ID RAC2_HUMAN Reviewed; 192 AA. AC P15153; Q9UDJ4; DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot. DT 01-APR-1990, sequence version 1. DT 21-MAR-2012, entry version 141. DE RecName: Full=Ras-related C3 botulinum toxin substrate 2; DE AltName: Full=GX; DE AltName: Full=Small G protein; DE AltName: Full=p21-Rac2; DE Flags: Precursor; GN Name=RAC2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX MEDLINE=89380250; PubMed=2674130; RA Didsbury J., Weber R.F., Bokoch G.M., Evans T., Snyderman R.; RT "Rac, a novel ras-related family of proteins that are botulinum toxin RT substrates."; RL J. Biol. Chem. 264:16378-16382(1989). 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 RT sequenced by 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]. RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84; RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., RA Beare D.M., Dunham I.; RT "A genome annotation-driven approach to cloning the human ORFeome."; RL Genome Biol. 5:R84.1-R84.11(2004). RN [4] 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 RT vector."; RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX MEDLINE=20057165; PubMed=10591208; DOI=10.1038/990031; RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., RA Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., RA Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., RA Bird C.P., Blakey S.E., Bridgeman A.M., Buck D., Burgess J., RA Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., RA Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., RA Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., RA Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., RA Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., RA Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., RA Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., RA Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., RA Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., RA Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., RA Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., RA Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., RA Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., RA Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., RA Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., RA Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., RA Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., RA Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., RA Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., RA Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., RA Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., RA Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., RA Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., RA Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., RA Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., RA Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., RA Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., RA Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., RA Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., RA O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., RA Khan A.S., Lane L., Tilahun Y., Wright H.; RT "The DNA sequence of human chromosome 22."; RL Nature 402:489-495(1999). RN [6] 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP PROTEIN SEQUENCE OF 6-15; 97-107 AND 134-165. RX MEDLINE=92268051; PubMed=1316893; RA Mizuno T., Kaibuchi K., Ando S., Musha T., Hiraoka K., Takaishi K., RA Asada M., Nunoi H., Matsuda I., Takai Y.; RT "Regulation of the superoxide-generating NADPH oxidase by a small GTP- RT binding protein and its stimulatory and inhibitory GDP/GTP exchange RT proteins."; RL J. Biol. Chem. 267:10215-10218(1992). RN [8] RP PROTEIN SEQUENCE OF 7-16; 19-49; 154-163 AND 175-183, AND FUNCTION. RC TISSUE=Neutrophil; RX MEDLINE=92073931; PubMed=1660188; DOI=10.1126/science.1660188; RA Knaus U.G., Heyworth P.G., Evans T., Curnutte J.T., Bokoch G.M.; RT "Regulation of phagocyte oxygen radical production by the GTP-binding RT protein Rac 2."; RL Science 254:1512-1515(1991). RN [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 13-192. RX MEDLINE=91207334; PubMed=1902092; DOI=10.1016/0006-291X(91)91585-Z; RA Reibel L., Dorseuil O., Stancou R., Bertoglio J., Gacon G.; RT "A hemopoietic specific gene encoding a small GTP binding protein is RT overexpressed during T cell activation."; RL Biochem. Biophys. Res. Commun. 