Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Entry version 197 (29 Sep 2021)
Sequence version 2 (21 Dec 2004)
Previous versions | rss
Add a publicationFeedback
Protein

Cytochrome P450 4F3

Gene

CYP4F3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and their oxygenated derivatives (oxylipins) (PubMed:8486631, PubMed:9675028, PubMed:11461919, PubMed:15145985, PubMed:16547005, PubMed:16820285, PubMed:18182499, PubMed:18065749, PubMed:18577768).

Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:9675028).

May play a role in inactivation of proinflammatory and anti-inflammatory oxylipins during the resolution of inflammation (PubMed:8486631, PubMed:9675028, PubMed:11461919, PubMed:15145985, PubMed:15364545, PubMed:16547005, PubMed:16820285, PubMed:18182499, PubMed:18065749, PubMed:18577768).

10 Publications

Catalyzes predominantly the oxidation of the terminal carbon (omega-oxidation) of oxylipins in myeloid cells, displaying higher affinity for arachidonate metabolite leukotriene B4 (LTB4) (PubMed:8486631, PubMed:9675028, PubMed:11461919, PubMed:15364545).

Inactivates LTB4 via three successive oxidative transformations to 20-hydroxy-LTB4, then to 20-oxo-LTB4 and to 20-carboxy-LTB4 (PubMed:9675028).

Has omega-hydroxylase activity toward long-chain fatty acid epoxides with preference for 8,9-epoxy-(5Z,11Z,14Z)-eicosatrienoate (EET) and 9,10-epoxyoctadecanoate (PubMed:15145985).

Omega-hydroxylates monohydroxy polyunsaturated fatty acids (PUFAs), including hydroxyeicosatetraenoates (HETEs) and hydroxyeicosapentaenoates (HEPEs), to dihydroxy compounds (PubMed:15364545, PubMed:9675028).

Contributes to the degradation of saturated very long-chain fatty acids (VLCFAs) such as docosanoic acid, by catalyzing successive omega-oxidations to the corresponding dicarboxylic acid, thereby initiating chain shortening (PubMed:18182499).

Has low hydroxylase activity toward PUFAs (PubMed:18577768, PubMed:11461919).

7 Publications

Catalyzes predominantly the oxidation of the terminal carbon (omega-oxidation) of polyunsaturated fatty acids (PUFAs) (PubMed:11461919, PubMed:16820285, PubMed:18577768).

Participates in the conversion of arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE), a signaling molecule acting both as vasoconstrictive and natriuretic with overall effect on arterial blood pressure (PubMed:11461919, PubMed:16820285, PubMed:18577768).

Has high omega-hydroxylase activity toward other PUFAs, including eicosatrienoic acid (ETA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (PubMed:16820285, PubMed:18577768).

Can also catalyze the oxidation of the penultimate carbon (omega-1 oxidation) of PUFAs with lower efficiency (PubMed:18577768).

Contributes to the degradation of saturated very long-chain fatty acids (VLCFAs) such as docosanoic acid and hexacosanoic acid, by catalyzing successive omega-oxidations to the corresponding dicarboxylic acids, thereby initiating chain shortening (PubMed:16547005, PubMed:18182499).

Omega-hydroxylates long-chain 3-hydroxy fatty acids, likely initiating the oxidative conversion to the corresponding 3-hydroxydicarboxylic fatty acids (PubMed:18065749).

Has omega-hydroxylase activity toward long-chain fatty acid epoxides with preference for 8,9-epoxy-(5Z,11Z,14Z)-eicosatrienoate (EET) and 9,10-epoxyoctadecanoate (PubMed:15145985).

7 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the 'Function' section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori

hemeBy similarity

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

Inhibited by carbon monoxide (CO).1 Publication

<p>This subsection of the 'Function' section describes biophysical and chemical properties, such as maximal absorption, kinetic parameters, pH dependence, redox potentials and temperature dependence.<p><a href='/help/biophysicochemical_properties' target='_top'>More...</a></p>Kineticsi

