Summary: Flavoprotein
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Flavoprotein Edit Wikipedia article
| Flavoprotein | |||||||||
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 the fmn binding protein athal3 | |||||||||
| Identifiers | |||||||||
| Symbol | Flavoprotein | ||||||||
| Pfam | PF02441 | ||||||||
| InterPro | IPR003382 | ||||||||
| SCOPe | 1e20 / SUPFAM | ||||||||
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Flavoproteins are proteins that contain a nucleic acid derivative of riboflavin: the flavin adenine dinucleotide (FAD) or flavin mononucleotide (FMN).
Flavoproteins are involved in a wide array of biological processes, including removal of radicals contributing to oxidative stress, photosynthesis, and DNA repair. The flavoproteins are some of the most-studied families of enzymes.
Flavoproteins have either FMN or FAD as a prosthetic group or as a cofactor. The flavin is generally tightly bound (see example adrenodoxin reductase wherein the FAD is deeply buried in the enzyme).[1] About 5-10% of flavoproteins have a covalently linked FAD.[2] Based on the available structural data, FAD-binding sites can be divided into more than 200 different types.[3]
90 flavoproteins are encoded in the human genome; about 84% require FAD, and around 16% require FMN, whereas 5 proteins require both.[4] Flavoproteins are mainly located in the mitochondria.[4] Of all flavoproteins, 90% perform redox reactions and the other 10% are transferases, lyases, isomerases, ligases.[5]
Discovery
Flavoproteins were first mentioned in 1879, when they isolated as a bright-yellow pigment from cow's milk. They were initially termed lactochrome. By the early 1930s, this same pigment had been isolated from a range of sources, and recognised as a component of the vitamin B complex. Its structure was determined was reported in 1935 and given the name riboflavin, derived from the ribityl side chain and yellow colour of the conjugated ring system.[6]
The first evidence for the requirement of flavin as an enzyme cofactor came in 1935. Hugo Theorell and coworkers showed that a bright-yellow-coloured yeast protein, identified previously as essential for cellular respiration, could be separated into apoprotein and a bright-yellow pigment. Neither apoprotein nor pigment alone could catalyse the oxidation of NADH, but mixing of the two restored the enzyme activity. However, replacing the isolated pigment with riboflavin did not restore enzyme activity, despite their being indistinguishable under spectroscopy. This led to the discovery that the protein studied required not riboflavin but flavin mononucleotide to be catalytically active.[6][7]
Similar experiments with D-amino acid oxidase[8] led to the identification of flavin adenine dinucleotide (FAD) as a second form of flavin utilised by enzymes.[9]
Examples
The flavoprotein family contains a diverse range of enzymes, including:
- Adrenodoxin reductase that is involved in steroid hormone synthesis in vertebrate species, and has a ubiquitous distribution in metazoa and prokaryotes.[1]
- Epidermin biosynthesis protein, EpiD, which has been shown to be a flavoprotein that binds FMN. This enzyme catalyses the removal of two reducing equivalents from the cysteine residue of the C-terminal meso-lanthionine of epidermin to form a --C==C-- double bond.[10]
- The B chain of dipicolinate synthase, an enzyme which catalyses the formation of dipicolinic acid from dihydroxydipicolinic acid.[11]
- Phenylacrylic acid decarboxylase EC 4.1.1.-, and enzyme which confers resistance to cinnamic acid in yeast[12]
See also
References
- ^ a b Hanukoglu I (2017). "Conservation of the Enzyme-Coenzyme Interfaces in FAD and NADP Binding Adrenodoxin Reductase-A Ubiquitous Enzyme". Journal of Molecular Evolution. 85 (5): 205–218. doi:10.1007/s00239-017-9821-9. PMID 29177972.
- ^ Abbas, Charles A.; Sibirny, Andriy A. (2011-06-01). "Genetic Control of Biosynthesis and Transport of Riboflavin and Flavin Nucleotides and Construction of Robust Biotechnological Producers". Microbiology and Molecular Biology Reviews. 75 (2): 321–360. doi:10.1128/MMBR.00030-10. ISSN 1092-2172. PMC 3122625. PMID 21646432.
- ^ Garma, Leonardo D.; Medina, Milagros; Juffer, André H. (2016-11-01). "Structure-based classification of FAD binding sites: A comparative study of structural alignment tools". Proteins: Structure, Function, and Bioinformatics. 84 (11): 1728–1747. doi:10.1002/prot.25158. ISSN 1097-0134. PMID 27580869.
- ^ a b Lienhart, Wolf-Dieter; Gudipati, Venugopal; Macheroux, Peter (2013-07-15). "The human flavoproteome". Archives of Biochemistry and Biophysics. 535 (2): 150–162. doi:10.1016/j.abb.2013.02.015. PMC 3684772. PMID 23500531.
- ^ Macheroux, Peter; Kappes, Barbara; Ealick, Steven E. (2011-08-01). "Flavogenomics – a genomic and structural view of flavin-dependent proteins". FEBS Journal. 278 (15): 2625–2634. doi:10.1111/j.1742-4658.2011.08202.x. ISSN 1742-4658. PMID 21635694.
- ^ a b Massey, V (2000). "The chemical and biological versatility of riboflavin". Biochemical Society Transactions. 28 (4): 283–96. doi:10.1042/0300-5127:0280283. PMID 10961912.
- ^ Theorell, H. (1935). "Preparation in pure state of the effect group of yellow enzymes". Biochemische Zeitschrift. 275: 344–46.
- ^ Warburg, O.; Christian, W. (1938). "Isolation of the prosthetic group of the amino acid oxydase". Biochemische Zeitschrift. 298: 150–68.
