Q02928 · CP4AB_HUMAN
- ProteinCytochrome P450 4A11
- GeneCYP4A11
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids519 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
A cytochrome P450 monooxygenase involved in the metabolism of fatty acids and their oxygenated derivatives (oxylipins) (PubMed:10553002, PubMed:10660572, PubMed:15611369, PubMed:1739747, PubMed:7679927, PubMed:8914854).
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:10553002, PubMed:10660572, PubMed:15611369, PubMed:1739747, PubMed:7679927, PubMed:8914854).
Catalyzes predominantly the oxidation of the terminal carbon (omega-oxidation) of saturated and unsaturated fatty acids, the catalytic efficiency decreasing in the following order: dodecanoic > tetradecanoic > (9Z)-octadecenoic > (9Z,12Z)-octadecadienoic > hexadecanoic acid (PubMed:10553002, PubMed:10660572).
Acts as a major omega-hydroxylase for dodecanoic (lauric) acid in liver (PubMed:15611369, PubMed:1739747, PubMed:7679927, PubMed:8914854).
Participates in omega-hydroxylation of (5Z,8Z,11Z,14Z)-eicosatetraenoic acid (arachidonate) to 20-hydroxyeicosatetraenoic acid (20-HETE), a signaling molecule acting both as vasoconstrictive and natriuretic with overall effect on arterial blood pressure (PubMed:10620324, PubMed:10660572, PubMed:15611369).
Can also catalyze the oxidation of the penultimate carbon (omega-1 oxidation) of fatty acids with lower efficiency (PubMed:7679927).
May contribute 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).
Omega-hydroxylates (9R,10S)-epoxy-octadecanoate stereoisomer (PubMed:15145985).
Plays a minor role in omega-oxidation of long-chain 3-hydroxy fatty acids (PubMed:18065749).
Has little activity toward prostaglandins A1 and E1 (PubMed:7679927).
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:10553002, PubMed:10660572, PubMed:15611369, PubMed:1739747, PubMed:7679927, PubMed:8914854).
Catalyzes predominantly the oxidation of the terminal carbon (omega-oxidation) of saturated and unsaturated fatty acids, the catalytic efficiency decreasing in the following order: dodecanoic > tetradecanoic > (9Z)-octadecenoic > (9Z,12Z)-octadecadienoic > hexadecanoic acid (PubMed:10553002, PubMed:10660572).
Acts as a major omega-hydroxylase for dodecanoic (lauric) acid in liver (PubMed:15611369, PubMed:1739747, PubMed:7679927, PubMed:8914854).
Participates in omega-hydroxylation of (5Z,8Z,11Z,14Z)-eicosatetraenoic acid (arachidonate) to 20-hydroxyeicosatetraenoic acid (20-HETE), a signaling molecule acting both as vasoconstrictive and natriuretic with overall effect on arterial blood pressure (PubMed:10620324, PubMed:10660572, PubMed:15611369).
Can also catalyze the oxidation of the penultimate carbon (omega-1 oxidation) of fatty acids with lower efficiency (PubMed:7679927).
May contribute 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).
Omega-hydroxylates (9R,10S)-epoxy-octadecanoate stereoisomer (PubMed:15145985).
Plays a minor role in omega-oxidation of long-chain 3-hydroxy fatty acids (PubMed:18065749).
Has little activity toward prostaglandins A1 and E1 (PubMed:7679927).
Catalytic activity
- an organic molecule + O2 + reduced [NADPH--hemoprotein reductase] = an alcohol + H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- dodecanoate + O2 + reduced [NADPH--hemoprotein reductase] = 12-hydroxydodecanoate + H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- O2 + reduced [NADPH--hemoprotein reductase] + tetradecanoate = 14-hydroxytetradecanoate + H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--hemoprotein reductase] = 20-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- 22-hydroxydocosanoate + O2 + reduced [NADPH--hemoprotein reductase] = 22-oxodocosanoate + H+ + 2 H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- 22-oxodocosanoate + O2 + reduced [NADPH--hemoprotein reductase] = docosanedioate + 2 H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- (9R,10S)-epoxy-octadecanoate + O2 + reduced [NADPH--hemoprotein reductase] = 18-hydroxy-(9R,10S)-epoxy-octadecanoate + H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- 3-hydroxyhexadecanoate + O2 + reduced [NADPH--hemoprotein reductase] = 3,16-dihydroxyhexadecanoate + H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
Cofactor
Activity regulation
Activated by cytochrome b5.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
11 μM | dodecanoic acid | |||||
37 μM | (5Z,8Z,11Z,14Z)-eicosatetraenoic acid |
kcat is 42 min-1 with dodecanoic acid as substrate. kcat is 50 min-1 with tetradecanoic acid as substrate. kcat is 10 min-1 with hexadecanoic acid as substrate. kcat is 0.4 min-1 with (9Z)-octadecenoic acid as substrate. kcat is 0.4 min-1 with (5Z,8Z,11Z,14Z)-eicosatetraenoic acid as substrate.
