MSRB2_HUMAN
ID MSRB2_HUMAN Reviewed; 182 AA.
AC Q9Y3D2; Q17R44; Q4G1C7; Q9Y5W6;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 08-APR-2008, sequence version 2.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Methionine-R-sulfoxide reductase B2, mitochondrial;
DE Short=MsrB2;
DE EC=1.8.4.12 {ECO:0000250|UniProtKB:Q9JLC3};
DE EC=1.8.4.14 {ECO:0000250|UniProtKB:Q9JLC3};
DE Flags: Precursor;
GN Name=MSRB2; Synonyms=CBS-1, MSRB; ORFNames=CGI-131;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Ocular ciliary body;
RX PubMed=10375640; DOI=10.1016/s0378-1119(99)00131-6;
RA Huang W., Escribano J., Sarfarazi M., Coca-Prados M.;
RT "Identification, expression and chromosome localization of a human gene
RT encoding a novel protein with similarity to the pilB family of
RT transcriptional factors (pilin) and to bacterial peptide methionine
RT sulfoxide reductases.";
RL Gene 233:233-240(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=10810093; DOI=10.1101/gr.10.5.703;
RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.;
RT "Identification of novel human genes evolutionarily conserved in
RT Caenorhabditis elegans by comparative proteomics.";
RL Genome Res. 10:703-713(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (FEB-2008) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC TISSUE=Brain;
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC TISSUE=Brain;
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=15914630; DOI=10.1167/iovs.05-0018;
RA Marchetti M.A., Pizarro G.O., Sagher D., Deamicis C., Brot N.,
RA Hejtmancik J.F., Weissbach H., Kantorow M.;
RT "Methionine sulfoxide reductases B1, B2, and B3 are present in the human
RT lens and confer oxidative stress resistance to lens cells.";
RL Invest. Ophthalmol. Vis. Sci. 46:2107-2112(2005).
RN [8]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=18424444; DOI=10.1074/jbc.m708580200;
RA Cabreiro F., Picot C.R., Perichon M., Castel J., Friguet B.,
RA Petropoulos I.;
RT "Overexpression of mitochondrial methionine sulfoxide reductase B2 protects
RT leukemia cells from oxidative stress-induced cell death and protein
RT damage.";
RL J. Biol. Chem. 283:16673-16681(2008).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Methionine-sulfoxide reductase that specifically reduces
CC methionine (R)-sulfoxide back to methionine. While in many cases,
CC methionine oxidation is the result of random oxidation following
CC oxidative stress, methionine oxidation is also a post-translational
CC modification that takes place on specific residue. Upon oxidative
CC stress, may play a role in the preservation of mitochondrial integrity
CC by decreasing the intracellular reactive oxygen species build-up
CC through its scavenging role, hence contributing to cell survival and
CC protein maintenance. {ECO:0000269|PubMed:18424444}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[thioredoxin]-disulfide + H2O + L-methionyl-[protein] =
CC [thioredoxin]-dithiol + L-methionyl-(R)-S-oxide-[protein];
CC Xref=Rhea:RHEA:24164, Rhea:RHEA-COMP:10698, Rhea:RHEA-COMP:10700,
CC Rhea:RHEA-COMP:12313, Rhea:RHEA-COMP:12314, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:16044, ChEBI:CHEBI:29950, ChEBI:CHEBI:45764,
CC ChEBI:CHEBI:50058; EC=1.8.4.12;
CC Evidence={ECO:0000250|UniProtKB:Q9JLC3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[thioredoxin]-disulfide + H2O + L-methionine = [thioredoxin]-
CC dithiol + L-methionine (R)-S-oxide; Xref=Rhea:RHEA:21260, 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:58773; EC=1.8.4.14;
CC Evidence={ECO:0000250|UniProtKB:Q9JLC3};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- INTERACTION:
CC Q9Y3D2; Q92870-2: APBB2; NbExp=3; IntAct=EBI-9092052, EBI-21535880;
CC Q9Y3D2; P02649: APOE; NbExp=3; IntAct=EBI-9092052, EBI-1222467;
CC Q9Y3D2; Q7Z3D6: DGLUCY; NbExp=3; IntAct=EBI-9092052, EBI-2807872;
CC Q9Y3D2; P26378-2: ELAVL4; NbExp=3; IntAct=EBI-9092052, EBI-21603100;
CC Q9Y3D2; P14136: GFAP; NbExp=3; IntAct=EBI-9092052, EBI-744302;
CC Q9Y3D2; P42858: HTT; NbExp=12; IntAct=EBI-9092052, EBI-466029;
CC Q9Y3D2; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-9092052, EBI-1055254;
CC Q9Y3D2; Q92597: NDRG1; NbExp=3; IntAct=EBI-9092052, EBI-716486;
CC Q9Y3D2; P19404: NDUFV2; NbExp=3; IntAct=EBI-9092052, EBI-713665;
CC Q9Y3D2; Q7Z412: PEX26; NbExp=3; IntAct=EBI-9092052, EBI-752057;
CC Q9Y3D2; D3DTS7: PMP22; NbExp=3; IntAct=EBI-9092052, EBI-25882629;
CC Q9Y3D2; P37840: SNCA; NbExp=3; IntAct=EBI-9092052, EBI-985879;
CC Q9Y3D2; Q12933: TRAF2; NbExp=3; IntAct=EBI-9092052, EBI-355744;
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:18424444}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. Detected in retina, ocular ciliary
CC body, skeletal muscle, heart, colon, bone marrow, cerebellum, small
CC intestine, fetal brain, fetal liver, kidney, spinal cord, lung,
CC placenta and prostate. {ECO:0000269|PubMed:10375640,
CC ECO:0000269|PubMed:15914630}.
CC -!- SIMILARITY: Belongs to the MsrB Met sulfoxide reductase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD34126.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF122004; AAD38899.1; -; mRNA.
DR EMBL; AF151889; AAD34126.1; ALT_FRAME; mRNA.
DR EMBL; EF444983; ACA05998.1; -; Genomic_DNA.
DR EMBL; AL139281; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471072; EAW86135.1; -; Genomic_DNA.
DR EMBL; BC018030; AAH18030.1; -; mRNA.
DR EMBL; BC117471; AAI17472.1; -; mRNA.
DR EMBL; BC130380; AAI30381.1; -; mRNA.
DR CCDS; CCDS41495.1; -.
DR RefSeq; NP_036360.3; NM_012228.3.
DR AlphaFoldDB; Q9Y3D2; -.
DR SMR; Q9Y3D2; -.
DR BioGRID; 116583; 55.
DR IntAct; Q9Y3D2; 16.
DR STRING; 9606.ENSP00000365693; -.
DR ChEMBL; CHEMBL3509603; -.
DR DrugBank; DB00134; Methionine.
DR iPTMnet; Q9Y3D2; -.
DR PhosphoSitePlus; Q9Y3D2; -.
DR SwissPalm; Q9Y3D2; -.
DR BioMuta; MSRB2; -.
DR DMDM; 182676405; -.
DR EPD; Q9Y3D2; -.
DR jPOST; Q9Y3D2; -.
DR MassIVE; Q9Y3D2; -.
DR MaxQB; Q9Y3D2; -.
DR PaxDb; Q9Y3D2; -.
DR PeptideAtlas; Q9Y3D2; -.
DR PRIDE; Q9Y3D2; -.
DR ProteomicsDB; 86019; -.
DR Antibodypedia; 25752; 185 antibodies from 28 providers.
DR DNASU; 22921; -.
DR Ensembl; ENST00000376510.8; ENSP00000365693.3; ENSG00000148450.13.
DR GeneID; 22921; -.
DR KEGG; hsa:22921; -.
DR MANE-Select; ENST00000376510.8; ENSP00000365693.3; NM_012228.4; NP_036360.3.
DR UCSC; uc001iro.4; human.
DR CTD; 22921; -.
DR DisGeNET; 22921; -.
DR GeneCards; MSRB2; -.
