ARHGAP35 Gene (Protein Coding)

Rho GTPase Activating Protein 35

GC19P046860
GIFtS:
39
The human glucocorticoid receptor DNA binding factor, which associates with the promoter region of the glucocorticoid receptor gene (hGR gene), is a repressor of glucocorticoid receptor transcription. The amino acid sequence deduced from the cDNA sequences show the presence of three sequence motifs characteristic of a zinc finger and one motif suggestive of a leucine zipper in ... See more...

Aliases for ARHGAP35 Gene

Aliases for ARHGAP35 Gene

  • Rho GTPase Activating Protein 35 2 3 5
  • Glucocorticoid Receptor DNA-Binding Factor 1 3 4
  • Glucocorticoid Receptor Repression Factor 1 3 4
  • Rho GTPase-Activating Protein 35 3 4
  • Rho GAP P190A 3 4
  • P190-A 3 4
  • GRLF1 3 4
  • GRF-1 3 4
  • P190A 3 4
  • Glucocorticoid Receptor DNA Binding Factor 1 2
  • P190ARhoGAP 3
  • P190ARHOGAP 4
  • P190RhoGAP 3
  • KIAA1722 4
  • GRF1 4

External Ids for ARHGAP35 Gene

Previous HGNC Symbols for ARHGAP35 Gene

  • GRLF1

Previous GeneCards Identifiers for ARHGAP35 Gene

  • GC19P047422
  • GC19P046918

Summaries for ARHGAP35 Gene

Entrez Gene Summary for ARHGAP35 Gene

  • The human glucocorticoid receptor DNA binding factor, which associates with the promoter region of the glucocorticoid receptor gene (hGR gene), is a repressor of glucocorticoid receptor transcription. The amino acid sequence deduced from the cDNA sequences show the presence of three sequence motifs characteristic of a zinc finger and one motif suggestive of a leucine zipper in which 1 cysteine is found instead of all leucines. The GRLF1 enhances the homologous down-regulation of wild-type hGR gene expression. Biochemical analysis suggests that GRLF1 interaction is sequence specific and that transcriptional efficacy of GRLF1 is regulated through its interaction with specific sequence motif. The level of expression is regulated by glucocorticoids. [provided by RefSeq, Jul 2008]

GeneCards Summary for ARHGAP35 Gene

ARHGAP35 (Rho GTPase Activating Protein 35) is a Protein Coding gene. Among its related pathways are Signaling events mediated by focal adhesion kinase and Signaling by GPCR. Gene Ontology (GO) annotations related to this gene include GTP binding and transcription corepressor activity. An important paralog of this gene is SYDE2.

UniProtKB/Swiss-Prot Summary for ARHGAP35 Gene

  • Rho GTPase-activating protein (GAP) (PubMed:19673492, PubMed:28894085). Binds several acidic phospholipids which inhibits the Rho GAP activity to promote the Rac GAP activity (PubMed:19673492). This binding is inhibited by phosphorylation by PRKCA (PubMed:19673492). Involved in cell differentiation as well as cell adhesion and migration, plays an important role in retinal tissue morphogenesis, neural tube fusion, midline fusion of the cerebral hemispheres and mammary gland branching morphogenesis (By similarity). Transduces signals from p21-ras to the nucleus, acting via the ras GTPase-activating protein (GAP) (By similarity). Transduces SRC-dependent signals from cell-surface adhesion molecules, such as laminin, to promote neurite outgrowth. Regulates axon outgrowth, guidance and fasciculation (By similarity). Modulates Rho GTPase-dependent F-actin polymerization, organization and assembly, is involved in polarized cell migration and in the positive regulation of ciliogenesis and cilia elongation (By similarity). During mammary gland development, is required in both the epithelial and stromal compartments for ductal outgrowth (By similarity). Represses transcription of the glucocorticoid receptor by binding to the cis-acting regulatory sequence 5'-GAGAAAAGAAACTGGAGAAACTC-3'; this function is however unclear and would need additional experimental evidences (PubMed:1894621).

Gene Wiki entry for ARHGAP35 Gene

Additional gene information for ARHGAP35 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for ARHGAP35 Gene

Genomics for ARHGAP35 Gene

GeneHancer (GH) Regulatory Elements for ARHGAP35 Gene

Promoters and enhancers for ARHGAP35 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around ARHGAP35 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for ARHGAP35

Genomic Locations for ARHGAP35 Gene

Genomic Locations for ARHGAP35 Gene
chr19:46,860,997-47,005,077
(GRCh38/hg38)
Size:
144,081 bases
Orientation:
Plus strand
chr19:47,421,933-47,508,334
(GRCh37/hg19)
Size:
86,402 bases
Orientation:
Plus strand

Genomic View for ARHGAP35 Gene

Genes around ARHGAP35 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ARHGAP35 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ARHGAP35 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for ARHGAP35 Gene

