Members of the ras superfamily highly conserved ras exchange motif. Medical search. Frequent questions

Cdc42 and Rac - ancient, highly conserved, small GTPases - mediate extracellular signals, triggering changes in transcription and in the actin cytoskeleton. (biomedcentral.com)
The basic signaling properties of two major subgroups of Rho GTPases - the Cdc42 and Rac subfamilies - are highly conserved amongst all eukaryotes, but the means by which they act are not well understood. (biomedcentral.com)
Rho GTPases are small (20-30 kDa) GTP-binding proteins of the Ras superfamily. (biomedcentral.com)
Interestingly, small GTPases related to Rac are found even in organisms that lack Ras, such as plants. (biomedcentral.com)
This broad distribution across widely divergent eukaryotic species suggests that Cdc42 and Rac GTPases have an ancient origin, perhaps even predating that of their cousin Ras. (biomedcentral.com)
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. (embl-heidelberg.de)
It does not share significant sequence homology with other subtypes of small G-protein GEF motifs such as the Cdc25 domain and the Sec7 domain, which specifically interact with Ras and ARF family small GTPases, respectively, nor with other Rho protein interactive motifs, indicating that the Dbl family proteins are evolutionarily unique. (embl-heidelberg.de)
We provide evidence that KRas translocation occurs through sequestration of the polybasic-prenyl motif by Ca 2+ /calmodulin (Ca 2+ /CaM) and subsequent release of KRas from the PM, in a process reminiscent of GDP dissociation inhibitor-mediated membrane recycling of Rab and Rho GTPases. (rupress.org)
Guanine nucleotide dissociation stimulators (GDSs, or exchange factors), such as RALGDS, are effectors of Ras-related GTPases (see MIM 190020) that participate in signaling for a variety of cellular processes. (cancerindex.org)
The exchange of GDP to GTP and thus the activation of Rho GTPases is catalyzed by guanine nucleotide exchange factors (GEFs), which act downstream of numerous growth factor receptors, integrins, cytokine receptors, and cadherins. (biomedcentral.com)

The GAP function of the amino-terminal extension of ARD1 required two arginines, an intact zinc finger motif, and a group of residues which resembles a sequence present in Rho/Rac GAPs. (embl.de)
The proteins encoded by members of the Dbl family share a common domain, presented in this entry, of about 200 residues (designated the Dbl homology or DH domain) that has been shown to encode a GEF activity specific for a number of Rho family members. (embl-heidelberg.de)
Despite conservation of active-site residues, the Ras-related Rab GTPase activation pathway differs from Ras and between different Rabs. (elifesciences.org)
Conserved active-site residues in the Rab switch II region stabilising the nucleotide-free form differentiate these pathways. (elifesciences.org)
This mutant shows altered subcellular localization and reduced S-palmitoylation, a phenotype copied by mutation of conserved cysteine residues in microbat IFITM3. (life-science-alliance.org)
Residues conserved across the rhoGAP family are largely confined to one face of this bundle, which may be an interaction site for target G proteins. (embl-heidelberg.de)
1987 ). This superfamily of proteases is defined by the presence of a Zn 2+ ion at the catalytic center, which is coordinated by three histidine residues in the zinc-binding consensus sequence HExxHxxGxxH that is present in all proteolytically active metzincins, and a characteristic, strictly conserved methionine-containing tight 1,4 beta turn forming a hydrophobic cleft for the catalytic zinc ion (Bode et al. (evelinvahter.com)

