RHOA (ras homolog family member A)

Gene

• Entrez ID: 387
• Gene name: Ras homolog family member A
• Gene symbol: RHOA
• Synonyms: ARH12, ARHA, EDFAOB, RHO12, RHOH12
• Chromosome: 3
• Chromosome location: 3p21.31
• Summary: This gene encodes a member of the Rho family of small GTPases, which cycle between inactive GDP-bound and active GTP-bound states and function as molecular switches in signal transduction cascades. Rho proteins promote reorganization of the actin cytoskeleton and regulate cell shape, attachment, and motility. Overexpression of this gene is associated with tumor cell proliferation and metastasis. Multiple alternatively spliced variants have been identified. [provided by RefSeq, Sep 2015]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs1057519951	C>G,T	Likely-pathogenic	Missense variant, 5 prime UTR variant, coding sequence variant
rs1057519952	G>A	Likely-pathogenic	Intron variant, missense variant, coding sequence variant
rs1057519953	C>A,T	Likely-pathogenic	Intron variant, missense variant, coding sequence variant
rs1057519954	T>A,C,G	Likely-pathogenic	Missense variant, 5 prime UTR variant, coding sequence variant
rs1575647025	G>A	Pathogenic	Intron variant, 5 prime UTR variant, coding sequence variant, missense variant
rs1575653629	C>T	Pathogenic	Intron variant, 5 prime UTR variant, coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT000088	hsa-miR-31-5p	Luciferase reporter assay, qRT-PCR, Western blot	19524507
MIRT000088	hsa-miR-31-5p	qRT-PCR, Western blot	22854067
MIRT000088	hsa-miR-31-5p	qRT-PCR, Western blot	22736314
MIRT000088	hsa-miR-31-5p	Immunohistochemistry, In situ hybridization, Luciferase reporter assay, qRT-PCR, Western blot	27904131
MIRT000717	hsa-miR-122-5p	Luciferase reporter assay	19617899
MIRT000717	hsa-miR-122-5p	Luciferase reporter assay,	19935707
MIRT001961	hsa-miR-155-5p	Luciferase reporter assay, Western blot, qRT-PCR	18794355
MIRT001961	hsa-miR-155-5p	qRT-PCR	28146427
MIRT004036	hsa-miR-185-5p	Luciferase reporter assay, qRT-PCR, Western blot	21186079
MIRT004036	hsa-miR-185-5p	qRT-PCR, Western blot	27250838
MIRT007065	hsa-miR-31-3p	qRT-PCR, Western blot	22854067
MIRT007345	hsa-miR-200c-3p	Luciferase reporter assay, qRT-PCR, Western blot	23272142
MIRT019977	hsa-miR-375	Western blot;qRT-PCR;Microarray	20584986
MIRT022883	hsa-miR-124-3p	Microarray	18668037
MIRT036175	hsa-miR-320c	CLASH	23622248
MIRT041611	hsa-miR-146b-5p	CLASH	23622248
MIRT046885	hsa-miR-221-3p	CLASH	23622248
MIRT053178	hsa-miR-133b	Immunoblot, Luciferase reporter assay, Microarray, qRT-PCR, Western blot	22179829
MIRT307754	hsa-miR-3613-3p	HITS-CLIP	19536157
MIRT307761	hsa-miR-4446-3p	PAR-CLIP	23592263
MIRT307761	hsa-miR-4446-3p	PAR-CLIP	26701625
MIRT355605	hsa-miR-1304-3p	HITS-CLIP	19536157
MIRT437799	hsa-miR-125a-3p	PAR-CLIP	23592263
MIRT437799	hsa-miR-125a-3p	Immunofluorescence, Luciferase reporter assay, qRT-PCR	23525486
MIRT437799	hsa-miR-125a-3p	Luciferase reporter assay, Microarray, qRT-PCR, Western blot	26148871
MIRT438245	hsa-miR-340-5p	Luciferase reporter assay, Microarray, qRT-PCR, Western blot	24980435
MIRT439772	hsa-miR-218-5p	HITS-CLIP	23212916
MIRT469280	hsa-miR-4722-5p	PAR-CLIP	23592263
MIRT469280	hsa-miR-4722-5p	PAR-CLIP	26701625
MIRT469281	hsa-miR-592	PAR-CLIP	23592263
MIRT469282	hsa-miR-3678-3p	PAR-CLIP	23592263
MIRT469283	hsa-miR-597-5p	PAR-CLIP	23592263
MIRT469284	hsa-miR-6778-5p	PAR-CLIP	23592263
MIRT469285	hsa-miR-1233-5p	PAR-CLIP	23592263
MIRT469286	hsa-miR-4741	PAR-CLIP	23592263
MIRT469286	hsa-miR-4741	PAR-CLIP	26701625
MIRT469287	hsa-miR-4675	PAR-CLIP	23592263
MIRT469287	hsa-miR-4675	PAR-CLIP	26701625
MIRT469288	hsa-miR-4687-3p	PAR-CLIP	23592263
MIRT469288	hsa-miR-4687-3p	PAR-CLIP	26701625
MIRT469289	hsa-miR-504-3p	PAR-CLIP	23592263
MIRT469290	hsa-miR-6499-3p	PAR-CLIP	23592263
MIRT469290	hsa-miR-6499-3p	PAR-CLIP	26701625
MIRT469291	hsa-miR-2467-3p	PAR-CLIP	23592263
MIRT469291	hsa-miR-2467-3p	PAR-CLIP	26701625
MIRT469292	hsa-miR-4721	PAR-CLIP	23592263
MIRT469292	hsa-miR-4721	PAR-CLIP	26701625
MIRT469293	hsa-miR-3934-5p	PAR-CLIP	23592263
MIRT469294	hsa-miR-764	PAR-CLIP	23592263
MIRT469295	hsa-miR-6847-5p	PAR-CLIP	23592263
MIRT469295	hsa-miR-6847-5p	PAR-CLIP	26701625
MIRT469296	hsa-miR-4779	PAR-CLIP	23592263
MIRT469296	hsa-miR-4779	PAR-CLIP	26701625
MIRT469297	hsa-miR-4519	PAR-CLIP	23592263
MIRT469297	hsa-miR-4519	PAR-CLIP	26701625
MIRT469298	hsa-miR-2278	PAR-CLIP	23592263
MIRT469298	hsa-miR-2278	PAR-CLIP	26701625
MIRT566013	hsa-miR-6509-5p	PAR-CLIP	20371350
MIRT566014	hsa-miR-2054	PAR-CLIP	20371350
MIRT566015	hsa-miR-331-5p	PAR-CLIP	20371350
MIRT566016	hsa-miR-577	PAR-CLIP	20371350
MIRT566017	hsa-miR-4753-5p	PAR-CLIP	20371350
MIRT566018	hsa-miR-1252-3p	PAR-CLIP	20371350
MIRT566019	hsa-miR-3646	PAR-CLIP	20371350
MIRT566020	hsa-miR-6768-3p	PAR-CLIP	20371350
MIRT573540	hsa-miR-1227-5p	PAR-CLIP	20371350
MIRT573541	hsa-miR-3187-3p	PAR-CLIP	20371350
MIRT573542	hsa-miR-6881-5p	PAR-CLIP	20371350
MIRT573543	hsa-miR-128-2-5p	PAR-CLIP	20371350
MIRT573544	hsa-miR-128-1-5p	PAR-CLIP	20371350
MIRT573545	hsa-miR-6845-5p	PAR-CLIP	20371350
MIRT573546	hsa-miR-6877-5p	PAR-CLIP	20371350
MIRT573547	hsa-miR-6762-5p	PAR-CLIP	20371350
MIRT573548	hsa-miR-4529-5p	PAR-CLIP	20371350
MIRT573549	hsa-miR-5583-3p	PAR-CLIP	20371350
MIRT573550	hsa-miR-4517	PAR-CLIP	20371350
MIRT573551	hsa-miR-3936	PAR-CLIP	20371350
MIRT712837	hsa-miR-607	HITS-CLIP	19536157
MIRT712838	hsa-miR-7110-3p	HITS-CLIP	19536157
MIRT712839	hsa-miR-6769b-3p	HITS-CLIP	19536157
MIRT712840	hsa-miR-4723-3p	HITS-CLIP	19536157
MIRT712841	hsa-miR-3183	HITS-CLIP	19536157
MIRT712842	hsa-miR-483-3p	HITS-CLIP	19536157
MIRT712843	hsa-miR-6800-3p	HITS-CLIP	19536157
MIRT712844	hsa-miR-548z	HITS-CLIP	19536157
MIRT712845	hsa-miR-548h-3p	HITS-CLIP	19536157
MIRT712846	hsa-miR-548d-3p	HITS-CLIP	19536157
MIRT712847	hsa-miR-548bb-3p	HITS-CLIP	19536157
MIRT712848	hsa-miR-548ac	HITS-CLIP	19536157
MIRT731596	hsa-miR-200b-3p	Luciferase reporter assay	26903801
MIRT732566	hsa-miR-146a-5p	Luciferase reporter assay	27175941
MIRT732822	hsa-miR-490-3p	Immunohistochemistry, Luciferase reporter assay, Western blot	27524906
MIRT733752	hsa-miR-101-3p	Luciferase reporter assay, qRT-PCR, Western blot	28109909
MIRT734647	hsa-miR-133a-5p	Luciferase reporter assay, qRT-PCR, Western blot	25445891
MIRT735214	hsa-miR-200b-5p	Immunofluorescence, Luciferase reporter assay, qRT-PCR, Western blot	25909223
MIRT735339	hsa-miR-483-5p	Luciferase reporter assay, Microarray, qRT-PCR, Western blot	26148871
MIRT735339	hsa-miR-483-5p	PAR-CLIP	26701625
MIRT744737	hsa-miR-4456	PAR-CLIP	26701625
MIRT745810	hsa-miR-4520-2-3p	PAR-CLIP	26701625
MIRT745819	hsa-miR-4520-3p	PAR-CLIP	26701625
MIRT746338	hsa-miR-4640-5p	PAR-CLIP	26701625
MIRT747738	hsa-miR-4725-5p	PAR-CLIP	26701625
MIRT747767	hsa-miR-4726-5p	PAR-CLIP	26701625
MIRT749562	hsa-miR-504-5p	PAR-CLIP	26701625
MIRT750384	hsa-miR-541-3p	PAR-CLIP	26701625
MIRT752976	hsa-miR-6508-3p	PAR-CLIP	26701625
MIRT753455	hsa-miR-654-5p	PAR-CLIP	26701625
MIRT754094	hsa-miR-6733-3p	PAR-CLIP	26701625
MIRT755201	hsa-miR-6769a-5p	PAR-CLIP	26701625
MIRT755248	hsa-miR-6769b-5p	PAR-CLIP	26701625
MIRT756791	hsa-miR-6816-3p	PAR-CLIP	26701625
MIRT760586	hsa-miR-92a-2-5p	PAR-CLIP	26701625

