ARHGI_HUMAN
ID ARHGI_HUMAN Reviewed; 1361 AA.
AC Q6ZSZ5; A8MV62; B5ME81; I3L1I5; O60274; Q6DD92;
DT 10-JUN-2008, integrated into UniProtKB/Swiss-Prot.
DT 10-OCT-2018, sequence version 4.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Rho guanine nucleotide exchange factor 18;
DE AltName: Full=114 kDa Rho-specific guanine nucleotide exchange factor;
DE Short=p114-Rho-GEF;
DE Short=p114RhoGEF;
DE AltName: Full=Septin-associated RhoGEF;
DE Short=SA-RhoGEF;
GN Name=ARHGEF18; Synonyms=KIAA0521;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), AND VARIANTS ARG-889
RP AND SER-1207.
RC TISSUE=Brain;
RX PubMed=9628581; DOI=10.1093/dnares/5.1.31;
RA Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N.,
RA Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. IX. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 5:31-39(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-1344 (ISOFORM 4), AND VARIANTS
RP ARG-889 AND SER-1207.
RC TISSUE=Lymph;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=11085924; DOI=10.1042/bj3520319;
RA Blomquist A., Schwoerer G., Schablowski H., Psoma A., Lehnen M.,
RA Jakobs K.H., Ruemenapp U.;
RT "Identification and characterization of a novel Rho-specific guanine
RT nucleotide exchange factor.";
RL Biochem. J. 352:319-325(2000).
RN [6]
RP IDENTIFICATION.
RX PubMed=11318610; DOI=10.1006/geno.2001.6526;
RA Acierno J.S. Jr., Kennedy J.C., Falardeau J.L., Leyne M., Bromley M.C.,
RA Colman M.W., Sun M., Bove C., Ashworth L.K., Chadwick L.H., Schiripo T.,
RA Ma S., Goldin E., Schiffmann R., Slaugenhaupt S.A.;
RT "A physical and transcript map of the MCOLN1 gene region on human
RT chromosome 19p13.3-p13.2.";
RL Genomics 73:203-210(2001).
RN [7]
RP FUNCTION, TISSUE SPECIFICITY, AND INTERACTION WITH GNB1 AND GNG2.
RX PubMed=14512443; DOI=10.1161/01.res.0000097607.14733.0c;
RA Niu J., Profirovic J., Pan H., Vaiskunaite R., Voyno-Yasenetskaya T.;
RT "G Protein betagamma subunits stimulate p114RhoGEF, a guanine nucleotide
RT exchange factor for RhoA and Rac1: regulation of cell shape and reactive
RT oxygen species production.";
RL Circ. Res. 93:848-856(2003).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INTERACTION WITH
RP SEPT9.
RX PubMed=15558029; DOI=10.1038/sj.onc.1208101;
RA Nagata K., Inagaki M.;
RT "Cytoskeletal modification of Rho guanine nucleotide exchange factor
RT activity: identification of a Rho guanine nucleotide exchange factor as a
RT binding partner for Sept9b, a mammalian septin.";
RL Oncogene 24:65-76(2005).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP FUNCTION, INTERACTION WITH EPB41L4B AND PATJ, AND SUBCELLULAR LOCATION.
RX PubMed=22006950; DOI=10.1083/jcb.201104118;
RA Nakajima H., Tanoue T.;
RT "Lulu2 regulates the circumferential actomyosin tensile system in
RT epithelial cells through p114RhoGEF.";
RL J. Cell Biol. 195:245-261(2011).
RN [12]
RP ALTERNATIVE SPLICING (ISOFORMS 1; 2 AND 3), SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY (ISOFORMS 1; 2; 3 AND 4), AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=29601110; DOI=10.1002/jlb.2ma1017-418rr;
RA Turton K.B., Wilkerson E.M., Hebert A.S., Fogerty F.J., Schira H.M.,
RA Botros F.E., Coon J.J., Mosher D.F.;
RT "Expression of novel 'LOCGEF' isoforms of ARHGEF18 in eosinophils.";
RL J. Leukoc. Biol. 104:135-145(2018).
