Q9WVM1 (RGAP1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

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:	Mgcracgap

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	628 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Component of the centralspindlin complex that serves as a microtubule-dependent and Rho-mediated signaling required for the myosin contractile ring formation during the cell cycle 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. Essential for the early stages of embryogenesis. May play a role in regulating cortical activity through RHOA during cytokinesis. May participate in the regulation of sulfate transport in male germ cells. Ref.1 Ref.2 Ref.3 Ref.6
Subunit structure	Heterotetramer of two molecules each of RACGAP1 and KIF23. Found in the centralspindlin complex composed of RACGAP1 and KIF23. 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. Interacts with SLC26A8 via its N-terminus. Interacts with RAB11FIP3. Interacts with ECT2; the interaction is direct, occurs at anaphase and during cytokinesis in a microtubule-dependent manner and is enhanced by phosphorylation by PLK1. Interacts with KIF23; the interaction is direct By similarity.
Subcellular location	Nucleus. Cytoplasm. Cytoplasm › cytoskeleton › spindle. Cytoplasmic vesicle › secretory vesicle › acrosome. Cleavage furrow By similarity. Midbody By similarity. 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 myosin contractile ring during cytokinesis. Colocalizes with ECT2 to the mitotic spindles during anaphase/metaphase, the cleavage furrow during telophase and at the midbody at the end of cytokinesis. Colocalizes with Cdc42 to spindle microtubules from prometaphase to telophase By similarity. Colocalizes with RND2 in Golgi-derived proacrosomal vesicles and the acrosome. Ref.7
Tissue specificity	Highly expressed in testis, thymus and spleen and weakly expressed in brain, heart, skeletal muscle and kidney. In testis, expression is restricted to germ cells with the highest levels of expression found in spermatocytes. Not detected in adult liver. Also expressed in fetal liver and in several hematopoietic cell lines. Ref.2 Ref.3 Ref.6
Developmental stage	At E6.5 expressed in primitive endoderm, embryonic ectoderm, extraembryonic ectoderm and the ectoplacental cone. By E7.5, a widespread expression was observed in all intra- and extraembryonic tissues and also in the giant cells lining the inner boundary of the deciduum. At E9.5, expression was elevated in the neuroepithelium of the brain ventricles and the neural tube. By E12.5, expression remains widespread and in the brain higher levels were observed in the ventricular zone of the two telencephalic lobes, and in the mesencephalon and diencephalon, with the exception of the median sulcus. In adult brain, highest levels of expression were detected in cerebellum, specifically the Purkinje cell layer extending into the molecular layer. Ref.3
Induction	Expression is down-regulated during macrophage differentiation of M1 cells. Ref.2
Domain	The coiled coil region is indispensible for localization to the midbody during cytokinesis By similarity. UniProtKB Q9P2W2
Post-translational modification	Phosphorylated at multiple sites in the midbody during cytokinesis. Phosphorylation by AURKB on Ser-388 at the midbody is, at least in part, responsible for exerting its latent GAP activity towards RhoA. Phosphorylation on multiple serine residues by PLK1 enhances its association with ECT2 and is critical for cleavage furrow formation By similarity.
Sequence similarities	Contains 1 phorbol-ester/DAG-type zinc finger. Contains 1 Rho-GAP domain.

