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Q7Z628 (ARHG8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 101. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Neuroepithelial cell-transforming gene 1 protein
Alternative name(s):
Proto-oncogene p65 Net1
Rho guanine nucleotide exchange factor 8
Gene names
Name:NET1
Synonyms:ARHGEF8
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length596 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.6

Subunit structure

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. Ref.1

Induction

By TGFB1. Up-regulated by DNA damaging agents like H2O2 or ionizing radiation (IR). Ref.3 Ref.6

Sequence similarities

Contains 1 DH (DBL-homology) domain.

Contains 1 PH domain.

Sequence caution

The sequence AAB08847.1 differs from that shown. Reason: Frameshift at position 586.

The sequence AAB37683.1 differs from that shown. Reason: Frameshift at positions 15 and 33.

The sequence CAA08974.1 differs from that shown. Reason: Frameshift at positions 8, 55, 59, 70 and 586.

Ontologies

Keywords
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseProto-oncogene
   Molecular functionGuanine-nucleotide releasing factor
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic signaling pathway

Traceable author statement. Source: Reactome

cellular response to hydrogen peroxide

Inferred from direct assay Ref.6. Source: UniProtKB

cellular response to ionizing radiation

Inferred from direct assay Ref.6. Source: UniProtKB

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

positive regulation of Rho GTPase activity

Inferred from mutant phenotype Ref.6. Source: UniProtKB

positive regulation of apoptotic process

Inferred from direct assay Ref.6. Source: UniProtKB

regulation of cell growth

Non-traceable author statement Ref.1. Source: UniProtKB

regulation of small GTPase mediated signal transduction

Traceable author statement. Source: Reactome

signal transduction

Traceable author statement Ref.1. Source: ProtInc

small GTPase mediated signal transduction

Traceable author statement. Source: Reactome

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionRho guanyl-nucleotide exchange factor activity

Inferred from electronic annotation. Source: InterPro

guanyl-nucleotide exchange factor activity

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q7Z628-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q7Z628-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-54: Missing.
     55-85: LTPGPNWDFTLKRKRREKDDDVVSLSSLDLK → MVAHDETGGLLPIKRTIRVLDVNNQSFREQE

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 596596Neuroepithelial cell-transforming gene 1 protein
PRO_0000080924

Regions

Domain174 – 356183DH
Domain386 – 501116PH
Region1 – 7474Necessary for nuclear localization By similarity
Motif12 – 198Nuclear localization signal By similarity
Motif66 – 727Nuclear localization signal By similarity

Amino acid modifications

Modified residue11N-acetylmethionine Ref.7
Modified residue211Phosphoserine Ref.5
Modified residue321Phosphoserine Ref.5
Modified residue1061Phosphoserine Ref.4 Ref.5
Modified residue5081Phosphoserine By similarity

Natural variations

Alternative sequence1 – 5454Missing in isoform 2.
VSP_011619
Alternative sequence55 – 8531LTPGP…SLDLK → MVAHDETGGLLPIKRTIRVL DVNNQSFREQE in isoform 2.
VSP_011620
Natural variant2021D → N in a breast cancer sample; somatic mutation. Ref.9
VAR_035972
Natural variant4171T → I.
Corresponds to variant rs34658946 [ dbSNP | Ensembl ].
VAR_051982

Experimental info

Sequence conflict391E → R in AAB37683. Ref.1
Sequence conflict611W → C in AAB37683. Ref.1
Sequence conflict143 – 1464TVPT → MDGW in AAB08847. Ref.1

Secondary structure

...................... 596
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 2003. Version 1.
Checksum: E1AD964F14650D2C

FASTA59667,740
        10         20         30         40         50         60 
MEPELAAQKQ PRPRRRSRRA SGLSTEGATG PSADTSGSEL DGRCSLRRGS SFTFLTPGPN 

        70         80         90        100        110        120 
WDFTLKRKRR EKDDDVVSLS SLDLKEPSNK RVRPLARVTS LANLISPVRN GAVRRFGQTI 

       130        140        150        160        170        180 
QSFTLRGDHR SPASAQKFSS RSTVPTPAKR RSSALWSEML DITMKESLTT REIRRQEAIY 

       190        200        210        220        230        240 
EMSRGEQDLI EDLKLARKAY HDPMLKLSIM SEEELTHIFG DLDSYIPLHE DLLTRIGEAT 

       250        260        270        280        290        300 
KPDGTVEQIG HILVSWLPRL NAYRGYCSNQ LAAKALLDQK KQDPRVQDFL QRCLESPFSR 

       310        320        330        340        350        360 
KLDLWSFLDI PRSRLVKYPL LLKEILKHTP KEHPDVQLLE DAILIIQGVL SDINLKKGES 

       370        380        390        400        410        420 
ECQYYIDKLE YLDEKQRDPR IEASKVLLCH GELRSKSGHK LYIFLFQDIL VLTRPVTRNE 

       430        440        450        460        470        480 
RHSYQVYRQP IPVQELVLED LQDGDVRMGG SFRGAFSNSE KAKNIFRIRF HDPSPAQSHT 

       490        500        510        520        530        540 
LQANDVFHKQ QWFNCIRAAI APFQSAGSPP ELQGLPELHE ECEGNHPSAR KLTAQRRAST 

       550        560        570        580        590 
VSSVTQVEVD ENAYRCGSGM QMAEDSKSLK THQTQPGIRR ARDKALSGGK RKETLV 

« Hide

Isoform 2 [UniParc].

