UniProtKB - P08516 (CP4AA_RAT)
Cytochrome P450 4A10
Cyp4a10
Functioni
A cytochrome P450 monooxygenase involved in the metabolism of fatty acids. Catalyzes predominantly the oxidation of the terminal carbon (omega-oxidation) of long-chain fatty acids (PubMed:10620324, PubMed:3027069, PubMed:10362749).
Acts as a major omega-hydroxylase for dodecanoic (lauric) acid in liver (PubMed:3027069).
In kidney, may play an important role 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:10362749, PubMed:10620324, PubMed:16212878).
Also participates in the formation of anti-inflammatory hydroxyepoxyeicosatrienoic acids (HEETs) in kidney by converting 8,9-epoxyeicosatrienoic acid (EET) to 20,8,9-HEET, an activator of PPARA (PubMed:14742258).
Displays substantially lower fatty acid omega-1 hydroxylase activity (PubMed:10362749, PubMed:10620324).
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:10620324, PubMed:3027069, PubMed:10362749).
5 PublicationsCatalytic activityi
- an ω-methyl-long-chain fatty acid + O2 + reduced [NADPH—hemoprotein reductase] = an ω-hydroxy-long-chain fatty acid + H+ + H2O + oxidized [NADPH—hemoprotein reductase]2 PublicationsEC:1.14.14.802 PublicationsThis reaction proceeds in the forward2 Publications direction.
- dodecanoate + O2 + reduced [NADPH—hemoprotein reductase] = 12-hydroxydodecanoate + H+ + H2O + oxidized [NADPH—hemoprotein reductase]3 PublicationsThis reaction proceeds in the forward3 Publications direction.
- dodecanoate + O2 + reduced [NADPH—hemoprotein reductase] = 11-hydroxydodecanoate + H+ + H2O + oxidized [NADPH—hemoprotein reductase]By similarityThis reaction proceeds in the forwardBy similarity direction.
- O2 + reduced [NADPH—hemoprotein reductase] + tetradecanoate = 14-hydroxytetradecanoate + H+ + H2O + oxidized [NADPH—hemoprotein reductase]1 PublicationThis reaction proceeds in the forward1 Publication direction.
- hexadecanoate + O2 + reduced [NADPH—hemoprotein reductase] = 16-hydroxyhexadecanoate + H+ + H2O + oxidized [NADPH—hemoprotein reductase]1 PublicationEC:1.14.14.801 PublicationThis reaction proceeds in the forward1 Publication direction.
- (9Z)-octadecenoate + O2 + reduced [NADPH—hemoprotein reductase] = 18-hydroxy-(9Z)-octadecenoate + H+ + H2O + oxidized [NADPH—hemoprotein reductase]1 PublicationEC:1.14.14.801 PublicationThis reaction proceeds in the forward1 Publication direction.
- (9Z,12Z)-octadecadienoate + O2 + reduced [NADPH—hemoprotein reductase] = 18-hydroxy-(9Z,12Z)-octadecadienoate + H+ + H2O + oxidized [NADPH—hemoprotein reductase]1 PublicationThis reaction proceeds in the forward1 Publication direction.
- (9Z,12Z)-octadecadienoate + O2 + reduced [NADPH—hemoprotein reductase] = 17-hydroxy-(9Z,12Z)-octadecadienoate + H+ + H2O + oxidized [NADPH—hemoprotein reductase]1 PublicationThis reaction proceeds in the forward1 Publication direction.
- (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH—hemoprotein reductase] = 20-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + H+ + H2O + oxidized [NADPH—hemoprotein reductase]2 PublicationsThis reaction proceeds in the forward1 Publication direction.
- 8,9-epoxy-(5Z,11Z,14Z)-eicosatrienoate + O2 + reduced [NADPH—hemoprotein reductase] = 20-hydroxy-8,9-epoxy-(5Z,11Z,14Z)-eicosatrienoate + H+ + H2O + oxidized [NADPH—hemoprotein reductase]1 PublicationThis reaction proceeds in the forward1 Publication direction.
