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Aliases for ARHGEF4 Gene

Aliases for ARHGEF4 Gene

  • Rho Guanine Nucleotide Exchange Factor 4 2 3 5
  • APC-Stimulated Guanine Nucleotide Exchange Factor 1 3 4
  • Rho Guanine Nucleotide Exchange Factor (GEF) 4 2 3
  • ASEF1 3 4
  • ASEF 3 4
  • APC-Stimulated Guanine Nucleotide Exchange Factor 2
  • KIAA1112 4
  • GEF4 3
  • STM6 3

External Ids for ARHGEF4 Gene

Previous GeneCards Identifiers for ARHGEF4 Gene

  • GC02P129362
  • GC02P129196
  • GC02P131696
  • GC02P131884
  • GC02P131507
  • GC02P131390
  • GC02P131595
  • GC02P123836

Summaries for ARHGEF4 Gene

Entrez Gene Summary for ARHGEF4 Gene

  • Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein coupled receptors. The protein encoded by this gene may form complex with G proteins and stimulate Rho-dependent signals. Multiple alternatively spliced transcript variants encoding different isoforms have been found, but the full-length nature of some variants has not been determined. [provided by RefSeq, Jun 2013]

GeneCards Summary for ARHGEF4 Gene

ARHGEF4 (Rho Guanine Nucleotide Exchange Factor 4) is a Protein Coding gene. Among its related pathways are p75 NTR receptor-mediated signalling and fMLP Pathway. Gene Ontology (GO) annotations related to this gene include protein domain specific binding and Rho guanyl-nucleotide exchange factor activity. An important paralog of this gene is SPATA13.

UniProtKB/Swiss-Prot for ARHGEF4 Gene

  • Acts as guanine nucleotide exchange factor (GEF) for RHOA, RAC1 and CDC42 GTPases. Binding of APC may activate RAC1 GEF activity. The APC-ARHGEF4 complex seems to be involved in cell migration as well as in E-cadherin-mediated cell-cell adhesion. Required for MMP9 up-regulation via the JNK signaling pathway in colorectal tumor cells. Involved in tumor angiogenesis and may play a role in intestinal adenoma formation and tumor progression.

Gene Wiki entry for ARHGEF4 Gene

Additional gene information for ARHGEF4 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for ARHGEF4 Gene

Genomics for ARHGEF4 Gene

GeneHancer (GH) Regulatory Elements for ARHGEF4 Gene

Promoters and enhancers for ARHGEF4 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH02I130836 Promoter/Enhancer 1.3 Ensembl ENCODE dbSUPER 550.8 +0.1 124 1.6 SP3 USF1 L3MBTL2 BHLHE40 SP2 E2F1 EGR1 POLR2A ZFX ZBTB26 ARHGEF4 ENSG00000233221 PIR32383 GC02P130572
GH02I130916 Promoter 0.6 EPDnew 550.2 +79.8 79750 0.1 EZH2 ARHGEF4 GC02M130875 PIR61426 GC02P130572
GH02I131103 Promoter/Enhancer 2.5 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 5.1 +268.5 268469 4.6 PKNOX1 FOXA2 ARID4B SIN3A DMAP1 IRF4 YY1 POLR2B ZNF766 ZNF213 PLEKHB2 PTPN18 ENSG00000227632 ARHGEF4 ENSG00000213222 PIR42706 GC02P130572
GH02I130826 Enhancer 1.3 FANTOM5 Ensembl ENCODE dbSUPER 5.4 -8.6 -8582 3 PKNOX1 JUN MAX BRCA1 ZFHX2 POLR2A FOS NFE2L2 CHD2 EGR2 ARHGEF4 ENSG00000233221 CYCSP8 GC02P130572
GH02I130823 Enhancer 1.2 Ensembl ENCODE dbSUPER 5.1 -12.3 -12329 1.9 HDGF BMI1 BATF IRF4 ZSCAN5C ZNF207 ZNF143 ATF7 ETV6 FOS GPR148 ARHGEF4 MZT2B CCDC74A CYCSP8 GC02P130572
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around ARHGEF4 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the ARHGEF4 gene promoter:

Genomic Locations for ARHGEF4 Gene

Genomic Locations for ARHGEF4 Gene
chr2:130,836,916-131,047,263
(GRCh38/hg38)
Size:
210,348 bases
Orientation:
Plus strand
chr2:131,594,489-131,804,836
(GRCh37/hg19)

Genomic View for ARHGEF4 Gene

Genes around ARHGEF4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ARHGEF4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ARHGEF4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ARHGEF4 Gene

Proteins for ARHGEF4 Gene

  • Protein details for ARHGEF4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9NR80-ARHG4_HUMAN
    Recommended name:
    Rho guanine nucleotide exchange factor 4
    Protein Accession:
    Q9NR80
    Secondary Accessions:
    • Q9HDC6
    • Q9UPP0

    Protein attributes for ARHGEF4 Gene

    Size:
    690 amino acids
    Molecular mass:
    79067 Da
    Quaternary structure:
    • Isoform 3 interacts with RHOA and RAC1, and (via ABR domain) with APC. Found in a complex consisting of ARHGEF4, APC and CTNNB1.
    SequenceCaution:
    • Sequence=AAF79955.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=AAF79955.1; Type=Frameshift; Positions=638, 643; Evidence={ECO:0000305}; Sequence=BAA83064.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for ARHGEF4 Gene

    Alternative splice isoforms for ARHGEF4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for ARHGEF4 Gene

Post-translational modifications for ARHGEF4 Gene

No Post-translational modifications

No data available for DME Specific Peptides for ARHGEF4 Gene

Domains & Families for ARHGEF4 Gene

Gene Families for ARHGEF4 Gene

Suggested Antigen Peptide Sequences for ARHGEF4 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q9NR80

UniProtKB/Swiss-Prot:

ARHG4_HUMAN :
  • In an autoinhibited form the SH3 domain binds intramolecularly to the DH domain, thus blocking the Rac-binding site.
Domain:
  • In an autoinhibited form the SH3 domain binds intramolecularly to the DH domain, thus blocking the Rac-binding site.
genes like me logo Genes that share domains with ARHGEF4: view

Function for ARHGEF4 Gene

Molecular function for ARHGEF4 Gene

UniProtKB/Swiss-Prot Function:
Acts as guanine nucleotide exchange factor (GEF) for RHOA, RAC1 and CDC42 GTPases. Binding of APC may activate RAC1 GEF activity. The APC-ARHGEF4 complex seems to be involved in cell migration as well as in E-cadherin-mediated cell-cell adhesion. Required for MMP9 up-regulation via the JNK signaling pathway in colorectal tumor cells. Involved in tumor angiogenesis and may play a role in intestinal adenoma formation and tumor progression.

Phenotypes From GWAS Catalog for ARHGEF4 Gene

Gene Ontology (GO) - Molecular Function for ARHGEF4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005085 guanyl-nucleotide exchange factor activity TAS --
GO:0005089 Rho guanyl-nucleotide exchange factor activity TAS,IEA --
GO:0005515 protein binding IPI 17588722
GO:0019904 protein domain specific binding IPI 10947987
GO:0030676 Rac guanyl-nucleotide exchange factor activity IMP 17599059
genes like me logo Genes that share ontologies with ARHGEF4: view
genes like me logo Genes that share phenotypes with ARHGEF4: view

Animal Models for ARHGEF4 Gene

MGI Knock Outs for ARHGEF4:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for ARHGEF4 Gene

Localization for ARHGEF4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ARHGEF4 Gene

Isoform 3: Cytoplasm. Cell projection, ruffle membrane; Peripheral membrane protein; Cytoplasmic side. Note=Associated with membrane ruffles. {ECO:0000305}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for ARHGEF4 gene
Compartment Confidence
cytosol 5
plasma membrane 3
nucleus 3
cytoskeleton 1
mitochondrion 1