The Rasd1 protein is a dexamethasone induced monomeric Ras-like G protein that oscillates in the suprachiasmatic nucleus (SCN). (biomedcentral.com)
This motif is found in Cdc42/Rac-associated proteins such as the protein kinases Pak, MRCK and Ack, the adaptor proteins Spec and WASP, and, in degenerate form, in the kinases MLK, Mekk4, adaptor Par6, scaffold protein IRSp53, and the Borg proteins. (biomedcentral.com)
Proteins called guanine nucleotide exchange factors, or GEFs for short, activate the Rab protein by promoting the release of GDP and the binding of GTP. (elifesciences.org)
IFITMs belong to the CD225/pfam04505 or "dispanin" protein superfamily ( http://pfam.xfam.org/family/PF04505 ) ( 3 ) that contains more than 2,000 members, including both prokaryotic and eukaryotic proteins, all of which encode a conserved CD225 protein domain. (life-science-alliance.org)
In doing so, this GEF-facilitated exchange of GDP for GTP is associated with structural changes in the GTP-binding protein which influence the degree to which the GTP-binding protein can interact with other molecules. (justia.com)
This gene is highly expressed in fetal brain and encodes a protein of relative molecular mass 91K, named oligophrenin-1, which contains a domain typical of a Rho-GTPase-activating protein (rhoGAP). (embl-heidelberg.de)
Matrix metalloproteases (MMPs) comprise a family of enzymes that cleave protein substrates based on a conserved mechanism involving activation of an active site-bound water molecule by a Zn 2+ ion. (evelinvahter.com)
1993 ). Catalysis of protein substrates is (most probably) carried out via a general base mechanism involving activation of a zinc-bound water molecule by the carboxylate group of the conserved glutamate residue in the catalytic pocket followed by attack of water on the polarized carbonyl group in the substrate's scissile bond (Browner et al. (evelinvahter.com)

Many, but not all, of these effectors contain a conserved 18 amino-acid binding motif that has been termed CRIB (Cdc42-Rac interactive binding), PBD (p21-binding domain) or GBD (GTPase-binding domain) [ 4 ]. (biomedcentral.com)
Both guanine nucleotide-exchange proteins and GTPase-activating proteins (GAPs) for ARFs have been cloned recently. (embl.de)
Biochemical data have established the role of the conserved DH domain in Rho GTPase interaction and activation, and the role of the tandem PH domain in intracellular targeting and/or regulation of DH domain function. (embl-heidelberg.de)
Ras superfamily GTPase activation and inactivation occur by canonical nucleotide exchange and GTP hydrolysis mechanisms. (elifesciences.org)
The active conformation is promoted by guanine-nucleotide exchange factors, and the inactive state by GTPase-activating proteins (GAPs) which stimulate the intrinsic GTPase activity of small G proteins. (embl-heidelberg.de)
By enhancing their GTPase activity, GAP proteins inactivate small Rho and Ras proteins, so inactivation of rhoGAP proteins might cause constitutive activation of their GTPase targets. (embl-heidelberg.de)
Our results demonstrate an association between cognitive impairment and a defect in a signalling pathway that depends on a Ras-like GTPase. (embl-heidelberg.de)
Ras is a small GTPase that operates as a binary molecular switch between a GDP-bound inactive and GTP-bound active state. (rupress.org)
Within their GTPase domains, they share approximately 30% amino acid identity with the Ras proteins and 40-95% identity within the family. (biomedcentral.com)

It has been hypothesized that inactivation of the RASSF1A tumor suppressor facilitates K-RAS-mediated transformation by uncoupling it from apoptotic pathways such as the Hippo pathway. (cancerindex.org)
In human lung tumors, combined activation of K-RAS and inactivation of RASSF1A is closely associated with the development of the most aggressive and worst prognosis tumors. (cancerindex.org)

We focus on six 'core' effectors that operate in almost all these species - members of the Pak, WASP/WAVE, formin, lipid-kinase, IQGAP and NADPH oxidase families. (biomedcentral.com)
When GTP is bound, for instance, Ras proteins can interact with effectors and other molecules to affect cell proliferation, differentiation and apoptosis. (justia.com)
Mutant K-RAS has been shown to have both tumor-promoting and -suppressing functions, and growing evidence suggests that the RASSF family of tumor suppressors can act as RAS apoptosis and senescence effectors. (cancerindex.org)
Among other members, we will focus our attention on the Rac and Rho subfamilies, as they are the main effectors of cell motility. (biomedcentral.com)

The 70 or so members of the Rab subfamily of proteins perform a wide range of important tasks inside cells. (elifesciences.org)
The Rab subfamily of proteins is part of the large Ras superfamily, and all members of this superfamily are activated and inactivated in a similar way, with the binding and unbinding of GDP and GTP taking place at a structure called the G-domain. (elifesciences.org)

