Reviewed, UniProtKB/Swiss-Prot Q923X4 (GLRX2_MOUSE)

Names and origin

Protein names

Recommended name:
    Glutaredoxin-2, mitochondrial

Gene names

Name:	Glrx2
Synonyms:	Grx2

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	156 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	Glutathione-dependent oxidoreductase that facilitates the maintenance of mitochondrial redox homeostasis upon induction of apoptosis by oxidative stress. Involved in response to hydrogen peroxide and regulation of apoptosis caused by oxidative stress. Acts as a very efficient catalyst of monothiol reactions because of its high affinity for protein glutathione-mixed disulfides. Can receive electrons not only from glutathione (GSH), but also from thioredoxin reductase supporting both monothiol and dithiol reactions. Efficiently catalyzes both glutathionylation and deglutathionylation of mitochondrial complex I, which in turn regulates the superoxide production by the complex. Overexpression decreases the susceptibility to apoptosis and prevents loss of cardiolipin and cytochrome c release. Ref.1 Ref.5
Enzyme regulation	The 2Fe-2S present in the homodimer leads to inactivation of the enzyme. The 2Fe-2S may serve as a redox sensor: the presence of one-electron oxidants or reductants leading to the loss of the 2Fe-2S cluster, subsequent monomerization and activation of the enzyme By similarity.
Subunit structure	Monomer; active form. Homodimer; inactive form. The homodimer is probably linked by 1 2Fe-2S cluster By similarity.
Subcellular location	Isoform 1: Mitochondrion. Ref.1 Isoform 2: Nucleus. Ref.1
Tissue specificity	Widely expressed. Highly expressed in testis, and at much lower level in kidney and brain. Ref.4
Developmental stage	During development, it is expressed at highest level at E11. Ref.4
Sequence similarities	Belongs to the glutaredoxin family. Contains 1 glutaredoxin domain.
Biophysicochemical properties	Kinetic parameters: KM=1.68 mM for HEDS KM=1.77 mM for S-sulfocysteine KM=0.3 mM for L-cystine
Sequence caution	The sequence AAF86465.1 differs from that shown. Reason: Frameshift at position 128.

Ontologies

Keywords
Biological process	Electron transport Transport
Cellular component	Mitochondrion Nucleus
Coding sequence diversity	Alternative splicing
Domain	Redox-active center Transit peptide
Ligand	2Fe-2S Iron Iron-sulfur Metal-binding
PTM	Disulfide bond Glutathionylation
Gene Ontology (GO)
Biological process	cell redox homeostasis Inferred from electronic annotation. Source: InterPro electron transport chain Inferred from electronic annotation. Source: UniProtKB-KW response to hydrogen peroxide Inferred from sequence or structural similarity. Source: UniProtKB response to organic substance Inferred from sequence or structural similarity. Source: UniProtKB transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	mitochondrion Inferred from sequence or structural similarity. Source: UniProtKB nucleus Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	2 iron, 2 sulfur cluster binding Inferred from electronic annotation. Source: UniProtKB-KW electron carrier activity Inferred from electronic annotation. Source: InterPro iron ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein disulfide oxidoreductase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q923X4-1)

Also known as: Grx2a;

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: Q923X4-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-33: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 19	19	Mitochondrion Potential
	Chain	20 – 156	137	Glutaredoxin-2, mitochondrial		PRO_0000011629
Regions
	Domain	50 – 150	101	Glutaredoxin
Sites
	Metal binding	61	1	Iron-sulfur (2Fe-2S); shared with dimeric partner; in inactive form By similarity
	Metal binding	146	1	Iron-sulfur (2Fe-2S); shared with dimeric partner; in inactive form By similarity
	Binding site	67	1	Glutathione By similarity
	Binding site	102	1	Glutathione By similarity
	Binding site	114	1	Glutathione; via amide nitrogen and carbonyl oxygen By similarity
Amino acid modifications
	Modified residue	70	1	S-glutathionyl cysteine; alternate By similarity
	Disulfide bond	70 ↔ 73		Redox-active; alternate By similarity
Natural variations
	Alternative sequence	1 – 33	33	Missing in isoform 2.		VSP_015222