Gene Ontology (GO) - Cellular Components for ARHGEF4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005622 intracellular IEA --
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol TAS --
GO:0005886 plasma membrane IEA --
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with ARHGEF4: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for ARHGEF4 Gene

Pathways & Interactions for ARHGEF4 Gene

genes like me logo Genes that share pathways with ARHGEF4: view

SIGNOR curated interactions for ARHGEF4 Gene

Is activated by:

Gene Ontology (GO) - Biological Process for ARHGEF4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007186 G-protein coupled receptor signaling pathway TAS --
GO:0030032 lamellipodium assembly IMP 17599059
GO:0035023 regulation of Rho protein signal transduction IEA --
GO:0035556 intracellular signal transduction IEA --
GO:0043065 positive regulation of apoptotic process TAS --
genes like me logo Genes that share ontologies with ARHGEF4: view

Drugs & Compounds for ARHGEF4 Gene

(3) Drugs for ARHGEF4 Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Guanosine diphosphate Experimental Pharma 0
Guanosine monophosphate Experimental Pharma 0
Guanosine triphosphate Experimental Pharma 0
genes like me logo Genes that share compounds with ARHGEF4: view

Transcripts for ARHGEF4 Gene

Unigene Clusters for ARHGEF4 Gene

Rho guanine nucleotide exchange factor (GEF) 4:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for ARHGEF4 Gene

ExUns: 1 ^ 2a · 2b ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17a · 17b
SP1: - - -
SP2: - - -
SP3: - -
SP4: -
SP5:

Relevant External Links for ARHGEF4 Gene

GeneLoc Exon Structure for
ARHGEF4
ECgene alternative splicing isoforms for
ARHGEF4

Expression for ARHGEF4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for ARHGEF4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for ARHGEF4 Gene

This gene is overexpressed in Brain - Cortex (x4.7).

Protein differential expression in normal tissues from HIPED for ARHGEF4 Gene

This gene is overexpressed in Tlymphocyte (48.3) and Peripheral blood mononuclear cells (17.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for ARHGEF4 Gene



Protein tissue co-expression partners for ARHGEF4 Gene

NURSA nuclear receptor signaling pathways regulating expression of ARHGEF4 Gene:

ARHGEF4

SOURCE GeneReport for Unigene cluster for ARHGEF4 Gene:

Hs.469935

mRNA Expression by UniProt/SwissProt for ARHGEF4 Gene:

Q9NR80-ARHG4_HUMAN
Tissue specificity: Expressed at high levels in the brain, skeletal muscle and testis and at low levels in the kidney, lung, small intestine, ovary and prostate. Expression is aberrantly enhanced in most colorectal tumors.

Evidence on tissue expression from TISSUES for ARHGEF4 Gene

  • Nervous system(4.7)
genes like me logo Genes that share expression patterns with ARHGEF4: view

Primer Products

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for ARHGEF4 Gene

Orthologs for ARHGEF4 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for ARHGEF4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia ARHGEF4 33 34
  • 98.91 (n)
dog
(Canis familiaris)
Mammalia ARHGEF4 34
  • 93 (a)
OneToOne
LOC483856 33
  • 85.75 (n)
mouse
(Mus musculus)
Mammalia Arhgef4 33 16 34
  • 88.41 (n)
cow
(Bos Taurus)
Mammalia ARHGEF4 33 34
  • 86.56 (n)
rat
(Rattus norvegicus)
Mammalia Arhgef4 33
  • 84.48 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia ARHGEF4 34
  • 78 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia ARHGEF4 34
  • 22 (a)
OneToOne
chicken
(Gallus gallus)
Aves ARHGEF4 33 34
  • 71.37 (n)
lizard
(Anolis carolinensis)
Reptilia ARHGEF4 34
  • 75 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100487089 33
  • 65.51 (n)
Str.13603 33
zebrafish
(Danio rerio)
Actinopterygii arhgef4 33 34
  • 72.6 (n)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes CDC24 36
sea squirt
(Ciona savignyi)
Ascidiacea CSA.7470 34
  • 30 (a)
OneToMany
Species where no ortholog for ARHGEF4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for ARHGEF4 Gene

