SRXN1 (sulfiredoxin 1)
2012-11-01 Hedy A Chawsheen  , Hong Jiang  , Qiou Wei   AffiliationGraduate 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.

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).
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 22490042 | 2012 | Peroxiredoxin III and sulfiredoxin together protect mice from pyrazole-induced oxidative liver injury. | Bae SH et al |
| 14586471 | 2003 | ATP-dependent reduction of cysteine-sulphinic acid by S. cerevisiae sulphiredoxin. | Biteau B et al |
| 22934964 | 2012 | Sulfiredoxin redox-sensitive interaction with S100A4 and non-muscle myosin IIA regulates cancer cell motility. | Bowers RR et al |
| 15448164 | 2004 | Characterization 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 |
| 16818657 | 2006 | A novel role for human sulfiredoxin in the reversal of glutathionylation. | Findlay VJ et al |
| 22964583 | 2012 | Genetic polymorphisms and protein expression of NRF2 and Sulfiredoxin predict survival outcomes in breast cancer. | Hartikainen JM et al |
| 22634055 | 2012 | Role of sulfiredoxin as a regulator of peroxiredoxin function and regulation of its expression. | Jeong W et al |
| 20718723 | 2010 | Cell-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 |
| 21884982 | 2011 | Life span extension and H(2)O(2) resistance elicited by caloric restriction require the peroxiredoxin Tsa1 in Saccharomyces cerevisiae. | Molin M et al |
| 19176523 | 2009 | Sulfiredoxin Translocation into Mitochondria Plays a Crucial Role in Reducing Hyperoxidized Peroxiredoxin III. | Noh YH et al |
| 19561357 | 2009 | Deglutathionylation of 2-Cys peroxiredoxin is specifically catalyzed by sulfiredoxin. | Park JW et al |
| 21083423 | 2011 | Sulfiredoxin protects mice from lipopolysaccharide-induced endotoxic shock. | Planson AG et al |
| 8118794 | 1994 | Molecular 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 |
| 21487000 | 2011 | Sulfiredoxin-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 ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000271303 | ENST00000381962 | Q9BYN0 |
Expression (GTEx)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38852489 | 2024 | Unraveling the role of sulfiredoxin-1 in early-onset preeclampsia: A key player in trophoblast ferroptosis. | 0 |
| 38852489 | 2024 | Unraveling the role of sulfiredoxin-1 in early-onset preeclampsia: A key player in trophoblast ferroptosis. | 0 |
| 37017121 | 2023 | CircABCA13 acts as a miR-4429 sponge to facilitate esophageal squamous cell carcinoma development by stabilizing SRXN1. | 4 |
| 37726767 | 2023 | Antioxidative stress protein SRXN1 can be used as a radiotherapy prognostic marker for prostate cancer. | 1 |
| 37017121 | 2023 | CircABCA13 acts as a miR-4429 sponge to facilitate esophageal squamous cell carcinoma development by stabilizing SRXN1. | 4 |
| 37726767 | 2023 | Antioxidative stress protein SRXN1 can be used as a radiotherapy prognostic marker for prostate cancer. | 1 |
| 32411320 | 2020 | Sulfiredoxin as a Potential Therapeutic Target for Advanced and Metastatic Prostate Cancer. | 11 |
| 32746503 | 2020 | SRXN1 stimulates hepatocellular carcinoma tumorigenesis and metastasis through modulating ROS/p65/BTG2 signalling. | 18 |
| 32955798 | 2020 | Sulfiredoxin-1 is a promising novel prognostic biomarker for hepatocellular carcinoma. | 5 |
| 32411320 | 2020 | Sulfiredoxin as a Potential Therapeutic Target for Advanced and Metastatic Prostate Cancer. | 11 |
| 32746503 | 2020 | SRXN1 stimulates hepatocellular carcinoma tumorigenesis and metastasis through modulating ROS/p65/BTG2 signalling. | 18 |
| 32955798 | 2020 | Sulfiredoxin-1 is a promising novel prognostic biomarker for hepatocellular carcinoma. | 5 |
| 30863778 | 2019 | Increased Sulfiredoxin Expression in Gastric Cancer Cells May Be a Molecular Target of the Anticancer Component Diallyl Trisulfide. | 8 |
| 31000628 | 2019 | The redox regulator sulfiredoxin forms a complex with thioredoxin domain-containing 5 protein in response to ER stress in lung cancer cells. | 13 |
| 30863778 | 2019 | Increased Sulfiredoxin Expression in Gastric Cancer Cells May Be a Molecular Target of the Anticancer Component Diallyl Trisulfide. | 8 |
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-(sulfiredoxin-1)