Ontologies

Keywords
Biological process	Cell cycle Cell division Differentiation Ion transport Spermatogenesis Transport
Cellular component	Cytoplasm Cytoplasmic vesicle Cytoskeleton Nucleus
Domain	Coiled coil Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Developmental protein GTPase activation
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cytokinesis, actomyosin contractile ring assembly Inferred from sequence or structural similarity. Source: UniProtKB cytokinesis, initiation of separation Inferred from sequence or structural similarity. Source: UniProtKB embryo development Inferred from mutant phenotype Ref.3. Source: UniProtKB intracellular signal transduction Inferred from electronic annotation. Source: InterPro neuroblast proliferation Inferred from expression pattern Ref.6. Source: UniProtKB positive regulation of cell cycle cytokinesis Inferred from sequence or structural similarity. Source: UniProtKB regulation of attachment of spindle microtubules to kinetochore Inferred from sequence or structural similarity. Source: UniProtKB spermatogenesis Inferred from sequence or structural similarity. Source: UniProtKB spindle midzone assembly involved in mitosis Inferred from sequence or structural similarity. Source: UniProtKB sulfate transport Inferred from electronic annotation. Source: Compara
Cellular_component	acrosomal vesicle Inferred from electronic annotation. Source: UniProtKB-SubCell centralspindlin complex Inferred from sequence or structural similarity. Source: UniProtKB cleavage furrow Inferred from sequence or structural similarity. Source: UniProtKB midbody Inferred from sequence or structural similarity. Source: UniProtKB nucleus Inferred from sequence or structural similarity. Source: UniProtKB spindle midzone Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	GTPase activator activity Inferred from sequence or structural similarity. Source: UniProtKB alpha-tubulin binding Inferred from sequence or structural similarity. Source: UniProtKB beta-tubulin binding Inferred from sequence or structural similarity. Source: UniProtKB gamma-tubulin binding Inferred from sequence or structural similarity. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW microtubule binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 628	628	Rac GTPase-activating protein 1		PRO_0000228809
Regions
	Domain	350 – 540	191	Rho-GAP
	Zinc finger	287 – 336	50	Phorbol-ester/DAG-type
	Region	107 – 286	180	Interaction with SLC26A8 By similarity
	Coiled coil	33 – 110	78	Potential
Amino acid modifications
	Modified residue	150	1	Phosphoserine; by PLK1 By similarity
	Modified residue	155	1	Phosphoserine By similarity
	Modified residue	158	1	Phosphoserine; by PLK1 By similarity
	Modified residue	162	1	Phosphothreonine By similarity
	Modified residue	165	1	Phosphoserine; by PLK1 By similarity
	Modified residue	171	1	Phosphoserine; by PLK1 By similarity
	Modified residue	204	1	Phosphoserine By similarity
	Modified residue	207	1	Phosphoserine By similarity
	Modified residue	215	1	Phosphoserine By similarity
	Modified residue	258	1	Phosphoserine By similarity
	Modified residue	343	1	Phosphothreonine By similarity
	Modified residue	388	1	Phosphoserine; by AURKB By similarity
	Modified residue	411	1	Phosphoserine; by AURKB By similarity
	Modified residue	564	1	Phosphothreonine By similarity
	Modified residue	577	1	Phosphothreonine By similarity
	Modified residue	585	1	Phosphothreonine By similarity
	Modified residue	602	1	Phosphothreonine By similarity
Experimental info
	Sequence conflict	29 – 31	3	IEF → MES in BAE38561. Ref.4
	Sequence conflict	100	1	Q → E in BAE40131. Ref.4
	Sequence conflict	100	1	Q → E in BAE40010. Ref.4
	Sequence conflict	398	1	K → E in BAE40005. Ref.4
	Sequence conflict	623	1	P → T in BAE40005. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Q9WVM1 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: 8D1B9DEC3CE057BE	FASTA	628	70,158
