ID RAC1_HUMAN STANDARD; PRT; 192 AA. AC P63000; O95501; P15154; Q9BTB4; DT 01-APR-1990 (Rel. 14, Created) DT 01-APR-1990 (Rel. 14, Last sequence update) DT 13-SEP-2005 (Rel. 48, Last annotation update) DE Ras-related C3 botulinum toxin substrate 1 (p21-Rac1) (Ras-like DE protein TC25). GN Name=RAC1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE (ISOFORM A). 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 (ISOFORM A). RX MEDLINE=90205863; PubMed=2108320; RA Drivas G.T., Shih A., Coutavas E., Rush M.G., D'Eustachio P.; RT "Characterization of four novel ras-like genes expressed in a human RT teratocarcinoma cell line."; RL Mol. Cell. Biol. 10:1793-1798(1990). RN [3] RP NUCLEOTIDE SEQUENCE (ISOFORMS A AND B). RX MEDLINE=20517245; PubMed=11062023; DOI=10.1006/bbrc.2000.3743; RA Matos P., Skaug J., Marques B., Beck S., Verissimo F., Gespach C., RA Boavida M.G., Scherer S.W., Jordan P.; RT "Small GTPase Rac1: structure, localization, and expression of the RT human gene."; RL Biochem. Biophys. Res. Commun. 277:741-751(2000). RN [4] RP NUCLEOTIDE SEQUENCE (ISOFORMS A AND B). RC TISSUE=Colon, and Skin; RX MEDLINE=20065162; PubMed=10597294; DOI=10.1038/sj.onc.1203233; RA Jordan P., Brazao R., Boavida M.G., Gespach C., Chastre E.; RT "Cloning of a novel human Rac1b splice variant with increased RT expression in colorectal tumors."; RL Oncogene 18:6835-6839(1999). RN [5] RP NUCLEOTIDE SEQUENCE (ISOFORM B). RA Schnelzer A., Knaus U., Prechtel D., Dehne K., Harbeck N., Gerhard M., RA Schmitt M., Lengyel E.; RT "Mutations and altered expression of Rac1 in human breast cancer -- RT characterization of a new Rac1 isoform, Rac1ins."; RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A). 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A). 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 (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX MEDLINE=22737999; PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., RA Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., RA Waterston R.H., Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A). RC TISSUE=Pancreas, and Skin; RX MEDLINE=22388257; PubMed=12477932; DOI=10.1073/pnas.242603899; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length human RT and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). RN [10] RP ISOPRENOID. 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 [11] RP INTERACTION WITH RALBP1. RX MEDLINE=95403450; PubMed=7673236; DOI=10.1074/jbc.270.38.22473; RA Jullien-Flores V., Dorseuil O., Romero F., Letourneur F., RA Saragosti S., Berger R., Tavitian A., Gacon G., Camonis J.H.; RT "Bridging Ral GTPase to Rho pathways. RLIP76, a Ral effector with RT CDC42/Rac GTPase-activating protein activity."; RL J. Biol. Chem. 270:22473-22477(1995). 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 INTERACTION WITH PARD6A, AND MUTAGENESIS OF GLN-61. RX MEDLINE=20411249; PubMed=10954424; RA Johansson A.-S., Driessens M., Aspenstroem P.; RT "The mammalian homologue of the Caenorhabditis elegans polarity RT protein PAR-6 is a binding partner for the Rho GTPases Cdc42 and RT Rac1."; RL J. Cell Sci. 113:3267-3275(2000). RN [14] RP INTERACTION WITH PLXNB1. RX PubMed=11035813; DOI=10.1073/pnas.220421797; RA Vikis H.G., Li W., He Z., Guan K.-L.; RT "The semaphorin receptor plexin-B1 specifically interacts with active RT Rac in a ligand-dependent manner."; RL Proc. Natl. Acad. Sci. U.S.A. 97:12457-12462(2000). RN [15] RP INTERACTIONS WITH PARD6A; PARD6B AND PARD6G; PRKCI AND PRKCZ, AND RP MUTAGENESIS OF GLY-12 AND THR-17. RX MEDLINE=21160560; PubMed=11260256; RA Noda Y., Takeya R., Ohno S., Naito S., Ito T., Sumimoto H.; RT "Human homologues of the Caenorhabditis elegans cell polarity protein RT PAR6 as an adaptor that links the small GTPases Rac and Cdc42 to RT atypical protein kinase C."; RL Genes Cells 6:107-119(2001). RN [16] RP ACTIVATION BY PREX1. RX MEDLINE=21952478; PubMed=11955434; DOI=10.1016/S0092-8674(02)00663-3; RA Welch H.C.E., Coadwell W.J., Ellson C.D., Ferguson G.J., Andrews S.R., RA Erdjument-Bromage H., Tempst P., Hawkins P.T., Stephens L.R.; RT "P-Rex1, a PtdIns(3,4,5)P3-and Gbetagamma-regulated guanine-nucleotide RT exchange factor for Rac."; RL Cell 108:809-821(2002). RN [17] RP SUBUNIT OF A COMPLEX CONTAINING ELMO1 AND DOCK1. RX MEDLINE=22144530; PubMed=12134158; DOI=10.1038/ncb824; RA Brugnera E., Haney L., Grimsley C., Lu M., Walk S.F., RA Tosello-Trampont A.-C., Macara I.G., Madhani H., Fink G.R., RA Ravichandran K.S.; RT "Unconventional Rac-GEF activity is mediated through the Dock180-ELMO RT complex."; RL Nat. Cell Biol. 4:574-582(2002). RN [18] RP X-RAY CRYSTALLOGRAPHY (1.38 ANGSTROMS) OF 1-184. RX MEDLINE=97185915; PubMed=9033596; RA Hirshberg M., Stockley R.W., Dodson G., Webb M.R.; RT "The crystal structure of human rac1, a member of the rho-family RT complexed with a GTP analogue."; RL Nat. Struct. Biol. 4:147-152(1997). RN [19] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF COMPLEX WITH NCF2. RX MEDLINE=21000498; PubMed=11090627; RA Lapouge K., Smith S.J., Walker P.A., Gamblin S.J., Smerdon S.J., RA Rittinger K.; RT "Structure of the TPR domain of p67phox in complex with Rac.GTP."; RL Mol. Cell 6:899-907(2000). RN [20] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1-177 IN COMPLEX WITH TIAM1. RX MEDLINE=21012003; PubMed=11130063; DOI=10.1038/35047014; RA Worthylake D.K., Rossman K.L., Sondek J.; RT "Crystal structure of Rac1 in complex with the guanine nucleotide RT exchange region of Tiam1."; RL Nature 408:682-688(2000). RN [21] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1-184. RX MEDLINE=21111053; PubMed=11163217; DOI=10.1016/S1097-2765(00)00141-6; RA Stebbins C.E., Galan J.E.; RT "Modulation of host signaling by a bacterial mimic: structure of the RT Salmonella effector SptP bound to Rac1."; RL Mol. Cell 6:1449-1460(2000). RN [22] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-176. RX MEDLINE=20577269; PubMed=11135665; DOI=10.1038/83007; RA Wurtele M., Wolf E., Pederson K.J., Buchwald G., Ahmadian M.R., RA Barbieri J.T., Wittinghofer A.; RT "How the Pseudomonas aeruginosa ExoS toxin downregulates Rac."; RL Nat. Struct. Biol. 8:23-26(2001). RN [23] RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) IN COMPLEX WITH ARHGDIA. RX MEDLINE=21404971; PubMed=11513578; DOI=10.1021/bi010288k; RA Grizot S., Faure J., Fieschi F., Vignais P.V., Dagher M.C., RA Pebay-Peyroula E.; RT "Crystal structure of the Rac1-RhoGDI complex involved in nadph RT oxidase activation."; RL Biochemistry 40:10007-10013(2001). RN [24] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH ARFIP2. RX MEDLINE=21244534; PubMed=11346801; DOI=10.1038/35075620; RA Tarricone C., Xiao B., Justin N., Walker P.A., Rittinger K., RA Gamblin S.J., Smerdon S.J.; RT "The structural basis of Arfaptin-mediated cross-talk between Rac and RT Arf signalling pathways."; RL Nature 411:215-219(2001). RN [25] RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF ISOFORM B, AND RP CHARACTERIZATION OF ISOFORM B. RX PubMed=14625275; DOI=10.1074/jbc.M310281200; RA Fiegen D., Haeusler L.C., Blumenstein L., Herbrand U., Dvorsky R., RA Vetter I.R., Ahmadian M.R.; RT "Alternative splicing of Rac1 generates Rac1b, a self-activating RT GTPase."; RL J. Biol. Chem. 279:4743-4749(2004). CC -!- FUNCTION: Plasma membrane-associated small GTPase which cycles CC between an active GTP-bond and inactive GDP-bound state. In active CC state binds to a variety of effector proteins to regulate cellular CC responses, such as secretory processes, phagocytose of apoptotic CC cells and epithelial cell polarization. CC -!- FUNCTION: Isoform B has an accelerated GEF-independent GDP/GTP CC exchange and an impaired GTP hydrolysis, which is restored CC partially by GTPase-activating proteins. It is able to bind to the CC GTPase-binding domain of PAK but not full-length PAK in a GTP- CC dependent manner, suggesting that the insertion does not CC completely abolish effector interaction. 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 the GEF proteins PREX1, DOCK1 and DOCK2, CC which promote the exchange between GDP and GTP, and therefore CC activate it. Interacts with PARD6A, PARD6B and PARD6G in a GTP- CC dependent manner. Part of a quaternary complex containing PARD3, CC some PARD6 protein (PARD6A, PARD6B or PARD6G) and some atypical CC PKC protein (PRKCI or PRKCZ), which plays a central role in CC epithelial cell polarization. Found in a trimeric complex composed CC of DOCK1 and ELMO1, which plays a central role in phagocytosis of CC apoptotic cells. Interacts with RALBP1 via its effector domain. CC Binds PLXNB1. CC -!- INTERACTION: CC Q14185:DOCK1; NbExp=2; IntAct=EBI-413628, EBI-446740; CC Q92608:DOCK2; NbExp=1; IntAct=EBI-413628, EBI-448771; CC P19878:NCF2; NbExp=2; IntAct=EBI-413628, EBI-489611; CC Q13153:PAK1; NbExp=2; IntAct=EBI-413628, EBI-1307; CC Q86W79:PAK1; NbExp=1; IntAct=EBI-413628, EBI-446619; CC O88643:Pak1 (xeno); NbExp=1; IntAct=EBI-413628, EBI-457240; CC Q61036:Pak3 (xeno); NbExp=1; IntAct=EBI-413628, EBI-457317; CC Q9NPB6:PARD6A; NbExp=1; IntAct=EBI-413628, EBI-81876; CC Q9BYG5:PARD6B; NbExp=1; IntAct=EBI-413628, EBI-295391; CC Q9BYG4:PARD6G; NbExp=1; IntAct=EBI-413628, EBI-295417; CC Q06409:YLR422W (xeno); NbExp=1; IntAct=EBI-413628, EBI-35964; CC -!- SUBCELLULAR LOCATION: Inner surface of plasma membrane possibly CC with attachment requiring acylation of the C-terminal cysteine (By CC similarity with RAS). CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=A; Synonyms=Rac1A; CC IsoId=P63000-1, P15154-1; CC Sequence=Displayed; CC Name=B; Synonyms=Rac1B, Rac1ins; CC IsoId=P63000-2, P15154-2; CC Sequence=VSP_005710; CC -!- TISSUE SPECIFICITY: Isoform B is predominantly identified in skin CC and epithelial tissues from the intestinal tract. The expression CC of isoform B is elevated in colorectal tumors at various stages of CC neoplastic progression, as compared to their respective adjacent CC tissues. CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rho family. 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; M29870; AAA36537.1; -; mRNA. DR EMBL; M31467; AAA36544.1; -; mRNA. DR EMBL; AJ132695; CAB53579.5; -; Genomic_DNA. DR EMBL; AJ132694; CAA10732.1; -; mRNA. DR EMBL; AJ132695; CAA10733.6; -; Genomic_DNA. DR EMBL; AF136373; AAD30547.1; -; mRNA. DR EMBL; AF498964; AAM21111.1; -; mRNA. DR EMBL; BT007121; AAP35785.1; -; mRNA. DR EMBL; AC009412; AAS07511.1; -; Genomic_DNA. DR EMBL; AC009412; AAS07512.1; -; Genomic_DNA. DR EMBL; BC004247; AAH04247.1; -; mRNA. DR EMBL; BC050687; AAH50687.1; -; mRNA. DR PIR; A34788; TVHUC1. DR PDB; 1E96; X-ray; A=2-192. DR PDB; 1FOE; X-ray; B/D/F/H=1-177. DR PDB; 1G4U; X-ray; R=1-184. DR PDB; 1HE1; X-ray; C/D=2-176. DR PDB; 1HH4; X-ray; A/B=2-192. DR PDB; 1I4D; X-ray; D=1-192. DR PDB; 1I4L; X-ray; D=1-192. DR PDB; 1I4T; X-ray; D=1-192. DR PDB; 1MH1; X-ray; @=2-184. DR PDB; 1RYF; X-ray; A/B=1-182. DR PDB; 1RYH; X-ray; A/B=1-182. DR SMR; P63000; 2-189. DR IntAct; P63000; -. DR Ensembl; ENSG00000136238; Homo sapiens. DR HGNC; HGNC:9801; RAC1. DR Reactome; P63000; -. DR MIM; 602048; -. DR InterPro; IPR003578; GTPase_Rho. DR InterPro; IPR001806; Ras_trnsfrmng. DR InterPro; IPR005225; Small_GTP. DR Pfam; PF00071; Ras; 1. DR TIGRFAMs; TIGR00231; small_GTP; 1. KW 3D-structure; Alternative splicing; GTP-binding; Lipoprotein; KW Nucleotide-binding; Polymorphism; Prenylation. 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 LIPID 189 189 S-geranylgeranyl cysteine. FT VARSPLIC 75 75 T -> TVGETYGKDITSRGKDKPIA (in isoform B). FT /FTId=VSP_005710. FT VARIANT 26 26 N -> D (in dbSNP:5830). FT /FTId=VAR_014540. FT VARIANT 28 28 F -> L (in dbSNP:5832). FT /FTId=VAR_014541. FT VARIANT 59 59 A -> T (in dbSNP:5837). FT /FTId=VAR_014542. FT VARIANT 63 63 D -> G (in dbSNP:5831). FT /FTId=VAR_014543. FT VARIANT 93 93 V -> G (in dbSNP:5826). FT /FTId=VAR_014545. FT VARIANT 93 93 V -> I (in dbSNP:5825). FT /FTId=VAR_014544. FT VARIANT 108 108 T -> I (in dbSNP:5838). FT /FTId=VAR_014546. FT VARIANT 130 130 K -> R (in dbSNP:5828). FT /FTId=VAR_014547. FT VARIANT 133 133 K -> E (in dbSNP:5835). FT /FTId=VAR_014548. FT VARIANT 180 180 P -> S (in dbSNP:16063). FT /FTId=VAR_014549. FT VARIANT 182 182 V -> E (in dbSNP:5836). FT /FTId=VAR_014550. FT MUTAGEN 12 12 G->V: Constitutively active. Interacts FT with PARD6 proteins. FT MUTAGEN 17 17 T->N: Constitutively inactivated. FT Abolishes interaction with PARD6 FT proteins. FT MUTAGEN 61 61 Q->L: Constitutively active. Interacts FT with PARD6 proteins. FT CONFLICT 135 135 T -> I (in Ref. 9; AAH04247). FT CONFLICT 192 192 Missing (in Ref. 2). FT STRAND 2 9 FT TURN 12 13 FT HELIX 16 25 FT STRAND 39 46 FT TURN 47 48 FT STRAND 49 56 FT HELIX 62 64 FT TURN 65 67 FT HELIX 68 71 FT TURN 73 74 FT STRAND 77 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 117 120 FT TURN 121 121 FT HELIX 123 131 FT TURN 132 133 FT HELIX 139 148 FT TURN 149 150 FT STRAND 153 156 FT TURN 159 161 FT TURN 163 164 FT HELIX 165 176 SQ SEQUENCE 192 AA; 21450 MW; ACEDF83A45E5EA67 CRC64; MQAIKCVVVG DGAVGKTCLL ISYTTNAFPG EYIPTVFDNY SANVMVDGKP VNLGLWDTAG QEDYDRLRPL SYPQTDVFLI CFSLVSPASF ENVRAKWYPE VRHHCPNTPI ILVGTKLDLR DDKDTIEKLK EKKLTPITYP QGLAMAKEIG AVKYLECSAL TQRGLKTVFD EAIRAVLCPP PVKKRKRKCL LL //