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P15153 (RAC2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 164. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ras-related C3 botulinum toxin substrate 2
Alternative name(s):
GX
Small G protein
p21-Rac2
Gene names
Name:RAC2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length192 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Plasma membrane-associated small GTPase which cycles between an active GTP-bound and inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses, such as secretory processes, phagocytose of apoptotic cells and epithelial cell polarization. Augments the production of reactive oxygen species (ROS) by NADPH oxidase. Ref.8

Enzyme regulation

Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase.

Subunit structure

Interacts with DOCK2, which may activate it. Interacts with S100A8 and calprotectin (S100A8/9). Ref.12 Ref.13

Subcellular location

Cytoplasm. Note: Membrane-associated when activated.

Tissue specificity

Hematopoietic specific.

Involvement in disease

Neutrophil immunodeficiency syndrome (NEUID) [MIM:608203]: An immunodeficiency syndrome due to defective neutrophils. Affected individuals present with leukocytosis, neutrophilia, severe recurrent bacterial infections and poor wound healing.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.17

Sequence similarities

Belongs to the small GTPase superfamily. Rho family.

Ontologies

Keywords
   Cellular componentCytoplasm
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   LigandGTP-binding
Nucleotide-binding
   PTMAcetylation
ADP-ribosylation
Lipoprotein
Methylation
Prenylation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processactin cytoskeleton organization

Inferred from electronic annotation. Source: Ensembl

axon guidance

Traceable author statement. Source: Reactome

blood coagulation

Traceable author statement. Source: Reactome

bone resorption

Inferred from electronic annotation. Source: Ensembl

cell projection assembly

Inferred from electronic annotation. Source: Ensembl

platelet activation

Traceable author statement. Source: Reactome

positive regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

regulation of hydrogen peroxide metabolic process

Traceable author statement PubMed 16636067. Source: BHF-UCL

regulation of respiratory burst

Inferred from direct assay PubMed 16636067. Source: BHF-UCL

regulation of small GTPase mediated signal transduction

Traceable author statement. Source: Reactome

signal transduction

Traceable author statement Ref.1. Source: ProtInc

small GTPase mediated signal transduction

Traceable author statement. Source: Reactome

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

extracellular vesicular exosome

Inferred from direct assay PubMed 20458337. Source: UniProt

nuclear envelope

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionGTP binding

Inferred from electronic annotation. Source: UniProtKB-KW

GTPase activity

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 189189Ras-related C3 botulinum toxin substrate 2
PRO_0000042046
Propeptide190 – 1923Removed in mature form By similarity
PRO_0000042047

Regions

Nucleotide binding10 – 178GTP By similarity
Nucleotide binding57 – 615GTP By similarity
Nucleotide binding115 – 1184GTP By similarity
Motif32 – 409Effector region Potential

Amino acid modifications

Modified residue391ADP-ribosylasparagine; by botulinum toxin By similarity
Modified residue1471N6-acetyllysine Ref.14
Modified residue1891Cysteine methyl ester By similarity
Lipidation1891S-geranylgeranyl cysteine Ref.11

Natural variations

Natural variant291P → L in a breast cancer sample; somatic mutation. Ref.18
VAR_036569
Natural variant571D → N in NEUID; dominant-negative mutant; binds GDP, but not GTP; inhibits oxidase activation and superoxide anion production in vitro. Ref.17
VAR_017452

Experimental info

Mutagenesis1891C → W: Abolishes in vitro prenylation. Ref.11

Secondary structure

.................................... 192
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P15153 [UniParc].

Last modified April 1, 1990. Version 1.
Checksum: 2A1F1266B07C3210

FASTA19221,429
        10         20         30         40         50         60 
MQAIKCVVVG DGAVGKTCLL ISYTTNAFPG EYIPTVFDNY SANVMVDSKP VNLGLWDTAG 

        70         80         90        100        110        120 
QEDYDRLRPL SYPQTDVFLI CFSLVSPASY ENVRAKWFPE VRHHCPSTPI ILVGTKLDLR 

       130        140        150        160        170        180 
DDKDTIEKLK EKKLAPITYP QGLALAKEID SVKYLECSAL TQRGLKTVFD EAIRAVLCPQ 

