Septin-2 (SEPT2)

The protein contains 361 amino acids for an estimated molecular weight of 41487 Da.

 

Filament-forming cytoskeletal GTPase. 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). Required for normal organization of the actin cytoskeleton. Plays a role in the biogenesis of polarized columnar-shaped epithelium by maintaining polyglutamylated microtubules, thus facilitating efficient vesicle transport, and by impeding MAP4 binding to tubulin. Required for the progression through mitosis. Forms a scaffold at the midplane of the mitotic splindle required to maintain CENPE localization at kinetochores and consequently chromosome congression. During anaphase, may be required for chromosome segregation and spindle elongation. Plays a role in ciliogenesis and collective cell movements. In cilia, required for the integrity of the diffusion barrier at the base of the primary cilium that prevents diffusion of transmembrane proteins between the cilia and plasma membranes: probably acts by regulating the assembly of the tectonic-like complex (also named B9 complex) by localizing TMEM231 protein. May play a role in the internalization of 2 intracellular microbial pathogens, Listeria monocytogenes and Shigella flexneri. (updated: July 3, 2019)

Protein identification was indicated in the following studies:

  1. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  2. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  3. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  4. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete		TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.


Interpro domains
Total structural coverage: 100%
Model score: 100
No model available.

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The reference OMIM entry for this protein is 601506

Septin 2; sept2
Neural precursor cell expressed, developmentally downregulated 5; nedd5
Diff6

CLONING

Mori et al. (1996) isolated a human cDNA that encodes a protein homologous to murine H5 and Diff6 and to yeast CDC10 (603151). The NEDD5 cDNA encodes a predicted protein of 406 amino acids. The deduced peptide sequence contains conserved domains rich in basic residues, a motif of the GTPase superfamily. Different poly(A) sites account for generation of 2 transcripts. The major 3.5-kb transcript was expressed ubiquitously in all human tissues examined, and a 2.0-kb alternative transcript lacking any long AU-rich element in the 3-prime noncoding region was expressed abundantly only in testis, heart, and skeletal muscle.

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, SEPT6 (300683), and SEPT7 (603151). SEPT6 and SEPT7 interacted through a parallel coiled-coil domain, and SEPT2 interacted with SEPT6 through its C-terminal coiled-coil domain. 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. Hu et al. (2010) demonstrated that ciliary membrane proteins are highly mobile, but their diffusion is impeded at the base of the cilium by a diffusion barrier. Sept2, a member of the septin family of guanosine triphosphatases that form a diffusion barrier in budding yeast, localized at the base of the ciliary membrane. Sept2 depletion resulted in loss of ciliary membrane protein localization and Sonic hedgehog (SHH; 600725) signal transduction, and inhibited ciliogenesis. Thus, Hu et al. (2010) concluded that SEPT2 is a part of a diffusion barrier at the base of the ciliary membrane and is essential for retaining receptor-signaling pathways in the primary cilium. These experiments used IMCD3 (mouse kidney inner medullary collecting duct) cells and murine embryonic fibroblasts.

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 requ ... More on the omim web site

Subscribe to this protein entry history

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

Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 25, 2017: Additional information
No protein expression data in P. Mayeux work for SEPT2

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 601506 was added.

Jan. 28, 2016: Protein entry updated
Automatic update: model status changed

Jan. 25, 2016: Protein entry updated
Automatic update: model status changed