title: Human ARHGDIG, a GDP-dissociation inhibitor for Rho proteins: genomic structure, sequence, expression analysis, and mapping to chromosome 16p13.3.
abstract: GDP-dissociation inhibitors (GDIs) play a primary role in modulating the activity of GTPases. We recently reported the identification of a new GDI for the Rho-related GTPases named RhoGDIgamma. This gene is now designated ARHGDIG by HUGO. Here, in a detailed analysis of tissue expression of ARHGDIG, we observe high levels in the entire brain, with regional variations. The mRNA is also present at high levels in kidney and pancreas and at moderate levels in spinal cord, stomach, and pituitary gland. In other tissues examined, the mRNA levels are very low (lung, trachea, small intestine, colon, placenta) or undetectable. RT-PCR analysis of total RNA isolated from exocrine pancreas and islets shows that the gene is expressed in both tissues. We also report the genomic structure of ARHGDIG. The gene spans over 4 kb and is organized into six exons and five introns. The upstream region lacks a canonical TATA box and contains several putative binding sites for ubiquitous and tissue-specific factors active in central nervous system development. Using FISH, we have mapped the gene to chromosome band 16p13.3. This band is rich in deletion mutants of genes involved in several human diseases, notably polycystic kidney disease, alpha-thalassemia, tuberous sclerosis, mental retardation, and cancer. The promoter structure and the chromosomal location of RhoGDIgamma suggest its importance and underscore the need for further investigation into its biology.
authors.affiliation: Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts, 02215, USA. cadra@bidmc.harvard.edu
authors.forename: C N
authors.initials: CN
authors.lastname: Adra
authors.forename: A R
authors.initials: AR
authors.lastname: Iyengar
authors.forename: F A
authors.initials: FA
authors.lastname: Syed
authors.forename: I N
authors.initials: IN
authors.lastname: Kanaan
authors.forename: H L
authors.initials: HL
authors.lastname: Rilo
authors.forename: W
authors.initials: W
authors.lastname: Yu
authors.forename: R
authors.initials: R
authors.lastname: Kheraj
authors.forename: S R
authors.initials: SR
authors.lastname: Lin
authors.forename: T
authors.initials: T
authors.lastname: Horiuchi
authors.forename: S
authors.initials: S
authors.lastname: Khan
authors.forename: S
authors.initials: S
authors.lastname: Weremowicz
authors.forename: B
authors.initials: B
authors.lastname: Lim
authors.forename: C C
authors.initials: CC
authors.lastname: Morton
authors.forename: D R
authors.initials: DR
authors.lastname: Higgs
mesh_terms: D001483:Base Sequence; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D003001:Cloning, Molecular; D019204:GTP-Binding Proteins / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D020730:Guanine Nucleotide Dissociation Inhibitors; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D017422:Sequence Analysis, DNA; D020741:rho GTP-Binding Proteins; D062950:rho Guanine Nucleotide Dissociation Inhibitor gamma
chemical_list: C569643:ARHGDIG protein, human; D020730:Guanine Nucleotide Dissociation Inhibitors; D012333:RNA, Messenger; D062950:rho Guanine Nucleotide Dissociation Inhibitor gamma; D019204:GTP-Binding Proteins; D020741:rho GTP-Binding Proteins