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Protein

Rho guanine nucleotide exchange factor 18

Gene

Arhgef18

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

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. Required for EPB41L4B-mediated regulation of the circumferential actomyosin belt in epithelial cells.By similarity

GO - Molecular functioni

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-2173791. TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition).
R-MMU-416482. G alpha (12/13) signalling events.

Names & Taxonomyi

Protein namesi
Recommended name:
Rho guanine nucleotide exchange factor 18
Gene namesi
Name:Arhgef18
Synonyms:Kiaa0521
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:2142567. Arhgef18.

Subcellular locationi

  • Cytoplasm By similarity
  • Cytoplasmcytoskeleton By similarity
  • Apical cell membrane By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoskeleton, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 10211021Rho guanine nucleotide exchange factor 18PRO_0000341416Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei568 – 5681PhosphothreonineCombined sources
Modified residuei577 – 5771PhosphoserineCombined sources
Modified residuei952 – 9521PhosphoserineCombined sources
Modified residuei954 – 9541PhosphoserineCombined sources

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ6P9R4.
MaxQBiQ6P9R4.
PaxDbiQ6P9R4.
PRIDEiQ6P9R4.

PTM databases

iPTMnetiQ6P9R4.
PhosphoSiteiQ6P9R4.

Expressioni

Gene expression databases

BgeeiQ6P9R4.
ExpressionAtlasiQ6P9R4. baseline and differential.
GenevisibleiQ6P9R4. MM.

Interactioni

Subunit structurei

Interacts with SEPT9; interaction may inhibit GEF activity. Interacts with Gbetagamma subunits GNB1 and GNG2 (By similarity). Interacts with EPB41L4B. Interacts with INADL (via C-terminus).By similarity

Protein-protein interaction databases

BioGridi221794. 1 interaction.
IntActiQ6P9R4. 1 interaction.
STRINGi10090.ENSMUSP00000004684.

Structurei

3D structure databases

ProteinModelPortaliQ6P9R4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini101 – 298198DHPROSITE-ProRule annotationAdd
BLAST
Domaini339 – 441103PHPROSITE-ProRule annotationAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili700 – 800101Sequence analysisAdd
BLAST

Sequence similaritiesi

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

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG3520. Eukaryota.
COG5422. LUCA.
GeneTreeiENSGT00760000119193.
HOGENOMiHOG000236361.
HOVERGENiHBG104846.
InParanoidiQ6P9R4.
OMAiPRKWSEN.
OrthoDBiEOG7JDQWP.
TreeFamiTF325887.

Family and domain databases

Gene3Di1.20.900.10. 1 hit.
2.30.29.30. 1 hit.
InterProiIPR000219. DH-domain.
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.
PROSITEiPS50010. DH_2. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q6P9R4-1) [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
MTISQKGGLQ PTPSPAGSGV RLGPIAGDMD EADSVFLKLK QTADDSLSLT
60 70 80 90 100
SSNAESVFIE DPYIASLRCE IESDAHEFEA ESWSLSVDLA YAKKQKKEVV
110 120 130 140 150
KRQDVLYELM QTEAHHVRTL KIMLKVYSRA LQEELQFSGQ AVSRLFPCAD
160 170 180 190 200
DLLDMHSHFL ARLKERRQEF LEEGSDRNYV IQKIGDVLVQ QFSGETGERM
210 220 230 240 250
KEKYAVFCSG HNDAVGQYKL LLQQSKKFQN LIKKIGNFSI VRRLGVQECI
260 270 280 290 300
LLVTQRITKY PVLVERIIQN TEAGTEDYKD LSQALSLIKD IISQVDAKVS
310 320 330 340 350
EYEKDQRLKE IAAKTDQKSS GKLKNGLTFR KEDMLQQRQL HLEGALCWKS
360 370 380 390 400
TSGRLKDVLA VLLTDVLLLL QEKDQKYVFA SVDSKPPVIS LQKLIVREVA
410 420 430 440 450
NEEKAMFLIS ASMQGPEMYE MYTSSKEDRN IWMAHIRRAV ESCPDEEEDV
460 470 480 490 500
FSEAEEKKIA EARTMKLQEF QERLSLKDQL IAQSLLEKQQ IYLEMAQLSG
510 520 530 540 550
LEESAQNRGL FRGGGDPSET LRGEQILRSA MSEIEGIQSL ICQRHLGSTS
560 570 580 590 600
SQVEEGSVSA GLPRRAETFG GYDSVGSPSK GGSFKRKVSN SDLRPQDWQG
610 620 630 640 650
PASSPDSRPC DNSAPSGCCE ESPQAVEMPS TESLPTVLEL ELVHRVQTLS
660 670 680 690 700
QLLLSLQAVI AQQDSYVEMQ RTAIQEREKQ FRLQSTRGNL LLEQERQRNF
710 720 730 740 750
EKQREERAGV EKLQSQLRQE QQRWERERAR QQQELELAGA RLQEREGEAR
760 770 780 790 800
QMRQRLDQER TELERQRQAY QHDLERLREA QRAVDRERER LELLRRFKKQ
810 820 830 840 850
NTVPGALPPE VLAEAQPASH PPSFNGDGLE GHSAPAKAPG TQGSAMLHGT
860 870 880 890 900
GPDNVERPEV ARWDSAPPES RPAKSDVPIQ LLSATNQIQR QTAVQQQIPT
910 920 930 940 950
KLAASTKGGK EKGSKSRGSQ RWESSASFDL KQQLLLSKFI GKDESASRNR
960 970 980 990 1000
RSLSPVLPAA HGSAPASDPC FPAPSPAPAA TPPEAFKFGG TSLPPVSPAS
1010 1020
SLPTTPLATT DEVSKEDVIF F
Length:1,021
Mass (Da):114,336
Last modified:July 27, 2011 - v2
Checksum:iC62C35875FE1FA89
GO
Isoform 2 (identifier: Q6P9R4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     926-1021: ASFDLKQQLL...EVSKEDVIFF → GELHPTPTTQ...QLHFCCDKIP

Note: No experimental confirmation available.
Show »
Length:983
Mass (Da):111,026
Checksum:i1F8C1006BAF352C3
GO
Isoform 3 (identifier: Q6P9R4-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     534-618: IEGIQSLICQ...PCDNSAPSGC → SKLASPLSYA...SGVGGGGDKA
     619-1021: Missing.

Note: No experimental confirmation available.
Show »
Length:618
Mass (Da):69,228
Checksum:iA0B550CC80D6FE32
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti53 – 531N → S in BAC30940 (PubMed:16141072).Curated
Sequence conflicti217 – 2171Q → H in AAH60639 (PubMed:15489334).Curated
Sequence conflicti967 – 9671S → P in AAH34512 (PubMed:15489334).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei534 – 61885IEGIQ…APSGC → SKLASPLSYAMIFQGGLPGG PKPGSVLYCSPRTTVILLFF IIQGMESSMCNGSTAELYPN PLSTYSTNAPWVTLCSGVGG GGDKA in isoform 3. 1 PublicationVSP_034317Add
BLAST
Alternative sequencei619 – 1021403Missing in isoform 3. 1 PublicationVSP_034318Add
BLAST
Alternative sequencei926 – 102196ASFDL…DVIFF → GELHPTPTTQRSCTPLPVDL SQQHIWNADREADRQAPVCA RRQRGSLFQLHFCCDKIP in isoform 2. 1 PublicationVSP_034319Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK041423 mRNA. Translation: BAC30940.1.
AC169677 Genomic DNA. No translation available.
BC034512 mRNA. Translation: AAH34512.1.
BC060639 mRNA. Translation: AAH60639.1.
AK172963 mRNA. Translation: BAD32241.1.
CCDSiCCDS22060.1. [Q6P9R4-1]
RefSeqiNP_598723.3. NM_133962.3. [Q6P9R4-1]
UniGeneiMm.170461.

