ARHGEF12 (Rho guanine nucleotide exchange factor 12)

Gene

• Entrez ID: 23365
• Gene name: Rho guanine nucleotide exchange factor 12
• Gene symbol: ARHGEF12
• Synonyms: LARG, PRO2792
• Chromosome: 11
• Chromosome location: 11q23.3
• Summary: Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli working through G protein-coupled receptors. The encoded protein may form a complex with G proteins and stimulate Rho-dependent signals. This protein has been observed to form a myeloid/lymphoid fusion partner in acute myeloid leukemia. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT030993	hsa-miR-21-5p	Microarray	18591254
MIRT036542	hsa-miR-1225-3p	CLASH	23622248
MIRT047997	hsa-miR-30c-5p	CLASH	23622248
MIRT705575	hsa-miR-6077	HITS-CLIP	23313552
MIRT705576	hsa-miR-7-5p	HITS-CLIP	23313552
MIRT705577	hsa-miR-1250-3p	HITS-CLIP	23313552
MIRT705578	hsa-miR-660-5p	HITS-CLIP	23313552
MIRT705579	hsa-miR-362-3p	HITS-CLIP	23313552
MIRT705580	hsa-miR-329-3p	HITS-CLIP	23313552

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001664	Function	G protein-coupled receptor binding	IDA	15755723
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	IEA
GO:0005096	Function	GTPase activator activity	IEA
GO:0005515	Function	Protein binding	IPI	11724822, 15364580, 15755723, 20300064, 20844236
GO:0005737	Component	Cytoplasm	IDA	15755723
GO:0005829	Component	Cytosol	TAS
GO:0007186	Process	G protein-coupled receptor signaling pathway	IDA	15755723
GO:0007186	Process	G protein-coupled receptor signaling pathway	TAS
GO:0007266	Process	Rho protein signal transduction	IEA
GO:0016020	Component	Membrane	IEA
GO:0043065	Process	Positive regulation of apoptotic process	TAS
GO:0043547	Process	Positive regulation of GTPase activity	IEA
GO:0051056	Process	Regulation of small GTPase mediated signal transduction	TAS
GO:0070062	Component	Extracellular exosome	HDA	19056867

Other IDs

• MIM: 604763
• HGNC: 14193
• e!Ensembl: ENSG00000196914

Protein

• UniProt ID: Q9NZN5
• Protein name: Rho guanine nucleotide exchange factor 12 (Leukemia-associated RhoGEF)
• Protein function: May play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase and may act as GTPase-activating protein (GAP) for GNA12 and GNA13.
• PDB: 1TXD, 1X86, 2OMJ, 2OS6
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00595	PDZ	73 → 145	PDZ domain	Domain
  PF09128	RGS-like	368 → 558	Regulator of G protein signalling-like domain	Domain
  PF00621	RhoGEF	791 → 975	RhoGEF domain	Domain
  PF17838	PH_16	1004 → 1132	PH domain	Domain

• Sequence:

  MSGTQSTITDRFPLKKPIRHGSILNRESPTDKKQKVERIASHDFDPTDSSSKKTKSSSEE
  SRSEIYGLVQRCVIIQKDDNGFGLTVSGDNPVFVQSVKEDGAAMRAGVQTGDRIIKVNGT
  LVTHSNHLEVVKLIKSGSYVALTVQGRPPGSPQIPLADSEVEPSVIGHMSPIMTSPHSPG
  ASGNMERITSPVLMGEENNVVHNQKVEILRKMLQKEQERLQLLQEDYNRTPAQRLLKEIQ
  EAKKHIPQLQEQLSKATGSAQDGAVVTPSRPLGDTLTVSEAETDPGDVLGRTDCSSGDAS
  RPSSDNADSPKSGPKERIYLEENPEKSETIQDTDTQSLVGSPSTRIAPHIIGAEDDDFGT
  EHEQINGQCSCFQSIELLKSRPAHLAVFLHHVVSQFDPATLLCYLYSDLYKHTNSKETRR
  IFLEFHQFFLDRSAHLKVSVPDEMSADLEKRRPELIPEDLHRHYIQTMQERVHPEVQRHL
  EDFRQKRSMGLTLAESELTKLDAERDKDRLTLEKERTCAEQIVAKIEEVLMTAQAVEEDK
  SSTMQYVILMYMKHLGVKVKEPRNLEHKRGRIGFLPKIKQSMKKDKEGEEKGKRRGFPSI
  LGPPRRPSRHDNSAIGRAMELQKARHPKHLSTPSSVSPEPQDSAKLRQSGLANEGTDAGY
  LPANSMSSVASGASFSQEGGKENDTGSKQVGETSAPGDTLDGTPRTLNTVFDFPPPPLDQ
  VQEEECEVERVTEHGTPKPFRKFDSVAFGESQSEDEQFENDLETDPPNWQQLVSREVLLG
  LKPCEIKRQEVINELFYTERAHVRTLKVLDQVFYQRVSREGILSPSELRKIFSNLEDILQ
  LHIGLNEQMKAVRKRNETSVIDQIGEDLLTWFSGPGEEKLKHAAATFCSNQPFALEMIKS
  RQKKDSRFQTFVQDAESNPLCRRLQLKDIIPTQMQRLTKYPLLLDNIAKYTEWPTEREKV
  KKAADHCRQILNYVNQAVKEAENKQRLEDYQRRLDTSSLKLSEYPNVEELRNLDLTKRKM
  IHEGPLVWKVNRDKTIDLYTLLLEDILVLLQKQDDRLVLRCHSKILASTADSKHTFSPVI
  KLSTVLVRQVATDNKALFVISMSDNGAQIYELVAQTVSEKTVWQDLICRMAASVKEQSTK
  PIPLPQSTPGEGDNDEEDPSKLKEEQHGISVTGLQSPDRDLGLESTLISSKPQSHSLSTS
  GKSEVRDLFVAERQFAKEQHTDGTLKEVGEDYQIAIPDSHLPVSEERWALDALRNLGLLK
  QLLVQQLGLTEKSVQEDWQHFPRYRTASQGPQTDSVIQNSENIKAYHSGEGHMPFRTGTG
  DIATCYSPRTSTESFAPRDSVGLAPQDSQASNILVMDHMIMTPEMPTMEPEGGLDDSGEH
  FFDAREAHSDENPSEGDGAVNKEEKDVNLRISGNYLILDGYDPVQESSTDEEVASSLTLQ
  PMTGIPAVESTHQQQHSPQNTHSDGAISPFTPEFLVQQRWGAMEYSCFEIQSPSSCADSQ
  SQIMEYIHKIEADLEHLKKVEESYTILCQRLAGSALTDKHSDKS

• Sequence length: 1544

Pathways

KEGG:

Vascular smooth muscle contraction
Axon guidance
Platelet activation
C-type lectin receptor signaling pathway
Regulation of actin cytoskeleton
Pathogenic Escherichia coli infection
Yersinia infection
Tuberculosis
Human cytomegalovirus infection
Pathways in cancer
Proteoglycans in cancer

Reactome:

NRAGE signals death through JNK
Rho GTPase cycle
G alpha (12/13) signalling events
Sema4D induced cell migration and growth-cone collapse

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Coronary artery disease	Coronary Artery Disease	rs137852988, rs121918313, rs-1, rs121918529, rs121918531, rs137852340, rs405509, rs1555800701, rs1215189537	30104761
Glaucoma	Glaucoma, Glaucoma, Open-Angle	rs121918355, rs1566660365, rs1566635134, rs121918356, rs1566634475, rs28936700, rs55771538, rs28936701, rs104893622, rs55989760, rs72549387, rs104893628, rs2125316417, rs104893629, rs74315328, rs121909193, rs74315330, rs74315329, rs74315332, rs74315334, rs74315336, rs74315338, rs74315341, rs121909194, rs74315331, rs1558603396, rs387907175, rs587778873, rs587778875, rs104894979, rs137854895, rs766425037, rs72549380, rs148542782, rs541217363, rs753021890, rs771076928, rs56010818, rs777678299, rs1446110883, rs1573274915, rs1587545234, rs751768343, rs944452644	30054594, 29891935