GDIR1_HUMAN
ID GDIR1_HUMAN Reviewed; 204 AA.
AC P52565; A8MXW0; B2R5X1; B4DDD3; B4DUV9; Q6IBM5;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 205.
DE RecName: Full=Rho GDP-dissociation inhibitor 1;
DE Short=Rho GDI 1;
DE AltName: Full=Rho-GDI alpha;
GN Name=ARHGDIA; Synonyms=GDIA1;
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 [MRNA] (ISOFORM 1).
RX PubMed=8262133; DOI=10.1006/excr.1993.1298;
RA Leffers H., Nielsen M.S., Andersen A.H., Honore B., Madsen P.,
RA Vandekerckhove J., Celis J.E.;
RT "Identification of two human Rho GDP dissociation inhibitor proteins whose
RT overexpression leads to disruption of the actin cytoskeleton.";
RL Exp. Cell Res. 209:165-174(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Maeda A., Kaibuchi K., Takai Y.;
RT "Molecular cloning of human rho GDI.";
RL Submitted (APR-1993) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Chuang T.H., Bokoch G.M.;
RT "cDNA sequence of human rho GDP dissociation inhibitor.";
RL Submitted (JUL-1992) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RA Mulheron J.G., Schwinn D.A., Caron M.G., Liggett S.B.;
RT "Genomic sequence of a human rho GDP dissociation inhibitor (GDI).";
RL Submitted (MAR-1992) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain cortex, and Neuroblastoma;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RA Puhl H.L. III, Ikeda S.R., Aronstam R.S.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon, Lung, Muscle, Skin, Tonsil, and Uterus;
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 [12]
RP PROTEIN SEQUENCE OF 2-42, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT
RP ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=T-cell;
RA Bienvenut W.V., Kanor S., Tissot J.-D., Quadroni M.;
RL Submitted (MAY-2006) to UniProtKB.
RN [13]
RP PROTEIN SEQUENCE OF 34-50; 139-167 AND 181-199, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [14]
RP PROTEIN SEQUENCE OF 34-37; 136-142 AND 181-199.
RC TISSUE=Neutrophil;
RX PubMed=8504089; DOI=10.1021/bi00072a029;
RA Kwong C.H., Malech H.L., Rotrosen D., Leto T.L.;
RT "Regulation of the human neutrophil NADPH oxidase by rho-related G-
RT proteins.";
RL Biochemistry 32:5711-5717(1993).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-141, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16916647; DOI=10.1016/j.molcel.2006.06.026;
RA Kim S.C., Sprung R., Chen Y., Xu Y., Ball H., Pei J., Cheng T., Kho Y.,
RA Xiao H., Xiao L., Grishin N.V., White M., Yang X.-J., Zhao Y.;
RT "Substrate and functional diversity of lysine acetylation revealed by a
RT proteomics survey.";
RL Mol. Cell 23:607-618(2006).
RN [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-105; LYS-127; LYS-141 AND
RP LYS-178, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [18]
RP INTERACTION WITH FER.
RX PubMed=21122136; DOI=10.1186/1471-2091-11-48;
RA Fei F., Kweon S.M., Haataja L., De Sepulveda P., Groffen J.,
RA Heisterkamp N.;
RT "The Fer tyrosine kinase regulates interactions of Rho GDP-Dissociation
RT Inhibitor alpha with the small GTPase Rac.";
RL BMC Biochem. 11:48-48(2010).
RN [19]
RP INTERACTION WITH PSMD10 AND RHOA.
RX PubMed=20628200; DOI=10.1172/jci42542;
RA Man J.H., Liang B., Gu Y.X., Zhou T., Li A.L., Li T., Jin B.F., Bai B.,
RA Zhang H.Y., Zhang W.N., Li W.H., Gong W.L., Li H.Y., Zhang X.M.;
RT "Gankyrin plays an essential role in Ras-induced tumorigenesis through
RT regulation of the RhoA/ROCK pathway in mammalian cells.";
RL J. Clin. Invest. 120:2829-2841(2010).
RN [20]
RP FUNCTION, INTERACTION WITH RHOA AND RHOC, AND MUTAGENESIS OF ASP-45 AND
RP ASP-185.