RN [13]
RP FUNCTION, INVOLVEMENT IN RP78, VARIANTS RP78 ALA-458; 854-ARG--PHE-1361
RP DEL; 1066-GLU--PHE-1361 DEL AND 1101-ARG--GLU-1108 DEL, AND
RP CHARACTERIZATION OF VARIANTS RP78 ALA-458 AND 1101-ARG--GLU-1108 DEL.
RX PubMed=28132693; DOI=10.1016/j.ajhg.2016.12.014;
RG UK Inherited Retinal Disease Consortium;
RG NIHR Bioresource - Rare Diseases Consortium;
RA Arno G., Carss K.J., Hull S., Zihni C., Robson A.G., Fiorentino A.,
RA Hardcastle A.J., Holder G.E., Cheetham M.E., Plagnol V., Moore A.T.,
RA Raymond F.L., Matter K., Balda M.S., Webster A.R.;
RT "Biallelic mutation of ARHGEF18, involved in the determination of
RT epithelial apicobasal polarity, causes adult-onset retinal degeneration.";
RL Am. J. Hum. Genet. 100:334-342(2017).
CC -!- FUNCTION: Acts as guanine nucleotide exchange factor (GEF) for RhoA
CC GTPases. Its activation induces formation of actin stress fibers. Also
CC acts as a GEF for RAC1, inducing production of reactive oxygen species
CC (ROS). Does not act as a GEF for CDC42. The G protein beta-gamma
CC (Gbetagamma) subunits of heterotrimeric G proteins act as activators,
CC explaining the integrated effects of LPA and other G-protein coupled
CC receptor agonists on actin stress fiber formation, cell shape change
CC and ROS production. Required for EPB41L4B-mediated regulation of the
CC circumferential actomyosin belt in epithelial cells (PubMed:22006950).
CC {ECO:0000269|PubMed:11085924, ECO:0000269|PubMed:14512443,
CC ECO:0000269|PubMed:15558029, ECO:0000269|PubMed:22006950,
CC ECO:0000269|PubMed:28132693}.
CC -!- SUBUNIT: Interacts with SEPT9; the interaction may inhibit GEF activity
CC (PubMed:15558029). Interacts with Gbetagamma subunits GNB1 and GNG2
CC (PubMed:14512443). Interacts with EPB41L4B (PubMed:22006950). Interacts
CC with PATJ (via C-terminus) (PubMed:22006950).
CC {ECO:0000269|PubMed:14512443, ECO:0000269|PubMed:15558029,
CC ECO:0000269|PubMed:22006950}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15558029}.
CC Cytoplasm, cytoskeleton {ECO:0000269|PubMed:15558029}. Cell membrane
CC {ECO:0000269|PubMed:29601110}. Apical cell membrane
CC {ECO:0000269|PubMed:22006950}. Note=In unactivated eosinophils,
CC distributed around the cell periphery in the perimembranous region
CC (PubMed:29601110). In activated eosinophils, relocates to the tip of
CC the nucleopod, a membrane structure formed during activation when the
CC nucleus moves to one end of the cell, and is also concentrated in
CC membrane protrusions at the opposite end of the cell (PubMed:29601110).
