ECT2 (epithelial cell transforming sequence 2 oncogene)

Alias (NCBI)	ARHGEF31
HGNC (Hugo)	ECT2
HGNC Alias symb	ARHGEF31
HGNC Previous name	epithelial cell transforming sequence 2 oncogene
LocusID (NCBI)	1894
Atlas_Id	40400
Location	3q26.31  [Link to chromosome band 3q26]
Location_base_pair	Starts at 172750726 and ends at 172821474 bp from pter ( according to hg19-Feb_2009)  [Mapping ECT2.png]
Local_order	The ECT2 gene is located between the RNU4-4P pseudogene in centromeric position and ATP5G1P4 in telomeric position (according to GeneLoc).
	Location sequence of ECT2 on Chromosome 3. ECT2 gene is indicated by red arrow.

	Exon-intron structure of the ECT2 gene. Blue vertical bars correspond to exons, orange represents 3'UTR.
Description	The ECT2 gene is composed of 23 exons and spans 70793 bases on plus strand.
Transcription	The ECT2 transcript (NCBI Reference Sequence: NM_018098.4) contains 3916 bases and the open reading frame spans from 29 to 2680. 17 transcript variants have been reported for ECT2.
Pseudogene	A pseudogene for ECT2 has not been reported.

	Schematic diagram of the domain structure of the Ect2 protein. N, Amino-terminal region; XRCC1, X-ray repair complementing defective repair in Chinese hamster cells 1 domain; Cyclin B6, cyclin B6-like domain; BRCT, BRAC1 C-terminal domain; S, small central region; NLS, nuclear localization sequence; DH, Dbl homology domain; PH, pleckstrin homology domain; C, Carboxyl-terminal region. Phosphorylation on T341 and T412 activate Ect2 during G2/M phase. T328 is phosphorylated by PKCι and required for Ect2 mediated transformation in NSCLC cells.
Description	Human ECT2 consist of 883 amino acids, with a predicted molecular weight of approximately 104kDa. The N-terminus of Ect2 serves regulatory functions and contains sequences that exhibit high homology to cell cycle control and repair proteins. The XRCC1 domain shows sequence homology to human XRCC1, a protein that repairs defective DNA strand breaks and functions in sister chromatid exchange. The Clb6 domain shows homology to yeast B-cyclin that promotes transition from the G1 to S phase of cell cycle. The Clb6 domain is followed by sequences that exhibit homology to yeast Rad4/Cut5, a protein required for entry into S phase and inhibition of M phase entry prior to completion of DNA synthesis Rad4/Cut5 also plays a critical role in replication checkpoint control in yeast. The Cut5 homology domain contains tandem repeats of the BRCT (Breast Cancer gene 1 Carboxyl-terminal) motif that is conserved in proteins involved in DNA repair and cell cycle checkpoint responses. A small central (S) domain contains two nuclear localization sequences that appear to be involved in the control of the intracellular localization of Ect2. The catalytic core of Ect2 is found within the C-terminus, and consists of a Dbl-homology (DH) and a pleckstrin homology (PH) domain which confer guanine nucleotide exchange activity toward Rho-GTPases. The extreme C-terminal (C) region of Ect2 does not exhibit significant homology to any known protein domains or motifs.
Expression	Northern blot analysis reveals that Ect2 is expressed in a broad range of adult tissues including kidney, liver, spleen, testis, lung, bladder, ovary and brain (Miki et al., 1993; Saito et al., 2003). In situ hybridization of fetal tissues shows Ect2 expression in the liver, thymus, proliferating epithelial cells of the nasal cavity and gut, tooth primordial, costal cartilage, heart, lung and pancreas (Saito et al., 2003).
Localisation	Ect2 expression is cell cycle dependent. During interphase, Ect2 is sequestered within the nucleus. Upon breakdown of the nuclear envelope during mitosis, Ect2 is dispersed throughout the cytoplasm. Ect2 becomes localized to the mitotic spindles during metaphase, the cleavage furrow at telophase, and then the mid-body at the end of cytokinesis (Tatsumoto et al., 1999). In MDCK cells, small amounts of Ect2 can be detected at cell-cell contacts where it is reported to directly interact with the Par6/Par3/PKCζ polarity complex (Liu et al., 2004).
Function	Ect2 is a guanine nucleotide exchange factor and is reported to catalyze GTP exchange on several members of the Rho GTPase family including, RhoA, RhoB, RhoC, RhoG, Rac1 and Cdc42 (Miki et al., 1993; Saito et al., 2004; Solski et al., 2004; Tatsumoto et al., 1999; Wennerberg et al., 2002). ECT2 regulates cytokinesis in mammalian cells through RhoA-mediated pathways (Burkard et al., 2007; Kamijo et al., 2006; Kimura et al., 2000; Nishimura and Yonemura, 2006; Yuce et al., 2005). ECT2 associates with GTPase activating protein, MgcRacGAP to regulate the activity of RhoA which controls contraction of the actomyosin ring and ingression of the cleavage furrow required for cytokinesis. Ect2 has also been implicated in the control of mitotic spindle assembly through activation of Cdc42 (Tatsumoto et al., 2003), and an Ect2→Cdc42→mDia3 signaling pathway has been implicated in facilitating attachment and stabilization of spindle fibers to kinetochores (Oceguera-Yanez et al., 2005). Ect2 may also play a role in cell polarity. In MDCK cells, small amounts of Ect2 can be detected at cell-cell contacts where ECT2 is reported to directly interact with the polarity complex Par6/Par3/PKCζ and to modulate PKCζ activity (Liu et al., 2004). In addition, Ect2 was found in the tight junction-containing detergent-insoluble fraction of Caco2 cells (Chen et al., 2012). Recently, it has been proposed that ECT2 may contribute to neuronal morphological differentiation through regulation of growth cone dynamics perhaps by directly participating in reorganization of the actin cytoskeleton at the tips of neurites (Tsuji et al., 2012).
Homology	ECT2 is highly evolutionarily conserved. Homologs of ECT2 are present in other mammals as well as aves, flies, worms and yeast.

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