Summary: Heme oxygenase

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Wikipedia: Heme oxygenase
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This is the Wikipedia entry entitled "Heme oxygenase". More...

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Heme oxygenase Edit Wikipedia article

heme oxygenase

Identifiers

Databases

PDB structures

AmiGO / EGO

Search
PMC	articles
PubMed	articles
NCBI	proteins

Heme oxygenase

crystal structures of ferrous and ferrous-no forms of verdoheme in a complex with human heme oxygenase-1: catalytic implications for heme cleavage

Identifiers

Symbol

Heme_oxygenase

Pfam clan

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe
PDBsum	structure summary

Heme oxygenase or haem oxygenase (HO) is an enzyme that catalyzes the degradation of heme. This produces biliverdin, iron, and carbon monoxide.^[1]

[edit] Reaction

Heme oxygenase cleaves the heme ring at the alpha-methene bridge to form either biliverdin or, if the heme is still attached to a globin, verdoglobin. Biliverdin is subsequently converted to bilirubin by biliverdin reductase.

The reaction occurs as follows:

Heme b + 3O₂ + 3½NADPH + 3½H⁺ + 7e^- → biliverdin + Fe²⁺ + CO + 3½NADP⁺ + 3H₂O^[2]

Heme b

Biliverdin

This reaction can occur in virtually every cell; the classic example is the formation of a bruise, which goes through different colors as it gradually heals: red heme to green biliverdin to yellow bilirubin. Under normal physiological conditions, the activity of heme oxygenase is highest in the spleen, where old erythrocytes are sequestrated and destroyed.

[edit] Isoforms

There are three known isoforms of heme oxygenase.

Heme oxygenase 1 (HO-1) is an inducible isoform in response to stress such as oxidative stress, hypoxia, heavy metals, cytokines, etc. Heme oxygenase 2 (HO-2) is a constitutive isoform that is expressed under homeostatic conditions. Both HO-1 and HO-2 are ubiquitously expressed and catalytically active.

A third heme oxygenase (HO-3) is not catalytically active, but is thought to work in oxygen sensing.

[edit] References

^ Kikuchi G, Yoshida T, Noguchi M (December 2005). "Heme oxygenase and heme degradation". Biochem. Biophys. Res. Commun. 338 (1): 558–67. doi:10.1016/j.bbrc.2005.08.020. PMID 16115609.
^ Evans JP, Niemevz F, Buldain G, de Montellano PO (July 2008). "Isoporphyrin intermediate in heme oxygenase catalysis. Oxidation of alpha-meso-phenylheme". J. Biol. Chem. 283 (28): 19530–9. doi:10.1074/jbc.M709685200. PMC 2443647. PMID 18487208.

[edit] External links

Heme Oxygenase at the US National Library of Medicine Medical Subject Headings (MeSH)
EC 1.14.99.3

Oxidoreductases: dioxygenases, including steroid hydroxylases (EC 1.14)

1.14.11: 2-oxoglutarate

1.14.13: NADH or NADPH

1.14.14: reduced flavin or flavoprotein

1.14.15: reduced iron-sulfur protein

1.14.16: reduced pteridine (BH4 dependent)

1.14.17: reduced ascorbate

Dopamine beta hydroxylase

1.14.18-19: other

1.14.99 - miscellaneous

B
enzm
1.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 10
- 11
- 13
- 14
- 15-18
2.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
2.7.10
2.7.11-12
3.1
- - 3.1.3.48
- 2
- 3
- 4
  - 3.4.21
- 5
- 6
- 7
- 22
- 23
- 24
4.1
- 2
- 3
- 4
- 5
- 6
5.1
- 2
- 3
- 4
- 99
6.1-3
- 4
- 5-6

Metabolism: amino acid metabolism · porphyrin/heme enzymes

Porphyrin biosynthesis

early mitochondrial: Aminolevulinic acid synthase (ALAS1, ALAS2) · Porphobilinogen synthase

cytosolic: Porphobilinogen deaminase · Uroporphyrinogen III synthase · Uroporphyrinogen III decarboxylase · Coproporphyrinogen III oxidase

late mitochondrial: Protoporphyrinogen oxidase · Ferrochelatase

Heme degradation
to bile

spleen: Heme oxygenase · Biliverdin reductase

liver: glucuronosyltransferase (UGT1A1)

M: MET

mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m

k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon

m (A16/C10), i (k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)

M: MYL

cell/phys (coag, heme, immu, gran), csfs

rbmg/mogr/tumr/hist, sysi/epon, btst

drug (B1/2/3+5+6), btst, trns

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No Pfam abstract.

External database links

HOMSTRAD:	Heme_oxygenase
PANDIT:	PF01126
PROSITE:	PDOC00512
Pseudofam:	PF01126
SCOP:	1qq8
SYSTERS:	Heme_oxygenase

This tab holds annotation information from the InterPro database.

