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97  structures 768  species 4  interactions 9643  sequences 273  architectures

Family: Cyt-b5 (PF00173)

Summary: Cytochrome b5-like Heme/Steroid binding domain

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

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​)
Identifiers
Symbol CYB5A
Alt. symbols CYB5
Entrez 1528
HUGO 2570
OMIM 250790
PDB 1JEX
RefSeq NM_001914
UniProt P00167
Other data
Locus Chr. 18 q23
Cytochrome b5
Identifiers
Symbol Cyt_B5
Pfam PF00173
InterPro IPR001199
PROSITE PDOC00170

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 1.1.2.3), sulfite oxidase (EC 1.8.3.1), plant and fungal nitrate reductases (EC 1.7.1.1, EC 1.7.1.2, EC 1.7.1.3), and plant and fungal cytochrome b5/acyl lipid desaturase fusion proteins.

Structure

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 1.6.2.2 cytochrome-b5 reductase

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

EC 1.10.2.1 L-ascorbate—cytochrome-b5 reductase

L-ascorbate + ferricytochrome b5 → monodehydroascorbate + ferrocytochrome b5

EC 1.14.18.2 CMP-N-acetylneuraminate monooxygenase

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

EC 1.14.19.1 stearoyl-CoA 9-desaturase

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

EC 1.14.19.3 linoleoyl-CoA 9-desaturase

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

See also

References

  • 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.; 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. 

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

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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


Internal database links

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 1.1.2.3) [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 1.8.3.1) [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 1.14.19.1) (gene OLE1). This enzyme contains a C-termainal heme-binding domain.
  • Yeast Scs7 (YMR272c), a sphingolipid alpha-hydroxylase.

Proteins containing this domain also includes:

  • TU-36B, a Drosophila muscle protein of unknown function [PUBMED:2549511].
  • Fission yeast hypothetical protein SpAC1F12.10c.
  • Yeast Irc21 (YMR073c), a putative protein with unknown function.

Domain organisation

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Alignments

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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.

  Seed
(85)
Full
(9643)
Representative proteomes UniProt
(17490)
NCBI
(18451)
Meta
(245)
RP15
(2356)
RP35
(5117)
RP55
(7459)
RP75
(9724)
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  Seed
(85)
Full
(9643)
Representative proteomes UniProt
(17490)
NCBI
(18451)
Meta
(245)
RP15
(2356)
RP35
(5117)
RP55
(7459)
RP75
(9724)
Alignment:
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  Seed
(85)
Full
(9643)
Representative proteomes UniProt
(17490)
NCBI
(18451)
Meta
(245)
RP15
(2356)
RP35
(5117)
RP55
(7459)
RP75
(9724)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download   Download  
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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.

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Curation and family details

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Curation View help on the curation process

Seed source: Bateman A
Previous IDs: heme_1;
Type: Domain
Author: Bateman A
Number in seed: 85
Number in full: 9643
Average length of the domain: 81.20 aa
Average identity of full alignment: 26 %
Average coverage of the sequence by the domain: 16.93 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 17690987 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 23.1 23.1
Trusted cut-off 23.1 23.1
Noise cut-off 23.0 23.0
Model length: 74
Family (HMM) version: 26
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 4 interactions for this family. More...

FMN_dh Cyt-b5 Oxidored_molyb FMN_dh

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 Cyt-b5 domain has been found. There are 97 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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