Primary Information
BoMiProt ID	Bomi7901
Protein Name	Peroxiredoxin-4
Organism	Bos taurus
Uniprot ID	Q9BGI2
Milk Fraction	Whey
Ref Sequence ID	NP_776858.1
Aminoacid Length	274
Molecular Weight	30741
FASTA Sequence	Download
Gene Name	PRDX4
Gene ID	281999
Protein Existence Status	reviewed
Secondary Information
Presence in other biological fluids/tissue/cells	expression of Prx1 in Cytosol, nucleus; prx2 in Cytosol, membrane; prx3 in Mitochondria; prx4 in Cytosol, Golgi, secreted; prx5 in Mitochondria, peroxisome, cytosol; prx 6 in Cytosol
Protein Function	Peroxiredoxins (Prxs) are a ubiquitous family of cysteine-dependent peroxidase enzymes that play dominant roles in regulating peroxide levels within cells; the peroxidase activity of Prx enzymes towards H2O2, organic hydroperoxides and peroxynitrite is critical to protect cellular components from oxidative damage; play cytoprotective antioxidant role in inflammation
Biochemical Properties	Mammalian cells express six Prx isoforms (PrxI to PrxVI), which can be classified into 2-Cys (PrxI to PrxIV), atypical 2-Cys (PrxV), and 1-Cys (PrxVI) subfamilies;hydrogen peroxide caused rapid inactivation of human Prx I by hyperoxidation during catalytic turnover; cysteine-based peroxidases that do not require any special cofactors for their activity; a peroxidatic Cys (CP) thiolate (CP-S−) attacks a hydroperoxide substrate and is oxidized to a CP-sulfenic acid (CP-SOH); In mammals, Prx1 subfamily enzymes are in the cytosol and nucleus (PrxI and PrxII), the mitochondria (PrxIII) and the endoplasmic reticulum (PrxIV); In Prxs, the CP pKa values determined for nearly a dozen representatives are clustered between 5.1 and 6.3; 83% of the CP residues being present in the thiolate form at pH 7; Factors promoting oligomerization in typical 2-Cys Prxs include high [37] or low [34,39] ionic strength, low pH [40], high magnesium [34] or calcium [41,42] concentrations, reduction of the redox-active disulfide center [20,22,36], and ‘overoxidation’ of the peroxidatic cysteine to a sulfinic acid
Significance in milk	induce the oxidation of various leuco compounds by hydrogen peroxide - distinguishes between raw and boiled milk; milk sterilized at or above 80’ C, do not show the peroxidase reaction; whereas raw milks, as a class, do give the reaction;
PTMs	phosphorylation of mammalian PrxI, PrxII, PrxIII and PrxIV at the conserved residue Thr89 (PrxII numbering) by cyclin-dependent kinases ;lipid raft associated prx1 undergoes phosphorylation at Tyr194; centrosomeassociated PrxI through phosphorylation at Thr9;
Significance of PTMs	phosphorylation leads to inactivation of this enxyme
Linking IDs	Bomi72
Bibliography	1. Kappeler, S. R., Heuberger, C., Farah, Z., & Puhan, Z. (2004). Expression of the peptidoglycan recognition protein, PGRP, in the lactating mammary gland. Journal of Dairy Science, 87(8), 2660–2668. https://doi.org/10.3168/jds.S0022-0302(04)73392-5. 2. Dziarski, R. (2004). Peptidoglycan recognition proteins (PGRPs). Molecular Immunology, 40(12), 877–886. https://doi.org/10.1016/j.molimm.2003.10.011. 3. Parsonage, D., Youngblood, D. S., Sarma, G. N., Wood, Z. A., Karplus, P. A., & Poole, L. B. (2005). Analysis of the link between enzymatic activity and oligomeric state in AhpC, a bacterial peroxiredoxin. Biochemistry, 44(31), 10583–10592. https://doi.org/10.1021/bi050448i. 4. Tydell, C. C., Yuan, J., Tran, P., & Selsted, M. E. (2006). Bovine peptidoglycan recognition protein-S: antimicrobial activity, localization, secretion, and binding properties. Journal of Immunology (Baltimore, Md. : 1950), 176(2), 1154–1162. https://doi.org/10.4049/jimmunol.176.2.1154.
Protein Function	Peroxiredoxin 4 (Prdx4) catalyzes disulfide bond formation in proteins via the action of hydrogen peroxide and hence decreases oxidative stress and supports oxidative protein folding for the secretion of lipoproteins.Cellular protection against oxidative stress by detoxifying peroxides and as sensor of hydrogen peroxide-mediated signaling events. Regulates the activation of NF-kappa-B in the cytosol by a modulation of I-kappa-B-alpha phosphorylation.
Biochemical Properties	Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively.Homodimer; disulfide-linked, upon oxidation. 5 homodimers assemble to form a ring-like decamer.
PTMs	Disulfide bond formation
Site(s) of PTM(s) N-glycosylation, O-glycosylation, Phosphorylation	NA
Predicted Disorder Regions	2 predicted disordered segment; (1-17), (77-79)
DisProt Annotation
TM Helix Prediction	No TM helices
Significance of PTMs	The enzyme can be inactivated by further oxidation of the cysteine sulfenic acid (C(P)-SOH) to sulphinic acid (C(P)-SO2H) and sulphonic acid (C(P)-SO3H) instead of its condensation to a disulfide bond.
Bibliography	Ahmed N, Naseem M, Farooq J. Protective role of peroxiredoxin-4 in heart failure. Clin Sci (Lond). 2020 Jan 17;134(1):71-72. doi: 10.1042/CS20191072. PMID: 31934724.