RHOD_HUMAN
ID RHOD_HUMAN Reviewed; 210 AA.
AC O00212;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 3.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Rho-related GTP-binding protein RhoD {ECO:0000305};
DE AltName: Full=Rho-related protein HP1;
DE Short=RhoHP1;
DE Flags: Precursor;
GN Name=RHOD {ECO:0000312|HGNC:HGNC:670}; Synonyms=ARHD;
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 [GENOMIC DNA].
RC TISSUE=Placenta;
RX PubMed=9116026; DOI=10.1016/s0167-4781(97)00008-0;
RA Shimizu F., Watanabe T.K., Okuno S., Omori Y., Fujiwara T., Takahashi E.,
RA Nakamura Y.;
RT "Isolation of a novel human cDNA (rhoHP1) homologous to rho genes.";
RL Biochim. Biophys. Acta 1351:13-16(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cervix;
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 INTERACTION WITH DIAPH2.
RX PubMed=12577064; DOI=10.1038/ncb935;
RA Gasman S., Kalaidzidis Y., Zerial M.;
RT "RhoD regulates endosome dynamics through diaphanous-related formin and Src
RT tyrosine kinase.";
RL Nat. Cell Biol. 5:195-204(2003).
RN [6]
RP INTERACTION WITH PAK5.
RX PubMed=17064668; DOI=10.1016/j.bbrc.2006.09.172;
RA Wu X., Frost J.A.;
RT "Multiple Rho proteins regulate the subcellular targeting of PAK5.";
RL Biochem. Biophys. Res. Commun. 351:328-335(2006).
RN [7]
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 [8]
RP FUNCTION IN REGULATION OF ACTIN CYTOSKELETON REORGANIZATION, AND
RP INTERACTION WITH FILIP1.
RX PubMed=23087206; DOI=10.1091/mbc.e12-07-0555;
RA Gad A.K., Nehru V., Ruusala A., Aspenstrom P.;
RT "RhoD regulates cytoskeletal dynamics via the actin nucleation-promoting
RT factor WASp homologue associated with actin Golgi membranes and
RT microtubules.";
RL Mol. Biol. Cell 23:4807-4819(2012).
RN [9]
RP FUNCTION IN REGULATION OF ACTIN CYTOSKELETON REORGANIZATION, INTERACTION
RP WITH DAPK3, AND MUTAGENESIS OF CYS-207.
RX PubMed=23454120; DOI=10.1016/j.bbrc.2013.02.046;
RA Nehru V., Almeida F.N., Aspenstrom P.;
RT "Interaction of RhoD and ZIP kinase modulates actin filament assembly and
RT focal adhesion dynamics.";
RL Biochem. Biophys. Res. Commun. 433:163-169(2013).
RN [10]
RP FUNCTION IN ENDOSOMAL TRAFFICKING AND RECEPTOR INTERNALIZATION, INTERACTION
RP WITH ANKFY1, AND SUBCELLULAR LOCATION.
RX PubMed=24102721; DOI=10.1111/tra.12121;
RA Nehru V., Voytyuk O., Lennartsson J., Aspenstroem P.;
RT "RhoD binds the Rab5 effector Rabankyrin-5 and has a role in trafficking of
RT the platelet-derived growth factor receptor.";
RL Traffic 14:1242-1254(2013).
CC -!- FUNCTION: Involved in endosome dynamics. May coordinate membrane
CC transport with the function of the cytoskeleton. Involved in the
CC internalization and trafficking of activated tyrosine kinase receptors
CC such as PDGFRB. Participates in the reorganization of actin
CC cytoskeleton; the function seems to involve WHAMM and includes
CC regulation of filopodia formation and actin filament bundling. Can
CC modulate the effect of DAPK3 in reorganization of actin cytoskeleton
CC and focal adhesion dissolution. {ECO:0000269|PubMed:23087206,
CC ECO:0000269|PubMed:23454120, ECO:0000269|PubMed:24102721}.
CC -!- SUBUNIT: Interacts (in GTP-bound form) with DIAPH2 isoform 3, DAPK3,
CC FILIP1 and WHAMM. Interacts with PAK5. Interacts (independent of GTP-
CC loaded status) with ANKFY1. {ECO:0000269|PubMed:12577064,
CC ECO:0000269|PubMed:17064668, ECO:0000269|PubMed:23087206,
CC ECO:0000269|PubMed:23454120, ECO:0000269|PubMed:24102721}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Lipid-anchor
CC {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Early endosome
CC {ECO:0000269|PubMed:24102721}. Note=Colocalizes with RAB5 to early
CC endosomes (By similarity). {ECO:0000250|UniProtKB:P97348}.
CC -!- TISSUE SPECIFICITY: Heart, placenta, liver, skeletal muscle, and
CC pancreas and, with weaker intensity, in several other tissues.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rho family.
CC {ECO:0000305}.
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DR EMBL; D85815; BAA19652.1; -; Genomic_DNA.
DR EMBL; AF498973; AAM21120.1; -; mRNA.
DR EMBL; AP000729; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001338; AAH01338.1; -; mRNA.
DR CCDS; CCDS8155.1; -.
DR RefSeq; NP_055393.1; NM_014578.3.
DR PDB; 2J1L; X-ray; 2.50 A; A=7-197.
DR PDB; 7KDC; X-ray; 3.10 A; A/B=8-194.
DR PDBsum; 2J1L; -.
DR PDBsum; 7KDC; -.
DR AlphaFoldDB; O00212; -.
DR BioGRID; 119010; 569.
DR CORUM; O00212; -.
DR IntAct; O00212; 13.
DR STRING; 9606.ENSP00000308576; -.
DR iPTMnet; O00212; -.
DR PhosphoSitePlus; O00212; -.
DR BioMuta; RHOD; -.
DR EPD; O00212; -.
DR jPOST; O00212; -.
DR MassIVE; O00212; -.
DR MaxQB; O00212; -.
DR PaxDb; O00212; -.
DR PeptideAtlas; O00212; -.
DR PRIDE; O00212; -.
DR ProteomicsDB; 47782; -.
DR Antibodypedia; 16425; 235 antibodies from 28 providers.
DR DNASU; 29984; -.
DR Ensembl; ENST00000308831.7; ENSP00000308576.2; ENSG00000173156.7.
DR GeneID; 29984; -.
DR KEGG; hsa:29984; -.
DR MANE-Select; ENST00000308831.7; ENSP00000308576.2; NM_014578.4; NP_055393.1.
DR UCSC; uc001ojv.4; human.
DR CTD; 29984; -.
DR DisGeNET; 29984; -.
DR GeneCards; RHOD; -.
DR HGNC; HGNC:670; RHOD.
DR HPA; ENSG00000173156; Tissue enhanced (esophagus, liver).
DR MIM; 605781; gene.
DR neXtProt; NX_O00212; -.
DR OpenTargets; ENSG00000173156; -.
DR PharmGKB; PA24952; -.
DR VEuPathDB; HostDB:ENSG00000173156; -.
DR eggNOG; KOG0393; Eukaryota.
DR GeneTree; ENSGT00940000161731; -.
DR HOGENOM; CLU_041217_21_2_1; -.
DR InParanoid; O00212; -.
DR OrthoDB; 1166960at2759; -.
DR PhylomeDB; O00212; -.
DR TreeFam; TF331746; -.
DR PathwayCommons; O00212; -.
DR Reactome; R-HSA-5663220; RHO GTPases Activate Formins.
DR Reactome; R-HSA-9013405; RHOD GTPase cycle.
DR SignaLink; O00212; -.
DR BioGRID-ORCS; 29984; 16 hits in 1070 CRISPR screens.
DR ChiTaRS; RHOD; human.
DR EvolutionaryTrace; O00212; -.
DR GeneWiki; RhoD; -.
DR GenomeRNAi; 29984; -.
DR Pharos; O00212; Tbio.
DR PRO; PR:O00212; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; O00212; protein.
DR Bgee; ENSG00000173156; Expressed in lower esophagus mucosa and 151 other tissues.
DR ExpressionAtlas; O00212; baseline and differential.
DR Genevisible; O00212; HS.
DR GO; GO:0005938; C:cell cortex; IBA:GO_Central.
DR GO; GO:0042995; C:cell projection; IBA:GO_Central.
DR GO; GO:0031410; C:cytoplasmic vesicle; IBA:GO_Central.
DR GO; GO:0005856; C:cytoskeleton; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0010008; C:endosome membrane; TAS:Reactome.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0005741; C:mitochondrial outer membrane; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005525; F:GTP binding; IBA:GO_Central.
