Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q8IXL7 (MSRB3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 93. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Methionine-R-sulfoxide reductase B3

Short name=MsrB3
EC=1.8.4.-
Gene names
Name:MSRB3
ORF Names:UNQ1965/PRO4487
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length192 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes the reduction of free and protein-bound methionine sulfoxide to methionine. Isoform 2 is essential for hearing. Ref.5 Ref.8

Catalytic activity

L-methionine + oxidized thioredoxin = L-methionine R-oxide + reduced thioredoxin. HAMAP-Rule MF_01400

Cofactor

Binds 1 zinc ion per subunit. Ref.5

Subunit structure

Monomer. Ref.7

Subcellular location

Isoform 1: Endoplasmic reticulum Ref.5.

Isoform 2: Mitochondrion Ref.5.

Tissue specificity

Widely expressed. Ref.6 Ref.8

Involvement in disease

Deafness, autosomal recessive, 74 (DFNB74) [MIM:613718]: A 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.
Note: 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. Ref.8

Sequence similarities

Belongs to the MsrB Met sulfoxide reductase family.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8IXL7-1)

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.
Isoform 2 (identifier: Q8IXL7-2)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3232 Potential
Chain33 – 192160Methionine-R-sulfoxide reductase B3 HAMAP-Rule MF_01400
PRO_0000327240

Regions

Motif189 – 1924Endoplasmic reticulum retention signal By similarity

Sites

Active site1581Nucleophile Probable
Metal binding861Zinc By similarity
Metal binding891Zinc By similarity
Metal binding1351Zinc By similarity
Metal binding1381Zinc By similarity

Amino acid modifications

Modified residue421N6-acetyllysine By similarity

Natural variations

Alternative sequence1 – 3131MSPRR…LGSAQ → MSAFNLLHLVTKSQPVALRA CGLP in isoform 2.
VSP_040883
Natural variant891C → G in DFNB74; abolishes zinc-binding and enzymatic activity. Ref.8
VAR_064904

Experimental info

Mutagenesis1411H → G: 30-fold reduction in activity. Ref.7
Mutagenesis1601N → F: 7000-fold reduction in activity. Ref.7
Mutagenesis1601N → Y: 500-fold reduction in activity. Ref.7
Sequence conflict491E → G in BAH14736. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (A) [UniParc].

Last modified April 5, 2011. Version 2.
Checksum: C3326F6103369083

FASTA19220,702
        10         20         30         40         50         60 
MSPRRTLPRP LSLCLSLCLC LCLAAALGSA QSGSCRDKKN CKVVFSQQEL RKRLTPLQYH 

        70         80         90        100        110        120 
VTQEKGTESA FEGEYTHHKD PGIYKCVVCG TPLFKSETKF DSGSGWPSFH DVINSEAITF 

       130        140        150        160        170        180 
TDDFSYGMHR VETSCSQCGA HLGHIFDDGP RPTGKRYCIN SAALSFTPAD SSGTAEGGSG 

       190 
VASPAQADKA EL 

« Hide

Isoform 2 (B) (C) (D) [UniParc].

Checksum: 37576AFCF88CE227
Show »

FASTA18520,010

References

« Hide 'large scale' references
[1]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.
Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]
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. expand/collapse author list , 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]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001026849.1. NM_001031679.2.
NP_001180389.1. NM_001193460.1.
NP_001180390.1. NM_001193461.1.
NP_932346.1. NM_198080.3.
UniGeneHs.339024.

3D structure databases

ProteinModelPortalQ8IXL7.
SMRQ8IXL7. Positions 49-166.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ8IXL7. 1 interaction.

PTM databases

PhosphoSiteQ8IXL7.

Polymorphism databases

DMDM327478523.

Proteomic databases

PaxDbQ8IXL7.
PRIDEQ8IXL7.

Protocols and materials databases

DNASU253827.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000308259; ENSP00000312274; ENSG00000174099. [Q8IXL7-2]
ENST00000355192; ENSP00000347324; ENSG00000174099. [Q8IXL7-1]
ENST00000535664; ENSP00000441650; ENSG00000174099. [Q8IXL7-2]
GeneID253827.
KEGGhsa:253827.
UCSCuc001ssm.3. human. [Q8IXL7-2]
uc001ssn.3. human. [Q8IXL7-1]

Organism-specific databases

CTD253827.
GeneCardsGC12P065672.
HGNCHGNC:27375. MSRB3.
HPAHPA014432.
MIM613718. phenotype.
613719. gene.
neXtProtNX_Q8IXL7.
Orphanet90636. Autosomal recessive nonsyndromic sensorineural deafness type DFNB.
PharmGKBPA134991350.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0229.
HOGENOMHOG000243424.
HOVERGENHBG002192.
KOK07305.
OMAFMERTEV.
OrthoDBEOG7VHSZD.
PhylomeDBQ8IXL7.
TreeFamTF329147.

Gene expression databases

ArrayExpressQ8IXL7.
BgeeQ8IXL7.
CleanExHS_MSRB3.
GenevestigatorQ8IXL7.

Family and domain databases

Gene3D2.170.150.20. 1 hit.
HAMAPMF_01400. MsrB.
InterProIPR028427. Met_Sox_Rdtase.
IPR002579. Met_Sox_Rdtase_MsrB.
IPR011057. Mss4-like.
[Graphical view]
PANTHERPTHR10173. PTHR10173. 1 hit.
PfamPF01641. SelR. 1 hit.
[Graphical view]
SUPFAMSSF51316. SSF51316. 1 hit.
TIGRFAMsTIGR00357. TIGR00357. 1 hit.
ProtoNetSearch...

Other

ChiTaRSMSRB3. human.
GenomeRNAi253827.
NextBio92177.
PROQ8IXL7.
SOURCESearch...

Entry information

Entry nameMSRB3_HUMAN
AccessionPrimary (citable) accession number: Q8IXL7
Secondary accession number(s): B4DR19, B7ZAQ0, Q6UXS2
Entry history
Integrated into UniProtKB/Swiss-Prot: April 8, 2008
Last sequence update: April 5, 2011
Last modified: April 16, 2014
This is version 93 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM