MSRA_DROME
ID MSRA_DROME Reviewed; 246 AA.
AC P08761; Q86NL3; Q8IQM6; Q8IT52; Q9VUP3; Q9VUP4; Q9VUP5;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2004, sequence version 2.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Peptide methionine sulfoxide reductase;
DE EC=1.8.4.11 {ECO:0000269|PubMed:12145281, ECO:0000269|PubMed:30529269};
DE AltName: Full=Ecdysone-induced protein 28/29 kDa;
DE AltName: Full=Methionine-S-sulfoxide reductase;
DE AltName: Full=Peptide-methionine (S)-S-oxide reductase;
GN Name=MsrA {ECO:0000303|PubMed:3097323, ECO:0000312|FlyBase:FBgn0000565};
GN Synonyms=Eip28/29 {ECO:0000303|PubMed:3097323},
GN Eip71CD {ECO:0000312|FlyBase:FBgn0000565};
GN ORFNames=CG7266 {ECO:0000312|FlyBase:FBgn0000565};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS EIP28 AND EIP29).
RC STRAIN=Canton-S;
RX PubMed=3097323; DOI=10.1016/0022-2836(86)90492-4;
RA Cherbas L., Schulz R.A., Koehler M.M.D., Savakis C., Cherbas P.;
RT "Structure of the Eip28/29 gene, an ecdysone-inducible gene from
RT Drosophila.";
RL J. Mol. Biol. 189:617-631(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM EIP28), FUNCTION, AND CATALYTIC
RP ACTIVITY.
RX PubMed=12145281; DOI=10.1074/jbc.m203496200;
RA Kumar R.A., Koc A., Cerny R.L., Gladyshev V.N.;
RT "Reaction mechanism, evolutionary analysis, and role of zinc in Drosophila
RT methionine-R-sulfoxide reductase.";
RL J. Biol. Chem. 277:37527-37535(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [4]
RP GENOME REANNOTATION, AND ALTERNATIVE SPLICING.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM EIP29).
RC STRAIN=Berkeley; TISSUE=Embryo;
RA Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J.W., Champe M.,
RA Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., George R.A.,
RA Gonzalez M., Guarin H., Kronmiller B., Li P.W., Liao G., Miranda A.,
RA Mungall C.J., Nunoo J., Pacleb J.M., Paragas V., Park S., Patel S.,
RA Phouanenavong S., Wan K.H., Yu C., Lewis S.E., Rubin G.M., Celniker S.E.;
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP URMYLATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=28953965; DOI=10.1371/journal.pone.0185611;
RA Khoshnood B., Dacklin I., Grabbe C.;
RT "A proteomics approach to identify targets of the ubiquitin-like molecule
RT Urm1 in Drosophila melanogaster.";
RL PLoS ONE 12:E0185611-E0185611(2017).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, MASS
RP SPECTROMETRY, DISULFIDE BOND, AND MUTAGENESIS OF CYS-232 AND CYS-246.
RX PubMed=30529269; DOI=10.1016/j.freeradbiomed.2018.12.001;
RA Tarafdar S., Kim G., Levine R.L.;
RT "Drosophila methionine sulfoxide reductase A (MSRA) lacks methionine
RT oxidase activity.";
RL Free Radic. Biol. Med. 131:154-161(2019).
CC -!- FUNCTION: Has an important function as a repair enzyme for proteins
CC that have been inactivated by oxidation. Catalyzes the reduction of
CC methionine sulfoxide in proteins to methionine (PubMed:12145281,
CC PubMed:30529269). Does not catalyze the reverse reaction involving the
CC oxidation of methionine residues (PubMed:30529269).
CC {ECO:0000269|PubMed:12145281, ECO:0000269|PubMed:30529269}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[thioredoxin]-disulfide + H2O + L-methionyl-[protein] =
CC [thioredoxin]-dithiol + L-methionyl-(S)-S-oxide-[protein];
CC Xref=Rhea:RHEA:14217, Rhea:RHEA-COMP:10698, Rhea:RHEA-COMP:10700,
CC Rhea:RHEA-COMP:12313, Rhea:RHEA-COMP:12315, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:16044, ChEBI:CHEBI:29950, ChEBI:CHEBI:44120,
CC ChEBI:CHEBI:50058; EC=1.8.4.11;
CC Evidence={ECO:0000269|PubMed:12145281, ECO:0000269|PubMed:30529269};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:14219;
CC Evidence={ECO:0000269|PubMed:30529269};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[thioredoxin]-disulfide + H2O + L-methionine = [thioredoxin]-
CC dithiol + L-methionine (S)-S-oxide; Xref=Rhea:RHEA:19993, Rhea:RHEA-
CC COMP:10698, Rhea:RHEA-COMP:10700, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:29950, ChEBI:CHEBI:50058, ChEBI:CHEBI:57844,
CC ChEBI:CHEBI:58772; EC=1.8.4.11;
CC Evidence={ECO:0000269|PubMed:12145281, ECO:0000269|PubMed:30529269};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:19995;
CC Evidence={ECO:0000269|PubMed:30529269};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3.6 mM for L-methionine sulfoxide {ECO:0000269|PubMed:30529269};
CC Vmax=0.15 umol/min/mg enzyme towards L-methionine sulfoxide (at 25
CC degrees Celsius) {ECO:0000269|PubMed:30529269};
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Eip28; Synonyms=A;
CC IsoId=P08761-1; Sequence=Displayed;
CC Name=Eip29; Synonyms=B;
CC IsoId=P08761-2; Sequence=VSP_003279;
CC -!- INDUCTION: By ecdysone.
CC -!- PTM: Conjugated to URM1, a ubiquitin-like protein.
CC {ECO:0000269|PubMed:28953965}.
CC -!- MASS SPECTROMETRY: Mass=27567.4; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:30529269};
CC -!- SIMILARITY: Belongs to the MsrA Met sulfoxide reductase family.
CC {ECO:0000305}.
CC -!- CAUTION: Unlike mammalian MSRA, lacks methionine oxidase activity
CC because Cys-232 cannot function as a resolving cysteine to perform the
CC disulfide exchange and instead remains as a free thiol
CC (PubMed:30529269). As a result, the active site cysteine is trapped in
CC disulfide linkage with Cys-246 and is therefore unable to react with a
CC second molecule of methionine sulfoxide to complete methionine
CC oxidation (PubMed:30529269). {ECO:0000269|PubMed:30529269}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA28205.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; X58286; CAA41223.1; ALT_FRAME; Genomic_DNA.
DR EMBL; X04024; CAA27657.1; ALT_FRAME; Genomic_DNA.
DR EMBL; X04024; CAA27658.1; ALT_FRAME; Genomic_DNA.
DR EMBL; X04521; CAA28205.1; ALT_FRAME; mRNA.
DR EMBL; AF541958; AAN28311.1; -; mRNA.
DR EMBL; AE014296; AAF49630.2; -; Genomic_DNA.
DR EMBL; AE014296; AAN11775.1; -; Genomic_DNA.
DR EMBL; BT004857; AAO45213.1; -; mRNA.
DR PIR; A24254; A24254.
DR RefSeq; NP_524085.2; NM_079361.3. [P08761-1]
DR RefSeq; NP_730047.1; NM_168622.2. [P08761-2]
DR AlphaFoldDB; P08761; -.
DR SMR; P08761; -.
DR BioGRID; 64995; 3.
DR IntAct; P08761; 2.
DR STRING; 7227.FBpp0075308; -.
DR PaxDb; P08761; -.
DR DNASU; 39675; -.
DR EnsemblMetazoa; FBtr0075553; FBpp0075308; FBgn0000565. [P08761-1]
DR EnsemblMetazoa; FBtr0075554; FBpp0075309; FBgn0000565. [P08761-2]
DR GeneID; 39675; -.
DR KEGG; dme:Dmel_CG7266; -.
DR CTD; 4482; -.
DR FlyBase; FBgn0000565; MsrA.
DR VEuPathDB; VectorBase:FBgn0000565; -.
DR eggNOG; KOG1635; Eukaryota.
DR GeneTree; ENSGT00940000171922; -.
DR InParanoid; P08761; -.
DR PhylomeDB; P08761; -.
DR BRENDA; 1.8.4.11; 1994.
DR BioGRID-ORCS; 39675; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 39675; -.
DR PRO; PR:P08761; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0000565; Expressed in seminal fluid secreting gland and 67 other tissues.
DR ExpressionAtlas; P08761; baseline and differential.
DR Genevisible; P08761; DM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0036456; F:L-methionine-(S)-S-oxide reductase activity; IBA:GO_Central.
DR GO; GO:0008113; F:peptide-methionine (S)-S-oxide reductase activity; IDA:FlyBase.
DR GO; GO:0034599; P:cellular response to oxidative stress; IEP:FlyBase.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:FlyBase.
DR GO; GO:0006979; P:response to oxidative stress; IMP:FlyBase.
DR GO; GO:0000096; P:sulfur amino acid metabolic process; NAS:FlyBase.
DR Gene3D; 3.30.1060.10; -; 1.
DR HAMAP; MF_01401; MsrA; 1.
DR InterPro; IPR002569; Met_Sox_Rdtase_MsrA_dom.
DR InterPro; IPR036509; Met_Sox_Rdtase_MsrA_sf.
DR Pfam; PF01625; PMSR; 1.
DR SUPFAM; SSF55068; SSF55068; 1.
DR TIGRFAMs; TIGR00401; msrA; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disulfide bond; Oxidoreductase; Redox-active center;
KW Reference proteome; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:12145281,
FT ECO:0000269|PubMed:30529269"
FT CHAIN 2..246
FT /note="Peptide methionine sulfoxide reductase"
FT /id="PRO_0000138629"
FT ACT_SITE 48
FT /note="Cysteine sulfenic acid (-SOH) intermediate"
FT /evidence="ECO:0000305|PubMed:30529269"
FT DISULFID 48..246
FT /note="Redox-active"
FT /evidence="ECO:0000269|PubMed:30529269"
FT VAR_SEQ 79..82
FT /note="Missing (in isoform Eip29)"
FT /evidence="ECO:0000303|PubMed:3097323, ECO:0000303|Ref.5"
FT /id="VSP_003279"
FT MUTAGEN 232
FT /note="C->S: No effect on methionine sulfoxide reductase
FT activity and still lacks methionine oxidase activity; when
FT associated with S-246."
FT /evidence="ECO:0000269|PubMed:30529269"
FT MUTAGEN 246
FT /note="C->S: No effect on methionine sulfoxide reductase
FT activity and still lacks methionine oxidase activity; when
FT associated with S-232."
FT /evidence="ECO:0000269|PubMed:30529269"
FT CONFLICT 218..219
FT /note="EA -> V (in Ref. 5; AAO45213)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 246 AA; 27698 MW; 8BB13B2092227D3E CRC64;
MSLTITSSVT HPELKDLSTV RNEQKELNIS PVHDVNVTKA TATFGMGCFW GAESLYGATR
GVLRTTVGYA GGSSDLPTYR KMGDHTEVLE IDYDPTVISF KELLDLFWNN HEYGLTTPIK
RQYASLILYH DEEQKQVAHA SKLEEQERRA PEIITTEIAS KENFYPAEAY HQKYRLQGHK
DLASSLNLSP KLLQTSYVAT KLNGYLAGVG GIEQFKAEAE TMGLTPTQRQ YCYYHVEQNE
GQGLYC
