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Protein

Neuroepithelial cell-transforming gene 1 protein

Gene

NET1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

GO - Biological processi

  • cellular response to hydrogen peroxide Source: UniProtKB
  • cellular response to ionizing radiation Source: UniProtKB
  • G-protein coupled receptor signaling pathway Source: Reactome
  • intracellular signal transduction Source: InterPro
  • myoblast migration Source: Ensembl
  • positive regulation of apoptotic process Source: UniProtKB
  • positive regulation of GTPase activity Source: UniProtKB
  • positive regulation of substrate adhesion-dependent cell spreading Source: Ensembl
  • regulation of cell growth Source: UniProtKB
  • regulation of Rho protein signal transduction Source: InterPro
  • regulation of small GTPase mediated signal transduction Source: Reactome
  • signal transduction Source: ProtInc

Keywordsi

Molecular functionGuanine-nucleotide releasing factor

Enzyme and pathway databases

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

Names & Taxonomyi

Protein namesi
Recommended name:
Neuroepithelial cell-transforming gene 1 protein
Alternative name(s):
Proto-oncogene p65 Net1
Rho guanine nucleotide exchange factor 8
Gene namesi
Name:NET1
Synonyms:ARHGEF8
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

EuPathDBiHostDB:ENSG00000173848.18
HGNCiHGNC:14592 NET1
MIMi606450 gene
neXtProtiNX_Q7Z628

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

DisGeNETi10276
OpenTargetsiENSG00000173848
PharmGKBiPA164742175

Polymorphism and mutation databases

BioMutaiNET1
DMDMi52782735

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000809241 – 596Neuroepithelial cell-transforming gene 1 proteinAdd BLAST596

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei21PhosphoserineCombined sources1
Modified residuei32PhosphoserineCombined sources1
Modified residuei100PhosphoserineCombined sources1
Modified residuei106PhosphoserineCombined sources1
Modified residuei122PhosphoserineCombined sources1
Modified residuei508PhosphoserineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ7Z628
MaxQBiQ7Z628
PaxDbiQ7Z628
PeptideAtlasiQ7Z628
PRIDEiQ7Z628

PTM databases

iPTMnetiQ7Z628
PhosphoSitePlusiQ7Z628

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Inductioni

By TGFB1. Up-regulated by DNA damaging agents like H2O2 or ionizing radiation (IR).2 Publications

Gene expression databases

BgeeiENSG00000173848
CleanExiHS_NET1
ExpressionAtlasiQ7Z628 baseline and differential
GenevisibleiQ7Z628 HS

Organism-specific databases

HPAiHPA020068

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 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
DLG1Q129592EBI-2511306,EBI-357481

GO - Molecular functioni

Protein-protein interaction databases

BioGridi115565, 18 interactors
IntActiQ7Z628, 5 interactors
MINTiQ7Z628
STRINGi9606.ENSP00000347134

Structurei

Secondary structure

1596
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi170 – 199Combined sources30
Helixi201 – 206Combined sources6
Helixi212 – 219Combined sources8
Turni220 – 225Combined sources6
Helixi226 – 238Combined sources13
Helixi250 – 256Combined sources7
Helixi257 – 263Combined sources7
Helixi264 – 279Combined sources16
Helixi280 – 282Combined sources3
Helixi284 – 295Combined sources12
Helixi297 – 299Combined sources3
Helixi304 – 308Combined sources5
Helixi310 – 315Combined sources6
Helixi318 – 327Combined sources10
Helixi335 – 366Combined sources32
Helixi374 – 376Combined sources3
Helixi379 – 382Combined sources4
Beta strandi387 – 395Combined sources9
Beta strandi400 – 416Combined sources17
Beta strandi418 – 420Combined sources3
Beta strandi423 – 426Combined sources4
Helixi433 – 435Combined sources3
Beta strandi436 – 440Combined sources5
Beta strandi464 – 470Combined sources7
Beta strandi478 – 482Combined sources5
Helixi486 – 501Combined sources16

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3EO2X-ray2.60A161-373[»]
4XH9X-ray2.00A/D149-501[»]
ProteinModelPortaliQ7Z628
SMRiQ7Z628
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ7Z628

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini174 – 356DHPROSITE-ProRule annotationAdd BLAST183
Domaini386 – 501PHPROSITE-ProRule annotationAdd BLAST116

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 74Necessary for nuclear localizationBy similarityAdd BLAST74

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi12 – 19Nuclear localization signalBy similarity8
Motifi66 – 72Nuclear localization signalBy similarity7

Phylogenomic databases

eggNOGiKOG4305 Eukaryota
COG5422 LUCA
GeneTreeiENSGT00760000119193
HOVERGENiHBG050567
InParanoidiQ7Z628
KOiK20683
OMAiGPNWDFT
OrthoDBiEOG091G05S7
PhylomeDBiQ7Z628
TreeFamiTF328974

