RAC2_HUMAN
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 03-AUG-2022, entry version 227.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2674130; DOI=10.1016/s0021-9258(19)84716-6;
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 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].
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 vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., 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., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., 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., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA 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 project:
RT 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 PubMed=1316893; DOI=10.1016/s0021-9258(19)50005-9;
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 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 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 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 PubMed=1903399; DOI=10.1016/s0021-9258(18)92889-9;
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 PubMed=10559471; DOI=10.1016/s0167-4889(99)00133-0;
RA Nishihara H., Kobayashi S., Hashimoto Y., Ohba F., Mochizuki N., Kurata T.,
RA Nagashima K., Matsuda M.;
RT "Non-adherent cell-specific expression of DOCK2, a member of the human CDM-
RT family proteins.";
RL Biochim. Biophys. Acta 1452:179-187(1999).
RN [13]
RP INTERACTION WITH S100A8 AND CALPROTECTIN.
RX PubMed=15642721; DOI=10.1096/fj.04-2377fje;
RA Kerkhoff C., Nacken W., Benedyk M., Dagher M.C., Sopalla C., Doussiere J.;
RT "The arachidonic acid-binding protein S100A8/A9 promotes NADPH oxidase
RT activation by interaction with p67phox and Rac-2.";
RL FASEB J. 19:467-469(2005).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-147, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [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 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 [16]
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 [17]
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 [18]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF COMPLEX WITH ARHGDIB.
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).
RN [19]
RP VARIANT IMD73A ASN-57.
RX 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 [20]
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., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [21]
RP INVOLVEMENT IN IMD73C, VARIANT IMD73C 56-TRP--LEU-192 DEL, AND
RP CHARACTERIZATION OF VARIANT IMD73C 56-TRP--LEU-192 DEL.
RX PubMed=25512081; DOI=10.1016/j.jaci.2014.10.039;
RA Alkhairy O.K., Rezaei N., Graham R.R., Abolhassani H., Borte S.,
RA Hultenby K., Wu C., Aghamohammadi A., Williams D.A., Behrens T.W.,
RA Hammarstroem L., Pan-Hammarstroem Q.;
RT "RAC2 loss-of-function mutation in 2 siblings with characteristics of
RT common variable immunodeficiency.";
RL J. Allergy Clin. Immunol. 135:1380-1384(2015).
RN [22]
RP INVOLVEMENT IN IMD73B, VARIANT IMD73B LYS-62, CHARACTERIZATION OF VARIANT
RP IMD73B LYS-62, FUNCTION, AND INTERACTION WITH PAK1.
RX PubMed=30723080; DOI=10.1182/blood-2018-11-886028;
RA Hsu A.P., Donko A., Arrington M.E., Swamydas M., Fink D., Das A.,
RA Escobedo O., Bonagura V., Szabolcs P., Steinberg H.N., Bergerson J.,
RA Skoskiewicz A., Makhija M., Davis J., Foruraghi L., Palmer C.,
RA Fuleihan R.L., Church J.A., Bhandoola A., Lionakis M.S., Campbell S.,
RA Leto T.L., Kuhns D.B., Holland S.M.;
RT "Dominant activating RAC2 mutation with lymphopenia, immunodeficiency, and
RT cytoskeletal defects.";
RL Blood 133:1977-1988(2019).
RN [23]
RP INVOLVEMENT IN IMD73B, VARIANT IMD73B THR-92, AND CHARACTERIZATION OF
RP VARIANT IMD73B THR-92.
RX PubMed=31071452; DOI=10.1016/j.clim.2019.05.003;
RA Sharapova S.O., Haapaniemi E., Sakovich I.S., Kostyuchenko L.V., Donko A.,
RA Dulau-Florea A., Malko O., Bondarenko A.V., Stegantseva M.V., Leto T.L.,
RA Uygun V., Karasu G.T., Holland S.M., Hsu A.P., Aleinikova O.V.;
RT "Heterozygous activating mutation in RAC2 causes infantile-onset combined
RT immunodeficiency with susceptibility to viral infections.";
RL Clin. Immunol. 205:1-5(2019).
RN [24]
RP INVOLVEMENT IN IMD73B, VARIANT IMD73B HIS-34, CHARACTERIZATION OF VARIANT
RP IMD73B HIS-34, AND INTERACTION WITH PAK1.
RX PubMed=30654050; DOI=10.1016/j.jaci.2019.01.001;
RA Lougaris V., Chou J., Beano A., Wallace J.G., Baronio M., Gazzurelli L.,
RA Lorenzini T., Moratto D., Tabellini G., Parolini S., Seleman M.,
RA Stafstrom K., Xu H., Harris C., Geha R.S., Plebani A.;
RT "A monoallelic activating mutation in RAC2 resulting in a combined
RT immunodeficiency.";
RL J. Allergy Clin. Immunol. 143:1649-1653(2019).
RN [25]
RP INVOLVEMENT IN IMD73B, VARIANT IMD73B LYS-62, AND CHARACTERIZATION OF
RP VARIANT IMD73B LYS-62.
RX PubMed=31382036; DOI=10.1016/j.clim.2019.108248;
RA Smits B.M., Lelieveld P.H.C., Ververs F.A., Turkenburg M., de Koning C.,
RA van Dijk M., Leavis H.L., Boelens J.J., Lindemans C.A., Bloem A.C.,
RA van de Corput L., van Montfrans J., Nierkens S., van Gijn M.E.,
RA Geerke D.P., Waterham H.R., Koenderman L., Boes M.;
RT "A dominant activating RAC2 variant associated with immunodeficiency and
RT pulmonary disease.";
RL Clin. Immunol. 212:108248-108248(2020).
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 secretory processes, phagocytose of apoptotic cells and epithelial
CC cell polarization. Augments the production of reactive oxygen species
CC (ROS) by NADPH oxidase. {ECO:0000269|PubMed:1660188,
CC ECO:0000269|PubMed:30723080}.
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.
CC -!- SUBUNIT: Interacts with DOCK2, which may activate it. Interacts with
CC S100A8 and calprotectin (S100A8/9) (PubMed:10559471, PubMed:15642721).
CC Found in a complex with SH3RF1, MAP3K7/TAK1, MAP2K7/MKK7,
CC MAPK8IP1/JIP1, MAPK8/JNK1 and MAPK9/JNK2 (By similarity). Interacts
CC with PAK1 (PubMed:30723080, PubMed:30654050).
CC {ECO:0000250|UniProtKB:Q05144, ECO:0000269|PubMed:10559471,
CC ECO:0000269|PubMed:15642721, ECO:0000269|PubMed:30654050,
CC ECO:0000269|PubMed:30723080}.
CC -!- INTERACTION:
CC P15153; P53365: ARFIP2; NbExp=3; IntAct=EBI-489652, EBI-638194;
CC P15153; Q8WUI4-6: HDAC7; NbExp=3; IntAct=EBI-489652, EBI-12094670;
CC P15153; O14939: PLD2; NbExp=4; IntAct=EBI-489652, EBI-1053996;
CC P15153; Q6P589: TNFAIP8L2; NbExp=2; IntAct=EBI-489652, EBI-9073209;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Note=Membrane-associated when
CC activated.
CC -!- TISSUE SPECIFICITY: Hematopoietic specific.
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: Immunodeficiency 73A with defective neutrophil chemotaxis and
CC leukocytosis (IMD73A) [MIM:608203]: An autosomal dominant immunologic
CC disorder characterized by onset of recurrent infections in early
CC infancy, leukocytosis, neutrophilia, invasive infections, and poor
CC wound healing. {ECO:0000269|PubMed:10758162}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Immunodeficiency 73B with defective neutrophil chemotaxis and
CC lymphopenia (IMD73B) [MIM:618986]: An autosomal dominant immunologic
CC disorder characterized by respiratory infections, cellulitis, severe
CC invasive infections, B- and T-cell lymphopenia, and impaired neutrophil
CC chemotaxis. Disease onset is in infancy or early childhood.
CC {ECO:0000269|PubMed:30654050, ECO:0000269|PubMed:30723080,
CC ECO:0000269|PubMed:31071452, ECO:0000269|PubMed:31382036}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Immunodeficiency 73C with defective neutrophil chemotaxis and
CC hypogammaglobulinemia (IMD73C) [MIM:618987]: An autosomal recessive
CC immunologic disorder characterized by recurrent respiratory infections,
CC decreased B cells, hypogammaglobulinemia, and impaired neutrophil
CC chemotaxis. Variable features are urticaria, recurrent erythematous
CC plaques, food allergy, arthralgia, bronchiectasis, and lymphadenopathy.
CC In addition, patients suffer from glomerulonephritis, coagulopathy,
CC multiple hormone deficiencies, and abnormalities of neutrophil
CC granules. {ECO:0000269|PubMed:25512081}. Note=The disease is caused by
CC variants 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/RAC2ID42021ch22q13.html";
CC -!- WEB RESOURCE: Name=RAC2base; Note=RAC2 mutation db;
CC URL="http://structure.bmc.lu.se/idbase/RAC2base/";
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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; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001485; AAH01485.1; -; mRNA.
DR EMBL; M64595; AAA35941.1; -; mRNA.
DR CCDS; CCDS13945.1; -.
DR PIR; B34386; B34386.
DR RefSeq; NP_002863.1; NM_002872.4.
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 AlphaFoldDB; P15153; -.
DR SMR; P15153; -.
DR BioGRID; 111818; 656.
DR ComplexPortal; CPX-6134; Phagocyte NADPH oxidase complex, RAC2 variant.
DR DIP; DIP-34291N; -.
DR IntAct; P15153; 25.
DR MINT; P15153; -.
DR STRING; 9606.ENSP00000249071; -.
DR ChEMBL; CHEMBL5581; -.
DR DrugBank; DB00514; Dextromethorphan.
DR GlyGen; P15153; 3 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; P15153; -.
DR PhosphoSitePlus; P15153; -.
DR SwissPalm; P15153; -.
DR BioMuta; RAC2; -.
DR DMDM; 131806; -.
DR EPD; P15153; -.
DR jPOST; P15153; -.
DR MassIVE; P15153; -.
DR MaxQB; P15153; -.
DR PaxDb; P15153; -.
DR PeptideAtlas; P15153; -.
DR PRIDE; P15153; -.
DR ProteomicsDB; 53114; -.
DR Antibodypedia; 25898; 412 antibodies from 35 providers.
DR DNASU; 5880; -.
DR Ensembl; ENST00000249071.11; ENSP00000249071.6; ENSG00000128340.15.
DR GeneID; 5880; -.
DR KEGG; hsa:5880; -.
DR MANE-Select; ENST00000249071.11; ENSP00000249071.6; NM_002872.5; NP_002863.1.
DR UCSC; uc003arc.5; human.
DR CTD; 5880; -.
DR DisGeNET; 5880; -.
DR GeneCards; RAC2; -.
DR HGNC; HGNC:9802; RAC2.
DR HPA; ENSG00000128340; Group enriched (bone marrow, lymphoid tissue).
DR MalaCards; RAC2; -.
DR MIM; 602049; gene.
DR MIM; 608203; phenotype.
DR MIM; 618986; phenotype.
DR MIM; 618987; phenotype.
DR neXtProt; NX_P15153; -.
DR OpenTargets; ENSG00000128340; -.
DR Orphanet; 183707; Neutrophil immunodeficiency syndrome.
DR PharmGKB; PA34163; -.
DR VEuPathDB; HostDB:ENSG00000128340; -.
DR eggNOG; KOG0393; Eukaryota.
DR GeneTree; ENSGT00940000155205; -.
DR InParanoid; P15153; -.
DR OMA; LICYSIM; -.
DR OrthoDB; 1091615at2759; -.
DR PhylomeDB; P15153; -.
DR TreeFam; TF101109; -.
DR BRENDA; 3.6.5.2; 2681.
DR PathwayCommons; P15153; -.
DR Reactome; R-HSA-114604; GPVI-mediated activation cascade.
DR Reactome; R-HSA-1222556; ROS and RNS production in phagocytes.
DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling.
DR Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer.
DR Reactome; R-HSA-4086400; PCP/CE pathway.
DR Reactome; R-HSA-5668599; RHO GTPases Activate NADPH Oxidases.
DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-HSA-9013404; RAC2 GTPase cycle.
DR SignaLink; P15153; -.
DR SIGNOR; P15153; -.
DR BioGRID-ORCS; 5880; 24 hits in 1078 CRISPR screens.
DR ChiTaRS; RAC2; human.
DR EvolutionaryTrace; P15153; -.
DR GeneWiki; RAC2; -.
DR GenomeRNAi; 5880; -.
DR Pharos; P15153; Tbio.
DR PRO; PR:P15153; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; P15153; protein.
DR Bgee; ENSG00000128340; Expressed in granulocyte and 165 other tissues.
DR ExpressionAtlas; P15153; baseline and differential.
DR Genevisible; P15153; 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; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB.
DR GO; GO:0005741; C:mitochondrial outer membrane; TAS:Reactome.
DR GO; GO:0043020; C:NADPH oxidase complex; IC:ComplexPortal.
DR GO; GO:0005635; C:nuclear envelope; IEA:Ensembl.
DR GO; GO:0030670; C:phagocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005525; F:GTP binding; IMP:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; IBA:GO_Central.
DR GO; GO:0019901; F:protein kinase binding; IBA:GO_Central.
DR GO; GO:0019887; F:protein kinase regulator activity; IEA:Ensembl.
DR GO; GO:0007015; P:actin filament organization; IMP:UniProtKB.
DR GO; GO:0030031; P:cell projection assembly; IBA:GO_Central.
DR GO; GO:0030865; P:cortical cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0043652; P:engulfment of apoptotic cell; IBA:GO_Central.
DR GO; GO:0007163; P:establishment or maintenance of cell polarity; IBA:GO_Central.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0071593; P:lymphocyte aggregation; IMP:UniProtKB.
DR GO; GO:0070662; P:mast cell proliferation; IEA:Ensembl.
DR GO; GO:0008045; P:motor neuron axon guidance; IBA:GO_Central.
DR GO; GO:0010592; P:positive regulation of lamellipodium assembly; IMP:UniProtKB.
DR GO; GO:0070668; P:positive regulation of mast cell proliferation; IEA:Ensembl.
DR GO; GO:0090023; P:positive regulation of neutrophil chemotaxis; IMP:UniProtKB.
DR GO; GO:1903955; P:positive regulation of protein targeting to mitochondrion; HMP:ParkinsonsUK-UCL.
DR GO; GO:0016601; P:Rac protein signal transduction; IBA:GO_Central.
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:0010810; P:regulation of cell-substrate adhesion; IMP:UniProtKB.
DR GO; GO:0010310; P:regulation of hydrogen peroxide metabolic process; TAS:BHF-UCL.
DR GO; GO:0060753; P:regulation of mast cell chemotaxis; IEA:Ensembl.
DR GO; GO:0043304; P:regulation of mast cell degranulation; IEA:Ensembl.
DR GO; GO:1902622; P:regulation of neutrophil migration; IMP:UniProtKB.
DR GO; GO:0060263; P:regulation of respiratory burst; IDA:BHF-UCL.
DR GO; GO:0042129; P:regulation of T cell proliferation; IEA:Ensembl.
DR GO; GO:0045730; P:respiratory burst; IC:ComplexPortal.
DR GO; GO:0007165; P: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; Acetylation; ADP-ribosylation; Cytoplasm;
KW Direct protein sequencing; Disease variant; Glycoprotein; GTP-binding;
KW Lipoprotein; Methylation; Nucleotide-binding; Prenylation;
KW Reference proteome.
FT CHAIN 1..189
FT /note="Ras-related C3 botulinum toxin substrate 2"
FT /id="PRO_0000042046"
FT PROPEP 190..192
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000042047"
FT MOTIF 32..40
FT /note="Effector region"
FT /evidence="ECO:0000255"
FT BINDING 10..17
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 57..61
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 115..118
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT MOD_RES 39
FT /note="ADP-ribosylasparagine; by botulinum toxin"
FT /evidence="ECO:0000250"
FT MOD_RES 147
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 189
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000250"
FT LIPID 189
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000269|PubMed:1903399"
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 a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036569"
FT VARIANT 34
FT /note="P -> H (in IMD73B; unknown pathological
FT significance; increased interaction with PAK1 compared to
FT wild-type; potential gain-of-function variant)"
FT /evidence="ECO:0000269|PubMed:30654050"
FT /id="VAR_085472"
FT VARIANT 56..192
FT /note="Missing (in IMD73C; strong decrease in protein
FT expression)"
FT /evidence="ECO:0000269|PubMed:25512081"
FT /id="VAR_085473"
FT VARIANT 57
FT /note="D -> N (in IMD73A; dominant-negative mutant; binds
FT GDP, but not GTP; inhibits oxidase activation and
FT superoxide anion production in vitro; dbSNP:rs74315507)"
FT /evidence="ECO:0000269|PubMed:10758162"
FT /id="VAR_017452"
FT VARIANT 62
FT /note="E -> K (in IMD73B; gain-of-function variant;
FT exhibits impaired GAP-mediated GTP hydrolysis, resulting in
FT sustained GTP association and prolonged RAC2-driven
FT activation of downstream effectors; when transfected into
FT cells, shows increased basal reactive oxygen species
FT production following stimulation by PMA compared to cells
FT transfected with wild-type; increased interaction with
FT PAK1, compared to wild-type; dbSNP:rs1555908409)"
FT /evidence="ECO:0000269|PubMed:30723080,
FT ECO:0000269|PubMed:31382036"
FT /id="VAR_085474"
FT VARIANT 92
FT /note="N -> T (in IMD73B; unknown pathological
FT significance; cells transfected with this variant show
FT higher production of reactive oxygen species compared to
FT wild-type; potential gain-of-function variant)"
FT /evidence="ECO:0000269|PubMed:31071452"
FT /id="VAR_085475"
FT MUTAGEN 189
FT /note="C->W: Abolishes in vitro prenylation."
FT /evidence="ECO:0000269|PubMed:1903399"
FT STRAND 3..11
FT /evidence="ECO:0007829|PDB:2W2T"
FT HELIX 16..25
FT /evidence="ECO:0007829|PDB:2W2T"
FT STRAND 39..46
FT /evidence="ECO:0007829|PDB:2W2T"
FT STRAND 49..56
FT /evidence="ECO:0007829|PDB:2W2T"
FT HELIX 62..64
FT /evidence="ECO:0007829|PDB:2W2T"
FT TURN 65..67
FT /evidence="ECO:0007829|PDB:2W2T"
FT HELIX 68..71
FT /evidence="ECO:0007829|PDB:2W2T"
FT STRAND 77..83
FT /evidence="ECO:0007829|PDB:2W2T"
FT HELIX 87..95
FT /evidence="ECO:0007829|PDB:2W2T"
FT HELIX 97..104
FT /evidence="ECO:0007829|PDB:2W2T"
FT STRAND 106..108
FT /evidence="ECO:0007829|PDB:2W2T"
FT STRAND 110..115
FT /evidence="ECO:0007829|PDB:2W2T"
FT HELIX 117..119
FT /evidence="ECO:0007829|PDB:2W2T"
FT HELIX 123..130
FT /evidence="ECO:0007829|PDB:2W2T"
FT TURN 131..133
FT /evidence="ECO:0007829|PDB:2W2T"
FT HELIX 139..149
FT /evidence="ECO:0007829|PDB:2W2T"
FT STRAND 152..156
FT /evidence="ECO:0007829|PDB:2W2T"
FT TURN 159..161
FT /evidence="ECO:0007829|PDB:2W2T"
FT HELIX 165..175
FT /evidence="ECO:0007829|PDB:2W2T"
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
