Summary: Cytochrome b5-like Heme/Steroid binding domain
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Cytochrome b5 Edit Wikipedia article
|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 184.108.40.206), sulfite oxidase (EC 220.127.116.11), plant and fungal nitrate reductases (EC 18.104.22.168, EC 22.214.171.124, EC 126.96.36.199), 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 Î±+Î² class, with two hydrophobic cores on each side of a Î²-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 180Â° rotation of the heme about an axis defined by the Î±- and Î³-meso carbons.
Cytochrome b5 in some biochemical reactions
- NADH + H+ + 2 ferricytochrome b5 â†’ NAD+ + 2 ferrocytochrome b5
- L-ascorbate + ferricytochrome b5 â†’ monodehydroascorbate + ferrocytochrome b5
- CMP-N-acetylneuraminate + 2 ferrocytochrome b5 + O2 + 2 H+ â†’ CMP-N-glycoloylneuraminate + 2 ferricytochrome b5 + H2O
- stearoyl-CoA + 2 ferrocytochrome b5 + O2 + 2 H+ â†’ oleoyl-CoA + 2 ferricytochrome b5 + H2O
- linoleoyl-CoA + 2 ferrocytochrome b5 + O2 + 2 H+ â†’ Î³-linolenoyl-CoA + 2 ferricytochrome b5 + H2O
- Lederer F (1994). "The cytochrome b5-fold: an adaptable module". Biochimie. 76 (7): 674â€“92. doi:10.1016/0300-9084(94)90144-9. PMID 7893819.
- Napier JA, Michaelson LV, Sayanova O (February 2003). "The role of cytochrome b5 fusion desaturases in the synthesis of polyunsaturated fatty acids". Prostaglandins, Leukotrienes, and Essential Fatty Acids. 68 (2): 135â€“43. doi:10.1016/S0952-3278(02)00263-6. PMID 12538077.
- Rivera M, Barillas-Mury C, Christensen KA, Little JW, Wells MA, Walker FA (December 1992). "Gene synthesis, bacterial expression, and 1H NMR spectroscopic studies of the rat outer mitochondrial membrane cytochrome b5". Biochemistry. 31 (48): 12233â€“40. doi:10.1021/bi00163a037. PMID 1333795.
- Schenkman JB, Jansson I (February 2003). "The many roles of cytochrome b5". Pharmacology & Therapeutics. 97 (2): 139â€“52. doi:10.1016/S0163-7258(02)00327-3. PMID 12559387.
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 IPR001199
Cytochrome b5 is a membrane-bound hemoprotein which acts as an electron carrier for several membrane-bound oxygenases [ PUBMED:2752049 ]. There are two homologous forms of b5, one found in microsomes and one found in the outer membrane of mitochondria. Two conserved histidine residues serve as axial ligands for the heme group. The structure of a number of oxidoreductases consists of the juxtaposition of a heme-binding domain homologous to that of b5 and either a flavodehydrogenase or a molybdopterin domain. These enzymes are:
- Lactate dehydrogenase (EC 188.8.131.52) [ PUBMED:3004948 ], an enzyme that consists of a flavodehydrogenase domain and a heme-binding domain called cytochrome b2.
- Nitrate reductase (EC 1.7.1.-), a key enzyme involved in the first step of nitrate assimilation in plants, fungi and bacteria [ PUBMED:3393528 ]. Consists of a molybdopterin domain, a heme-binding domain called cytochrome b557, as well as a cytochrome reductase domain.
- Sulfite oxidase (EC 184.108.40.206) [ PUBMED:510290 ], which catalyzes the terminal reaction in the oxidative degradation of sulfur-containing amino acids. Also consists of a molybdopterin domain and a heme-binding domain.
- Yeast acyl-CoA desaturase 1 (EC 220.127.116.11; gene OLE1). This enzyme contains a C-terminal heme-binding domain.
- Yeast Scs7 (YMR272c), a sphingolipid alpha-hydroxylase.
Proteins containing a cytochrome b5-like domain also include:
- TU-36B, a Drosophila muscle protein of unknown function [ PUBMED:2549511 ].
- Fission yeast hypothetical protein SpAC1F12.10c (C1F12.10c).
- Yeast Irc21 (YMR073c), a putative protein with unknown function.
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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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.
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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.
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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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|Seed source:||Bateman A|
|Number in seed:||80|
|Number in full:||28468|
|Average length of the domain:||81.20 aa|
|Average identity of full alignment:||26 %|
|Average coverage of the sequence by the domain:||15.57 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||31|
|Download:||download the raw HMM for this family|
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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:
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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.
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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.
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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.
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The tree shows the occurrence of this domain across different species. More...
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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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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 105 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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AlphaFold Structure Predictions
The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.