Arhgef12 Rho guanine nucleotide exchange factor 12 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Arhgef12provided by MGI
Official Full Name: Rho guanine nucleotide exchange factor 12provided by MGI
Primary source: MGI:MGI:1916882
See related: Ensembl:ENSMUSG00000059495 AllianceGenome:MGI:1916882
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Larg; mKIAA0382; 2310014B11Rik
Summary: Predicted to enable G protein-coupled receptor binding activity. Involved in multicellular organism aging and regulation of blood pressure. Predicted to be located in cytoplasm. Is expressed in several structures, including alimentary system; genitourinary system; nervous system; respiratory system; and skin. Orthologous to human ARHGEF12 (Rho guanine nucleotide exchange factor 12). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Ubiquitous expression in lung adult (RPKM 23.6), kidney adult (RPKM 17.6) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 9 A5.1; 9 24.14 cM

Exon count:: 42

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	9	NC_000075.7 (42875138..43017069, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	9	NC_000075.6 (42963842..43105718, complement)

Chromosome 9 - NC_000075.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Identification of Arhgef12 and Prkci as genetic modifiers of retinal dysplasia in the Crb1rd8 mouse model.
Title: Identification of Arhgef12 and Prkci as genetic modifiers of retinal dysplasia in the Crb1rd8 mouse model.
ARHGEF12 regulates erythropoiesis and is involved in erythroid regeneration after chemotherapy in acute lymphoblastic leukemia patients.
Title: ARHGEF12 regulates erythropoiesis and is involved in erythroid regeneration after chemotherapy in acute lymphoblastic leukemia patients.
Here, the authors show that small arteries from mice with smooth muscle-specific loss of G12/G13 or the Rho guanine nucleotide exchange factor ARHGEF12 have lost myogenic vasoconstriction.
Title: Myogenic vasoconstriction requires G(12)/G(13) and LARG to maintain local and systemic vascular resistance.
mechanical activation of RhoA in mesenchymal progenitors is dependent on LARG, while ARHGAP18 limits RhoA delineated cytoskeletal structure in static cultures
Title: LARG GEF and ARHGAP18 orchestrate RhoA activity to control mesenchymal stem cell lineage.
We studied the function of LARG in murine and human megakaryocytes and platelets with Larg knockout (KO), shRNA-mediated knockdown and small molecule-mediated inhibition. We found that LARG is important for human, but not murine, megakaryocyte maturation.
Title: Leukaemia-associated Rho guanine nucleotide exchange factor (LARG) plays an agonist specific role in platelet function through RhoA activation.
Data found an inverse relationship between the expression of miR-660 and ARHGEF12 in both gain- and loss-of-function studies: overexpression of miR-660 declined the mRNA and protein expressions of ARHGEF12 in C2C12 cells differentiation; however, knockdown of miR-660 had completely opposite results.
Title: Expression Profiles Analysis and Functional Characterization of MicroRNA-660 in Skeletal Muscle Differentiation.
This study demonstrated an almost 100-fold higher agonist sensitivity of the Galpha13 LARG interaction compared to the Galpha13 activation in the absence of LARG.
Title: Potentiation of receptor responses induced by prolonged binding of Gα(13) and leukemia-associated RhoGEF.
LARG may play a housekeeper role in regulating constitutive RhoA activity. Its role in regulating platelet function may principally be through RhoA-independent pathways.
Title: Leukemia-associated Rho guanine-nucleotide exchange factor is not critical for RhoA regulation, yet is important for platelet activation and thrombosis in mice.
The increase in LARG expression was accompanied by a significant increase in ACh-stimulated Rho kinase and ZIP kinase activities, and sustained muscle contraction
Title: Jun kinase-induced overexpression of leukemia-associated Rho GEF (LARG) mediates sustained hypercontraction of longitudinal smooth muscle in inflammation.
Agonist-induced Ca2+ sensitization in smooth muscle: redundancy of Rho guanine nucleotide exchange factors (RhoGEFs) and response kinetics, a caged compound study.
Title: Agonist-induced Ca2+ sensitization in smooth muscle: redundancy of Rho guanine nucleotide exchange factors (RhoGEFs) and response kinetics, a caged compound study.

