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Reviewed, UniProtKB/Swiss-Prot P63000 (RAC1_HUMAN)

Last modified November 25, 2008. Version 68. Feed History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Ras-related C3 botulinum toxin substrate 1
Alternative name(s):
    p21-Rac1
    Ras-like protein TC25
    Cell migration-inducing gene 5 protein
Gene names
Name: RAC1
ORF Names: MIG5
OrganismHomo sapiens (Human)
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 active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization and growth-factor induced formation of membrane ruffles.

Isoform B has an accelerated GEF-independent GDP/GTP exchange and an impaired GTP hydrolysis, which is restored partially by GTPase-activating proteins. It is able to bind to the GTPase-binding domain of PAK but not full-length PAK in a GTP-dependent manner, suggesting that the insertion does not completely abolish effector interaction.

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 the GEF proteins PREX1, RASGRF2, DOCK1, DOCK2 and DOCK7, which promote the exchange between GDP and GTP, and therefore activate it. Interacts with PARD6A, PARD6B and PARD6G in a GTP-dependent manner. Part of a quaternary complex containing PARD3, some PARD6 protein (PARD6A, PARD6B or PARD6G) and some atypical PKC protein (PRKCI or PRKCZ), which plays a central role in epithelial cell polarization. Found in a trimeric complex composed of DOCK1 and ELMO1, which plays a central role in phagocytosis of apoptotic cells. Interacts with RALBP1 via its effector domain. Interacts with PLXNB1. Part of a complex with MAP2K3, MAP3K3, CCM2 and DEF6. Interacts with BAIAP2, BAIAP2L1, CYFIP1/SRA-1 and DEF6. Interacts with Y.pseudotuberculosis YPKA and PLCB2. Interacts with NOXA1. Interacts with ARHGEF2. Interacts with NISCH By similarity.

Subcellular location

Cell membrane; Lipid-anchor; Cytoplasmic sideBy similarity. Melanosome. Note= Inner surface of plasma membrane possibly with attachment requiring prenylation of the C-terminal cysteine By similarity. Identified by mass spectrometry in melanosome fractions from stage I to stage IV.

Tissue specificity

Isoform B is predominantly identified in skin and epithelial tissues from the intestinal tract. The expression of isoform B is elevated in colorectal tumors at various stages of neoplastic progression, as compared to their respective adjacent tissues.

Domain

The effector region mediates interaction with DEF6.

Sequence similarities

Belongs to the small GTPase superfamily. Rho family.

Ontologies

Keywords

   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandGTP-binding
Nucleotide-binding
   PTMADP-ribosylation
Lipoprotein
Methylation
Prenylation
   Technical term3D-structure

Gene Ontology (GO)

   Biological processactin filament polymerization

Traceable author statement. Source: UniProtKB

cell adhesion

Traceable author statement. Source: ProtInc

cell motion

Traceable author statement. Source: ProtInc

inflammatory response

Traceable author statement. Source: ProtInc

lamellipodium biogenesis

Inferred from mutant phenotype. Source: UniProtKB

localization within membrane

Inferred from mutant phenotype. Source: UniProtKB

negative regulation of receptor-mediated endocytosis

Traceable author statement. Source: UniProtKB

positive regulation of Rho protein signal transduction

Traceable author statement. Source: UniProtKB

regulation of hydrogen peroxide metabolic process

Traceable author statement. Source: UniProtKB

regulation of respiratory burst

Inferred from direct assay. Source: UniProtKB

ruffle organization

Traceable author statement. Source: UniProtKB

   Cellular componentcytosol

Inferred from Experiment. Source: Reactome

melanosome

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular functionGTP binding

Inferred from electronic annotation. Source: InterPro

GTP-dependent protein binding Ref.17

Inferred from physical interaction. Source: ProtInc

GTPase activity Ref.1

Traceable author statement. Source: UniProtKB

enzyme binding

Inferred from physical interaction. Source: UniProtKB

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform A (identifier: P63000-1)

Also known as: Rac1A;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform B (identifier: P63000-2)

Also known as: Rac1B; Rac1ins;

The sequence of this isoform differs from the canonical sequence as follows:
     75-75: T → TVGETYGKDITSRGKDKPIA

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 189189Ras-related C3 botulinum toxin substrate 1
PRO_0000042036
Propeptide190 – 1923Removed in mature form By similarity
PRO_0000042037

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 residue1891Cysteine methyl ester
Lipidation1891S-geranylgeranyl cysteine

