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105  structures 2104  species 0  interactions 28468  sequences 710  architectures

Family: Cyt-b5 (PF00173)

Summary: Cytochrome b5-like Heme/Steroid binding domain

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This is the Wikipedia entry entitled "Cytochrome b5". More...

Cytochrome b5 Edit Wikipedia article

Cytochrome b5
CytB5 1icc.png
Cytochrome B5 (rat) bound to its cofactor. Haem in black, iron in orange and iron-binding histidine residues shown as sticks. (PDB: 1ICC​)
Alt. symbolsCYB5
NCBI gene1528
Other data
LocusChr. 18 q23
Cytochrome b5

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, sulfite oxidase (EC, plant and fungal nitrate reductases (EC, EC, EC, 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

EC cytochrome-b5 reductase

NADH + H+ + 2 ferricytochrome b5 → NAD+ + 2 ferrocytochrome b5

EC L-ascorbate—cytochrome-b5 reductase

L-ascorbate + ferricytochrome b5 → monodehydroascorbate + ferrocytochrome b5

EC CMP-N-acetylneuraminate monooxygenase

CMP-N-acetylneuraminate + 2 ferrocytochrome b5 + O2 + 2 H+ → CMP-N-glycoloylneuraminate + 2 ferricytochrome b5 + H2O

EC stearoyl-CoA 9-desaturase

stearoyl-CoA + 2 ferrocytochrome b5 + O2 + 2 H+ → oleoyl-CoA + 2 ferricytochrome b5 + H2O

EC linoleoyl-CoA 9-desaturase

linoleoyl-CoA + 2 ferrocytochrome b5 + O2 + 2 H+ → γ-linolenoyl-CoA + 2 ferricytochrome b5 + H2O

See also


  • Lederer F (1994). "The cytochrome b5-fold: an adaptable module". Biochimie. 76 (7): 674–92. 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): 135–43. 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): 12233–40. doi:10.1021/bi00163a037. PMID 1333795.
  • Schenkman JB, Jansson I (February 2003). "The many roles of cytochrome b5". Pharmacology & Therapeutics. 97 (2): 139–52. doi:10.1016/S0163-7258(02)00327-3. PMID 12559387.

External links

  • 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 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.

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.

Literature references

  1. Gerdes D, Wehling M, Leube B, Falkenstein E; , Biol Chem 1998;379:907-911.: Cloning and tissue expression of two putative steroid membrane receptors. PUBMED:9705155 EPMC:9705155

  2. 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

  3. Mifsud W, Bateman A; , Genome Biol 2002;3:0-0.: Membrane-bound progesterone receptors contain a cytochrome b5-like ligand-binding domain. PUBMED:12537557 EPMC:12537557

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 [ 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 [ 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; 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.

Domain organisation

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

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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 (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

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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.

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

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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...


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.

Curation View help on the curation process

Seed source: Bateman A
Previous IDs: heme_1;
Type: Domain
Sequence Ontology: SO:0000417
Author: 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 information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 23.7 23.7
Trusted cut-off 23.7 23.7
Noise cut-off 23.6 23.6
Model length: 75
Family (HMM) version: 31
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
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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 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.

Protein Predicted structure External Information
A0A0P0VUM5 View 3D Structure Click here
A0A0P0XKT8 View 3D Structure Click here
A0A0P0XWQ8 View 3D Structure Click here
A0A0R0EIY9 View 3D Structure Click here
A0A0R0FCM7 View 3D Structure Click here
A0A0R0JHB5 View 3D Structure Click here
A0A0R0K3S0 View 3D Structure Click here
A0A0R4IKF7 View 3D Structure Click here
A0A1D6EKZ2 View 3D Structure Click here
A0A1D6GGW7 View 3D Structure Click here
A0A1D6GMM7 View 3D Structure Click here
A0A1D6HBR0 View 3D Structure Click here
A0A1D6HEG7 View 3D Structure Click here
A0A1D6IX37 View 3D Structure Click here
A0A1D6JRQ6 View 3D Structure Click here
A0A1D6K136 View 3D Structure Click here
A0A1D6KPJ2 View 3D Structure Click here
A0A1D6KQP9 View 3D Structure Click here
A0A1D6KRE0 View 3D Structure Click here
A0A1D6L4Z2 View 3D Structure Click here
A0A1D6LHW0 View 3D Structure Click here
A0A1D6NMP2 View 3D Structure Click here
A0A1D6PI12 View 3D Structure Click here
A0A1D8PD35 View 3D Structure Click here
A0A1D8PHE5 View 3D Structure Click here
A0A1D8PHT9 View 3D Structure Click here
A0A1D8PIF4 View 3D Structure Click here
A0A1D8PQP7 View 3D Structure Click here
A0A368UGJ5 View 3D Structure Click here
A1ZBK6 View 3D Structure Click here
A2CES0 View 3D Structure Click here
A4FV48 View 3D Structure Click here
A4HRK7 View 3D Structure Click here
A4HT20 View 3D Structure Click here
A4HTA6 View 3D Structure Click here
A4HU71 View 3D Structure Click here
A4HU72 View 3D Structure Click here
A4HUW0 View 3D Structure Click here
A4HVZ3 View 3D Structure Click here
A4HWB7 View 3D Structure Click here