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Protein

Neuroepithelial cell-transforming gene 1 protein

Gene

Net1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

GO - Molecular functioni

  • GTP-Rho binding Source: MGI
  • Rho guanyl-nucleotide exchange factor activity Source: InterPro

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Guanine-nucleotide releasing factor

Enzyme and pathway databases

ReactomeiR-MMU-193648. NRAGE signals death through JNK.
R-MMU-194840. Rho GTPase cycle.
R-MMU-416482. G alpha (12/13) signalling events.

Names & Taxonomyi

Protein namesi
Recommended name:
Neuroepithelial cell-transforming gene 1 protein
Alternative name(s):
Rho guanine nucleotide exchange factor 8
Gene namesi
Name:Net1
Synonyms:Arhgef8
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 13

Organism-specific databases

MGIiMGI:1927138. Net1.

Subcellular locationi

  • Cytoplasm 1 Publication
  • Nucleus 1 Publication

GO - Cellular componenti

  • cytoplasm Source: UniProtKB-SubCell
  • nucleus Source: MGI
  • plasma membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi12 – 165RPRRR → APAAA: Leads to cytoplasmic relocalization; when associated with 67-A--A-70. 1 Publication
Mutagenesisi67 – 704RKRR → AAAA: Leads to cytoplasmic relocalization; when associated with 12-A--A-16. 1 Publication
Mutagenesisi321 – 3211L → E: Inhibits transformation by N-terminal truncated form. 1 Publication
Mutagenesisi492 – 4921W → L: Inhibits transformation by N-terminal truncated form. 1 Publication

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 595595Neuroepithelial cell-transforming gene 1 proteinPRO_0000080925Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionineBy similarity
Modified residuei21 – 211PhosphoserineBy similarity
Modified residuei100 – 1001PhosphoserineBy similarity
Modified residuei106 – 1061PhosphoserineBy similarity
Modified residuei122 – 1221PhosphoserineBy similarity
Modified residuei508 – 5081PhosphoserineCombined sources

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiQ9Z206.
PaxDbiQ9Z206.
PRIDEiQ9Z206.

PTM databases

iPTMnetiQ9Z206.
PhosphoSiteiQ9Z206.

Expressioni

Gene expression databases

BgeeiENSMUSG00000021215.
CleanExiMM_NET1.
ExpressionAtlasiQ9Z206. baseline and differential.
GenevisibleiQ9Z206. MM.

Interactioni

Subunit structurei

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 BAIAP1.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Magi1Q6RHR96EBI-7840997,EBI-7440897

GO - Molecular functioni

  • GTP-Rho binding Source: MGI

Protein-protein interaction databases

BioGridi207915. 5 interactions.
IntActiQ9Z206. 1 interaction.
MINTiMINT-1780869.
STRINGi10090.ENSMUSP00000089464.

Structurei

3D structure databases

ProteinModelPortaliQ9Z206.
SMRiQ9Z206. Positions 157-501.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini174 – 356183DHPROSITE-ProRule annotationAdd
BLAST
Domaini386 – 501116PHPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 7474Necessary for nuclear localizationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi12 – 198Nuclear localization signal
Motifi66 – 727Nuclear localization signal

Domaini

The PH domain is sufficient for the nuclear export of the oncogenic N-terminal truncated form. The relocalization is not affected by the Leu-492 mutation.

Sequence similaritiesi

Contains 1 DH (DBL-homology) domain.PROSITE-ProRule annotation
Contains 1 PH domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG4305. Eukaryota.
COG5422. LUCA.
GeneTreeiENSGT00840000129831.
HOGENOMiHOG000034044.
HOVERGENiHBG050567.
InParanoidiQ9Z206.
OMAiGPNWDFT.
OrthoDBiEOG091G05S7.
PhylomeDBiQ9Z206.
TreeFamiTF328974.