Cofactori
Kineticsi
- KM=10 µM for (5Z,8Z,11Z,14Z)-eicosatetraenoate1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 320 | Heme; covalent, via 1 link2 Publications | 1 | |
Metal bindingi | 456 | Iron (heme axial ligand)2 Publications | 1 |
GO - Molecular functioni
- 16-hydroxypalmitate dehydrogenase activity Source: RGD
- alkane 1-monooxygenase activity Source: RGD
- arachidonic acid monooxygenase activity Source: RGD
- heme binding Source: InterPro
- iron ion binding Source: InterPro
- laurate hydroxylase activity Source: RGD
- long-chain fatty acid omega-hydroxylase activity Source: UniProtKB-EC
GO - Biological processi
- arachidonic acid metabolic process Source: RGD
- icosanoid biosynthetic process Source: RGD
- kidney development Source: RGD
- lauric acid metabolic process Source: RGD
- linoleic acid metabolic process Source: RGD
- lipid hydroxylation Source: RGD
- placenta development Source: RGD
Keywordsi
Molecular function | Monooxygenase, Oxidoreductase |
Biological process | Fatty acid metabolism, Lipid metabolism |
Ligand | Heme, Iron, Metal-binding, NADP |
Enzyme and pathway databases
BRENDAi | 1.14.14.80, 5301 |
Reactomei | R-RNO-211935, Fatty acids R-RNO-211958, Miscellaneous substrates R-RNO-211979, Eicosanoids R-RNO-2142691, Synthesis of Leukotrienes (LT) and Eoxins (EX) |
Chemistry databases
SwissLipidsi | SLP:000000747 |
Names & Taxonomyi
Protein namesi | Recommended name: Cytochrome P450 4A10Alternative name(s): CYPIVA10 Cytochrome P450-LA-omega 1 Cytochrome P452 Lauric acid omega-hydroxylase Long-chain fatty acid omega-monooxygenase (EC:1.14.14.802 Publications) |
Gene namesi | Name:Cyp4a10 Synonyms:Cyp4a-1, Cyp4a11 Publication |
Organismi | Rattus norvegicus (Rat) |
Taxonomic identifieri | 10116 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
Proteomesi |
|
Organism-specific databases
RGDi | 68945, Cyp4a1 |
Subcellular locationi
Endoplasmic reticulum
- Endoplasmic reticulum membrane 1 Publication; Multi-pass membrane protein Sequence analysis
- Microsome membrane 1 Publication; Multi-pass membrane protein Sequence analysis
Endoplasmic reticulum
- endoplasmic reticulum membrane Source: UniProtKB-SubCell
Extracellular region or secreted
- extracellular space Source: RGD
Other locations
- integral component of membrane Source: UniProtKB-KW
- intracellular membrane-bounded organelle Source: RGD
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transmembranei | 11 – 31 | HelicalSequence analysisAdd BLAST | 21 | |
Transmembranei | 121 – 141 | HelicalSequence analysisAdd BLAST | 21 |
Keywords - Cellular componenti
Endoplasmic reticulum, Membrane, MicrosomePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 320 | E → A: Loss of heme binding. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000051816 | 1 – 509 | Cytochrome P450 4A10Sequence analysisAdd BLAST | 509 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 439 | PhosphoserineBy similarity | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
PaxDbi | P08516 |
PTM databases
iPTMneti | P08516 |
PhosphoSitePlusi | P08516 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSRNOG00000009597, Expressed in liver and 13 other tissues |
ExpressionAtlasi | P08516, baseline and differential |
Genevisiblei | P08516, RN |
Family & Domainsi
Sequence similaritiesi
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG0157, Eukaryota |
GeneTreei | ENSGT00940000163570 |
InParanoidi | P08516 |
OMAi | RHIPSKH |
OrthoDBi | 1247045at2759 |
PhylomeDBi | P08516 |
Family and domain databases
Gene3Di | 1.10.630.10, 1 hit |
InterProi | View protein in InterPro IPR001128, Cyt_P450 IPR017972, Cyt_P450_CS IPR002401, Cyt_P450_E_grp-I IPR036396, Cyt_P450_sf |
Pfami | View protein in Pfam PF00067, p450, 1 hit |
PRINTSi | PR00463, EP450I PR00385, P450 |
SUPFAMi | SSF48264, SSF48264, 1 hit |
PROSITEi | View protein in PROSITE PS00086, CYTOCHROME_P450, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
