Q6ZWL3 · CP4V2_HUMAN
- ProteinCytochrome P450 4V2
- GeneCYP4V2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids525 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
A cytochrome P450 monooxygenase involved in fatty acid metabolism in the eye. Catalyzes the omega-hydroxylation of polyunsaturated fatty acids (PUFAs) docosahexaenoate (DHA) and its precursor eicosapentaenoate (EPA), and may contribute to the homeostasis of these retinal PUFAs (PubMed:22772592).
Omega hydroxylates saturated fatty acids such as laurate, myristate and palmitate, the catalytic efficiency decreasing in the following order: myristate > laurate > palmitate (C14>C12>C16) (PubMed:19661213).
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)
Omega hydroxylates saturated fatty acids such as laurate, myristate and palmitate, the catalytic efficiency decreasing in the following order: myristate > laurate > palmitate (C14>C12>C16) (PubMed:19661213).
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)
Catalytic activity
- 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,17Z)-eicosapentaenoate + O2 + reduced [NADPH--hemoprotein reductase] = 20-hydroxy-(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
Cofactor
Activity regulation
Inhibited by N-hydroxy-N'-(4-n-butyl-2-methylphenyl formamidine)(HET0016) with an IC50 of 38 nM.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
65 μM | myristic acid | |||||
140 μM | lauric acid | |||||
430 μM | palmitic acid |
Vmax is nearly the same for myristic acid and for lauric acid and reduced about 30% for palmitic acid.
Pathway
Lipid metabolism; fatty acid metabolism.
Features
Showing features for binding site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | endoplasmic reticulum membrane | |
Molecular Function | heme binding | |
Molecular Function | iron ion binding | |
Molecular Function | long-chain fatty acid omega-hydroxylase activity | |
Molecular Function | monooxygenase activity | |
Biological Process | fatty acid omega-oxidation | |
Biological Process | retinoid metabolic process | |
Biological Process | sterol metabolic process | |
Biological Process | visual perception |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Chemistry
Names & Taxonomy
Protein names
- Recommended nameCytochrome P450 4V2
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ6ZWL3
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Endoplasmic reticulum membrane ; Single-pass membrane protein
Features
Showing features for transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transmembrane | 13-33 | Helical | ||||
Sequence: LLLWGAASALSLAGASLVLSL |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Bietti crystalline corneoretinal dystrophy (BCD)
- Note
- DescriptionAn autosomal recessive ocular disease characterized by retinal degeneration and marginal corneal dystrophy. Typical features include multiple glistening intraretinal crystals scattered over the fundus, a characteristic degeneration of the retina, and sclerosis of the choroidal vessels, ultimately resulting in progressive night blindness and constriction of the visual field. Most patients have similar crystals at the corneoscleral limbus. Patients develop decreased vision, nyctalopia, and paracentral scotomata between the 2nd and 4th decade of life. Later, they develop peripheral visual field loss and marked visual impairment, usually progressing to legal blindness by the 5th or 6th decade of life.