Family and domain databases

Gene3Di1.20.900.10. 1 hit.
2.30.29.30. 1 hit.
InterProiIPR000219. DH-domain.
IPR001331. GDS_CDC24_CS.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
[Graphical view]
PfamiPF00169. PH. 1 hit.
PF00621. RhoGEF. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
SM00325. RhoGEF. 1 hit.
[Graphical view]
SUPFAMiSSF48065. SSF48065. 1 hit.
SSF50729. SSF50729. 1 hit.
PROSITEiPS00741. DH_1. 1 hit.
PS50010. DH_2. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9Z206-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MEPEPAAQKQ PRPRRRSRRV SMLSEEPAAG LPADTPGPAA NERCSLRRGS
60 70 80 90 100
SFTFLTPGPH WDFTLKRKRR EKDDDAVSLS SLDLKEPSNK RVRPLARVTS
110 120 130 140 150
LANLISPVRN GAVRRFGQTI QSFTLRGDHR SPASAQKSFS RSTVPTPTKR
160 170 180 190 200
RSSALWSEML DINMKESLTT REIKRQEAIY ELSRGEQDLI EDLKLARKAY
210 220 230 240 250
HDPMLKLSIM SEEELTHIFG DLDAYIPLHE DLLARIGEAT KPDGTVEQIG
260 270 280 290 300
HILVNWLPGL NAYRGYCSNQ LAAKALLDQK KQDPRVQDFL QRCLESPFSR
310 320 330 340 350
KLDLWSFLDI PRSRLVKYPL LLKEILRHTP KDHRDVQLLE EAILIIQGVL
360 370 380 390 400
SDINLKKGES ECQYYINKLE YLDEKQKDPR IEASKVLLCH GELKNKSGHK
410 420 430 440 450
LYIFLFQDIL VLTRPVTRNE RHLYQVYRQP IPVQELVLED LQDGDVRMGG
460 470 480 490 500
SFRGAFGNSD KAKNIFRVRF QDPSPGHSHT LQANDVFHKQ QWFNCIRAAI
510 520 530 540 550
APFQRAASPL ELQGLPDLHE ECEENNPSAG NLRAQRRSCV VPGVMQIDEE
560 570 580 590
SALDCGSSVQ TVEDTRNMKA QRPQPGLRRA RDKAQSGGKK KETLV
Length:595
Mass (Da):67,734
Last modified:September 27, 2004 - v2
Checksum:i95614632A87EA4F3
GO
Isoform 2 (identifier: Q9Z206-2) [UniParc]FASTAAdd to basket
Also known as: Net1a

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

Show »
Length:541
Mass (Da):61,765
Checksum:i38993EDD3F34D2DD
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti116 – 1161F → S in BAC38417 (PubMed:16141072).Curated
Sequence conflicti412 – 4121L → W in AAC71772 (PubMed:9670022).Curated
Sequence conflicti418 – 4181R → G in AAC71772 (PubMed:9670022).Curated
Sequence conflicti473 – 4731P → L in AAC71772 (PubMed:9670022).Curated
Sequence conflicti581 – 5822RD → SH in AAC71772 (PubMed:9670022).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 5454Missing in isoform 2. 3 PublicationsVSP_011622Add
BLAST
Alternative sequencei55 – 8531LTPGP…SLDLK → MVAHDEIGGLLPIKRTIRVL DVNNQPFREQE in isoform 2. 3 PublicationsVSP_011623Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF094520 mRNA. Translation: AAC71772.1.
AJ010045 mRNA. Translation: CAA08973.1.
AK082128 mRNA. Translation: BAC38417.1.
AK088632 mRNA. Translation: BAC40466.1.
BC004699 mRNA. Translation: AAH04699.1.
CCDSiCCDS26216.1. [Q9Z206-1]
CCDS36583.1. [Q9Z206-2]
RefSeqiNP_001040624.1. NM_001047159.2. [Q9Z206-2]
NP_062645.2. NM_019671.3. [Q9Z206-1]
UniGeneiMm.22261.

