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Q7Z628

- ARHG8_HUMAN

UniProt

Q7Z628 - ARHG8_HUMAN

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Protein

Neuroepithelial cell-transforming gene 1 protein

Gene

NET1

Organism
Homo sapiens (Human)
Status
Reviewed - 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

  1. guanyl-nucleotide exchange factor activity Source: ProtInc
  2. Rho guanyl-nucleotide exchange factor activity Source: InterPro

GO - Biological processi

  1. apoptotic signaling pathway Source: Reactome
  2. cellular response to hydrogen peroxide Source: UniProtKB
  3. cellular response to ionizing radiation Source: UniProtKB
  4. myoblast migration Source: Ensembl
  5. neurotrophin TRK receptor signaling pathway Source: Reactome
  6. positive regulation of apoptotic process Source: UniProtKB
  7. positive regulation of Rho GTPase activity Source: UniProtKB
  8. positive regulation of substrate adhesion-dependent cell spreading Source: Ensembl
  9. regulation of cell growth Source: UniProtKB
  10. regulation of small GTPase mediated signal transduction Source: Reactome
  11. signal transduction Source: ProtInc
  12. small GTPase mediated signal transduction Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Guanine-nucleotide releasing factor

Enzyme and pathway databases

ReactomeiREACT_11051. Rho GTPase cycle.
REACT_13638. NRAGE signals death through JNK.
REACT_18407. 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
ProteomesiUP000005640: Chromosome 10

Organism-specific databases

HGNCiHGNC:14592. NET1.

Subcellular locationi

Cytoplasm By similarity. Nucleus By similarity

GO - Cellular componenti

  1. cytosol Source: Reactome
  2. nucleus Source: UniProtKB-KW
  3. plasma membrane Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

PharmGKBiPA164742175.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 596596Neuroepithelial cell-transforming gene 1 proteinPRO_0000080924Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionine1 Publication
Modified residuei21 – 211Phosphoserine1 Publication
Modified residuei32 – 321Phosphoserine1 Publication
Modified residuei106 – 1061Phosphoserine2 Publications
Modified residuei508 – 5081PhosphoserineBy similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiQ7Z628.
PaxDbiQ7Z628.
PRIDEiQ7Z628.

PTM databases

PhosphoSiteiQ7Z628.

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

BgeeiQ7Z628.
CleanExiHS_NET1.
ExpressionAtlasiQ7Z628. baseline and differential.
GenevestigatoriQ7Z628.

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

Protein-protein interaction databases

BioGridi115565. 8 interactions.
IntActiQ7Z628. 2 interactions.
STRINGi9606.ENSP00000347134.

Structurei

Secondary structure

1
596
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi170 – 19930Combined sources
Helixi201 – 2066Combined sources
Helixi212 – 2198Combined sources
Helixi222 – 23918Combined sources
Helixi250 – 2567Combined sources
Helixi257 – 2637Combined sources
Helixi264 – 2674Combined sources
Helixi270 – 28011Combined sources
Helixi284 – 29512Combined sources
Helixi304 – 3085Combined sources
Helixi309 – 32719Combined sources
Helixi335 – 35117Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3EO2X-ray2.60A161-373[»]
ProteinModelPortaliQ7Z628.
SMRiQ7Z628. Positions 166-499.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ7Z628.

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 localizationBy similarityAdd
BLAST

Motif

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

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiCOG5422.
GeneTreeiENSGT00760000119307.
HOVERGENiHBG050567.
InParanoidiQ7Z628.
OMAiTTREIKR.
OrthoDBiEOG7J446D.
PhylomeDBiQ7Z628.
TreeFamiTF328974.

Family and domain databases

Gene3Di1.20.900.10. 1 hit.
2.30.29.30. 1 hit.
InterProiIPR000219. DH-domain.
IPR001331. GDS_CDC24_CS.
IPR001849. PH_domain.
IPR011993. PH_like_dom.
IPR015721. RhoGEF-like.
[Graphical view]
PANTHERiPTHR22825. PTHR22825. 1 hit.
PfamiPF00169. PH. 1 hit.
PF00621. RhoGEF. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
SM00325. RhoGEF. 1 hit.
[Graphical view]
SUPFAMiSSF48065. SSF48065. 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. Align

