Rac GTPase-activating protein 1 - Homo sapiens (Human)

Names and origin

Protein names

Recommended name:
    Rac GTPase-activating protein 1
Alternative name(s):
    Male germ cell RacGap
      Short name=MgcRacGAP

Gene names

Name:	RACGAP1
Synonyms:	KIAA1478, MGCRACGAP

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	632 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Essential for the early stages of embryogenesis and may play a role in the microtubule-dependent steps in cytokinesis. Plays key roles in controlling cell growth and differentiation of hematopoietic cells through mechanisms other than regulating Rac GTPase activity. Also involved in the regulation of growth-related processes in adipocytes and myoblasts. May be involved in regulating spermatogenesis and in the RACGAP1 pathway in neuronal proliferation. Shows strong GAP (GTPase activation) activity towards CDC42 and RAC1 and less towards RHOA. Required for initiation of cleavage furrow ingression by regulating ECT2 and for assembly of the contractile ring. May play a role in regulating cortical activity through RHOA during cytokinesis. May participate in the regulation of sulfate transport in male germ cells.
Subunit structure	Associates with alpha-, beta- and gamma-tubulin and microtubules. Interacts via its Rho-GAP domain with RND2. Associates with AURKB during M phase. Interacts via its Rho-GAP domain and basic region with PRC1. The interaction with PRC1 inhibits its GAP activity towards CDC42 in vitro, which may be required for maintaining normal spindle morphology. Associates with ECT2 at anaphase and during cytokinesis. Interacts with SLC26A8 via its N-terminus.
Subcellular location	Nucleus. Cytoplasm. Spindle. Acrosome. Note= During interphase, localized to the nucleus and cytoplasm along with microtubules, in anaphase, is redistributed to the central spindle and, in telophase and cytokinesis, to the midbody. Colocalizes with RHOA at the contractile ring during cytokinesis. Colocalizes with RND2 in Golgi-derived proacrosomal vesicles and the acrosome.
Tissue specificity	Highly expressed in testis, thymus and placenta. Expressed at lower levels in spleen and peripheral blood lymphocytes. In testis, expression is restricted to germ cells with the highest levels of expression found in spermatocytes. Expression is regulated in a cell cycle-dependent manner and peaks during G2/M phase.
Induction	Expression is down-regulated during macrophage differention of HL-60 cells.
Domain	The coiled coil region is indispensible for localization to the midbody during cytokinesis.
Post-translational modification	Phosphorylated at multiple sites in the midbody during cytokinesis. Phosphorylation by AURKB on SER-387 at the midbody is, at least in part, responsible for exerting its latent GAP activity towards RhoA.
Sequence similarities	Contains 1 phorbol-ester/DAG-type zinc finger. Contains 1 Rho-GAP domain.
Sequence caution	The sequence AAH24144.1 differs from that shown. Reason: Frameshift at positions 171, 205 and 437.

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Ontologies

Keywords
Biological process	Cell cycle Cell division Differentiation Ion transport Spermatogenesis Transport
Cellular component	Cytoplasm Microtubule Nucleus
Domain	Coiled coil Phorbol-ester binding Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Developmental protein GTPase activation
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	cytokinesis, contractile ring formation Ref.14 Inferred from mutant phenotype. Source: UniProtKB cytokinesis, initiation of separation Ref.14 Inferred from mutant phenotype. Source: UniProtKB embryonic development Inferred from sequence or structural similarity. Source: UniProtKB neuroblast proliferation Inferred from sequence or structural similarity. Source: UniProtKB spermatogenesis Ref.10 Inferred from expression pattern. Source: UniProtKB sulfate transport Ref.9 Inferred from direct assay. Source: UniProtKB
Cellular component	nucleus Ref.8 Inferred from direct assay. Source: UniProtKB
Molecular function	GTPase activator activity Ref.1 Inferred from direct assay. Source: UniProtKB alpha-tubulin binding Ref.8 Inferred from direct assay. Source: UniProtKB beta-tubulin binding Ref.8 Inferred from direct assay. Source: UniProtKB gamma-tubulin binding Ref.8 Inferred from direct assay. Source: UniProtKB protein C-terminus binding Ref.9 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
YWHAB	P31946	1	EBI-717233,EBI-359815
YWHAG	P61981	1	EBI-717233,EBI-359832