CC Localizes to the apical cell membrane in epithelial cells
CC (PubMed:22006950). {ECO:0000269|PubMed:22006950,
CC ECO:0000269|PubMed:29601110}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1; Synonyms=LOCGEF-X3 {ECO:0000303|PubMed:29601110};
CC IsoId=Q6ZSZ5-4; Sequence=Displayed;
CC Name=2; Synonyms=LOCGEF-X4 {ECO:0000303|PubMed:29601110};
CC IsoId=Q6ZSZ5-5; Sequence=VSP_059877;
CC Name=3; Synonyms=LOCGEF-X5 {ECO:0000303|PubMed:29601110};
CC IsoId=Q6ZSZ5-6; Sequence=VSP_059876;
CC Name=4; Synonyms=p114 {ECO:0000303|PubMed:29601110};
CC IsoId=Q6ZSZ5-2; Sequence=VSP_059874;
CC Name=5;
CC IsoId=Q6ZSZ5-1; Sequence=VSP_059875;
CC -!- TISSUE SPECIFICITY: Expressed in all tissues tested with highest
CC expression in kidney and pancreas. Weakly or not expressed in liver,
CC skeletal muscle and testis. Isoform 1: Expressed in eosinophils
CC (PubMed:29601110). Isoform 2: Expressed in eosinophils
CC (PubMed:29601110). Isoform 3: Expressed in eosinophils
CC (PubMed:29601110). Isoform 4: Not detected in eosinophils
CC (PubMed:29601110). {ECO:0000269|PubMed:11085924,
CC ECO:0000269|PubMed:14512443, ECO:0000269|PubMed:15558029,
CC ECO:0000269|PubMed:29601110}.
CC -!- DISEASE: Retinitis pigmentosa 78 (RP78) [MIM:617433]: A form of
CC retinitis pigmentosa, a retinal dystrophy belonging to the group of
CC pigmentary retinopathies. Retinitis pigmentosa is characterized by
CC retinal pigment deposits visible on fundus examination and primary loss
CC of rod photoreceptor cells followed by secondary loss of cone
CC photoreceptors. Patients typically have night vision blindness and loss
CC of midperipheral visual field. As their condition progresses, they lose
CC their far peripheral visual field and eventually central vision as
CC well. RP78 inheritance is autosomal recessive.
CC {ECO:0000269|PubMed:28132693}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH77721.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305};
CC Sequence=BAA25447.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB011093; BAA25447.1; ALT_INIT; mRNA.
DR EMBL; AK127045; BAC86801.1; -; mRNA.
DR EMBL; AC008878; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC119396; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC126754; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC077721; AAH77721.1; ALT_SEQ; mRNA.
DR CCDS; CCDS12177.1; -. [Q6ZSZ5-2]
DR RefSeq; NP_001124427.1; NM_001130955.1.
DR RefSeq; NP_056133.2; NM_015318.3. [Q6ZSZ5-2]
DR RefSeq; XP_006722768.1; XM_006722705.3.
DR RefSeq; XP_006722769.1; XM_006722706.3. [Q6ZSZ5-4]
DR RefSeq; XP_006722771.1; XM_006722708.2.
DR RefSeq; XP_011526140.1; XM_011527838.2. [Q6ZSZ5-5]
DR RefSeq; XP_011526141.1; XM_011527839.2. [Q6ZSZ5-6]
DR RefSeq; XP_011526142.1; XM_011527840.1. [Q6ZSZ5-2]
DR AlphaFoldDB; Q6ZSZ5; -.
DR SMR; Q6ZSZ5; -.
DR BioGRID; 116950; 34.
DR CORUM; Q6ZSZ5; -.
DR IntAct; Q6ZSZ5; 7.
DR STRING; 9606.ENSP00000471635; -.
DR iPTMnet; Q6ZSZ5; -.
DR PhosphoSitePlus; Q6ZSZ5; -.
DR BioMuta; -; -.
DR BioMuta; ARHGEF18; -.
DR DMDM; 296439444; -.
DR EPD; Q6ZSZ5; -.
DR jPOST; Q6ZSZ5; -.
DR MassIVE; Q6ZSZ5; -.
DR MaxQB; Q6ZSZ5; -.
DR PaxDb; Q6ZSZ5; -.
DR PeptideAtlas; Q6ZSZ5; -.
DR PRIDE; Q6ZSZ5; -.
DR ProteomicsDB; 68246; -. [Q6ZSZ5-1]
DR ProteomicsDB; 68247; -. [Q6ZSZ5-2]
DR Antibodypedia; 24427; 291 antibodies from 31 providers.
