RASD1: Difference between revisions

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{{Infobox_gene}}
{{PBB_Controls
'''Dexamethasone-induced Ras-related protein 1''' (RASD1) is a [[protein]] that in humans is encoded by the ''RASD1'' [[gene]] on [[Chromosome 17 (human)|chromosome 17]].<ref name="pmid10947988">{{cite journal | vauthors = St Croix B, Rago C, Velculescu V, Traverso G, Romans KE, Montgomery E, Lal A, Riggins GJ, Lengauer C, Vogelstein B, Kinzler KW | title = Genes expressed in human tumor endothelium | journal = Science | volume = 289 | issue = 5482 | pages = 1197–202 | date = August 2000 | pmid = 10947988 | pmc =  | doi = 10.1126/science.289.5482.1197 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: RASD1 RAS, dexamethasone-induced 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=51655| accessdate = }}</ref> It is ubiquitously expressed in many tissues and cell types.<ref>{{Cite web|url=http://biogps.org/#goto=genereport&id=51655|title=BioGPS - your Gene Portal System|website=biogps.org|access-date=2016-10-12}}</ref> As a member of the [[Ras family|Ras superfamily]] of [[Small G protein|small G-proteins]], RASD1 regulates [[signal transduction pathways]] through both [[G protein]]s and [[G protein-coupled receptors]].<ref name="pmid11751935"/> RASD1 has been associated with several [[cancer]]s.<ref name="Tian_2013" /> The ''RASD1'' gene also contains one of 27 [[SNPs]] associated with increased risk of [[coronary artery disease]].<ref name=":0" />
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Structure ==
{{GNF_Protein_box
| image =
| image_source =
| PDB =  
| Name = RAS, dexamethasone-induced 1
| HGNCid = 15828
| Symbol = RASD1
| AltSymbols =; AGS1; DEXRAS1; MGC:26290
| OMIM = 605550
| ECnumber = 
| Homologene = 7509
| MGIid = 1270848
| GeneAtlas_image1 = PBB_GE_RASD1_gnf1h00203_at_tn.png
| Function = {{GNF_GO|id=GO:0000166 |text = nucleotide binding}} {{GNF_GO|id=GO:0003924 |text = GTPase activity}} {{GNF_GO|id=GO:0005085 |text = guanyl-nucleotide exchange factor activity}} {{GNF_GO|id=GO:0005525 |text = GTP binding}}
| Component = {{GNF_GO|id=GO:0005622 |text = intracellular}} {{GNF_GO|id=GO:0016020 |text = membrane}}
| Process = {{GNF_GO|id=GO:0007165 |text = signal transduction}} {{GNF_GO|id=GO:0007186 |text = G-protein coupled receptor protein signaling pathway}} {{GNF_GO|id=GO:0007264 |text = small GTPase mediated signal transduction}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 51655
    | Hs_Ensembl = ENSG00000108551
    | Hs_RefseqProtein = NP_057168
    | Hs_RefseqmRNA = NM_016084
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 17
    | Hs_GenLoc_start = 17338480
    | Hs_GenLoc_end = 17340432
    | Hs_Uniprot = Q9Y272
    | Mm_EntrezGene = 19416
    | Mm_Ensembl = ENSMUSG00000049892
    | Mm_RefseqmRNA = NM_009026
    | Mm_RefseqProtein = NP_033052
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 11
    | Mm_GenLoc_start = 59779376
    | Mm_GenLoc_end = 59781137
    | Mm_Uniprot = Q5SWR8
  }}
}}
'''RAS, dexamethasone-induced 1''', also known as '''RASD1''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: RASD1 RAS, dexamethasone-induced 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=51655| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
=== Gene ===
{{PBB_Summary
The ''RASD1'' gene resides on chromosome 17 at the band 17p11.2 and contains 2 [[exon]]s.<ref name="entrez" /> This gene produces 2 [[isoforms]] through [[alternative splicing]].<ref name=":1">{{Cite web|url=https://www.uniprot.org/uniprot/Q9Y272|title=RASD1 - Dexamethasone-induced Ras-related protein 1 precursor - Homo sapiens (Human) - RASD1 gene & protein|website=www.uniprot.org|access-date=2016-10-12}}</ref> A [[Glucocorticoid response elements|glucocorticoid response element]] (GRE) located in the 3'- flanking region of this gene allows glucocorticoids to induce expression of RASD1.<ref name=":2">{{cite journal | vauthors = Wie J, Kim BJ, Myeong J, Ha K, Jeong SJ, Yang D, Kim E, Jeon JH, So I | title = The Roles of Rasd1 small G proteins and leptin in the activation of TRPC4 transient receptor potential channels | journal = Channels | volume = 9 | issue = 4 | pages = 186–95 | date = 2015-01-01 | pmid = 26083271 | doi = 10.1080/19336950.2015.1058454 | pmc=4594510}}</ref>
| section_title =  
| summary_text = This gene encodes a Ras-related protein that is stimulated by dexamethasone. The exact function of this gene is unknown, but it may play a role in dexamethasone-induced alterations in cell morphology, growth and cell-extracellular matrix interactions.  In addition, studies of a similar rat protein suggest that it functions as as a novel physiologic nitric oxide (NO) effector. The gene product belongs to the Ras superfamily of small GTPases.<ref name="entrez">{{cite web | title = Entrez Gene: RASD1 RAS, dexamethasone-induced 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=51655| accessdate = }}</ref>
}}


==References==
=== Protein ===
{{reflist|2}}
This protein is a small GTPase belonging to the Ras superfamily.<ref name=":1" /> As a Ras superfamily member, RASD1 shares several motifs characteristic of Ras proteins, including four highly conserved GTP binding pocket domains: the phosphate/magnesium binding regions GXXXXGK(S/T) (domain Σ1), DXXG (domain Σ2), and the guanine base binding loops NKXD (domain Σ3) and EXSAK (domain Σ4). These four domains, along with an effector loop, are responsible for binding to other proteins and signaling molecules. Another common Ras motif, the CAAX motif, can be found in the [[C-terminus|C-terminal]] of RASD1 and promotes the [[subcellular localization]] of RASD1 to the [[plasma membrane]]. As a GTPase, RASD1 also shares motifs, such as in the regions G-1 to G-3, with other GTPases.
==Further reading==
The full-length RASD1 [[Complementary DNA|cDNA]] produces a protein with a length of 280 [[amino acid residue]]s and a [[molecular mass]] of 31.7 [[Unified atomic mass unit|kDa]].<ref name=":2" />
{{refbegin | 2}}
 
{{PBB_Further_reading
== Function ==
| citations =
 
*{{cite journal  | author=Kemppainen RJ, Behrend EN |title=Dexamethasone rapidly induces a novel ras superfamily member-related gene in AtT-20 cells. |journal=J. Biol. Chem. |volume=273 |issue= 6 |pages= 3129-31 |year= 1998 |pmid= 9452419 |doi=  }}
RASD1 is expressed in many tissues including brain, heart, liver, and kidney.<ref name="pmid9452419">{{cite journal | vauthors = Kemppainen RJ, Behrend EN | title = Dexamethasone rapidly induces a novel ras superfamily member-related gene in AtT-20 cells | journal = The Journal of Biological Chemistry | volume = 273 | issue = 6 | pages = 3129–31 | date = February 1998 | pmid = 9452419 | doi=10.1074/jbc.273.6.3129}}</ref><ref name="pmid10673050">{{cite journal | vauthors = Tu Y, Wu C | title = Cloning, expression and characterization of a novel human Ras-related protein that is regulated by glucocorticoid hormone | journal = Biochimica et Biophysica Acta | volume = 1489 | issue = 2-3 | pages = 452–6 | date = December 1999 | pmid = 10673050 | doi=10.1016/s0167-4781(99)00197-9}}</ref><ref name="pmid11086993">{{cite journal | vauthors = Fang M, Jaffrey SR, Sawa A, Ye K, Luo X, Snyder SH | title = Dexras1: a G protein specifically coupled to neuronal nitric oxide synthase via CAPON | journal = Neuron | volume = 28 | issue = 1 | pages = 183–93 | date = October 2000 | pmid = 11086993 | doi=10.1016/S0896-6273(00)00095-7}}</ref> It is also present in [[bone marrow]], but its expression is absent or at very low levels in spleen, lymph node, and peripheral blood [[leukocytes]].<ref name="pmid11086993" /><ref name="pmid15184869">{{cite journal | vauthors = Vaidyanathan G, Cismowski MJ, Wang G, Vincent TS, Brown KD, Lanier SM | title = The Ras-related protein AGS1/RASD1 suppresses cell growth | journal = Oncogene | volume = 23 | issue = 34 | pages = 5858–63 | date = July 2004 | pmid = 15184869 | doi = 10.1038/sj.onc.1207774 }}</ref> RASD1 modulates multiple signaling cascades. RASD1 could activate [[G proteins]] in a receptor-independent manner and inhibit signal transduction through several different G protein-coupled receptors.<ref name="pmid11842095">{{cite journal | vauthors = Takesono A, Nowak MW, Cismowski M, Duzic E, Lanier SM | title = Activator of G-protein signaling 1 blocks GIRK channel activation by a G-protein-coupled receptor: apparent disruption of receptor signaling complexes | journal = The Journal of Biological Chemistry | volume = 277 | issue = 16 | pages = 13827–30 | date = April 2002 | pmid = 11842095 | doi = 10.1074/jbc.M201064200 }}</ref><ref name="pmid11751935">{{cite journal | vauthors = Graham TE, Prossnitz ER, Dorin RI | title = Dexras1/AGS-1 inhibits signal transduction from the Gi-coupled formyl peptide receptor to Erk-1/2 MAP kinases | journal = The Journal of Biological Chemistry | volume = 277 | issue = 13 | pages = 10876–82 | date = March 2002 | pmid = 11751935 | doi = 10.1074/jbc.M110397200 }}</ref> Although RASD1 is a member of the [[Ras superfamily]] of small G-proteins, which often promotes cell growth and tumor expansion, it plays an active role in preventing aberrant cell growth.<ref name="pmid15184869"/> It can be induced by [[corticosteroids]] and may play a role in the negative feedback loop controlling [[adrenocorticotropic hormone]] (ACTH) secretion.<ref name="pmid 11598380">{{cite journal | vauthors = Brogan MD, Behrend EN, Kemppainen RJ | title = Regulation of Dexras1 expression by endogenous steroids | journal = Neuroendocrinology | volume = 74 | issue = 4 | pages = 244–50 | date = October 2001 | pmid = 11598380 | doi = 10.1159/000054691}}</ref> In the [[hypothalamus]], RASD1 expression is induced in two ways: one by elevated [[glucocorticoids]] in response to stress, and one in response to increased plasma [[osmolality]] resulting from osmotic stress. Based on its inhibitory actions on [[CREB]] [[phosphorylation]], increased RASD1 in [[vasopressin]]-expressing neurons may be essential in controlling the transcriptional responses to stressors in both the [[supraoptic nucleus]] and [[paraventricular nucleus]] via modulation of the cAMP-PKA-CREB signaling pathway.<ref name="pmid 26739966">{{cite journal | vauthors = Greenwood MP, Greenwood M, Mecawi AS, Antunes-Rodrigues J, Paton JF, Murphy D | title = Rasd1, a small G protein with a big role in the hypothalamic response to neuronal activation | journal = Molecular Brain | volume = 9 | pages = 1 | date = January 2016 | pmid = 26739966 | doi = 10.1186/s13041-015-0182-2 | pmc=4704412}}</ref> RASD1 is also reported to function with [[leptin]] in the activation of [[TRPC4]] transient receptor potential channels and, thus, plays a role in regulating electrical excitability in gastrointestinal myocytes, pancreatic [[β-cells]], and neurons.<ref name="pmid 26083271">{{cite journal | vauthors = Wie J, Kim BJ, Myeong J, Ha K, Jeong SJ, Yang D, Kim E, Jeon JH, So I | title = The Roles of Rasd1 small G proteins and leptin in the activation of TRPC4 transient receptor potential channels | journal = Channels | volume = 9 | issue = 4 | pages = 186–95 | date = 2015 | pmid = 26083271 | doi = 10.1080/19336950.2015.1058454 | pmc=4594510}}</ref> In addition, the interaction between RASD1 and [[Ear2]] is involved in [[renin]] transcriptional regulation.<ref name="pmid 21247419">{{cite journal | vauthors = Tan JJ, Ong SA, Chen KS | title = Rasd1 interacts with Ear2 (Nr2f6) to regulate renin transcription | journal = BMC Molecular Biology | volume = 12 | pages = 4 | date = 19 January 2011 | pmid = 21247419 | doi = 10.1186/1471-2199-12-4 | pmc=3036621}}</ref>
*{{cite journal  | author=Cismowski MJ, Takesono A, Ma C, ''et al.'' |title=Genetic screens in yeast to identify mammalian nonreceptor modulators of G-protein signaling. |journal=Nat. Biotechnol. |volume=17 |issue= 9 |pages= 878-83 |year= 1999 |pmid= 10471929 |doi= 10.1038/12867 }}
 