Proteins for ARHGAP35 Gene

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  • Protein details for ARHGAP35 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9NRY4-RHG35_HUMAN
    Recommended name:
    Rho GTPase-activating protein 35
    Protein Accession:
    Q9NRY4
    Secondary Accessions:
    • A7E2A4
    • Q14452
    • Q9C0E1

    Protein attributes for ARHGAP35 Gene

    Size:
    1499 amino acids
    Molecular mass:
    170514 Da
    Quaternary structure:
    • Interacts with RASA1 (By similarity). Interacts with the general transcription factor GTF2I, the interaction sequesters GTF2I in the cytoplasm (PubMed:19393245).
    SequenceCaution:
    • Sequence=AAA58618.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=AAF80386.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=AAF80386.1; Type=Miscellaneous discrepancy; Note=Unlikely isoform. Aberrant splice sites.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for ARHGAP35 Gene

neXtProt entry for ARHGAP35 Gene

Protein Expression for ARHGAP35 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for ARHGAP35 Gene

  • Phosphorylation of Tyr-1105 by PTK6 promotes the association with RASA1, inactivating RHOA while activating RAS. Phosphorylation at Tyr-308 by PDGFRA inhibits binding to GTF2I (PubMed:18829532, PubMed:19393245). Phosphorylated by PRKCA at Ser-1221 and Thr-1226, induces relocalization from the cytoplasm to regions of plasma membrane ruffling and prevents the binding and substrate specificity regulation by phospholipids (PubMed:19673492). In brain, phosphorylated by FYN and SRC (By similarity). During focal adhesion formation, phosphorylated by MAPK1 and MAPK3 at the C-terminal region, probably at Ser-1451, Ser-1476, Thr-1480 and Ser-1483. Phosphorylation by MAPK1 and MAPK3 inhibits GAP function and localizes ARGHAP35 away from newly forming focal adhesions and stress fibers in cells spreading on fibronectin (By similarity). Phosphorylation at Ser-1476 and Thr-1480 by GSK3B requires priming by MAPK and inhibits RhoGAP activity and modulates polarized cell migration (By similarity).
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for ARHGAP35 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for ARHGAP35 Gene

Domains & Families for ARHGAP35 Gene

Gene Families for ARHGAP35 Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Predicted intracellular proteins

Protein Domains for ARHGAP35 Gene

Blocks:
  • RhoGAP domain
  • FF domain
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for ARHGAP35 Gene

GenScript: Design optimal peptide antigens:
  • Rho GAP p190A (RHG35_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9NRY4

UniProtKB/Swiss-Prot:

RHG35_HUMAN :
  • N-terminal part (1-266) has GTPase activity. Required for proper cellular localization.
Domain:
  • N-terminal part (1-266) has GTPase activity. Required for proper cellular localization.
  • The pG1 pseudoGTPase domain does not bind GTP.
genes like me logo Genes that share domains with ARHGAP35: view

Function for ARHGAP35 Gene

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Molecular function for ARHGAP35 Gene

UniProtKB/Swiss-Prot Function:
Rho GTPase-activating protein (GAP) (PubMed:19673492, PubMed:28894085). Binds several acidic phospholipids which inhibits the Rho GAP activity to promote the Rac GAP activity (PubMed:19673492). This binding is inhibited by phosphorylation by PRKCA (PubMed:19673492). Involved in cell differentiation as well as cell adhesion and migration, plays an important role in retinal tissue morphogenesis, neural tube fusion, midline fusion of the cerebral hemispheres and mammary gland branching morphogenesis (By similarity). Transduces signals from p21-ras to the nucleus, acting via the ras GTPase-activating protein (GAP) (By similarity). Transduces SRC-dependent signals from cell-surface adhesion molecules, such as laminin, to promote neurite outgrowth. Regulates axon outgrowth, guidance and fasciculation (By similarity). Modulates Rho GTPase-dependent F-actin polymerization, organization and assembly, is involved in polarized cell migration and in the positive regulation of ciliogenesis and cilia elongation (By similarity). During mammary gland development, is required in both the epithelial and stromal compartments for ductal outgrowth (By similarity). Represses transcription of the glucocorticoid receptor by binding to the cis-acting regulatory sequence 5'-GAGAAAAGAAACTGGAGAAACTC-3'; this function is however unclear and would need additional experimental evidences (PubMed:1894621).
UniProtKB/Swiss-Prot EnzymeRegulation:
Binding of acidic phospholipids inhibits the Rho GAP activity and promotes the Rac GAP activity.

Phenotypes From GWAS Catalog for ARHGAP35 Gene

Gene Ontology (GO) - Molecular Function for ARHGAP35 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0000977 RNA polymerase II regulatory region sequence-specific DNA binding IDA 1894621
GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific IDA 1894621
GO:0003677 DNA binding TAS 1894621
GO:0003714 transcription corepressor activity TAS 1894621
genes like me logo Genes that share ontologies with ARHGAP35: view
genes like me logo Genes that share phenotypes with ARHGAP35: view

Animal Models for ARHGAP35 Gene

MGI Knock Outs for ARHGAP35:

Animal Model Products

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No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for ARHGAP35 Gene

Localization for ARHGAP35 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ARHGAP35 Gene

Cytoplasm, cytoskeleton, cilium basal body. Cytoplasm. Nucleus. Cell membrane. Note=In response to integrins and SDC4 and upon phosphorylation by PKC, relocalizes from the cytoplasm to regions of plasma membrane ruffling where it colocalizes with polymerized actin. {ECO:0000250 UniProtKB:Q91YM2}.

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 ARHGAP35 gene
Compartment Confidence
cytoskeleton 5
nucleus 5
cytosol 5
plasma membrane 4
extracellular 2
mitochondrion 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nuclear bodies (3)
  • Aggresome (1)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for ARHGAP35 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA,IC 1894621
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol TAS --
GO:0005856 cytoskeleton IEA --
GO:0005886 plasma membrane IEA --
genes like me logo Genes that share ontologies with ARHGAP35: view

Pathways & Interactions for ARHGAP35 Gene

genes like me logo Genes that share pathways with ARHGAP35: view

Pathways by source for ARHGAP35 Gene

3 GeneGo (Thomson Reuters) pathways for ARHGAP35 Gene
  • Cell adhesion Integrin-mediated cell adhesion and migration
  • Cytoskeleton remodeling FAK signaling
  • Cytoskeleton remodeling Fibronectin-binding integrins in cell motility
1 Cell Signaling Technology pathway for ARHGAP35 Gene

SIGNOR curated interactions for ARHGAP35 Gene

Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for ARHGAP35 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IDA 1894621
GO:0001843 neural tube closure IEA --
GO:0006351 transcription, DNA-templated TAS 1894621
GO:0007165 signal transduction IEA --
GO:0007411 axon guidance ISS --
genes like me logo Genes that share ontologies with ARHGAP35: view

Drugs & Compounds for ARHGAP35 Gene

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(1) Drugs for ARHGAP35 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
genes like me logo Genes that share compounds with ARHGAP35: view

Transcripts for ARHGAP35 Gene

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mRNA/cDNA for ARHGAP35 Gene

2 REFSEQ mRNAs :
15 NCBI additional mRNA sequence :
7 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for ARHGAP35 Gene

ExUns: 1 ^ 2a · 2b ^ 3 ^ 4 ^ 5a · 5b · 5c ^ 6a · 6b ^ 7a · 7b
SP1: - - - -
SP2: - - - -
SP3: - -
SP4:

Relevant External Links for ARHGAP35 Gene

GeneLoc Exon Structure for
ARHGAP35

Expression for ARHGAP35 Gene

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mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for ARHGAP35 Gene

mRNA expression in normal human tissues for ARHGAP35 Gene
mRNA expression by GTEx for ARHGAP35 GenemRNA expression by BioGPS for ARHGAP35 Gene

Protein differential expression in normal tissues from HIPED for ARHGAP35 Gene

This gene is overexpressed in Brain (13.1), Fetal Brain (11.6), Plasma (8.0), and Frontal cortex (7.8).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for ARHGAP35 Gene



Protein tissue co-expression partners for ARHGAP35 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for ARHGAP35

SOURCE GeneReport for Unigene cluster for ARHGAP35 Gene:

Hs.509447

mRNA Expression by UniProt/SwissProt for ARHGAP35 Gene:

Q9NRY4-RHG35_HUMAN
Tissue specificity: Detected in neutrophils (at protein level).

Evidence on tissue expression from TISSUES for ARHGAP35 Gene

  • Nervous system(4.8)
  • Liver(4.3)
  • Blood(4.1)
  • Lung(3.3)
  • Heart(2.2)
  • Kidney(2.1)
genes like me logo Genes that share expression patterns with ARHGAP35: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for ARHGAP35 Gene

Orthologs for ARHGAP35 Gene

This gene was present in the common ancestor of animals.

