Q9UJ68 (MSRA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Mitochondrial peptide methionine sulfoxide reductase
EC=1.8.4.11

Alternative name(s):
Peptide-methionine (S)-S-oxide reductase
Short name=Peptide Met(O) reductase
Protein-methionine-S-oxide reductase
Short name=PMSR

Gene names

Name:

MSRA

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	235 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	Has an important function as a repair enzyme for proteins that have been inactivated by oxidation. Catalyzes the reversible oxidation-reduction of methionine sulfoxide in proteins to methionine.
Catalytic activity	Peptide-L-methionine + thioredoxin disulfide + H2O = peptide-L-methionine (S)-S-oxide + thioredoxin. L-methionine + thioredoxin disulfide + H2O = L-methionine (S)-S-oxide + thioredoxin.
Subcellular location	Isoform 1: Mitochondrion Ref.2 Ref.3 Ref.10. Isoform 2: Cytoplasm. Isoform 3: Cytoplasm. Nucleus Ref.2 Ref.3 Ref.10. Isoform 5: Cytoplasm. Membrane; Lipid-anchor Ref.2 Ref.3 Ref.10.
Tissue specificity	Ubiquitous. Highest expression in adult kidney and cerebellum, followed by liver, heart ventricles, bone marrow and hippocampus.
Sequence similarities	Belongs to the MsrA Met sulfoxide reductase family.

Ontologies

Keywords
Cellular component	Cytoplasm Membrane Mitochondrion Nucleus
Coding sequence diversity	Alternative initiation Alternative promoter usage Alternative splicing
Domain	Transit peptide
Molecular function	Oxidoreductase
PTM	Lipoprotein Myristate
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular protein modification process Traceable author statement Ref.1. Source: ProtInc methionine metabolic process Traceable author statement Ref.1. Source: ProtInc response to oxidative stress Traceable author statement Ref.1. Source: ProtInc
Cellular_component	membrane Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrion Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	peptide-methionine (S)-S-oxide reductase activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative promoter usage, alternative splicing and alternative initiation. [Align] [Select]

Note: Only about 25% of mRNAs are initiated at the mitochondrial isoform 1 codon.

Isoform 1 (identifier: Q9UJ68-1)

Also known as: MsrA1; mitoMSRA; 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.

Note: Mitochondrial. Produced by alternative splicing.

Isoform 2 (identifier: Q9UJ68-2)

Also known as: MsrA2; d;

The sequence of this isoform differs from the canonical sequence as follows:
     1-66: Missing.

Note: Cytoplasmic. Produced by alternative promoter usage.

Isoform 3 (identifier: Q9UJ68-3)

Also known as: MsrA3; cytoMSRA; c;

The sequence of this isoform differs from the canonical sequence as follows:
     1-48: MLSATRRACQLLLLHSLFPVPRMGNSASNIVSPQEALPGRKEQTPVAA → MCSEP

Note: Cytoplasmic and nuclear. Produced by alternative promoter usage.

Isoform 4 (identifier: Q9UJ68-4)

Also known as: b;

The sequence of this isoform differs from the canonical sequence as follows:
     71-110: Missing.

Note: Produced by alternative splicing.

Isoform 5 (identifier: Q9UJ68-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-22: Missing.

Note: Cytoplasmic. Myristoylated at Gly-2. Produced by alternative initiation.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 23	23	Mitochondrion
	Chain	24 – 235	212	Mitochondrial peptide methionine sulfoxide reductase		PRO_0000138626
Natural variations
	Alternative sequence	1 – 66	66	Missing in isoform 2.		VSP_041405
	Alternative sequence	1 – 48	48	MLSAT…TPVAA → MCSEP in isoform 3.		VSP_041406
	Alternative sequence	1 – 22	22	Missing in isoform 5.		VSP_042132
	Alternative sequence	71 – 110	40	Missing in isoform 4.		VSP_041407
Experimental info
	Mutagenesis	6	1	R → A: Impaired subcellular location. Ref.10
	Mutagenesis	7	1	R → A: Impaired subcellular location. Ref.10
	Mutagenesis	11 – 13	3	Missing: Impaired subcellular location.
	Mutagenesis	22	1	R → A: Impaired subcellular location. Ref.10
	Sequence conflict	12 – 14	3	Missing in AAG09689. Ref.6
	Sequence conflict	134 – 137	4	LKVF → SRL in AAG09689. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (MsrA1) (mitoMSRA) (a) [UniParc]. Last modified May 1, 2000. Version 1. Checksum: B89A9BBBE4D58D90	FASTA	235	26,132
	10 20 30 40 50 60 MLSATRRACQ LLLLHSLFPV PRMGNSASNI VSPQEALPGR KEQTPVAAKH HVNGNRTVEP 70 80 90 100 110 120 FPEGTQMAVF GMGCFWGAER KFWVLKGVYS TQVGFAGGYT SNPTYKEVCS EKTGHAEVVR 130 140 150 160 170 180 VVYQPEHMSF EELLKVFWEN HDPTQGMRQG NDHGTQYRSA IYPTSAKQME AALSSKENYQ 190 200 210 220 230 KVLSEHGFGP ITTDIREGQT FYYAEDYHQQ YLSKNPNGYC GLGGTGVSCP VGIKK
	Isoform 2 (MsrA2) (d) [UniParc]. Checksum: 4741F1AF6ECA34DC	FASTA	169	18,963
	10 20 30 40 50 60 MAVFGMGCFW GAERKFWVLK GVYSTQVGFA GGYTSNPTYK EVCSEKTGHA EVVRVVYQPE 70 80 90 100 110 120 HMSFEELLKV FWENHDPTQG MRQGNDHGTQ YRSAIYPTSA KQMEAALSSK ENYQKVLSEH 130 140 150 160 GFGPITTDIR EGQTFYYAED YHQQYLSKNP NGYCGLGGTG VSCPVGIKK
	Isoform 3 (MsrA3) (cytoMSRA) (c) [UniParc]. Checksum: 0B919D21F23A79A6	FASTA	192	21,540
	10 20 30 40 50 60 MCSEPKHHVN GNRTVEPFPE GTQMAVFGMG CFWGAERKFW VLKGVYSTQV GFAGGYTSNP 70 80 90 100 110 120 TYKEVCSEKT GHAEVVRVVY QPEHMSFEEL LKVFWENHDP TQGMRQGNDH GTQYRSAIYP 130 140 150 160 170 180 TSAKQMEAAL SSKENYQKVL SEHGFGPITT DIREGQTFYY AEDYHQQYLS KNPNGYCGLG 190 GTGVSCPVGI KK
	Isoform 4 (b) [UniParc]. Checksum: ECDCC13F2C46BA89	FASTA	195	21,737
	10 20 30 40 50 60 MLSATRRACQ LLLLHSLFPV PRMGNSASNI VSPQEALPGR KEQTPVAAKH HVNGNRTVEP 70 80 90 100 110 120 FPEGTQMAVF EKTGHAEVVR VVYQPEHMSF EELLKVFWEN HDPTQGMRQG NDHGTQYRSA 130 140 150 160 170 180 IYPTSAKQME AALSSKENYQ KVLSEHGFGP ITTDIREGQT FYYAEDYHQQ YLSKNPNGYC 190 GLGGTGVSCP VGIKK
	Isoform 5 [UniParc]. Checksum: A25E9F9AB29DA412	FASTA	213	23,627
	10 20 30 40 50 60 MGNSASNIVS PQEALPGRKE QTPVAAKHHV NGNRTVEPFP EGTQMAVFGM GCFWGAERKF 70 80 90 100 110 120 WVLKGVYSTQ VGFAGGYTSN PTYKEVCSEK TGHAEVVRVV YQPEHMSFEE LLKVFWENHD 130 140 150 160 170 180 PTQGMRQGND HGTQYRSAIY PTSAKQMEAA LSSKENYQKV LSEHGFGPIT TDIREGQTFY 190 200 210 YAEDYHQQYL SKNPNGYCGL GGTGVSCPVG IKK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and functional expression of a human peptide methionine sulfoxide reductase (hMsrA)." Kuschel L., Hansel A., Schoenherr R., Weissbach H., Brot N., Hoshi T., Heinemann S.H. FEBS Lett. 456:17-21(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Lung.
[2]	"Heterogeneity and function of mammalian MSRs: enzymes for repair, protection and regulation." Hansel A., Heinemann S.H., Hoshi T. Biochim. Biophys. Acta 1703:239-247(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), ALTERNATIVE SPLICING, SUBCELLULAR LOCATION.
[3]	"Gene structure, localization and role in oxidative stress of methionine sulfoxide reductase A (MSRA) in the monkey retina." Lee J.W., Gordiyenko N.V., Marchetti M., Tserentsoodol N., Sagher D., Alam S., Weissbach H., Kantorow M., Rodriguez I.R. Exp. Eye Res. 82:816-827(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1; 2 AND 3), ALTERNATIVE PROMOTER USAGE, SUBCELLULAR LOCATION.
[4]	"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] (ISOFORM 2). Tissue: Cerebellum.
