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FLASH GENE
Symbol ARHGEF2 contributors: shn - updated : 06-09-2017
HGNC name Rho/Rac guanine nucleotide exchange factor (GEF) 2
HGNC id 682
Location 1q22      Physical location : 155.916.629 - 155.948.336
Synonym name
  • rho/rac guanine nucleotide exchange factor (GEF) 2
  • rho guanine nucleotide exchange factor 2
  • proliferating cell nucleolar antigen p40
  • protein GEF-H1
  • Synonym symbol(s) GEF, P40, GEFH1, LFP40, GEF-H1, FLJ45440, KIAA0651, DKFZp547L106, DKFZp547P1516
    DNA
    TYPE functioning gene
    STRUCTURE 31.34 kb     22 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map cen - D1S303 - D1S1595 - ARHGEF2 - D1S2721 - D1S2624 - qter
    Physical map
    HCN3 1q22 hyperpolarization activated cyclic nucleotide-gated potassium channel 3 PKLR 1q21 pyruvate kinase, liver and RBC FDPS 1q21.2 farnesyl diphosphate synthase (farnesyl pyrophosphate synthetase, dimethylallyltranstransferase, geranyltranstransferase) FLJ35976 1q22 hypothetical protein FLJ35976 RUSC1 1q21-q22 RUN and SH3 domain containing 1 ASH1L 1q21 ash1 (absent, small, or homeotic)-like (Drosophila) LOC284620 1q22 similar to CLDN6 MRPS29P1 1q21.3 mitochondrial ribosomal protein S29 pseudogene 1 FLJ10504 1q22 misato YAP 1q21.3 misato DAP3 1q21 death associated protein 3 LOC388705 1 similar to misato FLJ20203 1q22 hypothetical protein FLJ20203 SYT11 1q21.2 synaptotagmin XI RIT1 1q21.2 Ras-like without CAAX 1 KIAA0907 1q21 Ras-like without CAAX 1 GPR100 1q22 G protein-coupled receptor 100 ARHGEF2 1q11-q21 rho/rac guanine nucleotide exchange factor (GEF) 2 SSR2 1q21-q23 signal sequence receptor, beta (translocon-associated protein beta) C1orf6 1q21 chromosome 1 open reading Frame 6 MAPBPIP 1q22 mitogen-activated protein-binding protein-interacting protein RAB25 1q21.2 RAB25, member RAS oncogene family LOC92312 1q22-q23.1 hypothetical protein LOC92312 LMNA 1q21.2-q21.3 lamin A/C FLJ12287 1q22 hypothetical protein FLJ12287 similar to semaphorins LOC388706 1 LOC388706 KIAA0446 1q23.1 KIAA0446 gene product PMF1 1q12-q21.1 polyamine-modulated factor 1 BGLAP 1q25-q31 bone gamma-carboxyglutamate (gla) protein (osteocalcin) PAQR6 1q23.1 progestin and adipoQ receptor family member VI EST1B 1q21.2 Est1p-like protein B MGC13102 1q23.1 hypothetical protein MGC13102 MGC31963 1q23.1 kidney predominant protein NCU-G1 LOC391104 1 similar to Von Hippel-Lindau disease tumor suppressor (pVHL) (G7 protein) CCT3 1q23 chaperonin containing TCP1, subunit 3 (gamma) SSTK-IP 1q23.1 SSTK-interacting protein RHBG 1q21.3 Rhesus blood group, B glycoprotein CROC4 1q12-q25 Rhesus blood group, B glycoprotein MEF2D 1q12-q23 MADS box transcription enhancer factor 2, polypeptide D (myocyte enhancer factor 2D) IQGAP3 1q21.3 IQ motif containing GTPase activating protein 3
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    22 splicing 4119 - 958 - -
    22 splicing 4191 - 985 - -
    22 - 4194 - 986 - -
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestiveliver   highly
    Endocrinepancreas   highly
    Lymphoid/Immunespleen   highly
    Nervousbrain   highly
    Reproductivefemale systemovary  highly
     male systemtestis  highly
    Respiratorylung   highly
    Urinarykidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • associates with microtubules via its N-terminal C1 domain, which is known to regulate its activity
  • a Dbl homology domain in tandem with a pleckstin homology (PH) domain
  • a C terminal domain for suppression of guanine nucleotide exchange activity by microtubules
  • the C terminal domain contains a coiled-coil domain proline-rich motif that may interact with Src homology 3 domain-containing proteins and a potential binding site for 14-3-3 proteins