Pathway
Lipid metabolism; arachidonate metabolism.
Lipid metabolism; oxylipin biosynthesis.
Features
Showing features for binding site.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Chemistry
Names & Taxonomy
Protein names
- Recommended nameCytochrome P450 4A11
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ02928
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Endoplasmic reticulum membrane ; Peripheral membrane protein
Microsome membrane ; Peripheral membrane protein
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 130 | Loss of activity. | ||||
Sequence: G → S | ||||||
Natural variant | VAR_048452 | 226 | in dbSNP:rs12759923 | |||
Sequence: N → S | ||||||
Mutagenesis | 321 | Loss of covalent heme binding. | ||||
Sequence: E → A | ||||||
Natural variant | VAR_044377 | 353 | in dbSNP:rs3899049 | |||
Sequence: S → G | ||||||
Natural variant | VAR_019160 | 434 | risk factor for hypertension; significantly reduced arachidonic acid and lauric acid metabolizing activity; dbSNP:rs1126742 | |||
Sequence: F → S | ||||||
Natural variant | VAR_001257 | 500-519 | in CYP4A11V | |||
Sequence: NGIHLRLRRLPNPCEDKDQL → MESTCVSGGSLTLVKTRTSFEGLHLPSCLPDPRFCPLPVCPYPVFCLPTFPSSHLPAVPQSACPSLSHLSPGLPTCLSTCLLPTCISCWEKS |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 777 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for propeptide, chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Propeptide | PRO_0000003579 | 1-4 | ||||
Sequence: MSVS | ||||||
Chain | PRO_0000003580 | 5-519 | Cytochrome P450 4A11 | |||
Sequence: VLSPSRLLGDVSGILQAASLLILLLLLIKAVQLYLHRQWLLKALQQFPCPPSHWLFGHIQELQQDQELQRIQKWVETFPSACPHWLWGGKVRVQLYDPDYMKVILGRSDPKSHGSYRFLAPWIGYGLLLLNGQTWFQHRRMLTPAFHYDILKPYVGLMADSVRVMLDKWEELLGQDSPLEVFQHVSLMTLDTIMKCAFSHQGSIQVDRNSQSYIQAISDLNNLVFSRVRNAFHQNDTIYSLTSAGRWTHRACQLAHQHTDQVIQLRKAQLQKEGELEKIKRKRHLDFLDILLLAKMENGSILSDKDLRAEVDTFMFEGHDTTASGISWILYALATHPKHQERCREEIHSLLGDGASITWNHLDQMPYTTMCIKEALRLYPPVPGIGRELSTPVTFPDGRSLPKGIMVLLSIYGLHHNPKVWPNPEVFDPFRFAPGSAQHSHAFLPFSGGSRNCIGKQFAMNELKVATALTLLRFELLPDPTRIPIPIARLVLKSKNGIHLRLRRLPNPCEDKDQL | ||||||
Modified residue | 440 | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Structure
Sequence & Isoform
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 2 isoforms produced by Alternative splicing.
Q02928-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length519
- Mass (Da)59,348
- Last updated1997-11-01 v1
- ChecksumA8D3073EEFF48AE9
Q02928-2
- Name2
- Differences from canonical
- 356-519: Missing
Computationally mapped potential isoform sequences
There are 6 potential isoforms mapped to this entry
Features
Showing features for sequence conflict, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 5 | in Ref. 8; AA sequence | ||||
Sequence: V → A | ||||||
Alternative sequence | VSP_034595 | 356-519 | in isoform 2 | |||
Sequence: Missing | ||||||
Sequence conflict | 383 | in Ref. 4; AAO16078 | ||||
Sequence: Y → F | ||||||
Sequence conflict | 390 | in Ref. 9; CAA50586 | ||||
Sequence: G → S | ||||||
Sequence conflict | 410-412 | in Ref. 9; CAA50586 | ||||
Sequence: MVL → TVM |
Polymorphism
CYP4A11v seems to be a rare allelic variant of CYP4A11, it seems to be unstable and not to metabolize lauric acid.
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
L04751 EMBL· GenBank· DDBJ | AAA58436.1 EMBL· GenBank· DDBJ | mRNA | ||
D26481 EMBL· GenBank· DDBJ | BAA05491.1 EMBL· GenBank· DDBJ | mRNA | ||
S67580 EMBL· GenBank· DDBJ | AAB29502.1 EMBL· GenBank· DDBJ | mRNA | ||
S67581 EMBL· GenBank· DDBJ | AAB29503.1 EMBL· GenBank· DDBJ | mRNA | ||
AF525488 EMBL· GenBank· DDBJ | AAO16078.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AY369778 EMBL· GenBank· DDBJ | AAQ56847.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AL731892 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC041158 EMBL· GenBank· DDBJ | AAH41158.1 EMBL· GenBank· DDBJ | mRNA | ||
X71480 EMBL· GenBank· DDBJ | CAA50586.1 EMBL· GenBank· DDBJ | mRNA |