{PDOC51324} {PS51324; ERV_ALR} {BEGIN} ********************************************* * ERV/ALR sulfhydryl oxidase domain profile * ********************************************* The ~100-residue ERV/ALR sulfhydryl oxidase domain is a versatile module adapted for catalysis of disulfide bond formation in various organelles and biological settings. The ERV/ALR sulfhydryl oxidase domain has a Cys-X-X-Cys dithiol/disulfide motif adjacent to a bound FAD cofactor, enabling transfer of electrons from thiol substrates to non-thiol electron acceptors. ERV/ALR family members differ in their N- or C-terminal extensions, which typically contain at least one additional disulfide bond, the hypothesized 'shuttle' disulfide. In yeast ERV1, a mitochondrial enzyme, the shuttle disulfide is N- terminal to the catalytic core; in yeast ERV2, present in the endoplasmic reticulum, it is C-terminal. The N- and C-terminal extensions can be entire domains, such as the thioredoxin-like domains (see ) or short segments that do not seem to be distinct domains. Proteins of the ERV/ALR family are encoded by all eukaryotes and cytoplasmic DNA viruses (poxviruses, African swine fever virus, iridoviruses, and Paramecium bursaria Chlorella virus 1) [1-5]. The ERV/ALR sulfhydryl oxidase domain contains a four-helix bundle (helices alpha1-alpha4) and an additional single turn of helix (alpha5) packed perpendicular to the bundle (see ) [3,4]. The FAD prosthetic group is housed at the mouth of the 4-helix bundle and communicates with the pair of juxtaposed cysteine residues that form the proximal redox active site [5]. Some proteins known to contain an ERV/ALR sulfhydryl oxidase domain are listed below: - Yeast essential for respiration and viability proteins 1 and 2 (ERV1 and ERV2). ERV1 is required for mitochondrial biogenesis. - Mammalian Augmenter of Liver Regeneration (ALR), the homolog of ERV1. - Animal and plant quiescin-sulfhydryl oxidase (QSOX). - Poxviruses E10R protein, that promotes disulfide-bond formation in coat proteins assembling in the reducing environment of the cell cytosol. The profile we developed covers the entire ERV/ALR sulfhydryl oxidase domain. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: July 2007 / First entry. [ 1] Hoober K.L., Glynn N.M., Burnside J., Coppock D.L., Thorpe C. "Homology between egg white sulfhydryl oxidase and quiescin Q6 defines a new class of flavin-linked sulfhydryl oxidases." J. Biol. Chem. 274:31759-31762(1999). PubMed=10542195 [ 2] Senkevich T.G., White C.L., Koonin E.V., Moss B. "A viral member of the ERV1/ALR protein family participates in a cytoplasmic pathway of disulfide bond formation." Proc. Natl. Acad. Sci. U.S.A. 97:12068-12073(2000). PubMed=11035794; DOI=10.1073/pnas.210397997 [ 3] Gross E., Sevier C.S., Vala A., Kaiser C.A., Fass D. "A new FAD-binding fold and intersubunit disulfide shuttle in the thiol oxidase Erv2p." Nat. Struct. Biol. 9:61-67(2002). PubMed=11740506; DOI=10.1038/nsb740 [ 4] Vitu E., Bentzur M., Lisowsky T., Kaiser C.A., Fass D. "Gain of function in an ERV/ALR sulfhydryl oxidase by molecular engineering of the shuttle disulfide." J. Mol. Biol. 362:89-101(2006). PubMed=16893552; DOI=10.1016/j.jmb.2006.06.070 [ 5] Wang W., Winther J.R., Thorpe C. "Erv2p: characterization of the redox behavior of a yeast sulfhydryl oxidase." Biochemistry 46:3246-3254(2007). PubMed=17298084; DOI=10.1021/bi602499t -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}