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Chain

1 – 632

632

Rac GTPase-activating protein 1

Regions

Domain

349 – 539

191

Rho-GAP

Zinc finger

286 – 335

50

Phorbol-ester/DAG-type

Region

106 – 285

180

Interaction with SLC26A8

Coiled coil

53 – 110

58

Potential

Amino acid modifications

Modified residue

161

1

Phosphothreonine

Modified residue

164

1

Phosphoserine

Modified residue

170

1

Phosphoserine

Modified residue

185

1

Phosphoserine

Modified residue

187

1

Phosphoserine

Modified residue

203

1

Phosphoserine

Modified residue

206

1

Phosphoserine

Modified residue

214

1

Phosphoserine

Modified residue

342

1

Phosphothreonine

Modified residue

387

1

Phosphoserine

Modified residue

580

1

Phosphothreonine

Modified residue

588

1

Phosphothreonine

Modified residue

590

1

Phosphoserine

Modified residue

606

1

Phosphothreonine

Modified residue

628

1

Phosphoserine

Experimental info

Mutagenesis

385

1

R → A: Abolishes GAP activity towards RAC1 and CDC42 and induces multiple blebs during cytokinesis

Sequence conflict

155

1

D → H in BAA91347. Ref.3

Sequence conflict

518

1

L → S in BAA90247. Ref.1

Secondary structure

1

.

632

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

Q9H0H5-1 [UniParc].

Last modified March 1, 2001. Version 1.
Checksum: 032B7DF9CEA8F39D
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FASTA

632

71,027

        10         20         30         40         50         60 
MDTMMLNVRN LFEQLVRRVE ILSEGNEVQF IQLAKDFEDF RKKWQRTDHE LGKYKDLLMK 

        70         80         90        100        110        120 
AETERSALDV KLKHARNQVD VEIKRRQRAE ADCEKLERQI QLIREMLMCD TSGSIQLSEE 

       130        140        150        160        170        180 
QKSALAFLNR GQPSSSNAGN KRLSTIDESG SILSDISFDK TDESLDWDSS LVKTFKLKKR 

       190        200        210        220        230        240 
EKRRSTSRQF VDGPPGPVKK TRSIGSAVDQ GNESIVAKTT VTVPNDGGPI EAVSTIETVP 

       250        260        270        280        290        300 
YWTRSRRKTG TLQPWNSDST LNSRQLEPRT ETDSVGTPQS NGGMRLHDFV SKTVIKPESC 

       310        320        330        340        350        360 
VPCGKRIKFG KLSLKCRDCR VVSHPECRDR CPLPCIPTLI GTPVKIGEGM LADFVSQTSP 

       370        380        390        400        410        420 
MIPSIVVHCV NEIEQRGLTE TGLYRISGCD RTVKELKEKF LRVKTVPLLS KVDDIHAICS 

       430        440        450        460        470        480 
LLKDFLRNLK EPLLTFRLNR AFMEAAEITD EDNSIAAMYQ AVGELPQANR DTLAFLMIHL 

       490        500        510        520        530        540 
QRVAQSPHTK MDVANLAKVF GPTIVAHAVP NPDPVTMLQD IKRQPKVVER LLSLPLEYWS 

       550        560        570        580        590        600 
QFMMVEQENI DPLHVIENSN AFSTPQTPDI KVSLLGPVTT PEHQLLKTPS SSSLSQRVRS 

       610        620        630 
TLTKNTPRFG SKSKSATNLG RQGNFFASPM LK

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"MgcRacGAP is involved in the control of growth and differentiation of hematopoietic cells." Kawashima T., Hirose K., Satoh T., Kaneko A., Ikeda Y., Kaziro Y., Nosaka T., Kitamura T. Blood 96:2116-2124(2000) [PubMed: 10979956] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, MUTAGENESIS OF ARG-385, INDUCTION.
[2]	"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs." Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. Poustka A. Genome Res. 11:422-435(2001) [PubMed: 11230166] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Hepatoma.
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"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]. Tissue: Placenta and Testis.
[6]	"Prediction of the coding sequences of unidentified human genes. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O. DNA Res. 7:143-150(2000) [PubMed: 10819331] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 63-632. Tissue: Brain.
[7]	"MgcRacGAP, a new human GTPase-activating protein for Rac and Cdc42 similar to Drosophila rotundRacGAP gene product, is expressed in male germ cells." Toure A., Dorseuil O., Morin L., Timmons P., Jegou B., Reibel L., Gacon G. J. Biol. Chem. 273:6019-6023(1998) [PubMed: 9497316] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 106-632, FUNCTION, TISSUE SPECIFICITY. Tissue: Placenta.
[8]	"MgcRacGAP is involved in cytokinesis through associating with mitotic spindle and midbody." Hirose K., Kawashima T., Iwamoto I., Nosaka T., Kitamura T. J. Biol. Chem. 276:5821-5828(2001) [PubMed: 11085985] [Abstract] Cited for: FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, DOMAIN.
[9]	"Tat1, a novel sulfate transporter specifically expressed in human male germ cells and potentially linked to rhogtpase signaling." Toure A., Morin L., Pineau C., Becq F., Dorseuil O., Gacon G. J. Biol. Chem. 276:20309-20315(2001) [PubMed: 11278976] [Abstract] Cited for: FUNCTION, INTERACTION WITH SLC26A8, TISSUE SPECIFICITY.
[10]	"Rho family GTPase Rnd2 interacts and co-localizes with MgcRacGAP in male germ cells." Naud N., Toure A., Liu J., Pineau C., Morin L., Dorseuil O., Escalier D., Chardin P., Gacon G. Biochem. J. 372:105-112(2003) [PubMed: 12590651] [Abstract] Cited for: INTERACTION WITH RND2, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[11]	"Phosphorylation by aurora B converts MgcRacGAP to a RhoGAP during cytokinesis." Minoshima Y., Kawashima T., Hirose K., Tonozuka Y., Kawajiri A., Bao Y.C., Deng X., Tatsuka M., Narumiya S., May W.S. Jr., Nosaka T., Semba K., Inoue T., Satoh T., Inagaki M., Kitamura T. Dev. Cell 4:549-560(2003) [PubMed: 12689593] [Abstract] Cited for: INTERACTION WITH AURKB, PHOSPHORYLATION AT SER-387.
[12]	"MgcRacGAP regulates cortical activity through RhoA during cytokinesis." Lee J.S., Kamijo K., Ohara N., Kitamura T., Miki T. Exp. Cell Res. 293:275-282(2004) [PubMed: 14729465] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF ARG-385.
[13]	"Human mitotic spindle-associated protein PRC1 inhibits MgcRacGAP activity toward Cdc42 during the metaphase." Ban R., Irino Y., Fukami K., Tanaka H. J. Biol. Chem. 279:16394-16402(2004) [PubMed: 14744859] [Abstract] Cited for: INTERACTION WITH PRC1.
[14]	"MgcRacGAP controls the assembly of the contractile ring and the initiation of cytokinesis." Zhao W.-M., Fang G. Proc. Natl. Acad. Sci. U.S.A. 102:13158-13163(2005) [PubMed: 16129829] [Abstract] Cited for: FUNCTION, INTERACTION WITH ECT2, SUBCELLULAR LOCATION.
[15]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-161; SER-164; SER-203 AND SER-206, MASS SPECTROMETRY. Tissue: Epithelium.
[16]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-203, MASS SPECTROMETRY. Tissue: Epithelium.
[17]	"Phosphoproteome analysis of the human mitotic spindle." Nousiainen M., Sillje H.H.W., Sauer G., Nigg E.A., Koerner R. Proc. Natl. Acad. Sci. U.S.A. 103:5391-5396(2006) [PubMed: 16565220] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-161; SER-164; SER-170; SER-203; SER-214; THR-342; THR-580; THR-588; SER-590 AND SER-628, MASS SPECTROMETRY. Tissue: Epithelium.
[18]	"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-606 AND SER-628, MASS SPECTROMETRY. Tissue: Epithelium.
[19]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-185 AND SER-187, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Keywords

Gene Ontology (GO)

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Experimental info

Secondary structure

Sequences

References