DR GO; GO:0003924; F:GTPase activity; IBA:GO_Central.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; TAS:Reactome.
DR GO; GO:0019901; F:protein kinase binding; IBA:GO_Central.
DR GO; GO:0051017; P:actin filament bundle assembly; IMP:UniProtKB.
DR GO; GO:0007015; P:actin filament organization; IBA:GO_Central.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0030865; P:cortical cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0007163; P:establishment or maintenance of cell polarity; IBA:GO_Central.
DR GO; GO:0048041; P:focal adhesion assembly; IMP:UniProtKB.
DR GO; GO:0030032; P:lamellipodium assembly; IMP:UniProtKB.
DR GO; GO:0045785; P:positive regulation of cell adhesion; IMP:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; IMP:UniProtKB.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0008360; P:regulation of cell shape; IBA:GO_Central.
DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; TAS:Reactome.
DR GO; GO:0007266; P:Rho protein signal transduction; TAS:ProtInc.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR001806; Small_GTPase.
DR InterPro; IPR003578; Small_GTPase_Rho.
DR PANTHER; PTHR24072; PTHR24072; 1.
DR Pfam; PF00071; Ras; 1.
DR SMART; SM00174; RHO; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51420; RHO; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Endosome; GTP-binding; Lipoprotein; Membrane;
KW Methylation; Nucleotide-binding; Prenylation; Reference proteome.
FT CHAIN 1..207
FT /note="Rho-related GTP-binding protein RhoD"
FT /id="PRO_0000198863"
FT PROPEP 208..210
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000223365"
FT MOTIF 46..54
FT /note="Effector region"
FT /evidence="ECO:0000255"
FT BINDING 24..31
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 71..75
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 129..132
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT MOD_RES 207
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000250"
FT LIPID 207
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250"
FT VARIANT 134
FT /note="R -> C (in dbSNP:rs4930409)"
FT /id="VAR_058408"
FT MUTAGEN 207
FT /note="C->S: Abolishes endosomal localization."
FT /evidence="ECO:0000269|PubMed:23454120"
FT STRAND 17..24
FT /evidence="ECO:0007829|PDB:2J1L"
FT HELIX 30..38
FT /evidence="ECO:0007829|PDB:2J1L"
FT STRAND 52..60
FT /evidence="ECO:0007829|PDB:2J1L"
FT STRAND 63..71
FT /evidence="ECO:0007829|PDB:2J1L"
FT HELIX 76..78
FT /evidence="ECO:0007829|PDB:7KDC"
FT TURN 79..81
FT /evidence="ECO:0007829|PDB:7KDC"
FT HELIX 82..85
FT /evidence="ECO:0007829|PDB:7KDC"
FT STRAND 89..97
FT /evidence="ECO:0007829|PDB:2J1L"
FT HELIX 101..109
FT /evidence="ECO:0007829|PDB:2J1L"
FT HELIX 111..118
FT /evidence="ECO:0007829|PDB:2J1L"
FT STRAND 120..122
FT /evidence="ECO:0007829|PDB:7KDC"
FT STRAND 124..129
FT /evidence="ECO:0007829|PDB:2J1L"
FT HELIX 131..134
FT /evidence="ECO:0007829|PDB:2J1L"
FT HELIX 137..145
FT /evidence="ECO:0007829|PDB:2J1L"
FT HELIX 153..162
FT /evidence="ECO:0007829|PDB:2J1L"
FT STRAND 166..170
FT /evidence="ECO:0007829|PDB:2J1L"
FT TURN 173..176
FT /evidence="ECO:0007829|PDB:2J1L"
FT HELIX 179..192
FT /evidence="ECO:0007829|PDB:2J1L"
SQ SEQUENCE 210 AA; 23466 MW; 7B960AE8863C6DA5 CRC64;
MTAAQAAGEE APPGVRSVKV VLVGDGGCGK TSLLMVFADG AFPESYTPTV FERYMVNLQV
KGKPVHLHIW DTAGQDDYDR LRPLFYPDAS VLLLCFDVTS PNSFDNIFNR WYPEVNHFCK
KVPIIVVGCK TDLRKDKSLV NKLRRNGLEP VTYHRGQEMA RSVGAVAYLE CSARLHDNVH
AVFQEAAEVA LSSRGRNFWR RITQGFCVVT