10 20 30 40 50
MSVSALSSTR FTGSISGFLQ VASVLGLLLL LVKAVQFYLQ RQWLLKAFQQ
60 70 80 90 100
FPSPPFHWFF GHKQFQGDKE LQQIMTCVEN FPSAFPRWFW GSKAYLIVYD
110 120 130 140 150
PDYMKVILGR SDPKANGVYR LLAPWIGYGL LLLNGQPWFQ HRRMLTPAFH
160 170 180 190 200
YDILKPYVKN MADSIRLMLD KWEQLAGQDS SIEIFQHISL MTLDTVMKCA
210 220 230 240 250
FSHNGSVQVD GNYKSYIQAI GNLNDLFHSR VRNIFHQNDT IYNFSSNGHL
260 270 280 290 300
FNRACQLAHD HTDGVIKLRK DQLQNAGELE KVKKKRRLDF LDILLLARME
310 320 330 340 350
NGDSLSDKDL RAEVDTFMFE GHDTTASGVS WIFYALATHP EHQQRCREEV
360 370 380 390 400
QSVLGDGSSI TWDHLDQIPY TTMCIKEALR LYPPVPGIVR ELSTSVTFPD
410 420 430 440 450
GRSLPKGIQV TLSIYGLHHN PKVWPNPEVF DPSRFAPDSP RHSHSFLPFS
460 470 480 490 500
GGARNCIGKQ FAMSEMKVIV ALTLLRFELL PDPTKVPIPL PRLVLKSKNG
IYLYLKKLH
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketD3ZHZ6 | D3ZHZ6_RAT | Cytochrome P450, family 4, subfamil... | Cyp4a1 | 488 | Annotation score: | ||
D3ZJX6 | D3ZJX6_RAT | Cytochrome P450, family 4, subfamil... | Cyp4a1 | 452 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 341 | E → K in AAA41061 (PubMed:3027069).Curated | 1 | |
Sequence conflicti | 341 | E → K in CAA30245 (PubMed:3410047).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M14972 mRNA Translation: AAA41061.1 X07259 mRNA Translation: CAA30245.1 M57718 Genomic DNA Translation: AAA41038.1 BC089761 mRNA Translation: AAH89761.1 |
PIRi | S01336, O4RTLO |
RefSeqi | NP_787031.1, NM_175837.1 XP_006238774.1, XM_006238712.3 |
Genome annotation databases
Ensembli | ENSRNOT00000012888; ENSRNOP00000012888; ENSRNOG00000009597 |
GeneIDi | 50549 |
KEGGi | rno:50549 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M14972 mRNA Translation: AAA41061.1 X07259 mRNA Translation: CAA30245.1 M57718 Genomic DNA Translation: AAA41038.1 BC089761 mRNA Translation: AAH89761.1 |
PIRi | S01336, O4RTLO |
RefSeqi | NP_787031.1, NM_175837.1 XP_006238774.1, XM_006238712.3 |
3D structure databases
SMRi | P08516 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 10116.ENSRNOP00000041025 |
Chemistry databases
SwissLipidsi | SLP:000000747 |
PTM databases
iPTMneti | P08516 |
PhosphoSitePlusi | P08516 |
Proteomic databases
PaxDbi | P08516 |
Genome annotation databases
Ensembli | ENSRNOT00000012888; ENSRNOP00000012888; ENSRNOG00000009597 |
GeneIDi | 50549 |
KEGGi | rno:50549 |
Organism-specific databases
CTDi | 50549 |
RGDi | 68945, Cyp4a1 |
Phylogenomic databases
eggNOGi | KOG0157, Eukaryota |
GeneTreei | ENSGT00940000163570 |
InParanoidi | P08516 |
OMAi | RHIPSKH |
OrthoDBi | 1247045at2759 |
PhylomeDBi | P08516 |
Enzyme and pathway databases
BRENDAi | 1.14.14.80, 5301 |
Reactomei | R-RNO-211935, Fatty acids R-RNO-211958, Miscellaneous substrates R-RNO-211979, Eicosanoids R-RNO-2142691, Synthesis of Leukotrienes (LT) and Eoxins (EX) |
Miscellaneous databases
PROi | PR:P08516 |
Gene expression databases
Bgeei | ENSRNOG00000009597, Expressed in liver and 13 other tissues |
ExpressionAtlasi | P08516, baseline and differential |
Genevisiblei | P08516, RN |
Family and domain databases
Gene3Di | 1.10.630.10, 1 hit |
InterProi | View protein in InterPro IPR001128, Cyt_P450 IPR017972, Cyt_P450_CS IPR002401, Cyt_P450_E_grp-I IPR036396, Cyt_P450_sf |
Pfami | View protein in Pfam PF00067, p450, 1 hit |
PRINTSi | PR00463, EP450I PR00385, P450 |
SUPFAMi | SSF48264, SSF48264, 1 hit |
PROSITEi | View protein in PROSITE PS00086, CYTOCHROME_P450, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | CP4AA_RAT | |
Accessioni | P08516Primary (citable) accession number: P08516 Secondary accession number(s): Q5EBD8 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 1, 1988 |
Last sequence update: | May 1, 2007 | |
Last modified: | February 23, 2022 | |
This is version 182 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencing, Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families