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ARHGEF12 Rho guanine nucleotide exchange factor 12 [ Homo sapiens (human) ]

Gene ID: 23365, updated on 18-Sep-2018

Summary

Official Symbol
ARHGEF12provided by HGNC
Official Full Name
Rho guanine nucleotide exchange factor 12provided by HGNC
Primary source
HGNC:HGNC:14193
See related
Ensembl:ENSG00000196914 MIM:604763; Vega:OTTHUMG00000166143
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
LARG; PRO2792
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]
Expression
Ubiquitous expression in kidney (RPKM 33.3), thyroid (RPKM 28.1) and 25 other tissues See more
Orthologs

Genomic context

See ARHGEF12 in Genome Data Viewer
Location:
11q23.3
Exon count:
43
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 11 NC_000011.10 (120336276..120489936)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (120207264..120360645)

Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105369531 Neighboring gene POU class 2 homeobox 3 Neighboring gene transmembrane protein 136 Neighboring gene uncharacterized LOC107984400 Neighboring gene glutamate ionotropic receptor kainate type subunit 4 Neighboring gene elongin C pseudogene 22

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Jun 15 11:32:44 2016

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

HIV-1 interactions

Replication interactions

Interaction Pubs
Knockdown of Rho guanine nucleotide exchange factor 12 (ARHGEF12) by siRNA inhibits HIV-1 replication in HeLa-derived TZM-bl cells PubMed

Protein interactions

Protein Gene Interaction Pubs
retropepsin gag-pol HIV-1 PR is identified to have a physical interaction with Rho guanine nucleotide exchange factor (GEF) 12 (ARHGEF12) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

