Alternative titles; symbols
HGNC Approved Gene Symbol: POM121
Cytogenetic location: 7q11.23 Genomic coordinates (GRCh38): 7:72,879,357-72,951,459 (from NCBI)
Nuclear pore complexes (NPCs) span the inner and outer nuclear membranes and act as gateways that regulate transport of macromolecules across the nuclear envelope. NPCs also influence gene expression, chromatin organization, and inheritance. POM121 is a membrane-bound NPC protein that interacts with other NPC subunits and stabilizes the NPC within the nuclear envelope (Mitchell et al., 2010).
Hallberg et al. (1993) cloned rat Pom121. The deduced 1,199-amino acid protein has a calculated molecular mass of 120.7 kD, but it had an apparent molecular mass of 145 kD by SDS-PAGE. Pom121 has a potential transmembrane domain near its N terminus, and its C-terminal region has characteristics of a nucleoporin (NUP; see 170285), including the presence of a repetitive pentapeptide motif separated by serine- and threonine-rich sequences. Pom121 has several potential phosphorylation and glycosylation sites. Immunofluorescence analysis of buffalo rat liver cells revealed a punctate nuclear rim staining pattern. Immunoelectron microscopy revealed colocalization of Pom121 with nuclear pores.
By sequencing clones obtained from a size-fractionated human brain cDNA library, Ishikawa et al. (1998) cloned POM121, which they designated KIAA0618. The transcript contains several repetitive elements in its 3-prime end, and the deduced 999-amino acid protein shares 57.3% identity with rat Pom121. RT-PCR detected high expression in all human tissues examined.
By searching databases for Pom121 orthologs, followed by 5-prime RACE of HeLa cell total RNA, Funakoshi et al. (2007) cloned full-length human POM121, which they called POM121A. The deduced 1,249-amino acid protein has a transmembrane domain near the N terminus. Database analysis revealed 3 additional POM121 splice variants: 2 encode identical 984-amino acid proteins that are N-terminally truncated and lack the transmembrane domain compared with full-length POM121, and 1 encodes a deduced 989-amino acid protein that is N-terminally truncated and has a short C-terminal extension. Immunohistochemical analysis showed that endogenous full-length POM121 and fluorescence-tagged POM121 were expressed at nuclear speckles. Western blot and mass spectrometric analyses revealed that HeLa cell nuclear envelope fractions contained full-length POM121 and a related protein, POM121C (615754), both of which had apparent molecular masses of approximately 150 kD.
Using small interfering RNA (siRNA), Funakoshi et al. (2007) found that knockdown of either POM121 or POM121C alone caused clustering of NPCs in HeLa cells. Knockdown of both reduced assembly of NPCs on the nuclear envelope, in addition to causing NPC clustering. Deletion analysis revealed that the N-terminal regions of POM121 and POM121C, including the transmembrane domains, were required to target the proteins to NPCs.
Using protein binding assays and domain analyses, Mitchell et al. (2010) found that the N-terminal third of POM121, which is predicted to be in close proximity to the nuclear membrane, interacted directly with the N-terminal beta-propeller regions of the NPC core subunits NUP155 (606694) and NUP160 (607614) in HeLa cells and rat liver nuclei. POM121 did not interact with NUP155 and NUP160 simultaneously. Knockdown of NUP155 in HeLa cells via siRNA disrupted the NPC, causing cytoplasmic distribution of NPC subunits and inner nuclear membrane proteins. Mitchell et al. (2010) concluded that POM121 anchors the NPC core by positioning NUP155 and NUP160 and their binding partners in close proximity to the nuclear membrane.
The NPC assembles twice during the cell cycle: once at the end of mitosis, when the nuclear envelope reforms around the daughter chromosomes, and during interphase on a preexisting nuclear envelope. Funakoshi et al. (2011) stated that POM121 is recruited to sister chromatids early during postmitotic NPC assembly. Using RNA interference with human cell lines, they found that POM121 was also recruited early and was required for assembly of interphase NPCs. Sequence and mutation analyses revealed a cluster of 5 central nuclear localization signals that were required for targeting of POM121 to immature interphase NPCs. This region bound importin-beta (see 602738) via importin-alpha (see 600685), and binding appeared to require the small GTPase RAN (601179). POM121 also interacted with the lamin B receptor (600024) at the inner nuclear membrane in the absence of mature NPCs. Funakoshi et al. (2011) proposed that nuclear targeting of POM121 is followed by interaction of POM121 with inner nuclear membrane proteins, and that POM121 is required to initiate assembly of interphase NPCs.
Funakoshi et al. (2007) determined that the POM121 gene contains 18 exons, including alternate exons 4a and 16a. Exons 1 through 4 are untranslated, and exons 4a and 5 contain alternative translational start codons.
By radiation hybrid analysis, Ishikawa et al. (1998) mapped the POM121 gene to chromosome 7.
By genomic sequence analysis, Funakoshi et al. (2007) mapped the POM121 gene to a POM121 gene cluster of about 3.3 Mb on chromosome 7q11.23. POM121 is the most centromeric POM121 gene in the cluster, which also includes POM121C and POM121B, a nontranscribed pseudogene.
Funakoshi, T., Clever, M., Watanabe, A., Imamoto, N. Localization of Pom121 to the inner nuclear membrane is required for an early step of interphase nuclear pore complex assembly. Molec. Biol. Cell 22: 1058-1069, 2011. [PubMed: 21289085] [Full Text: https://doi.org/10.1091/mbc.E10-07-0641]
Funakoshi, T., Maeshima, K., Yahata, K., Sugano, S., Imamoto, F., Imamoto, N. Two distinct human POM121 genes: requirement for the formation of nuclear pore complexes. FEBS Lett. 581: 4910-4916, 2007. [PubMed: 17900573] [Full Text: https://doi.org/10.1016/j.febslet.2007.09.021]
Hallberg, E., Wozniak, R. W., Blobel, G. An integral membrane protein of the pore membrane domain of the nuclear envelope contains a nucleoporin-like region. J. Cell Biol. 122: 513-521, 1993. [PubMed: 8335683] [Full Text: https://doi.org/10.1083/jcb.122.3.513]
Ishikawa, K., Nagase, T., Suyama, M., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O. Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro. DNA Res. 5: 169-176, 1998. [PubMed: 9734811] [Full Text: https://doi.org/10.1093/dnares/5.3.169]
Mitchell, J. M., Mansfeld, J., Capitanio, J., Kutay, U., Wozniak, R. W. Pom121 links two essential subcomplexes of the nuclear pore complex core to the membrane. J. Cell Biol. 191: 505-521, 2010. [PubMed: 20974814] [Full Text: https://doi.org/10.1083/jcb.201007098]