Q8IXL7 (MSRB3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Methionine-R-sulfoxide reductase B3
Short name=MsrB3
EC=1.8.4.-

Gene names

Name:	MSRB3
ORF Names:	UNQ1965/PRO4487

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	192 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.
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	Defects in MSRB3 are the cause of deafness autosomal recessive type 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=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.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Mitochondrion
Coding sequence diversity	Alternative splicing
Disease	Deafness Disease mutation Non-syndromic deafness
Domain	Signal
Ligand	Metal-binding Zinc
Molecular function	Oxidoreductase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	protein repair Inferred from direct assay Ref.5. Source: HGNC
Cellular component	endoplasmic reticulum Inferred from direct assay Ref.5. Source: HGNC mitochondrion Inferred from direct assay Ref.5. Source: HGNC
Molecular function	peptide-methionine-(S)-S-oxide reductase activity Inferred from electronic annotation. Source: InterPro protein-methionine-R-oxide reductase activity Inferred from direct assay Ref.5. Source: HGNC zinc ion binding Inferred from direct assay Ref.5. Source: HGNC
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 32	32	Potential
	Chain	33 – 192	160	Methionine-R-sulfoxide reductase B3		PRO_0000327240
Regions
	Motif	189 – 192	4	Endoplasmic reticulum retention signal By similarity
Sites
	Active site	158	1	Nucleophile Probable
	Metal binding	86	1	Zinc By similarity
	Metal binding	89	1	Zinc By similarity
	Metal binding	135	1	Zinc By similarity
	Metal binding	138	1	Zinc By similarity
Natural variations
	Alternative sequence	1 – 31	31	MSPRR…LGSAQ → MSAFNLLHLVTKSQPVALRA CGLP in isoform 2.		VSP_040883
	Natural variant	89	1	C → G in DFNB74; abolishes zinc-binding and enzymatic activity. Ref.8		VAR_064904
Experimental info
	Mutagenesis	141	1	H → G: 30-fold reduction in activity. Ref.7
	Mutagenesis	160	1	N → F: 7000-fold reduction in activity. Ref.7
	Mutagenesis	160	1	N → Y: 500-fold reduction in activity. Ref.7
	Sequence conflict	49	1	E → G in BAH14736. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (A) [UniParc]. Last modified April 5, 2011. Version 2. Checksum: C3326F6103369083	FASTA	192	20,702
	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
	Isoform 2 (B) (C) (D) [UniParc]. Checksum: 37576AFCF88CE227	FASTA	185	20,010
	10 20 30 40 50 60 MSAFNLLHLV TKSQPVALRA CGLPSGSCRD KKNCKVVFSQ QELRKRLTPL QYHVTQEKGT 70 80 90 100 110 120 ESAFEGEYTH HKDPGIYKCV VCGTPLFKSE TKFDSGSGWP SFHDVINSEA ITFTDDFSYG 130 140 150 160 170 180 MHRVETSCSQ CGAHLGHIFD DGPRPTGKRY CINSAALSFT PADSSGTAEG GSGVASPAQA DKAEL

References

	« Hide 'large scale' referencesShow '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. , 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: 12975309] [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. , 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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Oesophageal 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: 17974005] [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: 15489334] [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: 14699060] [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: 15914630] [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: 16262444] [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: 21185009] [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.
IPI	IPI00217550. IPI00479793.
RefSeq	NP_001026849.1. NM_001031679.2. NP_001180389.1. NM_001193460.1. NP_001180390.1. NM_001193461.1. NP_932346.1. NM_198080.3.
UniGene	Hs.339024.
3D structure databases
HSSP	HSSP built from PDB template 1L1D based on UniProtKB P14930.
ProteinModelPortal	Q8IXL7.
SMR	Q8IXL7. Positions 49-166.
ModBase	Search...
Protein-protein interaction databases
STRING	Q8IXL7.
PTM databases
PhosphoSite	Q8IXL7.
Polymorphism databases
DMDM	74728209.
Proteomic databases
PRIDE	Q8IXL7.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000308259; ENSP00000312274; ENSG00000174099.
GeneID	253827.
KEGG	hsa:253827.
UCSC	uc001ssm.1. human. uc001ssn.1. human.
Organism-specific databases
CTD	253827.
GeneCards	GC12P065672.
H-InvDB	HIX0010788.
HGNC	HGNC:27375. MSRB3.
HPA	HPA014432.
MIM	613718. phenotype. 613719. gene.
neXtProt	NX_Q8IXL7.
Orphanet	90636. Autosomal recessive nonsyndromic sensorineural deafness type DFNB.
GenAtlas	Search...
Phylogenomic databases
GeneTree	ENSGT00510000046802.
HOVERGEN	HBG002192.
OMA	FTDGPVD.
OrthoDB	EOG4N30PZ.
PhylomeDB	Q8IXL7.
Gene expression databases
ArrayExpress	Q8IXL7.
Bgee	Q8IXL7.
CleanEx	HS_MSRB3.
Genevestigator	Q8IXL7.
Family and domain databases
InterPro	IPR002579. Methionine_sulphoxide_MsrB. IPR011057. Mss4-like. [Graphical view]
Gene3D	G3DSA:2.170.150.20. MsrB. 1 hit.
Pfam	PF01641. SelR. 1 hit. [Graphical view]
SUPFAM	SSF51316. Mss4_like. 1 hit.
TIGRFAMs	TIGR00357. TIGR00357. 1 hit.
ProtoNet	Search...
Other
NextBio	92177.
SOURCE	Search...

Entry information

Entry name

MSRB3_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 71 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.