*{{cite journal | author=Tu Y, Wu C |title=Cloning, expression and characterization of a novel human Ras-related protein that is regulated by glucocorticoid hormone. |journal=Biochim. Biophys. Acta |volume=1489 |issue= 2-3 |pages= 452-6 |year= 2000 |pmid= 10673050 |doi= }}
== Clinical significance ==
*{{cite journal | author=Cismowski MJ, Ma C, Ribas C, ''et al.'' |title=Activation of heterotrimeric G-protein signaling by a ras-related protein. Implications for signal integration. |journal=J. Biol. Chem. |volume=275 |issue= 31 |pages= 23421-4 |year= 2000 |pmid= 10840027 |doi= 10.1074/jbc.C000322200 }}
In humans, upregulation of RASD1 leading to increased apoptosis has been observed in several human cancer cell lines such as DU-154 human prostate cancer cells<ref>{{cite journal | vauthors = Liu XJ, Li YQ, Chen QY, Xiao SJ, Zeng SE | title = Up-regulating of RASD1 and apoptosis of DU-145 human prostate cancer cells induced by formononetin in vitro | journal = Asian Pacific Journal of Cancer Prevention | volume = 15 | issue = 6 | pages = 2835–9 | date = 2014-01-01 | pmid = 24761910 | doi=10.7314/apjcp.2014.15.6.2835}}</ref> and in human [[breast cancer]] cells MCF-7.<ref name = "Tian_2013">{{cite journal | vauthors = Tian J, Duan YX, Bei CY, Chen J | title = Calycosin induces apoptosis by upregulation of RASD1 in human breast cancer cells MCF-7 | journal = Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Métabolisme | volume = 45 | issue = 8 | pages = 593–8 | date = August 2013 | pmid = 23609007 | doi = 10.1055/s-0033-1341510 }}</ref> In the latter, high concentrations of calycosin significantly suppressed the proliferation of MCF-7 cells, thereby promoting [[apoptosis]] of the cells. Moreover, compared with a control group, the expression of [[Bcl-2]] decreased with calycosin while [[Bcl-2-associated X protein|Bax]] increased, and these changes correlated with an elevated expression of RASD1. Together, it appears that, at relatively high concentrations, calycosin can trigger the [[Mitochondrion|mitochondrial]] apoptotic pathway by upregulating RASD1.<ref name = "Tian_2013"/>
*{{cite journal | author=St Croix B, Rago C, Velculescu V, ''et al.'' |title=Genes expressed in human tumor endothelium. |journal=Science |volume=289 |issue= 5482 |pages= 1197-202 |year= 2000 |pmid= 10947988 |doi= }}
 
