SEPT2 (septin 2)
2007-09-01 Nuno Cerveira , Manuel R Teixeira AffiliationDepartment of Genetics, Portuguese Oncology Institute, Rua Dr. Antonio Bernardino de Almeida, 4200-072 Porto, Portugal (MRT)
Identity
HGNC
LOCATION
2q37.3
LOCUSID
ALIAS
DIFF6,NEDD-5,NEDD5,Pnutl3,SEPT2,hNedd5
FUSION GENES
DNA/RNA
Genomic structure of published SEPT2 alternatively spliced transcripts. Boxes indicate exons with coding regions in red. Exons are tentatively positioned in relative genomic order with overlapping exons indicating identical sequences.
Description
The SEPT2 gene has 14 exons.
Transcription
SEPT2 has four types of transcripts with 3.6 kb, 3.5 kb, 3.4 kb and 3.3 kb encoding the same protein, as a result of alternative splicing.
Proteins
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 Alzheimers disease suggesting a role in neurodegeneration.
Implicated in
Entity name
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
Hybrid gene
MLL SEPT2. MLL exon 6 or 7 fused with SEPT2 exon 3.
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.
Fusion 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.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 16682951 | 2006 | SEPT2 is a new fusion partner of MLL in acute myeloid leukemia with t(2;11)(q37;q23). | Cerveira N et al |
| 15915442 | 2005 | Expression profiling the human septin gene family. | Hall PA et al |
| 15495264 | 2004 | The pathobiology of the septin gene family. | Hall PA et al |
| 9811347 | 1998 | Identification of septins in neurofibrillary tangles in Alzheimer's disease. | Kinoshita A et al |
| 15774761 | 2005 | A mitotic septin scaffold required for Mammalian chromosome congression and segregation. | Spiliotis ET et al |
| 17574968 | 2007 | 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 et al |
Citation
Nuno Cerveira ; Manuel R Teixeira
SEPT2 (septin 2)
Atlas Genet Cytogenet Oncol Haematol. 2007-09-01
Online version: http://atlasgeneticsoncology.org/gene/44125/sept2
