SRXN1 (sulfiredoxin 1)

2012-11-01   Hedy A Chawsheen , Hong Jiang , Qiou Wei 

Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, Kentucky 40513, USA

Identity

HGNC
LOCATION
20p13
LOCUSID
ALIAS
C20orf139,Npn3,SRX,SRX1
FUSION GENES

DNA/RNA

Note

Human Srx is located on chromosome 20 in the region of p13.

Description

Human Srx gene is 6632 bp in length, composed of 2 exons and located at chromosome 20p13.

Transcription

The size of Srx mRNA is 2580 bp. Srx transcript contains two exons. Exon 1 is 271 bp and exon 2 is 2300 bp. The catalytic domain of Srx reducing enzyme activity is localized in exon 2.

Proteins

Note

Human Srx protein has a total of 137 amino acids and a 14 kDa molecular weight.

Description

Srx is a member of antioxidant protein family containing a ParB-like nuclease domain. It forms 5 beta strands and 6 helix secondary structures. Srxn1 binds to peroxiredoxins (Prxs) and reduces overoxidized Prxs in the presence of cofactors including magnesium and ATP.
Atlas Image
Structure of Human Srx bound to an ATP molecule and Mg2+ in solution (NCBI).

Expression

In adult, Srx protein was found in internal organs such as mouse liver and kidney. Expression pattern of Srx in embryonic development is not clear. Transcriptional regulation of Srx expression is mainly mediated through AP-1 and/or Nrf-2 activation (Jeong et al., 2012). In yeast, it may also be negatively regulated at the translational level through Ras-PKA pathway (Molin et al., 2011).

Localisation

Srx is mainly localized in the cytosol. In the presence of severe oxidative stress, it may also translocate to mitochondria (Noh et al., 2009).

Function

Srx was first identified as a gene preferentially expressed in transformed JB6 cells (Sun et al., 1994). The primary biochemical function of Srx is to reduce the overoxidized cysteine residues of Prx I, Prx II, Prx III and Prx IV under severe oxidative stress (Biteau et al., 2003; Chang et al., 2004). The spectrum and specificity of its enzymatic function remains elusive. Srx may also cause the deglutathionylation of Prx II and others (Park et al., 2009; Findlay et al., 2006). The biological function of Srx may involve in the regulation of various cell signaling pathways to promote tumorigenesis and cancer progression. Abnormally high expression of Srx has been demonstrated in many malignant tumors including those of skin, lung, and colon (Wei et al., 2008). Srx may not be essential for development since Srx null mice are viable and normal (Planson et al., 2011).

Homology

Srx gene is conserved among species, from metazoan to human.

Implicated in

Entity name
Tissue injury
Note
Srx, together with Prxs, are required for the protection of tissues from oxidative stress induced damages by alcohol and Pyrazole (Bae et al., 2012; Bae et al., 2011).
Entity name
Lung fibrosis
Note
Srx is found to be expressed in alveolar macrophages in non-specific interstitial pneumonia and may contribute to the process of idiopathic pulmonary fibrosis (Mazur et al., 2010).

Bibliography

Pubmed IDLast YearTitleAuthors
224900422012Peroxiredoxin III and sulfiredoxin together protect mice from pyrazole-induced oxidative liver injury.Bae SH et al
145864712003ATP-dependent reduction of cysteine-sulphinic acid by S. cerevisiae sulphiredoxin.Biteau B et al
229349642012Sulfiredoxin redox-sensitive interaction with S100A4 and non-muscle myosin IIA regulates cancer cell motility.Bowers RR et al
154481642004Characterization of mammalian sulfiredoxin and its reactivation of hyperoxidized peroxiredoxin through reduction of cysteine sulfinic acid in the active site to cysteine.Chang TS et al
168186572006A novel role for human sulfiredoxin in the reversal of glutathionylation.Findlay VJ et al
229645832012Genetic polymorphisms and protein expression of NRF2 and Sulfiredoxin predict survival outcomes in breast cancer.Hartikainen JM et al
226340552012Role of sulfiredoxin as a regulator of peroxiredoxin function and regulation of its expression.Jeong W et al
207187232010Cell-specific elevation of NRF2 and sulfiredoxin-1 as markers of oxidative stress in the lungs of idiopathic pulmonary fibrosis and non-specific interstitial pneumonia.Mazur W et al
218849822011Life span extension and H(2)O(2) resistance elicited by caloric restriction require the peroxiredoxin Tsa1 in Saccharomyces cerevisiae.Molin M et al
191765232009Sulfiredoxin Translocation into Mitochondria Plays a Crucial Role in Reducing Hyperoxidized Peroxiredoxin III.Noh YH et al
195613572009Deglutathionylation of 2-Cys peroxiredoxin is specifically catalyzed by sulfiredoxin.Park JW et al
210834232011Sulfiredoxin protects mice from lipopolysaccharide-induced endotoxic shock.Planson AG et al
81187941994Molecular cloning of five messenger RNAs differentially expressed in preneoplastic or neoplastic JB6 mouse epidermal cells: one is homologous to human tissue inhibitor of metalloproteinases-3.Sun Y et al
214870002011Sulfiredoxin-Peroxiredoxin IV axis promotes human lung cancer progression through modulation of specific phosphokinase signaling.Wei Q et al

Other Information

Locus ID:

NCBI: 140809
MIM: 617583
HGNC: 16132
Ensembl: ENSG00000271303

Variants:

dbSNP: 140809
ClinVar: 140809
TCGA: ENSG00000271303
COSMIC: SRXN1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000271303ENST00000381962Q9BYN0

Expression (GTEx)

0
10
20
30
40
50
60
70
80
90

References

Pubmed IDYearTitleCitations
168186572006A novel role for human sulfiredoxin in the reversal of glutathionylation.79
181725042008Structure of the sulphiredoxin-peroxiredoxin complex reveals an essential repair embrace.52
190270642009Nrf2-dependent sulfiredoxin-1 expression protects against cigarette smoke-induced oxidative stress in lungs.50
195613572009Deglutathionylation of 2-Cys peroxiredoxin is specifically catalyzed by sulfiredoxin.49
165650852006Molecular mechanism of the reduction of cysteine sulfinic acid of peroxiredoxin to cysteine by mammalian sulfiredoxin.48
214870002011Sulfiredoxin-Peroxiredoxin IV axis promotes human lung cancer progression through modulation of specific phosphokinase signaling.46
190570132008Sulfiredoxin is an AP-1 target gene that is required for transformation and shows elevated expression in human skin malignancies.32
185795292008Reduction of cysteine sulfinic acid in peroxiredoxin by sulfiredoxin proceeds directly through a sulfinic phosphoryl ester intermediate.28
220869242012Sulfiredoxin protein is critical for redox balance and survival of cells exposed to low steady-state levels of H2O2.28
185937142008Identification of intact protein thiosulfinate intermediate in the reduction of cysteine sulfinic acid in peroxiredoxin by human sulfiredoxin.26

Citation

Hedy A Chawsheen ; Hong Jiang ; Qiou Wei

SRXN1 (sulfiredoxin 1)

Atlas Genet Cytogenet Oncol Haematol. 2012-11-01

Online version: http://atlasgeneticsoncology.org/gene/52295/srxn1