Transforming protein RhoA precursor

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Reviewed, UniProtKB/Swiss-Prot P61586 (RHOA_HUMAN)

Last modified November 25, 2008. Version 64. History...

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

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Names and origin

Protein names

Recommended name:
Transforming protein RhoA
Alternative name(s):
H12

Gene names

Name:	RHOA
Synonyms:	ARH12, ARHA, RHO12

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	193 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Regulates a signal transduction pathway linking plasma membrane receptors to the assembly of focal adhesions and actin stress fibers. Serves as a target for the yopT cysteine peptidase from Yersinia pestis, vector of the plague, and Yersinia pseudotuberculosis, which causes gastrointestinal disorders. May be an activator of PLCE1. Activated by ARHGEF2, which promotes the exchange of GDP for GTP.
Cofactor	Magnesium.
Subunit structure	Interacts with RGNEF By similarity. Binds PRKCL1, ROCK1 and ROCK2. Interacts with ARHGEF2, ARHGEF3, NET1 and RTKN. Interacts with PLCE1 and AKAP13.
Subcellular location	Cell membrane; Lipid-anchor; Cytoplasmic side. Cytoplasm › cytoskeleton.
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.
Sequence similarities	Belongs to the small GTPase superfamily. Rho family.

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Ontologies

Keywords
Cellular component	Cell membrane Cytoplasm Cytoskeleton Membrane
Disease	Proto-oncogene
Ligand	GTP-binding Magnesium Nucleotide-binding
PTM	ADP-ribosylation Lipoprotein Methylation Prenylation
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	Rho protein signal transduction Traceable author statement. Source: UniProtKB positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from expression pattern. Source: UniProtKB positive regulation of NF-kappaB import into nucleus Non-traceable author statement. Source: UniProtKB
Cellular component	cytoskeleton Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	GTP binding Inferred from electronic annotation. Source: InterPro GTPase activity Traceable author statement. Source: UniProtKB magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Ref.23 Ref.24 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
ARHGAP1	Q07960	1	EBI-446668,EBI-602762
ARHGDIA	P52565	1	EBI-446668,EBI-712693
ARHGEF5	Q12774	1	EBI-446668,EBI-602199
CNKSR1	Q969H4	2	EBI-446668,EBI-741671
Mcf2l	Q6PDM6	3	EBI-446668,EBI-602149	From a different organism.
PKN1	Q16512	1	EBI-446668,EBI-602382
Rabac1	Q9Z0S9	1	EBI-446668,EBI-476965	From a different organism.
RTKN	Q9BST9	1	EBI-446668,EBI-446694

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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

Removed in mature form

PRO_0000030412

Regions

Nucleotide binding

12 – 19

GTP

Nucleotide binding

59 – 63

GTP By similarity

Nucleotide binding

117 – 120

GTP

Motif

34 – 42

Effector region Potential

Compositional bias

182 – 187

Arg/Lys-rich (basic)

Sites

Site

189 – 190

Cleavage; by yopT

Amino acid modifications

Modified residue

ADP-ribosylasparagine; by botulinum toxin Probable

Modified residue

190

Cysteine methyl ester

Lipidation

190

S-geranylgeranyl cysteine

Experimental info

Mutagenesis

G → V: Causes constitutive activation

Mutagenesis

Q → L: Causes constitutive activation

Mutagenesis

193

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

Secondary structure

193

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

P61586-1 [UniParc].

Last modified January 1, 1988. Version 1.
Checksum: C4DA2DC31FF858BC
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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

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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: 3822842] [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: 7835413] [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]	The German cDNA consortium Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Oesophageal carcinoma.
[5]	"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].
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain and Colon.
[7]	"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: 8039707] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 5-193. Tissue: Mammary cancer.
[8]	"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: 1328215] [Abstract] Cited for: PROTEIN SEQUENCE OF 28-39; 45-57; 78-86; 130-144; 146-162 AND 165-184, ADP-RIBOSYLATION AT ASN-41.
[9]	"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: 1556108] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 137-193.
[10]	"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: 8617235] [Abstract] Cited for: INTERACTION WITH ROCK1.
[11]	"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: 8641286] [Abstract] Cited for: INTERACTION WITH ROCK2.
[12]	"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: 9857026] [Abstract] Cited for: INTERACTION WITH ARHGEF2.
[13]	"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: 10940294] [Abstract] Cited for: INTERACTION WITH RTKN.
[14]	"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: 11696353] [Abstract] Cited for: INTERACTION WITH AKAP13.
[15]	"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: 12221096] [Abstract] Cited for: INTERACTION WITH ARHGEF3.
[16]	"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: 12062101] [Abstract] Cited for: INTERACTION WITH YERSINIA PESTIS YOPT, CLEAVAGE.
[17]	"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: 12900402] [Abstract] Cited for: FUNCTION, INTERACTION WITH PLCE1.
[18]	"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: 12538863] [Abstract] Cited for: INTERACTION WITH YERSINIA PSEUDOTUBERCULOSIS YOPT, CLEAVAGE, MUTAGENESIS OF LEU-193.
[19]	"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: 9302995] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
[20]	"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: 9545299] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 4-181 OF MUTANT VAL-14.
[21]	"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: 10388627] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-181 IN COMPLEX WITH PRKCL1.
[22]	"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: 10748207] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 3-180 IN COMPLEX WITH GDP.
[23]	"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: 11927263] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
[24]	"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: 12006984] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.81 ANGSTROMS) IN COMPLEX WITH MCF2.
[25]	"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: 12777804] [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.

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Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Cross-references

Sequence databases

X05026 mRNA. Translation: CAA28690.1.
L25080 mRNA. Translation: AAC33178.1.
AF498970 mRNA. Translation: AAM21117.1.
BX647063 mRNA. Translation: CAE46190.1.
BT019870 mRNA. Translation: AAV38673.1.
BC001360 mRNA. Translation: AAH01360.1.
BC005976 mRNA. Translation: AAH05976.1.
L09159 mRNA. Translation: AAA50612.1.
M83094 Genomic DNA. Translation: AAA67539.1.

PIR

TVHU12. A26675.

RefSeq

NP_001655.1.

UniGene

Hs.247077
Hs.657976

3D structure databases

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	[»]