  • Axon guidance, organism-specific biosystem (from KEGG)
    Axon guidance, organism-specific biosystemAxon guidance represents a key stage in the formation of neuronal network. Axons are guided by a variety of guidance factors, such as netrins, ephrins, Slits, and semaphorins. These guidance cues are...
  • Axon guidance, conserved biosystem (from KEGG)
    Axon guidance, conserved biosystemAxon guidance represents a key stage in the formation of neuronal network. Axons are guided by a variety of guidance factors, such as netrins, ephrins, Slits, and semaphorins. These guidance cues are...
  • Axon guidance, organism-specific biosystem (from REACTOME)
    Axon guidance, organism-specific biosystemAxon guidance / axon pathfinding is the process by which neurons send out axons to reach the correct targets. Growing axons have a highly motile structure at the growing tip called the growth cone, w...
  • Cell death signalling via NRAGE, NRIF and NADE, organism-specific biosystem (from REACTOME)
    Cell death signalling via NRAGE, NRIF and NADE, organism-specific biosystemp75NTR is a key regulator of neuronal apoptosis, both during development and after injury. Apoptosis is triggered by binding of either mature neurotrophin or proneurotrophin (proNGF, proBDNF). ProNG...
  • Developmental Biology, organism-specific biosystem (from REACTOME)
    Developmental Biology, organism-specific biosystemAs a first step towards capturing the array of processes by which a fertilized egg gives rise to the diverse tissues of the body, examples of three kinds of processes have been annotated. These are a...
  • G alpha (12/13) signalling events, organism-specific biosystem (from REACTOME)
    G alpha (12/13) signalling events, organism-specific biosystemThe G12/13 family is probably the least well characterized subtype, partly because G12/13 coupling is difficult to determine when compared with the other subtypes which predominantly rely on assay te...
  • GPCR downstream signaling, organism-specific biosystem (from REACTOME)
    GPCR downstream signaling, organism-specific biosystemG protein-coupled receptors (GPCRs) are classically defined as the receptor, G-protein and downstream effectors, the alpha subunit of the G-protein being the primary signaling molecule. However, it h...
  • NRAGE signals death through JNK, organism-specific biosystem (from REACTOME)
    NRAGE signals death through JNK, organism-specific biosystemOnce bound by either NGF or proNGF, p75NTR interacts with NRAGE, thus leading to phosphorylation and activation of JUN Kinase (JNK). JNK controls apoptosis in two ways: it induces transcription of pr...
  • Pathways in cancer, organism-specific biosystem (from KEGG)
    Pathways in cancer, organism-specific biosystem
    Pathways in cancer
  • Platelet activation, organism-specific biosystem (from KEGG)
    Platelet activation, organism-specific biosystemPlatelets play a key and beneficial role for primary hemostasis on the disruption of the integrity of vessel wall. Platelet adhesion and activation at sites of vascular wall injury is initiated by ad...
  • Proteoglycans in cancer, organism-specific biosystem (from KEGG)
    Proteoglycans in cancer, organism-specific biosystemMany proteoglycans (PGs) in the tumor microenvironment have been shown to be key macromolecules that contribute to biology of various types of cancer including proliferation, adhesion, angiogenesis a...
  • Proteoglycans in cancer, conserved biosystem (from KEGG)
    Proteoglycans in cancer, conserved biosystemMany proteoglycans (PGs) in the tumor microenvironment have been shown to be key macromolecules that contribute to biology of various types of cancer including proliferation, adhesion, angiogenesis a...
  • Regulation of RhoA activity, organism-specific biosystem (from Pathway Interaction Database)
    Regulation of RhoA activity, organism-specific biosystem
    Regulation of RhoA activity
  • Regulation of actin cytoskeleton, organism-specific biosystem (from KEGG)
    Regulation of actin cytoskeleton, organism-specific biosystem
    Regulation of actin cytoskeleton
  • Regulation of actin cytoskeleton, conserved biosystem (from KEGG)
    Regulation of actin cytoskeleton, conserved biosystem
    Regulation of actin cytoskeleton
  • Rho GTPase cycle, organism-specific biosystem (from REACTOME)
    Rho GTPase cycle, organism-specific biosystemThe cycling of Rho GTPases is tightly controlled by three classes of protein. These are (1) guanine nucleotide dissociation inhibitors or GDIs, which maintain Rho proteins in an inactive state in the...
  • Sema4D in semaphorin signaling, organism-specific biosystem (from REACTOME)
    Sema4D in semaphorin signaling, organism-specific biosystemSemaphorin 4D (Sema 4D/CD100) is an axon guidance molecule with two disulfide-linked 150-kDa subunits. SEMA4D is structurally defined by a conserved 500-amino acid extracellular domain with 16 cyste...
  • Sema4D induced cell migration and growth-cone collapse, organism-specific biosystem (from REACTOME)
    Sema4D induced cell migration and growth-cone collapse, organism-specific biosystemSema4D-mediated attraction of endothelial cells requires Rho, but not R-Ras, signaling. Sema4D-mediated plexinB1 activation activates Rho and its downstream effector ROCK. ROCK then phosphorylates ML...
  • Semaphorin interactions, organism-specific biosystem (from REACTOME)
    Semaphorin interactions, organism-specific biosystemSemaphorins are a large family of cell surface and secreted guidance molecules divided into eight classes on the basis of their structures. They all have an N-terminal conserved sema domain. Semaphor...
  • Signal Transduction, organism-specific biosystem (from REACTOME)
    Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
  • Signaling by GPCR, organism-specific biosystem (from REACTOME)
    Signaling by GPCR, organism-specific biosystemG protein-coupled receptors (GPCRs; 7TM receptors; seven transmembrane domain receptors; heptahelical receptors; G protein-linked receptors [GPLR]) are the largest family of transmembrane receptors i...
  • Signaling by Rho GTPases, organism-specific biosystem (from REACTOME)
    Signaling by Rho GTPases, organism-specific biosystemThe Rho family of small guanine nucleotide binding proteins is one of five generally recognized branches of the Ras superfamily. Like most Ras superfamily members, typical Rho proteins function as bi...
  • Signalling by NGF, organism-specific biosystem (from REACTOME)
    Signalling by NGF, organism-specific biosystemNeurotrophins (NGF, BDNF, NT-3, NT-4/5) play pivotal roles in survival, differentiation, and plasticity of neurons in the peripheral and central nervous system. They are produced, and secreted in mi...
  • Tuberculosis, organism-specific biosystem (from KEGG)
    Tuberculosis, organism-specific biosystemTuberculosis, or TB, is an infectious disease caused by Mycobacterium tuberculosis. One third of the world's population is thought to be infected with TB. About 90% of those infected result in latent...
  • Tuberculosis, conserved biosystem (from KEGG)
    Tuberculosis, conserved biosystemTuberculosis, or TB, is an infectious disease caused by Mycobacterium tuberculosis. One third of the world's population is thought to be infected with TB. About 90% of those infected result in latent...
  • Vascular smooth muscle contraction, organism-specific biosystem (from KEGG)
    Vascular smooth muscle contraction, organism-specific biosystemThe vascular smooth muscle cell (VSMC) is a highly specialized cell whose principal function is contraction. On contraction, VSMCs shorten, thereby decreasing the diameter of a blood vessel to regula...
  • Vascular smooth muscle contraction, conserved biosystem (from KEGG)
    Vascular smooth muscle contraction, conserved biosystemThe vascular smooth muscle cell (VSMC) is a highly specialized cell whose principal function is contraction. On contraction, VSMCs shorten, thereby decreasing the diameter of a blood vessel to regula...
  • p75 NTR receptor-mediated signalling, organism-specific biosystem (from REACTOME)
    p75 NTR receptor-mediated signalling, organism-specific biosystemBesides signalling through the tyrosine kinase receptors TRK A, B, and C, the mature neurotrophins NGF, BDNF, and NT3/4 signal through their common receptor p75NTR. NGF binding to p75NTR activates a ...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • KIAA0382, DKFZp686O2372

