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Q6ZSZ5 (ARHGI_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 98. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Rho guanine nucleotide exchange factor 18
Alternative name(s):
114 kDa Rho-specific guanine nucleotide exchange factor
Short name=p114-Rho-GEF
Short name=p114RhoGEF
Septin-associated RhoGEF
Short name=SA-RhoGEF
Gene names
Name:ARHGEF18
Synonyms:KIAA0521
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1173 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPases. May play a role in actin cytoskeleton reorganization in different tissues since its activation induces formation of actin stress fibers. Also act as a GEF for RAC1, inducing production of reactive oxygen species (ROS). Does not act as a GEF for CDC42. The G protein beta-gamma (Gbetagamma) subunits of heterotrimeric G proteins act as activators, explaining the integrated effects of LPA and other G-protein coupled receptor agonists on actin stress fiber formation, cell shape change and ROS production. Ref.5 Ref.7 Ref.8

Subunit structure

Interacts with SEPT9; interaction may inhibit GEF activity. Interacts with Gbetagamma subunits GNB1 and GNG2. Ref.7 Ref.8

Subcellular location

Cytoplasm. Note: Colocalizes with actin stress fibers. Ref.8

Tissue specificity

Expressed in all tissues tested with highest expression in kidney and pancreas. Weakly or not expressed in liver, skeletal muscle and testis. Ref.5 Ref.7 Ref.8

Sequence similarities

Contains 1 DH (DBL-homology) domain.

Contains 1 PH domain.

Sequence caution

The sequence AAH77721.1 differs from that shown. Reason: Aberrant splicing.

The sequence BAA25447.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainCoiled coil
   Molecular functionGuanine-nucleotide releasing factor
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactin cytoskeleton organization

Inferred from direct assay Ref.7. Source: MGI

apoptotic signaling pathway

Traceable author statement. Source: Reactome

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

positive regulation of apoptotic process

Traceable author statement. Source: Reactome

regulation of GTPase activity

Inferred from direct assay Ref.7. Source: GOC

regulation of cell shape

Inferred from direct assay Ref.7. Source: MGI

regulation of small GTPase mediated signal transduction

Traceable author statement. Source: Reactome

small GTPase mediated signal transduction

Inferred from direct assay Ref.7. Source: MGI

transforming growth factor beta receptor signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentapical part of cell

Inferred from direct assay PubMed 22006950. Source: MGI

cell junction

Traceable author statement. Source: Reactome

cytoplasm

Inferred from direct assay. Source: HPA

cytosol

Traceable author statement. Source: Reactome

   Molecular_functionRho guanyl-nucleotide exchange factor activity

Inferred from electronic annotation. Source: InterPro

guanyl-nucleotide exchange factor activity

Inferred from direct assay Ref.7. Source: MGI

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q6ZSZ5-1)

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: Q6ZSZ5-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-158: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11731173Rho guanine nucleotide exchange factor 18
PRO_0000341415

Regions

Domain259 – 456198DH
Domain496 – 598103PH
Coiled coil799 – 81921 Potential
Coiled coil850 – 960111 Potential
Compositional bias1104 – 115855Pro-rich

Natural variations

Alternative sequence1 – 158158Missing in isoform 2.
VSP_034315
Natural variant7011Q → R. Ref.1 Ref.4
Corresponds to variant rs2287918 [ dbSNP | Ensembl ].
VAR_044066
Natural variant7521R → Q.
Corresponds to variant rs2287920 [ dbSNP | Ensembl ].
VAR_044067
Natural variant10191N → S. Ref.1 Ref.4
Corresponds to variant rs9329368 [ dbSNP | Ensembl ].
VAR_063099

Experimental info

Sequence conflict1031V → M in BAC86801. Ref.2
Sequence conflict1831I → V in BAC86801. Ref.2
Sequence conflict11071P → S in BAC86801. Ref.2

Sequences

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

Last modified May 18, 2010. Version 3.
Checksum: D986A1F85D48EE24

FASTA1,173130,780
        10         20         30         40         50         60 
MVTVGTNILP SRPAASANTA REDAALFSRR IPPRHKNGAA QPGAAPGPGA PGANMGNAHS 

