NET1 (neuroepithelial cell transforming gene 1)

2008-04-01 David Murray , Peter Doran Affiliation

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

Identity

HGNC

NET1

LOCATION

10p15.1

LOCUSID

10276

ALIAS

ARHGEF8,NET1A

FUSION GENES

Show Gene Fusions

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:	rs34821922	rs34658946	rs34821949
Wild type nucleotide:	A	T	A
Wild type amino acid:	K	I	K
Variant nucleotide:	G	C	G
Variant amino acid:	R	T	E
Amino Acid Position:	28	363	466

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.

Article Bibliography

Pubmed ID	Last Year	Title	Authors
15684429	2005	PAK1 negatively regulates the activity of the Rho exchange factor NET1.	Alberts AS et al
8649828	1996	Isolation of a novel oncogene, NET1, from neuroepithelioma cells by expression cDNA cloning.	Chan AM et al
11350080	2001	Identification of mNET1 as a candidate ligand for the first PDZ domain of MAGI-1.	Dobrosotskaya IY et al
17938206	2007	The 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
16344560	2006	Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.	Kimura K et al
16552434	2006	Net1 and Myeov: computationally identified mediators of gastric cancer.	Leyden J et al
15611121	2005	Characterization of the biochemical and transforming properties of the neuroepithelial transforming protein 1.	Qin H et al
11278519	2001	The 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 ID	Transcript ID	Uniprot
ENSG00000173848	ENST00000355029	Q7Z628
ENSG00000173848	ENST00000355029	Q5SQI5
ENSG00000173848	ENST00000380359	Q7Z628
ENSG00000173848	ENST00000380359	Q5SQI7
ENSG00000173848	ENST00000449083	Q5SQI6

Expression (GTEx)

100

150

200

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Signal Transduction	REACTOME	R-HSA-162582
Signalling by NGF	REACTOME	R-HSA-166520
p75 NTR receptor-mediated signalling	REACTOME	R-HSA-193704
Cell death signalling via NRAGE, NRIF and NADE	REACTOME	R-HSA-204998
NRAGE signals death through JNK	REACTOME	R-HSA-193648
Signaling by Rho GTPases	REACTOME	R-HSA-194315
Rho GTPase cycle	REACTOME	R-HSA-194840
Signaling by GPCR	REACTOME	R-HSA-372790
GPCR downstream signaling	REACTOME	R-HSA-388396
G alpha (12/13) signalling events	REACTOME	R-HSA-416482

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
37171948	2023	Association between NET-1 Level in Placenta from Preeclampsia Pregnancies and Trophoblast Proliferation and Apoptosis: A Correlation Analysis.	0
37171948	2023	Association between NET-1 Level in Placenta from Preeclampsia Pregnancies and Trophoblast Proliferation and Apoptosis: A Correlation Analysis.	0
34957935	2022	Circ_0000745 promotes acute lymphoblastic leukemia progression through mediating miR-494-3p/NET1 axis.	17
34957935	2022	Circ_0000745 promotes acute lymphoblastic leukemia progression through mediating miR-494-3p/NET1 axis.	17
31910717	2021	Monoaminergic Genetic Variants, Prefrontal Cortex-Amygdala Circuit, and Emotional Symptoms in Children With ADHD: Exploration Based on the Gene-Brain-Behavior Relationship.	2
33465404	2021	Cdk1 phosphorylation negatively regulates the activity of Net1 towards RhoA during mitosis.	3
33740419	2021	Simultaneous binding of Guidance Cues NET1 and RGM blocks extracellular NEO1 signaling.	16
33839702	2021	NET1 promotes HCC growth and metastasis in vitro and in vivo via activating the Akt signaling pathway.	3
31910717	2021	Monoaminergic Genetic Variants, Prefrontal Cortex-Amygdala Circuit, and Emotional Symptoms in Children With ADHD: Exploration Based on the Gene-Brain-Behavior Relationship.	2
33465404	2021	Cdk1 phosphorylation negatively regulates the activity of Net1 towards RhoA during mitosis.	3
33740419	2021	Simultaneous binding of Guidance Cues NET1 and RGM blocks extracellular NEO1 signaling.	16
33839702	2021	NET1 promotes HCC growth and metastasis in vitro and in vivo via activating the Akt signaling pathway.	3
30332929	2020	Regulation of RhoA activation and cell motility by c-Jun N-terminal kinases and Net1.	5
31451992	2020	LncRNA CTC-497E21.4 promotes the progression of gastric cancer via modulating miR-22/NET1 axis through RhoA signaling pathway.	0
32420320	2020	Neuroepithelial Cell Transforming Gene 1 Acts as an Oncogene and Is Mediated by miR-22 in Human Non-Small-Cell Lung Cancer.	1

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