*{{cite journal | author=Hartley JL, Temple GF, Brasch MA |title=DNA cloning using in vitro site-specific recombination. |journal=Genome Res. |volume=10 |issue= 11 |pages= 1788-95 |year= 2001 |pmid= 11076863 |doi= }}
=== Clinical marker ===
*{{cite journal | author=Fang M, Jaffrey SR, Sawa A, ''et al.'' |title=Dexras1: a G protein specifically coupled to neuronal nitric oxide synthase via CAPON. |journal=Neuron |volume=28 |issue= 1 |pages= 183-93 |year= 2000 |pmid= 11086993 |doi= }}
Additionally, in the cardiovascular field, a genome-wide analysis of common variants demonstrated a substantial overlap in the genetic risk of ischemic stroke and coronary artery disease, such as the link between RASD1 and other loci such as RAI1 and PEMT.<ref>{{cite journal | vauthors = Dichgans M, Malik R, König IR, Rosand J, Clarke R, Gretarsdottir S, Thorleifsson G, Mitchell BD, Assimes TL, Levi C, O'Donnell CJ, Fornage M, Thorsteinsdottir U, Psaty BM, Hengstenberg C, Seshadri S, Erdmann J, Bis JC, Peters A, Boncoraglio GB, März W, Meschia JF, Kathiresan S, Ikram MA, McPherson R, Stefansson K, Sudlow C, Reilly MP, Thompson JR, Sharma P, Hopewell JC, Chambers JC, Watkins H, Rothwell PM, Roberts R, Markus HS, Samani NJ, Farrall M, Schunkert H | display-authors = 6 | title = Shared genetic susceptibility to ischemic stroke and coronary artery disease: a genome-wide analysis of common variants | journal = Stroke: A Journal of Cerebral Circulation | volume = 45 | issue = 1 | pages = 24–36 | date = January 2014 | pmid = 24262325 | doi = 10.1161/STROKEAHA.113.002707 | pmc=4112102}}</ref> A multi-locus genetic risk score study based on a combination of 27 loci, including the RASD1 gene, identified individuals at increased risk for both incident and recurrent coronary artery disease events, as well as an enhanced clinical benefit from statin therapy. The study was based on a community cohort study (the Malmo Diet and Cancer study) and four additional randomized controlled trials of primary prevention cohorts (JUPITER and ASCOT) and secondary prevention cohorts (CARE and PROVE IT-TIMI 22).<ref name=":0">{{cite journal | vauthors = Mega JL, Stitziel NO, Smith JG, Chasman DI, Caulfield MJ, Devlin JJ, Nordio F, Hyde CL, Cannon CP, Sacks FM, Poulter NR, Sever PS, Ridker PM, Braunwald E, Melander O, Kathiresan S, Sabatine MS | title = Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials | journal = Lancet | volume = 385 | issue = 9984 | pages = 2264–71 | date = June 2015 | pmid = 25748612 | doi = 10.1016/S0140-6736(14)61730-X | pmc=4608367}}</ref>
*{{cite journal | author=Ognjanovic S, Bao S, Yamamoto SY, ''et al.'' |title=Genomic organization of the gene coding for human pre-B-cell colony enhancing factor and expression in human fetal membranes. |journal=J. Mol. Endocrinol. |volume=26 |issue= 2 |pages= 107-17 |year= 2001 |pmid= 11241162 |doi= }}
 
*{{cite journal  | author=Takesono A, Nowak MW, Cismowski M, ''et al.'' |title=Activator of G-protein signaling 1 blocks GIRK channel activation by a G-protein-coupled receptor: apparent disruption of receptor signaling complexes. |journal=J. Biol. Chem. |volume=277 |issue= 16 |pages= 13827-30 |year= 2002 |pmid= 11842095 |doi= 10.1074/jbc.M201064200 }}
==  Interactions ==
*{{cite journal  | author=Bi W, Yan J, Stankiewicz P, ''et al.'' |title=Genes in a refined Smith-Magenis syndrome critical deletion interval on chromosome 17p11.2 and the syntenic region of the mouse. |journal=Genome Res. |volume=12 |issue= 5 |pages= 713-28 |year= 2002 |pmid= 11997338 |doi= 10.1101/gr.73702 }}
RASD1 has been shown to [[Protein-protein interaction|interact]] with [[NOS1AP]].<ref name="pmid11086993"/>
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
 
