P61586 (RHOA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transforming protein RhoA

Alternative name(s):
Rho cDNA clone 12
Short name=h12

Gene names

Name:	RHOA
Synonyms:	ARH12, ARHA, RHO12

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	193 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	Regulates a signal transduction pathway linking plasma membrane receptors to the assembly of focal adhesions and actin stress fibers. Involved in a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis. Plays an essential role in cleavage furrow formation. Required for the apical junction formation of keratinocyte cell-cell adhesion. Serves as a target for the yopT cysteine peptidase from Yersinia pestis, vector of the plague, and Yersinia pseudotuberculosis, which causes gastrointestinal disorders. Stimulates PKN2 kinase activity. May be an activator of PLCE1. Activated by ARHGEF2, which promotes the exchange of GDP for GTP. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. The MEMO1-RHOA-DIAPH1 signaling pathway plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. It controls the localization of APC and CLASP2 to the cell membrane, via the regulation of GSK3B activity. In turn, membrane-bound APC allows the localization of the MACF1 to the cell membrane, which is required for microtubule capture and stabilization. Ref.14 Ref.15 Ref.24 Ref.26 Ref.27 Ref.29 Ref.33 Ref.37
Cofactor	Magnesium.
Enzyme regulation	GTP hydrolysis is stimulated by ARHGAP30. Ref.35
Subunit structure	Interacts with ARHGEF28 By similarity. Binds PRKCL1, ROCK1 and ROCK2. Interacts with ARHGEF2, ARHGEF3, NET1 and RTKN. Interacts with PLCE1 and AKAP13. Interacts (in the constitutively activated, GTP-bound form) with DGKQ. Interacts with human respiratory syncytial virus (HRSV) protein F; this interaction facilitates virus-induced syncytium formation. Interacts with GNB2L1/RACK1; enhances RHOA activation. Interacts with PKP4; the interaction is detected at the midbody. Interacts (GTP-bound form preferentially) with PKN2; the interaction stimulates autophosphorylation and phosphorylation of PKN2. Ref.12 Ref.13 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.28 Ref.36 Ref.37
Subcellular location	Cell membrane; Lipid-anchor; Cytoplasmic side. Cytoplasm › cytoskeleton. Cleavage furrow. Cytoplasm › cell cortex. Midbody. Note: Localized to cell-cell contacts in calcium-treated keratinocytes By similarity. Translocates to the equatorial region before furrow formation in a ECT2-dependent manner. Localizes to the equatorial cell cortex (at the site of the presumptive furrow) in early anaphase in a activated form and in a myosin- and actin-independent manner. Ref.26 Ref.27 Ref.28
Domain	The basic-rich region is essential for yopT recognition and cleavage.
Post-translational modification	Substrate for botulinum ADP-ribosyltransferase. Cleaved by yopT protease when the cell is infected by some Yersinia pathogens. This removes the lipid attachment, and leads to its displacement from plasma membrane and to subsequent cytoskeleton cleavage. AMPylation at Tyr-34 and Thr-37 are mediated by bacterial enzymes in case of infection by H.somnus and V.parahaemolyticus, respectively. AMPylation occurs in the effector region and leads to inactivation of the GTPase activity by preventing the interaction with downstream effectors, thereby inhibiting actin assembly in infected cells. It is unclear whether some human enzyme mediates AMPylation; FICD has such ability in vitro but additional experiments remain to be done to confirm results in vivo. Phosphorylation by PRKG1 at Ser-188 inactivates RHOA signaling. Ubiquitinated by the BCR(BACURD1) and BCR(BACURD2) E3 ubiquitin ligase complexes, leading to its degradation by the proteasome, thereby regulating the actin cytoskeleton and cell migration. Ref.31
Sequence similarities	Belongs to the small GTPase superfamily. Rho family.

