• It is caused by stereotyped missense mutations in the transmembrane receptor Notch3, which alter the number of cysteine residues in the extracellular domain (ECD). (uni-muenchen.de)
  • While the vast majority of CADASIL mutations alter the number of cysteine residues within the Notch3-ECD, over the last years several mutations not involving a cysteine have been reported to be associated with a CADASIL-like phenotype provoking a debate about their clinical significance. (uni-muenchen.de)
  • Over 100 pathogenic mutations in the NOTCH3 gene, an evolutionarily highly conserved transmembrane receptor protein regulating cell fate, 4 are known to almost always lead to an odd number of cysteine residues in one of the 34 epidermal growth factor like repeats in the extracellular domain of the Notch3 protein. (bmj.com)
  • Three of them showed an aggregation behavior similar to cysteine-affecting mutations, a finding supported by the typical CADASIL-like clinical appearance of the mutation carriers and we thus classified them as pathogenic mutations. (uni-muenchen.de)
  • Structure of the functional domain of the LRRK2 protein and the pathogenic mutations associated with PD. (biomedcentral.com)
  • The use of recombinant proteins is common in this context, but heterologous expression of plant proteins is particularly difficult, in part because the presence of many cysteine residues promotes denaturation, aggregation and/or protein misfolding. (vtt.fi)
  • cDNAs encoding wild-type expansin (PpEXP1_WT) and a mutant in which all cysteine residues were replaced with serine (PpEXP1_CS) were each inserted into expression vectors, and the protein expression levels were compared. (vtt.fi)
  • The information within the KdpD protein that confers SRP interaction was found in the amino-terminal cytoplasmic domain of KdpD, particularly at residues 22-48. (nature.com)
  • To determine whether a mutation in the RP1-like protein 1 ( RP1L1 ) gene is present in a Japanese patient with sporadic occult macular dystrophy (OMD) and to examine the characteristics of focal macular electroretinograms (ERGs) of the patient with genetically identified OMD. (molvis.org)
  • Four out of five computational assessment tools predicted that this mutation is damaging to the protein function. (molvis.org)
  • Keap1 is a cysteine-rich protein, known to be anchored to actin cytoskeleton [ 5 ], serving as an adaptor protein for the Cul3-dependent E3 ubiquitin ligase complex. (springer.com)
  • Critical cysteine residues of Keap1 in suppression of Nrf2 basal activity and arsenic-sensing by regulating the ubiquitination-proteasomal degradation of Nrf2 protein. (cdc.gov)
  • Mutation of C273 or C288A in linker region resulted in higher level expression of Nrf2 protein in the absence of inducers. (cdc.gov)
  • These mainly missense mutations are thought to result in conformational changes of the Notch3 protein. (bmj.com)
  • Mutation screening of the coding regions and exon/intron boundaries of both collagen type I genes did not reveal any mutations, and type I collagen protein analyses were normal. (wiley.com)
  • Successful plasma therapy for atypical hemolytic uremic syndrome caused by factor H deficiency owing to a novel mutation in the complement cofactor protein domain 15. (lu.se)
  • Acts as a cysteine-protein sulfhydrase by mediating sulfhydration of target proteins: sulfhydration consists of converting -SH groups into -SSH on specific cysteine residues of target proteins such as GAPDH, PTPN1 and NF-kappa-B subunit RELA, thereby regulating their function. (nih.gov)
  • Fibrillin's structure and function are altered by abnormal protein folding due to the alteration of bonding between cysteine residues, which in turn causes defective microfibril production. (medscape.com)
  • Peptide exclusion was used to identify the epitope targeted by this antibody within the cysteine-rich region of the EphB4 protein, a sequence defined as a potential ligand interacting interface. (oncotarget.com)
