PROSITE documentation PDOC51324ERV/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 <PDOC00172>) 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) [1,2,3,4,5].
The ERV/ALR sulfhydryl oxidase domain contains a four-helix bundle (helices α1-α4) and an additional single turn of helix (α5) packed perpendicular to the bundle (see <PDB:1JRA>) [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.
Last update:July 2007 / First entry.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Hoober K.L. Glynn N.M. Burnside J. Coppock D.L. Thorpe C. |
| Title | Homology between egg white sulfhydryl oxidase and quiescin Q6 defines a new class of flavin-linked sulfhydryl oxidases. | |
| Source | J. Biol. Chem. 274:31759-31762(1999). | |
| PubMed ID | 10542195 |
| 2 | Authors | Senkevich T.G. White C.L. Koonin E.V. Moss B. |
| Title | A viral member of the ERV1/ALR protein family participates in a cytoplasmic pathway of disulfide bond formation. | |
| Source | Proc. Natl. Acad. Sci. U.S.A. 97:12068-12073(2000). | |
| PubMed ID | 11035794 | |
| DOI | 10.1073/pnas.210397997 |
| 3 | Authors | Gross E. Sevier C.S. Vala A. Kaiser C.A. Fass D. |
| Title | A new FAD-binding fold and intersubunit disulfide shuttle in the thiol oxidase Erv2p. | |
| Source | Nat. Struct. Biol. 9:61-67(2002). | |
| PubMed ID | 11740506 | |
| DOI | 10.1038/nsb740 |
| 4 | Authors | Vitu E. Bentzur M. Lisowsky T. Kaiser C.A. Fass D. |
| Title | Gain of function in an ERV/ALR sulfhydryl oxidase by molecular engineering of the shuttle disulfide. | |
| Source | J. Mol. Biol. 362:89-101(2006). | |
| PubMed ID | 16893552 | |
| DOI | 10.1016/j.jmb.2006.06.070 |
| 5 | Authors | Wang W. Winther J.R. Thorpe C. |
| Title | Erv2p: characterization of the redox behavior of a yeast sulfhydryl oxidase. | |
| Source | Biochemistry 46:3246-3254(2007). | |
| PubMed ID | 17298084 | |
| DOI | 10.1021/bi602499t |
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