Submit: New GeneRIF Correction See all GeneRIFs (23)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Chemically induced (ENU) (1) 1 citation
Endonuclease-mediated (1)
Targeted (5) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:236103

RH136306 (e-PCR)
- UniSTS:210298

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables G protein-coupled receptor binding	IBA Inferred from Biological aspect of Ancestor more info
enables G protein-coupled receptor binding	ISO Inferred from Sequence Orthology more info
enables GTPase activator activity	IEA Inferred from Electronic Annotation more info
enables guanyl-nucleotide exchange factor activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in G protein-coupled receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within G protein-coupled receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in Rho protein signal transduction	IEA Inferred from Electronic Annotation more info
involved_in intracellular signal transduction	IEA Inferred from Electronic Annotation more info
involved_in regulation of blood pressure	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: rho guanine nucleotide exchange factor 12

Names: Rho guanine nucleotide exchange factor (GEF) 12; leukemia-associated Rho guanine-nucleotide exchange factor; leukemia-associated RhoGEF

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001359232.1 → NP_001346161.1 rho guanine nucleotide exchange factor 12 isoform 2

Status: VALIDATED

Description

Transcript Variant: This variant (2) lacks a three-nucleotide segment in the central coding region, compared to variant 1. The encoded protein (isoform 2) is shorter, compared to isoform 1.

Source sequence(s)

AC110169, AC160123, AC173346

Consensus CDS

CCDS90543.1

UniProtKB/Swiss-Prot

E9QPW9, Q80U18, Q8R4H2

Related

ENSMUSP00000072547.7, ENSMUST00000072767.7

Conserved Domains (4) summary

cd08754
Location:349 → 570

RGS_LARG; Regulator of G protein signaling (RGS) domain found in the leukemia-associated Rho guanine nucleotide exchange factor (RhoGEF) protein (LARG)

smart00325
Location:791 → 976

RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases

cd00992
Location:71 → 145

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

cd13390
Location:995 → 1132

PH_LARG; Leukemia-associated Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain
NM_027144.2 → NP_081420.2 rho guanine nucleotide exchange factor 12 isoform 1

See identical proteins and their annotated locations for NP_081420.2

Status: VALIDATED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

AC110169, AC160123

Consensus CDS

CCDS40595.1

UniProtKB/TrEMBL

F8VQN6

Related

ENSMUSP00000126598.2, ENSMUST00000165665.9

Conserved Domains (4) summary

cd08754
Location:350 → 571

RGS_LARG; Regulator of G protein signaling (RGS) domain found in the leukemia-associated Rho guanine nucleotide exchange factor (RhoGEF) protein (LARG)

cd00992
Location:71 → 145

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

cd13390
Location:996 → 1133

PH_LARG; Leukemia-associated Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain

pfam00621
Location:792 → 977

RhoGEF; RhoGEF domain

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000075.7 Reference GRCm39 C57BL/6J

Range

42875138..43017069 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_036155253.1 → XP_036011146.1 rho guanine nucleotide exchange factor 12 isoform X4

Conserved Domains (4) summary

cd08754
Location:323 → 544

RGS_LARG; Regulator of G protein signaling (RGS) domain found in the leukemia-associated Rho guanine nucleotide exchange factor (RhoGEF) protein (LARG)

smart00325
Location:765 → 950

RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases

cd00992
Location:44 → 118

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

cd13390
Location:969 → 1106

PH_LARG; Leukemia-associated Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain
XM_017313565.3 → XP_017169054.1 rho guanine nucleotide exchange factor 12 isoform X1

Conserved Domains (4) summary

cd08754
Location:342 → 563

RGS_LARG; Regulator of G protein signaling (RGS) domain found in the leukemia-associated Rho guanine nucleotide exchange factor (RhoGEF) protein (LARG)

smart00325
Location:784 → 969

RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases

cd00992
Location:63 → 137

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

cd13390
Location:988 → 1125

PH_LARG; Leukemia-associated Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain
XM_011242597.3 → XP_011240899.1 rho guanine nucleotide exchange factor 12 isoform X3

