GDIR2_HUMAN
ID GDIR2_HUMAN Reviewed; 201 AA.
AC P52566; B5BU79;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Rho GDP-dissociation inhibitor 2;
DE Short=Rho GDI 2;
DE AltName: Full=Ly-GDI {ECO:0000303|PubMed:8356058};
DE AltName: Full=Rho-GDI beta;
GN Name=ARHGDIB; Synonyms=GDIA2, GDID4, RAP1GN1;
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], FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=8356058; DOI=10.1073/pnas.90.16.7568;
RA Scherle P., Behrens T., Staudt L.M.;
RT "Ly-GDI, a GDP-dissociation inhibitor of the RhoA GTP-binding protein, is
RT expressed preferentially in lymphocytes.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:7568-7572(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8434008; DOI=10.1073/pnas.90.4.1479;
RA Lelias J.M., Adra C.N., Wulf G.M., Guillemot J.-C., Caput D., Lim B.;
RT "cDNA cloning of a human mRNA preferentially expressed in hematopoietic
RT cells and with homology to a GDP-dissociation inhibitor for the rho GTP-
RT binding proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:1479-1483(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=19054851; DOI=10.1038/nmeth.1273;
RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y.,
RA Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A.,
RA Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y.,
RA Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T.,
RA Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y.,
RA Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S.,
RA Nomura N.;
RT "Human protein factory for converting the transcriptome into an in vitro-
RT expressed proteome.";
RL Nat. Methods 5:1011-1017(2008).
RN [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [8]
RP PROTEIN SEQUENCE OF 2-20; 33-46 AND 50-62, CLEAVAGE OF INITIATOR
RP METHIONINE, ACETYLATION AT THR-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 [9]
RP PROTEIN SEQUENCE OF 10-19; 21-25; 51-58; 142-148 AND 150-156.
RX PubMed=2226408; DOI=10.1002/elps.1150110702;
RA Aebersold R., Leavitt J.;
RT "Sequence analysis of proteins separated by polyacrylamide gel
RT electrophoresis: towards an integrated protein database.";
RL Electrophoresis 11:517-527(1990).
RN [10]
RP FUNCTION, AND INTERACTION WITH CDC42 AND RAC1.
RX PubMed=7512369; DOI=10.1002/gcc.2870080408;
RA Adra C.N., Ko J., Leonard D., Wirth L.J., Cerione R.A., Lim B.;
RT "Identification of a novel protein with GDP dissociation inhibitor activity
RT for the ras-like proteins CDC42Hs and rac I.";
RL Genes Chromosomes Cancer 8:253-261(1993).
RN [11]
RP SUBCELLULAR LOCATION.
RX PubMed=10802295; DOI=10.1016/s0165-2427(00)00176-8;
RA Davis A.R., Clements M.K., Bunger P.L., Siemsen D.W., Quinn M.T.;
RT "Cloning of bovine low molecular weight GTPases (Rac1 and Rac2) and Rho
RT GDP-dissociation inhibitor 2 (D4-GDI).";
RL Vet. Immunol. Immunopathol. 74:285-301(2000).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-24, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-145, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-21; LYS-25; LYS-40; LYS-47;
RP LYS-102; LYS-124 AND LYS-175, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [15]
RP INTERACTION WITH RHOA.
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 [16]
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 [17]
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 [18]
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 [19]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF COMPLEX WITH RAC2.
RX PubMed=10655614; DOI=10.1038/72392;
RA Scheffzek K., Stephan I., Jensen O.N., Illenberger D., Gierschik P.;
RT "The Rac-RhoGDI complex and the structural basis for the regulation of Rho
RT proteins by RhoGDI.";
RL Nat. Struct. Biol. 7:122-126(2000).
CC -!- FUNCTION: Regulates the GDP/GTP exchange reaction of the Rho proteins
CC by inhibiting the dissociation of GDP from them, and the subsequent
CC binding of GTP to them (PubMed:8356058, PubMed:7512369). Regulates
CC reorganization of the actin cytoskeleton mediated by Rho family members
CC (PubMed:8262133). {ECO:0000269|PubMed:7512369,
CC ECO:0000269|PubMed:8262133, ECO:0000269|PubMed:8356058}.
CC -!- SUBUNIT: Interacts with RHOA (PubMed:20400958). Interacts with RAC1
CC (PubMed:7512369). Interacts with RAC2 (PubMed:10655614). Interacts with
CC CDC42 (PubMed:7512369). {ECO:0000269|PubMed:10655614,
CC ECO:0000269|PubMed:20400958, ECO:0000269|PubMed:7512369}.
CC -!- INTERACTION:
CC P52566; P01100: FOS; NbExp=3; IntAct=EBI-2806617, EBI-852851;
CC P52566; P62993: GRB2; NbExp=3; IntAct=EBI-2806617, EBI-401755;
CC P52566; P31930: UQCRC1; NbExp=3; IntAct=EBI-2806617, EBI-1052596;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:10802295}.
CC -!- TISSUE SPECIFICITY: Detected in bone marrow, thymus and spleen.
CC {ECO:0000269|PubMed:8356058}.
CC -!- SIMILARITY: Belongs to the Rho GDI family. {ECO:0000305}.
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DR EMBL; L20688; AAA59539.1; -; mRNA.
DR EMBL; X69549; CAA49280.1; -; mRNA.
DR EMBL; L07916; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AF498927; AAM21075.1; -; mRNA.
DR EMBL; AB451315; BAG70129.1; -; mRNA.
DR EMBL; AB451445; BAG70259.1; -; mRNA.
DR EMBL; CH471094; EAW96336.1; -; Genomic_DNA.
DR EMBL; BC009200; AAH09200.1; -; mRNA.
DR CCDS; CCDS8671.1; -.
DR PIR; A47742; A47742.
DR RefSeq; NP_001166.3; NM_001175.6.
DR RefSeq; NP_001308349.1; NM_001321420.1.
DR RefSeq; NP_001308350.1; NM_001321421.1.
DR RefSeq; NP_001308351.1; NM_001321422.1.
DR RefSeq; NP_001308352.1; NM_001321423.1.
DR PDB; 1DS6; X-ray; 2.35 A; B=23-199.
DR PDB; 5H1D; X-ray; 1.49 A; A=61-201.
DR PDBsum; 1DS6; -.
DR PDBsum; 5H1D; -.
DR AlphaFoldDB; P52566; -.
DR SMR; P52566; -.
DR BioGRID; 106890; 33.
DR DIP; DIP-40959N; -.
DR ELM; P52566; -.
DR IntAct; P52566; 18.
DR MINT; P52566; -.
DR STRING; 9606.ENSP00000228945; -.
DR GlyGen; P52566; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; P52566; -.
DR MetOSite; P52566; -.
DR PhosphoSitePlus; P52566; -.
DR SwissPalm; P52566; -.
DR BioMuta; ARHGDIB; -.
DR OGP; P52566; -.
DR SWISS-2DPAGE; P52566; -.
DR EPD; P52566; -.
DR jPOST; P52566; -.
DR MassIVE; P52566; -.
DR MaxQB; P52566; -.
DR PaxDb; P52566; -.
DR PeptideAtlas; P52566; -.
DR PRIDE; P52566; -.
DR ProteomicsDB; 56490; -.
DR TopDownProteomics; P52566; -.
DR Antibodypedia; 12089; 540 antibodies from 39 providers.
DR DNASU; 397; -.
DR Ensembl; ENST00000228945.9; ENSP00000228945.4; ENSG00000111348.9.
DR Ensembl; ENST00000541546.5; ENSP00000440560.1; ENSG00000111348.9.
DR Ensembl; ENST00000541644.5; ENSP00000444860.1; ENSG00000111348.9.
DR GeneID; 397; -.
DR KEGG; hsa:397; -.
DR MANE-Select; ENST00000228945.9; ENSP00000228945.4; NM_001175.7; NP_001166.3.
DR UCSC; uc001rcq.2; human.
DR CTD; 397; -.
DR DisGeNET; 397; -.
DR GeneCards; ARHGDIB; -.
DR HGNC; HGNC:679; ARHGDIB.
DR HPA; ENSG00000111348; Group enriched (bone marrow, lymphoid tissue).
DR MIM; 602843; gene.
DR neXtProt; NX_P52566; -.
DR OpenTargets; ENSG00000111348; -.
DR PharmGKB; PA24964; -.
DR VEuPathDB; HostDB:ENSG00000111348; -.
DR eggNOG; KOG3205; Eukaryota.
DR GeneTree; ENSGT00390000006233; -.
DR InParanoid; P52566; -.
DR OMA; HLKFEWS; -.
DR OrthoDB; 1265661at2759; -.
DR PhylomeDB; P52566; -.
DR TreeFam; TF105387; -.
DR PathwayCommons; P52566; -.
DR Reactome; R-HSA-8980692; RHOA GTPase cycle.
DR Reactome; R-HSA-9013148; CDC42 GTPase cycle.