        70         80         90        100        110        120 
KSGDRHSALP GRPELSFYGS FPRKWSENVF LDNELLTSKI LSVLRPQSER GFRAGDLRYP 

       130        140        150        160        170        180 
THFLSTNSVL ASVTASLKEH PRGTLLSDGS PALSRNVGMT VSQKGGPQPT PSPAGPGTQL 

       190        200        210        220        230        240 
GPITGEMDEA DSAFLKFKQT ADDSLSLTSP NTESIFVEDP YTASLRSEIE SDGHEFEAES 

       250        260        270        280        290        300 
WSLAVDAAYA KKQKREVVKR QDVLYELMQT EVHHVRTLKI MLKVYSRALQ EELQFSSKAI 

       310        320        330        340        350        360 
GRLFPCADDL LETHSHFLAR LKERRQESLE EGSDRNYVIQ KIGDLLVQQF SGENGERMKE 

       370        380        390        400        410        420 
KYGVFCSGHN EAVSHYKLLL QQNKKFQNLI KKIGNFSIVR RLGVQECILL VTQRITKYPV 

       430        440        450        460        470        480 
LVERIIQNTE AGTEDYEDLT QALNLIKDII SQVDAKVSEC EKGQRLREIA GKMDLKSSSK 

       490        500        510        520        530        540 
LKNGLTFRKE DMLQRQLHLE GMLCWKTTSG RLKDILAILL TDVLLLLQEK DQKYVFASVD 

       550        560        570        580        590        600 
SKPPVISLQK LIVREVANEE KAMFLISASL QGPEMYEIYT SSKEDRNAWM AHIQRAVESC 

       610        620        630        640        650        660 
PDEEEGPFSL PEEERKVVEA RATRLRDFQE RLSMKDQLIA QSLLEKQQIY LEMAEMGGLE 

       670        680        690        700        710        720 
DLPQPRGLFR GGDPSETLQG ELILKSAMSE IEGIQSLICR QLGSANGQAE DGGSSTGPPR 

       730        740        750        760        770        780 
RAETFAGYDC TNSPTKNGSF KKKVSSTDPR PRDWRGPPNS PDLKLSDSDI PGSSEESPQV 

       790        800        810        820        830        840 
VEAPGTESDP RLPTVLESEL VQRIQTLSQL LLNLQAVIAH QDSYVETQRA AIQEREKQFR 

       850        860        870        880        890        900 
LQSTRGNLLL EQERQRNFEK QREERAALEK LQSQLRHEQQ RWERERQWQH QELERAGARL 

       910        920        930        940        950        960 
QEREGEARQL RERLEQERAE LERQRQAYQH DLERLREAQR AVERERERLE LLRRLKKQNT 

       970        980        990       1000       1010       1020 
APGALPPDTL AEAQPPSHPP SFNGEGLEGP RVSMLPSGVG PEYAERPEVA RRDSAPTENR 

      1030       1040       1050       1060       1070       1080 
LAKSDVPIQL LSATNQFQRQ AAVQQQIPTK LAASTKGGKD KGGKSRGSQR WESSASFDLK 

      1090       1100       1110       1120       1130       1140 
QQLLLNKLMG KDESTSRNRR SLSPILPGRH SPAPPPDPGF PAPSPPPADS PSEGFSLKAG 

      1150       1160       1170 
GTALLPGPPA PSPLPATPLS AKEDASKEDV IFF 

« Hide

Isoform 2 [UniParc].

Checksum: 03BD1D9224E422BD
Show »