Orthologs for ARHGAP35 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
 Mammalia ARHGAP35 31 30
  • 99.71 (n)
 OneToOne
oppossum
(Monodelphis domestica)
 Mammalia ARHGAP35 31
  • 95 (a)
 OneToOne
dog
(Canis familiaris)
 Mammalia ARHGAP35 31 30
  • 93.93 (n)
 OneToOne
cow
(Bos Taurus)
 Mammalia ARHGAP35 31 30
  • 91.44 (n)
 OneToOne
mouse
(Mus musculus)
 Mammalia Grlf1 31 30
  • 89.72 (n)
 OneToOne
Arhgap35 17
rat
(Rattus norvegicus)
 Mammalia Arhgap35 30
  • 89.54 (n)
platypus
(Ornithorhynchus anatinus)
 Mammalia ARHGAP35 31
  • 69 (a)
 OneToOne
chicken
(Gallus gallus)
 Aves ARHGAP35 31 30
  • 73.1 (n)
 OneToOne
lizard
(Anolis carolinensis)
 Reptilia ARHGAP35 31
  • 92 (a)
 OneToOne
tropical clawed frog
(Silurana tropicalis)
 Amphibia arhgap35 30
  • 71.38 (n)
zebrafish
(Danio rerio)
 Actinopterygii arhgap35a 31
  • 68 (a)
 OneToMany
LOC100004299 30
  • 67.27 (n)
arhgap35 31
  • 67 (a)
 OneToMany
African malaria mosquito
(Anopheles gambiae)
 Insecta AgaP_AGAP000870 30
  • 49.17 (n)
fruit fly
(Drosophila melanogaster)
 Insecta RhoGAPp190 31 30
  • 48.47 (n)
 OneToMany
worm
(Caenorhabditis elegans)
 Secernentea rga-5 31
  • 26 (a)
 OneToMany
sea squirt
(Ciona savignyi)
 Ascidiacea -- 31
  • 54 (a)
 ManyToMany
-- 31
  • 37 (a)
 ManyToMany
Species where no ortholog for ARHGAP35 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • 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)
  • 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)

Evolution for ARHGAP35 Gene

ENSEMBL:
Gene Tree for ARHGAP35 (if available)
TreeFam:
Gene Tree for ARHGAP35 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for ARHGAP35: view image

Paralogs for ARHGAP35 Gene

Paralogs for ARHGAP35 Gene

(5) SIMAP similar genes for ARHGAP35 Gene using alignment to 1 proteins:

  • RHG35_HUMAN
genes like me logo Genes that share paralogs with ARHGAP35: view

Variants for ARHGAP35 Gene

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Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for ARHGAP35 Gene

SNP ID Clinical significance and condition Chr 19 pos Variation AA Info Type
774356 Benign: not provided 46,919,050(+) T/C SYNONYMOUS_VARIANT
774357 Benign: not provided 46,922,167(+) G/T SYNONYMOUS_VARIANT
782652 Benign: not provided 46,920,418(+) G/A SYNONYMOUS_VARIANT
rs1555757156 Uncertain Significance: not provided 46,919,973(+) GA/G FRAMESHIFT_VARIANT
rs869312173 Uncertain Significance: Ductal breast carcinoma 46,920,634(+) GC/AA MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for ARHGAP35 Gene

Structural Variations from Database of Genomic Variants (DGV) for ARHGAP35 Gene

Variant ID Type Subtype PubMed ID
esv2750638 CNV gain 17666407
esv33665 CNV loss 17666407
nsv472531 CNV novel sequence insertion 20440878
nsv520664 CNV gain+loss 19592680

Variation tolerance for ARHGAP35 Gene

Residual Variation Intolerance Score: 0.892% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.90; 35.47% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ARHGAP35 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
ARHGAP35

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ARHGAP35 Gene

Disorders for ARHGAP35 Gene

Additional Disease Information for ARHGAP35

ATLAS of Genetics and Cytogenetics in Oncology and Haematology

No disorders were found for ARHGAP35 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for ARHGAP35 Gene

Publications for ARHGAP35 Gene

  1. Molecular cloning and characterization of a factor that binds the human glucocorticoid receptor gene and represses its expression. (PMID: 1894621) LeClerc S … Govindan MV (The Journal of biological chemistry 1991) 2 3 4 23 54
  2. Neutrophil functions and autoimmune arthritis in the absence of p190RhoGAP: generation and analysis of a novel null mutation in mice. (PMID: 20675588) Németh T … Mócsai A (Journal of immunology (Baltimore, Md. : 1950) 2010) 2 3 4 54
  3. Regulation of the substrate preference of p190RhoGAP by protein kinase C-mediated phosphorylation of a phospholipid binding site. (PMID: 19673492) Lévay M … Ligeti E (Biochemistry 2009) 3 4 23 54
  4. p190-A, a human tumor suppressor gene, maps to the chromosomal region 19q13.3 that is reportedly deleted in some gliomas. (PMID: 11054565) Tikoo A … Maruta H (Gene 2000) 3 4 23 54
  5. NMR structural studies on human p190-A RhoGAPFF1 revealed that domain phosphorylation by the PDGF-receptor alpha requires its previous unfolding. (PMID: 19393245) Bonet R … Macias MJ (Journal of molecular biology 2009) 3 4 54

ExternalLinks

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