Ontologies

Keywords
Biological process	Cell cycle Cell division Host-virus interaction
Cellular component	Cell membrane Cytoplasm Cytoskeleton Membrane
Disease	Proto-oncogene
Ligand	GTP-binding Magnesium Nucleotide-binding
PTM	ADP-ribosylation Lipoprotein Methylation Phosphoprotein Prenylation Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	Rho protein signal transduction Traceable author statement PubMed 10436159. Source: UniProtKB actin cytoskeleton organization Traceable author statement PubMed 10436159. Source: UniProtKB androgen receptor signaling pathway Inferred from electronic annotation. Source: Compara apical junction assembly Inferred from mutant phenotype Ref.37. Source: UniProtKB axon guidance Traceable author statement. Source: Reactome cell-matrix adhesion Inferred from electronic annotation. Source: Compara cleavage furrow formation Inferred from direct assay Ref.26. Source: UniProtKB negative regulation of I-kappaB kinase/NF-kappaB cascade Inferred from electronic annotation. Source: Compara negative regulation of axonogenesis Traceable author statement. Source: Reactome negative regulation of intracellular steroid hormone receptor signaling pathway Inferred from electronic annotation. Source: Compara negative regulation of neuron apoptotic process Inferred from electronic annotation. Source: Compara negative regulation of neuron differentiation Inferred from electronic annotation. Source: Compara nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome ossification involved in bone maturation Inferred from sequence or structural similarity. Source: BHF-UCL phosphatidylinositol-mediated signaling Traceable author statement. Source: Reactome platelet activation Traceable author statement. Source: Reactome positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from expression pattern PubMed 12761501. Source: UniProtKB positive regulation of NF-kappaB import into nucleus Non-traceable author statement PubMed 12761501. Source: UniProtKB positive regulation of actin filament polymerization Inferred from electronic annotation. Source: Compara positive regulation of axonogenesis Traceable author statement. Source: Reactome positive regulation of cell adhesion Inferred from electronic annotation. Source: Compara positive regulation of cell cycle cytokinesis Inferred from mutant phenotype Ref.26Ref.28. Source: UniProtKB positive regulation of cell growth Inferred from electronic annotation. Source: Compara positive regulation of cell migration Inferred from electronic annotation. Source: Compara positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from electronic annotation. Source: Compara positive regulation of neuron apoptotic process Inferred from electronic annotation. Source: Compara positive regulation of neuron differentiation Inferred from mutant phenotype PubMed 17488780. Source: MGI positive regulation of podosome assembly Inferred from electronic annotation. Source: Compara positive regulation of stress fiber assembly Inferred from direct assay PubMed 15467718. Source: MGI positive regulation of translation Inferred from electronic annotation. Source: Compara positive regulation of vasoconstriction Inferred from electronic annotation. Source: Compara regulation of calcium ion transport Inferred from electronic annotation. Source: Compara regulation of cell migration Inferred from mutant phenotype Ref.29. Source: UniProtKB regulation of dendrite development Inferred from electronic annotation. Source: Compara regulation of osteoblast proliferation Inferred from sequence or structural similarity. Source: BHF-UCL regulation of small GTPase mediated signal transduction Traceable author statement. Source: Reactome regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara response to amino acid stimulus Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara response to ethanol Inferred from electronic annotation. Source: Compara response to glucocorticoid stimulus Inferred from electronic annotation. Source: Compara response to glucose stimulus Inferred from electronic annotation. Source: Compara response to hypoxia Inferred from electronic annotation. Source: Compara response to mechanical stimulus Inferred from electronic annotation. Source: Compara skeletal muscle tissue development Inferred from electronic annotation. Source: Compara spindle assembly involved in mitosis Inferred from mutant phenotype PubMed 19635168. Source: BHF-UCL stress fiber assembly Inferred from electronic annotation. Source: Compara stress-activated protein kinase signaling cascade Inferred from electronic annotation. Source: Compara trabecula morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL transforming growth factor beta receptor signaling pathway Traceable author statement. Source: Reactome virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	apical junction complex Inferred from direct assay Ref.37. Source: UniProtKB axon Inferred from electronic annotation. Source: Compara cell cortex Inferred from direct assay Ref.26. Source: UniProtKB cleavage furrow Inferred from electronic annotation. Source: UniProtKB-SubCell cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Traceable author statement. Source: Reactome lamellipodium Inferred from electronic annotation. Source: Compara midbody Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrion Inferred from electronic annotation. Source: Compara nucleus Inferred from electronic annotation. Source: Compara plasma membrane Traceable author statement. Source: Reactome ruffle membrane Inferred from electronic annotation. Source: Compara
Molecular_function	GTP binding Inferred from electronic annotation. Source: UniProtKB-KW GTPase activity Traceable author statement PubMed 10436159. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ARHGAP1	Q07960	2	EBI-446668,EBI-602762
ARHGDIA	P52565	2	EBI-446668,EBI-712693
ARHGEF11	O15085	2	EBI-446668,EBI-311099
CNKSR1	Q969H4	4	EBI-446668,EBI-741671
DAAM1	Q9Y4D1	4	EBI-446668,EBI-2817289
DIAPH1	O60610	3	EBI-446668,EBI-3959709
Diaph1	O08808	3	EBI-446668,EBI-1026445	From a different organism.
Mcf2l	Q6PDM6	3	EBI-446668,EBI-602149	From a different organism.
Rabac1	Q9Z0S9	3	EBI-446668,EBI-476965	From a different organism.
Rtkn	Q8C6B2	2	EBI-446668,EBI-1162441	From a different organism.
SMAD2	Q15796	2	EBI-446668,EBI-1040141