Checksum: 770F252F0FCA7E92
Show »

FASTA54261,885

References

« Hide 'large scale' references
[1]"Isolation of a novel oncogene, NET1, from neuroepithelioma cells by expression cDNA cloning."
Chan A.M.-L., Takai S., Yamada K., Miki T.
Oncogene 12:1259-1266(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY.
Tissue: Neuroepithelium.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Eye and Placenta.
[3]"The activity of guanine exchange factor NET1 is essential for transforming growth factor-beta-mediated stress fiber formation."
Shen X., Li J., Hu P.P.-C., Waddell D., Zhang J., Wang X.-F.
J. Biol. Chem. 276:15362-15368(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION BY TGFB1.
[4]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-106, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[5]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21; SER-32 AND SER-106, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[6]"The nuclear guanine nucleotide exchange factors Ect2 and Net1 regulate RhoB-mediated cell death after DNA damage."
Srougi M.C., Burridge K.
PLoS ONE 6:E17108-E17108(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INDUCTION.
[7]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]"Crystal structure of the RhoGEF domain of human neuroepithelial cell-transforming gene 1 protein."
Structural genomics consortium (SGC)
Submitted (FEB-2009) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 161-373.
[9]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] ASN-202.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
S82401 mRNA. Translation: AAB37683.1. Frameshift.
U02081 mRNA. Translation: AAB08847.1. Frameshift.
AJ010046 mRNA. Translation: CAA08974.1. Frameshift.
BC010285 mRNA. Translation: AAH10285.1.
BC053553 mRNA. Translation: AAH53553.1.
CCDSCCDS41483.1. [Q7Z628-1]
CCDS7067.1. [Q7Z628-2]
PIRG01210.
RefSeqNP_001040625.1. NM_001047160.2. [Q7Z628-1]
NP_005854.2. NM_005863.4. [Q7Z628-2]
UniGeneHs.25155.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3EO2X-ray2.60A161-373[»]
ProteinModelPortalQ7Z628.
SMRQ7Z628. Positions 166-499.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115565. 7 interactions.
IntActQ7Z628. 2 interactions.
STRING9606.ENSP00000347134.

PTM databases

PhosphoSiteQ7Z628.

Polymorphism databases

DMDM52782735.

Proteomic databases

MaxQBQ7Z628.
PaxDbQ7Z628.
PRIDEQ7Z628.

Protocols and materials databases

DNASU10276.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000355029; ENSP00000347134; ENSG00000173848. [Q7Z628-1]
ENST00000380359; ENSP00000369717; ENSG00000173848. [Q7Z628-2]
GeneID10276.
KEGGhsa:10276.
UCSCuc001iia.4. human. [Q7Z628-1]

Organism-specific databases

CTD10276.
GeneCardsGC10P005444.
HGNCHGNC:14592. NET1.
HPAHPA020068.
MIM606450. gene.
neXtProtNX_Q7Z628.
PharmGKBPA164742175.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5422.
HOVERGENHBG050567.
InParanoidQ7Z628.
OMATTREIKR.
OrthoDBEOG7J446D.
PhylomeDBQ7Z628.
TreeFamTF328974.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

ArrayExpressQ7Z628.
BgeeQ7Z628.
CleanExHS_NET1.
GenevestigatorQ7Z628.

Family and domain databases

Gene3D1.20.900.10. 1 hit.
2.30.29.30. 1 hit.
InterProIPR000219. DH-domain.
IPR001331. GDS_CDC24_CS.
IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
IPR015721. RhoGEF-like.
[Graphical view]
PANTHERPTHR22825. PTHR22825. 1 hit.
PfamPF00169. PH. 1 hit.
PF00621. RhoGEF. 1 hit.
[Graphical view]
SMARTSM00233. PH. 1 hit.
SM00325. RhoGEF. 1 hit.
[Graphical view]
SUPFAMSSF48065. SSF48065. 1 hit.
PROSITEPS00741. DH_1. 1 hit.
PS50010. DH_2. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSNET1. human.
EvolutionaryTraceQ7Z628.
GeneWikiNET1.
GenomeRNAi10276.
NextBio38926.
PROQ7Z628.
SOURCESearch...

Entry information

Entry nameARHG8_HUMAN
AccessionPrimary (citable) accession number: Q7Z628
Secondary accession number(s): Q12773 expand/collapse secondary AC list , Q96D82, Q99903, Q9UEN6
Entry history
Integrated into UniProtKB/Swiss-Prot: September 27, 2004
Last sequence update: October 1, 2003
Last modified: July 9, 2014
This is version 101 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM