P15153 (RAC2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ras-related C3 botulinum toxin substrate 2

Alternative name(s):
GX
Small G protein
p21-Rac2

Gene names

Name:

RAC2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	192 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 component	Cytoplasm
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Ligand	GTP-binding Nucleotide-binding
PTM	ADP-ribosylation Acetylation Lipoprotein Methylation Prenylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	actin cytoskeleton organization Inferred from electronic annotation. Source: Compara axon guidance Traceable author statement. Source: Reactome bone resorption Inferred from electronic annotation. Source: Compara cell projection assembly Inferred from electronic annotation. Source: Compara platelet activation Traceable author statement. Source: Reactome positive regulation of cell proliferation Inferred from electronic annotation. Source: Compara 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 small GTPase mediated signal transduction Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome nuclear envelope Inferred from electronic annotation. Source: Compara plasma membrane Traceable author statement. Source: Reactome
Molecular_function	GTP binding Inferred from electronic annotation. Source: UniProtKB-KW GTPase activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 189

189

Ras-related C3 botulinum toxin substrate 2

PRO_0000042046

Propeptide

190 – 192

3

Removed in mature form By similarity

PRO_0000042047

Regions

Nucleotide binding

10 – 17

8

GTP By similarity

Nucleotide binding

57 – 61

5

GTP By similarity

Nucleotide binding

115 – 118

4

GTP By similarity

Motif

32 – 40

9

Effector region Potential

Amino acid modifications

Modified residue

39

1

ADP-ribosylasparagine; by botulinum toxin By similarity

Modified residue

147

1

N6-acetyllysine Ref.14

Modified residue

189

1

Cysteine methyl ester Probable

Lipidation

189

1

S-geranylgeranyl cysteine Ref.11

Natural variations

Natural variant

29

1

P → L in a breast cancer sample; somatic mutation. Ref.18

VAR_036569

Natural variant

57

1

D → 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

Mutagenesis

189

1

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

Secondary structure

1

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192

Helix Strand Turn

Details...

Beta strand

3 – 11

9

Helix

16 – 25

10

Beta strand

39 – 46

8

Beta strand

49 – 56

8

Helix

62 – 64

3

Turn

65 – 67

3

Helix

68 – 71

4

Beta strand

77 – 83

7

Helix

87 – 95

9

Helix

97 – 104

8

Beta strand

106 – 108

3

Beta strand

110 – 115

6

Helix

117 – 119

3

Helix

123 – 130

8

Turn

131 – 133

3

Helix

139 – 149

11

Beta strand

152 – 156

5

Turn

159 – 161

3

Helix

165 – 175

11

Sequences

	Sequence		Length	Mass (Da)
	P15153 [UniParc]. Last modified April 1, 1990. Version 1. Checksum: 2A1F1266B07C3210	FASTA	192	21,429
	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

References

	« Hide 'large scale' referencesShow '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. , 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, MASS SPECTROMETRY.
[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. , 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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

RAC2base

RAC2 mutation db

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.

IPI

IPI00010270.

PIR

B34386.

RefSeq

NP_002863.1. NM_002872.3.

UniGene

Hs.517601.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1DS6	X-ray	2.35	A	1-192	[»]
2W2T	X-ray	1.95	A	2-179	[»]
2W2V	X-ray	2.00	A/B/C/D	1-177	[»]
2W2X	X-ray	2.30	A/B	2-179	[»]

ProteinModelPortal

P15153.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-34291N.

IntAct

P15153. 8 interactions.

MINT

MINT-1616362.

STRING

9606.ENSP00000249071.

PTM databases

PhosphoSite

P15153.

Polymorphism databases

DMDM

131806.

Proteomic databases

PaxDb

P15153.

PeptideAtlas

P15153.

PRIDE

P15153.

Protocols and materials databases

DNASU

5880.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000249071; ENSP00000249071; ENSG00000128340.

GeneID

5880.

KEGG

hsa:5880.

UCSC

uc003arc.3. human.

Organism-specific databases

CTD

5880.

GeneCards

GC22M037621.

HGNC

HGNC:9802. RAC2.

HPA

CAB022946.

MIM

602049. gene.
608203. phenotype.

neXtProt

NX_P15153.

Orphanet

183707. Neutrophil immunodeficiency syndrome.

PharmGKB

PA34163.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1100.

HOGENOM

HOG000233974.

HOVERGEN

HBG009351.

InParanoid

P15153.

KO

K07860.

OMA

REDRSYL.

OrthoDB

EOG466VN1.

PhylomeDB

P15153.

Enzyme and pathway databases

Reactome

REACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_604. Hemostasis.

Gene expression databases

ArrayExpress

P15153.

Bgee

P15153.

CleanEx

HS_RAC2.

Genevestigator

P15153.

GermOnline

ENSG00000128340. Homo sapiens.

Family and domain databases

InterPro

IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR003578. Small_GTPase_Rho.
[Graphical view]

Pfam

PF00071. Ras. 1 hit.
[Graphical view]

PRINTS

PR00449. RASTRNSFRMNG.

SMART

SM00174. RHO. 1 hit.
[Graphical view]

TIGRFAMs

TIGR00231. small_GTP. 1 hit.

PROSITE

PS51420. RHO. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL5581.

EvolutionaryTrace

P15153.

GenomeRNAi

5880.

NextBio

22854.

SOURCE

Search...

Entry information

Entry name

RAC2_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 152 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.