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14  structures 5631  species 0  interactions 6300  sequences 21  architectures

Family: Cu-oxidase_4 (PF02578)

Summary: Multi-copper polyphenol oxidoreductase laccase

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This is the Wikipedia entry entitled "Multicopper oxidase". More...

Multicopper oxidase Edit Wikipedia article

Multicopper oxidase (type 1)
PDB 2fqg EBI.jpg
crystal structures of e. coli laccase cueo under different copper binding situations
Pfam clanCL0026
Multicopper oxidase (type 2)
PDB 1kya EBI.jpg
active laccase from trametes versicolor complexed with 2,5-xylidine
Pfam clanCL0026
Multicopper oxidase (type 3)
PDB 2fqe EBI.jpg
crystal structures of e. coli laccase cueo under different copper binding situations
Pfam clanCL0026
CMulti-copper polyphenol oxidoreductase laccase
PDB 1xfj EBI.jpg
crystal structure of protein cc_0490 from caulobacter crescentus, pfam duf152

In molecular biology, multicopper oxidases are enzymes which oxidise their substrate by accepting electrons at a mononuclear copper centre and transferring them to a trinuclear copper centre; dioxygen binds to the trinuclear centre and, following the transfer of four electrons, is reduced to two molecules of water.[1] There are three spectroscopically different copper centres found in multicopper oxidases: type 1 (or blue), type 2 (or normal) and type 3 (or coupled binuclear).[2][3] Multicopper oxidases consist of 2, 3 or 6 of these homologous domains, which also share homology with the cupredoxins azurin and plastocyanin. Structurally, these domains consist of a cupredoxin-like fold, a beta-sandwich consisting of 7 strands in 2 beta-sheets, arranged in a Greek-key beta-barrel.[4] Multicopper oxidases include:

In addition to the above enzymes there are a number of other proteins that are similar to the multi-copper oxidases in terms of structure and sequence, some of which have lost the ability to bind copper. These include: copper resistance protein A (copA) from a plasmid in Pseudomonas syringae; domain A of (non-copper binding) blood coagulation factors V (Fa V) and VIII (Fa VIII);[7] yeast Fet3p (FET3) required for ferrous iron uptake;[8] yeast hypothetical protein YFL041w; and the fission yeast homologue SpAC1F7.08.


  1. ^ Bento I, Martins LO, Gato Lopes G, Arménia Carrondo M, Lindley PF (November 2005). "Dioxygen reduction by multi-copper oxidases; a structural perspective". Dalton Transactions (21): 3507–13. doi:10.1039/b504806k. PMID 16234932.
  2. ^ Messerschmidt A, Huber R (January 1990). "The blue oxidases, ascorbate oxidase, laccase and ceruloplasmin. Modelling and structural relationships". Eur. J. Biochem. 187 (2): 341–52. doi:10.1111/j.1432-1033.1990.tb15311.x. PMID 2404764.
  3. ^ Ouzounis C, Sander C (February 1991). "A structure-derived sequence pattern for the detection of type I copper binding domains in distantly related proteins". FEBS Lett. 279 (1): 73–8. doi:10.1016/0014-5793(91)80254-Z. PMID 1995346.
  4. ^ a b Roberts SA, Weichsel A, Grass G, Thakali K, Hazzard JT, Tollin G, Rensing C, Montfort WR (March 2002). "Crystal structure and electron transfer kinetics of CueO, a multicopper oxidase required for copper homeostasis in Escherichia coli". Proc. Natl. Acad. Sci. U.S.A. 99 (5): 2766–71. doi:10.1073/pnas.052710499. PMC 122422. PMID 11867755.
  5. ^ Nakamura K, Kawabata T, Yura K, Go N (October 2003). "Novel types of two-domain multi-copper oxidases: possible missing links in the evolution". FEBS Lett. 553 (3): 239–44. doi:10.1016/S0014-5793(03)01000-7. PMID 14572631.
  6. ^ Suzuki S, Kataoka K, Yamaguchi K (October 2000). "Metal coordination and mechanism of multicopper nitrite reductase". Acc. Chem. Res. 33 (10): 728–35. doi:10.1021/ar9900257. PMID 11041837.
  7. ^ Mann KG, Jenny RJ, Krishnaswamy S (1988). "Cofactor proteins in the assembly and expression of blood clotting enzyme complexes". Annu. Rev. Biochem. 57: 915–56. doi:10.1146/ PMID 3052293.
  8. ^ Askwith C, Eide D, Van Ho A, Bernard PS, Li L, Davis-Kaplan S, Sipe DM, Kaplan J (January 1994). "The FET3 gene of S. cerevisiae encodes a multicopper oxidase required for ferrous iron uptake". Cell. 76 (2): 403–10. doi:10.1016/0092-8674(94)90346-8. PMID 8293473.
This article incorporates text from the public domain Pfam and InterPro: IPR001117
This article incorporates text from the public domain Pfam and InterPro: IPR011706
This article incorporates text from the public domain Pfam and InterPro: IPR011707
This article incorporates text from the public domain Pfam and InterPro: IPR003730