175:451-458(1991). RN [10] RP PROTEIN SEQUENCE OF 97-102 AND 167-174. RC TISSUE=Neutrophil; RX MEDLINE=93277853; 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 [11] RP ISOPRENYLATION AT CYS-189, AND MUTAGENESIS OF CYS-189. RX MEDLINE=91236758; PubMed=1903399; RA Kinsella B.T., Erdman R.A., Maltese W.A.; RT "Carboxyl-terminal isoprenylation of ras-related GTP-binding proteins RT encoded by rac1, rac2, and ralA."; RL J. Biol. Chem. 266:9786-9794(1991). RN [12] RP INTERACTION WITH DOCK2. RX MEDLINE=20025468; PubMed=10559471; DOI=10.1016/S0167-4889(99)00133-0; RA Nishihara H., Kobayashi S., Hashimoto Y., Ohba F., Mochizuki N., RA Kurata T., Nagashima K., Matsuda M.; RT "Non-adherent cell-specific expression of DOCK2, a member of the human RT CDM-family proteins."; RL Biochim. Biophys. Acta 1452:179-187(1999). RN [13] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-147, AND MASS SPECTROMETRY. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., 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 [14] 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., RA Buerckstuemmer T., 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 [15] RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF COMPLEX WITH ARHGDIB. RX MEDLINE=20122627; 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 RT Rho proteins by RhoGDI."; RL Nat. Struct. Biol. 7:122-126(2000). RN [16] RP VARIANT NEUID ASN-57. RX MEDLINE=20243751; PubMed=10758162; DOI=10.1073/pnas.080074897; RA Ambruso D.R., Knall C., Abell A.N., Panepinto J., Kurkchubasche A., RA Thurman G., Gonzalez-Aller C., Hiester A., deBoer M., Harbeck R.J., RA Oyer R., Johnson G.L., Roos D.; RT "Human neutrophil immunodeficiency syndrome is associated with an RT inhibitory Rac2 mutation."; RL Proc. Natl. Acad. Sci. U.S.A. 97:4654-4659(2000). RN [17] RP VARIANT [LARGE SCALE ANALYSIS] LEU-29. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C., RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., RA Vogelstein B., Kinzler K.W., Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal RT cancers."; RL Science 314:268-274(2006). CC -!- FUNCTION: Plasma membrane-associated small GTPase which cycles CC between an active GTP-bound and inactive GDP-bound state. In CC active state binds to a variety of effector proteins to regulate CC cellular responses, such as secretory processes, phagocytose of CC apoptotic cells and epithelial cell polarization. Augments the CC production of reactive oxygen species (ROS) by NADPH oxidase. CC -!- ENZYME REGULATION: Regulated by guanine nucleotide exchange CC factors (GEFs) which promote the exchange of bound GDP for free CC GTP, GTPase activating proteins (GAPs) which increase the GTP CC hydrolysis activity, and GDP dissociation inhibitors which inhibit CC the dissociation of the nucleotide from the GTPase. CC -!- SUBUNIT: Interacts with DOCK2, which may activate it. CC -!- SUBCELLULAR LOCATION: Cytoplasm. Note=Membrane-associated when CC activated. CC -!- TISSUE SPECIFICITY: Hematopoietic specific. CC -!- DISEASE: Defects in RAC2 are the cause of neutrophil CC immunodeficiency syndrome (NEUID) [MIM:608203]. CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rho family. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/RAC2ID42021ch22q13.html"; CC -!