DR Reactome; R-HSA-9013149; RAC1 GTPase cycle.
DR Reactome; R-HSA-9013407; RHOH GTPase cycle.
DR Reactome; R-HSA-9013408; RHOG GTPase cycle.
DR Reactome; R-HSA-9013423; RAC3 GTPase cycle.
DR SignaLink; P52566; -.
DR SIGNOR; P52566; -.
DR BioGRID-ORCS; 397; 13 hits in 1075 CRISPR screens.
DR ChiTaRS; ARHGDIB; human.
DR EvolutionaryTrace; P52566; -.
DR GeneWiki; ARHGDIB; -.
DR GenomeRNAi; 397; -.
DR Pharos; P52566; Tbio.
DR PRO; PR:P52566; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P52566; protein.
DR Bgee; ENSG00000111348; Expressed in blood and 206 other tissues.
DR ExpressionAtlas; P52566; baseline and differential.
DR Genevisible; P52566; HS.
DR GO; GO:0005737; C:cytoplasm; TAS:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; TAS:ProtInc.
DR GO; GO:0005856; C:cytoskeleton; TAS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005096; F:GTPase activator activity; IEA:UniProtKB-KW.
DR GO; GO:0003924; F:GTPase activity; IMP:CACAO.
DR GO; GO:0005094; F:Rho GDP-dissociation inhibitor activity; IDA:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; IDA:UniProtKB.
DR GO; GO:1901164; P:negative regulation of trophoblast cell migration; IDA:CACAO.
DR GO; GO:2000249; P:regulation of actin cytoskeleton reorganization; IMP:UniProtKB.
DR GO; GO:0035023; P:regulation of Rho protein signal transduction; IDA:UniProtKB.
DR GO; GO:0007266; P:Rho protein signal transduction; IBA:GO_Central.
DR Gene3D; 2.70.50.30; -; 1.
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; Cytoplasm; Direct protein sequencing;
KW GTPase activation; Phosphoprotein; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.8"
FT CHAIN 2..201
FT /note="Rho GDP-dissociation inhibitor 2"
FT /id="PRO_0000219016"
FT REGION 1..38
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylthreonine"
FT /evidence="ECO:0000269|Ref.8"
FT MOD_RES 21
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 24
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:15592455"
FT MOD_RES 25
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 40
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 47
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 102
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 124
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 145
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 175
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT CONFLICT 153
FT /note="Y -> V (in Ref. 9; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 169..170
FT /note="RG -> QD (in Ref. 3; L07916)"
FT /evidence="ECO:0000305"
FT HELIX 32..37
FT /evidence="ECO:0007829|PDB:1DS6"
FT TURN 38..41
FT /evidence="ECO:0007829|PDB:1DS6"
FT HELIX 43..52
FT /evidence="ECO:0007829|PDB:1DS6"
FT STRAND 62..64
FT /evidence="ECO:0007829|PDB:1DS6"
FT STRAND 67..75
FT /evidence="ECO:0007829|PDB:5H1D"
FT STRAND 79..81
FT /evidence="ECO:0007829|PDB:5H1D"
FT STRAND 84..86
FT /evidence="ECO:0007829|PDB:5H1D"
FT HELIX 91..94
FT /evidence="ECO:0007829|PDB:5H1D"
FT STRAND 99..102
FT /evidence="ECO:0007829|PDB:5H1D"
FT STRAND 106..115
FT /evidence="ECO:0007829|PDB:5H1D"
FT STRAND 120..131
FT /evidence="ECO:0007829|PDB:5H1D"
FT STRAND 134..146
FT /evidence="ECO:0007829|PDB:5H1D"
FT STRAND 153..156
FT /evidence="ECO:0007829|PDB:5H1D"
FT HELIX 166..168
FT /evidence="ECO:0007829|PDB:5H1D"
FT STRAND 170..180
FT /evidence="ECO:0007829|PDB:5H1D"
FT STRAND 186..197
FT /evidence="ECO:0007829|PDB:5H1D"
SQ SEQUENCE 201 AA; 22988 MW; F1E840134F643E5F CRC64;
MTEKAPEPHV EEDDDDELDS KLNYKPPPQK SLKELQEMDK DDESLIKYKK TLLGDGPVVT
DPKAPNVVVT RLTLVCESAP GPITMDLTGD LEALKKETIV LKEGSEYRVK IHFKVNRDIV
SGLKYVQHTY RTGVKVDKAT FMVGSYGPRP EEYEFLTPVE EAPKGMLARG TYHNKSFFTD
DDKQDHLSWE WNLSIKKEWT E
