The reference OMIM entry for this protein is 300683

Septin 6; sept6
Sep2, drosophila, homolog of; sep2
Kiaa0128 sept6/mll fusion gene, included

DESCRIPTION

Septins, such as SEPT6, are conserved GTP-binding proteins that function as dynamic, regulatable scaffolds for the recruitment of other proteins. They are involved in membrane dynamics, vesicle trafficking, apoptosis, and cytoskeletal remodeling (Kim et al., 2007).

CLONING

By screening a myeloid cell line cDNA library for cDNAs encoding large proteins, Nagase et al. (1995) cloned SEPT6, which they called KIAA0128. The deduced 424-amino acid protein shares 40% identity with CDC10 (SEPT7; 603151) and contains an ATP/GTP-binding site motif. Northern blot analysis detected nearly ubiquitous expression, with highest level in thymus.

GENE FUNCTION

Low and Macara (2006) noted that specific combinations of septins can hetero-oligomerize and form filaments in vitro and in vivo. Using fluorescence resonance energy transfer, size exclusion chromatography, and multi-angle light scattering analyses, they characterized the complex formed by SEPT2 (601506), SEPT6, and SEPT7. SEPT6 and SEPT7 interacted through a parallel coiled-coil domain, and SEPT2 interacted with SEPT6 through its C-terminal coiled-coil domain. By yeast 2-hybrid screening, Kim et al. (2007) found that the hepatitis C virus (HCV; see 609532) NS5b RNA polymerase interacted with SEPT6. SEPT6 also interacted with another NS5b-binding protein, HNRNPA1 (164017), suggesting the existence of a trimolecular complex. Knockdown of either HNRNPA1 or SEPT6 inhibited HCV replication. Kremer et al. (2007) showed that knockdown of SEPT2, SEPT6, and SEPT7 in HeLa cells caused actin stress fibers to disintegrate and cells to lose polarity. They found that these septins acted through SOCS7 (608788) to restrict nuclear accumulation of NCK (NCK1; 600508). In the absence of septin filaments, SOCS7 recruited NCK into the nucleus. Moreover, depletion of NCK from the cytoplasm triggered dissolution of actin stress fibers and loss of cell polarity. Kremer et al. (2007) also showed that the association between septins, SOCS7, and NCK played a role in the DNA damage checkpoint response. NCK entered the nucleus following DNA damage and was required for ultraviolet (UV)-induced cell cycle arrest. Furthermore, nuclear NCK was essential for activation of p53 (TP53; 191170) in response to UV-induced DNA damage. Kremer et al. (2007) concluded that septins, SOCS7, and NCK are part of a signaling pathway that couples regulation of the DNA damage response to the cytoskeleton.

BIOCHEMICAL FEATURES

- Crystal Structure Sirajuddin et al. (2007) presented the crystal structures of the human SEPT2 G domain and the heterotrimeric human SEPT2-SEPT6-SEPT7 complex. This structure revealed a universal bipolar polymer building block, composed of an extended G domain, which forms oligomers and filaments by conserved interactions between adjacent nucleotide-binding sites and/or the amino- and carboxy-terminal extensions. Unexpectedly, x-ray crystallography and electron microscopy showed that the predicted coiled coils are not involved in or required for complex and/or filament formation. The asymmetric heterotrimers associate head-to-head to form a hexameric unit that is nonpolarized along the filament axis but is rotationally asymmetric. Sirajuddin et al. (2007) concluded that the architecture of septin filaments differs fundamentally from that of other cytoskeletal structures.

MAPPING

By PCR analysis of human/rodent hybrid panels, Nagase et al. (1995) mapped the SE ... More on the omim web site

Subscribe to this protein entry history

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 300683 was added.

July 4, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).