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 27-MAR-2024, entry version 168. 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 a 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 CCDS; CCDS92502.1; -. [Q6ZSZ5-4] 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. DR RefSeq; XP_011526141.1; XM_011527839.2. [Q6ZSZ5-6] DR RefSeq; XP_011526142.1; XM_011527840.1. DR AlphaFoldDB; Q6ZSZ5; -. DR SMR; Q6ZSZ5; -. DR BioGRID; 116950; 45. DR CORUM; Q6ZSZ5; -. DR IntAct; Q6ZSZ5; 8. DR MINT; Q6ZSZ5; -. DR STRING; 9606.ENSP00000499655; -. 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; 9606-ENSP00000471635; -. DR PeptideAtlas; Q6ZSZ5; -. DR ProteomicsDB; 68246; -. [Q6ZSZ5-1] DR ProteomicsDB; 68247; -. [Q6ZSZ5-2] DR Pumba; Q6ZSZ5; -. DR Antibodypedia; 24427; 324 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 AGR; HGNC:17090; -. 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; 2917157at2759; -. 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; 13 hits in 1155 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 197 other cell types or tissues. DR ExpressionAtlas; Q6ZSZ5; baseline and differential. 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; IDA:HPA. 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; Dbl homology (DH) domain; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 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 PANTHER; PTHR47440:SF1; RHO_RAC GUANINE NUCLEOTIDE EXCHANGE FACTOR 18; 1. DR PANTHER; PTHR47440; RIKEN CDNA A430078G23 GENE; 1. DR Pfam; PF17838; PH_16; 1. DR Pfam; PF00621; RhoGEF; 1. DR SMART; SM00233; PH; 1. DR SMART; SM00325; RhoGEF; 1. DR SUPFAM; SSF48065; DBL homology domain (DH-domain); 1. DR SUPFAM; SSF50729; PH domain-like; 1. DR PROSITE; PS50010; DH_2; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 1. DR Genevisible; Q6ZSZ5; HS. 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 //