytoplasm (Grandi et al., 1997).
By sequencing clones obtained from a size-fractionated KG-1 immature myeloid cell line cDNA library, Nagase et al. (1996) cloned NUP205, which they designated KIAA0225. The deduced protein contains 2,013 amino acids. Northern blot analysis detected NUP205 expression in all tissues and cell lines examined.
Using mass spectrometry to identify proteins that immunoprecipitated with NUP93 (614351), Grandi et al. (1997) identified NUP205. The deduced 2,012-amino acid protein has a calculated molecular mass of 228 kD. NUP205 contains a putative leucine zipper and several potential phosphorylation sites. Database analysis revealed orthologs of NUP205 in C. elegans and S. cerevisiae.
Grandi et al. (1997) found that the interaction of NUP93 with NUP205 appeared to be stable. During nuclear pore disassembly in mitotic Xenopus eggs, the Nup93-Nup205 subcomplex localized to cytosol.
Using an in vitro nuclear pore reconstitution assay, followed by protein interaction assays, Western blot analysis, and peptide sequencing, Miller et al. (2000) found that Xenopus Nup188 (615587) interacted directly with Nup93 and Nup205 in a specific subcomplex within the nuclear pore complex (NPC). Based on the similarity of these proteins with their yeast orthologs, for which function had been inferred, Miller et al. (2000) predicted that NUP188, NUP93, and NUP205 form an essential scaffold for formation of the nuclear pore.
Hawryluk-Gara et al. (2005) identified human NUP205, NUP93, NUP155 (606694), and NUP53 (NUP35; 608140) as components of a nucleoporin subcomplex. In vitro protein binding assays showed that both NUP53 and NUP93 could bind NUP155 and NUP205 and that NUP53 and NUP93 could bind each other. Small interfering RNA (siRNA)-mediated knockdown of NUP53 in HeLa cells resulted in slow growth, abnormal nuclear morphology, and loss of NUP93, NUP155, and NUP205 proteins. Knockdown of NUP53 also reduced the level of MAD1 (MXD1; 600021), which binds to NPCs during interphase. Depletion of NUP93 via siRNA resulted in changes similar to those seen with NUP53 depletion, except that NUP93 depletion had no effect on MAD1 level.
By immunoprecipitation analysis, Theerthagiri et al. (2010) demonstrated that Nup93 formed 2 distinct complexes, one with Nup188 and the other with Nup205, in Xenopus egg extracts.
In fetal rat kidney, Braun et al. (2016) found expression of the Nup205 gene in developing podocytes at the capillary loop stage during glomerular development.
By radiation hybrid and human-rodent hybrid analysis, Nagase et al. (1996) mapped the NUP205 gene to chromosome 7. Hartz (2011) mapped the NUP205 gene to chromosome 7q33 based on an alignment of the NUP205 sequence (GenBank D86978) with the genomic sequence (GRCh37).
In 2 sibs, born of unrelated Turkish parents, with nephrotic syndrome-13 (NPHS13; 616893), Braun et al. (2016) identified a homozygous missense mutation in the NUP205 gene (F1995S; 614352.0001). The mutation, which was found by genetic mapping and whole-exome sequencing, segregated with the disorder in the family. In vitro functional expression studies showed that the mutation abrogated the interaction with NUP93 (614351).
In 2 sibs, born of unrelated Turkish parents (family A1733), with nephrotic syndrome-13 (NPHS13; 616893), Braun et al. (2016) identified a homozygous c.5984T-C transition (c.5984T-C, NM_015135.2) in exon 43 of the NUP205 gene, resulting in a phe1995-to-ser (F1995S) substitution at a highly conserved residue. The mutation, which was found by genetic mapping and whole-exome sequencing, segregated with the disorder in the family. In vitro functional expression studies showed that the mutation abrogated the interaction with NUP93 (614351).
Braun, D. A., Sadowski, C. E., Kohl, S., Lovric, S., Astrinidis, S. A., Pabst, W. L., Gee, H. Y., Ashraf, S., Lawson, J. A., Shril, S., Airik,, M., Tan, W., and 15 others. Mutations in nuclear pore genes NUP93, NUP205 and XPO5 cause steroid-resistant nephrotic syndrome. Nature Genet. 48: 457-465, 2016. [PubMed: 26878725] [Full Text: https://doi.org/10.1038/ng.3512]
Grandi, P., Dang, T., Pane, N., Shevchenko, A., Mann, M., Forbes, D., Hurt, E. Nup93, a vertebrate homologue of yeast Nic96p, forms a complex with a novel 205-kDa protein and is required for correct nuclear pore assembly. Molec. Biol. Cell 8: 2017-2038, 1997. [PubMed: 9348540] [Full Text: https://doi.org/10.1091/mbc.8.10.2017]
Hartz, P. A. Personal Communication. Baltimore, Md. 9/15/2011.
Hawryluk-Gara, L. A., Shibuya, E. K., Wozniak, R. W. Vertebrate Nup53 interacts with the nuclear lamina and is required for the assembly of a Nup93-containing complex. Molec. Biol. Cell 16: 2382-2394, 2005. [PubMed: 15703211] [Full Text: https://doi.org/10.1091/mbc.e04-10-0857]
Miller, B. R., Powers, M., Park, M., Fischer, W., Forbes, D. J. Identification of a new vertebrate nucleoporin, Nup188, with the use of a novel organelle trap assay. Molec. Biol. Cell 11: 3381-3396, 2000. [PubMed: 11029043] [Full Text: https://doi.org/10.1091/mbc.11.10.3381]
Nagase, T., Seki, N., Ishikawa, K., Ohira, M., Kawarabayasi, Y., Ohara, O., Tanaka, A., Kotani, H., Miyajima, N., Nomura, N. Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain. DNA Res. 3: 321-329, 1996. [PubMed: 9039502] [Full Text: https://doi.org/10.1093/dnares/3.5.321]
Theerthagiri, G., Eisenhardt, N., Schwarz, H., Antonin, W. The nucleoporin Nup188 controls passage of membrane proteins across the nuclear pore complex. J. Cell Biol. 189: 1129-1142, 2010. [PubMed: 20566687] [Full Text: https://doi.org/10.1083/jcb.200912045]