| Gene Name | POM121 (POM121 transmembrane nucleoporin) |
| Location | 7q11.23 |
| Protein | 1249 amino acids (aa); from N-term to C-term, POM121 is made of a cisternal side domain (aa 1-34), a transmembrane (Helical) domain (aa 35-55), and a pore side domain (aa 56-1249), and contains: a region for inner nuclear membrane - outer nuclear membrane fusion: aa 1-129, a nuclear envelope binding region: aa 137-265; a Pro-rich region: aa 144-214; a Ser-rich region: aa 378-445; a Thr-rich region: aa 751-947; there are also phosphoserines aa: 345; 351; 371; 393; 5 nuclear localization signals (NLS): aa 321-323 (KKR); 339-342 (KRRR); 387-390 (KRSR); 453-456 (KKIR); 504-507 (RKRK); and xFxFG motifs (repeats based on cores containing Phenylalanine and Glycine (X denotes any amino acid) separated by linkers rich in serines and threonines): aa 703-707; 835-839; 861-865; 881-885; 916-922; 994-998; 1096-1100; 1126-1130. These FG repeats are thought to bind transport receptors such as importin beta and transportin.
POM121 anchors the nuclear pore complex (NPC) to the nuclear envelope; the N-terminal domain required for nuclear targeting, the N-terminal and transmembrane domain are required for NPC targeting; POM121 makes complexes with NUP210 (nucleoporin 210kDa, also called GP210, 3p25.1).
Nuclear pore complexes (NPCs) assemble 1) at the end of mitosis during nuclear envelope reformation (where the nuclear envelope has not fully formed, and NPCs are inserted into chromatin-bound ER sheets), and 2) into an intact nuclear envelope during interphase when the nuclear envelope is completely closed and the process has to be coordinated across the highly organized structure with separated inner nuclear membrane and outer nuclear membrane.
Interphase NPC formation is initiated by recruitment of POM121 followed by the incorporation of the Nup107-160 complex and POM121 is required for interphase NPC formation (the order is reverse in post-mitotic NPC formation, and POM121 is dispensable).
POM121 and SUN1 (Sad1 and UNC84 domain containing 1, 7p22.3) promote early steps of interphase NPC assembly, prior to the incorporation of the Nup107-160 complex (made of NUP160, NUP133, NUP107, NUP98, NUP85, NUP43, NUP37, SEC13, and SEH1L), which interacts with POM121.
POM121 is required for the inner nuclear membrane (INM) - outer nuclear membrane fusion (ONM) and NPC formation. POM121 region aa 1-129 is sufficient to induce bending of the ONM and INM toward each other.
POM121 localized to the inner nuclear membrane. The 5 nuclear localization signals of POM121 have an active role in its targeting to nuclear pore complexes during interphase. Interaction of POM121 with importin beta is dependent on direct binding of importin alpha to the nuclear localization signals of POM121. POM121 is transported into the nucleus through nuclear pores by a mechanism involving RAN (12q24.33) and importins and subsequently binds to inner nuclear membrane proteins prior to its incorporation into the nuclear pore complexes.
POM121 contains a nuclear envelope-binding region involved in nuclear pore complex targeting. The nuclear envelope-binding domain is involved in postmitotic nuclear pore complex assembly, The nuclear envelope-binding region of POM121 interacts with LBR (lamin B receptor, 1q42.12), a component of the inner nuclear membrane.
The chromatin-binding protein AHCTF1 (AT hook containing transcription factor 1, also called ELYS, 1q44) targets nuclear pore assembly to the surface of chromosomes as nuclei form at the end of mitosis (Koser et al., 2005; Funakoshi et al., 2011; Talamas and Hetzer, 2011). |
| Pax5: the guardian of B cell identity and function. |
| Cobaleda C, Schebesta A, Delogu A, Busslinger M. |
| Nat Immunol. 2007 May;8(5):463-70. |
| PMID 17440452 |
| |
| Wide diversity of PAX5 alterations in B-ALL: a Groupe Francophone de Cytogenetique Hematologique study. |
| Coyaud E, Struski S, Prade N, Familiades J, Eichner R, Quelen C, Bousquet M, Mugneret F, Talmant P, Pages MP, Lefebvre C, Penther D, Lippert E, Nadal N, Taviaux S, Poppe B, Luquet I, Baranger L, Eclache V, Radford I, Barin C, Mozziconacci MJ, Lafage-Pochitaloff M, Antoine-Poirel H, Charrin C, Perot C, Terre C, Brousset P, Dastugue N, Broccardo C. |
| Blood. 2010 Apr 15;115(15):3089-97. doi: 10.1182/blood-2009-07-234229. Epub 2010 Feb 16. |
| PMID 20160164 |
| |
| Localization of Pom121 to the inner nuclear membrane is required for an early step of interphase nuclear pore complex assembly. |
| Funakoshi T, Clever M, Watanabe A, Imamoto N. |
| Mol Biol Cell. 2011 Apr;22(7):1058-69. doi: 10.1091/mbc.E10-07-0641. Epub 2011 Feb 2. |
| PMID 21289085 |
| |
| Pax5 induces V-to-DJ rearrangements and locus contraction of the immunoglobulin heavy-chain gene. |
| Fuxa M, Skok J, Souabni A, Salvagiotto G, Roldan E, Busslinger M. |
| Genes Dev. 2004 Feb 15;18(4):411-22. |
| PMID 15004008 |
| |
| B cell-specific loss of histone 3 lysine 9 methylation in the V(H) locus depends on Pax5. |
| Johnson K, Pflugh DL, Yu D, Hesslein DG, Lin KI, Bothwell AL, Thomas-Tikhonenko A, Schatz DG, Calame K. |
| Nat Immunol. 2004 Aug;5(8):853-61. Epub 2004 Jul 18. |
| PMID 15258579 |
| |
| The nuclear pore complex becomes alive: new insights into its dynamics and involvement in different cellular processes. |
| Koser J, Maco B, Aebi U, Fahrenkrog B. |
| Atlas Genet Cytogenet Oncol Haematol. 2005; 9(2):191-209. http://atlasgeneticsoncology.org/Deep/NuclearPoreComplID20048.html |
| |
| Pax5: a master regulator of B cell development and leukemogenesis. |
| Medvedovic J, Ebert A, Tagoh H, Busslinger M. |
| Adv Immunol. 2011;111:179-206. doi: 10.1016/B978-0-12-385991-4.00005-2. (REVIEW) |
| PMID 21970955 |
| |
| Incidence and diversity of PAX5 fusion genes in childhood acute lymphoblastic leukemia. |
| Nebral K, Denk D, Attarbaschi A, Konig M, Mann G, Haas OA, Strehl S. |
| Leukemia. 2009 Jan;23(1):134-43. doi: 10.1038/leu.2008.306. Epub 2008 Nov 20. |
| PMID 19020546 |
| |
| POM121 and Sun1 play a role in early steps of interphase NPC assembly. |
| Talamas JA, Hetzer MW. |
| J Cell Biol. 2011 Jul 11;194(1):27-37. doi: 10.1083/jcb.201012154. Epub 2011 Jul 4. |
| PMID 21727197 |
| |
| Transcription factor Pax5 (BSAP) transactivates the RAG-mediated V(H)-to-DJ(H) rearrangement of immunoglobulin genes. |
| Zhang Z, Espinoza CR, Yu Z, Stephan R, He T, Williams GS, Burrows PD, Hagman J, Feeney AJ, Cooper MD. |
| Nat Immunol. 2006 Jun;7(6):616-24. Epub 2006 May 7. |
| PMID 16680144 |
| |