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 190

190

Transforming protein RhoA

PRO_0000030411

Propeptide

191 – 193

3

Removed in mature form

PRO_0000030412

Regions

Nucleotide binding

12 – 19

8

GTP

Nucleotide binding

59 – 63

5

GTP By similarity

Nucleotide binding

117 – 120

4

GTP

Motif

34 – 42

9

Effector region Potential

Compositional bias

182 – 187

6

Arg/Lys-rich (basic)

Sites

Site

189 – 190

2

Cleavage; by yopT

Amino acid modifications

Modified residue

34

1

O-AMP-tyrosine; by Haemophilus IbpA

Modified residue

37

1

O-AMP-threonine; by Vibrio VopS

Modified residue

41

1

ADP-ribosylasparagine; by botulinum toxin Probable

Modified residue

188

1

Phosphoserine; by PKG/PRKG1 Ref.20

Modified residue

190

1

Cysteine methyl ester

Lipidation

190

1

S-geranylgeranyl cysteine

Experimental info

Mutagenesis

14

1

G → V: Causes constitutive activation.

Mutagenesis

34

1

Y → A: Abolishes interaction with DGKQ. Ref.17 Ref.30

Mutagenesis

34

1

Y → F: Abolishes AMPylation by Haemophilus IbpA. Ref.17 Ref.30

Mutagenesis

63

1

Q → L: Causes constitutive activation.

Mutagenesis

193

1

L → M: Converts geranyl-geranylation to farnesylation; does not prevent the cleavage by yopT. Ref.25

Sequence conflict

23

1

I → T in BAD96276. Ref.5

Secondary structure

1

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193

Helix Strand Turn

Details...

Beta strand

5 – 13

9

Turn

15 – 17

3

Helix

18 – 27

10

Beta strand

38 – 48

11

Beta strand

51 – 60

10

Helix

64 – 66

3

Turn

67 – 69

3

Helix

70 – 73

4

Beta strand

78 – 85

8

Helix

89 – 97

9

Helix

99 – 106

8

Beta strand

112 – 117

6

Helix

119 – 121

3

Helix

125 – 133

9

Helix

141 – 150

10

Beta strand

154 – 158

5

Turn

161 – 163

3

Helix

167 – 179

13

Sequences

	Sequence		Length	Mass (Da)
	P61586 [UniParc]. Last modified January 1, 1988. Version 1. Checksum: C4DA2DC31FF858BC	FASTA	193	21,768
	10 20 30 40 50 60 MAAIRKKLVI VGDGACGKTC LLIVFSKDQF PEVYVPTVFE NYVADIEVDG KQVELALWDT 70 80 90 100 110 120 AGQEDYDRLR PLSYPDTDVI LMCFSIDSPD SLENIPEKWT PEVKHFCPNV PIILVGNKKD 130 140 150 160 170 180 LRNDEHTRRE LAKMKQEPVK PEEGRDMANR IGAFGYMECS AKTKDGVREV FEMATRAALQ 190 ARRGKKKSGC LVL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nucleotide sequence of human rho cDNA clone 12." Yeramian P., Chardin P., Madaule P., Tavitian A. Nucleic Acids Res. 15:1869-1869(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Sequence of rho small GTP-binding protein cDNAs from human retina and identification of novel 5' end cloning artifacts." Fagan K.P., Oliveira L., Pittler S.J. Exp. Eye Res. 59:235-237(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Retina.
[3]	"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]. Tissue: Brain.
[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]	Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Adipose tissue.
[6]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Esophageal carcinoma.
[7]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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 and Colon.
[9]	"Utilization of multiple polyadenylation signals in the human RHOA protooncogene." Moscow J.A., He R., Gudas J.M., Cowan K.H. Gene 144:229-236(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 5-193. Tissue: Mammary cancer.
[10]	"A rho gene product in human blood platelets. I. Identification of the platelet substrate for botulinum C3 ADP-ribosyltransferase as rhoA protein." Nemoto Y., Namba T., Teru-uchi T., Ushikubi F., Morii N., Narumiya S. J. Biol. Chem. 267:20916-20920(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 28-39; 45-57; 78-86; 130-144; 146-162 AND 165-184, ADP-RIBOSYLATION AT ASN-41. Tissue: Platelet.
[11]	"Structure and function of the 5'-flanking sequence of the human cytosolic selenium-dependent glutathione peroxidase gene (hgpx1)." Moscow J.A., Morrow C.S., He R., Mullenbach G.T., Cowan K.H. J. Biol. Chem. 267:5949-5958(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 137-193.
[12]	"The small GTP-binding protein Rho binds to and activates a 160 kDa Ser/Thr protein kinase homologous to myotonic dystrophy kinase." Ishizaki T., Maekawa M., Fujisawa K., Okawa K., Iwamatsu A., Fujita A., Watanabe N., Saito Y., Kakizuka A., Morii N., Narumiya S. EMBO J. 15:1885-1893(1996) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ROCK1.
[13]	"Rho-associated kinase, a novel serine/threonine kinase, as a putative target for small GTP binding protein Rho." Matsui T., Amano M., Yamamoto T., Chihara K., Nakafuku M., Ito M., Nakano T., Okawa K., Iwamatsu A., Kaibuchi K. EMBO J. 15:2208-2216(1996) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ROCK2.
[14]	"Isolation of a NCK-associated kinase, PRK2, an SH3-binding protein and potential effector of Rho protein signaling." Quilliam L.A., Lambert Q.T., Mickelson-Young L.A., Westwick J.K., Sparks A.B., Kay B.K., Jenkins N.A., Gilbert D.J., Copeland N.G., Der C.J. J. Biol. Chem. 271:28772-28776(1996) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[15]	"The PRK2 kinase is a potential effector target of both Rho and Rac GTPases and regulates actin cytoskeletal organization." Vincent S., Settleman J. Mol. Cell. Biol. 17:2247-2256(1997) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH PKN2.
[16]	"Cloning and characterization of GEF-H1, a microtubule-associated guanine nucleotide exchange factor for Rac and Rho GTPases." Ren Y., Li R., Zheng Y., Busch H. J. Biol. Chem. 273:34954-34960(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ARHGEF2.
[17]	"Diacylglycerol kinase theta binds to and is negatively regulated by active RhoA." Houssa B., de Widt J., Kranenburg O., Moolenaar W.H., van Blitterswijk W.J. J. Biol. Chem. 274:6820-6822(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DGKQ, MUTAGENESIS OF TYR-34.
[18]	"RhoA interacts with the fusion glycoprotein of respiratory syncytial virus and facilitates virus-induced syncytium formation." Pastey M.K., Crowe J.E. Jr., Graham B.S. J. Virol. 73:7262-7270(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HRSV PROTEIN F.
[19]	"The PDZ protein TIP-1 interacts with the Rho effector rhotekin and is involved in Rho signaling to the serum response element." Reynaud C., Fabre S., Jalinot P. J. Biol. Chem. 275:33962-33968(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RTKN.
[20]	"cGMP-dependent protein kinase phosphorylates and inactivates RhoA." Sawada N., Itoh H., Yamashita J., Doi K., Inoue M., Masatsugu K., Fukunaga Y., Sakaguchi S., Sone M., Yamahara K., Yurugi T., Nakao K. Biochem. Biophys. Res. Commun. 280:798-805(2001) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-188 BY PRKG1.
[21]	"Ht31: the first protein kinase A anchoring protein to integrate protein kinase A and Rho signaling." Klussmann E., Edemir B., Pepperle B., Tamma G., Henn V., Klauschenz E., Hundsrucker C., Maric K., Rosenthal W. FEBS Lett. 507:264-268(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH AKAP13.
[22]	"XPLN, a guanine nucleotide exchange factor for RhoA and RhoB, but not RhoC." Arthur W.T., Ellerbroek S.M., Der C.J., Burridge K., Wennerberg K. J. Biol. Chem. 277:42964-42972(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ARHGEF3.
[23]	"A Yersinia effector and a Pseudomonas avirulence protein define a family of cysteine proteases functioning in bacterial pathogenesis." Shao F., Merritt P.M., Bao Z., Innes R.W., Dixon J.E. Cell 109:575-588(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH YERSINIA PESTIS YOPT, CLEAVAGE.
