PROSITE documentation PDOC00076Multicopper oxidases signatures
Multicopper oxidases [1,2] are enzymes that possess three spectroscopically different copper centers. These centers are called: type 1 (or blue), type 2 (or normal) and type 3 (or coupled binuclear). The enzymes that belong to this family are:
- Laccase (EC 1.10.3.2) (urishiol oxidase), an enzyme found in fungi and plants, which oxidizes many different types of phenols and diamines.
- L-ascorbate oxidase (EC 1.10.3.3), a higher plant enzyme.
- Ceruloplasmin (EC 1.16.3.1) (ferroxidase), a protein found in the serum of mammals and birds, which oxidizes a great variety of inorganic and organic substances. Structurally ceruloplasmin exhibits internal sequence homology, and seem to have evolved from the triplication of a copper-binding domain similar to that found in laccase and ascorbate oxidase.
In addition to the above enzymes there are a number of proteins which, on the basis of sequence similarities, can be said to belong to this family. These proteins are:
- Copper resistance protein A (copA) from a plasmid in Pseudomonas syringae. This protein seems to be involved in the resistance of the microbial host to copper.
- Blood coagulation factor V (Fa V).
- Blood coagulation factor VIII (Fa VIII) [E1].
- Yeast FET3 [3], which is required for ferrous iron uptake.
- Yeast hypothetical protein YFL041w and SpAC1F7.08, the fission yeast homolog.
Factors V and VIII act as cofactors in blood coagulation and are structurally similar [4]. Their sequence consists of a triplicated A domain, a B domain and a duplicated C domain; in the following order: A-A-B-A-C-C. The A-type domain is related to the multicopper oxidases.
We have developed two signature patterns for these proteins. Both patterns are derived from the same region, which in ascorbate oxidase, laccase, in the third domain of ceruloplasmin, and in copA, contains five residues that are known to be involved in the binding of copper centers. The first pattern does not make any assumption on the presence of copper-binding residues and thus can detect domains that have lost the ability to bind copper (such as those in Fa V and Fa VIII), while the second pattern is specific to copper-binding domains.
Last update:April 2006 / Pattern revised.
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PROSITE methods (with tools and information) covered by this documentation:
| 1 | Authors | Messerschmidt A. Huber R. |
| Title | The blue oxidases, ascorbate oxidase, laccase and ceruloplasmin. Modelling and structural relationships. | |
| Source | Eur. J. Biochem. 187:341-352(1990). | |
| PubMed ID | 2404764 |
| 2 | Authors | Ouzounis C. Sander C. |
| Title | A structure-derived sequence pattern for the detection of type I copper binding domains in distantly related proteins. | |
| Source | FEBS Lett. 279:73-78(1991). | |
| PubMed ID | 1995346 |
| 3 | Authors | Askwith C. Eide D. Van Ho A. Bernard P.S. Li L. Davis-Kaplan S. Sipe D.M. Kaplan J. |
| Title | The FET3 gene of S. cerevisiae encodes a multicopper oxidase required for ferrous iron uptake. | |
| Source | Cell 76:403-410(1994). | |
| PubMed ID | 8293473 |
| 4 | Authors | Mann K.G. Jenny R.J. Krishnaswamy S. |
| Title | Cofactor proteins in the assembly and expression of blood clotting enzyme complexes. | |
| Source | Annu. Rev. Biochem. 57:915-956(1988). | |
| PubMed ID | 3052293 | |
| DOI | 10.1146/annurev.bi.57.070188.004411 |
| E1 | Source | http://www.factorviii-db.org/ |
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