Last update 19 Sep 2024

SEPTIN6

Last update 19 Sep 2024

Basic Info

Synonyms

KIAA0128, MGC16619, MGC20339

+ [6]

Introduction

Filament-forming cytoskeletal GTPase. Required for normal organization of the actin cytoskeleton. Involved in cytokinesis. May play a role in HCV RNA replication. Forms a filamentous structure with SEPTIN12, SEPTIN6, SEPTIN2 and probably SEPTIN4 at the sperm annulus which is required for the structural integrity and motility of the sperm tail during postmeiotic differentiation (PubMed:25588830).

Drugs associated with SEPTIN6

REM-127

Target

SEPTIN6

Mechanism

SEPTIN6 modulators

Active Org.

reMYND NV

Originator Org.

reMYND NV

Active Indication

Alzheimer Disease

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with SEPTIN6

100 Translational Medicine associated with SEPTIN6

0 Patents (Medical) associated with SEPTIN6

137

Literatures (Medical) associated with SEPTIN6

25 Jun 2024·Blood Advances

Optimized cytogenetic risk-group stratification of KMT2A-rearranged pediatric acute myeloid leukemia

Article

Author: Tierens, Anne ; Polychronopoulou, Sophia ; Gamis, Alan ; Leverger, Guy ; Kaspers, Gertjan J L ; Rasche, Mareike ; Hasle, Henrik ; Miyamura, Takako ; Elitzur, Sarah ; Bart-Delabesse, Emmanuelle ; Stary, Jan ; Kelaidi, Charikleia ; Buldini, Barbara ; Rubnitz, Jeffrey E ; Dworzak, Michael N ; Aplenc, Richard ; Jiang, Yilin ; Guest, Erin ; Zwaan, C Michel ; Goemans, Bianca F ; Harrison, Christine J ; van Weelderen, Romy E ; Ha, Shau-Yin ; Fernández Navarro, José M ; Gerbing, Robert B ; Tomizawa, Daisuke ; Klein, Kim ; Norén-Nyström, Ulrika ; Locatelli, Franco ; De Moerloose, Barbara ; Arad-Cohen, Nira ; Lapillonne, Hélène ; de Groot-Kruseman, Hester A ; Abrahamsson, Jonas ; Alonzo, Todd

AbstractA comprehensive international consensus on the cytogenetic risk-group stratification of KMT2A-rearranged (KMT2A-r) pediatric acute myeloid leukemia (AML) is lacking. This retrospective (2005-2016) International Berlin-Frankfurt-Münster Study Group study on 1256 children with KMT2A-r AML aims to validate the prognostic value of established recurring KMT2A fusions and additional cytogenetic aberrations (ACAs) and to define additional, recurring KMT2A fusions and ACAs, evaluating their prognostic relevance. Compared with our previous study, 3 additional, recurring KMT2A-r groups were defined: Xq24/KMT2A::SEPT6, 1p32/KMT2A::EPS15, and 17q12/t(11;17)(q23;q12). Across 13 KMT2A-r groups, 5-year event-free survival probabilities varied significantly (21.8%-76.2%; P < .01). ACAs occurred in 46.8% of 1200 patients with complete karyotypes, correlating with inferior overall survival (56.8% vs 67.9%; P < .01). Multivariable analyses confirmed independent associations of 4q21/KMT2A::AFF1, 6q27/KMT2A::AFDN, 10p12/KMT2A::MLLT10, 10p11.2/KMT2A::ABI1, and 19p13.3/KMT2A::MLLT1 with adverse outcomes, but not those of 1q21/KMT2A::MLLT11 and trisomy 19 with favorable and adverse outcomes, respectively. Newly identified ACAs with independent adverse prognoses were monosomy 10, trisomies 1, 6, 16, and X, add(12p), and del(9q). Among patients with 9p22/KMT2A::MLLT3, the independent association of French-American-British–type M5 with favorable outcomes was confirmed, and those of trisomy 6 and measurable residual disease at end of induction with adverse outcomes were identified. We provide evidence to incorporate 5 adverse-risk KMT2A fusions into the cytogenetic risk-group stratification of KMT2A-r pediatric AML, to revise the favorable-risk classification of 1q21/KMT2A::MLLT11 to intermediate risk, and to refine the risk-stratification of 9p22/KMT2A::MLLT3 AML. Future studies should validate the associations between the newly identified ACAs and outcomes and unravel the underlying biological pathogenesis of KMT2A fusions and ACAs.