Family and domain databases

CDDicd13224 PH_Net1, 1 hit
cd00160 RhoGEF, 1 hit
Gene3Di1.20.900.10, 1 hit
2.30.29.30, 1 hit
InterProiView protein in InterPro
IPR035899 DBL_dom_sf
IPR000219 DH-domain
IPR001331 GDS_CDC24_CS
IPR037853 Net1_PH
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
PfamiView protein in Pfam
PF00169 PH, 1 hit
PF00621 RhoGEF, 1 hit
SMARTiView protein in SMART
SM00233 PH, 1 hit
SM00325 RhoGEF, 1 hit
SUPFAMiSSF48065 SSF48065, 1 hit
PROSITEiView protein in PROSITE
PS00741 DH_1, 1 hit
PS50010 DH_2, 1 hit
PS50003 PH_DOMAIN, 1 hit

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q7Z628-1) [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
MEPELAAQKQ PRPRRRSRRA SGLSTEGATG PSADTSGSEL DGRCSLRRGS
60 70 80 90 100
SFTFLTPGPN WDFTLKRKRR EKDDDVVSLS SLDLKEPSNK RVRPLARVTS
110 120 130 140 150
LANLISPVRN GAVRRFGQTI QSFTLRGDHR SPASAQKFSS RSTVPTPAKR
160 170 180 190 200
RSSALWSEML DITMKESLTT REIRRQEAIY EMSRGEQDLI EDLKLARKAY
210 220 230 240 250
HDPMLKLSIM SEEELTHIFG DLDSYIPLHE DLLTRIGEAT KPDGTVEQIG
260 270 280 290 300
HILVSWLPRL NAYRGYCSNQ LAAKALLDQK KQDPRVQDFL QRCLESPFSR
310 320 330 340 350
KLDLWSFLDI PRSRLVKYPL LLKEILKHTP KEHPDVQLLE DAILIIQGVL
360 370 380 390 400
SDINLKKGES ECQYYIDKLE YLDEKQRDPR IEASKVLLCH GELRSKSGHK
410 420 430 440 450
LYIFLFQDIL VLTRPVTRNE RHSYQVYRQP IPVQELVLED LQDGDVRMGG
460 470 480 490 500
SFRGAFSNSE KAKNIFRIRF HDPSPAQSHT LQANDVFHKQ QWFNCIRAAI
510 520 530 540 550
APFQSAGSPP ELQGLPELHE ECEGNHPSAR KLTAQRRAST VSSVTQVEVD
560 570 580 590
ENAYRCGSGM QMAEDSKSLK THQTQPGIRR ARDKALSGGK RKETLV
Length:596
Mass (Da):67,740
Last modified:October 1, 2003 - v1
Checksum:iE1AD964F14650D2C
GO
Isoform 2 (identifier: Q7Z628-2) [UniParc]FASTAAdd to basket

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

Show »
Length:542
Mass (Da):61,885
Checksum:i770F252F0FCA7E92
GO

Sequence cautioni

The sequence AAB08847 differs from that shown. Reason: Frameshift at position 586.Curated
The sequence AAB37683 differs from that shown. Reason: Frameshift at positions 15 and 33.Curated
The sequence CAA08974 differs from that shown. Reason: Frameshift at positions 8, 55, 59, 70 and 586.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti39E → R in AAB37683 (PubMed:8649828).Curated1
Sequence conflicti61W → C in AAB37683 (PubMed:8649828).Curated1
Sequence conflicti143 – 146TVPT → MDGW in AAB08847 (PubMed:8649828).Curated4

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_035972202D → N in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_051982417T → I. Corresponds to variant dbSNP:rs34658946Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0116191 – 54Missing in isoform 2. 2 PublicationsAdd BLAST54
Alternative sequenceiVSP_01162055 – 85LTPGP…SLDLK → MVAHDETGGLLPIKRTIRVL DVNNQSFREQE in isoform 2. 2 PublicationsAdd BLAST31

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS41483.1 [Q7Z628-1]
CCDS7067.1 [Q7Z628-2]
PIRiG01210
RefSeqiNP_001040625.1, NM_001047160.2 [Q7Z628-1]
NP_005854.2, NM_005863.4 [Q7Z628-2]
UniGeneiHs.25155

Genome annotation databases

EnsembliENST00000355029; ENSP00000347134; ENSG00000173848 [Q7Z628-1]
ENST00000380359; ENSP00000369717; ENSG00000173848 [Q7Z628-2]
GeneIDi10276
KEGGihsa:10276
UCSCiuc001iia.5 human [Q7Z628-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiARHG8_HUMAN
AccessioniPrimary (citable) accession number: Q7Z628
Secondary accession number(s): Q12773
, Q96D82, Q99903, Q9UEN6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 27, 2004
Last sequence update: October 1, 2003
Last modified: March 28, 2018
This is version 136 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
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Main funding by: National Institutes of Health