Gene Ontology Provided by GOA

Function Evidence Code Pubs
G protein-coupled receptor binding IDA
Inferred from Direct Assay
more info
PubMed 
GTPase activator activity IEA
Inferred from Electronic Annotation
more info
 
Rho guanyl-nucleotide exchange factor activity TAS
Traceable Author Statement
more info
 
guanyl-nucleotide exchange factor activity TAS
Traceable Author Statement
more info
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
G protein-coupled receptor signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
G protein-coupled receptor signaling pathway TAS
Traceable Author Statement
more info
 
Rho protein signal transduction IEA
Inferred from Electronic Annotation
more info
 
positive regulation of GTPase activity IEA
Inferred from Electronic Annotation
more info
 
positive regulation of apoptotic process TAS
Traceable Author Statement
more info
 
regulation of Rho protein signal transduction IEA
Inferred from Electronic Annotation
more info
 
regulation of small GTPase mediated signal transduction TAS
Traceable Author Statement
more info
 
Component Evidence Code Pubs
cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
cytosol TAS
Traceable Author Statement
more info
 
extracellular exosome HDA PubMed 
membrane IEA
Inferred from Electronic Annotation
more info
 

General protein information

Preferred Names
rho guanine nucleotide exchange factor 12
Names
Rho guanine nucleotide exchange factor (GEF) 12
leukemia-associated RhoGEF
leukemia-associated rho guanine nucleotide exchange factor

NCBI Reference Sequences (RefSeq)

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.

Genomic

  1. NG_027960.1 RefSeqGene

    Range
    5001..158028
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001198665.1NP_001185594.1  rho guanine nucleotide exchange factor 12 isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.
    Source sequence(s)
    AF180681, AK304316, AP000758, BC063117
    Consensus CDS
    CCDS55794.1
    UniProtKB/Swiss-Prot
    Q9NZN5
    UniProtKB/TrEMBL
    B4E2K6
    Related
    ENSP00000349056.3, OTTHUMP00000274700, ENST00000356641.7, OTTHUMT00000473776
    Conserved Domains (4) summary
    cd08754
    Location:330551
    RGS_LARG; Regulator of G protein signaling (RGS) domain found in the leukemia-associated Rho guanine nucleotide exchange factor (RhoGEF) protein (LARG)
    cd00992
    Location:52126
    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:9761113
    PH_LARG; Leukemia-associated Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain
    pfam00621
    Location:772957
    RhoGEF; RhoGEF domain
  2. NM_001301084.1NP_001288013.1  rho guanine nucleotide exchange factor 12 isoform 3

    See identical proteins and their annotated locations for NP_001288013.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) uses an alternate first exon and initiates translation at a downstream AUG compared to variant 1. Thd resulting isoform (3) is shorter at the N-terminus compared to isoform 1.
    Source sequence(s)
    AF180681, AP000659, AP000758, BX647785, DC350360
    Consensus CDS
    CCDS76487.1
    UniProtKB/Swiss-Prot
    Q9NZN5
    UniProtKB/TrEMBL
    E9PMR6
    Related
    ENSP00000432984.1, OTTHUMP00000231994, ENST00000532993.5, OTTHUMT00000388053
    Conserved Domains (4) summary
    cd08754
    Location:246467
    RGS_LARG; Regulator of G protein signaling (RGS) domain found in the leukemia-associated Rho guanine nucleotide exchange factor (RhoGEF) protein (LARG)
    cd00992
    Location:242
    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:8921029
    PH_LARG; Leukemia-associated Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain
    pfam00621
    Location:688873
    RhoGEF; RhoGEF domain
  3. NM_015313.2NP_056128.1  rho guanine nucleotide exchange factor 12 isoform 1

    See identical proteins and their annotated locations for NP_056128.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    AF180681, AK304316, AP000758, BC063117
    Consensus CDS
    CCDS41727.1
    UniProtKB/Swiss-Prot
    Q9NZN5
    UniProtKB/TrEMBL
    B4E2K6
    Related
    ENSP00000380942.2, OTTHUMP00000231993, ENST00000397843.6, OTTHUMT00000388052
    Conserved Domains (4) summary
    cd08754
    Location:349570
    RGS_LARG; Regulator of G protein signaling (RGS) domain found in the leukemia-associated Rho guanine nucleotide exchange factor (RhoGEF) protein (LARG)
    cd00992
    Location:71145
    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:9951132
    PH_LARG; Leukemia-associated Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain
    pfam00621
    Location:791976
    RhoGEF; RhoGEF domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000011.10 Reference GRCh38.p12 Primary Assembly

    Range
    120336276..120489936
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017017420.1XP_016872909.1  rho guanine nucleotide exchange factor 12 isoform X3

  2. XM_011542720.2XP_011541022.1  rho guanine nucleotide exchange factor 12 isoform X1

    See identical proteins and their annotated locations for XP_011541022.1

    UniProtKB/Swiss-Prot
    Q9NZN5
    UniProtKB/TrEMBL
    E9PMR6
    Conserved Domains (4) summary
    cd08754
    Location:246467
    RGS_LARG; Regulator of G protein signaling (RGS) domain found in the leukemia-associated Rho guanine nucleotide exchange factor (RhoGEF) protein (LARG)
    cd00992
    Location:242
    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:8921029
    PH_LARG; Leukemia-associated Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain
    pfam00621
    Location:688873
    RhoGEF; RhoGEF domain
  3. XM_006718805.3XP_006718868.1  rho guanine nucleotide exchange factor 12 isoform X2

    Conserved Domains (4) summary
    cd08754
    Location:324545
    RGS_LARG; Regulator of G protein signaling (RGS) domain found in the leukemia-associated Rho guanine nucleotide exchange factor (RhoGEF) protein (LARG)
    cd00992
    Location:71145
    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:9701107
    PH_LARG; Leukemia-associated Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain
    pfam00621
    Location:766951
    RhoGEF; RhoGEF domain
  4. XM_017017421.1XP_016872910.1  rho guanine nucleotide exchange factor 12 isoform X1

    UniProtKB/Swiss-Prot
    Q9NZN5
    UniProtKB/TrEMBL
    E9PMR6
    Conserved Domains (4) summary
    cd08754
    Location:246467
    RGS_LARG; Regulator of G protein signaling (RGS) domain found in the leukemia-associated Rho guanine nucleotide exchange factor (RhoGEF) protein (LARG)
    cd00992
    Location:242
    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:8921029
    PH_LARG; Leukemia-associated Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain
    pfam00621
    Location:688873
    RhoGEF; RhoGEF domain
  5. XM_017017422.2XP_016872911.1  rho guanine nucleotide exchange factor 12 isoform X4

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