       190 
PTRQQKRACS LL 

« Hide

References

« Hide 'large scale' references
[1]"Rac, a novel ras-related family of proteins that are botulinum toxin substrates."
Didsbury J., Weber R.F., Bokoch G.M., Evans T., Snyderman R.
J. Biol. Chem. 264:16378-16382(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
Puhl H.L. III, Ikeda S.R., Aronstam R.S.
Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]"A genome annotation-driven approach to cloning the human ORFeome."
Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I.
Genome Biol. 5:R84.1-R84.11(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]"The DNA sequence of human chromosome 22."
Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. expand/collapse author list , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H.
Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[7]"Regulation of the superoxide-generating NADPH oxidase by a small GTP-binding protein and its stimulatory and inhibitory GDP/GTP exchange proteins."
Mizuno T., Kaibuchi K., Ando S., Musha T., Hiraoka K., Takaishi K., Asada M., Nunoi H., Matsuda I., Takai Y.
J. Biol. Chem. 267:10215-10218(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 6-15; 97-107 AND 134-165.
[8]"Regulation of phagocyte oxygen radical production by the GTP-binding protein Rac 2."
Knaus U.G., Heyworth P.G., Evans T., Curnutte J.T., Bokoch G.M.
Science 254:1512-1515(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 7-16; 19-49; 154-163 AND 175-183, FUNCTION.
Tissue: Neutrophil.
[9]"A hemopoietic specific gene encoding a small GTP binding protein is overexpressed during T cell activation."
Reibel L., Dorseuil O., Stancou R., Bertoglio J., Gacon G.
Biochem. Biophys. Res. Commun. 175:451-458(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 13-192.
[10]"Regulation of the human neutrophil NADPH oxidase by rho-related G-proteins."
Kwong C.H., Malech H.L., Rotrosen D., Leto T.L.
Biochemistry 32:5711-5717(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 97-102 AND 167-174.
Tissue: Neutrophil.
[11]"Carboxyl-terminal isoprenylation of ras-related GTP-binding proteins encoded by rac1, rac2, and ralA."
Kinsella B.T., Erdman R.A., Maltese W.A.
J. Biol. Chem. 266:9786-9794(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: ISOPRENYLATION AT CYS-189, MUTAGENESIS OF CYS-189.
[12]"Non-adherent cell-specific expression of DOCK2, a member of the human CDM-family proteins."
Nishihara H., Kobayashi S., Hashimoto Y., Ohba F., Mochizuki N., Kurata T., Nagashima K., Matsuda M.
Biochim. Biophys. Acta 1452:179-187(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DOCK2.
[13]"The arachidonic acid-binding protein S100A8/A9 promotes NADPH oxidase activation by interaction with p67phox and Rac-2."
Kerkhoff C., Nacken W., Benedyk M., Dagher M.C., Sopalla C., Doussiere J.
FASEB J. 19:467-469(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH S100A8 AND CALPROTECTIN.
[14]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-147, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]"The Rac-RhoGDI complex and the structural basis for the regulation of Rho proteins by RhoGDI."
Scheffzek K., Stephan I., Jensen O.N., Illenberger D., Gierschik P.
Nat. Struct. Biol. 7:122-126(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF COMPLEX WITH ARHGDIB.
[17]"Human neutrophil immunodeficiency syndrome is associated with an inhibitory Rac2 mutation."
Ambruso D.R., Knall C., Abell A.N., Panepinto J., Kurkchubasche A., Thurman G., Gonzalez-Aller C., Hiester A., deBoer M., Harbeck R.J., Oyer R., Johnson G.L., Roos D.
Proc. Natl. Acad. Sci. U.S.A. 97:4654-4659(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NEUID ASN-57.
[18]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] LEU-29.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M29871 mRNA. Translation: AAA36538.1.
AF498965 mRNA. Translation: AAM21112.1.
CR456555 mRNA. Translation: CAG30441.1.
BT006919 mRNA. Translation: AAP35565.1.
Z82188 Genomic DNA. Translation: CAB45265.1.
BC001485 mRNA. Translation: AAH01485.1.
M64595 mRNA. Translation: AAA35941.1.
CCDSCCDS13945.1.
PIRB34386.
RefSeqNP_002863.1. NM_002872.4.
UniGeneHs.517601.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1DS6X-ray2.35A1-192[»]
2W2TX-ray1.95A2-179[»]
2W2VX-ray2.00A/B/C/D1-177[»]
2W2XX-ray2.30A/B2-179[»]
ProteinModelPortalP15153.
SMRP15153. Positions 1-181.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111818. 19 interactions.
DIPDIP-34291N.
IntActP15153. 12 interactions.
MINTMINT-1616362.
STRING9606.ENSP00000249071.

Chemistry

ChEMBLCHEMBL5581.

PTM databases

PhosphoSiteP15153.

Polymorphism databases

DMDM131806.

Proteomic databases

MaxQBP15153.
PaxDbP15153.
PeptideAtlasP15153.
PRIDEP15153.

Protocols and materials databases

DNASU5880.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000249071; ENSP00000249071; ENSG00000128340.
GeneID5880.
KEGGhsa:5880.
UCSCuc003arc.3. human.

Organism-specific databases

CTD5880.
GeneCardsGC22M037621.
HGNCHGNC:9802. RAC2.
HPACAB022946.
HPA047820.
MIM602049. gene.
608203. phenotype.
neXtProtNX_P15153.
Orphanet183707. Neutrophil immunodeficiency syndrome.
PharmGKBPA34163.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1100.
HOGENOMHOG000233974.
HOVERGENHBG009351.
InParanoidP15153.
KOK07860.
OMAREDRSYL.
OrthoDBEOG764747.
PhylomeDBP15153.
TreeFamTF101109.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_604. Hemostasis.
SignaLinkP15153.

Gene expression databases

ArrayExpressP15153.
BgeeP15153.
CleanExHS_RAC2.
GenevestigatorP15153.

Family and domain databases

Gene3D3.40.50.300. 1 hit.
InterProIPR027417. P-loop_NTPase.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR003578. Small_GTPase_Rho.
[Graphical view]
PfamPF00071. Ras. 1 hit.
[Graphical view]
PRINTSPR00449. RASTRNSFRMNG.
SMARTSM00174. RHO. 1 hit.
[Graphical view]
SUPFAMSSF52540. SSF52540. 1 hit.
TIGRFAMsTIGR00231. small_GTP. 1 hit.
PROSITEPS51420. RHO. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP15153.
GeneWikiRAC2.
GenomeRNAi5880.
NextBio22854.
PROP15153.
SOURCESearch...

Entry information

Entry nameRAC2_HUMAN
AccessionPrimary (citable) accession number: P15153
Secondary accession number(s): Q9UDJ4
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: July 9, 2014
This is version 164 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 22

Human chromosome 22: entries, gene names and cross-references to MIM