BioPAX pathway converted from "Protein repair" in the Reactome database.Protein repairProtein repairThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>1.8.4.11MSRA reduces L-methyl-(S)-S-oxide to L-MethionineMSRA reduces L-methyl-(S)-S-oxide to L-MethionineThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 56769251cytosolGO0005829L-methionine (S)-S-oxide [ChEBI:49031]L-methionine (S)-S-oxideReactomehttp://www.reactome.orgChEBI49031Reactome DB_ID: 100952511UniProt:P82460Sus scrofaNCBI Taxonomy9823UniProtP82460Chain Coordinates2EQUAL105EQUALReactome DB_ID: 100952491Intra-chain Crosslink via L-cystine (cross-link) at 32 and 35 (in Homo sapiens)32EQUALL-cystine (cross-link)2EQUAL105EQUALReactome DB_ID: 1743901L-methionine zwitterion [ChEBI:57844]L-methionine zwitterionC5H11NO2S(2S)-2-azaniumyl-4-(methylsulfanyl)butanoateFFEARJCKVFRZRR-BYPYZUCNSA-NL-methionine(2S)-2-ammonio-4-(methylsulfanyl)butanoate149.21100InChI=1S/C5H11NO2S/c1-9-3-2-4(6)5(7)8/h4H,2-3,6H2,1H3,(H,7,8)/t4-/m0/s1CSCC[C@H]([NH3+])C([O-])=OChEBI57844PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 10160286UniProt:F1RJP8PRSS55UniProtF1RJP824EQUAL235EQUALGO0008113GO molecular functionReactome Database ID Release 7510160287Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10160287Reactome Database ID Release 7510160289Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10160289ReactomeR-SSC-56769401Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-5676940.1Methionine Sulfoxide Reductase A (MSRA) is a peptide-methionine-(S)-S-oxide reductase (1.8.4.11.) (Kim & Gladyshev 2007, Sreekumar et al. 2011) that can reduce both free and protein-based methionine-(S)-S-oxide (Brot et al. 1981, Boschi-Muller et al. 2008). It has been implicated in processes ranging from protection of cells against oxidative damage to the maintenance of cellular homeostasis, prevention of disease and extension of longevity (Kim & Gladyshev 2007, Brennan & Kantorow 2009). MRSA has little or no target specificity and is therefore likely to act on surface-exposed methionine sulphoxide residues of many proteins (Weissbach et al. 2002, Kantorow et al. 2012).11795868Pubmed2002Peptide methionine sulfoxide reductase: structure, mechanism of action, and biological functionWeissbach, HerbertEtienne, FrantzyHoshi, ToshinoriHeinemann, Stefan HLowther, W ToddMatthews, BrianSt John, GregoryNathan, CarlBrot, NathanArch. Biochem. Biophys. 397:172-820888813Pubmed2012Focus on Molecules: methionine sulfoxide reductase AKantorow, MarcLee, WandaChauss, DanielExp. Eye Res. 100:110-110452521Pubmed1999Molecular cloning and functional expression of a human peptide methionine sulfoxide reductase (hMsrA)Kuschel, LHansel, ASchönherr, RWeissbach, HBrot, NHoshi, THeinemann, S HFEBS Lett. 456:17-2117922679Pubmed2007Methionine sulfoxide reductases: selenoprotein forms and roles in antioxidant protein repair in mammalsKim, Hwa-YoungGladyshev, Vadim NBiochem. J. 407:321-921909460Pubmed2011Methionine sulfoxide reductase A: Structure, function and role in ocular pathologySreekumar, Parameswaran GHinton, David RKannan, RamWorld J Biol Chem 2:184-9218588875Pubmed2009Mitochondrial function and redox control in the aging eye: role of MsrA and other repair systems in cataract and macular degenerationsBrennan, Lisa AKantorow, MarcExp. Eye Res. 88:195-2037017726Pubmed1981Enzymatic reduction of protein-bound methionine sulfoxideBrot, NWeissbach, LWerth, JWeissbach, HProc. Natl. Acad. Sci. U.S.A. 78:2155-818302927Pubmed2008The methionine sulfoxide reductases: Catalysis and substrate specificitiesBoschi-Muller, SandrineGand, AdelineBranlant, GuyArch. Biochem. Biophys. 