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SEPT2 (septin 2)

Identity

Other namesKIAA0158
hNedd5
Pnutl3
HGNC (Hugo) SEPT2
LocusID (NCBI) 4735
Location 2q37.3
Location_base_pair Starts at 242254602 and ends at 242293441 bp from pter ( according to hg19-Feb_2009)  [Mapping]

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.

Protein

 
  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.

Implicated in

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.
  

Other Leukemias implicated (Data extracted from papers in the Atlas)

Leukemias 11q23ChildAMLID1615 11q23ID1030

External links

Nomenclature
HGNC (Hugo)SEPT2   7729
Cards
AtlasSEPT2ID44125ch2q37
Entrez_Gene (NCBI)SEPT2  4735  septin 2
GeneCards (Weizmann)SEPT2
Ensembl (Hinxton)ENSG00000168385 [Gene_View]  chr2:242254602-242293441 [Contig_View]  SEPT2 [Vega]
ICGC DataPortalENSG00000168385
cBioPortalSEPT2
AceView (NCBI)SEPT2
Genatlas (Paris)SEPT2
WikiGenes4735
SOURCE (Princeton)NM_001008491 NM_001008492 NM_001282972 NM_001282973 NM_004404 NM_006155
Genomic and cartography
GoldenPath (UCSC)SEPT2  -  2q37.3   chr2:242254602-242293441 +  2q37.3   [Description]    (hg19-Feb_2009)
EnsemblSEPT2 - 2q37.3 [CytoView]
Mapping of homologs : NCBISEPT2 [Mapview]
OMIM601506   
Gene and transcription
Genbank (Entrez)AA482233 AF038404 AK294563 BC014455 BC033559
RefSeq transcript (Entrez)NM_001008491 NM_001008492 NM_001282972 NM_001282973 NM_004404 NM_006155
RefSeq genomic (Entrez)AC_000134 NC_000002 NC_018913 NT_005403 NW_001838874 NW_004929308
Consensus coding sequences : CCDS (NCBI)SEPT2
Cluster EST : UnigeneHs.721234 [ NCBI ]
CGAP (NCI)Hs.721234
Alternative Splicing : Fast-db (Paris)GSHG0017358
Alternative Splicing GalleryENSG00000168385
Gene ExpressionSEPT2 [ NCBI-GEO ]     SEPT2 [ SEEK ]   SEPT2 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ15019 (Uniprot)
NextProtQ15019  [Medical]
With graphics : InterProQ15019
Splice isoforms : SwissVarQ15019 (Swissvar)
Domains : Interpro (EBI)Cell_div_GTP-bd [organisation]   P-loop_NTPase [organisation]   Septin [organisation]   Septin2 [organisation]  
Related proteins : CluSTrQ15019
Domain families : Pfam (Sanger)Septin (PF00735)   
Domain families : Pfam (NCBI)pfam00735   
DMDM Disease mutations4735
Blocks (Seattle)Q15019
PDB (SRS)2QA5    2QAG    2QNR   
PDB (PDBSum)2QA5    2QAG    2QNR   
PDB (IMB)2QA5    2QAG    2QNR   
PDB (RSDB)2QA5    2QAG    2QNR   
Human Protein AtlasENSG00000168385 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasQ15019
HPRD03297
IPIIPI00014177   IPI00871851   IPI00892518   IPI00894340   IPI00893645   IPI00893788   IPI00893329   IPI00893477   IPI00893096   IPI00893240   IPI00892810   IPI00892932   IPI00892697   IPI00894322   IPI00894457   IPI00894088   IPI00894199   IPI00894283   IPI00894055   IPI00893658   
Protein Interaction databases
DIP (DOE-UCLA)Q15019
IntAct (EBI)Q15019
FunCoupENSG00000168385
BioGRIDSEPT2
InParanoidQ15019
Interologous Interaction database Q15019
IntegromeDBSEPT2
STRING (EMBL)SEPT2
Ontologies - Pathways
Ontology : AmiGOexocyst  condensed chromosome kinetochore  regulation of L-glutamate transport  protein binding  GTP binding  nucleus  nucleolus  cytoplasm  spindle  cell cortex  mitotic nuclear division  smoothened signaling pathway  actin cytoskeleton  enzyme regulator activity  midbody  septin complex  neuron projection development  cleavage furrow  regulation of protein localization  protein complex scaffold  cilium assembly  synapse  perinuclear region of cytoplasm  regulation of catalytic activity  ciliary membrane  extracellular vesicular exosome  
Ontology : EGO-EBIexocyst  condensed chromosome kinetochore  regulation of L-glutamate transport  protein binding  GTP binding  nucleus  nucleolus  cytoplasm  spindle  cell cortex  mitotic nuclear division  smoothened signaling pathway  actin cytoskeleton  enzyme regulator activity  midbody  septin complex  neuron projection development  cleavage furrow  regulation of protein localization  protein complex scaffold  cilium assembly  synapse  perinuclear region of cytoplasm  regulation of catalytic activity  ciliary membrane  extracellular vesicular exosome  
Pathways : KEGGBacterial invasion of epithelial cells   
Protein Interaction DatabaseSEPT2
Wikipedia pathwaysSEPT2
Gene fusion - rearrangments
Rearrangement : TICdbKMT2A [11q23.3]  -  SEPT2 [12p13.2]
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)SEPT2
snp3D : Map Gene to Disease4735
SNP (GeneSNP Utah)SEPT2
SNP : HGBaseSEPT2
Genetic variants : HAPMAPSEPT2
Exome VariantSEPT2
1000_GenomesSEPT2 
ICGC programENSG00000168385 
Somatic Mutations in Cancer : COSMICSEPT2 
CONAN: Copy Number AnalysisSEPT2 
Mutations and Diseases : HGMDSEPT2
Genomic VariantsSEPT2  SEPT2 [DGVbeta]
dbVarSEPT2
ClinVarSEPT2
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM601506   
MedgenSEPT2
GENETestsSEPT2
Disease Genetic AssociationSEPT2
Huge Navigator SEPT2 [HugePedia]  SEPT2 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneSEPT2
Homology/Alignments : Family Browser (UCSC)SEPT2
Phylogenetic Trees/Animal Genes : TreeFamSEPT2
Chemical/Protein Interactions : CTD4735
Chemical/Pharm GKB GenePA31535
Clinical trialSEPT2
Cancer Resource (Charite)ENSG00000168385
Other databases
Probes
Litterature
PubMed70 Pubmed reference(s) in Entrez
CoreMineSEPT2
iHOPSEPT2
OncoSearchSEPT2

Bibliography

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
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written09-2007Nuno Cerveira, Manuel R Teixeira
Department of Genetics, Portuguese Oncology Institute, Rua Dr. Antonio Bernardino de Almeida, 4200-072 Porto, Portugal (MRT)

Citation

This paper should be referenced as such :
Cerveira, N ; Teixeira, MR
SEPT2 (septin 2)
Atlas Genet Cytogenet Oncol Haematol. 2008;12(2):153-155.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/SEPT2ID44125ch2q37.html

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indexed on : Fri Aug 8 11:08:09 CEST 2014

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