*{{cite journal  | author=Jaffrey SR, Fang M, Snyder SH |title=Nitrosopeptide mapping: a novel methodology reveals s-nitrosylation of dexras1 on a single cysteine residue. |journal=Chem. Biol. |volume=9 |issue= 12 |pages= 1329-35 |year= 2003 |pmid= 12498886 |doi= }}
== References ==
*{{cite journal | author=Kemppainen RJ, Cox E, Behrend EN, ''et al.'' |title=Identification of a glucocorticoid response element in the 3'-flanking region of the human Dexras1 gene. |journal=Biochim. Biophys. Acta |volume=1627 |issue= 2-3 |pages= 85-9 |year= 2003 |pmid= 12818426 |doi= }}
{{reflist|33em}}
*{{cite journal | author=Vaidyanathan G, Cismowski MJ, Wang G, ''et al.'' |title=The Ras-related protein AGS1/RASD1 suppresses cell growth. |journal=Oncogene |volume=23 |issue= 34 |pages= 5858-63 |year= 2004 |pmid= 15184869 |doi= 10.1038/sj.onc.1207774 }}
 
*{{cite journal  | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
== Further reading ==
*{{cite journal | author=Wiemann S, Arlt D, Huber W, ''et al.'' |title=From ORFeome to biology: a functional genomics pipeline. |journal=Genome Res. |volume=14 |issue= 10B |pages= 2136-44 |year= 2004 |pmid= 15489336 |doi= 10.1101/gr.2576704 }}
{{refbegin|33em}}
*{{cite journal  | author=Rual JF, Venkatesan K, Hao T, ''et al.'' |title=Towards a proteome-scale map of the human protein-protein interaction network. |journal=Nature |volume=437 |issue= 7062 |pages= 1173-8 |year= 2005 |pmid= 16189514 |doi= 10.1038/nature04209 }}
* {{cite journal | vauthors = Kemppainen RJ, Behrend EN | title = Dexamethasone rapidly induces a novel ras superfamily member-related gene in AtT-20 cells | journal = The Journal of Biological Chemistry | volume = 273 | issue = 6 | pages = 3129–31 | date = Feb 1998 | pmid = 9452419 | doi = 10.1074/jbc.273.6.3129 }}
*{{cite journal  | author=Hiskens R, Vatish M, Hill C, ''et al.'' |title=Specific in vivo binding of activator of G protein signalling 1 to the Gbeta1 subunit. |journal=Biochem. Biophys. Res. Commun. |volume=337 |issue= 4 |pages= 1038-46 |year= 2005 |pmid= 16225846 |doi= 10.1016/j.bbrc.2005.09.149 }}
* {{cite journal | vauthors = Cismowski MJ, Takesono A, Ma C, Lizano JS, Xie X, Fuernkranz H, Lanier SM, Duzic E | title = Genetic screens in yeast to identify mammalian nonreceptor modulators of G-protein signaling | journal = Nature Biotechnology | volume = 17 | issue = 9 | pages = 878–83 | date = Sep 1999 | pmid = 10471929 | doi = 10.1038/12867 }}
*{{cite journal | author=Mehrle A, Rosenfelder H, Schupp I, ''et al.'' |title=The LIFEdb database in 2006. |journal=Nucleic Acids Res. |volume=34 |issue= Database issue |pages= D415-8 |year= 2006 |pmid= 16381901 |doi= 10.1093/nar/gkj139 }}
* {{cite journal | vauthors = Tu Y, Wu C | title = Cloning, expression and characterization of a novel human Ras-related protein that is regulated by glucocorticoid hormone | journal = Biochimica et Biophysica Acta | volume = 1489 | issue = 2-3 | pages = 452–6 | date = Dec 1999 | pmid = 10673050 | doi = 10.1016/s0167-4781(99)00197-9 }}
*{{cite journal | author=Nguyen CH, Watts VJ |title=Dexamethasone-induced Ras protein 1 negatively regulates protein kinase C delta: implications for adenylyl cyclase 2 signaling. |journal=Mol. Pharmacol. |volume=69 |issue= 5 |pages= 1763-71 |year= 2006 |pmid= 16489124 |doi= 10.1124/mol.105.019133 }}
* {{cite journal | vauthors = Cismowski MJ, Ma C, Ribas C, Xie X, Spruyt M, Lizano JS, Lanier SM, Duzic E | title = Activation of heterotrimeric G-protein signaling by a ras-related protein. Implications for signal integration | journal = The Journal of Biological Chemistry | volume = 275 | issue = 31 | pages = 23421–4 | date = Aug 2000 | pmid = 10840027 | doi = 10.1074/jbc.C000322200 }}
}}
* {{cite journal | vauthors = Hartley JL, Temple GF, Brasch MA | title = DNA cloning using in vitro site-specific recombination | journal = Genome Research | volume = 10 | issue = 11 | pages = 1788–95 | date = Nov 2000 | pmid = 11076863 | pmc = 310948 | doi = 10.1101/gr.143000 }}
* {{cite journal | vauthors = Fang M, Jaffrey SR, Sawa A, Ye K, Luo X, Snyder SH | title = Dexras1: a G protein specifically coupled to neuronal nitric oxide synthase via CAPON | journal = Neuron | volume = 28 | issue = 1 | pages = 183–93 | date = Oct 2000 | pmid = 11086993 | doi = 10.1016/S0896-6273(00)00095-7 }}
* {{cite journal | vauthors = Ognjanovic S, Bao S, Yamamoto SY, Garibay-Tupas J, Samal B, Bryant-Greenwood GD | title = Genomic organization of the gene coding for human pre-B-cell colony enhancing factor and expression in human fetal membranes | journal = Journal of Molecular Endocrinology | volume = 26 | issue = 2 | pages = 107–17 | date = Apr 2001 | pmid = 11241162 | doi = 10.1677/jme.0.0260107 }}
* {{cite journal | vauthors = Takesono A, Nowak MW, Cismowski M, Duzic E, Lanier SM | title = Activator of G-protein signaling 1 blocks GIRK channel activation by a G-protein-coupled receptor: apparent disruption of receptor signaling complexes | journal = The Journal of Biological Chemistry | volume = 277 | issue = 16 | pages = 13827–30 | date = Apr 2002 | pmid = 11842095 | doi = 10.1074/jbc.M201064200 }}
* {{cite journal | vauthors = Bi W, Yan J, Stankiewicz P, Park SS, Walz K, Boerkoel CF, Potocki L, Shaffer LG, Devriendt K, Nowaczyk MJ, Inoue K, Lupski JR | title = Genes in a refined Smith-Magenis syndrome critical deletion interval on chromosome 17p11.2 and the syntenic region of the mouse | journal = Genome Research | volume = 12 | issue = 5 | pages = 713–28 | date = May 2002 | pmid = 11997338 | pmc = 186594 | doi = 10.1101/gr.73702 | url = http://genome.cshlp.org/content/12/5/713.full.pdf }}
* {{cite journal | vauthors = Jaffrey SR, Fang M, Snyder SH | title = Nitrosopeptide mapping: a novel methodology reveals s-nitrosylation of dexras1 on a single cysteine residue | journal = Chemistry & Biology | volume = 9 | issue = 12 | pages = 1329–35 | date = Dec 2002 | pmid = 12498886 | doi = 10.1016/S1074-5521(02)00293-4 }}
* {{cite journal | vauthors = Kemppainen RJ, Cox E, Behrend EN, Brogan MD, Ammons JM | title = Identification of a glucocorticoid response element in the 3'-flanking region of the human Dexras1 gene | journal = Biochimica et Biophysica Acta | volume = 1627 | issue = 2-3 | pages = 85–9 | date = Jun 2003 | pmid = 12818426 | doi = 10.1016/s0167-4781(03)00079-4 }}
* {{cite journal | vauthors = Vaidyanathan G, Cismowski MJ, Wang G, Vincent TS, Brown KD, Lanier SM | title = The Ras-related protein AGS1/RASD1 suppresses cell growth | journal = Oncogene | volume = 23 | issue = 34 | pages = 5858–63 | date = Jul 2004 | pmid = 15184869 | doi = 10.1038/sj.onc.1207774 }}
* {{cite journal | vauthors = Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A | title = From ORFeome to biology: a functional genomics pipeline | journal = Genome Research | volume = 14 | issue = 10B | pages = 2136–44 | date = Oct 2004 | pmid = 15489336 | pmc = 528930 | doi = 10.1101/gr.2576704 }}
* {{cite journal | vauthors = Hiskens R, Vatish M, Hill C, Davey J, Ladds G | title = Specific in vivo binding of activator of G protein signalling 1 to the Gbeta1 subunit | journal = Biochemical and Biophysical Research Communications | volume = 337 | issue = 4 | pages = 1038–46 | date = Dec 2005 | pmid = 16225846 | doi = 10.1016/j.bbrc.2005.09.149 }}
* {{cite journal | vauthors = Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, Bechtel S, Simpson J, Hofmann O, Hide W, Glatting KH, Huber W, Pepperkok R, Poustka A, Wiemann S | title = The LIFEdb database in 2006 | journal = Nucleic Acids Research | volume = 34 | issue = Database issue | pages = D415-8 | date = Jan 2006 | pmid = 16381901 | pmc = 1347501 | doi = 10.1093/nar/gkj139 }}
* {{cite journal | vauthors = Nguyen CH, Watts VJ | title = Dexamethasone-induced Ras protein 1 negatively regulates protein kinase C delta: implications for adenylyl cyclase 2 signaling | journal = Molecular Pharmacology | volume = 69 | issue = 5 | pages = 1763–71 | date = May 2006 | pmid = 16489124 | doi = 10.1124/mol.105.019133 }}
* {{cite journal | vauthors = Compton SL, Kemppainen RJ, Behrend EN | title = Prenylated Rab acceptor domain family member 1 is involved in stimulated ACTH secretion and inhibition | journal = Cellular Signalling | volume = 21 | issue = 12 | pages = 1901–9 | date = Dec 2009 | pmid = 19733236 | doi = 10.1016/j.cellsig.2009.08.007 }}
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Latest revision as of 18:42, 25 October 2018

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
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Ensembl

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UniProt

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Dexamethasone-induced Ras-related protein 1 (RASD1) is a protein that in humans is encoded by the RASD1 gene on chromosome 17.[1][2] It is ubiquitously expressed in many tissues and cell types.[3] As a member of the Ras superfamily of small G-proteins, RASD1 regulates signal transduction pathways through both G proteins and G protein-coupled receptors.[4] RASD1 has been associated with several cancers.[5] The RASD1 gene also contains one of 27 SNPs associated with increased risk of coronary artery disease.[6]

