|  |
| |
Description | SEPT7 belongs to the septin family that is known to be a highly conserved subfamily of GTPases and is well recognized as a novel component of the cytoskeleton. It consists of an open reading frame (ORF) having 1254 nucleotides which encodes 418 amino acids, consisting of a GTP-binding motif (Nakatsuru et al., 1994). The amino acid sequence of SEPT7 protein is shown in Figure 2. Septins are GTP-binding proteins which are known to contain all the necessary elements to perform the general GDP-to-GTP conformational switch. Sept7, the only member of the Sept7 subgroup, forms a very tight G-interface dimer in the GDP-bound state. It has been shown that the stability of the interface is dramatically decreased by exchanging GDP with a nucleoside triphosphate, which is believed to influence filament formation and dynamics via Sept7 (Zent & Wittinghofer, 2014). SEPT7 is having a molecular mass of approximately 51 kDa and has a basal isoelectric point of 8.76. The protein encoded by this gene has a high similarity to the CDC10 protein of Saccharomyces cerevisiae. It also shows similarity to Diff 6 of Drosophila and H5 of mouse. All of these similar proteins contain a GTP-binding motif. The GTPase activity of SEPT7 is required for filament formation. It is also required for the association of centromere-associated protein E (CENPE) with the kinetochore. Multiple transcript variants are formed as a result of alternative splicing. This protein has a role in ciliogenesis and collective cell movements. The GTPase domain of SEPT7 is unique as it contains a conserved sequence near its end - the Septin Unique Element (SUE) (Pan et al., 2007, Steels et al., 2007, Versele et al., 2004). SEPT7 has additional conserved elements that flank the GTPase domain. It possesses a polybasic region at N-terminal to the GTPase domain that has been shown to bind phosphoinositides (Casamayor & Snyder, 2003, Zhang et al., 1999). In fact, mammalian SEPT7 exist solely as 6- to 8-unit heteromeric complexes within the cell (Sellin et al., 2011). In mammals, SEPT7 forms a complex with SEPT2, SEPT4 and SEPT6 which was first identified in brain tissue (Hsu et al., 1998). SEPT7 monomers within the unit complex interact through G-G and NC-NC interfaces, thereby pairing up with other septin members. These G-G and NC-NC interactions alternate along the unit complex, and are necessary for its formation (Sirajuddin et al., 2007). SEPT7 also shows non-septin interactions. 9% of the interactors have been identified to be non-septins for SEPT7 (Nakahira et al., 2010). SEPT7 was identified as a mutual partner with SEPT9 at a very high percentage (Nakahira et al., 2010). SEPT7 is known to be expressed in several tissues. It is therefore believed to be much more involved in processes like cell division. It does belong to the group of septins with the least members (SEPT7 and 13, only) and is found in almost all of the heterofilaments known till date. It is therefore a basic element for filament formation (Nakahira et al., 2010) |
Expression | SEPT7 has cytoplasmic expression in most tissues but is always found associated to actin filaments as well as several regions through-out mitosis (Zhu et al., 2008). There are already cytoplasmic, nuclear, and overall (total) SEPT7 protein expression levels which have also been determined in PTC (Igci et al., 2014). SEPT7 was also shown to be negatively regulated by miR-30a-5p in glioma cells (Jia et al., 2013). There is very high expression of SEPT7 proteins in cerebral cortex but moderate expression in hippocampus, lateral ventricle and cerebellum of CNS. SEPT7 is also moderately expressed in gall bladder, pancreas, stomach, colon, kidney, testis, prostate, breast, thyroid gland. It has low expression in liver, small intestine, bone marrow and lung. But it has not been detected in skeletal muscles, smooth muscles and heart muscles. |