Genome annotation databases

EnsembliENSMUST00000091853; ENSMUSP00000089464; ENSMUSG00000021215. [Q9Z206-1]
ENSMUST00000099946; ENSMUSP00000097529; ENSMUSG00000021215. [Q9Z206-2]
GeneIDi56349.
KEGGimmu:56349.
UCSCiuc007pje.3. mouse. [Q9Z206-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF094520 mRNA. Translation: AAC71772.1.
AJ010045 mRNA. Translation: CAA08973.1.
AK082128 mRNA. Translation: BAC38417.1.
AK088632 mRNA. Translation: BAC40466.1.
BC004699 mRNA. Translation: AAH04699.1.
CCDSiCCDS26216.1. [Q9Z206-1]
CCDS36583.1. [Q9Z206-2]
RefSeqiNP_001040624.1. NM_001047159.2. [Q9Z206-2]
NP_062645.2. NM_019671.3. [Q9Z206-1]
UniGeneiMm.22261.

3D structure databases

ProteinModelPortaliQ9Z206.
SMRiQ9Z206. Positions 157-501.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi207915. 5 interactions.
IntActiQ9Z206. 1 interaction.
MINTiMINT-1780869.
STRINGi10090.ENSMUSP00000089464.

PTM databases

iPTMnetiQ9Z206.
PhosphoSiteiQ9Z206.

Proteomic databases

MaxQBiQ9Z206.
PaxDbiQ9Z206.
PRIDEiQ9Z206.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000091853; ENSMUSP00000089464; ENSMUSG00000021215. [Q9Z206-1]
ENSMUST00000099946; ENSMUSP00000097529; ENSMUSG00000021215. [Q9Z206-2]
GeneIDi56349.
KEGGimmu:56349.
UCSCiuc007pje.3. mouse. [Q9Z206-1]

Organism-specific databases

CTDi10276.
MGIiMGI:1927138. Net1.

Phylogenomic databases

eggNOGiKOG4305. Eukaryota.
COG5422. LUCA.
GeneTreeiENSGT00840000129831.
HOGENOMiHOG000034044.
HOVERGENiHBG050567.
InParanoidiQ9Z206.
OMAiGPNWDFT.
OrthoDBiEOG091G05S7.
PhylomeDBiQ9Z206.
TreeFamiTF328974.

Enzyme and pathway databases

ReactomeiR-MMU-193648. NRAGE signals death through JNK.
R-MMU-194840. Rho GTPase cycle.
R-MMU-416482. G alpha (12/13) signalling events.

Miscellaneous databases

PROiQ9Z206.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000021215.
CleanExiMM_NET1.
ExpressionAtlasiQ9Z206. baseline and differential.
GenevisibleiQ9Z206. MM.

Family and domain databases

Gene3Di1.20.900.10. 1 hit.
2.30.29.30. 1 hit.
InterProiIPR000219. DH-domain.
IPR001331. GDS_CDC24_CS.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
[Graphical view]
PfamiPF00169. PH. 1 hit.
PF00621. RhoGEF. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
SM00325. RhoGEF. 1 hit.
[Graphical view]
SUPFAMiSSF48065. SSF48065. 1 hit.
SSF50729. SSF50729. 1 hit.
PROSITEiPS00741. DH_1. 1 hit.
PS50010. DH_2. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiARHG8_MOUSE
AccessioniPrimary (citable) accession number: Q9Z206
Secondary accession number(s): Q8C4I0, Q9Z1L7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 27, 2004
Last sequence update: September 27, 2004
Last modified: September 7, 2016
This is version 133 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Can be converted to an oncogenic protein by N-terminal deletion that leads to nuclear export and cytoplasmic localization. Transformation seems to require the activity of multiple signaling pathways. The physiological conditions for cytoplasmic relocalization are not known yet.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.