[24]	"Direct activation of phospholipase C-epsilon by Rho." Wing M.R., Snyder J.T., Sondek J., Harden T.K. J. Biol. Chem. 278:41253-41258(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH PLCE1.
[25]	"Biochemical characterization of the Yersinia YopT protease: cleavage site and recognition elements in Rho GTPases." Shao F., Vacratsis P.O., Bao Z., Bowers K.E., Fierke C.A., Dixon J.E. Proc. Natl. Acad. Sci. U.S.A. 100:904-909(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH YERSINIA PSEUDOTUBERCULOSIS YOPT, CLEAVAGE, MUTAGENESIS OF LEU-193.
[26]	"An ECT2-centralspindlin complex regulates the localization and function of RhoA." Yuce O., Piekny A., Glotzer M. J. Cell Biol. 170:571-582(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[27]	"Dissecting the role of Rho-mediated signaling in contractile ring formation." Kamijo K., Ohara N., Abe M., Uchimura T., Hosoya H., Lee J.S., Miki T. Mol. Biol. Cell 17:43-55(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[28]	"The armadillo protein p0071 regulates Rho signalling during cytokinesis." Wolf A., Keil R., Gotzl O., Mun A., Schwarze K., Lederer M., Huttelmaier S., Hatzfeld M. Nat. Cell Biol. 8:1432-1440(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PKP4, SUBCELLULAR LOCATION.
[29]	"The Rho-family GEF Asef2 activates Rac to modulate adhesion and actin dynamics and thereby regulate cell migration." Bristow J.M., Sellers M.H., Majumdar D., Anderson B., Hu L., Webb D.J. J. Cell Sci. 122:4535-4546(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[30]	"The fic domain: regulation of cell signaling by adenylylation." Worby C.A., Mattoo S., Kruger R.P., Corbeil L.B., Koller A., Mendez J.C., Zekarias B., Lazar C., Dixon J.E. Mol. Cell 34:93-103(2009) [PubMed] [Europe PMC] [Abstract] Cited for: AMPYLATION AT TYR-34, MUTAGENESIS OF TYR-34.
[31]	"Cullin mediates degradation of RhoA through evolutionarily conserved BTB adaptors to control actin cytoskeleton structure and cell movement." Chen Y., Yang Z., Meng M., Zhao Y., Dong N., Yan H., Liu L., Ding M., Peng H.B., Shao F. Mol. Cell 35:841-855(2009) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION.
[32]	"AMPylation of Rho GTPases by Vibrio VopS disrupts effector binding and downstream signaling." Yarbrough M.L., Li Y., Kinch L.N., Grishin N.V., Ball H.L., Orth K. Science 323:269-272(2009) [PubMed] [Europe PMC] [Abstract] Cited for: AMPYLATION AT THR-37.
[33]	"ErbB2 receptor controls microtubule capture by recruiting ACF7 to the plasma membrane of migrating cells." Zaoui K., Benseddik K., Daou P., Salaun D., Badache A. Proc. Natl. Acad. Sci. U.S.A. 107:18517-18522(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[34]	"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].
[35]	"ARHGAP30 is a Wrch-1-interacting protein involved in actin dynamics and cell adhesion." Naji L., Pacholsky D., Aspenstrom P. Biochem. Biophys. Res. Commun. 409:96-102(2011) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION.
[36]	"RACK1 promotes breast carcinoma migration/metastasis via activation of the RhoA/Rho kinase pathway." Cao X.X., Xu J.D., Xu J.W., Liu X.L., Cheng Y.Y., Li Q.Q., Xu Z.D., Liu X.P. Breast Cancer Res. Treat. 126:555-563(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GNB2L1.
[37]	"The Rho target PRK2 regulates apical junction formation in human bronchial epithelial cells." Wallace S.W., Magalhaes A., Hall A. Mol. Cell. Biol. 31:81-91(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH PKN2.
[38]	"Crystal structure of RhoA-GDP and its functional implications." Wei Y., Zhang Y., Derewenda U., Liu X., Minor W., Nakamoto R.K., Somlyo A.V., Somlyo A.P., Derewenda Z.S. Nat. Struct. Biol. 4:699-703(1997) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
[39]	"Crystal structure of human RhoA in a dominantly active form complexed with a GTP analogue." Ihara K., Muraguchi S., Kato M., Shimizu T., Shirakawa M., Kuroda S., Kaibuchi K., Hakoshima T. J. Biol. Chem. 273:9656-9666(1998) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 4-181 OF MUTANT VAL-14.
[40]	"Biochemical and crystallographic characterization of a Rho effector domain of the protein serine/threonine kinase N in a complex with RhoA." Maesaki R., Shimizu T., Ihara K., Kuroda S., Kaibuchi K., Hakoshima T. J. Struct. Biol. 126:166-170(1999) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-181 IN COMPLEX WITH PRKCL1.
[41]	"An open conformation of switch I revealed by the crystal structure of a Mg2+-free form of RHOA complexed with GDP. Implications for the GDP/GTP exchange mechanism." Shimizu T., Ihara K., Maesaki R., Kuroda S., Kaibuchi K., Hakoshima T. J. Biol. Chem. 275:18311-18317(2000) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 3-180 IN COMPLEX WITH GDP.
[42]	"MgF(3)(-) as a transition state analog of phosphoryl transfer." Graham D.L., Lowe P.N., Grime G.W., Marsh M., Rittinger K., Smerdon S.J., Gamblin S.J., Eccleston J.F. Chem. Biol. 9:375-381(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
[43]	"Structural basis for the selective activation of Rho GTPases by Dbl exchange factors." Snyder J.T., Worthylake D.K., Rossman K.L., Betts L., Pruitt W.M., Siderovski D.P., Der C.J., Sondek J. Nat. Struct. Biol. 9:468-475(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.81 ANGSTROMS) IN COMPLEX WITH MCF2.
[44]	"Structure of a constitutively activated RhoA mutant (Q63L) at 1.55 A resolution." Longenecker K., Read P., Lin S.-K., Somlyo A.P., Nakamoto R.K., Derewenda Z.S. Acta Crystallogr. D 59:876-880(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF MUTANT LEU-63 IN COMPLEX WITH A GTP ANALOG AND MG(2+).
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X05026 mRNA. Translation: CAA28690.1.
L25080 mRNA. Translation: AAC33178.1.
AF498970 mRNA. Translation: AAM21117.1.
BT019870 mRNA. Translation: AAV38673.1.
AK222556 mRNA. Translation: BAD96276.1.
BX647063 mRNA. Translation: CAE46190.1.
AC104452 Genomic DNA. No translation available.
AC121247 Genomic DNA. No translation available.
AC137114 Genomic DNA. No translation available.
BC001360 mRNA. Translation: AAH01360.1.
BC005976 mRNA. Translation: AAH05976.1.
L09159 mRNA. Translation: AAA50612.1.
M83094 Genomic DNA. Translation: AAA67539.1.