Localisation | SEPT7 is distributed throughout the cytoplasm in prometaphase cells. During metaphase it is associated with the spindle. While at anaphase it is associated with the central spindle and at the cleavage furrow in anaphase cells. It has been detected at the midbody in telophase and is associated with actin stress fibers (Zhu et al., 2008). |
Function | SEPT7 has cytoskeletal GTPase which is responsible for filament-forming. It is needed for normal orientation of the actin cytoskeleton. It is needed for normal progress through mitosis. It is also involved in cytokinesis. It has been revealed that septins are extremely necessary for cytokinesis in fibroblasts, but of relatively little significance in cells of the hematopoietic system by studying genetic loss of the septin subunit SEPT7 in vivo (Menon et al., 2014). SEPT7 is of utmost requirement for associating centromere-associated protein E (CENPE) with the kinetochore. It is known to play a role in ciliogenesis and collective cell movements. SEPT7 is a GTP-binding protein that is known to form hetero-oligomeric complexes as well as higher-order structures for example filaments and rings (Mostowy & Cossart, 2012). It has been shown that Septin 7 is required for axonal association of Schwann cells (Roth et al., 2013). It also helps in glucose transporter trafficking. Septin 7 regulates glucose transporter trafficking by forming a complex with CD2AP and nephrin (Wasik et al., 2012). It is known to function in gliomagenesis as well as in suppression of glioma cell growth (Jia et al., 2010). |
Homology | SEPT7 is highly similar to the CDC10 (cell division cycle 10) protein of Saccharomyces cerevisiae. A novel human gene (418-amino acid product) has been cloned which shared almost 39% and 54% sequence identity with yeast CDC10 and mouse H5 proteins, respectively (Nakatsuru et al., 1994). This protein is also similar to Diff 6 of Drosophila to a good extent. Each of these known sequence homologues contains a common GTP-binding motif. |
Molecular dissection of a yeast septin: distinct domains are required for septin interaction, localization, and function |
Casamayor A, Snyder M |
Mol Cell Biol 2003 Apr;23(8):2762-77 |
PMID 12665577 |
|
The expression pattern of SEPT7 correlates with sperm morphology |
Chao HC, Lin YH, Kuo YC, Shen CJ, Pan HA, Kuo PL |
J Assist Reprod Genet 2010 Jun;27(6):299-307 |
PMID 20352323 |
|
Expression profiling the human septin gene family |
Hall PA, Jung K, Hillan KJ, Russell SE |
J Pathol 2005 Jul;206(3):269-78 |
PMID 15915442 |
|
Subunit composition, protein interactions, and structures of the mammalian brain sec6/8 complex and septin filaments |
Hsu SC, Hazuka CD, Roth R, Foletti DL, Heuser J, Scheller RH |
Neuron 1998 Jun;20(6):1111-22 |
PMID 9655500 |
|
Differential expression of a set of genes in follicular and classic variants of papillary thyroid carcinoma |
Igci YZ, Arslan A, Akarsu E, Erkilic S, Igci M, Oztuzcu S, Cengiz B, Gogebakan B, Cakmak EA, Demiryurek AT |
Endocr Pathol 2011 Jun;22(2):86-96 |
PMID 21509594 |
|
Septin 7 immunoexpression in papillary thyroid carcinoma: a preliminary study |
Igci YZ, Erkilic S, Arslan A |
Pathol Res Pract 2014 Jul;210(7):426-31 |
PMID 24685401 |
|
MiR-30a-5p antisense oligonucleotide suppresses glioma cell growth by targeting SEPT7 |
Jia Z, Wang K, Wang G, Zhang A, Pu P |
PLoS One 2013;8(1):e55008 |
PMID 23383034 |
|
Overexpression of septin 7 suppresses glioma cell growth |
Jia ZF, Huang Q, Kang CS, Yang WD, Wang GX, Yu SZ, Jiang H, Pu PY |
J Neurooncol 2010 Jul;98(3):329-40 |
|
Genetic deletion of SEPT7 reveals a cell type-specific role of septins in microtubule destabilization for the completion of cytokinesis |