Conserved Domains (4) summary

cd08754
Location:330 → 551

RGS_LARG; Regulator of G protein signaling (RGS) domain found in the leukemia-associated Rho guanine nucleotide exchange factor (RhoGEF) protein (LARG)

smart00325
Location:772 → 957

RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases

cd00992
Location:52 → 126

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

cd13390
Location:976 → 1113

PH_LARG; Leukemia-associated Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain
XM_017313566.3 → XP_017169055.1 rho guanine nucleotide exchange factor 12 isoform X2

Conserved Domains (4) summary

cd08754
Location:331 → 552

RGS_LARG; Regulator of G protein signaling (RGS) domain found in the leukemia-associated Rho guanine nucleotide exchange factor (RhoGEF) protein (LARG)

smart00325
Location:773 → 958

RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases

cd00992
Location:52 → 126

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

cd13390
Location:977 → 1114

PH_LARG; Leukemia-associated Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain
XM_036155254.1 → XP_036011147.1 rho guanine nucleotide exchange factor 12 isoform X7

Conserved Domains (3) summary

cd08754
Location:182 → 403

RGS_LARG; Regulator of G protein signaling (RGS) domain found in the leukemia-associated Rho guanine nucleotide exchange factor (RhoGEF) protein (LARG)

smart00325
Location:624 → 809

RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases

cd13390
Location:828 → 965

PH_LARG; Leukemia-associated Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain
XM_030244573.2 → XP_030100433.1 rho guanine nucleotide exchange factor 12 isoform X6

Conserved Domains (4) summary

cd08754
Location:246 → 467

RGS_LARG; Regulator of G protein signaling (RGS) domain found in the leukemia-associated Rho guanine nucleotide exchange factor (RhoGEF) protein (LARG)

smart00325
Location:688 → 873

RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases

cd00992
Location:2 → 42

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

cd13390
Location:892 → 1029

PH_LARG; Leukemia-associated Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain
XM_017313567.3 → XP_017169056.1 rho guanine nucleotide exchange factor 12 isoform X5

Conserved Domains (4) summary

cd08754
Location:247 → 468

RGS_LARG; Regulator of G protein signaling (RGS) domain found in the leukemia-associated Rho guanine nucleotide exchange factor (RhoGEF) protein (LARG)

smart00325
Location:689 → 874

RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases

cd00992
Location:2 → 42

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

cd13390
Location:893 → 1030

PH_LARG; Leukemia-associated Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain
XM_011242598.4 → XP_011240900.1 rho guanine nucleotide exchange factor 12 isoform X7

Conserved Domains (3) summary

cd08754
Location:182 → 403

RGS_LARG; Regulator of G protein signaling (RGS) domain found in the leukemia-associated Rho guanine nucleotide exchange factor (RhoGEF) protein (LARG)

smart00325
Location:624 → 809

RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases

cd13390
Location:828 → 965

PH_LARG; Leukemia-associated Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain
XM_030244572.2 → XP_030100432.1 rho guanine nucleotide exchange factor 12 isoform X6

Conserved Domains (4) summary

cd08754
Location:246 → 467

RGS_LARG; Regulator of G protein signaling (RGS) domain found in the leukemia-associated Rho guanine nucleotide exchange factor (RhoGEF) protein (LARG)

smart00325
Location:688 → 873

RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases

cd00992
Location:2 → 42

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

cd13390
Location:892 → 1029

PH_LARG; Leukemia-associated Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain
XM_030244571.2 → XP_030100431.1 rho guanine nucleotide exchange factor 12 isoform X5

Conserved Domains (4) summary

cd08754
Location:247 → 468

RGS_LARG; Regulator of G protein signaling (RGS) domain found in the leukemia-associated Rho guanine nucleotide exchange factor (RhoGEF) protein (LARG)

smart00325
Location:689 → 874

RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases

cd00992
Location:2 → 42

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

cd13390
Location:893 → 1030

PH_LARG; Leukemia-associated Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain