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Database: UniProt
Entry: P60763
LinkDB: P60763
Original site: P60763 
ID   RAC3_HUMAN              Reviewed;         192 AA.
AC   P60763; O14658; Q5U0M8;
DT   13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT   13-APR-2004, sequence version 1.
DT   26-FEB-2020, entry version 162.
DE   RecName: Full=Ras-related C3 botulinum toxin substrate 3 {ECO:0000305};
DE            EC=3.6.5.2 {ECO:0000269|PubMed:16982419};
DE   AltName: Full=p21-Rac3;
DE   Flags: Precursor;
GN   Name=RAC3 {ECO:0000312|HGNC:HGNC:9803};
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].
RX   PubMed=9252344; DOI=10.1074/jbc.272.33.20384;
RA   Haataja L., Groffen J., Heisterkamp N.;
RT   "Characterization of RAC3, a novel member of the Rho family.";
RL   J. Biol. Chem. 272:20384-20388(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 MRNA].
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 (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
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 C1D.
RX   PubMed=9852280; DOI=10.3892/ijmm.1.4.665;
RA   Haataja L., Groffen J., Heisterkamp N.;
RT   "Identification of a novel Rac3-interacting protein C1D.";
RL   Int. J. Mol. Med. 1:665-670(1998).
RN   [6]
RP   FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH NRBP.
RX   PubMed=11956649;
RA   De Langhe S., Haataja L., Senadheera D., Groffen J., Heisterkamp N.;
RT   "Interaction of the small GTPase Rac3 with NRBP, a protein with a kinase-
RT   homology domain.";
RL   Int. J. Mol. Med. 9:451-459(2002).
RN   [7]
RP   FUNCTION, INTERACTION WITH CIB1, AND SUBCELLULAR LOCATION.
RX   PubMed=11756406; DOI=10.1074/jbc.m105363200;
RA   Haataja L., Kaartinen V., Groffen J., Heisterkamp N.;
RT   "The small GTPase Rac3 interacts with the integrin-binding protein CIB and
RT   promotes integrin alpha(IIb)beta(3)-mediated adhesion and spreading.";
RL   J. Biol. Chem. 277:8321-8328(2002).
RN   [8]
RP   INTERACTION WITH DOCK7, ACTIVITY REGULATION, AND CATALYTIC ACTIVITY.
RX   PubMed=16982419; DOI=10.1016/j.neuron.2006.07.020;
RA   Watabe-Uchida M., John K.A., Janas J.A., Newey S.E., Van Aelst L.;
RT   "The Rac activator DOCK7 regulates neuronal polarity through local
RT   phosphorylation of stathmin/Op18.";
RL   Neuron 51:727-739(2006).
RN   [9]
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   [10]
RP   GLYCOSYLATION AT TYR-32 (MICROBIAL INFECTION).
RX   PubMed=24141704; DOI=10.1038/nsmb.2688;
RA   Jank T., Bogdanovic X., Wirth C., Haaf E., Spoerner M., Boehmer K.E.,
RA   Steinemann M., Orth J.H., Kalbitzer H.R., Warscheid B., Hunte C.,
RA   Aktories K.;
RT   "A bacterial toxin catalyzing tyrosine glycosylation of Rho and deamidation
RT   of Gq and Gi proteins.";
RL   Nat. Struct. Mol. Biol. 20:1273-1280(2013).
RN   [11]
RP   VARIANTS NEDBAF LEU-29; LEU-61 AND LYS-62.
RX   PubMed=30293988; DOI=10.1038/s41436-018-0323-y;
RA   Costain G., Callewaert B., Gabriel H., Tan T.Y., Walker S.,
RA   Christodoulou J., Lazar T., Menten B., Orkin J., Sadedin S., Snell M.,
RA   Vanlander A., Vergult S., White S.M., Scherer S.W., Hayeems R.Z.,
RA   Blaser S., Wodak S.J., Chitayat D., Marshall C.R., Meyn M.S.;
RT   "De novo missense variants in RAC3 cause a novel neurodevelopmental
RT   syndrome.";
RL   Genet. Med. 21:1021-1026(2019).
CC   -!- FUNCTION: Plasma membrane-associated small GTPase which cycles between
CC       an active GTP-bound and inactive GDP-bound state. In active state binds
CC       to a variety of effector proteins to regulate cellular responses, such
CC       as cell spreading and the formation of actin-based protusions including
CC       lamellipodia and membrane ruffles. Promotes cell adhesion and spreading
CC       on fibrinogen in a CIB1 and alpha-IIb/beta3 integrin-mediated manner.
CC       {ECO:0000269|PubMed:11756406, ECO:0000269|PubMed:11956649}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565,
CC         ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; EC=3.6.5.2;
CC         Evidence={ECO:0000269|PubMed:16982419};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670;
CC         Evidence={ECO:0000305};
CC   -!- ACTIVITY REGULATION: Regulated by guanine nucleotide exchange factors
CC       (GEFs) which promote the exchange of bound GDP for free GTP, GTPase
CC       activating proteins (GAPs) which increase the GTP hydrolysis activity,
CC       and GDP dissociation inhibitors which inhibit the dissociation of the
CC       nucleotide from the GTPase. Regulated by the GEF protein DOCK7.
CC       {ECO:0000269|PubMed:16982419}.
CC   -!- SUBUNIT: Interacts with the GEF protein DOCK7, which promotes the
CC       exchange between GDP and GTP, and therefore activates it
CC       (PubMed:16982419). Interacts with C1D (PubMed:9852280). Interacts (via
CC       C-terminal region) with CIB1; the interaction induces their association
CC       with the cytoskeleton upon alpha-IIb/beta3 integrin-mediated adhesion
CC       (PubMed:11756406). Interacts with NRBP (PubMed:11956649).
CC       {ECO:0000269|PubMed:11756406, ECO:0000269|PubMed:11956649,
CC       ECO:0000269|PubMed:16982419, ECO:0000269|PubMed:9852280}.
CC   -!- INTERACTION:
CC       P03372:ESR1; NbExp=5; IntAct=EBI-767084, EBI-78473;
CC       Q9UHY1:NRBP1; NbExp=3; IntAct=EBI-767084, EBI-749731;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm. Endomembrane system. Cell projection,
CC       lamellipodium. Cytoplasm, perinuclear region. Cell membrane. Cytoplasm,
CC       cytoskeleton. Note=Membrane-associated when activated. Colocalizes with
CC       NRBP to endomembranes and at the cell periphery in lamellipodia.
CC       Colocalized with CIB1 in the perinuclear area and at the cell
CC       periphery.
CC   -!- TISSUE SPECIFICITY: Highest levels in brain, also detected in heart,
CC       placenta and pancreas.
CC   -!- INDUCTION: Expression down-regulated in quiescent fibroblasts and
CC       clearly induced by serum stimulation.
CC   -!- PTM: (Microbial infection) Glycosylated at Tyr-32 by Photorhabdus
CC       asymbiotica toxin PAU_02230. Mono-O-GlcNAcylation by PAU_02230 inhibits
CC       downstream signaling by an impaired interaction with diverse regulator
CC       and effector proteins of Rac and leads to actin disassembly.
CC       {ECO:0000269|PubMed:24141704}.
CC   -!- DISEASE: Neurodevelopmental disorder with structural brain anomalies
CC       and dysmorphic facies (NEDBAF) [MIM:618577]: An autosomal dominant
CC       neurodevelopmental disorder characterized by global developmental
CC       delay, severe intellectual disability, poor language, seizures,
CC       dysmorphic features, and thin corpus callosum.
CC       {ECO:0000269|PubMed:30293988}. Note=The disease is caused by mutations
CC       affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the small GTPase superfamily. Rho family.
CC       {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC       Haematology;
CC       URL="http://atlasgeneticsoncology.org/Genes/RAC3ID42022ch17q25.html";
DR   EMBL; AF008591; AAC51667.1; -; mRNA.
DR   EMBL; AF498966; AAM21113.1; -; mRNA.
DR   EMBL; BT019443; AAV38250.1; -; mRNA.
DR   EMBL; BC009605; AAH09605.1; -; mRNA.
DR   EMBL; BC015197; AAH15197.1; -; mRNA.
DR   CCDS; CCDS11798.1; -.
DR   RefSeq; NP_005043.1; NM_005052.2.
DR   PDB; 2C2H; X-ray; 1.85 A; A/B=1-192.
DR   PDB; 2G0N; X-ray; 1.90 A; A/B=1-177.
DR   PDB; 2IC5; X-ray; 1.90 A; A/B=1-178.
DR   PDB; 2OV2; X-ray; 2.10 A; A/B/C/D/E/F/G/H=1-177.
DR   PDB; 2QME; X-ray; 1.75 A; A=1-177.
DR   PDBsum; 2C2H; -.
DR   PDBsum; 2G0N; -.
DR   PDBsum; 2IC5; -.
DR   PDBsum; 2OV2; -.
DR   PDBsum; 2QME; -.
DR   SMR; P60763; -.
DR   BioGrid; 111819; 17.
DR   DIP; DIP-33881N; -.
DR   IntAct; P60763; 29.
DR   MINT; P60763; -.
DR   STRING; 9606.ENSP00000304283; -.
DR   ChEMBL; CHEMBL6087; -.
DR   iPTMnet; P60763; -.
DR   PhosphoSitePlus; P60763; -.
DR   SwissPalm; P60763; -.
DR   BioMuta; RAC3; -.
DR   DMDM; 46397673; -.
DR   EPD; P60763; -.
DR   jPOST; P60763; -.
DR   MassIVE; P60763; -.
DR   MaxQB; P60763; -.
DR   PaxDb; P60763; -.
DR   PeptideAtlas; P60763; -.
DR   PRIDE; P60763; -.
DR   ProteomicsDB; 57225; -.
DR   TopDownProteomics; P60763; -.
DR   DNASU; 5881; -.
DR   Ensembl; ENST00000306897; ENSP00000304283; ENSG00000169750.
DR   GeneID; 5881; -.
DR   KEGG; hsa:5881; -.
DR   UCSC; uc002kdf.4; human.
DR   CTD; 5881; -.
DR   DisGeNET; 5881; -.
DR   GeneCards; RAC3; -.
DR   HGNC; HGNC:9803; RAC3.
DR   HPA; HPA047820; -.
DR   MIM; 602050; gene.
DR   MIM; 618577; phenotype.
DR   neXtProt; NX_P60763; -.
DR   OpenTargets; ENSG00000169750; -.
DR   PharmGKB; PA34164; -.
DR   eggNOG; KOG0393; Eukaryota.
DR   eggNOG; COG1100; LUCA.
DR   GeneTree; ENSGT00940000153500; -.
DR   HOGENOM; CLU_041217_21_3_1; -.
DR   InParanoid; P60763; -.
DR   KO; K07861; -.
DR   OMA; GKKCTMF; -.
DR   OrthoDB; 1091615at2759; -.
DR   PhylomeDB; P60763; -.
DR   TreeFam; TF101109; -.
DR   BRENDA; 3.6.5.2; 2681.
DR   Reactome; R-HSA-194840; Rho GTPase cycle.
DR   Reactome; R-HSA-4086400; PCP/CE pathway.
DR   SIGNOR; P60763; -.
DR   EvolutionaryTrace; P60763; -.
DR   GeneWiki; RAC3; -.
DR   GenomeRNAi; 5881; -.
DR   Pharos; P60763; Tbio.
DR   PRO; PR:P60763; -.
DR   Proteomes; UP000005640; Chromosome 17.
DR   RNAct; P60763; protein.
DR   Bgee; ENSG00000169750; Expressed in cerebellar hemisphere and 110 other tissues.
DR   ExpressionAtlas; P60763; baseline and differential.
DR   Genevisible; P60763; HS.
DR   GO; GO:0005938; C:cell cortex; IBA:GO_Central.
DR   GO; GO:0071944; C:cell periphery; IDA:UniProtKB.
DR   GO; GO:0042995; C:cell projection; IBA:GO_Central.
DR   GO; GO:0005737; C:cytoplasm; 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:0012505; C:endomembrane system; IDA:UniProtKB.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0031941; C:filamentous actin; IDA:MGI.
DR   GO; GO:0030426; C:growth cone; IDA:MGI.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR   GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell.
DR   GO; GO:0043005; C:neuron projection; IDA:MGI.
DR   GO; GO:0043025; C:neuronal cell body; IDA:MGI.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0045202; C:synapse; IEA:GOC.
DR   GO; GO:0048306; F:calcium-dependent protein binding; IPI:UniProtKB.
DR   GO; GO:0005525; F:GTP binding; IBA:GO_Central.
DR   GO; GO:0003924; F:GTPase activity; IDA:UniProtKB.
DR   GO; GO:0019901; F:protein kinase binding; IBA:GO_Central.
DR   GO; GO:0030036; P:actin cytoskeleton organization; IDA:UniProtKB.
DR   GO; GO:0007015; P:actin filament organization; IBA:GO_Central.
DR   GO; GO:0030031; P:cell projection assembly; IDA:UniProtKB.
DR   GO; GO:0021894; P:cerebral cortex GABAergic interneuron development; IEA:Ensembl.
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:0048873; P:homeostasis of number of cells within a tissue; IEA:Ensembl.
DR   GO; GO:0035556; P:intracellular signal transduction; TAS:UniProtKB.
DR   GO; GO:0050885; P:neuromuscular process controlling balance; IEA:Ensembl.
DR   GO; GO:0031175; P:neuron projection development; IEA:Ensembl.
DR   GO; GO:0033630; P:positive regulation of cell adhesion mediated by integrin; IDA:UniProtKB.
DR   GO; GO:1900026; P:positive regulation of substrate adhesion-dependent cell spreading; IDA: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:0014041; P:regulation of neuron maturation; IEA:Ensembl.
DR   GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; TAS:Reactome.
DR   GO; GO:0007266; P:Rho protein signal transduction; IBA:GO_Central.
DR   GO; GO:0051932; P:synaptic transmission, GABAergic; IEA:Ensembl.
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   Pfam; PF00071; Ras; 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; Cell projection; Cytoplasm; Cytoskeleton;
KW   Disease mutation; Glycoprotein; GTP-binding; Hydrolase; Lipoprotein;
KW   Membrane; Mental retardation; Methylation; Nucleotide-binding; Prenylation;
KW   Reference proteome.
FT   CHAIN           1..189
FT                   /note="Ras-related C3 botulinum toxin substrate 3"
FT                   /id="PRO_0000198889"
FT   PROPEP          190..192
FT                   /note="Removed in mature form"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000281240"
FT   NP_BIND         10..17
FT                   /note="GTP"
FT                   /evidence="ECO:0000250"
FT   NP_BIND         57..61
FT                   /note="GTP"
FT                   /evidence="ECO:0000250"
FT   NP_BIND         115..118
FT                   /note="GTP"
FT                   /evidence="ECO:0000250"
FT   MOTIF           32..40
FT                   /note="Effector region"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         189
FT                   /note="Cysteine methyl ester"
FT                   /evidence="ECO:0000250"
FT   LIPID           189
FT                   /note="S-geranylgeranyl cysteine"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        32
FT                   /note="O-linked (GlcNAc) tyrosine; by Photorhabdus
FT                   PAU_02230"
FT                   /evidence="ECO:0000269|PubMed:24141704"
FT   VARIANT         29
FT                   /note="P -> L (in NEDBAF)"
FT                   /evidence="ECO:0000269|PubMed:30293988"
FT                   /id="VAR_083040"
FT   VARIANT         61
FT                   /note="Q -> L (in NEDBAF)"
FT                   /evidence="ECO:0000269|PubMed:30293988"
FT                   /id="VAR_083041"
FT   VARIANT         62
FT                   /note="E -> K (in NEDBAF)"
FT                   /evidence="ECO:0000269|PubMed:30293988"
FT                   /id="VAR_083042"
FT   STRAND          2..10
FT                   /evidence="ECO:0000244|PDB:2QME"
FT   HELIX           16..25
FT                   /evidence="ECO:0000244|PDB:2QME"
FT   STRAND          36..46
FT                   /evidence="ECO:0000244|PDB:2QME"
FT   STRAND          49..58
FT                   /evidence="ECO:0000244|PDB:2QME"
FT   HELIX           62..64
FT                   /evidence="ECO:0000244|PDB:2QME"
FT   TURN            65..67
FT                   /evidence="ECO:0000244|PDB:2QME"
FT   HELIX           68..71
FT                   /evidence="ECO:0000244|PDB:2QME"
FT   STRAND          76..83
FT                   /evidence="ECO:0000244|PDB:2QME"
FT   HELIX           87..95
FT                   /evidence="ECO:0000244|PDB:2QME"
FT   HELIX           97..104
FT                   /evidence="ECO:0000244|PDB:2QME"
FT   STRAND          105..108
FT                   /evidence="ECO:0000244|PDB:2C2H"
FT   STRAND          110..115
FT                   /evidence="ECO:0000244|PDB:2QME"
FT   HELIX           117..119
FT                   /evidence="ECO:0000244|PDB:2QME"
FT   HELIX           123..130
FT                   /evidence="ECO:0000244|PDB:2QME"
FT   TURN            131..133
FT                   /evidence="ECO:0000244|PDB:2QME"
FT   HELIX           139..148
FT                   /evidence="ECO:0000244|PDB:2QME"
FT   STRAND          152..156
FT                   /evidence="ECO:0000244|PDB:2QME"
FT   TURN            159..161
FT                   /evidence="ECO:0000244|PDB:2QME"
FT   HELIX           165..177
FT                   /evidence="ECO:0000244|PDB:2QME"
SQ   SEQUENCE   192 AA;  21379 MW;  560BBC26BB7CDF4A CRC64;
     MQAIKCVVVG DGAVGKTCLL ISYTTNAFPG EYIPTVFDNY SANVMVDGKP VNLGLWDTAG
     QEDYDRLRPL SYPQTDVFLI CFSLVSPASF ENVRAKWYPE VRHHCPHTPI LLVGTKLDLR
     DDKDTIERLR DKKLAPITYP QGLAMAREIG SVKYLECSAL TQRGLKTVFD EAIRAVLCPP
     PVKKPGKKCT VF
//
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