Summary

Multicopper oxidase

This entry contains many divergent copper oxidase-like domains that are not recognised by the PF00394 model.

Literature references

Messerschmidt A, Huber R; , Eur J Biochem 1990;187:341-352.: The blue oxidases, ascorbate oxidase, laccase and ceruloplasmin. Modelling and structural relationships. PUBMED:2404764
Messerschmidt A, Ladenstein R, Huber R, Bolognesi M, Avigliano L, Petruzzelli R, Rossi A, Finazzi-Agro A; , J Mol Biol 1992;224:179-205.: Refined crystal structure of ascorbate oxidase at 1.9 A resolution. PUBMED:1548698
Page CC, Moser CC, Chen X, Dutton PL; , Nature 1999;402:47-52.: Natural engineering principles of electron tunnelling in biological oxidation-reduction. PUBMED:10573417
Grossmann JG, Ingledew WJ, Harvey I, Strange RW, Hasnain SS; , Biochemistry 1995;34:8406-8414.: X-ray absorption studies and homology modeling define the structural features that specify the nature of the copper site in rusticyanin. PUBMED:7599131

InterPro entry IPR011706

Copper is one of the most prevalent transition metals in living organisms and its biological function is intimately related to its redox properties. Since free copper is toxic, even at very low concentrations, its homeostasis in living organisms is tightly controlled by subtle molecular mechanisms. In eukaryotes, before being transported inside the cell via the high-affinity copper transporters of the CTR family, the copper (II) ion is reduced to copper (I). In blue copper proteins such as cupredoxin, the copper (I) ion form is stabilised by a constrained His2Cys coordination environment.

Multicopper oxidases 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 PUBMED:16234932. 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) PUBMED:2404764, PUBMED:1995346. Multicopper oxidases consist of 2, 3 or 6 of these homologous domains, which also share homology to 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 PUBMED:11867755. Multicopper oxidases include:

Ceruloplasmin () (ferroxidase), a 6-domain enzyme found in the serum of mammals and birds that oxidizes different inorganic and organic substances; exhibits internal sequence homology that appears to have evolved from the triplication of a Cu-binding domain similar to that of laccase and ascorbate oxidase.
Laccase () (urishiol oxidase), a 3-domain enzyme found in fungi and plants, which oxidizes different phenols and diamines. CueO is a laccase found in Escherichia coli that is involved in copper-resistance PUBMED:11867755.
Ascorbate oxidase (), a 3-domain enzyme found in higher plants.
Nitrite reductase (), a 2-domain enzyme containing type-1 and type-2 copper centres PUBMED:14572631, PUBMED:11041837.

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) PUBMED:3052293; yeast FET3 required for ferrous iron uptake PUBMED:8293473; yeast hypothetical protein YFL041w; and the fission yeast homologue SpAC1F7.08.

This entry represents multicopper oxidase type 2 domains.

Clan

This family is a member of clan CU_oxidase (CL0026), which contains the following 8 members:

Copper-bind COX2 Cu-oxidase Cu-oxidase_2 Cu-oxidase_3 Cu_bind_like Ephrin SoxE

Gene Ontology

Molecular function	copper ion binding (GO:0005507)
	oxidoreductase activity (GO:0016491)

Internal database links

SCOOP:

Cu-oxidase_3 PAD_N

External database links

HOMSTRAD:	Cu-oxidase Cu_nir
PANDIT:	PF07731
SCOP:	1aoz
SYSTERS:	Cu-oxidase_2

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Alignments

There are various ways to view or download the sequence alignments that we store. You can use a sequence viewer to look at either the seed or full alignment for the family, or you can look at a plain text version of the sequence in a variety of different formats. More...

View options

Alignment:	Seed (127) Full (2972) NCBI (3891) Metagenomics (436)
Viewer:

Formatting options

Alignment:	Seed (127) Full (2972)
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

Download options

Very large alignments can often cause problems for the formatting tool above. If you find that downloading or viewing a large alignment is problematic, you can also download a gzip-compressed, Stockholm-format file containing the seed or full alignment for this family.

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

The main seed and full alignments are generated using sequences from the UniProt sequence database. However, we also generate alignments using sequences from the NCBI sequence database and the "metaseq" metagenomics dataset.

You can view alignments from these two additional datasets using the form above, or you can download alignments of NCBI or metagenomics sequences, as gzip-compressed files.

Pfam alignments:	Seed (127) Full (2972) NCBI (3891) Metagenomics (436)
Full length sequences	Full-sequences (2972)

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER2.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family. 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 or full alignments.

Note: You can also download the data files for the seed, full, NCBI or metagenomics trees.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation

Seed source:

PfamB-49 (Release 14.0)

Previous IDs:

none

Type:

Domain

Author:

Studholme DJ

Number in seed:

127

Number in full:

2972

Average length of the domain:

133.50 aa

Average identity of full alignment:

21 %

Average coverage of the sequence by the domain:

23.96 %

HMM information

HMM build commands:

build method: hmmbuild -o /dev/null HMM SEED

search method: hmmsearch -Z 9421015 -E 1000 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	20.4	20.4
Trusted cut-off	20.6	20.4
Noise cut-off	20.3	20.3

Model length:

130

Family (HMM) version:

7

Download:

download the raw HMM for this family

Species distribution

Tree controls

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The tree shows the occurrence of this domain across different species. More...

Species trees

We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.

Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.

If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.

Interactive tree

For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.

We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.

Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.

We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.

You can use the tree controls to manipulate how the interactive tree is displayed:

show/hide the summary boxes
highlight species that are represented in the seed alignment
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Interactions

There are 2 interactions for this family. More...

Cu-oxidase_3 Cu-oxidase

Structures

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_2 domain has been found.

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Family: Cu-oxidase_2 (PF07731)

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