Download Gene Section NET1 (neuroepithelial cell transforming gene 1) in Oncology and Haematology

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Gene Section
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NET1 (neuroepithelial cell transforming gene 1)
David Murray, Peter Doran
UCD School of Medicine and Medical Sciences, UCD-Mater Clinical Research Centre, Mater Misericordiae
University Hospital, Dublin 7, Ireland (DM, PD)
Published in Atlas Database: April 2008
Online updated version : http://AtlasGeneticsOncology.org/Genes/NET1ID41526ch10p15.html
DOI: 10.4267/2042/44429
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2009 Atlas of Genetics and Cytogenetics in Oncology and Haematology
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Identity
Other names: ARHGEF8; NAT1; NET1A; SLC6A2
HGNC (Hugo): NET1
Location: 10p15.1
Local order: The NET1 gene is located on
chromosome 10 in a 11832 bp sequence (5478574 to
5490426).
DNA/RNA
Description
This gene, found on chromosome 10 at location 10p15
(5,444,518-5,490,401) encompasses 11832 bp of
genomic DNA. The gene has 10 exons and the mRNA
transcript is 3414 nucleotides in length.
Expression
This protein is widely expressed in mammalian tissue.
Protein
Localisation
Description
It is localized to both the cytoplasm and the nucleus.
Function
The protein encoded by this gene acts as guanine
nucleotide exchange factor (gef) for RhoA gtpase. This
gene encodes for a protein of 596 amino acids with a
molecular weight of 67.74 kDa. The protein contains
the following domains: a Rho guanine nucleotide
exchange factor (RhoGEF) activity domain from amino
acid 178 - 355 and a pleckstrin homology domain from
amino acid 387-503. The 596 amino acid sequence is:
Acts as guanine nucleotide exchange factor (GEF) for
RhoA GTPase.
Homology
Holomogy with Pan troglodytes (97%); Canis lupus
familiaris (92%); Mus musculus (93%), Rattus
norvegicus (92%), Gallus gallus (88%).
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Atlas Genet Cytogenet Oncol Haematol. 2009; 13(3)
Mutations
Note
NET1 is subject to the following misense mutations:
213
NET1 (neuroepithelial cell transforming gene 1)
Murray D, Doran P
References
Source ID:
rs34821922
rs34658946
rs34821949
Wild type
nucleotide:
A
T
A
Wild type
amino
acid:
Chan AM, Takai S, Yamada K, Miki T. Isolation of a novel
oncogene, NET1, from neuroepithelioma cells by expression
cDNA cloning. Oncogene. 1996 Mar 21;12(6):1259-66
K
I
K
Alberts AS, Treisman R. Activation of RhoA and SAPK/JNK
signalling pathways by the RhoA-specific exchange factor
mNET1. EMBO J. 1998 Jul 15;17(14):4075-85
Variant
nucleotide:
G
C
G
Dobrosotskaya IY. Identification of mNET1 as a candidate
ligand for the first PDZ domain of MAGI-1. Biochem Biophys
Res Commun. 2001 May 18;283(4):969-75
R
T
E
28
363
466
Shen X, Li J, Hu PP, Waddell D, Zhang J, Wang XF. The
activity of guanine exchange factor NET1 is essential for
transforming growth factor-beta-mediated stress fiber
formation. J Biol Chem. 2001 May 4;276(18):15362-8
Variant
amino
acid:
Amino
Acid
Position:
Alberts AS, Qin H, Carr HS, Frost JA. PAK1 negatively
regulates the activity of the Rho exchange factor NET1. J Biol
Chem. 2005 Apr 1;280(13):12152-61
Implicated in
Qin H, Carr HS, Wu X, Muallem D, Tran NH, Frost JA.
Characterization of the biochemical and transforming
properties of the neuroepithelial transforming protein 1. J Biol
Chem. 2005 Mar 4;280(9):7603-13
Gastric Cancer
Disease
Gastric or stomach cancer is a malignant epithelial
malignancy of the stomach mucosa. The vast majority
of gastric carcinomas are adenocarci nomas, arising
from the gastric glandular epithelium.
Prognosis
Prognosis depends on the stage of the cancer. Because
most stomach cancers are at an advanced stage upon
diagnosis, the average 5 years survival rate is 12%.
This is often due to the fact that the tumor has spread
beyond the primary site.
Oncogenesis
NET1 has been shown to be up-regulated in Gastric
Cancer (Leyden J et al., 2006). NET1 is a GEF
exchange factor for Rho GTPase proteins (Alberts AS
et al., 1998) and is therefore implicated in Rhomediated processes such as cytoskeletal organiza-tion
and cell migration. NET1 has been shown to drive
gastric tumor cell invasion (Leyden J et al., 2006). It is
this aggressive phenotype of the disease that accounts
for the dismal prognosis as the majority of gastric
tumors are at an advanced stage upon diagnosis where
they have spread beyond the primary site.
Atlas Genet Cytogenet Oncol Haematol. 2009; 13(3)
Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T,
Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri
H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N,
Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H,
Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, TakahashiFujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T,
Sugano S. Diversification of transcriptional modulation: largescale identification and characterization of putative alternative
promoters of human genes. Genome Res. 2006 Jan;16(1):5565
Leyden J, Murray D, Moss A, Arumuguma M, Doyle E,
McEntee G, O'Keane C, Doran P, MacMathuna P. Net1 and
Myeov: computationally identified mediators of gastric cancer.
Br J Cancer. 2006 Apr 24;94(8):1204-12
García-Mata R, Dubash AD, Sharek L, Carr HS, Frost JA,
Burridge K. The nuclear RhoA exchange factor Net1 interacts
with proteins of the Dlg family, affects their localization, and
influences their tumor suppressor activity. Mol Cell Biol. 2007
Dec;27(24):8683-97
This article should be referenced as such:
Murray D, Doran P. NET1 (neuroepithelial cell transforming
gene 1). Atlas Genet Cytogenet Oncol Haematol. 2009;
13(3):213-214.
214