  1. KM=0.64 µM for leukotriene B41 Publication
  2. KM=6.5 µM for 20-hydroxy-leukotriene B41 Publication
  3. KM=0.68 µM for leukotriene B41 Publication
  4. KM=185.6 µM for arachidonate1 Publication
  5. KM=17.9 µM for lipoxin B41 Publication
  6. KM=25.7 µM for 5-HETE1 Publication
  7. KM=40.9 µM for 12-HETE1 Publication
  8. KM=49.5 µM for 5-HEPE1 Publication
  9. KM=14.2 µM for 12-hydroxyoctadecanoate1 Publication
  10. KM=22.8 µM for (12R)-hydroxy-(9Z)-octadecenoate1 Publication
  11. KM=6.3 µM for 9(10)-epoxyoctadecanoate1 Publication
  12. KM=46.6 µM for 9(10)-epoxy-(12Z)-octadecenoate1 Publication
  13. KM=61.8 µM for 12(13)-epoxy-(9Z)-octadecenoate1 Publication
  14. KM=0.6 µM for 22-hydroxydocosanoate1 Publication
  1. Vmax=34.0 nmol/min/nmol enzyme toward leukotriene B41 Publication
  2. Vmax=66.7 nmol/min/nmol enzyme toward 20-hydroxy-leukotriene B41 Publication
  3. Vmax=32.8 pmol/min/pmol enzyme toward leukotriene B41 Publication
  4. Vmax=11.5 pmol/min/pmol enzyme toward arachidonate1 Publication
  5. Vmax=38.5 nmol/min/nmol enzyme toward lipoxin B41 Publication
  6. Vmax=21.6 nmol/min/nmol enzyme toward 5-HETE1 Publication
  7. Vmax=43.2 nmol/min/nmol enzyme toward 12-HETE1 Publication
  8. Vmax=95.1 nmol/min/nmol enzyme toward 5-HEPE1 Publication
  9. Vmax=54.5 nmol/min/nmol enzyme toward 12-hydroxyoctadecanoate1 Publication
  10. Vmax=19.0 nmol/min/nmol enzyme toward (12R)-hydroxy-(9Z)-octadecenoate1 Publication
  11. Vmax=10.8 nmol/min/nmol enzyme toward 9(10)-epoxyoctadecanoate1 Publication
  12. Vmax=21.2 nmol/min/nmol enzyme toward 9(10)-epoxy-(12Z)-octadecenoate1 Publication
  13. Vmax=3 nmol/min/nmol enzyme toward 12(13)-epoxy-(9Z)-octadecenoate1 Publication
  14. Vmax=0.2 pmol/min/pmol enzyme toward 22-hydroxydocosanoate1 Publication
The omega-hydroxylation of VLCFAs follows dual-enzyme Michaelis-Menten kinetics, suggesting simultaneous binding of two substrate molecules. The high affinity Michaelis-Menten constants are shown.1 Publication
  1. KM=20.6 µM for leukotriene B41 Publication
  2. KM=22.0 µM for arachidonate1 Publication
  3. KM=35.7 µM for 9(10)-epoxyoctadecanoate1 Publication
  4. KM=108.1 µM for 9(10)-epoxy-(12Z)-octadecenoate1 Publication
  5. KM=100.6 µM for 12(13)-epoxy-(9Z)-octadecenoate1 Publication
  6. KM=1.6 µM for docosanoate1 Publication
  7. KM=3.8 µM for tetracosanoate1 Publication
  8. KM=1.3 µM for hexacosanoate1 Publication
  9. KM=13.1 µM for 22-hydroxydocosanoate1 Publication
  10. KM=5.2 µM for 26-hydroxyhexacosanoate1 Publication
  1. Vmax=23.3 pmol/min/pmol enzyme toward leukotriene B41 Publication
  2. Vmax=13.3 pmol/min/pmol enzyme toward arachidonate1 Publication
  3. Vmax=13.2 nmol/min/nmol enzyme toward 9(10)-epoxyoctadecanoate1 Publication
  4. Vmax=15.02 nmol/min/nmol enzyme toward 9(10)-epoxy-(12Z)-octadecenoate1 Publication
  5. Vmax=3.93 nmol/min/nmol enzyme toward 12(13)-epoxy-(9Z)-octadecenoate1 Publication
  6. Vmax=5.0 pmol/min/pmol enzyme toward docosanoate1 Publication
  7. Vmax=9.8 pmol/min/pmol enzyme toward tetracosanoate1 Publication
  8. Vmax=2.2 pmol/min/pmol enzyme toward hexacosanoate1 Publication
  9. Vmax=0.3 pmol/min/pmol enzyme toward 22-hydroxydocosanoate1 Publication
  10. Vmax=0.8 pmol/min/pmol enzyme toward 26-hydroxyhexacosanoate1 Publication

pH dependencei

Optimum pH is 7.5.1 Publication

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section describes the metabolic pathway(s) associated with a protein.<p><a href='/help/pathway' target='_top'>More...</a></p>Pathwayi: leukotriene B4 degradation

This protein is involved in the pathway leukotriene B4 degradation, which is part of Lipid metabolism.1 Publication
View all proteins of this organism that are known to be involved in the pathway leukotriene B4 degradation and in Lipid metabolism.

Pathwayi: arachidonate metabolism

This protein is involved in the pathway arachidonate metabolism, which is part of Lipid metabolism.1 Publication
View all proteins of this organism that are known to be involved in the pathway arachidonate metabolism and in Lipid metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei328Heme; covalent, via 1 linkBy similarity1
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the 'Description' field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi468Iron (heme axial ligand)By similarity1

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionMonooxygenase, Oxidoreductase
Biological processFatty acid metabolism, Lipid metabolism
LigandHeme, Iron, Metal-binding

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

More...
BRENDAi
1.14.14.79, 2681
1.14.14.94, 2681

Pathway Commons web resource for biological pathway data

More...
PathwayCommonsi
Q08477

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-HSA-211935, Fatty acids
R-HSA-211958, Miscellaneous substrates
R-HSA-211979, Eicosanoids
R-HSA-2142691, Synthesis of Leukotrienes (LT) and Eoxins (EX)

SABIO-RK: Biochemical Reaction Kinetics Database

More...
SABIO-RKi
Q08477

UniPathway: a resource for the exploration and annotation of metabolic pathways

More...
UniPathwayi
UPA00383
UPA00883

Chemistry databases

SwissLipids knowledge resource for lipid biology

More...
SwissLipidsi
SLP:000000422 [Q08477-1]
SLP:000000423 [Q08477-2]

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Cytochrome P450 4F3 (EC:1.14.14.13 Publications)
Alternative name(s):
20-hydroxyeicosatetraenoic acid synthase1 Publication
Short name:
20-HETE synthase1 Publication
CYPIVF3
Cytochrome P450-LTB-omega
Docosahexaenoic acid omega-hydroxylase CYP4F31 Publication (EC:1.14.14.792 Publications)
Leukotriene-B(4) 20-monooxygenase 2
Leukotriene-B(4) omega-hydroxylase 2 (EC:1.14.14.944 Publications