DR DNASU; 23370; -.
DR Ensembl; ENST00000594665.2; ENSP00000470729.2; ENSG00000104880.19. [Q6ZSZ5-2]
DR Ensembl; ENST00000617428.4; ENSP00000482647.4; ENSG00000104880.19. [Q6ZSZ5-2]
DR Ensembl; ENST00000668164.2; ENSP00000499655.2; ENSG00000104880.19. [Q6ZSZ5-4]
DR GeneID; 23370; -.
DR KEGG; hsa:23370; -.
DR MANE-Select; ENST00000668164.2; ENSP00000499655.2; NM_001367823.1; NP_001354752.1.
DR UCSC; uc002mgh.4; human. [Q6ZSZ5-4]
DR CTD; 23370; -.
DR DisGeNET; 23370; -.
DR GeneCards; ARHGEF18; -.
DR HGNC; HGNC:17090; ARHGEF18.
DR HPA; ENSG00000104880; Low tissue specificity.
DR MalaCards; ARHGEF18; -.
DR MIM; 616432; gene.
DR MIM; 617433; phenotype.
DR neXtProt; NX_Q6ZSZ5; -.
DR OpenTargets; ENSG00000104880; -.
DR Orphanet; 791; Retinitis pigmentosa.
DR PharmGKB; PA128394630; -.
DR VEuPathDB; HostDB:ENSG00000104880; -.
DR eggNOG; ENOG502SGX7; Eukaryota.
DR eggNOG; KOG3520; Eukaryota.
DR GeneTree; ENSGT00940000157375; -.
DR HOGENOM; CLU_002466_0_0_1; -.
DR InParanoid; Q6ZSZ5; -.
DR OMA; PRHKNGA; -.
DR OrthoDB; 69816at2759; -.
DR PhylomeDB; Q6ZSZ5; -.
DR TreeFam; TF325887; -.
DR TreeFam; TF353495; -.
DR PathwayCommons; Q6ZSZ5; -.
DR Reactome; R-HSA-193648; NRAGE signals death through JNK.
DR Reactome; R-HSA-2173791; TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition).
DR Reactome; R-HSA-416482; G alpha (12/13) signalling events.
DR Reactome; R-HSA-8980692; RHOA GTPase cycle.
DR Reactome; R-HSA-9013149; RAC1 GTPase cycle.
DR SignaLink; Q6ZSZ5; -.
DR SIGNOR; Q6ZSZ5; -.
DR BioGRID-ORCS; 23370; 12 hits in 1074 CRISPR screens.
DR ChiTaRS; ARHGEF18; human.
DR GenomeRNAi; 23370; -.
DR Pharos; Q6ZSZ5; Tbio.
DR PRO; PR:Q6ZSZ5; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q6ZSZ5; protein.
DR Bgee; ENSG00000104880; Expressed in pancreatic ductal cell and 195 other tissues.
DR ExpressionAtlas; Q6ZSZ5; baseline and differential.
DR Genevisible; Q6ZSZ5; HS.
DR GO; GO:0045177; C:apical part of cell; IDA:MGI.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030054; C:cell junction; TAS:Reactome.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0030036; P:actin cytoskeleton organization; IDA:MGI.
DR GO; GO:0051497; P:negative regulation of stress fiber assembly; IMP:ARUK-UCL.
DR GO; GO:0150105; P:protein localization to cell-cell junction; IMP:ARUK-UCL.
DR GO; GO:0008360; P:regulation of cell shape; IDA:MGI.
DR GO; GO:0035023; P:regulation of Rho protein signal transduction; IBA:GO_Central.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IDA:MGI.
DR CDD; cd15794; PH_ARHGEF18; 1.
DR CDD; cd00160; RhoGEF; 1.
DR Gene3D; 1.20.900.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR037744; ARHGEF18_PH.
DR InterPro; IPR035899; DBL_dom_sf.
DR InterPro; IPR000219; DH-domain.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR041020; PH_16.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR013087; Znf_C2H2_type.
DR Pfam; PF17838; PH_16; 1.
DR Pfam; PF00621; RhoGEF; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00325; RhoGEF; 1.
DR SUPFAM; SSF48065; SSF48065; 1.
DR PROSITE; PS50010; DH_2; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Coiled coil; Cytoplasm; Cytoskeleton;
KW Disease variant; Guanine-nucleotide releasing factor; Membrane;
KW Metal-binding; Phosphoprotein; Reference proteome; Retinitis pigmentosa;
KW Zinc; Zinc-finger.
FT CHAIN 1..1361
FT /note="Rho guanine nucleotide exchange factor 18"
FT /id="PRO_0000341415"
FT DOMAIN 447..644
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 684..786
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT ZN_FING 310..334
FT /note="C2H2-type; degenerate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 33..88
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 131..156
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 244..292
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 348..368
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 893..980
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1143..1211
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1229..1264
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1277..1361
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 1038..1148
FT /evidence="ECO:0000255"
FT COMPBIAS 244..260
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 267..292
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 916..930
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 954..969
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1193..1207
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1296..1318
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 912
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q6P9R4"
FT MOD_RES 921
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6P9R4"
FT MOD_RES 1289
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6P9R4"
FT MOD_RES 1291
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6P9R4"
FT VAR_SEQ 1..346
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:29601110"
FT /id="VSP_059874"
FT VAR_SEQ 1..322
FT /note="MGDDQEDDFPRRLSESMEDLSLDLGALQGSEYLQDLGLGAPSHSQPGETPDS
FT RPTGEEPGRDSLFSSLAGSQDLSRRRSWERSRSCSESWRRLSLDASAVDEEPCLPRTLA
FT SLALNLPGGGLKTWTQGCLSGGGTPAESPGKECDSPKKRGRSRSVPVSFYEIRSPEISP
FT GLEVPTPPVQGLEPPVLECMEKDHVEPDHVLIVQQVLQELRQYHGARQRACMSASPGGA
FT HSNLTWFEFLSESEDGAGKNEKSDKSTSVKRRLSCLRSRVTRQKEKGKSPAHLKDKGQD
FT ARERRECVNGHQLLQGTFSGPSSCPLCGKPFLSS -> MVTVGTNILPSRPAASANTAR
FT EDAALFSRRIPPRHKNGAAQPGAAPGPGAPGANMGNAHSKSGDRHSALPGRPELSFYGS
FT FPRKWSENVFLDNELLTSKILSMLRPQSERGFRAGDLRYPTHFLSTNSVLASVT (in
FT isoform 5)"
FT /evidence="ECO:0000305"
FT /id="VSP_059875"
FT VAR_SEQ 1..16
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:29601110"
FT /id="VSP_059876"
FT VAR_SEQ 1..5
FT /note="MGDDQ -> MTTVA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:29601110"