Menon MB, Sawada A, Chaturvedi A, Mishra P, Schuster-Gossler K, Galla M, Schambach A, Gossler A, Förster R, Heuser M, Kotlyarov A, Kinoshita M, Gaestel M |
PLoS Genet 2014 Aug 14;10(8):e1004558 |
PMID 25122120 |
|
Septins: the fourth component of the cytoskeleton |
Mostowy S, Cossart P |
Nat Rev Mol Cell Biol 2012 Feb 8;13(3):183-94 |
PMID 22314400 |
|
A draft of the human septin interactome |
Nakahira M, Macedo JN, Seraphim TV, Cavalcante N, Souza TA, Damalio JC, Reyes LF, Assmann EM, Alborghetti MR, Garratt RC, Araujo AP, Zanchin NI, Barbosa JA, Kobarg J |
PLoS One 2010 Nov 2;5(11):e13799 |
PMID 21082023 |
|
Molecular cloning of a novel human cDNA homologous to CDC10 in Saccharomyces cerevisiae |
Nakatsuru S, Sudo K, Nakamura Y |
Biochem Biophys Res Commun 1994 Jul 15;202(1):82-7 |
PMID 8037772 |
|
Analysis of septins across kingdoms reveals orthology and new motifs |
Pan F, Malmberg RL, Momany M |
BMC Evol Biol 2007 Jul 1;7:103 |
PMID 17601340 |
|
Septin 7: actin cross-organization is required for axonal association of Schwann cells |
Roth AD, Liazoghli D, Perez De Arce F, Colman DR |
Biol Res 2013;46(3):243-9 |
PMID 24346071 |
|
Characterization of human septin interactions |
Sandrock K, Bartsch I, Bläser S, Busse A, Busse E, Zieger B |
Biol Chem 2011 Aug;392(8-9):751-61 |
PMID 21767235 |
|
Deciphering the rules governing assembly order of mammalian septin complexes |
Sellin ME, Sandblad L, Stenmark S, Gullberg M |
Mol Biol Cell 2011 Sep;22(17):3152-64 |
PMID 21737677 |
|
Structural insight into filament formation by mammalian septins |
Sirajuddin M, Farkasovsky M, Hauer F, Kühlmann D, Macara IG, Weyand M, Stark H, Wittinghofer A |
Nature 2007 Sep 20;449(7160):311-5 |
PMID 17637674 |
|
Sept12 is a component of the mammalian sperm tail annulus |
Steels JD, Estey MP, Froese CD, Reynaud D, Pace-Asciak C, Trimble WS |
Cell Motil Cytoskeleton 2007 Oct;64(10):794-807 |
PMID 17685441 |
|
Protein-protein interactions governing septin heteropentamer assembly and septin filament organization in Saccharomyces cerevisiae |
Versele M, Gullbrand B, Shulewitz MJ, Cid VJ, Bahmanyar S, Chen RE, Barth P, Alber T, Thorner J |
Mol Biol Cell 2004 Oct;15(10):4568-83 |
PMID 15282341 |
|
Septin 7 forms a complex with CD2AP and nephrin and regulates glucose transporter trafficking |
Wasik AA, Polianskyte-Prause Z, Dong MQ, Shaw AS, Yates JR 3rd, Farquhar MG, Lehtonen S |
Mol Biol Cell 2012 Sep;23(17):3370-9 |
PMID 22809625 |
|
Upregulation of SEPT7 gene inhibits invasion of human glioma cells |
Xu S, Jia ZF, Kang C, Huang Q, Wang G, Liu X, Zhou X, Xu P, Pu P |
Cancer Invest 2010 Mar;28(3):248-58 |
PMID 19916744 |
|
[Expression of cell cycle molecules in human azoospermic testes] |
Yang B, Yuan JL, Gao XK, Qin WJ, Liu F, Shao C, Liu HL, Kang FX |
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2009 May;25(5):393-5 |
PMID 19426592 |
|
Human septin isoforms and the GDP-GTP cycle |
Zent E, Wittinghofer A |
Biol Chem 2014 Feb;395(2):169-80 |
PMID 24246286 |
|
Phosphatidylinositol polyphosphate binding to the mammalian septin H5 is modulated by GTP |
Zhang J, Kong C, Xie H, McPherson PS, Grinstein S, Trimble WS |
Curr Biol 1999 Dec 16-30;9(24):1458-67 |
PMID 10607590 |
|
MicroRNA-127 post-transcriptionally downregulates Sept7 and suppresses cell growth in hepatocellular carcinoma cells |
Zhou J, Lu S, Yang S, Chen H, Shi H, Miao M, Jiao B |
Cell Physiol Biochem 2014;33(5):1537-46 |
PMID 24854842 |
|
Septin 7 interacts with centromere-associated protein E and is required for its kinetochore localization |
Zhu M, Wang F, Yan F, Yao PY, Du J, Gao X, Wang X, Wu Q, Ward T, Li J, Kioko S, Hu R, Xie W, Ding X, Yao X |
J Biol Chem 2008 Jul 4;283(27):18916-25 |
PMID 18460473 |
|