  • The current view of protein folding and stability is largely based on SAXS and DLS data13-16 and the extensive exposure of hydropho- a generic structural classification into native (N), compact dena- bic residues suggested by the finding that the heat capacity of the tured or molten globule (MG), and unfolded or denatured (D) MG state is midway between that of the N and D states7 have been conformational states1-10. (lu.se)
  • Short in-frame deletions in exon 19 (19-Del) and point mutations in EGFR exon 21 p.L858R are the most common activating mutations in EGFR , accounting for approximately 90% of all EGFR mutations in NSCLC [ 5 , 6 ]. (biomedcentral.com)
  • Several point mutations have now been identified in the fibrillin gene, most of which affect cysteine residues within the microfibril. (medscape.com)
  • Specific point mutations in human anion exchanger 1 (AE1) convert this electroneutral anion exchanger into a monovalent cation conductance. (tcdb.org)
  • Sequence comparison of L. mexicana, yeast and human GPI8 proteins identified two potential active site cysteine residues. (gla.ac.uk)
  • Most expressed proteins are far from perfect and contain mutations called SNPs (single nucleotide polymorphisms) in which a single amino acid is out of place. (walshinstitute.org)
  • Many birth defects and mental illnesses are caused by SNP mutations that alter the structure and functioning of genetically-expressed proteins. (walshinstitute.org)
  • The animal AE proteins consist of homodimeric complexes of integral membrane proteins that vary in size from about 900 amino acyl residues to about 1250 residues. (tcdb.org)
  • Mutations in NOTCH3 have been identified as the underlying cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). (wikipedia.org)
  • Mutations in NOTCH3 have also been identified in families with Alzheimer's disease. (wikipedia.org)
  • Mutations in NOTCH3 are associated to lateral meningocele syndrome. (wikipedia.org)
  • Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most common form of monogenic SVD leading to early-onset stroke and vascular dementia, is caused by mutations in the Notch3 transmembrane receptor. (uni-muenchen.de)
  • Thus, our in vitro assay offers new insights into the Notch3 aggregation mechanism and may serve as diagnostic tool determining the clinical relevance of cysteine-sparing mutations. (uni-muenchen.de)
  • The remaining two cysteines, Cys-6 and Cys-111, remain unpaired and have been implicated in mutant SOD1 aggregation. (edu.au)
  • In this study, we examined the relationship between the SOD1 A4V cysteine residues and aggregation, ER stress induction and toxicity. (edu.au)
  • The residue C291, located in the transmembrane segment (TM) VIII of SteT, is the unique target of inactivation by MTSET and of activaction by DTT. (tesisenred.net)
  • G in exon 4 resulted in the substitution of cysteine for serine at amino acid position 1199. (molvis.org)
  • A missense mutation (Ser267Pro) in exon IIIa and a splice site mutation (940-2A→G) in exon IIIc were detected in gastric cancer patients. (aacrjournals.org)
  • We retrospectively studied the next-generation sequencing (NGS) data of treatment-naïve tumors from 1025 NSCLC patients with compound EGFR mutations, which were sub-categorized into different combinations of common mutations (19-Del and EGFR exon 21 p.L858R), rare mutations, and variants of uncertain significance (VUSs). (biomedcentral.com)
  • Besides 19-Del and EGFR exon 21 p.L858R, extensive research has uncovered a wide array of rare EGFR activating or resistant mutations in NSCLC, including EGFR exon 18 p.G719X, EGFR exon 20 p.S768I, EGFR exon 21 p.L861Q, EGFR exon 20 p.T790M, and EGFR exon 20 insertions (20ins). (biomedcentral.com)
  • Our findings support the notion that arsenic binds to different sets of Keap1 cysteine residues to regulate divergent functions in Nrf2 signaling. (cdc.gov)
  • Sulfur mustard binds to reactive cysteine residues, forming a stable sulfur-hydroxyethylthioethyl [S-HETE] adduct that can be used as a long-term biomarker of sulfur mustard exposure in humans. (cdc.gov)