IPI

IPI00478231.

PIR

TVHU12. A26675.

RefSeq

NP_001655.1. NM_001664.2.

UniGene

Hs.247077.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1A2B	X-ray	2.40	A	1-181	[»]
1CC0	X-ray	5.00	A/C	1-190	[»]
1CXZ	X-ray	2.20	A	1-181	[»]
1DPF	X-ray	2.00	A	1-180	[»]
1FTN	X-ray	2.10	A	1-193	[»]
1KMQ	X-ray	1.55	A	4-181	[»]
1LB1	X-ray	2.81	B/D/F/H	1-189	[»]
1OW3	X-ray	1.80	B	1-193	[»]
1S1C	X-ray	2.60	A/B	1-181	[»]
1TX4	X-ray	1.65	B	3-179	[»]
1X86	X-ray	3.22	B/D/F/H	1-193	[»]
1XCG	X-ray	2.50	B/F	3-180	[»]
2RGN	X-ray	3.50	C/F	1-193	[»]
3KZ1	X-ray	2.70	E/F	1-181	[»]
3LW8	X-ray	1.85	A/B/C/D	2-181	[»]
3LWN	X-ray	2.28	A/B	2-181	[»]
3LXR	X-ray	1.68	A	2-181	[»]
3MSX	X-ray	1.65	A	1-180	[»]
3T06	X-ray	2.84	B/F	3-180	[»]

ProteinModelPortal

P61586.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29642N.