DR HGNC; HGNC:17061; MSRB2.
DR HPA; ENSG00000148450; Low tissue specificity.
DR MIM; 613782; gene.
DR neXtProt; NX_Q9Y3D2; -.
DR OpenTargets; ENSG00000148450; -.
DR PharmGKB; PA134979691; -.
DR VEuPathDB; HostDB:ENSG00000148450; -.
DR eggNOG; KOG0856; Eukaryota.
DR GeneTree; ENSGT00940000161673; -.
DR HOGENOM; CLU_031040_8_2_1; -.
DR InParanoid; Q9Y3D2; -.
DR OMA; RTEEHCA; -.
DR OrthoDB; 1549489at2759; -.
DR PhylomeDB; Q9Y3D2; -.
DR TreeFam; TF329147; -.
DR BRENDA; 1.8.4.12; 2681.
DR BRENDA; 1.8.4.B3; 2681.
DR PathwayCommons; Q9Y3D2; -.
DR Reactome; R-HSA-5676934; Protein repair.
DR SignaLink; Q9Y3D2; -.
DR BioGRID-ORCS; 22921; 4 hits in 1073 CRISPR screens.
DR ChiTaRS; MSRB2; human.
DR GeneWiki; MSRB2; -.
DR GenomeRNAi; 22921; -.
DR Pharos; Q9Y3D2; Tbio.
DR PRO; PR:Q9Y3D2; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q9Y3D2; protein.
DR Bgee; ENSG00000148450; Expressed in heart right ventricle and 207 other tissues.
DR ExpressionAtlas; Q9Y3D2; baseline and differential.
DR Genevisible; Q9Y3D2; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; ISS:HGNC-UCL.
DR GO; GO:0003779; F:actin binding; ISS:UniProtKB.
DR GO; GO:0033745; F:L-methionine-(R)-S-oxide reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0033743; F:peptide-methionine (R)-S-oxide reductase activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; ISS:HGNC-UCL.
DR GO; GO:0030041; P:actin filament polymerization; ISS:UniProtKB.
DR GO; GO:0030091; P:protein repair; ISS:HGNC-UCL.
DR GO; GO:0006979; P:response to oxidative stress; IEA:InterPro.
DR InterPro; IPR028427; Met_Sox_Rdtase_MsrB.
DR InterPro; IPR002579; Met_Sox_Rdtase_MsrB_dom.
DR InterPro; IPR011057; Mss4-like_sf.
DR PANTHER; PTHR10173; PTHR10173; 1.
DR Pfam; PF01641; SelR; 1.
DR SUPFAM; SSF51316; SSF51316; 1.
DR TIGRFAMs; TIGR00357; TIGR00357; 1.
DR PROSITE; PS51790; MSRB; 1.
PE 1: Evidence at protein level;
KW Metal-binding; Mitochondrion; Oxidoreductase; Reference proteome;
KW Transit peptide; Zinc.
FT TRANSIT 1..20
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 21..182
FT /note="Methionine-R-sulfoxide reductase B2, mitochondrial"
FT /id="PRO_0000140324"
FT DOMAIN 51..180
FT /note="MsrB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01126"
FT ACT_SITE 169
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01126"
FT BINDING 90
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01126"
FT BINDING 93
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01126"
FT BINDING 146
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01126"
FT BINDING 149
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01126"
FT VARIANT 46
FT /note="E -> G (in dbSNP:rs2296466)"
FT /id="VAR_050448"
FT CONFLICT 63
FT /note="F -> L (in Ref. 6; AAH18030)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 182 AA; 19536 MW; DFD1D0BF249D45BE CRC64;
MARLLWLLRG LTLGTAPRRA VRGQAGGGGP GTGPGLGEAG SLATCELPLA KSEWQKKLTP
EQFYVTREKG TEPPFSGIYL NNKEAGMYHC VCCDSPLFSS EKKYCSGTGW PSFSEAHGTS
GSDESHTGIL RRLDTSLGSA RTEVVCKQCE AHLGHVFPDG PGPNGQRFCI NSVALKFKPR
KH
