Human Gene NET1 (uc010qar.3)
  Description: Homo sapiens neuroepithelial cell transforming 1 (NET1), transcript variant 1, mRNA.
RefSeq Summary (NM_005863): This gene is part of the family of Rho guanine nucleotide exchange factors. Members of this family activate Rho proteins by catalyzing the exchange of GDP for GTP. The protein encoded by this gene interacts with RhoA within the cell nucleus and may play a role in repairing DNA damage after ionizing radiation. Pseudogenes of this gene are located on the long arms of chromosomes 1, 7 and 18. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Jul 2012].
Transcript (Including UTRs)
   Position: hg19 chr10:5,455,752-5,501,019 Size: 45,268 Total Exon Count: 12 Strand: +
Coding Region
   Position: hg19 chr10:5,494,833-5,498,957 Size: 4,125 Coding Exon Count: 7 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesModel Information
Methods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr10:5,455,752-5,501,019)mRNA (may differ from genome)Protein (415 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCLynxMalacardsMGI
neXtProtOMIMPubMedReactomeUniProtKBWikipedia
BioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: ARHG8_HUMAN
DESCRIPTION: RecName: Full=Neuroepithelial cell-transforming gene 1 protein; AltName: Full=Proto-oncogene p65 Net1; AltName: Full=Rho guanine nucleotide exchange factor 8;
FUNCTION: Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase. May be involved in activation of the SAPK/JNK pathway Stimulates genotoxic stress-induced RHOB activity in breast cancer cells leading to their cell death.
SUBUNIT: Interacts with RHOA in its GTP- and GDP-bound states, and with CDC42 in its GTP-bound state. Interacts with the PDZ 1 domain of BAIAP1 (By similarity).
SUBCELLULAR LOCATION: Cytoplasm (By similarity). Nucleus (By similarity).
TISSUE SPECIFICITY: Widely expressed.
INDUCTION: By TGFB1. Up-regulated by DNA damaging agents like H(2)O(2) or ionizing radiation (IR).
SIMILARITY: Contains 1 DH (DBL-homology) domain.
SIMILARITY: Contains 1 PH domain.
SEQUENCE CAUTION: Sequence=AAB08847.1; Type=Frameshift; Positions=586; Sequence=AAB37683.1; Type=Frameshift; Positions=15, 33; Sequence=CAA08974.1; Type=Frameshift; Positions=8, 55, 59, 70, 586;
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org//Genes/NET1ID41526ch10p15.html";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): NET1
CDC HuGE Published Literature: NET1
Positive Disease Associations: attention deficit hyperactivity disorder
Related Studies:
  1. attention deficit hyperactivity disorder
    Bobb, A. J. et al. 2005, Support for association between ADHD and two candidate genes: NET1 and DRD1., American journal of medical genetics Part B, Neuropsychiatric genetics. 2005 Apr;134(1):67-72. [PubMed 15717291]
    This study provides support for an association between ADHD and polymorphisms in both NET1 and DRD1; polymorphisms in ten other candidate genes were not associated with ADHD. Because family-based and case-control methods gave divergent results, both should be used in genetic studies of ADHD.

-  MalaCards Disease Associations
  MalaCards Gene Search: NET1
Diseases sorted by gene-association score: breast cancer (3)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene
  • D013749 Tetrachlorodibenzodioxin
  • D000082 Acetaminophen
  • D016604 Aflatoxin B1
  • D001564 Benzo(a)pyrene
  • D014635 Valproic Acid
  • C111118 2',3,3',4',5-pentachloro-4-hydroxybiphenyl
  • C548651 2-(1'H-indolo-3'-carbonyl)thiazole-4-carboxylic acid methyl ester
  • D015123 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide
  • D015127 9,10-Dimethyl-1,2-benzanthracene
  • D002117 Calcitriol
          more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 51.25 RPKM in Artery - Tibial
Total median expression: 964.96 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -136.34467-0.292 Picture PostScript Text
3' UTR -526.892062-0.256 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000219 - DH-domain
IPR001331 - GDS_CDC24_CS
IPR011993 - PH_like_dom
IPR001849 - Pleckstrin_homology
IPR015721 - RhoGEF-like

Pfam Domains:
PF00169 - PH domain
PF00621 - RhoGEF domain
PF15405 - Pleckstrin homology domain
PF16652 - Pleckstrin homology domain

SCOP Domains:
48065 - DBL homology domain (DH-domain)
50729 - PH domain-like

Protein Data Bank (PDB) 3-D Structure
MuPIT help
3EO2 - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q7Z628
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserNo orthologNo orthologNo orthologNo ortholog
 Gene Details    
 Gene Sorter    
 RGD    
 Protein Sequence    
 Alignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005085 guanyl-nucleotide exchange factor activity
GO:0005089 Rho guanyl-nucleotide exchange factor activity
GO:0005515 protein binding
GO:0017049 GTP-Rho binding