Transcription factors

Transcription factor	Regulation	Reference
PTTG1	Activation	22081074
STAT6	Activation	19857574

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0003924	Function	GTPase activity	EXP	18829532
GO:0003924	Function	GTPase activity	IBA	21873635
GO:0003924	Function	GTPase activity	IDA	19734146, 19787194, 26529257, 27917469
GO:0003924	Function	GTPase activity	TAS	10436159
GO:0005515	Function	Protein binding	IPI	9214622, 10051605, 10066731, 10489445, 11067852, 11335720, 11889037, 11927263, 12006984, 12879077, 14660612, 15364580, 15530360, 15644318, 16189514, 17115030, 18218625, 18256687, 19470470, 19887681, 19944695, 20195357, 20300064, 20348415, 20711218, 20974804, 21029865, 21281639, 2170
GO:0005525	Function	GTP binding	IBA	21873635
GO:0005525	Function	GTP binding	IDA	12777804, 15601624
GO:0005768	Component	Endosome	IMP	19887681
GO:0005789	Component	Endoplasmic reticulum membrane	TAS
GO:0005829	Component	Cytosol	IDA	1328215
GO:0005829	Component	Cytosol	TAS
GO:0005856	Component	Cytoskeleton	IBA	21873635
GO:0005886	Component	Plasma membrane	IBA	21873635
GO:0005886	Component	Plasma membrane	TAS
GO:0005925	Component	Focal adhesion	HDA	21423176
GO:0005938	Component	Cell cortex	IBA	21873635
GO:0005938	Component	Cell cortex	IDA	16103226
GO:0007015	Process	Actin filament organization	IBA	21873635
GO:0007163	Process	Establishment or maintenance of cell polarity	IBA	21873635
GO:0007179	Process	Transforming growth factor beta receptor signaling pathway	TAS
GO:0007186	Process	G protein-coupled receptor signaling pathway	TAS
GO:0007266	Process	Rho protein signal transduction	IDA	26529257
GO:0007266	Process	Rho protein signal transduction	IMP	23241886, 31570889
GO:0007266	Process	Rho protein signal transduction	TAS	10436159
GO:0008360	Process	Regulation of cell shape	IBA	21873635
GO:0010812	Process	Negative regulation of cell-substrate adhesion	ISS
GO:0016032	Process	Viral process	IEA
GO:0016477	Process	Cell migration	IBA	21873635
GO:0016477	Process	Cell migration	IDA	26529257
GO:0016477	Process	Cell migration	IMP	19782033
GO:0016579	Process	Protein deubiquitination	TAS
GO:0017022	Function	Myosin binding	IPI	15644318
GO:0019901	Function	Protein kinase binding	IBA	21873635
GO:0021762	Process	Substantia nigra development	HEP	22926577
GO:0030027	Component	Lamellipodium	ISS
GO:0030036	Process	Actin cytoskeleton organization	TAS	10436159
GO:0030054	Component	Cell junction	TAS
GO:0030334	Process	Regulation of cell migration	IMP	19934221
GO:0030496	Component	Midbody	IEA
GO:0030667	Component	Secretory granule membrane	TAS
GO:0030865	Process	Cortical cytoskeleton organization	IBA	21873635
GO:0031122	Process	Cytoplasmic microtubule organization	IMP	31570889
GO:0031234	Component	Extrinsic component of cytoplasmic side of plasma membrane	IDA	1328215
GO:0031410	Component	Cytoplasmic vesicle	IBA	21873635
GO:0031532	Process	Actin cytoskeleton reorganization	IMP	19782033
GO:0031982	Component	Vesicle	IDA	19887681
GO:0032154	Component	Cleavage furrow	IDA	16103226
GO:0032467	Process	Positive regulation of cytokinesis	IMP	16103226, 17115030
GO:0032956	Process	Regulation of actin cytoskeleton organization	IBA	21873635
GO:0032956	Process	Regulation of actin cytoskeleton organization	IDA	25911094
GO:0033688	Process	Regulation of osteoblast proliferation	ISS
GO:0034329	Process	Cell junction assembly	IMP	22891260
GO:0034446	Process	Substrate adhesion-dependent cell spreading	IMP	31570889
GO:0035385	Process	Roundabout signaling pathway	IDA	26529257
GO:0036089	Process	Cleavage furrow formation	IDA	16103226
GO:0038027	Process	Apolipoprotein A-I-mediated signaling pathway	IMP	23726972
