Summary: Cytochrome b5-like Heme/Steroid binding domain
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Cytochrome b5 Edit Wikipedia article
Rat cytochrome b5 bound to heme
|PDB||1JEX (RCSB PDB PDBe PDBj)|
|Locus||Chr. 18 q23|
Cytochromes b5 are ubiquitous electron transport hemoproteins found in animals, plants, fungi and purple phototrophic bacteria. The microsomal and mitochondrial variants are membrane-bound, while bacterial and those from erythrocytes and other animal tissues are water-soluble. The family of cytochrome b5-like proteins includes (besides cytochrome b5 itself) hemoprotein domains covalently associated with other redox domains in flavocytochrome cytochrome b2 (L-lactate dehydrogenase; EC 18.104.22.168), sulfite oxidase (EC 22.214.171.124), plant and fungal nitrate reductases (EC 126.96.36.199, EC 188.8.131.52, EC 184.108.40.206), and plant and fungal cytochrome b5/acyl lipid desaturase fusion proteins.
3-D structures of a number of cytochrome b5 and yeast flavocytochrome b2 are known. The fold belongs to the α+β class, with two hydrophobic cores on each side of a β-sheet. The larger hydrophobic core constitutes the heme-binding pocket, closed off on each side by a pair of helices connected by a turn. The smaller hydrophobic core may have only a structural role and is formed by spatially close N-terminal and C-terminal segments. The two histidine residues provide the fifth and sixth heme ligands, and the propionate edge of the heme group lies at the opening of the heme crevice. Two isomers of cytochrome b5, referred to as the A (major) and B (minor) forms, differ by a 180° rotation of the heme about an axis defined by the α- and γ-meso carbons.
Cytochrome b5 in some biochemical reactions
- NADH + H+ + 2 ferricytochrome b5 → NAD+ + 2 ferrocytochrome b5
- L-ascorbate + ferricytochrome b5 → monodehydroascorbate + ferrocytochrome b5
- CMP-N-acetylneuraminate + 2 ferrocytochrome b5 + O2 + 2 H+ → CMP-N-glycoloylneuraminate + 2 ferricytochrome b5 + H2O
- stearoyl-CoA + 2 ferrocytochrome b5 + O2 + 2 H+ → oleoyl-CoA + 2 ferricytochrome b5 + H2O
- linoleoyl-CoA + 2 ferrocytochrome b5 + O2 + 2 H+ → γ-linolenoyl-CoA + 2 ferricytochrome b5 + H2O
- Lederer, F. (1994). "The cytochrome b5-fold: an adaptable module". Biochimie 76 (7): 674–692. doi:10.1016/0300-9084(94)90144-9. PMID 7893819.
- Napier, J.A., Michaelson, L.V. and Sayanova, O. (2003). "The role of cytochrome b5 fusion desaturases in the synthesis of polyunsaturated fatty acids". Prostaglandins, Leukotrienes and Essential Fatty Acids 68 (2): 135–143. doi:10.1016/S0952-3278(02)00263-6. PMID 12538077.
- Rivera, M., Barillas-Mury, C., Christensen, K.A., Little, J.W., Wells, M.A. and Walker, F.A. (1992). "Gene synthesis, bacterial expression, and 1H NMR spectroscopic studies of the rat outer mitochondrial membrane cytochrome b5". Biochemistry 31 (48): 12233–12240. doi:10.1021/bi00163a037. PMID 1333795.
- Schenkman, J.B. and Jansson, I. (2003). "The many roles of cytochrome b5". Pharmacol. Ther. 97 (2): 139–152. doi:10.1016/S0163-7258(02)00327-3. PMID 12559387.
- PDB 1B5A - Solution structure of rat cytochrome b5 (form A)
- PDB 1B5B - Solution structure of rat cytochrome b5 (form B)
- PDB 1CXY - X-ray structure of cytochrome b558 from Ectothiorhodospira vacuolata
- Online 'Mendelian Inheritance in Man' (OMIM) 250790 - Methemoglobinemia due to deficiency of cytochrome b5
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.
Cytochrome b5-like Heme/Steroid binding domain Provide feedback
This family includes heme binding domains from a diverse range of proteins. This family also includes proteins that bind to steroids. The family includes progesterone receptors such as O00264 [1,2]. Many members of this subfamily are membrane anchored by an N-terminal transmembrane alpha helix. This family also includes a domain in some chitin synthases. There is no known ligand for this domain in the chitin synthases.
Meyer C, Schmid R, Scriba PC, Wehling M; , Eur J Biochem 1996;239:726-731.: Purification and partial sequencing of high-affinity progesterone-binding site(s) from porcine liver membranes. PUBMED:8774719 EPMC:8774719
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR001199Cytochromes b5 are ubiquitous electron transport proteins found in animals, plants and yeasts [PUBMED:2752049]. The microsomal and mitochondrial variants are membrane-bound, while those from erythrocytes and other animal tissues are water-soluble [PUBMED:4030743, PUBMED:8439576].
The 3D structure of bovine cyt b5 is known, the fold belonging to the alpha+beta class, with 5 strands and 5 short helices forming a framework for supporting a central haem group [PUBMED:1167544]. The cytochrome b5 domain is similar to that of a number of oxidoreductases, such as plant and fungal nitrate reductases, sulphite oxidase, yeast flavocytochrome b2 (L-lactate dehydrogenase) and plant cyt b5/acyl lipid desaturase fusion protein.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||heme binding (GO:0020037)|
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
The graphic that is shown by default represents the longest sequence with a given architecture. Each row contains the following information:
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a textual description of the architecture, e.g. Gla, EGF x 2, Trypsin.
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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.
We make a range of alignments for each Pfam-A family:
- the curated alignment from which the HMM for the family is built
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- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the NCBI sequence database using the family HMM
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You can see the alignments as HTML or in three different sequence viewers:
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You can download (or view in your browser) a text representation of a Pfam alignment in various formats:
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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.
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
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.
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
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.
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...
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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
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.
|Seed source:||Bateman A|
|Number in seed:||210|
|Number in full:||5879|
|Average length of the domain:||82.90 aa|
|Average identity of full alignment:||25 %|
|Average coverage of the sequence by the domain:||17.81 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||23|
|Download:||download the raw HMM for this family|
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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 More....
This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.
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:
Colouring and labels
Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.
As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.
Anomalies in the taxonomy tree
There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.
Missing taxonomic levels
Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.
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".
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.
Too many species/sequences
For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.
The tree shows the occurrence of this domain across different species. More...
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.
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:
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There are 3 interactions for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
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 Cyt-b5 domain has been found. There are 98 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.
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