474:266-73inferred by electronic annotationIEAGOIEA1.8.4.12MRSBs reduce L-methyl-(R)-S-oxide to L-methionineMRSBs reduce L-methyl-(R)-S-oxide to L-methionineThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 56769321L-methionine (R)-S-oxide [ChEBI:49032]L-methionine (R)-S-oxideChEBI49032Reactome DB_ID: 1009525112EQUAL105EQUALReactome DB_ID: 100952491Intra-chain Crosslink via L-cystine (cross-link) at 32 and 35 (in Homo sapiens)32EQUAL2EQUAL105EQUALReactome DB_ID: 1743901PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 10160279MSRBs [cytosol]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityMSRB3 [cytosol]MSRB2 [cytosol]UniProtI3LV38UniProtF1RVI8GO0033743GO molecular functionReactome Database ID Release 7510160280Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10160280Reactome Database ID Release 7510160282Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10160282ReactomeR-SSC-56769171Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-5676917.1Methionine Sulfoxide Reductase B (MSRBs) are able to reduce methyl-(R)-S-oxide to methionine (Grimaud et al. 2001). They are specific for the reduction of protein-based methyl-(R)-S-oxide, reducing free methyl-(R)-S-oxide with very low efficiency (Lee et al. 2009). Mammals have at least 3 MSRB genes (Kryukov et al. 1999, Huang et al. 1999, Jung et al. 2002, Kim & Gladyshev 2004). They are ubiquitously expressed, no clear substrate specificities are known, all three contain a zinc atom and can use thioredoxin as an in vivo reducing agent (Kim & Gladyshev 2007).10375640Pubmed1999Identification, expression and chromosome localization of a human gene encoding a novel protein with similarity to the pilB family of transcriptional factors (pilin) and to bacterial peptide methionine sulfoxide reductasesHuang, WEscribano, JSarfarazi, MCoca-Prados, MGene 233:233-4011677230Pubmed2001Repair of oxidized proteins. Identification of a new methionine sulfoxide reductaseGrimaud, REzraty, BMitchell, J KLafitte, DBriand, CDerrick, P JBarras, FJ. Biol. Chem. 276:48915-2019406207Pubmed2009Functions and evolution of selenoprotein methionine sulfoxide reductasesLee, Byung CheonDikiy, AlexanderKim, Hwa-YoungGladyshev, Vadim NBiochim. Biophys. Acta 1790:1471-712220640Pubmed2002Activity, tissue distribution and site-directed mutagenesis of a human peptide methionine sulfoxide reductase of type B: hCBS1Jung, StephanHansel, AlfredKasperczyk, HubertHoshi, ToshinoriHeinemann, Stefan HFEBS Lett. 527:91-415249228Pubmed2004Characterization of mouse endoplasmic reticulum methionine-R-sulfoxide reductaseKim, Hwa-YoungGladyshev, Vadim NBiochem. Biophys. Res. Commun. 320:1277-8310567350Pubmed1999New mammalian selenocysteine-containing proteins identified with an algorithm that searches for selenocysteine insertion sequence elementsKryukov, G VKryukov, V MGladyshev, Vadim NJ. Biol. Chem. 274:33888-97inferred by electronic annotationIEAGOIEAReactome Database ID Release 7510187273Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10187273ReactomeR-SSC-56769341Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-5676934.1GO0030091GO biological processReactive oxygen species (ROS) such as H2O2, superoxide anions and hydroxyl radicals interact with molecules in the cell causing damage that impairs cellular functions. Although cells have mechanisms to destroy ROS and repair the damage caused by ROS, it is considered to be a major factor in age-related diseases and the ageing process (Zhang & Weissbach 2008, Kim et al. 2014). ROS-scavenging systems include enzymes such as peroxiredoxins, superoxide dismutases, catalases and