  • In another example, APOE gene mutations in which cysteine residues are replaced by arginine residues result in APOE-3 or APOE-4 and a higher likelihood of Alzheimers Disease. (walshinstitute.org)
  • Contrary to previous reports, we also show that rare mutations are consistently predicted to be deleterious as often as commonly occurring nsSNPs. (biomedcentral.com)
  • Here we analyzed arsenic-Keap1 cysteine thiol interactions for Nrf2 activation. (cdc.gov)
  • Castaman G, Novella E, Castiglia E, Eikenboom JCJ, Rodeghiero F: A novel family with recessive von Willebrand disease due to compound heterozygosity for a splice site mutation and a missense mutation in the von Willebrand factor gene. (karger.com)
  • Pirtobrutinib is a highly selective, noncovalent BTKi with substantial clinical activity in patients whose disease has progressed on covalent BTKi, regardless of BTK mutation status. (lu.se)
  • We employed longitudinal whole-exome sequencing on 2 patients whose disease progressed on pirtobrutinib and identified selection of alternative-site BTK mutations, providing clinical evidence that secondary BTK mutations lead to resistance to noncovalent BTKis. (lu.se)
  • Clinical, neurophysiological and genetic data of 37 neuropathy patients with MPZ mutations were retrospectively collected. (nih.gov)
  • Patients with LRRK2 mutations exhibit a clinical and pathological phenotype indistinguishable from sporadic PD. (biomedcentral.com)
  • However, the detailed clinical characteristics and prognosis of various compound EGFR mutations remain to be elucidated. (biomedcentral.com)
  • Different subtypes of compound EGFR mutations displayed distinct clinical features and genetic architectures, and rare mutation-dominant compound EGFR mutations were associated with enriched kinase domain-resided VUSs and poor clinical outcomes. (biomedcentral.com)
  • Mutations in the FBN1 locus of the fibrillin gene on chromosome 15 have been linked to MFS and other distinct clinical entities with similar findings. (medscape.com)
  • In silico target docking of ATP to the P2K2-binding site predicted interaction with several residues through hydrophobic interactions and hydrogen bonding. (bvsalud.org)
  • All identified mutations occurred at highly conserved sequences, not only in the FGFR family of molecules, but also throughout evolution and clustered in the immunoglobulin-like loop-III domain, highlighting the functional importance of this domain. (aacrjournals.org)
  • Using a combination of targeted high-throughput screening and structure-based drug design, we have developed a series of aminopyrazole based FGFR inhibitors that covalently target a cysteine residue on the P-loop of the kinase. (rcsb.org)
  • The most common resistance mechanism in patients whose disease progresses on covalent BTK inhibitors (BTKis) is a mutation in the BTK 481 cysteine residue to which the inhibitors bind covalently. (lu.se)
  • This cysteine (at position 117) appears important in the association of phenoxybenzamine with receptor with PB likely covalently coupled to this amino acid. (pharmacology2000.com)
  • however, mutation p.Val232Valfs*19 was associated with a relatively milder childhood-onset CMT1 phenotype. (nih.gov)
  • De novo mutations accounted for 30.4% and were most related to a severe infantile-onset phenotype. (nih.gov)
  • However, although each solitary mutation favorably affects cleft stability, the phenotype of the double mutant is clearly synergistic. (bioskinrevive.com)
  • The source of the E522C phenotype is definitely unclear but may be due to the removal of cross-cleft steric clashes observed with the glutamate residue. (bioskinrevive.com)
  • We previously described a group of patients initially classified with OI type IV who had a discrete phenotype including hyperplastic callus formation without evidence of mutations in type I collagen. (wiley.com)
  • A left-shifted concentration-response curve offers been previously reported for the I691C mutant, attributed to the stabilizing effects of an interlobe hydrogen bond with Glu522 (30), and replacing Glu522 with the smaller cysteine residue appears to get rid of potential clashes with the cross-cleft isoleucine. (bioskinrevive.com)