InterPro entry IPR016053

Haem oxygenase (EC) (HO) [PUBMED:3290025] is the microsomal enzyme that, in animals, carries out the oxidation of haem, it cleaves the haem ring at the alpha-methene bridge to form biliverdin and carbon monoxide [PUBMED:3032976]. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. In mammals there are three isozymes of haem oxygenase: HO-1 to HO-3. The first two isozymes differ in their tissue expression and their inducibility: HO-1 is highly inducible by its substrate haem and by various non-haem substances, while HO-2 is non-inducible. It has been suggested [PUBMED:8093563] that HO-2 could be implicated in the production of carbon monoxide in the brain where it is said to act as a neurotransmitter. In the genome of the chloroplast of red algae as well as in cyanobacteria, there is a haem oxygenase (gene pbsA) that is the key enzyme in the synthesis of the chromophoric part of the photosynthetic antennae [PUBMED:9326680]. A haem oxygenase is also present in the bacteria Corynebacterium diphtheriae (gene hmuO), where it is involved in the acquisition of iron from the host haem [PUBMED:9006041]. There is, in the central section of these enzymes, a well-conserved region centred on a histidine residue.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Molecular function	heme oxygenase (decyclizing) activity (GO:0004392)
Biological process	heme oxidation (GO:0006788)
Biological process	oxidation-reduction process (GO:0055114)

Domain organisation

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

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Pfam Clan

This family is a member of clan HO (CL0230), which contains the following 5 members:

DUF3050 DUF3865 Haem_oxygenas_2 Heme_oxygenase TENA_THI-4

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.

Alignment types

We make a range of alignments for each Pfam-A family:

seed: the curated alignment from which the HMM for the family is built
full: the alignment generated by searching the sequence database using the HMM
RP15/RP35/RP55/RP75: Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
NCBI: alignment generated by searching the NCBI sequence database using the family HMM
meta: alignment generated by searching the metagenomics sequence database using the family HMM

Viewing

You can see the alignments as HTML or in three different sequence viewers:

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Pfam viewer: an HTML-based viewer that uses DAS to retrieve alignment fragments on request

Reformatting

You can download (or view in your browser) a text representation of a Pfam alignment in various formats:

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Downloading

You may find that large alignments cause problems for the viewers and the reformatting tool, so we also provide all alignments in Stockholm format. You can download either the plain text alignment, or a gzipped version of it.

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

	Seed (18)	Full (1215)	Representative proteomes				NCBI (1089)	Meta (282)
	Seed (18)	Full (1215)	RP15 (109)	RP35 (241)	RP55 (359)	RP75 (452)	NCBI (1089)	Meta (282)
Jalview	View	View	View	View	View	View	View	View
HTML	View	View	View	View	View	View
PP/heatmap	₁	View	View	View	View	View
Pfam viewer	View	View

¹Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: available, not generated, — not available.

Format an alignment

	Seed (18)	Full (1215)	Representative proteomes				NCBI (1089)	Meta (282)
	Seed (18)	Full (1215)	RP15 (109)	RP35 (241)	RP55 (359)	RP75 (452)	NCBI (1089)	Meta (282)
Alignment:
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

	Seed (18)	Full (1215)	Representative proteomes				NCBI (1089)	Meta (282)
	Seed (18)	Full (1215)	RP15 (109)	RP35 (241)	RP55 (359)	RP75 (452)	NCBI (1089)	Meta (282)
Raw Stockholm	Download	Download	Download	Download	Download	Download	Download	Download
Gzipped	Download	Download	Download	Download	Download	Download	Download	Download

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

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 HMMER3.

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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'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.

Note: You can also download the data file for the tree.

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:

Prosite

Previous IDs:

Heme_oxygnease;

Type:

Domain

Author:

Finn RD, Bateman A

Number in seed:

18

Number in full:

1215

Average length of the domain:

182.30 aa

Average identity of full alignment:

20 %

Average coverage of the sequence by the domain:

75.77 %

HMM information

HMM build commands:

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

search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	20.2	20.2
Trusted cut-off	20.3	20.2
Noise cut-off	20.0	20.0

Model length:

205

Family (HMM) version:

15

Download:

download the raw HMM for this family

Species distribution

Sunburst
Tree

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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

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How the sunburst is generated

The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.

In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:

superkingdom
kingdom
phylum
class
order
family
genus
species

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Unmapped species names

The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.

So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".

Sub-species

Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.

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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.

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Interactions

There is 1 interaction for this family. More...

Heme_oxygenase

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 Heme_oxygenase domain has been found. There are 120 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 seqence.

Loading structure mapping...

Archea	Eukaryota
Bacteria	Other sequences
Viruses	Unclassified
Viroids	Unclassified sequence

Family: Heme_oxygenase (PF01126)

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Summary: Heme oxygenase

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Heme oxygenase Edit Wikipedia article

Contents

[edit] Reaction

[edit] Isoforms

[edit] References

[edit] External links

Heme oxygenase Provide feedback

External database links

InterPro entry IPR016053

Gene Ontology

Domain organisation

Pfam Clan

Alignments

Alignment types

Viewing

Reformatting

Downloading

View options

Format an alignment

Download options

External links

HMM logo

Trees

Curation and family details

Curation

HMM information

Species distribution

Sunburst controls

Weight segments by...

Change the size of the sunburst

Colour assignments

Selections

Currently selected:

How the sunburst is generated

Colouring and labels

Anomalies in the taxonomy tree

Missing taxonomic levels

Unmapped species names

Sub-species

Too many species/sequences

Tree controls

Annotation

Download tree

Selected sequences

Species trees

Interactive tree

Interactions

Structures