Studies of IFITM topology suggest a type II transmembrane configuration with a cytosolic N terminus, cytosolic conserved intracellular loop (CIL) domain, transmembrane domain, and extracellular (or intraluminal) C terminus ( 4 , 5 ), although there is evidence that other IFITM topologies exist ( 6 , 7 , 8 ). (life-science-alliance.org)
Cell membranes are highly enriched in signaling receptors, transmembrane mechanosensors, pumps and channels, and, depending on their makeup, can recruit and retain a pool of mechanosensors important in the field of mechanobiology. (mechanobio.info)
The IV.3 monoclonal antibody reacts with human CD32 also known as FcγRII and FCRII, a 40 kDa polymorphic transmembrane glycoprotein and an Ig superfamily member. (bioxcell.com)

Under inflammatory conditions, abnormal osteoclast differentiation and function often results in excessive bone resorption, which is a common characteristic of many diseases, such as osteoporosis, rheumatoid arthritis (RA), psoriatic arthritis and periodontitis ( 1 - 5 ). (frontiersin.org)
These proteins contain a characteristic zinc finger motif (Cys-x2-Cys-x(16,17)-x2-Cys) which displays some similarity to the C4-type GATA zinc finger. (embl.de)
All members contain the sequence motifs characteristic of all GTP-binding proteins, bind to GDP and GTP with high affinity. (biomedcentral.com)

02:23.0 Innate immunity deals with the evolutionarily conserved components 02:25.3 and adaptive immunity 02:27.3 is something that was added in the vertebrates 02:29.2 to basically defend against, 02:31.2 essentially, more advanced 02:33.2 and highly evolved pathogens 02:35.0 that could evade innate immunity. (ibiology.org)

Corynebacterium pseudotuberculosis is a facultative intracellular pathogen that belongs to the so-called CMN ( Corynebacterium-Mycobacterium-Nocardia ) group, a distinct subgroup of the Actinobacteria that also includes other highly important bacterial pathogens, such as Corynebacterium diphtheriae and Mycobacterium tuberculosis . (biomedcentral.com)

All three Ras isoforms have a CAAX sequence at the COOH terminus that specifies farnesylation and further processing of the COOH-terminal cysteine residue. (rupress.org)

More than 30 mammalian genes comprise the TGFβ superfamily of growth factors. (nature.com)

Oncogenic BRAF V600E signals as an active monomer in the absence of active RAS, however, in many tumors BRAF dimers mediate ERK signaling. (nature.com)

The comparison of several polyisoprenol-based glycosylation pathways from the three domains of life shows that most of the implicated proteins belong to a limited number of superfamilies. (biomedcentral.com)
Rho proteins belong to the Ras superfamily. (biomedcentral.com)

Given the obligate nature of the symbiosis between tubeworms and their gammaproteobacterial chemoautotrophic endosymbiont, one may reasonably expect adaptations in several cellular mechanisms and pathways (e.g., nutrition, gas exchange, self-defense/self-recognition, control of cell proliferation) to promote efficacy in the symbiotic relationship. (biomedcentral.com)

Activation of Rho proteins through release of bound GDP and subsequent binding of GTP, is catalysed by guanine nucleotide exchange factors (GEFs) in the Dbl family. (embl-heidelberg.de)
Guanine nucleotide exchange factors ("GEFs") stimulate the dissociation of the GTP hydrolytic product, GDP, from small GTP-binding proteins, to promote the binding of a new GTP molecule. (justia.com)

ARD1 is an ARF family member that differs from other ARFs by the presence of a 46-kDa amino-terminal extension. (embl.de)
The targeting motif of Ras is part of the COOH-terminal hypervariable region, which significantly differs amongst the otherwise highly conserved Ras isoforms. (rupress.org)

Multiple sequence alignment revealed that AIBCA contains the two sequence motifs, CXDXR and HXXC, typical for β-CAs. (biomedcentral.com)

