NET1 (neuroepithelial cell transforming gene 1)

2008-04-01   David Murray , Peter Doran 

UCD School of Medicine, Medical Sciences, UCD-Mater Clinical Research Centre, Mater Misericordiae University Hospital, Dublin 7, Ireland

Identity

HGNC
LOCATION
10p15.1
LOCUSID
ALIAS
ARHGEF8,NET1A
FUSION GENES

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.

Proteins

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%).

Description

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

Mutations

Note

NET1 is subject to the following misense mutations :







Source ID:rs34821922rs34658946rs34821949
Wild type nucleotide:ATA
Wild type amino acid: KIK
Variant nucleotide:GCG
Variant amino acid: RTE
Amino Acid Position:28363466

Implicated in

Entity name
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.

Bibliography

Pubmed IDLast YearTitleAuthors
156844292005PAK1 negatively regulates the activity of the Rho exchange factor NET1.Alberts AS et al
86498281996Isolation of a novel oncogene, NET1, from neuroepithelioma cells by expression cDNA cloning.Chan AM et al
113500802001Identification of mNET1 as a candidate ligand for the first PDZ domain of MAGI-1.Dobrosotskaya IY et al
179382062007The nuclear RhoA exchange factor Net1 interacts with proteins of the Dlg family, affects their localization, and influences their tumor suppressor activity.García-Mata R et al
163445602006Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.Kimura K et al
165524342006Net1 and Myeov: computationally identified mediators of gastric cancer.Leyden J et al
156111212005Characterization of the biochemical and transforming properties of the neuroepithelial transforming protein 1.Qin H et al
112785192001The activity of guanine exchange factor NET1 is essential for transforming growth factor-beta-mediated stress fiber formation.Shen X et al

Other Information

Locus ID:

NCBI: 10276
MIM: 606450
HGNC: 14592
Ensembl: ENSG00000173848

Variants:

dbSNP: 10276
ClinVar: 10276
TCGA: ENSG00000173848
COSMIC: NET1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000173848ENST00000355029Q7Z628
ENSG00000173848ENST00000355029Q5SQI5
ENSG00000173848ENST00000380359Q7Z628
ENSG00000173848ENST00000380359Q5SQI7
ENSG00000173848ENST00000449083Q5SQI6

Expression (GTEx)

0
50
100
150
200

Pathways

PathwaySourceExternal ID
Signal TransductionREACTOMER-HSA-162582
Signalling by NGFREACTOMER-HSA-166520
p75 NTR receptor-mediated signallingREACTOMER-HSA-193704
Cell death signalling via NRAGE, NRIF and NADEREACTOMER-HSA-204998
NRAGE signals death through JNKREACTOMER-HSA-193648
Signaling by Rho GTPasesREACTOMER-HSA-194315
Rho GTPase cycleREACTOMER-HSA-194840
Signaling by GPCRREACTOMER-HSA-372790
GPCR downstream signalingREACTOMER-HSA-388396
G alpha (12/13) signalling eventsREACTOMER-HSA-416482

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
163854512006A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease.69
157172912005Support for association between ADHD and two candidate genes: NET1 and DRD1.53
264563322015Identification of AMPK Phosphorylation Sites Reveals a Network of Proteins Involved in Cell Invasion and Facilitates Large-Scale Substrate Prediction.46
213903282011The small GTPase RhoA localizes to the nucleus and is activated by Net1 and DNA damage signals.39
188278182008NET1-mediated RhoA activation facilitates lysophosphatidic acid-induced cell migration and invasion in gastric cancer.35
156844292005PAK1 negatively regulates the activity of the Rho exchange factor NET1.33
213736442011The nuclear guanine nucleotide exchange factors Ect2 and Net1 regulate RhoB-mediated cell death after DNA damage.32
185094762008A bacterial cytotoxin identifies the RhoA exchange factor Net1 as a key effector in the response to DNA damage.30
165524342006Net1 and Myeov: computationally identified mediators of gastric cancer.24
179382062007The nuclear RhoA exchange factor Net1 interacts with proteins of the Dlg family, affects their localization, and influences their tumor suppressor activity.24

Citation

David Murray ; Peter Doran

NET1 (neuroepithelial cell transforming gene 1)

Atlas Genet Cytogenet Oncol Haematol. 2008-04-01

Online version: http://atlasgeneticsoncology.org/gene/41526/net1