GO:0042995	Component	Cell projection	IBA	21873635
GO:0043123	Process	Positive regulation of I-kappaB kinase/NF-kappaB signaling	IEP	12761501
GO:0043149	Process	Stress fiber assembly	IBA	21873635
GO:0043149	Process	Stress fiber assembly	IMP	19782033, 31570889
GO:0043197	Component	Dendritic spine	IBA	21873635
GO:0043197	Component	Dendritic spine	IDA	24352656
GO:0043231	Component	Intracellular membrane-bounded organelle	IBA	21873635
GO:0043296	Component	Apical junction complex	IDA	20974804
GO:0043297	Process	Apical junction assembly	IMP	20974804
GO:0043312	Process	Neutrophil degranulation	TAS
GO:0043542	Process	Endothelial cell migration	IGI	20208559
GO:0043931	Process	Ossification involved in bone maturation	ISS
GO:0044319	Process	Wound healing, spreading of cells	ISS
GO:0045198	Process	Establishment of epithelial cell apical/basal polarity	IMP	22891260
GO:0045666	Process	Positive regulation of neuron differentiation	IMP	17488780
GO:0045792	Process	Negative regulation of cell size	IMP	8625410
GO:0048010	Process	Vascular endothelial growth factor receptor signaling pathway	TAS
GO:0048013	Process	Ephrin receptor signaling pathway	TAS
GO:0048015	Process	Phosphatidylinositol-mediated signaling	TAS
GO:0050771	Process	Negative regulation of axonogenesis	TAS
GO:0050772	Process	Positive regulation of axonogenesis	TAS
GO:0050919	Process	Negative chemotaxis	IMP	23726972
GO:0051056	Process	Regulation of small GTPase mediated signal transduction	TAS
GO:0051496	Process	Positive regulation of stress fiber assembly	IDA	15467718
GO:0051496	Process	Positive regulation of stress fiber assembly	IMP	8625410
GO:0051893	Process	Regulation of focal adhesion assembly	TAS	18981818
GO:0060071	Process	Wnt signaling pathway, planar cell polarity pathway	NAS	24431302
GO:0060071	Process	Wnt signaling pathway, planar cell polarity pathway	TAS
GO:0060193	Process	Positive regulation of lipase activity	IDA	19887681
GO:0060193	Process	Positive regulation of lipase activity	IMP	22740689
GO:0061383	Process	Trabecula morphogenesis	ISS
GO:0070062	Component	Extracellular exosome	HDA	19056867, 20458337
GO:0071222	Process	Cellular response to lipopolysaccharide	IDA	19734146
GO:0071345	Process	Cellular response to cytokine stimulus	IMP	25515214
GO:0071902	Process	Positive regulation of protein serine/threonine kinase activity	IDA	8617235
GO:0071944	Component	Cell periphery	IMP	25911094
GO:0090051	Process	Negative regulation of cell migration involved in sprouting angiogenesis	IGI	20208559
GO:0090307	Process	Mitotic spindle assembly	IMP	19635168
GO:0097498	Process	Endothelial tube lumen extension	IGI	20208559
GO:0098794	Component	Postsynapse	IDA	24352656
GO:0098794	Component	Postsynapse	IMP	21423166, 24352656
GO:0098978	Component	Glutamatergic synapse	IDA	24352656
GO:0098978	Component	Glutamatergic synapse	IMP	21423166, 24352656
GO:0101003	Component	Ficolin-1-rich granule membrane	TAS
GO:1901224	Process	Positive regulation of NIK/NF-kappaB signaling	IMP	25515214
GO:1901224	Process	Positive regulation of NIK/NF-kappaB signaling	NAS	12761501
GO:1902766	Process	Skeletal muscle satellite cell migration	ISS
GO:1903673	Process	Mitotic cleavage furrow formation	IMP	16103226
GO:1904996	Process	Positive regulation of leukocyte adhesion to vascular endothelial cell	IMP	25515214
GO:1905274	Process	Regulation of modification of postsynaptic actin cytoskeleton	IMP	21423166
GO:1990869	Process	Cellular response to chemokine	IMP	23241886
GO:2000145	Process	Regulation of cell motility	TAS
GO:2000406	Process	Positive regulation of T cell migration	IMP	23241886