  • Converts two cysteine molecules to lanthionine and hydrogen sulfide. (nih.gov)
  • Residues lack either the hydrogen atoms of the amino group, an oxygen from the carboxyl group, or both. (flashcardmachine.com)
  • Compound epidermal growth factor receptor ( EGFR ) mutations are less responsive to tyrosine kinase inhibitors (TKIs) than single EGFR mutations in non-small cell lung cancer (NSCLC). (biomedcentral.com)
  • The PCMBS-caused inhibition of the transport via rMATE1 was protected by an excess of various organic cations such as TEA, suggesting that cysteine residues act as substrate-binding sites. (aspetjournals.org)
  • These results suggest that histidine and cysteine residues are required for MATE1 to function and that cysteine residues may serve as substrate-recognition sites. (aspetjournals.org)
  • Here we define the precise Rab29 binding region of the LRRK2 Armadillo domain between residues 360-450 and show that this domain, termed 'Site #1', can also bind additional LRRK2 substrates, Rab8A and Rab10. (stanford.edu)
  • when two or more amino acids combine to form a peptide bond, the element of water is removed, and what remains of each amino acid is called an amino acid residue. (flashcardmachine.com)
  • About 10 million SNP mutations are present in each person's DNA, which suggests we all could be considered mutants. (walshinstitute.org)
  • This mutation was not present in 294 control alleles. (molvis.org)
  • In our previous study using RT-PCR products, we identified 14 different mutations in 19 alleles from 11 patients, and failed to detect mutations in the remaining three alleles. (bmj.com)
  • Hot spot mutation p.Thr124Met was detected in four unrelated families, and seven patients carried de novo mutations. (nih.gov)
  • Complement mutation-associated de novo thrombotic microangiopathy following kidney transplantation. (lu.se)
  • The discovery of the antioxidant response element (ARE) have led to the conclusion that the battery of genes, including glutamate-cysteine ligase (GCL), thioredoxin reductase 1 (Txnrd1), NAD(P)H-quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HMOX1) is regulated through Nrf2 binding to this consensus binding sequence [ 3 ]. (springer.com)
  • We give examples of mutations in genes that are predicted to be deleterious and may have a role in disease. (biomedcentral.com)
  • Activating mutations in the Leucine Rich Repeat Kinase 2 (LRRK2) cause Parkinson's disease and previously we showed that activated LRRK2 phosphorylates a subset of Rab GTPases (Steger et al. (stanford.edu)
  • Recent studies have shown that pathological mutations of LRRK2 can reduce the rate of guanosine triphosphate (GTP) hydrolysis, increase kinase activity and GTP binding activity, and subsequently cause cell death. (biomedcentral.com)
  • 0.001), implying these tumors might select additional mutations to disrupt the regulation/function of the kinase domain. (biomedcentral.com)
  • Previous studies using rat renal brush-border membrane vesicles indicated that cysteine and histidine residues played critical roles in H + /organic cation antiport activity. (aspetjournals.org)
  • Furthermore, it is suggested that the binding of SRP to the signal sequence is promoted by the presence of basic amino acid residues through electrostatic interactions 18 . (nature.com)
  • When 7 histidine and 12 cysteine residues of rat (r)MATE1 conserved among species were mutated, substitution of His-385, Cys-62, and Cys-126 led to a significant loss of tetraethylammonium (TEA) transport activity. (aspetjournals.org)
  • A number of autosomal dominant skeletal dysplasias are associated with mutations in FGFR1, -2, and -3 (reviewed in Ref. 5 ). (aacrjournals.org)
  • For example, mutations that reduce the mRNA stability may escape the screening. (bmj.com)
  • In the first part of this work, the in vitro assay was applied to study the pathogenic potential of five of these mutations. (uni-muenchen.de)
  • Our confirmation of the modeling was obtained by showing that H99, R144, and S256 are key residues essential for in vitro binding of ATP by P2K2. (bvsalud.org)