[5]	"Cloning of a novel human cDNA which shows great homology to Bos taurus methionine sulfoxide reductase (msrA) mRNA." Zhao Y., Yu L., Tu Q., Yue P., Zhang M., Zhao S.Y. Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[6]	"A novel gene expressed in human hypothalamus." Peng Y., Huang C., Gu Y., Xu S., Han Z., Fu G., Chen Z. Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Hypothalamus.
[7]	"DNA sequence and analysis of human chromosome 8." Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S. Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"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 1). Tissue: Uterus.
[10]	"Mitochondrial targeting of the human peptide methionine sulfoxide reductase (MSRA), an enzyme involved in the repair of oxidized proteins." Hansel A., Kuschel L., Hehl S., Lemke C., Agricola H.J., Hoshi T., Heinemann S.H. FASEB J. 16:911-913(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF ARG-6; ARG-7; ARG-22 AND 11-LEU--LEU-14.
[11]	"Dual sites of protein initiation control the localization and myristoylation of methionine sulfoxide reductase A." Kim G., Cole N.B., Lim J.C., Zhao H., Levine R.L. J. Biol. Chem. 285:18085-18094(2010) [PubMed] [Europe PMC] [Abstract] Cited for: MYRISTOYLATION (ISOFORM 5), ALTERNATIVE INITIATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ242973 mRNA. Translation: CAB59628.1. AY690665 mRNA. Translation: AAU11088.1. AY958429 mRNA. Translation: AAY17426.1. AY958430 mRNA. Translation: AAY17427.1. AY958431 mRNA. Translation: AAY17428.1. AY958432 Genomic DNA. Translation: AAY17429.1. AY958432 Genomic DNA. Translation: AAY17430.1. AY958432 Genomic DNA. Translation: AAY17431.1. AK293488 mRNA. Translation: BAH11521.1. AF086925 mRNA. Translation: AAP97154.1. AF183420 mRNA. Translation: AAG09689.1. AC023385 Genomic DNA. No translation available. AC034111 Genomic DNA. No translation available. AC079200 Genomic DNA. No translation available. AC112673 Genomic DNA. No translation available. CH471157 Genomic DNA. Translation: EAW65584.1. CH471157 Genomic DNA. Translation: EAW65585.1. BC054033 mRNA. Translation: AAH54033.1.
IPI	IPI00006592. IPI00794951. IPI00796388. IPI01016029.
RefSeq	NP_001129142.1. NM_001135670.1. NP_001129143.1. NM_001135671.1. NP_001186658.1. NM_001199729.1. NP_036463.1. NM_012331.3.
UniGene	Hs.490981.
3D structure databases
ProteinModelPortal	Q9UJ68.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000313921.
PTM databases
PhosphoSite	Q9UJ68.
Polymorphism databases
DMDM	12230350.
Proteomic databases
PaxDb	Q9UJ68.
PRIDE	Q9UJ68.
Protocols and materials databases
DNASU	4482.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000317173; ENSP00000313921; ENSG00000175806. ENST00000382490; ENSP00000371930; ENSG00000175806. ENST00000441698; ENSP00000410912; ENSG00000175806. ENST00000528246; ENSP00000436839; ENSG00000175806.
GeneID	4482.
KEGG	hsa:4482.
UCSC	uc003wsx.3. human. uc003wsz.3. human. uc011kwx.2. human.
Organism-specific databases
CTD	4482.
GeneCards	GC08P009949.
H-InvDB	HIX0168875.
HGNC	HGNC:7377. MSRA.
HPA	HPA023804.
MIM	601250. gene.
neXtProt	NX_Q9UJ68.
PharmGKB	PA31182.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0225.
HOGENOM	HOG000263862.
HOVERGEN	HBG006401.
InParanoid	Q9UJ68.
KO	K07304.
OMA	QPFYPAE.
OrthoDB	EOG4H19WS.
PhylomeDB	Q9UJ68.
Gene expression databases
ArrayExpress	Q9UJ68.
Bgee	Q9UJ68.
CleanEx	HS_MSRA.
Genevestigator	Q9UJ68.
GermOnline	ENSG00000175806. Homo sapiens.
Family and domain databases
Gene3D	3.30.1060.10. 1 hit.
InterPro	IPR002569. Met_Sox_Rdtase_MsrA. [Graphical view]
Pfam	PF01625. PMSR. 1 hit. [Graphical view]
SUPFAM	SSF55068. MsrA. 1 hit.
TIGRFAMs	TIGR00401. msrA. 1 hit.
ProtoNet	Search...
Other
ChiTaRS	MSRA. human.
DrugBank	DB00134. L-Methionine.
GenomeRNAi	4482.
NextBio	17345.
SOURCE	Search...

Entry information

Entry name

MSRA_HUMAN

Accession

Primary (citable) accession number: Q9UJ68
Secondary accession number(s): E9PAS8 , Q52TC4, Q549N4, Q66MI7

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 11, 2001
Last sequence update:	May 1, 2000
Last modified:	May 1, 2013
This is version 106 of the entry and version 1 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.