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 27-MAR-2024, entry version 236. 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="https://atlasgeneticsoncology.org/gene/42021/RAC2"; CC -!- WEB RESOURCE: Name=RAC2base; Note=RAC2 mutation db; CC URL="http://structure.bmc.lu.se/idbase/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; -; 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; 663. DR ComplexPortal; CPX-6134; Phagocyte NADPH oxidase complex, RAC2 variant. DR DIP; DIP-34291N; -. DR IntAct; P15153; 26. DR MINT; P15153; -. DR STRING; 9606.ENSP00000249071; -. DR ChEMBL; CHEMBL5581; -. DR DrugBank; DB00514; Dextromethorphan. DR GlyCosmos; P15153; 3 sites, 1 glycan. 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; 9606-ENSP00000249071; -. DR PeptideAtlas; P15153; -. DR ProteomicsDB; 53114; -. DR Pumba; P15153; -. DR Antibodypedia; 25898; 429 antibodies from 35 providers. DR DNASU; 5880; -. DR Ensembl; ENST00000249071.11; ENSP00000249071.6; ENSG00000128340.16. 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 AGR; HGNC:9802; -. 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; EIRTHCP; -. DR OrthoDB; 20499at2759; -. 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; 32 hits in 1163 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 167 other cell types or tissues. DR ExpressionAtlas; P15153; baseline and differential. 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; NAS: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:0019887; F:protein kinase regulator activity; IEA:Ensembl. DR GO; GO:0007015; P:actin filament organization; IMP:UniProtKB. DR GO; GO:0045453; P:bone resorption; IEA:Ensembl. DR GO; GO:0030031; P:cell projection assembly; IEA:Ensembl. DR GO; GO:0006935; P:chemotaxis; IBA:GO_Central. DR GO; GO:0043131; P:erythrocyte enucleation; IEA:Ensembl. 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: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:0030334; P:regulation of cell migration; 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; NAS:ComplexPortal. DR GO; GO:0007165; P:signal transduction; IBA:GO_Central. DR GO; GO:0007264; P:small GTPase mediated signal transduction; IEA:InterPro. DR CDD; cd01871; Rac1_like; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 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 NCBIfam; TIGR00231; small_GTP; 1. DR PANTHER; PTHR24072:SF169; RAS-RELATED C3 BOTULINUM TOXIN SUBSTRATE 2; 1. DR PANTHER; PTHR24072; RHO FAMILY GTPASE; 1. DR Pfam; PF00071; Ras; 1. DR PRINTS; PR00449; RASTRNSFRMNG. DR SMART; SM00175; RAB; 1. DR SMART; SM00176; RAN; 1. DR SMART; SM00173; RAS; 1. DR SMART; SM00174; RHO; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR PROSITE; PS51420; RHO; 1. DR Genevisible; P15153; HS. 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; uncertain significance; increased FT interaction with PAK1 compared to wild-type; potential FT gain-of-function variant; dbSNP:rs1927393826)" 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; uncertain significance; cells FT transfected with this variant show higher production of FT reactive oxygen species compared to wild-type; potential FT gain-of-function variant; dbSNP:rs1927078072)" 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 //