RX PubMed=20400958; DOI=10.1038/ncb2049;
RA Boulter E., Garcia-Mata R., Guilluy C., Dubash A., Rossi G.,
RA Brennwald P.J., Burridge K.;
RT "Regulation of Rho GTPase crosstalk, degradation and activity by RhoGDI1.";
RL Nat. Cell Biol. 12:477-483(2010).
RN [21]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [22]
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 [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-47, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [24]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [25]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-138 AND LYS-141, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25114211; DOI=10.1073/pnas.1413825111;
RA Impens F., Radoshevich L., Cossart P., Ribet D.;
RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by
RT external stimuli.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014).
RN [26]
RP INTERACTION WITH KANK2.
RX PubMed=25961457; DOI=10.1172/jci79504;
RA Gee H.Y., Zhang F., Ashraf S., Kohl S., Sadowski C.E., Vega-Warner V.,
RA Zhou W., Lovric S., Fang H., Nettleton M., Zhu J.Y., Hoefele J.,
RA Weber L.T., Podracka L., Boor A., Fehrenbach H., Innis J.W., Washburn J.,
RA Levy S., Lifton R.P., Otto E.A., Han Z., Hildebrandt F.;
RT "KANK deficiency leads to podocyte dysfunction and nephrotic syndrome.";
RL J. Clin. Invest. 125:2375-2384(2015).
RN [27]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 59-204.
RX PubMed=9195882; DOI=10.1016/s0969-2126(97)00218-9;
RA Keep N.H., Barnes M., Barsukov I., Badii R., Lian L.-Y., Segal A.W.,
RA Moody P.C.E., Roberts G.C.K.;
RT "A modulator of rho family G proteins, rhoGDI, binds these G proteins via
RT an immunoglobulin-like domain and a flexible N-terminal arm.";
RL Structure 5:623-633(1997).
RN [29] {ECO:0007744|PDB:2N80}
RP STRUCTURE BY NMR OF 31-204 IN COMPLEX WITH NGFR, INTERACTION WITH RHOA AND
RP NGFR, AND MUTAGENESIS OF LYS-99 AND LYS-199.
RX PubMed=26646181; DOI=10.7554/elife.11692;
RA Lin Z., Tann J.Y., Goh E.T., Kelly C., Lim K.B., Gao J.F., Ibanez C.F.;
RT "Structural basis of death domain signaling in the p75 neurotrophin
RT receptor.";
RL Elife 4:e11692-e11692(2015).
RN [30]
RP VARIANT NPHS8 ASP-185 DEL, CHARACTERIZATION OF VARIANT NPHS8 ASP-185 DEL,
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH RAC1; RHOA AND CDC42.
RX PubMed=23434736; DOI=10.1136/jmedgenet-2012-101442;
RA Gupta I.R., Baldwin C., Auguste D., Ha K.C., El Andalousi J.,
RA Fahiminiya S., Bitzan M., Bernard C., Akbari M.R., Narod S.A.,
RA Rosenblatt D.S., Majewski J., Takano T.;
RT "ARHGDIA: a novel gene implicated in nephrotic syndrome.";
RL J. Med. Genet. 50:330-338(2013).
CC -!- FUNCTION: Controls Rho proteins homeostasis. Regulates the GDP/GTP
CC exchange reaction of the Rho proteins by inhibiting the dissociation of
CC GDP from them, and the subsequent binding of GTP to them. Retains Rho
CC proteins such as CDC42, RAC1 and RHOA in an inactive cytosolic pool,
CC regulating their stability and protecting them from degradation.
CC Actively involved in the recycling and distribution of activated Rho
CC GTPases in the cell, mediates extraction from membranes of both
CC inactive and activated molecules due its exceptionally high affinity
CC for prenylated forms. Through the modulation of Rho proteins, may play
CC a role in cell motility regulation. In glioma cells, inhibits cell
CC migration and invasion by mediating the signals of SEMA5A and PLXNB3
CC that lead to inactivation of RAC1. {ECO:0000269|PubMed:20400958,
CC ECO:0000269|PubMed:23434736}.
CC -!- SUBUNIT: Monomer (By similarity). Interacts with FER (PubMed:21122136).
CC Interacts with PLXNB3 (By similarity). Forms a heterodimer with RAC1
CC (PubMed:23434736). Interacts with RHOA, the affinity is increased by
CC three orders of magnitude when RHOA is prenylated (PubMed:20628200,
CC PubMed:20400958, PubMed:26646181, PubMed:23434736). Interacts with
CC PSMD10; the interaction increases ARHGDIA association with RHOA,
CC leading to ARHGDIA-mediated inactivation of RHOA and ROCK and prolonged
CC AKT activation (PubMed:20628200). Interacts with KANK2; the interaction
CC is direct and may regulate the interaction of ARHGDIA with RHOA, RAC1
CC and CDC42 (PubMed:25961457). Interacts with RHOC (PubMed:20400958).
CC Interacts with CDC42 (PubMed:23434736). Interacts with NGFR (via death
CC domain); NGFR binding decreases the affinity for RHOA
CC (PubMed:26646181). {ECO:0000250|UniProtKB:Q99PT1,
CC ECO:0000269|PubMed:20400958, ECO:0000269|PubMed:20628200,
CC ECO:0000269|PubMed:21122136, ECO:0000269|PubMed:23434736,
CC ECO:0000269|PubMed:25961457, ECO:0000269|PubMed:26646181}.
CC -!- INTERACTION:
CC P52565; P60953: CDC42; NbExp=4; IntAct=EBI-712693, EBI-81752;
CC P52565; P63000: RAC1; NbExp=9; IntAct=EBI-712693, EBI-413628;
CC P52565; P61586: RHOA; NbExp=5; IntAct=EBI-712693, EBI-446668;
CC P52565; Q9BSI4: TINF2; NbExp=2; IntAct=EBI-712693, EBI-717399;
CC P52565; Q9NS68: TNFRSF19; NbExp=3; IntAct=EBI-712693, EBI-530381;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:23434736}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P52565-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P52565-2; Sequence=VSP_046699;
CC -!- DISEASE: Nephrotic syndrome 8 (NPHS8) [MIM:615244]: A form of nephrotic
CC syndrome, a renal disease clinically characterized by progressive renal
CC failure, severe proteinuria, hypoalbuminemia, hyperlipidemia and edema.
CC Kidney biopsies show diffuse mesangial sclerosis, with small glomeruli,
CC hypercellularity, increased extracellular matrix, and
CC contracted/collapsed glomerular tufts surrounded by immature or
CC abnormal podocytes. {ECO:0000269|PubMed:23434736}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the Rho GDI family. {ECO:0000305}.
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DR EMBL; X69550; CAA49281.1; -; mRNA.
DR EMBL; D13989; BAA03096.1; -; mRNA.
DR EMBL; M97579; AAA36566.1; -; mRNA.
DR EMBL; X63863; CAA45344.1; -; Genomic_DNA.
DR EMBL; AK300816; BAG62471.1; -; mRNA.
DR EMBL; AK312347; BAG35268.1; -; mRNA.
DR EMBL; AF498926; AAM21074.1; -; mRNA.
DR EMBL; BT006884; AAP35530.1; -; mRNA.
DR EMBL; CR456777; CAG33058.1; -; mRNA.
DR EMBL; AC145207; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471099; EAW89697.1; -; Genomic_DNA.
DR EMBL; BC005851; AAH05851.1; -; mRNA.
DR EMBL; BC005875; AAH05875.1; -; mRNA.
DR EMBL; BC008701; AAH08701.1; -; mRNA.
DR EMBL; BC009759; AAH09759.1; -; mRNA.
DR EMBL; BC016031; AAH16031.1; -; mRNA.
DR EMBL; BC016185; AAH16185.1; -; mRNA.
DR EMBL; BC024258; AAH24258.1; -; mRNA.
DR EMBL; BC027730; AAH27730.1; -; mRNA.
DR EMBL; BC075827; AAH75827.1; -; mRNA.
DR EMBL; BC106044; AAI06045.1; -; mRNA.
DR CCDS; CCDS11788.1; -. [P52565-1]
DR CCDS; CCDS58609.1; -. [P52565-2]
DR PIR; I38156; I38156.
DR RefSeq; NP_001172006.1; NM_001185077.2. [P52565-1]
DR RefSeq; NP_001172007.1; NM_001185078.2. [P52565-2]
DR RefSeq; NP_001288169.1; NM_001301240.1.
DR RefSeq; NP_001288170.1; NM_001301241.1.
DR RefSeq; NP_001288171.1; NM_001301242.1.
DR RefSeq; NP_001288172.1; NM_001301243.1.
DR RefSeq; NP_004300.1; NM_004309.5. [P52565-1]
DR PDB; 1CC0; X-ray; 5.00 A; E/F=1-204.
DR PDB; 1FSO; X-ray; 2.00 A; A=67-204.
DR PDB; 1FST; X-ray; 2.70 A; A/B=24-204.
DR PDB; 1FT0; X-ray; 2.60 A; A/B=67-204.
DR PDB; 1FT3; X-ray; 2.80 A; A/B=67-204.
DR PDB; 1HH4; X-ray; 2.70 A; D/E=1-204.
DR PDB; 1KMT; X-ray; 1.30 A; A/B=67-204.
DR PDB; 1QVY; X-ray; 1.60 A; A/B/C/D=67-204.
DR PDB; 1RHO; X-ray; 2.50 A; A/B/C=59-203.
DR PDB; 2BXW; X-ray; 2.40 A; A/B=67-204.
DR PDB; 2JHS; X-ray; 1.95 A; A=67-202.
DR PDB; 2JHT; X-ray; 1.88 A; A/B/C/D=67-202.
DR PDB; 2JHU; X-ray; 1.65 A; A/B=67-202.
DR PDB; 2JHV; X-ray; 2.07 A; A/B/C/D/E/F=67-202.
DR PDB; 2JHW; X-ray; 2.50 A; A/B=67-202.
DR PDB; 2JHX; X-ray; 1.60 A; A/B=67-202.
DR PDB; 2JHY; X-ray; 1.90 A; A=67-202.
DR PDB; 2JHZ; X-ray; 2.20 A; A/B=67-202.
DR PDB; 2JI0; X-ray; 2.10 A; A=67-202.
DR PDB; 2N80; NMR; -; B=31-204.
DR PDBsum; 1CC0; -.
DR PDBsum; 1FSO; -.
DR PDBsum; 1FST; -.
DR PDBsum; 1FT0; -.
DR PDBsum; 1FT3; -.
DR PDBsum; 1HH4; -.
DR PDBsum; 1KMT; -.
DR PDBsum; 1QVY; -.
DR PDBsum; 1RHO; -.
DR PDBsum; 2BXW; -.
DR PDBsum; 2JHS; -.
DR PDBsum; 2JHT; -.
DR PDBsum; 2JHU; -.
DR PDBsum; 2JHV; -.
DR PDBsum; 2JHW; -.
DR PDBsum; 2JHX; -.
DR PDBsum; 2JHY; -.
DR PDBsum; 2JHZ; -.
DR PDBsum; 2JI0; -.
DR PDBsum; 2N80; -.
DR AlphaFoldDB; P52565; -.
DR SMR; P52565; -.
DR BioGRID; 106889; 145.
DR ELM; P52565; -.
DR IntAct; P52565; 56.
DR MINT; P52565; -.
DR STRING; 9606.ENSP00000269321; -.
DR ChEMBL; CHEMBL3638327; -.
DR GlyGen; P52565; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P52565; -.
DR MetOSite; P52565; -.
DR PhosphoSitePlus; P52565; -.
DR SwissPalm; P52565; -.
DR BioMuta; ARHGDIA; -.
DR DMDM; 1707892; -.
DR DOSAC-COBS-2DPAGE; P52565; -.
DR OGP; P52565; -.
DR REPRODUCTION-2DPAGE; IPI00003815; -.
DR EPD; P52565; -.
DR jPOST; P52565; -.
DR MassIVE; P52565; -.
DR MaxQB; P52565; -.
DR PaxDb; P52565; -.
DR PeptideAtlas; P52565; -.
DR PRIDE; P52565; -.
DR ProteomicsDB; 2358; -.
DR ProteomicsDB; 56489; -. [P52565-1]
DR TopDownProteomics; P52565-1; -. [P52565-1]
DR Antibodypedia; 3880; 580 antibodies from 39 providers.
DR DNASU; 396; -.
DR Ensembl; ENST00000269321.12; ENSP00000269321.7; ENSG00000141522.12. [P52565-1]
DR Ensembl; ENST00000400721.8; ENSP00000383556.4; ENSG00000141522.12. [P52565-2]
DR Ensembl; ENST00000541078.6; ENSP00000441348.2; ENSG00000141522.12. [P52565-1]
DR Ensembl; ENST00000580685.5; ENSP00000464205.1; ENSG00000141522.12. [P52565-1]
DR GeneID; 396; -.
DR KEGG; hsa:396; -.
DR MANE-Select; ENST00000269321.12; ENSP00000269321.7; NM_004309.6; NP_004300.1.
DR UCSC; uc021ufg.2; human. [P52565-1]
DR CTD; 396; -.
DR DisGeNET; 396; -.
DR GeneCards; ARHGDIA; -.
DR HGNC; HGNC:678; ARHGDIA.
DR HPA; ENSG00000141522; Low tissue specificity.
DR MalaCards; ARHGDIA; -.
DR MIM; 601925; gene.
DR MIM; 615244; phenotype.
DR neXtProt; NX_P52565; -.
DR OpenTargets; ENSG00000141522; -.
DR Orphanet; 656; Genetic steroid-resistant nephrotic syndrome.
DR PharmGKB; PA24963; -.
DR VEuPathDB; HostDB:ENSG00000141522; -.
DR eggNOG; KOG3205; Eukaryota.
DR GeneTree; ENSGT00390000006233; -.
DR HOGENOM; CLU_076228_1_1_1; -.
DR InParanoid; P52565; -.
DR OMA; DDDKRCH; -.
DR OrthoDB; 1265661at2759; -.
DR PhylomeDB; P52565; -.
DR TreeFam; TF105387; -.
DR PathwayCommons; P52565; -.
DR Reactome; R-HSA-193634; Axonal growth inhibition (RHOA activation).
DR Reactome; R-HSA-209563; Axonal growth stimulation.
DR Reactome; R-HSA-8980692; RHOA GTPase cycle.
DR Reactome; R-HSA-9013106; RHOC GTPase cycle.
DR Reactome; R-HSA-9013148; CDC42 GTPase cycle.
DR Reactome; R-HSA-9013149; RAC1 GTPase cycle.
DR Reactome; R-HSA-9013404; RAC2 GTPase cycle.
DR Reactome; R-HSA-9013407; RHOH GTPase cycle.
DR Reactome; R-HSA-9013408; RHOG GTPase cycle.
DR SignaLink; P52565; -.
DR SIGNOR; P52565; -.
DR BioGRID-ORCS; 396; 34 hits in 1081 CRISPR screens.
DR ChiTaRS; ARHGDIA; human.
DR EvolutionaryTrace; P52565; -.
DR GeneWiki; ARHGDIA; -.
DR GenomeRNAi; 396; -.
DR Pharos; P52565; Tchem.
DR PRO; PR:P52565; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P52565; protein.
DR Bgee; ENSG00000141522; Expressed in granulocyte and 202 other tissues.
DR ExpressionAtlas; P52565; baseline and differential.
DR Genevisible; P52565; HS.
DR GO; GO:0005856; C:cytoskeleton; TAS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0001772; C:immunological synapse; IEA:Ensembl.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0005096; F:GTPase activator activity; IEA:UniProtKB-KW.
DR GO; GO:0005094; F:Rho GDP-dissociation inhibitor activity; IBA:GO_Central.
DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:UniProtKB.
DR GO; GO:0007162; P:negative regulation of cell adhesion; TAS:ProtInc.
DR GO; GO:2000249; P:regulation of actin cytoskeleton reorganization; IMP:UniProtKB.
DR GO; GO:0032880; P:regulation of protein localization; IEA:Ensembl.
DR GO; GO:0035023; P:regulation of Rho protein signal transduction; IMP:UniProtKB.
DR GO; GO:0007266; P:Rho protein signal transduction; IBA:GO_Central.
DR GO; GO:0071526; P:semaphorin-plexin signaling pathway; ISS:UniProtKB.
DR Gene3D; 2.70.50.30; -; 1.
DR IDEAL; IID00273; -.
DR InterPro; IPR014756; Ig_E-set.
DR InterPro; IPR000406; Rho_GDI.
DR InterPro; IPR024792; RhoGDI_dom_sf.
DR PANTHER; PTHR10980; PTHR10980; 1.
DR Pfam; PF02115; Rho_GDI; 1.
DR PRINTS; PR00492; RHOGDI.
DR SUPFAM; SSF81296; SSF81296; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm;
KW Direct protein sequencing; Disease variant; GTPase activation;
KW Isopeptide bond; Phosphoprotein; Reference proteome; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.12, ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:20068231"
FT CHAIN 2..204
FT /note="Rho GDP-dissociation inhibitor 1"
FT /id="PRO_0000219013"
FT REGION 1..36
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|Ref.12, ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 34
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99PT1"
FT MOD_RES 43
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99PT1"
FT MOD_RES 47
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 105
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 127
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 141
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:16916647,
FT ECO:0007744|PubMed:19608861"
FT MOD_RES 141
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99PT1"
FT MOD_RES 178
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT CROSSLNK 138
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0007744|PubMed:25114211"
FT CROSSLNK 138
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:25114211"
FT CROSSLNK 141
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0007744|PubMed:25114211"
FT CROSSLNK 141
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:25114211"
FT VAR_SEQ 139..183
FT /note="IDKTDYMVGSYGPRAEEYEFLTPVEEAPKGMLARGSYSIKSRFTD -> N
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046699"
FT VARIANT 185
FT /note="Missing (in NPHS8; produces mislocalization into the
FT nucleus, hyperactivation of Rho-GTPases RHOA, RAC1 and
FT CDC42 and impaired cell motility)"
FT /evidence="ECO:0000269|PubMed:23434736"
FT /id="VAR_069814"
FT MUTAGEN 45
FT /note="D->A: Loss of RHOA interaction; when associated with
FT A-185."
FT /evidence="ECO:0000269|PubMed:20400958"
FT MUTAGEN 99
FT /note="K->A: Loss of interaction with NGFR."
FT /evidence="ECO:0000269|PubMed:26646181"
FT MUTAGEN 185
FT /note="D->A: Loss of RHOA interaction; when associated with
FT A-45."
FT /evidence="ECO:0000269|PubMed:20400958"
FT MUTAGEN 199
FT /note="K->A: Loss of interaction with NGFR."
FT /evidence="ECO:0000269|PubMed:26646181"
FT CONFLICT 139
FT /note="I -> V (in Ref. 3; CAA45344 and 5; BAG35268)"
FT /evidence="ECO:0000305"
FT CONFLICT 188
FT /note="D -> R (in Ref. 13; AA sequence)"
FT /evidence="ECO:0000305"
FT HELIX 35..39
FT /evidence="ECO:0007829|PDB:1HH4"
FT HELIX 46..56
FT /evidence="ECO:0007829|PDB:1HH4"
FT TURN 59..63
FT /evidence="ECO:0007829|PDB:2N80"
FT STRAND 69..78
FT /evidence="ECO:0007829|PDB:1KMT"
FT STRAND 82..84
FT /evidence="ECO:0007829|PDB:1KMT"
FT STRAND 87..89
FT /evidence="ECO:0007829|PDB:1KMT"
FT HELIX 94..99
FT /evidence="ECO:0007829|PDB:1KMT"
FT STRAND 102..105
FT /evidence="ECO:0007829|PDB:1KMT"
FT STRAND 109..118
FT /evidence="ECO:0007829|PDB:1KMT"
FT STRAND 123..134
FT /evidence="ECO:0007829|PDB:1KMT"
FT STRAND 137..149
FT /evidence="ECO:0007829|PDB:1KMT"
FT STRAND 156..159
FT /evidence="ECO:0007829|PDB:1KMT"
FT TURN 169..171
FT /evidence="ECO:0007829|PDB:1KMT"
FT STRAND 173..182
FT /evidence="ECO:0007829|PDB:1KMT"
FT STRAND 189..200
FT /evidence="ECO:0007829|PDB:1KMT"
SQ SEQUENCE 204 AA; 23207 MW; 59CB6F42E3B3BCCA CRC64;
MAEQEPTAEQ LAQIAAENEE DEHSVNYKPP AQKSIQEIQE LDKDDESLRK YKEALLGRVA
VSADPNVPNV VVTGLTLVCS SAPGPLELDL TGDLESFKKQ SFVLKEGVEY RIKISFRVNR
EIVSGMKYIQ HTYRKGVKID KTDYMVGSYG PRAEEYEFLT PVEEAPKGML ARGSYSIKSR
FTDDDKTDHL SWEWNLTIKK DWKD