- ^ Christie, S. M. H.; Kenner, G. W.; Todd, A. R. (1954). "Nucleotides. Part XXV. A synthesis of flavin?adenine dinucleotide". Journal of the Chemical Society: 46–52. doi:10.1039/JR9540000046.
- ^ Kupke, T; Stevanović, S; Sahl, H. G.; Götz, F (1992). "Purification and characterization of EpiD, a flavoprotein involved in the biosynthesis of the lantibiotic epidermin". Journal of Bacteriology. 174 (16): 5354–61. doi:10.1128/jb.174.16.5354-5361.1992. PMC 206373. PMID 1644762.
- ^ Daniel, R.A.; Errington, J. (1993). "Cloning, DNA Sequence, Functional Analysis and Transcriptional Regulation of the Genes Encoding Dipicolinic Acid Synthetase Required for Sporulation in Bacillus subtilis". Journal of Molecular Biology. 232 (2): 468–83. doi:10.1006/jmbi.1993.1403. PMID 8345520.
- ^ Clausen, Monika; Lamb, Christopher J.; Megnet, Roland; Doerner, Peter W. (1994). "PAD1 encodes phenylacrylic acid decarboxylase which confers resistance to cinnamic acid in Saccharomyces cerevisiae". Gene. 142 (1): 107–12. doi:10.1016/0378-1119(94)90363-8. PMID 8181743.
External links
- The menu "science" of the program STRAP provides A comprehensive collection of all flavo-proteins with known 3D-structure. It compares the protein structures to elucidate phylogenetic relationships.
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.
Flavoprotein Provide feedback
This family contains diverse flavoprotein enzymes. This family includes epidermin biosynthesis protein, EpiD P30197 which has been shown to be a flavoprotein that binds FMN [1]. This enzyme catalyses the removal of two reducing equivalents from the cysteine residue of the C-terminal meso-lanthionine of epidermin to form a --C==C-- double bond. This family also includes the B chain of dipicolinate synthase a small polar molecule that accumulates to high concentrations in bacterial endospores, and is thought to play a role in spore heat resistance, or the maintenance of heat resistance [2]. dipicolinate synthase catalyses the formation of dipicolinic acid from dihydroxydipicolinic acid. This family also includes phenyl-acrylic acid decarboxylase P33751 ( EC:4.1.1.-) [3].
Literature references
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Kupke T, Stevanovic S, Sahl HG, Gotz F; , J Bacteriol 1992;174:5354-5361.: Purification and characterization of EpiD, a flavoprotein involved in the biosynthesis of the lantibiotic epidermin. PUBMED:1644762 EPMC:1644762
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Daniel RA, Errington J; , J Mol Biol 1993;232:468-483.: Cloning, DNA sequence, functional analysis and transcriptional regulation of the genes encoding dipicolinic acid synthetase required for sporulation in Bacillus subtilis. PUBMED:8345520 EPMC:8345520
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Clausen M, Lamb CJ, Megnet R, Doerner PW; , Gene 1994;142:107-112.: PAD1 encodes phenylacrylic acid decarboxylase which confers resistance to cinnamic acid in Saccharomyces cerevisiae. PUBMED:8181743 EPMC:8181743
External database links
| SCOP: | 1e20 |
This tab holds annotation information from the InterPro database.
InterPro entry IPR003382
This entry contains a diverse range of flavoprotein enzymes, including epidermin biosynthesis protein, EpiD, which has been shown to be a flavoprotein that binds FMN [PUBMED:1644762]. This enzyme catalyzes the removal of two reducing equivalents from the cysteine residue of the C-terminal meso-lanthionine of epidermin to form a --C==C-- double bond. This family also includes the B chain of dipicolinate synthase a small polar molecule that accumulates to high concentrations in bacterial endospores, and is thought to play a role in spore heat resistance, or the maintenance of heat resistance [PUBMED:8345520]. Dipicolinate synthase catalyses the formation of dipicolinic acid from dihydroxydipicolinic acid. This family also includes phenylacrylic acid decarboxylase EC [PUBMED:8181743].
Gene Ontology
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
| Molecular function | catalytic activity (GO:0003824) |
Domain organisation
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Alignments
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Full (13824) |
Representative proteomes | UniProt (58811) |
NCBI (77293) |
Meta (2712) |
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| RP15 (1767) |
RP35 (6324) |
RP55 (13104) |
RP75 (22696) |
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| PP/heatmap | 1 | ||||||||
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
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| Seed (90) |
Full (13824) |
Representative proteomes | UniProt (58811) |
NCBI (77293) |
Meta (2712) |
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|---|---|---|---|---|---|---|---|---|---|
| RP15 (1767) |
RP35 (6324) |
RP55 (13104) |
RP75 (22696) |
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| Raw Stockholm | |||||||||
| Gzipped | |||||||||
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
HMM logo
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.
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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
| Seed source: | Pfam-B_1622 (release 5.4) |
| Previous IDs: | none |
| Type: | Family |
| Sequence Ontology: | SO:0100021 |
| Author: |
Bateman A 
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| Number in seed: | 90 |
| Number in full: | 13824 |
| Average length of the domain: | 176.50 aa |
| Average identity of full alignment: | 24 % |
| Average coverage of the sequence by the domain: | 56.65 % |
HMM information
| HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 47079205 -E 1000 --cpu 4 HMM pfamseq
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| Model details: |
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| Model length: | 158 | ||||||||||||
| Family (HMM) version: | 20 | ||||||||||||
| Download: | download the raw HMM for this family |
Species distribution
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Interactions
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FlavoproteinStructures
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 Flavoprotein 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 sequence.
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