Structure

Gene

The RASD1 gene resides on chromosome 17 at the band 17p11.2 and contains 2 exons.[2] This gene produces 2 isoforms through alternative splicing.[7] A glucocorticoid response element (GRE) located in the 3'- flanking region of this gene allows glucocorticoids to induce expression of RASD1.[8]

Protein

This protein is a small GTPase belonging to the Ras superfamily.[7] As a Ras superfamily member, RASD1 shares several motifs characteristic of Ras proteins, including four highly conserved GTP binding pocket domains: the phosphate/magnesium binding regions GXXXXGK(S/T) (domain Σ1), DXXG (domain Σ2), and the guanine base binding loops NKXD (domain Σ3) and EXSAK (domain Σ4). These four domains, along with an effector loop, are responsible for binding to other proteins and signaling molecules. Another common Ras motif, the CAAX motif, can be found in the C-terminal of RASD1 and promotes the subcellular localization of RASD1 to the plasma membrane. As a GTPase, RASD1 also shares motifs, such as in the regions G-1 to G-3, with other GTPases. The full-length RASD1 cDNA produces a protein with a length of 280 amino acid residues and a molecular mass of 31.7 kDa.[8]

Function

RASD1 is expressed in many tissues including brain, heart, liver, and kidney.[9][10][11] It is also present in bone marrow, but its expression is absent or at very low levels in spleen, lymph node, and peripheral blood leukocytes.[11][12] RASD1 modulates multiple signaling cascades. RASD1 could activate G proteins in a receptor-independent manner and inhibit signal transduction through several different G protein-coupled receptors.[13][4] Although RASD1 is a member of the Ras superfamily of small G-proteins, which often promotes cell growth and tumor expansion, it plays an active role in preventing aberrant cell growth.[12] It can be induced by corticosteroids and may play a role in the negative feedback loop controlling adrenocorticotropic hormone (ACTH) secretion.[14] In the hypothalamus, RASD1 expression is induced in two ways: one by elevated glucocorticoids in response to stress, and one in response to increased plasma osmolality resulting from osmotic stress. Based on its inhibitory actions on CREB phosphorylation, increased RASD1 in vasopressin-expressing neurons may be essential in controlling the transcriptional responses to stressors in both the supraoptic nucleus and paraventricular nucleus via modulation of the cAMP-PKA-CREB signaling pathway.[15] RASD1 is also reported to function with leptin in the activation of TRPC4 transient receptor potential channels and, thus, plays a role in regulating electrical excitability in gastrointestinal myocytes, pancreatic β-cells, and neurons.[16] In addition, the interaction between RASD1 and Ear2 is involved in renin transcriptional regulation.[17]

Clinical significance

In humans, upregulation of RASD1 leading to increased apoptosis has been observed in several human cancer cell lines such as DU-154 human prostate cancer cells[18] and in human breast cancer cells MCF-7.[5] In the latter, high concentrations of calycosin significantly suppressed the proliferation of MCF-7 cells, thereby promoting apoptosis of the cells. Moreover, compared with a control group, the expression of Bcl-2 decreased with calycosin while Bax increased, and these changes correlated with an elevated expression of RASD1. Together, it appears that, at relatively high concentrations, calycosin can trigger the mitochondrial apoptotic pathway by upregulating RASD1.[5]

Clinical marker

Additionally, in the cardiovascular field, a genome-wide analysis of common variants demonstrated a substantial overlap in the genetic risk of ischemic stroke and coronary artery disease, such as the link between RASD1 and other loci such as RAI1 and PEMT.[19] A multi-locus genetic risk score study based on a combination of 27 loci, including the RASD1 gene, identified individuals at increased risk for both incident and recurrent coronary artery disease events, as well as an enhanced clinical benefit from statin therapy. The study was based on a community cohort study (the Malmo Diet and Cancer study) and four additional randomized controlled trials of primary prevention cohorts (JUPITER and ASCOT) and secondary prevention cohorts (CARE and PROVE IT-TIMI 22).[6]

Interactions

RASD1 has been shown to interact with NOS1AP.[11]