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Multi-copper polyphenol oxidoreductase laccase Provide feedback

Laccases are multi-copper oxidoreductases able to oxidise a wide variety of phenolic and non-phenolic compounds and are widely distributed among both prokaryotes and eukaryotes. There are two main active catalytic sites with conserved histidines that are capable of binding four copper atoms [1].

Literature references

  1. Beloqui A, Pita M, Polaina J, Martinez-Arias A, Golyshina OV, Zumarraga M, Yakimov MM, Garcia-Arellano H, Alcalde M, Fernandez VM, Elborough K, Andreu JM, Ballesteros A, Plou FJ, Timmis KN, Ferrer M, Golyshin PN; , J Biol Chem. 2006;281:22933-22942.: Novel polyphenol oxidase mined from a metagenome expression library of bovine rumen: biochemical properties, structural analysis, and phylogenetic relationships. PUBMED:16740638 EPMC:16740638

This tab holds annotation information from the InterPro database.

InterPro entry IPR003730

Laccases are multi-copper oxidoreductases able to oxidise a wide variety of phenolic and non-phenolic compounds and are widely distributed among both prokaryotes and eukaryotes. There are two main active catalytic sites with conserved histidines that are capable of binding four copper atoms [ PUBMED:16740638 ].

This family consists of polyphenol oxidases with laccase activity from bacteria. They may constitute a new laccase subfamily, as they lack sequence relatedness to known laccases [ PUBMED:16740638 ]. This family also includes laccase domain-containing protein 1 (Lacc1, FAMIN), which is thought to be a central regulator of immunometabolic function in humans [ PUBMED:27478939 , PUBMED:28593945 ].

Domain organisation

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Pfam Clan

This family is a member of clan CNF1_YfiH (CL0663), which has the following description:

Members of this clan are structurally similar. Families are a class of deamidases with a common fold consisting of three-layered alpha/beta/beta sandwich, wherein two mixed 5-stranded beta sheets are flanked by a layer of two alpha helices. In a shallow cavity at the top of the alpha/beta/beta sandwich, an invariant Cys-His pair forms a catalytic dyad that is required by the toxins for deamidation activity [1]. Deamidation is used by some bacterial virulance factors to modulate eukaryotic host cell signaling systems [2].

The clan contains the following 4 members:

BLF1 CheD CNF1 Cu-oxidase_4


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This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

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Curation View help on the curation process

Seed source: COG1496
Previous IDs: DUF152; Cu_oxidase_4;
Type: Family
Sequence Ontology: SO:0100021
Author: Mian N , Bateman A
Number in seed: 582
Number in full: 6300
Average length of the domain: 226.00 aa
Average identity of full alignment: 32 %
Average coverage of the sequence by the domain: 86.94 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 22.9 22.9
Trusted cut-off 23.0 25.3
Noise cut-off 22.3 22.8
Model length: 236
Family (HMM) version: 17
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Species distribution

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Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Cu-oxidase_4 domain has been found. There are 14 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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