01 May 2024·Gene

Genome-wide 5′-C-phosphate-G-3′ methylation patterns reveal the effect of heat stress on the altered semen quality in Bubalus bubalis

Article

Author: Mukesh, Manishi ; Gurao, Ankita ; Ranganatha Sriranga, Karpenahalli ; Chitkara, Meenakshi ; Shivanand Dige, Mahesh ; Singh Kataria, Ranjit ; Vasisth, Rashi ; Kumar, Gautam ; Singh, Ravinder ; Singh, Pawan

Semen production and quality are closely correlated with different environmental factors in bovines, particularly for the buffalo (Bubalus bubalis) bulls reared under tropical and sub-tropical conditions. Factors including DNA methylation patterns, an intricate process in sperm cells, have an impact on the production of quality semen in buffalo bulls under abiotic stress conditions. The present study was conducted to identify DNA methylome signatures for semen quality in Murrah buffalo bulls, acclaimed as a major dairy breed globally, under summer heat stress. Based on semen quality parameters that significantly varied between the two groups over the seasons, the breeding bulls were classified into seasonally affected (SA = 6) and seasonally non-affected (SNA = 6) categories. DNA was isolated from purified sperm cells and sequenced using the RRBS (Reduced Representation Bisulfite Sequencing) technique for genome-wide methylome data generation. During the hot summer months, the physiological parameters such as scrotal surface temperature, rectal temperature, and respiration rate for both the SA and SNA bulls were significantly higher in the afternoon than in the morning. Whereas, the global CpG% of SA bulls was positively correlated with the afternoon's scrotal surface and rectal temperature. The RRBS results conveyed differentially methylated cytosines in the promoter region of the genes encoding the channels responsible for Ca²⁺ exchange, NPTN, Ca²⁺ activated chloride channels, ANO1, and a few structure-related units such as septins (SEPT4 and SEPT6), SPATA, etc. Additionally, the hypermethylated set of genes in SA was significantly enriched for pathways such as the FOXO signaling pathway and oocyte meiosis. The methylation patterns suggest promoter methylation in the genes regulating the sperm structure as well as surface transporters, which could contribute to the reduced semen quality in the Murrah buffalo bulls during the season-related heat stress.

01 Oct 2023·Acta crystallographica. Section D, Structural biology

X-ray structure of the metastable SEPT14-SEPT7 coiled coil reveals a hendecad region crucial for heterodimerization.

Article

Author: Crump, Matthew P ; Garratt, Richard C ; Woolfson, Derek N ; Cavini, Italo A ; D'Muniz Pereira, Humberto ; Winter, Ashley J

Septins are membrane-associated, GTP-binding proteins that are present in most eukaryotes. They polymerize to play important roles as scaffolds and/or diffusion barriers as part of the cytoskeleton. α-Helical coiled-coil domains are believed to contribute to septin assembly, and those observed in both human SEPT6 and SEPT8 form antiparallel homodimers. These are not compatible with their parallel heterodimeric organization expected from the current model for protofilament assembly, but they could explain the interfilament cross-bridges observed by microscopy. Here, the first structure of a heterodimeric septin coiled coil is presented, that between SEPT14 and SEPT7; the former is a SEPT6/SEPT8 homolog. This new structure is parallel, with two long helices that are axially shifted by a full helical turn with reference to their sequence alignment. The structure also has unusual knobs-into-holes packing of side chains. Both standard seven-residue (heptad) and the less common 11-residue (hendecad) repeats are present, creating two distinct regions with opposite supercoiling, which gives rise to an overall straight coiled coil. Part of the hendecad region is required for heterodimerization and therefore may be crucial for selective septin recognition. These unconventional sequences and structural features produce a metastable heterocomplex that nonetheless has enough specificity to promote correct protofilament assembly. For instance, the lack of supercoiling may facilitate unzipping and transitioning to the antiparallel homodimeric state.

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