  • conjugated
    HOMOLOGY
    interspecies ortholog to Arhgef2, Mus musculus
    ortholog to Arhgef2, Rattus norvegicus
    Homologene
    FAMILY
  • Dbl family GEFs specific for Rho
  • CATEGORY regulatory , signaling
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle
    intracellular,cytoplasm,cytoskeleton,microtubule
    text
  • colocalizing with microtubules
  • colocalized with ASAP1 in podosomes
  • basic FUNCTION
  • involved in regulation of signal transduction cascades from extracellular stimuli to cell nucleus and cytoskeleton
  • stimulating guanine nucleotide exchange for Rac and Rho
  • modulates localized RhoA activation during cytokinesis under the control of mitotic kinases
  • guanine exchange factor-H1 for RhoA, that is transcriptionally activated by the induction of mutant TP53 proteins, thereby accelerating tumor cell proliferation
  • mediates cross-talk between microtubules and the actin cytoskeleton
  • regulate spindle orientation in non-neural cells
  • required to determine the orientation of mitotic precursor cell divisions in vivo and its interaction with Tctex-1 is necessary to regulate cortical neurogenesis
  • important in embryonic neural precursors, a part of an essential pathway that regulates the genesis of neurons from cortical precursor cells, potentially by regulating mitotic spindle orientation
  • essential for the normal genesis of neurons from embryonic radial precursors
  • negative regulator of podosomes
  • potentially responsible for the increased RhoA activity necessary for podosome belt disassembly
  • may affect the regulation of the microtubule organization
  • may promotes tubulin-acetylation following microtubule binding and stabilization
  • with ARHGEF10, ARHGEF2, ARHGEF12, PLEKHG1 and ARHGEF28, are involved in cyclic-stretch-induced perpendicular reorientation of endothelial cells
  • CELLULAR PROCESS cell cycle, division, mitosis
    PHYSIOLOGICAL PROCESS neurogenesis
    text essential for neurogenesis
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • tight junction-associated adaptor cingulin (CGN)
  • semaphorin 4D (Sema4D)
  • dynein, light chain, Tctex-type 1 (DYNLT1)
  • ARHGEF2 and EXOC1 interact in trans-Golgi network and centrosomes, as well as in exocyst structures or complexes that move along microtubules to the plasma membrane, consistent with a functional association in both early and late stages of vesicular trafficking
  • ARHGEF2, a guanine nucleotide exchange factor for RHOA, directly interacts with cingulin, a junctional adaptor
  • binding partner of the BAR domain of ASAP1
  • MARK2 is a substrate for ARHGEF2
  • CAMSAP3-anchored non-centrosomal microtubules capture ARHGEF2 more efficiently than other microtubules do and a balance between these microtubules is important to maintain proper actin organization
  • role for association of ARHGEF2 with CGN as the mechanism of RHOA pathway inactivation
  • cell & other
    REGULATION
    Phosphorylated by MARK2, that phosphorylates ARHGEF2 at three serine residues located close to the C1 domain and regulates the microtubule binding ability of ARHGEF2
    Other
  • phosphorylated and regulated by p21-activated kinase 1
  • regulated by an interaction with microtubules
  • negatively regulated by Tctex-1 (Dynlt1)
  • activated when it is released from microtubules
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    contributes to the tumor progression phenotype associated with the TP53 mutation
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
    genetic knockdown of mouse Arhgef2 in cortical precursors either in culture or in vivo inhibits neurogenesis and maintained cells as cycling radial precursors