{PDOC00076}
{PS00079; MULTICOPPER_OXIDASE1}
{PS00080; MULTICOPPER_OXIDASE2}
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* Multicopper oxidases signatures *
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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.

-Consensus pattern: G-x-[FYW]-x-[LIVMFYW]-x-[CST]-x-{PR}-{K}-x(2)-{S}-x-{LFH}-
                    G-[LM]-x(3)-[LIVMFYW]
-Sequences known to belong to this class detected by the pattern: ALL,  except
 for Emericella nidulans laccase.
-Other sequence(s) detected in Swiss-Prot: 33 other proteins and  Thiobacillus
 ferrooxidans rusticyanin which is  also  a copper-binding protein,  but which
 belong to the type-1 copper proteins family (see <PDOC00174>).

-Consensus pattern: H-C-H-x(3)-H-x(3)-[AG]-[LM]
                    [The first 2 H's are copper type 3 binding residues]
                    [The C, the third H, and L or M are copper type 1 ligands]
-Sequences known to belong to this class detected by the pattern: only domains
 that bind copper.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Last update: April 2006 / Pattern revised.

[ 1] Messerschmidt A., Huber R.
     "The blue oxidases, ascorbate oxidase, laccase and ceruloplasmin.
     Modelling and structural relationships."
     Eur. J. Biochem. 187:341-352(1990).
     PubMed=2404764
[ 2] Ouzounis C., Sander C.
     "A structure-derived sequence pattern for the detection of type I
     copper binding domains in distantly related proteins."
     FEBS Lett. 279:73-78(1991).
     PubMed=1995346
[ 3] Askwith C., Eide D., Van Ho A., Bernard P.S., Li L., Davis-Kaplan S.,
     Sipe D.M., Kaplan J.
     "The FET3 gene of S. cerevisiae encodes a multicopper oxidase required
     for ferrous iron uptake."
     Cell 76:403-410(1994).
     PubMed=8293473
[ 4] Mann K.G., Jenny R.J., Krishnaswamy S.
     "Cofactor proteins in the assembly and expression of blood clotting
     enzyme complexes."
     Annu. Rev. Biochem. 57:915-956(1988).
     PubMed=3052293; DOI=10.1146/annurev.bi.57.070188.004411
[E1] http://www.factorviii-db.org/

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