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Grx2a) [UniParc]. Last modified December 1, 2001. Version 1. Checksum: 605BA5C62A139C3E	FASTA	156	17,307
	10 20 30 40 50 60 MSWRRAASVG RRLVASGRIL AGRRGAAGAA GSGMGNSTSS FWGKSTTTPV NQIQETISNN 70 80 90 100 110 120 CVVIFSKTSC SYCSMAKKIF HDMNVNYKAV ELDMLEYGNQ FQDALHKMTG ERTVPRIFVN 130 140 150 GRFIGGAADT HRLHKEGKLL PLVHQCYLKK KQEERH
	Isoform 2. Checksum: 803375159539AECD	FASTA	123	14,042
	10 20 30 40 50 60 MGNSTSSFWG KSTTTPVNQI QETISNNCVV IFSKTSCSYC SMAKKIFHDM NVNYKAVELD 70 80 90 100 110 120 MLEYGNQFQD ALHKMTGERT VPRIFVNGRF IGGAADTHRL HKEGKLLPLV HQCYLKKKQE ERH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and characterization of a new mammalian glutaredoxin (thioltransferase), Grx2." Gladyshev V.N., Liu A., Novoselov S.V., Krysan K., Sun Q.-A., Kryukov V.M., Kryukov G.V., Lou M.F. J. Biol. Chem. 276:30374-30380(2001) [PubMed: 11397793] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE SPLICING (ISOFORMS 1 AND 2), FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION.
[2]	Reddy P.G., Bhuyan D.K., Bhuyan K.C. Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Strain: CFW. Tissue: Lens.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Strain: C57BL/6J. Tissue: Testis.
[4]	"Absolute gene expression patterns of thioredoxin and glutaredoxin redox systems in mouse." Jurado J., Prieto-Alamo M.-J., Madrid-Risquez J., Pueyo C. J. Biol. Chem. 278:45546-45554(2003) [PubMed: 12954614] [Abstract] Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[5]	"Glutaredoxin 2 catalyzes the reversible oxidation and glutathionylation of mitochondrial membrane thiol proteins: implications for mitochondrial redox regulation and antioxidant defense." Beer S.M., Taylor E.R., Brown S.E., Dahm C.C., Costa N.J., Runswick M.J., Murphy M.P. J. Biol. Chem. 279:47939-47951(2004) [PubMed: 15347644] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF380337 mRNA. Translation: AAK85319.1. AF276918 mRNA. Translation: AAF86465.1. Frameshift. AK005853 mRNA. Translation: BAB24276.1.
IPI	IPI00124817. IPI00649425.
RefSeq	NP_001033681.1. NP_001033682.1. NP_075994.2.
UniGene	Mm.272727
3D structure databases
HSSP	HSSP built from PDB template 1JHB based on UniProtKB P35754.
SMR	Q923X4. Positions 47-154.
ModBase	Search...
PTM databases
PhosphoSite	Q923X4.
Proteomic databases
PRIDE	Q923X4.
Genome annotation databases
Ensembl	ENSMUSG00000018196. Mus musculus. [Contig view]
GeneID	69367.
KEGG	mmu:69367.
Organism-specific databases
MGI	MGI:1916617. Glrx2.
Phylogenomic databases
HOVERGEN	Q923X4.
OMA	Q923X4. QCYLNKS.
Gene expression databases
ArrayExpress	Q923X4.
Bgee	Q923X4.
CleanEx	MM_GLRX2.
GermOnline	ENSMUSG00000018196. Mus musculus.
Family and domain databases
InterPro	IPR011767. GLR_AS. IPR002109. Glutaredoxin. IPR014025. Glutaredoxin_sub. IPR015450. Grx-2. IPR011899. GRX_euk. IPR012335. Thioredoxin_fold. [Graphical view]
Gene3D	G3DSA:3.40.30.10. Thioredoxin_fold. 1 hit.
PANTHER	PTHR10168:SF17. Grx-2. 1 hit.
Pfam	PF00462. Glutaredoxin. 1 hit. [Graphical view]
PRINTS	PR00160. GLUTAREDOXIN.
TIGRFAMs	TIGR02180. GRX_euk. 1 hit.
PROSITE	PS00195. GLUTAREDOXIN_1. False negative. PS51354. GLUTAREDOXIN_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	329240.
SOURCE	Search...

Entry information

Entry name

GLRX2_MOUSE

Accession

Primary (citable) accession number: Q923X4
Secondary accession number(s): Q9DAG8, Q9JHY6

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 30, 2005
Last sequence update:	December 1, 2001
Last modified:	June 16, 2009
This is version 58 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)