ENSEMBL:
Gene Tree for ARHGEF4 (if available)
TreeFam:
Gene Tree for ARHGEF4 (if available)

Paralogs for ARHGEF4 Gene

genes like me logo Genes that share paralogs with ARHGEF4: view

Variants for ARHGEF4 Gene

Sequence variations from dbSNP and Humsavar for ARHGEF4 Gene

SNP ID Clin Chr 02 pos Variation AA Info Type
VAR_035970 A breast cancer sample p.Lys100Arg
VAR_035971 A breast cancer sample p.Thr441Arg
rs1000028610 -- 131,005,184(+) C/G genic_downstream_transcript_variant, genic_upstream_transcript_variant, intron_variant
rs1000031829 -- 130,837,099(+) C/T genic_upstream_transcript_variant, intron_variant
rs1000033115 -- 130,919,462(+) C/T genic_downstream_transcript_variant, genic_upstream_transcript_variant, intron_variant

Structural Variations from Database of Genomic Variants (DGV) for ARHGEF4 Gene

Variant ID Type Subtype PubMed ID
nsv953168 CNV deletion 24416366
nsv7327 OTHER inversion 18451855
nsv583135 CNV loss 21841781
nsv524021 CNV loss 19592680
nsv428404 CNV loss 18775914
nsv1147463 OTHER inversion 26484159
nsv1144915 CNV deletion 24896259
nsv1118880 CNV deletion 24896259
nsv1072454 CNV deletion 25765185
nsv1072031 CNV deletion 25765185
nsv1014723 CNV loss 25217958
nsv1005040 CNV gain 25217958
nsv1000507 CNV gain 25217958
esv3893337 CNV loss 25118596
esv2760576 CNV gain+loss 21179565
esv2759092 CNV gain+loss 17122850
esv2670824 CNV deletion 23128226
esv1708111 CNV insertion 17803354
dgv731e199 CNV deletion 23128226
dgv616e201 CNV deletion 23290073
dgv4075n100 CNV gain 25217958
dgv4074n100 CNV gain 25217958
dgv2246e59 CNV duplication 20981092
dgv2032n106 OTHER inversion 24896259

Variation tolerance for ARHGEF4 Gene

Residual Variation Intolerance Score: 33.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 7.76; 83.25% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ARHGEF4 Gene

Human Gene Mutation Database (HGMD)
ARHGEF4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
ARHGEF4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ARHGEF4 Gene

Disorders for ARHGEF4 Gene

Additional Disease Information for ARHGEF4

No disorders were found for ARHGEF4 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for ARHGEF4 Gene

Publications for ARHGEF4 Gene

  1. Isolation of two novel human RhoGEFs, ARHGEF3 and ARHGEF4, in 3p13-21 and 2q22. (PMID: 10873612) Thiesen S … Nothwang HG (Biochemical and biophysical research communications 2000) 2 3 4 22 58
  2. Identification and characterization of Asef2, a guanine-nucleotide exchange factor specific for Rac1 and Cdc42. (PMID: 17599059) Kawasaki Y … Akiyama T (Oncogene 2007) 3 4 58
  3. Mutated APC and Asef are involved in the migration of colorectal tumour cells. (PMID: 12598901) Kawasaki Y … Akiyama T (Nature cell biology 2003) 3 4 58
  4. Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones. (PMID: 12168954) Nakajima D … Nagase T (DNA research : an international journal for rapid publication of reports on genes and genomes 2002) 3 4 58
  5. Asef, a link between the tumor suppressor APC and G-protein signaling. (PMID: 10947987) Kawasaki Y … Akiyama T (Science (New York, N.Y.) 2000) 3 4 58

Products for ARHGEF4 Gene

Sources for ARHGEF4 Gene

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