- WEB RESOURCE: Name=RAC2base; Note=RAC2 mutation db; CC URL="http://bioinf.uta.fi/RAC2base/"; 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; M29871; AAA36538.1; -; mRNA. DR EMBL; AF498965; AAM21112.1; -; mRNA. DR EMBL; CR456555; CAG30441.1; -; mRNA. DR EMBL; BT006919; AAP35565.1; -; mRNA. DR EMBL; Z82188; CAB45265.1; -; Genomic_DNA. DR EMBL; BC001485; AAH01485.1; -; mRNA. DR EMBL; M64595; AAA35941.1; -; mRNA. DR IPI; IPI00010270; -. DR PIR; B34386; B34386. DR RefSeq; NP_002863.1; NM_002872.3. DR UniGene; Hs.517601; -. DR PDB; 1DS6; X-ray; 2.35 A; A=1-192. DR PDB; 2W2T; X-ray; 1.95 A; A=2-179. DR PDB; 2W2V; X-ray; 2.00 A; A/B/C/D=1-177. DR PDB; 2W2X; X-ray; 2.30 A; A/B=2-179. DR PDBsum; 1DS6; -. DR PDBsum; 2W2T; -. DR PDBsum; 2W2V; -. DR PDBsum; 2W2X; -. DR ProteinModelPortal; P15153; -. DR SMR; P15153; 1-181. DR DIP; DIP-34291N; -. DR IntAct; P15153; 4. DR MINT; MINT-1616362; -. DR STRING; P15153; -. DR PhosphoSite; P15153; -. DR DMDM; 131806; -. DR PeptideAtlas; P15153; -. DR PRIDE; P15153; -. DR DNASU; 5880; -. DR Ensembl; ENST00000249071; ENSP00000249071; ENSG00000128340. DR Ensembl; ENST00000458421; ENSP00000396686; ENSG00000128340. DR GeneID; 5880; -. DR KEGG; hsa:5880; -. DR UCSC; uc003arc.1; human. DR CTD; 5880; -. DR GeneCards; GC22M037621; -. DR H-InvDB; HIX0016439; -. DR HGNC; HGNC:9802; RAC2. DR HPA; CAB022946; -. DR MIM; 602049; gene. DR MIM; 608203; phenotype. DR neXtProt; NX_P15153; -. DR Orphanet; 183707; Neutrophil immunodeficiency syndrome. DR PharmGKB; PA34163; -. DR eggNOG; COG1100; -. DR GeneTree; ENSGT00640000091266; -. DR HOGENOM; HBG745225; -. DR HOVERGEN; HBG009351; -. DR InParanoid; P15153; -. DR KO; K07860; -. DR OMA; CPQPTRT; -. DR OrthoDB; EOG466VN1; -. DR PhylomeDB; P15153; -. DR Reactome; REACT_111045; Developmental Biology. DR Reactome; REACT_111102; Signal Transduction. DR Reactome; REACT_604; Hemostasis. DR NextBio; 22854; -. DR ArrayExpress; P15153; -. DR Bgee; P15153; -. DR CleanEx; HS_RAC2; -. DR Genevestigator; P15153; -. DR GermOnline; ENSG00000128340; Homo sapiens. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW. DR GO; GO:0003924; F:GTPase activity; TAS:ProtInc. DR GO; GO:0007411; P:axon guidance; TAS:Reactome. DR GO; GO:0030168; P:platelet activation; TAS:Reactome. DR GO; GO:0010310; P:regulation of hydrogen peroxide metabolic process; TAS:BHF-UCL. DR GO; GO:0060263; P:regulation of respiratory burst; IDA:BHF-UCL. DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; TAS:Reactome. DR GO; GO:0007264; P:small GTPase mediated signal transduction; TAS:Reactome. DR InterPro; IPR005225; Small_GTP-bd_dom. DR InterPro; IPR001806; Small_GTPase. DR InterPro; IPR003578; Small_GTPase_Rho. DR Pfam; PF00071; Ras; 1. DR PRINTS; PR00449; RASTRNSFRMNG. DR SMART; SM00174; RHO; 1. DR TIGRFAMs; TIGR00231; Small_GTP; 1. DR PROSITE; PS51420; RHO; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; ADP-ribosylation; Complete proteome; KW Cytoplasm; Direct protein sequencing; Disease mutation; GTP-binding; KW Lipoprotein; Methylation; Nucleotide-binding; Polymorphism; KW Prenylation; Reference proteome. FT CHAIN 1 189 Ras-related C3 botulinum toxin substrate FT 2. FT /FTId=PRO_0000042046. FT PROPEP 190 192 Removed in mature form (By similarity). FT /FTId=PRO_0000042047. FT NP_BIND 10 17 GTP (By similarity). FT NP_BIND 57 61 GTP (By similarity). FT NP_BIND 115 118 GTP (By similarity). FT MOTIF 32 40 Effector region (Potential). FT MOD_RES 39 39 ADP-ribosylasparagine; by botulinum toxin FT (By similarity). FT MOD_RES 147 147 N6-acetyllysine. FT MOD_RES 189 189 Cysteine methyl ester (Probable). FT LIPID 189 189 S-geranylgeranyl cysteine. FT VARIANT 29 29 P -> L (in a breast cancer sample; FT somatic mutation). FT /FTId=VAR_036569. FT VARIANT 57 57 D -> N (in NEUID; dominant-negative FT mutant; binds GDP, but not GTP; inhibits FT oxidase activation and superoxide anion FT production in vitro). FT /FTId=VAR_017452. FT MUTAGEN 189 189 C->W: Abolishes in vitro prenylation. FT STRAND 2 10 FT TURN 12 13 FT HELIX 16 25 FT STRAND 40 48 FT STRAND 50 56 FT HELIX 62 64 FT TURN 65 67 FT HELIX 68 71 FT TURN 73 74 FT STRAND 76 83 FT TURN 84 85 FT HELIX 87 95 FT TURN 96 96 FT HELIX 97 104 FT TURN 106 107 FT STRAND 110 115 FT HELIX 117 119 FT TURN 120 121 FT HELIX 123 131 FT TURN 132 133 FT HELIX 139 148 FT TURN 149 150 FT STRAND 152 156 FT TURN 159 161 FT TURN 163 164 FT HELIX 165 177 SQ SEQUENCE 192 AA; 21429 MW; 2A1F1266B07C3210 CRC64; MQAIKCVVVG DGAVGKTCLL ISYTTNAFPG EYIPTVFDNY SANVMVDSKP VNLGLWDTAG QEDYDRLRPL SYPQTDVFLI CFSLVSPASY ENVRAKWFPE VRHHCPSTPI ILVGTKLDLR DDKDTIEKLK EKKLAPITYP QGLALAKEID SVKYLECSAL TQRGLKTVFD EAIRAVLCPQ PTRQQKRACS LL //