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 AAB08847.1 differs from that shown. Reason: Frameshift at position 586. Curated
The sequence AAB37683.1 differs from that shown. Reason: Frameshift at positions 15 and 33. Curated
The sequence CAA08974.1 differs from that shown. Reason: Frameshift at positions 8, 55, 59, 70 and 586. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti39 – 391E → R in AAB37683. (PubMed:8649828)Curated
Sequence conflicti61 – 611W → C in AAB37683. (PubMed:8649828)Curated
Sequence conflicti143 – 1464TVPT → MDGW in AAB08847. (PubMed:8649828)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti202 – 2021D → N in a breast cancer sample; somatic mutation. 1 Publication
VAR_035972
Natural varianti417 – 4171T → I.
Corresponds to variant rs34658946 [ dbSNP | Ensembl ].
VAR_051982

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 5454Missing in isoform 2. 2 PublicationsVSP_011619Add
BLAST
Alternative sequencei55 – 8531LTPGP…SLDLK → MVAHDETGGLLPIKRTIRVL DVNNQSFREQE in isoform 2. 2 PublicationsVSP_011620Add
BLAST

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.4. human. [Q7Z628-1]

Polymorphism databases

DMDMi52782735.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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 .
CCDSi CCDS41483.1. [Q7Z628-1 ]
CCDS7067.1. [Q7Z628-2 ]
PIRi G01210.
RefSeqi NP_001040625.1. NM_001047160.2. [Q7Z628-1 ]
NP_005854.2. NM_005863.4. [Q7Z628-2 ]
UniGenei Hs.25155.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
3EO2 X-ray 2.60 A 161-373 [» ]
ProteinModelPortali Q7Z628.
SMRi Q7Z628. Positions 166-499.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 115565. 8 interactions.
IntActi Q7Z628. 2 interactions.
STRINGi 9606.ENSP00000347134.

PTM databases

PhosphoSitei Q7Z628.

Polymorphism databases

DMDMi 52782735.

Proteomic databases

MaxQBi Q7Z628.
PaxDbi Q7Z628.
PRIDEi Q7Z628.

Protocols and materials databases

DNASUi 10276.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000355029 ; ENSP00000347134 ; ENSG00000173848 . [Q7Z628-1 ]
ENST00000380359 ; ENSP00000369717 ; ENSG00000173848 . [Q7Z628-2 ]
GeneIDi 10276.
KEGGi hsa:10276.
UCSCi uc001iia.4. human. [Q7Z628-1 ]

Organism-specific databases

CTDi 10276.
GeneCardsi GC10P005444.
HGNCi HGNC:14592. NET1.
HPAi HPA020068.
MIMi 606450. gene.
neXtProti NX_Q7Z628.
PharmGKBi PA164742175.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG5422.
GeneTreei ENSGT00760000119307.
HOVERGENi HBG050567.
InParanoidi Q7Z628.
OMAi TTREIKR.
OrthoDBi EOG7J446D.
PhylomeDBi Q7Z628.
TreeFami TF328974.

Enzyme and pathway databases

Reactomei REACT_11051. Rho GTPase cycle.
REACT_13638. NRAGE signals death through JNK.
REACT_18407. G alpha (12/13) signalling events.

Miscellaneous databases

ChiTaRSi NET1. human.
EvolutionaryTracei Q7Z628.
GeneWikii NET1.
GenomeRNAii 10276.
NextBioi 38926.
PROi Q7Z628.
SOURCEi Search...

Gene expression databases

Bgeei Q7Z628.
CleanExi HS_NET1.
ExpressionAtlasi Q7Z628. baseline and differential.
Genevestigatori Q7Z628.

Family and domain databases

Gene3Di 1.20.900.10. 1 hit.
2.30.29.30. 1 hit.
InterProi IPR000219. DH-domain.
IPR001331. GDS_CDC24_CS.
IPR001849. PH_domain.
IPR011993. PH_like_dom.
IPR015721. RhoGEF-like.
[Graphical view ]
PANTHERi PTHR22825. PTHR22825. 1 hit.
Pfami PF00169. PH. 1 hit.
PF00621. RhoGEF. 1 hit.
[Graphical view ]
SMARTi SM00233. PH. 1 hit.
SM00325. RhoGEF. 1 hit.
[Graphical view ]
SUPFAMi SSF48065. SSF48065. 1 hit.
PROSITEi PS00741. DH_1. 1 hit.
PS50010. DH_2. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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. 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. Cited for: VARIANT [LARGE SCALE ANALYSIS] ASN-202.

Entry informationi

Entry nameiARHG8_HUMAN
AccessioniPrimary (citable) accession number: Q7Z628
Secondary accession number(s): Q12773
, Q96D82, Q99903, Q9UEN6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 27, 2004
Last sequence update: October 1, 2003
Last modified: November 26, 2014
This is version 105 of the entry and version 1 of the sequence. [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

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3