Other IDs

• MIM: 165390
• HGNC: 667
• e!Ensembl: ENSG00000067560

Protein

• UniProt ID: P61586
• Protein name: Transforming protein RhoA (EC 3.6.5.2) (Rho cDNA clone 12) (h12)
• Protein function: Small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. Mainly associated with cytoskeleton organization, in active state binds to a variety of effector proteins to regulate cellular responses such as cytoskeletal dynamics, cell migration and cell cycle. Regulates a signal transduction pathway linking plasma membrane receptors to the assembly of focal adhesions and actin stress fibers (PubMed:8910519, PubMed:9121475, PubMed:31570889). Involved in a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis (PubMed:16236794, PubMed:12900402). Plays an essential role in cleavage furrow formation. Required for the apical junction formation of keratinocyte cell-cell adhesion (PubMed:20974804, PubMed:23940119). Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly (PubMed:19934221). 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 (PubMed:20937854). Regulates KCNA2 potassium channel activity by reducing its location at the cell surface in response to CHRM1 activation; promotes KCNA2 endocytosis (PubMed:9635436, PubMed:19403695). Acts as an allosteric activator of guanine nucleotide exchange factor ECT2 by binding in its activated GTP-bound form to the PH domain of ECT2 which stimulates the release of PH inhibition and promotes the binding of substrate RHOA to the ECT2 catalytic center (PubMed:31888991). May be an activator of PLCE1 (PubMed:16103226). In neurons, involved in the inhibiton of the initial spine growth. Upon activation by CaMKII, modulates dendritic spine structural plasticity by relaying CaMKII transient activation to synapse-specific, long-term signaling (By similarity). Acts as a regulator of platelet alpha-granule release during activation and aggregation of platelets (By similarity). ; (Microbial infection) Serves as a target for the yopT cysteine peptidase from Yersinia pestis, vector of the plague.
• PDB: 1A2B, 1CC0, 1CXZ, 1DPF, 1FTN, 1KMQ, 1LB1, 1OW3, 1S1C, 1TX4, 1X86, 1XCG, 2RGN, 3KZ1, 3LW8, 3LWN, 3LXR, 3MSX, 3T06, 4D0N, 4XH9, 4XOI, 4XSG, 4XSH, 5A0F, 5BWM, 5C2K, 5C4M, 5EZ6, 5FR1, 5FR2, 5HPY, 5IRC, 5JCP, 5JHG, 5JHH, 5M6X, 5M70, 5ZHX, 6BC0, 6BCA, 6BCB, 6KX2, 6KX3, 6R3V, 6V6M, 6V6U, 6V6V
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00071	Ras	7 → 180	Ras family	Domain

• Sequence:

  MAAIRKKLVIVGDGACGKTCLLIVFSKDQFPEVYVPTVFENYVADIEVDGKQVELALWDT
  AGQEDYDRLRPLSYPDTDVILMCFSIDSPDSLENIPEKWTPEVKHFCPNVPIILVGNKKD
  LRNDEHTRRELAKMKQEPVKPEEGRDMANRIGAFGYMECSAKTKDGVREVFEMATRAALQ
  ARRGKKKSGCLVL

• Sequence length: 193