Natural variations

Alternative sequence751T → TVGETYGKDITSRGKDKPIA in isoform B.
VSP_005710
Natural variant261N → D: dbSNP rs5830.
VAR_014540
Natural variant281F → L: dbSNP rs5832.
VAR_014541
Natural variant591A → T: dbSNP rs5837.
VAR_014542
Natural variant631D → G: dbSNP rs5831.
VAR_014543
Natural variant931V → G: dbSNP rs5826.
VAR_014545
Natural variant931V → I: dbSNP rs5825.
VAR_014544
Natural variant1081T → I: dbSNP rs5838.
VAR_014546
Natural variant1301K → R: dbSNP rs5828.
VAR_014547
Natural variant1331K → E: dbSNP rs5835.
VAR_014548
Natural variant1351T → I: dbSNP rs11540455.
VAR_033303
Natural variant1801P → S: dbSNP rs16063.
VAR_014549
Natural variant1821V → E: dbSNP rs5836.
VAR_014550

Experimental info

Mutagenesis121G → V: Constitutively active. Interacts with PARD6 proteins
Mutagenesis171T → N: Constitutively inactivated. Abolishes interaction with PARD6 proteins
Mutagenesis371F → A: Strongly reduced interaction with PLCB2
Mutagenesis561W → A: Strongly reduced interaction with PLCB2
Mutagenesis611Q → L: Constitutively active. Interacts with PARD6 proteins
Mutagenesis671L → A: Strongly reduced interaction with PLCB2
Mutagenesis701L → A: Strongly reduced interaction with PLCB2
Sequence conflict1921Missing in AAA36544. Ref.2

Secondary structure

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

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform A (Rac1A) [UniParc].

Last modified August 31, 2004. Version 1.
Checksum: ACEDF83A45E5EA67

FASTA19221,450
        10         20         30         40         50         60 
MQAIKCVVVG DGAVGKTCLL ISYTTNAFPG EYIPTVFDNY SANVMVDGKP VNLGLWDTAG 

        70         80         90        100        110        120 
QEDYDRLRPL SYPQTDVFLI CFSLVSPASF ENVRAKWYPE VRHHCPNTPI ILVGTKLDLR 

       130        140        150        160        170        180 
DDKDTIEKLK EKKLTPITYP QGLAMAKEIG AVKYLECSAL TQRGLKTVFD EAIRAVLCPP 

       190 
PVKKRKRKCL LL 

« Hide

Isoform B (Rac1B) (Rac1ins) [UniParc] [UniParc].

Checksum: 93745E0CFBA5281F
Show »

21123,467

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: 2674130] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
[2]"Characterization of four novel ras-like genes expressed in a human teratocarcinoma cell line."
Drivas G.T., Shih A., Coutavas E., Rush M.G., D'Eustachio P.
Mol. Cell. Biol. 10:1793-1798(1990) [PubMed: 2108320] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
[3]"Small GTPase Rac1: structure, localization, and expression of the human gene."
Matos P., Skaug J., Marques B., Beck S., Verissimo F., Gespach C., Boavida M.G., Scherer S.W., Jordan P.
Biochem. Biophys. Res. Commun. 277:741-751(2000) [PubMed: 11062023] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS A AND B).
[4]"Cloning of a novel human Rac1b splice variant with increased expression in colorectal tumors."
Jordan P., Brazao R., Boavida M.G., Gespach C., Chastre E.
Oncogene 18:6835-6839(1999) [PubMed: 10597294] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B).
Tissue: Colon and Skin.
[5]"Mutations and altered expression of Rac1 in human breast cancer --characterization of a new Rac1 isoform, Rac1ins."
Schnelzer A., Knaus U., Prechtel D., Dehne K., Harbeck N., Gerhard M., Schmitt M., Lengyel E.
Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B).
[6]"Identification of a human migration-inducing gene."
Kim J.W.
Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
[7]"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] (ISOFORM A), VARIANT ILE-135.
[8]"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 (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
[9]"NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu)."
Livingston R.J., Rieder M.J., Shaffer T., Bertucci C., Baier C.N., Rajkumar N., Willa H.T., Daniels M., Downing T.K., Stanaway I.B., Nguyen C.P., Gildersleeve H., Cassidy C.M., Johnson E.J., Swanson J.E., McFarland I., Yool B., Park C., Nickerson D.A.
Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[10]"The DNA sequence of human chromosome 7."
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. expand/collapse author list , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
Nature 424:157-164(2003) [PubMed: 12853948] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[11]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
Tissue: Pancreas and Skin.
[12]"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: 1903399] [Abstract]
Cited for: ISOPRENYLATION AT CYS-189.
[13]"The small GTP-binding protein rac regulates growth factor-induced membrane ruffling."
Ridley A.J., Paterson H.F., Johnston C.L., Diekmann D., Hall A.
Cell 70:401-410(1992) [PubMed: 1643658] [Abstract]
Cited for: FUNCTION.
[14]"Bridging Ral GTPase to Rho pathways. RLIP76, a Ral effector with CDC42/Rac GTPase-activating protein activity."
Jullien-Flores V., Dorseuil O., Romero F., Letourneur F., Saragosti S., Berger R., Tavitian A., Gacon G., Camonis J.H.
J. Biol. Chem. 270:22473-22477(1995) [PubMed: 7673236] [Abstract]
Cited for: INTERACTION WITH RALBP1.