	10 20 30 40 50 60 MDTTMVNLWT LFEQLVRRME IINEGNESIE FIQVVKDFED FRKKYQRTNQ ELEKFKDLLL 70 80 90 100 110 120 KAETGRSALD VKLKHARNQV DVEIKRRQRA EAECAKLEQQ IQLIRDILMC DTSGSIQLSE 130 140 150 160 170 180 EQKSALAFLN RGQASSGHAG NNRLSTIDES GSILSDISFD KTDESLDWDS SLVKNFKMKK 190 200 210 220 230 240 REKRRSNSRQ FIDGPPGPVK KTCSIGSTVD QANESIVAKT TVTVPSDGGP IEAVSTIETL 250 260 270 280 290 300 PSWTRSRGKS GPLQPVNSDS ALNSRPLEPR TDTDNLGTPQ NTGGMRLHDF VSKTVIKPES 310 320 330 340 350 360 CVPCGKRIKF GKLSLKCRDC RLVSHPECRD RCPLPCIPPL VGTPVKIGEG MLADFVSQAS 370 380 390 400 410 420 PMIPAIVVSC VNEIEQRGLT EAGLYRISGC DRTVKELKEK FLKVKTVPLL SKVDDIHVIC 430 440 450 460 470 480 SLLKDFLRNL KEPLLTFWLS KAFMEAAEIT DEDNSTAAMY QAVSELPQAN RDTLAFLMIH 490 500 510 520 530 540 LQRVSQSPDT KMDIANLAKV FGPTIVAHTV PNPDPVTMFQ DIKRQLKVVE RLLSLPLEYW 550 560 570 580 590 600 NQFMMVDQEN IDSQRGNGNS TPRTPDVKVS LLGPVTTPEF QLVKTPLSSS LSQRLYNLSK 610 620 STPRFGNKSK SATNLGQQGK FFPAPYLK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and characterization of a transcript for a novel Rac GTPase-activating protein in terminally differentiating 3T3-L1 adipocytes." Wooltorton E.J., Haliotis T., Mueller C.R. DNA Cell Biol. 18:265-273(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION. Tissue: Erythroleukemia.
[2]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, INDUCTION.
[3]	"Mice with a homozygous gene trap vector insertion in mgcRacGAP die during pre-implantation development." Van de Putte T., Zwijsen A., Lonnoy O., Rybin V., Cozijnsen M., Francis A., Baekelandt V., Kozak C.A., Zerial M., Huylebroeck D. Mech. Dev. 102:33-44(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE. Strain: CD-1.
[4]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J, DBA/2 and NOD. Tissue: Heart and Lung.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: FVB/N. Tissue: Mammary gland.
[6]	"Structure and expression of murine mgcRacGAP: its developmental regulation suggests a role for the Rac/MgcRacGAP signalling pathway in neurogenesis." Arar C., Ott M.-O., Toure A., Gacon G. Biochem. J. 343:225-230(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
[7]	"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] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF079974 mRNA. Translation: AAD40487.1. AB030252 mRNA. Translation: BAA90248.1. AF212320 mRNA. Translation: AAG43539.1. AF212321 mRNA. Translation: AAG43540.1. AK144608 mRNA. Translation: BAE25967.1. AK154929 mRNA. Translation: BAE32931.1. AK165897 mRNA. Translation: BAE38446.1. AK166084 mRNA. Translation: BAE38561.1. AK168020 mRNA. Translation: BAE40005.1. AK168025 mRNA. Translation: BAE40010.1. AK168170 mRNA. Translation: BAE40131.1. AK168679 mRNA. Translation: BAE40528.1. BC010715 mRNA. Translation: AAH10715.1.
IPI	IPI00126176.
RefSeq	NP_001240737.1. NM_001253808.1. NP_001240738.1. NM_001253809.1. NP_036155.1. NM_012025.7.
UniGene	Mm.273804.
3D structure databases
ProteinModelPortal	Q9WVM1.
SMR	Q9WVM1. Positions 283-547.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-42340N.
IntAct	Q9WVM1. 9 interactions.
MINT	MINT-1202825.
PTM databases
PhosphoSite	Q9WVM1.
Proteomic databases
PaxDb	Q9WVM1.
PRIDE	Q9WVM1.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000023756; ENSMUSP00000023756; ENSMUSG00000023015. ENSMUST00000171702; ENSMUSP00000126417; ENSMUSG00000023015.
GeneID	26934.
KEGG	mmu:26934.
UCSC	uc007xpx.1. mouse.
Organism-specific databases
CTD	29127.
MGI	MGI:1349423. Racgap1.
Phylogenomic databases
eggNOG	NOG305341.
GeneTree	ENSGT00700000104344.
HOGENOM	HOG000230702.
HOVERGEN	HBG062009.
InParanoid	Q9WVM1.
KO	K16733.
OMA	CIPTLIG.
OrthoDB	EOG4CRKZM.
Gene expression databases
ArrayExpress	Q9WVM1.
Bgee	Q9WVM1.
CleanEx	MM_RACGAP1.
Genevestigator	Q9WVM1.
GermOnline	ENSMUSG00000023015. Mus musculus.
Family and domain databases
Gene3D	1.10.555.10. 1 hit.
InterPro	IPR002219. Prot_Kinase_C-like_PE/DAG-bd. IPR008936. Rho_GTPase_activation_prot. IPR000198. RhoGAP_dom. [Graphical view]
Pfam	PF00130. C1_1. 1 hit. PF00620. RhoGAP. 1 hit. [Graphical view]
SMART	SM00109. C1. 1 hit. SM00324. RhoGAP. 1 hit. [Graphical view]
SUPFAM	SSF48350. Rho_GAP. 1 hit.
PROSITE	PS50238. RHOGAP. 1 hit. PS00479. ZF_DAG_PE_1. 1 hit. PS50081. ZF_DAG_PE_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	RACGAP1. mouse.
NextBio	304839.
SOURCE	Search...

Entry information

Entry name

RGAP1_MOUSE

Accession

Primary (citable) accession number: Q9WVM1
Secondary accession number(s): Q3THR5, Q3TI41, Q3TM81

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 21, 2006
Last sequence update:	November 1, 1999
Last modified:	May 1, 2013
This is version 108 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program