Q7Z628 (ARHG8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	596 AA.
Sequence status	Complete.
Protein existence	Evidence 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 component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Proto-oncogene
Molecular function	Guanine-nucleotide releasing factor
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic 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 small GTPase mediated signal transduction Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	Rho guanyl-nucleotide exchange factor activity Inferred from electronic annotation. Source: InterPro guanyl-nucleotide exchange factor activity Traceable author statement Ref.1. Source: ProtInc phospholipid binding Inferred from electronic annotation. Source: InterPro
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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 596

596

Neuroepithelial cell-transforming gene 1 protein

PRO_0000080924

Regions

Domain

174 – 356

183

DH

Domain

386 – 501

116

PH

Region

1 – 74

74

Necessary for nuclear localization By similarity

Motif

12 – 19

8

Nuclear localization signal By similarity

Motif

66 – 72

7

Nuclear localization signal By similarity

Amino acid modifications

Modified residue

21

1

Phosphoserine Ref.5

Modified residue

32

1

Phosphoserine Ref.5

Modified residue

106

1

Phosphoserine Ref.4 Ref.5

Modified residue

508

1

Phosphoserine By similarity

Natural variations

Alternative sequence

1 – 54

54

Missing in isoform 2.

VSP_011619

Alternative sequence

55 – 85

31

LTPGP…SLDLK → MVAHDETGGLLPIKRTIRVL DVNNQSFREQE in isoform 2.

VSP_011620

Natural variant

202

1

D → N in a breast cancer sample; somatic mutation. Ref.8

VAR_035972

Natural variant

417

1

T → I.
Corresponds to variant rs34658946 [ dbSNP | Ensembl ].

VAR_051982

Experimental info

Sequence conflict

39

1

E → R in AAB37683. Ref.1

Sequence conflict

61

1

W → C in AAB37683. Ref.1

Sequence conflict

143 – 146

4

TVPT → MDGW in AAB08847. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

596

Helix Strand Turn

Details...

Helix

170 – 199

30

Helix

201 – 206

6

Helix

212 – 219

8

Helix

222 – 239

18

Helix

250 – 256

7

Helix

257 – 263

7

Helix

264 – 267

4

Helix

270 – 280

11

Helix

284 – 295

12

Helix

304 – 308

5

Helix

309 – 327

19

Helix

335 – 351

17

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2003. Version 1. Checksum: E1AD964F14650D2C	FASTA	596	67,740
	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
	Isoform 2 [UniParc]. Checksum: 770F252F0FCA7E92	FASTA	542	61,885
	10 20 30 40 50 60 MVAHDETGGL LPIKRTIRVL DVNNQSFREQ EEPSNKRVRP LARVTSLANL ISPVRNGAVR 70 80 90 100 110 120 RFGQTIQSFT LRGDHRSPAS AQKFSSRSTV PTPAKRRSSA LWSEMLDITM KESLTTREIR 130 140 150 160 170 180 RQEAIYEMSR GEQDLIEDLK LARKAYHDPM LKLSIMSEEE LTHIFGDLDS YIPLHEDLLT 190 200 210 220 230 240 RIGEATKPDG TVEQIGHILV SWLPRLNAYR GYCSNQLAAK ALLDQKKQDP RVQDFLQRCL 250 260 270 280 290 300 ESPFSRKLDL WSFLDIPRSR LVKYPLLLKE ILKHTPKEHP DVQLLEDAIL IIQGVLSDIN 310 320 330 340 350 360 LKKGESECQY YIDKLEYLDE KQRDPRIEAS KVLLCHGELR SKSGHKLYIF LFQDILVLTR 370 380 390 400 410 420 PVTRNERHSY QVYRQPIPVQ ELVLEDLQDG DVRMGGSFRG AFSNSEKAKN IFRIRFHDPS 430 440 450 460 470 480 PAQSHTLQAN DVFHKQQWFN CIRAAIAPFQ SAGSPPELQG LPELHEECEG NHPSARKLTA 490 500 510 520 530 540 QRRASTVSSV TQVEVDENAY RCGSGMQMAE DSKSLKTHQT QPGIRRARDK ALSGGKRKET LV

References

	« Hide 'large scale' referencesShow '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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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]	"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.
[8]	"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. , 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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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.

IPI

IPI00180559.
IPI00385312.

PIR

G01210.

RefSeq

NP_001040625.1. NM_001047160.2.
NP_005854.2. NM_005863.4.

UniGene

Hs.25155.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3EO2	X-ray	2.60	A	161-373	[»]

ProteinModelPortal

Q7Z628.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q7Z628. 2 interactions.

STRING

9606.ENSP00000347134.

PTM databases

PhosphoSite

Q7Z628.

Polymorphism databases

DMDM

52782735.

Proteomic databases

PaxDb

Q7Z628.

PRIDE

Q7Z628.

Protocols and materials databases

DNASU

10276.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000355029; ENSP00000347134; ENSG00000173848.
ENST00000380359; ENSP00000369717; ENSG00000173848.

GeneID

10276.

KEGG

hsa:10276.

UCSC

uc001iia.3. human.

Organism-specific databases

CTD

10276.

GeneCards

GC10P005444.

HGNC

HGNC:14592. NET1.

HPA

HPA020068.

MIM

606450. gene.

neXtProt

NX_Q7Z628.

PharmGKB

PA164742175.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5422.

HOVERGEN

HBG050567.

InParanoid

Q7Z628.

OMA

SAQKFSS.

OrthoDB

EOG4BVRTK.

PhylomeDB

Q7Z628.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

Q7Z628.

Bgee

Q7Z628.

CleanEx

HS_NET1.

Genevestigator

Q7Z628.

GermOnline

ENSG00000173848. Homo sapiens.

Family and domain databases

Gene3D

1.20.900.10. 1 hit.
2.30.29.30. 1 hit.

InterPro

IPR000219. DH-domain.
IPR001331. GDS_CDC24_CS.
IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
IPR015721. RhoGEF-like.
[Graphical view]

PANTHER

PTHR22825. PTHR22825. 1 hit.

Pfam

PF00169. PH. 1 hit.
PF00621. RhoGEF. 1 hit.
[Graphical view]

SMART

SM00233. PH. 1 hit.
SM00325. RhoGEF. 1 hit.
[Graphical view]

SUPFAM

SSF48065. DH-domain. 1 hit.

PROSITE

PS00741. DH_1. 1 hit.
PS50010. DH_2. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

NET1. human.

EvolutionaryTrace

Q7Z628.

GenomeRNAi

10276.

NextBio

38926.

SOURCE

Search...

Entry information

Entry name

ARHG8_HUMAN

Accession

Primary (citable) accession number: Q7Z628
Secondary accession number(s): Q12773 , Q96D82, Q99903, Q9UEN6

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 27, 2004
Last sequence update:	October 1, 2003
Last modified:	May 29, 2013
This is version 91 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.