  • Mutations in the meprin MAM domain affect noncovalent associations within meprin oligomers. (embl.de)
  • For example, if a particular cysteine residue located in the TM3 domain was changed to valine (by mutation), the receptor becomes resistant to phenoxybenzamine inactivation. (pharmacology2000.com)
  • This review summarizes the cellular function and pathophysiology of LRRK2 ROCO domain mutations in PD and the perspective of therapeutic approaches. (biomedcentral.com)
  • Mutation of a single cysteine residue in the ARNIP RING-H2 domain (Cys145Ala) abolished this E3 ubiquitin ligase activity. (endocrinology-journals.org)
  • Haemolytic uraemic syndrome caused by factor H mutation: is single kidney transplantation under intensive plasmatherapy an option? (lu.se)
  • Plasma therapy in atypical haemolytic uremic syndrome: lessons from a family with a factor H mutation. (lu.se)
  • Haemolytic uraemic syndrome and mutations of the factor H gene: a registry-based study of German speaking countries. (lu.se)
  • Human SLC4A1/AE1 mutations cause either the erythroid disorders spherocytic haemolytic anaemia or ovalocytosis, or distal renal tubular acidosis. (tcdb.org)
  • Glutathione synthesis in the liver is dependent upon the availability of cysteine. (nih.gov)
  • DNA adducts are quickly repaired, or DNA synthesis is blocked to avoid further replication of the mutation. (cdc.gov)
  • We found that the amino acid residues R22, K24 and K26 are important for SRP interaction, whereas the residues G30, G34 and G36, essential for a functional Walker A motif, can be replaced with alanines without affecting the affinity to SRP-FtsY and membrane targeting. (nature.com)
  • This gene encodes a cytoplasmic enzyme in the trans-sulfuration pathway that converts cystathione derived from methionine into cysteine. (nih.gov)
  • A single missense mutation allows AE1 to mediate both electrogenic SO 4 2- -Cl - exchange or electroneutral, H + -independent SO 4 2- -SO 4 2- exchange ( Alper 2006 ). (tcdb.org)
  • Sequential mannose trimming of N -glycan, from M9 to M8B and then to oligosaccharides exposing the α1,6-linked mannosyl residue (M7A, M6, and M5), facilitates endoplasmic reticulum-associated degradation of misfolded glycoproteins (gpERAD). (elifesciences.org)
  • Mutation screening of all coding regions and flanking intron sequences of the RP1L1 gene were performed with DNA sequencing analysis in this case with OMD. (molvis.org)
  • 5 6 The number of NPC1 mutations known to date is not far off 100, 7-11 taking into account the accumulated data from seven groups presented in a recent international workshop (International Workshop, The Niemann-Pick C Lesion and the Role of Intracellular Lipid Sorting in Human Disease, Bethesda, USA, October 1999). (bmj.com)
  • We show that, in general, the prediction tools are able distinguish disease causing mutations from those mutations which are thought to have a neutral affect. (biomedcentral.com)
  • Mutations that changed the cysteine residue (p.Arg98Cys, p.Cys127Trp, p.Ser140Cys and p.Cys127Arg) in the extracellular region were more likely to cause severe early-onset Charcot-Marie-Tooth disease type 1B (CMT1B) or Dejerine-Sottas syndrome. (nih.gov)
  • Mutation of the corresponding residues in human (h)MATE1 and hMATE2-K also diminished the transport activity. (aspetjournals.org)
  • We have demonstrated in a Japanese patient the possibility that sporadic OMD may also be caused by an RP1L1 mutation. (molvis.org)
  • Our findings help better understand the oncogenesis of compound EGFR mutations and forecast prognostic outcomes of personalized treatments. (biomedcentral.com)
  • By analyzing specific amino acid mutations of the α 2A - receptor with respect to changes in PB binding, certain sites were identified that may serve as the molecular target for phenoxybenzamine-mediated receptor blockade. (pharmacology2000.com)
  • Our specific SNP mutations help define our personality, abilities, and vulnerability to diseases. (walshinstitute.org)