- See alsoMIM:210370
Natural variants in BCD
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_023084 | 44 | W>R | in BCD; dbSNP:rs119103282 | |
VAR_023085 | 61 | G>S | in BCD; dbSNP:rs119103285 | |
VAR_023086 | 79 | E>D | in BCD; dbSNP:rs199476185 | |
VAR_023087 | 111 | I>T | in BCD; dbSNP:rs119103283 | |
VAR_023088 | 123 | M>V | in BCD; dbSNP:rs149684063 | |
VAR_023089 | 331 | H>P | in BCD; impaired omega hydroxylase activity; dbSNP:rs199476197 | |
VAR_023090 | 341 | S>P | in BCD; dbSNP:rs199476199 | |
VAR_023091 | 508 | R>H | in BCD; dbSNP:rs119103284 |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_038606 | 22 | in dbSNP:rs1055138 | |||
Sequence: L → V | ||||||
Natural variant | VAR_023084 | 44 | in BCD; dbSNP:rs119103282 | |||
Sequence: W → R | ||||||
Natural variant | VAR_023085 | 61 | in BCD; dbSNP:rs119103285 | |||
Sequence: G → S | ||||||
Natural variant | VAR_023086 | 79 | in BCD; dbSNP:rs199476185 | |||
Sequence: E → D | ||||||
Natural variant | VAR_023087 | 111 | in BCD; dbSNP:rs119103283 | |||
Sequence: I → T | ||||||
Natural variant | VAR_023088 | 123 | in BCD; dbSNP:rs149684063 | |||
Sequence: M → V | ||||||
Natural variant | VAR_038607 | 213 | in dbSNP:rs34331648 | |||
Sequence: S → N | ||||||
Natural variant | VAR_033821 | 259 | in dbSNP:rs13146272 | |||
Sequence: Q → K | ||||||
Natural variant | VAR_055379 | 275 | in dbSNP:rs34745240 | |||
Sequence: E → K | ||||||
Natural variant | VAR_023089 | 331 | in BCD; impaired omega hydroxylase activity; dbSNP:rs199476197 | |||
Sequence: H → P | ||||||
Natural variant | VAR_023090 | 341 | in BCD; dbSNP:rs199476199 | |||
Sequence: S → P | ||||||
Natural variant | VAR_055380 | 372 | in dbSNP:rs61755911 | |||
Sequence: V → I | ||||||
Natural variant | VAR_055381 | 443 | in dbSNP:rs72646291 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_023091 | 508 | in BCD; dbSNP:rs119103284 | |||
Sequence: R → H |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 695 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000051859 | 1-525 | Cytochrome P450 4V2 | |||
Sequence: MAGLWLGLVWQKLLLWGAASALSLAGASLVLSLLQRVASYARKWQQMRPIPTVARAYPLVGHALLMKPDGREFFQQIIEYTEEYRHMPLLKLWVGPVPMVALYNAENVEVILTSSKQIDKSSMYKFLEPWLGLGLLTSTGNKWRSRRKMLTPTFHFTILEDFLDIMNEQANILVKKLEKHINQEAFNCFFYITLCALDIICETAMGKNIGAQSNDDSEYVRAVYRMSEMIFRRIKMPWLWLDLWYLMFKEGWEHKKSLQILHTFTNSVIAERANEMNANEDCRGDGRGSAPSKNKRRAFLDLLLSVTDDEGNRLSHEDIREEVDTFMFEGHDTTAAAINWSLYLLGSNPEVQKKVDHELDDVFGKSDRPATVEDLKKLRYLECVIKETLRLFPSVPLFARSVSEDCEVAGYRVLKGTEAVIIPYALHRDPRYFPNPEEFQPERFFPENAQGRHPYAYVPFSAGPRNCIGQKFAVMEEKTILSCILRHFWIESNQKREELGLEGQLILRPSNGIWIKLKRRNADER |
Proteomic databases
PTM databases
Interaction
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q6ZWL3 | GATC O43716 | 2 | EBI-3925755, EBI-6929453 |
Protein-protein interaction databases
Miscellaneous
Structure
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q6ZWL3-1
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
- Length525
- Mass (Da)60,724
- Last updated2010-05-18 v2
- ChecksumA26F0A517C9569AD
Q6ZWL3-2
- Name2
- Differences from canonical
- 42-63: Missing
Features
Showing features for alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_014918 | 42-63 | in isoform 2 | |||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AY422002 EMBL· GenBank· DDBJ | AAR31180.1 EMBL· GenBank· DDBJ | mRNA | ||
AK122600 EMBL· GenBank· DDBJ | BAC85487.1 EMBL· GenBank· DDBJ | mRNA | ||
AK126473 EMBL· GenBank· DDBJ | BAC86562.1 EMBL· GenBank· DDBJ | mRNA | ||
FJ440682 EMBL· GenBank· DDBJ | ACK44069.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AC110771 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC060857 EMBL· GenBank· DDBJ | AAH60857.1 EMBL· GenBank· DDBJ | mRNA |