FASTA1,015114,077

References

« Hide 'large scale' references
[1]"Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro."
Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
DNA Res. 5:31-39(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANTS ARG-701 AND SER-1019.
Tissue: Brain.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[3]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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] OF 1-1156 (ISOFORM 2), VARIANTS ARG-701 AND SER-1019.
Tissue: Lymph.
[5]"Identification and characterization of a novel Rho-specific guanine nucleotide exchange factor."
Blomquist A., Schwoerer G., Schablowski H., Psoma A., Lehnen M., Jakobs K.H., Ruemenapp U.
Biochem. J. 352:319-325(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
[6]"A physical and transcript map of the MCOLN1 gene region on human chromosome 19p13.3-p13.2."
Acierno J.S. Jr., Kennedy J.C., Falardeau J.L., Leyne M., Bromley M.C., Colman M.W., Sun M., Bove C., Ashworth L.K., Chadwick L.H., Schiripo T., Ma S., Goldin E., Schiffmann R., Slaugenhaupt S.A.
Genomics 73:203-210(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION.
[7]"G Protein betagamma subunits stimulate p114RhoGEF, a guanine nucleotide exchange factor for RhoA and Rac1: regulation of cell shape and reactive oxygen species production."
Niu J., Profirovic J., Pan H., Vaiskunaite R., Voyno-Yasenetskaya T.
Circ. Res. 93:848-856(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH GNB1 AND GNG2.
[8]"Cytoskeletal modification of Rho guanine nucleotide exchange factor activity: identification of a Rho guanine nucleotide exchange factor as a binding partner for Sept9b, a mammalian septin."
Nagata K., Inagaki M.
Oncogene 24:65-76(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH SEPT9.
[9]"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB011093 mRNA. Translation: BAA25447.1. Different initiation.
AK127045 mRNA. Translation: BAC86801.1.
AC008878 Genomic DNA. No translation available.
AC119396 Genomic DNA. No translation available.
BC077721 mRNA. Translation: AAH77721.1. Sequence problems.
CCDSCCDS12177.1. [Q6ZSZ5-2]
CCDS45946.1. [Q6ZSZ5-1]
RefSeqNP_001124427.1. NM_001130955.1. [Q6ZSZ5-1]
NP_056133.2. NM_015318.3. [Q6ZSZ5-2]
XP_006722771.1. XM_006722708.1. [Q6ZSZ5-2]
XP_006722772.1. XM_006722709.1. [Q6ZSZ5-2]
UniGeneHs.465761.
Hs.736818.

3D structure databases

ProteinModelPortalQ6ZSZ5.
SMRQ6ZSZ5. Positions 220-606.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116950. 5 interactions.
IntActQ6ZSZ5. 1 interaction.
STRING9606.ENSP00000352995.

PTM databases

PhosphoSiteQ6ZSZ5.

Polymorphism databases

DMDM296439444.

Proteomic databases

MaxQBQ6ZSZ5.
PaxDbQ6ZSZ5.
PRIDEQ6ZSZ5.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000319670; ENSP00000319200; ENSG00000104880. [Q6ZSZ5-2]
ENST00000359920; ENSP00000352995; ENSG00000104880. [Q6ZSZ5-1]
GeneID23370.
KEGGhsa:23370.
UCSCuc002mgh.3. human. [Q6ZSZ5-1]

Organism-specific databases

CTD23370.
GeneCardsGC19P007459.
HGNCHGNC:17090. ARHGEF18.
HPAHPA042689.
neXtProtNX_Q6ZSZ5.
PharmGKBPA128394630.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG243163.
HOGENOMHOG000236361.
HOVERGENHBG104846.
InParanoidQ6ZSZ5.
OMAPRKWSEN.
OrthoDBEOG7JDQWP.
PhylomeDBQ6ZSZ5.
TreeFamTF325887.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.

Gene expression databases

ArrayExpressQ6ZSZ5.
BgeeQ6ZSZ5.
CleanExHS_ARHGEF18.
GenevestigatorQ6ZSZ5.

Family and domain databases

Gene3D1.20.900.10. 1 hit.
2.30.29.30. 1 hit.
InterProIPR000219. DH-domain.
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.
PROSITEPS50010. DH_2. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSARHGEF18. human.
GenomeRNAi23370.
NextBio45444.
PROQ6ZSZ5.

Entry information

Entry nameARHGI_HUMAN
AccessionPrimary (citable) accession number: Q6ZSZ5
Secondary accession number(s): A8MV62 expand/collapse secondary AC list , B5ME81, O60274, Q6DD92
Entry history
Integrated into UniProtKB/Swiss-Prot: June 10, 2008
Last sequence update: May 18, 2010
Last modified: July 9, 2014
This is version 98 of the entry and version 3 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

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 19

Human chromosome 19: entries, gene names and cross-references to MIM