A zinc finger motif near the amino terminus of the ARF1 GAP was required for stimulation of GTP hydrolysis. (embl.de)
An amino-terminal portion conserved among a subset of Dbl family proteins is sufficient for the binding of Gbetagamma. (embl-heidelberg.de)
The fact that the detailed structure of this domain (at the level of individual amino acids) has been conserved over evolution is often taken as an indication that its mechanism has also been conserved. (elifesciences.org)

The DH domain is composed of three structurally conserved regions separated by more variable regions. (embl-heidelberg.de)
Although the catalytic domain of MMPs is structurally highly similar, there are many differences with respect to substrate specificity, cellular and tissue localization, membrane binding and regulation that make this a very versatile family of enzymes with a multitude of physiological functions, many of which are still not fully understood. (evelinvahter.com)

Contrary to previous analyses, the sulfide binding mediated by zinc ions is not conserved across tubeworms. (biomedcentral.com)
Metzincins are a ubiquitously expressed family of multi-domain zinc (II)-dependent endopeptidases (Stocker and Bode 1995 ), the members of which include well-known metalloproteases such as the matrix metalloproteases (MMPs) (Nagase and Woessner 1999 ), a disintegrin and metalloproteases (ADAMs) (White 2003 ), the ADAMs with a thrombospondin motif (ADAMTS) (Tang 2001 ), the bacterial serralysins (Nakahama et al. (evelinvahter.com)

Members of the Rho family of small G proteins transduce signals from plasma-membrane receptors and control cell adhesion, motility and shape by actin cytoskeleton formation. (embl-heidelberg.de)
Ras activity relies on proper anchoring to the cytoplasmic leaflet of the plasma membrane (PM) by means of a lipid-based PM targeting motif. (rupress.org)

The guanine nucleotide exchange factor (GEF) Dbl targets Rho family proteins thereby stimulating their GDP/GTP exchange, and thus is believed to be involved in receptor-mediated regulation of the proteins. (embl-heidelberg.de)
The present invention relates to diagnosing abnormal cell proliferation in biological samples and screening for drugs which inhibit, reduce or abolish cell growth, especially tumorigenic cell growth, by detecting a phosphovariant isoform of a guanine nucleotide exchange factor biomarker, such as the novel GEF-H1S. (justia.com)
This study reveals a noncanonical role of AMP-activated kinase in which the α subunit C-terminal regulatory domain serves as a guanine-nucleotide-exchange factor for Arf6 during glucose deprivation. (biologists.com)

Mutations in each member of the exocyst complex block the polarized trafficking that allows the bud to grow, but do not disrupt bud site selection. (sdbonline.org)

In addition to an essential role in regulating cell growth and differentiation, Ras signaling has more recently been linked to a wide range of neuronal functions including synaptic and behavioral plasticity (for review see Thomas and Huganir, 2004 ). (rupress.org)

The Ras/MAPK pathway regulates synaptic plasticity and cell survival in neurons of the central nervous system. (rupress.org)

However, the mechanisms underlying receptor-dependent regulation of Rho family members remain incompletely understood. (embl-heidelberg.de)
Ligands of the transforming growth factor-β (TGFβ) superfamily of growth factors initiate signal transduction through a bewildering complexity of ligand-receptor interactions. (nature.com)

and proteins that interact with members of the Arp2/3 complex and hence the actin cytoskeleton (Table 1 ). (biomedcentral.com)

Other members of this family are able hydrolyze other phospholipid substrates, such as cardiolipin, or even the phosphodiester bond constituting the backbone of DNA. (wikipedia.org)
Thus, we propose a new viral genus Oceanospirivirus within the Siphoviridae family to reconcile this cluster, with vB_OliS_GJ44 as a representative member. (biomedcentral.com)
Motor proteins of the conserved kinesin-14 family have important roles in mitotic spindle organization and chromosome segregation. (elifesciences.org)
Essentially, all members of the MMP family have been linked to disease development, notably to cancer metastasis, chronic inflammation and the ensuing tissue damage as well as to neurological disorders. (evelinvahter.com)
In this review, we will give an overview of 23 members of the human MMP family and describe functions, linkages to disease and structural and mechanistic features. (evelinvahter.com)