FT /id="VSP_059877"
FT VARIANT 458
FT /note="T -> A (in RP78; decreased function in positive
FT regulation of Rho protein signal transduction; loss of
FT function in regulation of actomyosin structure
FT organization; dbSNP:rs987233144)"
FT /evidence="ECO:0000269|PubMed:28132693"
FT /id="VAR_078919"
FT VARIANT 854..1361
FT /note="Missing (in RP78)"
FT /evidence="ECO:0000269|PubMed:28132693"
FT /id="VAR_078920"
FT VARIANT 889
FT /note="Q -> R (in dbSNP:rs2287918)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:9628581"
FT /id="VAR_044066"
FT VARIANT 940
FT /note="R -> Q (in dbSNP:rs2287920)"
FT /id="VAR_044067"
FT VARIANT 1066..1361
FT /note="Missing (in RP78)"
FT /evidence="ECO:0000269|PubMed:28132693"
FT /id="VAR_078921"
FT VARIANT 1101..1108
FT /note="Missing (in RP78; no effect on function in positive
FT regulation of Rho protein signal transduction; decreased
FT function in regulation of actomyosin structure
FT organization)"
FT /evidence="ECO:0000269|PubMed:28132693"
FT /id="VAR_078922"
FT VARIANT 1207
FT /note="N -> S (in dbSNP:rs9329368)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:9628581"
FT /id="VAR_063099"
FT CONFLICT 371
FT /note="I -> V (in Ref. 2; BAC86801)"
FT /evidence="ECO:0000305"
FT CONFLICT 1295
FT /note="P -> S (in Ref. 2; BAC86801)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1361 AA; 151642 MW; 3028B14BC119FBDC CRC64;
MGDDQEDDFP RRLSESMEDL SLDLGALQGS EYLQDLGLGA PSHSQPGETP DSRPTGEEPG
RDSLFSSLAG SQDLSRRRSW ERSRSCSESW RRLSLDASAV DEEPCLPRTL ASLALNLPGG
GLKTWTQGCL SGGGTPAESP GKECDSPKKR GRSRSVPVSF YEIRSPEISP GLEVPTPPVQ
GLEPPVLECM EKDHVEPDHV LIVQQVLQEL RQYHGARQRA CMSASPGGAH SNLTWFEFLS
ESEDGAGKNE KSDKSTSVKR RLSCLRSRVT RQKEKGKSPA HLKDKGQDAR ERRECVNGHQ
LLQGTFSGPS SCPLCGKPFL SSASLKEHPR GTLLSDGSPA LSRNVGMTVS QKGGPQPTPS
PAGPGTQLGP ITGEMDEADS AFLKFKQTAD DSLSLTSPNT ESIFVEDPYT ASLRSEIESD
GHEFEAESWS LAVDAAYAKK QKREVVKRQD VLYELMQTEV HHVRTLKIML KVYSRALQEE
LQFSSKAIGR LFPCADDLLE THSHFLARLK ERRQESLEEG SDRNYVIQKI GDLLVQQFSG
ENGERMKEKY GVFCSGHNEA VSHYKLLLQQ NKKFQNLIKK IGNFSIVRRL GVQECILLVT
QRITKYPVLV ERIIQNTEAG TEDYEDLTQA LNLIKDIISQ VDAKVSECEK GQRLREIAGK
MDLKSSSKLK NGLTFRKEDM LQRQLHLEGM LCWKTTSGRL KDILAILLTD VLLLLQEKDQ
KYVFASVDSK PPVISLQKLI VREVANEEKA MFLISASLQG PEMYEIYTSS KEDRNAWMAH
IQRAVESCPD EEEGPFSLPE EERKVVEARA TRLRDFQERL SMKDQLIAQS LLEKQQIYLE
MAEMGGLEDL PQPRGLFRGG DPSETLQGEL ILKSAMSEIE GIQSLICRQL GSANGQAEDG
GSSTGPPRRA ETFAGYDCTN SPTKNGSFKK KVSSTDPRPR DWRGPPNSPD LKLSDSDIPG
SSEESPQVVE APGTESDPRL PTVLESELVQ RIQTLSQLLL NLQAVIAHQD SYVETQRAAI
QEREKQFRLQ STRGNLLLEQ ERQRNFEKQR EERAALEKLQ SQLRHEQQRW ERERQWQHQE
LERAGARLQE REGEARQLRE RLEQERAELE RQRQAYQHDL ERLREAQRAV ERERERLELL
RRLKKQNTAP GALPPDTLAE AQPPSHPPSF NGEGLEGPRV SMLPSGVGPE YAERPEVARR
DSAPTENRLA KSDVPIQLLS ATNQFQRQAA VQQQIPTKLA ASTKGGKDKG GKSRGSQRWE
SSASFDLKQQ LLLNKLMGKD ESTSRNRRSL SPILPGRHSP APPPDPGFPA PSPPPADSPS
EGFSLKAGGT ALLPGPPAPS PLPATPLSAK EDASKEDVIF F