References

  1. ↑ St Croix B, Rago C, Velculescu V, Traverso G, Romans KE, Montgomery E, Lal A, Riggins GJ, Lengauer C, Vogelstein B, Kinzler KW (August 2000). "Genes expressed in human tumor endothelium". Science. 289 (5482): 1197–202. doi:10.1126/science.289.5482.1197. PMID 10947988.
  2. ↑ 2.0 2.1 "Entrez Gene: RASD1 RAS, dexamethasone-induced 1".
  3. ↑ "BioGPS - your Gene Portal System". biogps.org. Retrieved 2016-10-12.
  4. ↑ 4.0 4.1 Graham TE, Prossnitz ER, Dorin RI (March 2002). "Dexras1/AGS-1 inhibits signal transduction from the Gi-coupled formyl peptide receptor to Erk-1/2 MAP kinases". The Journal of Biological Chemistry. 277 (13): 10876–82. doi:10.1074/jbc.M110397200. PMID 11751935.
  5. ↑ 5.0 5.1 5.2 Tian J, Duan YX, Bei CY, Chen J (August 2013). "Calycosin induces apoptosis by upregulation of RASD1 in human breast cancer cells MCF-7". Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Métabolisme. 45 (8): 593–8. doi:10.1055/s-0033-1341510. PMID 23609007.
  6. ↑ 6.0 6.1 Mega JL, Stitziel NO, Smith JG, Chasman DI, Caulfield MJ, Devlin JJ, Nordio F, Hyde CL, Cannon CP, Sacks FM, Poulter NR, Sever PS, Ridker PM, Braunwald E, Melander O, Kathiresan S, Sabatine MS (June 2015). "Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials". Lancet. 385 (9984): 2264–71. doi:10.1016/S0140-6736(14)61730-X. PMC 4608367. PMID 25748612.
  7. ↑ 7.0 7.1 "RASD1 - Dexamethasone-induced Ras-related protein 1 precursor - Homo sapiens (Human) - RASD1 gene & protein". www.uniprot.org. Retrieved 2016-10-12.
  8. ↑ 8.0 8.1 Wie J, Kim BJ, Myeong J, Ha K, Jeong SJ, Yang D, Kim E, Jeon JH, So I (2015-01-01). "The Roles of Rasd1 small G proteins and leptin in the activation of TRPC4 transient receptor potential channels". Channels. 9 (4): 186–95. doi:10.1080/19336950.2015.1058454. PMC 4594510. PMID 26083271.
  9. ↑ Kemppainen RJ, Behrend EN (February 1998). "Dexamethasone rapidly induces a novel ras superfamily member-related gene in AtT-20 cells". The Journal of Biological Chemistry. 273 (6): 3129–31. doi:10.1074/jbc.273.6.3129. PMID 9452419.
  10. ↑ Tu Y, Wu C (December 1999). "Cloning, expression and characterization of a novel human Ras-related protein that is regulated by glucocorticoid hormone". Biochimica et Biophysica Acta. 1489 (2–3): 452–6. doi:10.1016/s0167-4781(99)00197-9. PMID 10673050.
  11. ↑ 11.0 11.1 11.2 Fang M, Jaffrey SR, Sawa A, Ye K, Luo X, Snyder SH (October 2000). "Dexras1: a G protein specifically coupled to neuronal nitric oxide synthase via CAPON". Neuron. 28 (1): 183–93. doi:10.1016/S0896-6273(00)00095-7. PMID 11086993.
  12. ↑ 12.0 12.1 Vaidyanathan G, Cismowski MJ, Wang G, Vincent TS, Brown KD, Lanier SM (July 2004). "The Ras-related protein AGS1/RASD1 suppresses cell growth". Oncogene. 23 (34): 5858–63. doi:10.1038/sj.onc.1207774. PMID 15184869.
  13. ↑ Takesono A, Nowak MW, Cismowski M, Duzic E, Lanier SM (April 2002). "Activator of G-protein signaling 1 blocks GIRK channel activation by a G-protein-coupled receptor: apparent disruption of receptor signaling complexes". The Journal of Biological Chemistry. 277 (16): 13827–30. doi:10.1074/jbc.M201064200. PMID 11842095.
  14. ↑ Brogan MD, Behrend EN, Kemppainen RJ (October 2001). "Regulation of Dexras1 expression by endogenous steroids". Neuroendocrinology. 74 (4): 244–50. doi:10.1159/000054691. PMID 11598380.
  15. ↑ Greenwood MP, Greenwood M, Mecawi AS, Antunes-Rodrigues J, Paton JF, Murphy D (January 2016). "Rasd1, a small G protein with a big role in the hypothalamic response to neuronal activation". Molecular Brain. 9: 1. doi:10.1186/s13041-015-0182-2. PMC 4704412. PMID 26739966.
  16. ↑ Wie J, Kim BJ, Myeong J, Ha K, Jeong SJ, Yang D, Kim E, Jeon JH, So I (2015). "The Roles of Rasd1 small G proteins and leptin in the activation of TRPC4 transient receptor potential channels". Channels. 9 (4): 186–95. doi:10.1080/19336950.2015.1058454. PMC 4594510. PMID 26083271.
  17. ↑ Tan JJ, Ong SA, Chen KS (19 January 2011). "Rasd1 interacts with Ear2 (Nr2f6) to regulate renin transcription". BMC Molecular Biology. 12: 4. doi:10.1186/1471-2199-12-4. PMC 3036621. PMID 21247419.
  18. ↑ Liu XJ, Li YQ, Chen QY, Xiao SJ, Zeng SE (2014-01-01). "Up-regulating of RASD1 and apoptosis of DU-145 human prostate cancer cells induced by formononetin in vitro". Asian Pacific Journal of Cancer Prevention. 15 (6): 2835–9. doi:10.7314/apjcp.2014.15.6.2835. PMID 24761910.
  19. ↑ Dichgans M, Malik R, König IR, Rosand J, Clarke R, Gretarsdottir S, et al. (January 2014). "Shared genetic susceptibility to ischemic stroke and coronary artery disease: a genome-wide analysis of common variants". Stroke: A Journal of Cerebral Circulation. 45 (1): 24–36. doi:10.1161/STROKEAHA.113.002707. PMC 4112102. PMID 24262325.

Further reading

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