Specific members of the Myosin superfamily of motor proteins are known to transport cargo along actin filaments. (mechanobio.info)

An in-depth understanding of the pleiotropic cellular functions that can be evoked by TGFβ superfamily signalling will depend on a more quantitative knowledge of temporal and spatial characteristics of the pathway. (nature.com)
The cytoskeleton is a highly dynamic network of filamentous proteins that enables the active transport of cellular cargo, transduces force, and when assembled into higher-order structures, forms the basis for motile cellular structures that promote cell movement. (mechanobio.info)

However, αC-IN inhibitors strongly promote RAF binding to active RAS (RAF priming) and therefore induce increased RAF dimerization. (nature.com)
features been in members are purified to induce only recommendations and download Your Brain on Latino Comics: From Gus Arriola to Los Bros Hernandez (Cognitive Approaches to. (evakoch.com)

Signal duration and signal magnitude are crucial determinants of the outcome of TGFβ superfamily signalling, in particular in early embryonic patterning, in which TGFβ superfamily ligands act as morphogens that elicit distinct responses in a dose-dependent fashion. (nature.com)

Recent studies have uncovered key intrinsic mechanisms by which TNF acts on osteoclast precursors to restrain osteoclastogenesis, including the mechanisms mediated by RBP-J signaling, RBP-J and ITAM (Immunoreceptor tyrosine-based activation motif) crosstalk, RBP-J mediated regulatory network, NF- κ B p100, IRF8, and Def6. (frontiersin.org)
Here, we describe the first transgenic mouse model for activation of K-RAS in the lung in a RASSF1A-defective background. (cancerindex.org)

This activity is strongly conserved and probably represents a primordial function of these proteins. (biomedcentral.com)

The DH domain is composed of 11 alpha helices that are folded into a flattened, elongated alpha-helix bundle in which two of the three conserved regions, conserved region 1 (CR1) and conserved region 3 (CR3), are exposed near the centre of one surface. (embl-heidelberg.de)
Here, we show that bat IFITMs are characterized by strong adaptive evolution and identify a highly variable and functionally important site-codon 70-within the conserved CD225 domain of IFITMs. (life-science-alliance.org)
RBD, Ras-binding domain of Raf-1. (rupress.org)

Like all members of the Ras superfamily, the Rho proteins cycle between active GTP-bound and inactive GDP-bound conformational states. (embl-heidelberg.de)

systematic name phosphatidylcholine phosphatidohydrolase) is an enzyme of the phospholipase superfamily that catalyses the following reaction a phosphatidylcholine + H2O = choline + a phosphatidate Phospholipases occur widely, and can be found in a wide range of organisms, including bacteria, yeast, plants, animals, and viruses. (wikipedia.org)
Using TNFi has shown to help treat inflammation and joint erosion that occur in RA. (frontiersin.org)

We conclude that the polybasic-prenyl motif acts as a Ca 2+ /CaM-regulated molecular switch that controls PM concentration of KRas and redistributes its activity to internal sites. (rupress.org)

In addition, some members of the PLD superfamily may employ primary alcohols such as ethanol or 1-butanol in the cleavage of the phospholipid, effectively catalyzing the exchange the polar lipid headgroup. (wikipedia.org)

Anatomy14

Organisms12

Diseases1

Chemicals and Drugs108

Analytical, Diagnostic and Therapeutic Techniques and Equipment35

Phenomena and Processes81

Disciplines and Occupations1

Information Science7

Health Care1

GTPases10

Residues7

Protein8

GTPase9

Inactivation2

Effectors4

Subfamily2

Transmembrane3

Characteristic3

Evolutionarily1

Intracellular1

Residue1

Genes1

Tumors1

Proteins belong2

Pathways1

GEFs2

Differs2

Sequence1

Amino3

Structurally2

Zinc2

Plasma membrane2

Nucleotide-exchange3

Mutations1

Differentiation1

Regulates1

Receptor2

Interact1

Family5

Actin1

Cellular2

Induce2

Distinct1

Activation2

Strongly1

Domain3

Active1

Occur2

Activity1

Primary1