IntAct

P61586. 32 interactions.

MINT

MINT-1454858.

STRING

9606.ENSP00000400175.

PTM databases

PhosphoSite

P61586.

Polymorphism databases

DMDM

47606458.

Proteomic databases

PaxDb

P61586.

PeptideAtlas

P61586.

PRIDE

P61586.

Protocols and materials databases

DNASU

387.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000418115; ENSP00000400175; ENSG00000067560.

GeneID

387.

KEGG

hsa:387.

UCSC

uc003cwu.3. human.

Organism-specific databases

CTD

387.

GeneCards

GC03M049371.

HGNC

HGNC:667. RHOA.

HPA

CAB005052.

MIM

165390. gene.

neXtProt

NX_P61586.

PharmGKB

PA134865095.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1100.

HOGENOM

HOG000233974.

HOVERGEN

HBG009351.

InParanoid

P61586.

KO

K04513.

OMA

KHFCPTV.

OrthoDB

EOG4G4GRD.

Enzyme and pathway databases

Pathway_Interaction_DB

amb2_neutrophils_pathway. amb2 Integrin signaling.
arf6downstreampathway. Arf6 downstream pathway.
aurora_b_pathway. Aurora B signaling.
pi3kcipathway. Class I PI3K signaling events.
endothelinpathway. Endothelins.
epha_fwdpathway. EPHA forward signaling.
epha2_fwdpathway. EPHA2 forward signaling.
ephbfwdpathway. EPHB forward signaling.
il2_1pathway. IL2-mediated signaling events.
avb3_integrin_pathway. Integrins in angiogenesis.
lis1pathway. Lissencephaly gene (LIS1) in neuronal migration and development.
lysophospholipid_pathway. LPA receptor mediated events.
trkrpathway. Neurotrophic factor-mediated Trk receptor signaling.
avb3_opn_pathway. Osteopontin-mediated events.
p75ntrpathway. p75(NTR)-mediated signaling.
a4b1_paxindep_pathway. Paxillin-independent events mediated by a4b1 and a4b7.
er_nongenomic_pathway. Plasma membrane estrogen receptor signaling.
s1p_s1p1_pathway. S1P1 pathway.
s1p_s1p2_pathway. S1P2 pathway.
s1p_s1p3_pathway. S1P3 pathway.
s1p_s1p4_pathway. S1P4 pathway.
s1p_s1p5_pathway. S1P5 pathway.
prlsignalingeventspathway. Signaling events mediated by PRL.
ptp1bpathway. Signaling events mediated by PTP1B.
vegfr1_2_pathway. Signaling events mediated by VEGFR1 and VEGFR2.
ret_pathway. Signaling events regulated by Ret tyrosine kinase.
syndecan_2_pathway. Syndecan-2-mediated signaling events.
syndecan_4_pathway. Syndecan-4-mediated signaling events.
tcrpathway. TCR signaling in naive CD4+ T cells.
tgfbrpathway. TGF-beta receptor signaling.
txa2pathway. Thromboxane A2 receptor signaling.

Reactome

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

Gene expression databases

ArrayExpress

P61586.

Bgee

P61586.

CleanEx

HS_RHOA.

Genevestigator

P61586.

GermOnline

ENSG00000067560. 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

BindingDB

P61586.

ChEMBL

CHEMBL6052.

ChiTaRS

RHOA. human.

DrugBank

DB01076. Atorvastatin.
DB00641. Simvastatin.

EvolutionaryTrace

P61586.

GenomeRNAi

387.

NextBio

1611.

PMAP-CutDB

P61586.

SOURCE

Search...

Entry information

Entry name

RHOA_HUMAN

Accession

Primary (citable) accession number: P61586
Secondary accession number(s): P06749 , Q53HM4, Q5U024, Q9UDJ0, Q9UEJ4

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1988
Last sequence update:	January 1, 1988
Last modified:	May 1, 2013
This is version 117 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.