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Protein

Methionine-R-sulfoxide reductase B3

Gene

MSRB3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the reduction of free and protein-bound methionine sulfoxide to methionine. Isoform 2 is essential for hearing.2 Publications

Catalytic activityi

L-methionine + oxidized thioredoxin = L-methionine R-oxide + reduced thioredoxin.

Cofactori

Zn2+1 PublicationNote: Binds 1 zinc ion per subunit.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi86 – 861ZincBy similarity
Metal bindingi89 – 891ZincBy similarity
Metal bindingi135 – 1351ZincBy similarity
Metal bindingi138 – 1381ZincBy similarity
Active sitei158 – 1581NucleophileCurated

GO - Molecular functioni

  • peptide-methionine (R)-S-oxide reductase activity Source: HGNC
  • zinc ion binding Source: HGNC

GO - Biological processi

  • protein repair Source: HGNC
  • response to oxidative stress Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BRENDAi1.8.4.12. 2681.
1.8.4.B3. 2681.

Names & Taxonomyi

Protein namesi
Recommended name:
Methionine-R-sulfoxide reductase B3 (EC:1.8.4.-)
Short name:
MsrB3
Gene namesi
Name:MSRB3
ORF Names:UNQ1965/PRO4487
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:27375. MSRB3.

Subcellular locationi

GO - Cellular componenti

  • endoplasmic reticulum Source: HGNC
  • mitochondrion Source: HGNC
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Deafness, autosomal recessive, 74 (DFNB74)1 Publication

The disease is caused by mutations affecting the gene represented in this entry. A nonsense mutation affecting exclusively mitochondrial isoform 2 is sufficient to produce hearing loss.

Disease descriptionA form of non-syndromic sensorineural deafness characterized by prelingual, bilateral, profound hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.

See also OMIM:613718
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti89 – 891C → G in DFNB74; abolishes zinc-binding and enzymatic activity. 1 Publication
VAR_064904

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi141 – 1411H → G: 30-fold reduction in activity. 1 Publication
Mutagenesisi160 – 1601N → F: 7000-fold reduction in activity. 1 Publication
Mutagenesisi160 – 1601N → Y: 500-fold reduction in activity. 1 Publication

Keywords - Diseasei

Deafness, Disease mutation, Non-syndromic deafness

Organism-specific databases

MIMi613718. phenotype.
Orphaneti90636. Autosomal recessive non-syndromic sensorineural deafness type DFNB.
PharmGKBiPA134991350.

Polymorphism and mutation databases

BioMutaiMSRB3.
DMDMi327478523.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3232Sequence AnalysisAdd
BLAST
Chaini33 – 192160Methionine-R-sulfoxide reductase B3PRO_0000327240Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei42 – 421N6-acetyllysineBy similarity

Keywords - PTMi

Acetylation

Proteomic databases

MaxQBiQ8IXL7.
PaxDbiQ8IXL7.
PRIDEiQ8IXL7.

PTM databases

PhosphoSiteiQ8IXL7.

Expressioni

Tissue specificityi

Widely expressed.2 Publications

Gene expression databases

BgeeiQ8IXL7.
CleanExiHS_MSRB3.
ExpressionAtlasiQ8IXL7. baseline and differential.
GenevisibleiQ8IXL7. HS.

Organism-specific databases

HPAiHPA014432.

Interactioni

Subunit structurei

Monomer.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
GOLGA2Q083793EBI-8634060,EBI-618309
PRDM4Q9UKN53EBI-8634060,EBI-2803427
TCF4P158843EBI-8634060,EBI-533224
TRIP6Q156543EBI-8634060,EBI-742327

Protein-protein interaction databases

BioGridi128990. 13 interactions.
IntActiQ8IXL7. 6 interactions.
STRINGi9606.ENSP00000347324.

Structurei

3D structure databases

ProteinModelPortaliQ8IXL7.
SMRiQ8IXL7. Positions 49-166.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi189 – 1924Endoplasmic reticulum retention signalBy similarity

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiCOG0229.
GeneTreeiENSGT00510000046802.
HOGENOMiHOG000243424.
HOVERGENiHBG002192.
InParanoidiQ8IXL7.
KOiK07305.
OMAiITVMSAF.
OrthoDBiEOG7VHSZD.
PhylomeDBiQ8IXL7.
TreeFamiTF329147.

Family and domain databases

Gene3Di2.170.150.20. 1 hit.
HAMAPiMF_01400. MsrB.
InterProiIPR028427. Met_Sox_Rdtase.
IPR002579. Met_Sox_Rdtase_MsrB.
IPR011057. Mss4-like.
[Graphical view]
PANTHERiPTHR10173. PTHR10173. 1 hit.
PfamiPF01641. SelR. 1 hit.
[Graphical view]
SUPFAMiSSF51316. SSF51316. 1 hit.
TIGRFAMsiTIGR00357. TIGR00357. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8IXL7-1) [UniParc]FASTAAdd to basket

Also known as: A

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSPRRTLPRP LSLCLSLCLC LCLAAALGSA QSGSCRDKKN CKVVFSQQEL
60 70 80 90 100
RKRLTPLQYH VTQEKGTESA FEGEYTHHKD PGIYKCVVCG TPLFKSETKF
110 120 130 140 150
DSGSGWPSFH DVINSEAITF TDDFSYGMHR VETSCSQCGA HLGHIFDDGP
160 170 180 190
RPTGKRYCIN SAALSFTPAD SSGTAEGGSG VASPAQADKA EL
Length:192
Mass (Da):20,702
Last modified:April 5, 2011 - v2
Checksum:iC3326F6103369083
GO
Isoform 2 (identifier: Q8IXL7-2) [UniParc]FASTAAdd to basket

Also known as: B, C, D

The sequence of this isoform differs from the canonical sequence as follows:
     1-31: MSPRRTLPRPLSLCLSLCLCLCLAAALGSAQ → MSAFNLLHLVTKSQPVALRACGLP

Note: Has a transit peptide.
Show »
Length:185
Mass (Da):20,010
Checksum:i37576AFCF88CE227
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti49 – 491E → G in BAH14736 (PubMed:14702039).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti89 – 891C → G in DFNB74; abolishes zinc-binding and enzymatic activity. 1 Publication
VAR_064904

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 3131MSPRR…LGSAQ → MSAFNLLHLVTKSQPVALRA CGLP in isoform 2. 3 PublicationsVSP_040883Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY358229 mRNA. Translation: AAQ88596.1.
AK293084 mRNA. Translation: BAF85773.1.
AK299065 mRNA. Translation: BAG61131.1.
AK316365 mRNA. Translation: BAH14736.1.
BX648776 mRNA. Translation: CAI46018.1.
BC040053 mRNA. Translation: AAH40053.1.
CCDSiCCDS31853.1. [Q8IXL7-2]
CCDS8973.1. [Q8IXL7-1]
RefSeqiNP_001026849.1. NM_001031679.2. [Q8IXL7-2]
NP_001180389.1. NM_001193460.1. [Q8IXL7-2]
NP_001180390.1. NM_001193461.1. [Q8IXL7-2]
NP_932346.1. NM_198080.3. [Q8IXL7-1]
UniGeneiHs.339024.

Genome annotation databases

EnsembliENST00000308259; ENSP00000312274; ENSG00000174099. [Q8IXL7-2]
ENST00000355192; ENSP00000347324; ENSG00000174099. [Q8IXL7-1]
ENST00000535664; ENSP00000441650; ENSG00000174099. [Q8IXL7-2]
ENST00000614640; ENSP00000481483; ENSG00000174099. [Q8IXL7-2]
GeneIDi253827.
KEGGihsa:253827.
UCSCiuc001ssm.3. human. [Q8IXL7-2]
uc001ssn.3. human. [Q8IXL7-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY358229 mRNA. Translation: AAQ88596.1.
AK293084 mRNA. Translation: BAF85773.1.
AK299065 mRNA. Translation: BAG61131.1.
AK316365 mRNA. Translation: BAH14736.1.
BX648776 mRNA. Translation: CAI46018.1.
BC040053 mRNA. Translation: AAH40053.1.
CCDSiCCDS31853.1. [Q8IXL7-2]
CCDS8973.1. [Q8IXL7-1]
RefSeqiNP_001026849.1. NM_001031679.2. [Q8IXL7-2]
NP_001180389.1. NM_001193460.1. [Q8IXL7-2]
NP_001180390.1. NM_001193461.1. [Q8IXL7-2]
NP_932346.1. NM_198080.3. [Q8IXL7-1]
UniGeneiHs.339024.

3D structure databases

ProteinModelPortaliQ8IXL7.
SMRiQ8IXL7. Positions 49-166.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi128990. 13 interactions.
IntActiQ8IXL7. 6 interactions.
STRINGi9606.ENSP00000347324.

PTM databases

PhosphoSiteiQ8IXL7.

Polymorphism and mutation databases

BioMutaiMSRB3.
DMDMi327478523.

Proteomic databases

MaxQBiQ8IXL7.
PaxDbiQ8IXL7.
PRIDEiQ8IXL7.

Protocols and materials databases

DNASUi253827.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000308259; ENSP00000312274; ENSG00000174099. [Q8IXL7-2]
ENST00000355192; ENSP00000347324; ENSG00000174099. [Q8IXL7-1]
ENST00000535664; ENSP00000441650; ENSG00000174099. [Q8IXL7-2]
ENST00000614640; ENSP00000481483; ENSG00000174099. [Q8IXL7-2]
GeneIDi253827.
KEGGihsa:253827.
UCSCiuc001ssm.3. human. [Q8IXL7-2]
uc001ssn.3. human. [Q8IXL7-1]

Organism-specific databases

CTDi253827.
GeneCardsiGC12P065672.
HGNCiHGNC:27375. MSRB3.
HPAiHPA014432.
MIMi613718. phenotype.
613719. gene.
neXtProtiNX_Q8IXL7.
Orphaneti90636. Autosomal recessive non-syndromic sensorineural deafness type DFNB.
PharmGKBiPA134991350.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0229.
GeneTreeiENSGT00510000046802.
HOGENOMiHOG000243424.
HOVERGENiHBG002192.
InParanoidiQ8IXL7.
KOiK07305.
OMAiITVMSAF.
OrthoDBiEOG7VHSZD.
PhylomeDBiQ8IXL7.
TreeFamiTF329147.

Enzyme and pathway databases

BRENDAi1.8.4.12. 2681.
1.8.4.B3. 2681.

Miscellaneous databases

ChiTaRSiMSRB3. human.
GenomeRNAii253827.
NextBioi92177.
PROiQ8IXL7.
SOURCEiSearch...

Gene expression databases

BgeeiQ8IXL7.
CleanExiHS_MSRB3.
ExpressionAtlasiQ8IXL7. baseline and differential.
GenevisibleiQ8IXL7. HS.

Family and domain databases

Gene3Di2.170.150.20. 1 hit.
HAMAPiMF_01400. MsrB.
InterProiIPR028427. Met_Sox_Rdtase.
IPR002579. Met_Sox_Rdtase_MsrB.
IPR011057. Mss4-like.
[Graphical view]
PANTHERiPTHR10173. PTHR10173. 1 hit.
PfamiPF01641. SelR. 1 hit.
[Graphical view]
SUPFAMiSSF51316. SSF51316. 1 hit.
TIGRFAMsiTIGR00357. TIGR00357. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Tissue: Esophageal carcinoma, Teratocarcinoma and Uterus.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Tissue: Uterus.
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Tissue: Pancreas.
  5. "Methionine sulfoxide reduction in mammals: characterization of methionine-R-sulfoxide reductases."
    Kim H.-Y., Gladyshev V.N.
    Mol. Biol. Cell 15:1055-1064(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, COFACTOR, SUBCELLULAR LOCATION, ALTERNATIVE SPLICING.
  6. "Methionine sulfoxide reductases B1, B2, and B3 are present in the human lens and confer oxidative stress resistance to lens cells."
    Marchetti M.A., Pizarro G.O., Sagher D., Deamicis C., Brot N., Hejtmancik J.F., Weissbach H., Kantorow M.
    Invest. Ophthalmol. Vis. Sci. 46:2107-2112(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  7. "Different catalytic mechanisms in mammalian selenocysteine- and cysteine-containing methionine-R-sulfoxide reductases."
    Kim H.-Y., Gladyshev V.N.
    PLoS Biol. 3:2080-2089(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF HIS-141 AND ASN-160, SUBUNIT.
  8. "Functional null mutations of MSRB3 encoding methionine sulfoxide reductase are associated with human deafness DFNB74."
    Ahmed Z.M., Yousaf R., Lee B.C., Khan S.N., Lee S., Lee K., Husnain T., Rehman A.U., Bonneux S., Ansar M., Ahmad W., Leal S.M., Gladyshev V.N., Belyantseva I.A., Van Camp G., Riazuddin S., Friedman T.B., Riazuddin S.
    Am. J. Hum. Genet. 88:19-29(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT DFNB74 GLY-89, FUNCTION, ALTERNATIVE SPLICING, TISSUE SPECIFICITY.

Entry informationi

Entry nameiMSRB3_HUMAN
AccessioniPrimary (citable) accession number: Q8IXL7
Secondary accession number(s): B4DR19, B7ZAQ0, Q6UXS2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 8, 2008
Last sequence update: April 5, 2011
Last modified: June 24, 2015
This is version 105 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.