Genome annotation databases

EnsembliENSMUST00000004684; ENSMUSP00000004684; ENSMUSG00000004568. [Q6P9R4-1]
GeneIDi102098.
KEGGimmu:102098.
UCSCiuc009kri.1. mouse. [Q6P9R4-3]
uc009krj.1. mouse. [Q6P9R4-1]
uc009krk.1. mouse. [Q6P9R4-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK041423 mRNA. Translation: BAC30940.1.
AC169677 Genomic DNA. No translation available.
BC034512 mRNA. Translation: AAH34512.1.
BC060639 mRNA. Translation: AAH60639.1.
AK172963 mRNA. Translation: BAD32241.1.
CCDSiCCDS22060.1. [Q6P9R4-1]
RefSeqiNP_598723.3. NM_133962.3. [Q6P9R4-1]
UniGeneiMm.170461.

3D structure databases

ProteinModelPortaliQ6P9R4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi221794. 1 interaction.
IntActiQ6P9R4. 1 interaction.
STRINGi10090.ENSMUSP00000004684.

PTM databases

iPTMnetiQ6P9R4.
PhosphoSiteiQ6P9R4.

Proteomic databases

EPDiQ6P9R4.
MaxQBiQ6P9R4.
PaxDbiQ6P9R4.
PRIDEiQ6P9R4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000004684; ENSMUSP00000004684; ENSMUSG00000004568. [Q6P9R4-1]
GeneIDi102098.
KEGGimmu:102098.
UCSCiuc009kri.1. mouse. [Q6P9R4-3]
uc009krj.1. mouse. [Q6P9R4-1]
uc009krk.1. mouse. [Q6P9R4-2]

Organism-specific databases

CTDi23370.
MGIiMGI:2142567. Arhgef18.
RougeiSearch...

Phylogenomic databases

eggNOGiKOG3520. Eukaryota.
COG5422. LUCA.
GeneTreeiENSGT00760000119193.
HOGENOMiHOG000236361.
HOVERGENiHBG104846.
InParanoidiQ6P9R4.
OMAiPRKWSEN.
OrthoDBiEOG7JDQWP.
TreeFamiTF325887.

Enzyme and pathway databases

ReactomeiR-MMU-193648. NRAGE signals death through JNK.
R-MMU-194840. Rho GTPase cycle.
R-MMU-2173791. TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition).
R-MMU-416482. G alpha (12/13) signalling events.

Miscellaneous databases

ChiTaRSiArhgef18. mouse.
PROiQ6P9R4.
SOURCEiSearch...

Gene expression databases

BgeeiQ6P9R4.
ExpressionAtlasiQ6P9R4. baseline and differential.
GenevisibleiQ6P9R4. MM.

Family and domain databases

Gene3Di1.20.900.10. 1 hit.
2.30.29.30. 1 hit.
InterProiIPR000219. DH-domain.
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.
PROSITEiPS50010. DH_2. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
    Strain: C57BL/6J.
    Tissue: Thymus.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  3. "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] (ISOFORM 1).
    Strain: C57BL/6J and Czech II.
    Tissue: Brain and Mammary tumor.
  4. "Prediction of the coding sequences of mouse homologues of KIAA gene: IV. The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries."
    Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S., Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H., Nagase T., Ohara O., Koga H.
    DNA Res. 11:205-218(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 244-1021 (ISOFORM 2).
  5. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-568; SER-577; SER-952 AND SER-954, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain, Lung, Pancreas and Testis.

Entry informationi

Entry nameiARHGI_MOUSE
AccessioniPrimary (citable) accession number: Q6P9R4
Secondary accession number(s): E9QK59
, Q6A055, Q8BYA4, Q8K227
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 10, 2008
Last sequence update: July 27, 2011
Last modified: June 8, 2016
This is version 100 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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.