| |  |
| |
| | The SEPT2 protein showing the localization of the three function-defining domains: a P loop-based GTP-binding domain flanked by a polybasic domain and the coiled-coil-region. |
| |
| Description | SEPT2 belongs to an evolutionarily conserved family of genes that encode a P loop-based GTP-binding domain flanked by a polybasic domain and (usually) a coiled-coil region, and assemble into homo- and hetero-oligomers and filaments with key roles in cell division cytoskeletal dynamics and secretion. The SEPT2 gene codes for a protein with 361 amino acids and a molecular weight of 41.5 kDa. |
| Expression | SEPT2 was identified as a gene expressed in early embryonic mouse brain and down-regulated during development. It is ubiquitously expressed in cell lines and tissues with the highest protein levels found in brain tissue. |
| Localisation | The SEPT2 protein, like other septin family members, is thought to be cytoplasmic. SEPT2 co-localises with actin filaments in interphase cells, and in dividing cells concentrates at the cleavage furrow. |
| Function | SEPT2 is a multifunctional protein that was shown to be required for cytokinesis and to bind actin and associate with focal adhesions. Recent data support the idea that SEPT2 can have a role in chromosome congression and segregation. Additional functions have also been suggested; for instance, in rat brain lysates SEPT2 is part of a multi-septin complex that interacts with the exocyst complex, which plays a role in secretion and neurite outgrowth. SEPT2 has also been localised to senile plaques of brains in patients with Alzheimer's disease suggesting a role in neurodegeneration. |
| Homology | The SEPT2 protein belongs to an evolutionarily family of proteins with at least 14 members and shares a very high homology with septin 1, septin 4 and septin 5. |
| Entity | Acute myeloid leukemia |
| Disease | Therapy-related AML-M2 and AML-M4 |
| Prognosis | To date, the prognosis of acute leukaemia patients with the MLL-SEPT2 fusion is not known. |
| Cytogenetics | t(2;11)(q37;q23) |
| |  |
| |
| Schematic representation of the known MLL-SEPT6 genomic breakpoints as a result of the t(2;11)(q37;q23) translocation. To date, two different fusions between MLL and SEPT2 have been reported:
A: MLL intron 6 fused with SEPT2 intron 2, and
B: MLL intron 7 fused with SEPT2 intron 2. |
| |
| Hybrid/Mutated Gene | MLLSEPT2. MLL exon 6 or 7 fused with SEPT2 exon 3. |
| Abnormal Protein | The N-terminal region of the MLL protein, including the AT hook, SNL-1, SNL-2 and DNA methyltransferase domains, is fused to almost the entire open-reading frame of SEPT2, containing all the three septin function-defining domains, except for the first three aminoacids. So far, no studies regarding the MLL-SEPT2 localization and function in the leukemic cell were performed. |
| |  |
| |
| Structure of the normal MLL and SEPT2 proteins and the resulting MLL-SEPT2 fusion protein. |
| Oncogenesis | Although the presently available data suggest that the involvement of septins in MLL-related leukemia is only related to their capacity to oligomerize, there is some evidence that altered expression of SEPT2 may underlie the development of aneuploidy. |
| | |
| Identification of septins in neurofibrillary tangles in Alzheimer's disease. |
| Kinoshita A, Kinoshita M, Akiyama H, Tomimoto H, Akiguchi I, Kumar S, Noda M, Kimura J |
| The American journal of pathology. 1998 ; 153 (5) : 1551-1560. |
| PMID 9811347 |
| |
| The pathobiology of the septin gene family. |
| Hall PA, Russell SE |
| The Journal of pathology. 2004 ; 204 (4) : 489-505. |
| PMID 15495264 |
| |
| Expression profiling the human septin gene family. |
| Hall PA, Jung K, Hillan KJ, Russell SE |
| The Journal of pathology. 2005 ; 206 (3) : 269-278. |
| PMID 15915442 |
| |
| A mitotic septin scaffold required for Mammalian chromosome congression and segregation. |
| Spiliotis ET, Kinoshita M, Nelson WJ |
| Science (New York, N.Y.). 2005 ; 307 (5716) : 1781-1785. |
| PMID 15774761 |
| |
| SEPT2 is a new fusion partner of MLL in acute myeloid leukemia with t(2;11)(q37;q23). |
| Cerveira N, Correia C, Bizarro S, Pinto C, Lisboa S, Mariz JM, Marques M, Teixeira MR |
| Oncogene. 2006 ; 25 (45) : 6147-6152. |
| PMID 16682951 |
| |
| A new subtype of MLL-SEPT2 fusion transcript in therapy-related acute myeloid leukemia with t(2;11)(q37;q23): a case report and literature review. |
| van Binsbergen E, de Weerdt O, Buijs A |
| Cancer genetics and cytogenetics. 2007 ; 176 (1) : 72-75. |
| PMID 17574968 |
| |
