| Identity |
| Other names | ARHGEF8 |
| NAT1 | |
| NET1A | |
| SLC6A2 | |
| HGNC | NET1 |
| Location | 10p15.1 |
| Location_base_pair | Starts at 5444518 and ends at 5490426 bp from pter ( according to hg18-Mar_2006). |
| 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 11832bp of genomic DNA. The gene has 10 exons and the mRNA transcript is 3414 nucleotides in length. |
| Protein |
| Description | 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 : 1 mepelaaqkq prprrrsrra sglstegatg psadtsgsel dgrcslrrgs sftfltpgpn 61 wdftlkrkrr ekdddvvsls sldlkepsnk rvrplarvts lanlispvrn gavrrfgqti 121 qsftlrgdhr spasaqkfss rstvptpakr rssalwseml ditmkesltt reirrqeaiy 181 emsrgeqdli edlklarkay hdpmlklsim seeelthifg dldsyiplhe dlltrigeat 241 kpdgtveqig hilvswlprl nayrgycsnq laakalldqk kqdprvqdfl qrclespfsr 301 kldlwsfldi prsrlvkypl llkeilkhtp kehpdvqlle dailiiqgvl sdinlkkges 361 ecqyyidkle yldekqrdpr ieaskvllch gelrsksghk lyiflfqdil vltrpvtrne 421 rhsyqvyrqp ipvqelvled lqdgdvrmgg sfrgafsnse kaknifrirf hdpspaqsht 481 lqandvfhkq qwfnciraai apfqsagspp elqglpelhe ecegnhpsar kltaqrrast 541 vssvtqvevd enayrcgsgm qmaedskslk thqtqpgirr ardkalsggk rketlv |
| Expression | This protein is widely expressed in mammalian tissue. |
| Localisation | It is localized to both the cytoplasm and the nucleus. |
| Function | 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%). |
| Mutations |
| Note | NET1 is subject to the following misense mutations :
|
| Implicated in |
| Entity | Gastric Cancer |
| Disease | Gastric or stomach cancer is a malignant epithelial malignancy of the stomach mucosa. The vast majority of gastric carcinomas are adenocarcinomas, 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 Rho-mediated processes such as cytoskeletal organization 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. |
| External links |
| Bibliography |
| Isolation of a novel oncogene, NET1, from neuroepithelioma cells by expression cDNA cloning. |
| Chan AM, Takai S, Yamada K, Miki T. |
| Oncogene. 1996 Mar 21;12(6):1259-66. |
| PMID 8649828 |
| Activation of RhoA and SAPK/JNK signalling pathways by the RhoA-specific exchange factor mNET1. |
| Alberts AS, Treisman R. |
| EMBO J. 1998 Jul 15;17(14):4075-85. |
| PMID 9670022 |
| Identification of mNET1 as a candidate ligand for the first PDZ domain of MAGI-1. |
| Dobrosotskaya IY. |
| Biochem Biophys Res Commun. 2001 May 18;283(4):969-75. |
| PMID 11350080 |
| The activity of guanine exchange factor NET1 is essential for transforming growth factor-beta-mediated stress fiber formation. |
| Shen X, Li J, Hu PP, Waddell D, Zhang J, Wang XF. |
| J Biol Chem. 2001 May 4;276(18):15362-8. |
| PMID 11278519 |
| PAK1 negatively regulates the activity of the Rho exchange factor NET1. |
| Alberts AS, Qin H, Carr HS, Frost JA. |
| J Biol Chem. 2005 Apr 1;280(13):12152-61. |
| PMID 15684429 |
| Characterization of the biochemical and transforming properties of the neuroepithelial transforming protein 1. |
| J Biol Chem. 2005 Mar 4;280(9):7603-13. |
| PMID 15611121 |
| Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. |
| 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, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S. |
| Genome Res. 2006 Jan;16(1):55-65. |
| PMID 16344560 |
| Net1 and Myeov: computationally identified mediators of gastric cancer. |
| Leyden J, Murray D, Moss A, Arumuguma M, Doyle E, McEntee G, O'Keane C, Doran P, MacMathuna P. |
| Br J Cancer. 2006 Apr 24;94(8):1204-12. |
| PMID 16552434 |
| The nuclear RhoA exchange factor Net1 interacts with proteins of the Dlg family, affects their localization, and influences their tumor suppressor activity. |
| Garcia-Mata R, Dubash AD, Sharek L, Carr HS, Frost JA, Burridge K. |
| Mol Cell Biol. 2007 Dec;27(24):8683-97. |
| PMID 17938206 |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| Contributor(s) |
| Written | 04-2008 | David Murray, Peter Doran |
| UCD School of Medicine and Medical Sciences, UCD-Mater Clinical Research Centre, Mater Misericordiae University Hospital, Dublin 7, Ireland |
| Citation |
| This paper should be referenced as such : |
| Murray D, Doran P . NET1 (neuroepithelial cell transforming gene 1). Atlas Genet Cytogenet Oncol Haematol. April 2008 . URL : http://AtlasGeneticsOncology.org/Genes/NET1ID41526ch10p15.html |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Sun Nov 9 19:44:23 2008 |
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