glutathione peroxidases exist to minimise the potential damage. <br><br>ROS reactions can also cause specific modifications to amino acid side chains that result in structural changes to proteins/enzymes. Methionine (Met) and cysteine (Cys) can be oxidised by ROS to sulfoxide and further oxidised to sulfone derivatives. Both free Met and protein-based Met are readily oxidized to form methionine sulphoxide (MetO) (Brot & Weissbach 1991). Many proteins have been demonstrated to undergo such oxidation and as a consequence have altered function (Levine et al. 2000). Sulphoxide formation can be reversed by the action of the methionine sulphoxide reductase system (MSR) which catalyses the reduction of MetO to Met (Brot et al. 1981). This repair uses one ROS equivalent, so MSR proteins can act as catalytic antioxidants, removing ROS (Levine et al. 1996). Methionine oxidation results in a mixture of methionine (S)-S- and (R)-S-oxides of methionine, diastereomers which are reduced by MSRA and MSRB, respectively. MSRA can reduce both free and protein-based methionine-(S)-S-oxide, whereas MSRB is specific for protein-based methionine-(R)-S-oxide. Mammals typically have only one gene encoding MSRA, but at least three genes encoding MSRBs (Hansel et al. 2005). Although structurally distinct, MRSA and MRSB share a common three-step catalytic mechanism. In the first step, the MSR catalytic cysteine residue interacts with the MetO substrate, which leads to product release and formation of the sulfenic acid. In the second step, an intramolecular disulfide bridge is formed between the catalytic cysteine and the regenerating cysteine. In the final step, the disulfide bridge is reduced by an electron donor, the NADPH-dependent thioredoxin/TR system, leading to the regeneration of the MSR active site (Boschi-Muller et al. 2008).<br><br>Beta-linked isoaspartyl (isoAsp) peptide bonds can arise spontaneously via succinimide-linked deamidation of asparagine (Asn) or dehydration of aspartate (Asp). Protein-L-isoaspartate (D-aspartate) O-methyltransferase (PCMT1, PIMT EC 2.1.1.77) transfers the methyl group from S-adenosyl-L-methionine (AdoMet) to the alpha side-chain carboxyl group of L-isoaspartyl and D-aspartatyl amino acids. The resulting methyl ester undergoes spontaneous transformation to L-succinimide, which spontaneously hydrolyses to generates L-aspartyl residues or L-isoaspartyl residues (Knorre et al. 2009). This repair process helps to maintain overall protein integrity.1910456Pubmed1991Biochemistry of methionine sulfoxide residues in proteinsBrot, NWeissbach, HBiofactors 3:91-611327324Pubmed2000Oxidation of methionine in proteins: roles in antioxidant defense and cellular regulationLevine, R LMoskovitz, JStadtman, E RIUBMB Life 50:301-718557976Pubmed2008Origin and evolution of the protein-repairing enzymes methionine sulphoxide reductasesZhang, Xing-HaiWeissbach, HerbertBiol Rev Camb Philos Soc 83:249-5723648414Pubmed2014Methionine oxidation and reduction in proteinsKim, GeumsooWeiss, Stephen JLevine, Rodney LBiochim. Biophys. Acta 1840:901-515680232Pubmed2005Heterogeneity and function of mammalian MSRs: enzymes for repair, protection and regulationHansel, AlfredHeinemann, Stefan HHoshi, ToshinoriBiochim. Biophys. Acta 1703:239-4722649613Pubmed2009Chemical and functional aspects of posttranslational modification of proteinsKnorre, D GKudryashova, N VGodovikova, T SActa Naturae 1:29-518986759Pubmed1996Methionine residues as endogenous antioxidants in proteinsLevine, R LMosoni, LBerlett, B SStadtman, E RProc. Natl. Acad. Sci. U.S.A. 93:15036-40inferred by electronic annotationIEAGOIEA