Biological Process:
GO:0001558 regulation of cell growth
GO:0007165 signal transduction
GO:0007186 G-protein coupled receptor signaling pathway
GO:0035023 regulation of Rho protein signal transduction
GO:0035556 intracellular signal transduction
GO:0043065 positive regulation of apoptotic process
GO:0043547 positive regulation of GTPase activity
GO:0051056 regulation of small GTPase mediated signal transduction
GO:0051451 myoblast migration
GO:0070301 cellular response to hydrogen peroxide
GO:0071479 cellular response to ionizing radiation
GO:1900026 positive regulation of substrate adhesion-dependent cell spreading

Cellular Component:
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005886 plasma membrane


-  Descriptions from all associated GenBank mRNAs
  AK299335 - Homo sapiens cDNA FLJ50843 complete cds, highly similar to Neuroepithelial cell-transforming gene 1 protein.
BC053553 - Homo sapiens neuroepithelial cell transforming 1, mRNA (cDNA clone MGC:61640 IMAGE:6137683), complete cds.
AB209852 - Homo sapiens premature mRNA for neuroepithelial cell transforming gene 1 protein variant.
S82401 - NET1=neuroepithelioma transforming gene 1 [human, immortalized mammary epithelial cell line, B5/589, mRNA Partial, 460 nt].
AB587387 - Synthetic construct DNA, clone: pF1KB5507, Homo sapiens NET1 gene for neuroepithelial cell transforming 1, without stop codon, in Flexi system.
CU690984 - Synthetic construct Homo sapiens gateway clone IMAGE:100021745 5' read NET1 mRNA.
KJ892985 - Synthetic construct Homo sapiens clone ccsbBroadEn_02379 NET1 gene, encodes complete protein.
GQ891307 - Homo sapiens clone HEL-S-30a epididymis secretory sperm binding protein mRNA, complete cds.
AK302687 - Homo sapiens cDNA FLJ50300 complete cds, highly similar to Neuroepithelial cell-transforming gene 1protein.
AK315566 - Homo sapiens cDNA, FLJ96638, Homo sapiens neuroepithelial cell transforming gene 1 (NET1), mRNA.
AK294244 - Homo sapiens cDNA FLJ54782 complete cds, highly similar to Neuroepithelial cell-transforming gene 1protein.
AK304028 - Homo sapiens cDNA FLJ53956 complete cds, highly similar to Neuroepithelial cell-transforming gene 1 protein.
AK024919 - Homo sapiens cDNA: FLJ21266 fis, clone COL01684, highly similar to HS010046 Homo sapiens mRNA for Rho guanine nucleotide-exchange factor.
AJ010046 - Homo sapiens mRNA for Rho guanine nucleotide-exchange factor, splice variant NET1A.
BC010285 - Homo sapiens neuroepithelial cell transforming 1, mRNA (cDNA clone MGC:5367 IMAGE:3048980), complete cds.
CU679671 - Synthetic construct Homo sapiens gateway clone IMAGE:100019824 5' read NET1 mRNA.
KJ898188 - Synthetic construct Homo sapiens clone ccsbBroadEn_07582 NET1 gene, encodes complete protein.
BX537509 - Homo sapiens mRNA; cDNA DKFZp686F1849 (from clone DKFZp686F1849).
U02081 - Human guanine nucleotide regulatory protein (NET1) mRNA, complete cds.
JD276600 - Sequence 257624 from Patent EP1572962.
JD551580 - Sequence 532604 from Patent EP1572962.
JD320545 - Sequence 301569 from Patent EP1572962.
JD360498 - Sequence 341522 from Patent EP1572962.
JD303782 - Sequence 284806 from Patent EP1572962.
JD318956 - Sequence 299980 from Patent EP1572962.
JD065413 - Sequence 46437 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q7Z628 (Reactome details) participates in the following event(s):

R-HSA-194913 GEFs activate Rho GTPase:GDP
R-HSA-419166 GEFs activate RhoA,B,C
R-HSA-205039 p75NTR indirectly activates RAC and Cdc42 via a guanyl-nucleotide exchange factor
R-HSA-194840 Rho GTPase cycle
R-HSA-416482 G alpha (12/13) signalling events
R-HSA-193648 NRAGE signals death through JNK
R-HSA-194315 Signaling by Rho GTPases
R-HSA-388396 GPCR downstream signalling
R-HSA-204998 Cell death signalling via NRAGE, NRIF and NADE
R-HSA-162582 Signal Transduction
R-HSA-372790 Signaling by GPCR
R-HSA-193704 p75 NTR receptor-mediated signalling
R-HSA-73887 Death Receptor Signalling

-  Other Names for This Gene
  Alternate Gene Symbols: AK302687, ARHG8_HUMAN, ARHGEF8, NM_005863, NP_005854, Q12773, Q7Z628, Q96D82, Q99903, Q9UEN6, uc010qar.2
UCSC ID: uc010qar.3
RefSeq Accession: NM_005863
Protein: Q7Z628 (aka ARHG8_HUMAN or ARH8_HUMAN)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: AK302687.1
exon count: 12CDS single in 3' UTR: no RNA size: 2016
ORF size: 1248CDS single in intron: no Alignment % ID: 99.85
txCdsPredict score: 2170.50frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.