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Protein

Cytochrome P450 4A11

Gene

CYP4A11

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the omega- and (omega-1)-hydroxylation of various fatty acids such as laurate, myristate and palmitate. Has little activity toward prostaglandins A1 and E1. Oxidizes arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE).3 Publications

Catalytic activityi

A long-chain fatty acid + NADPH + O2 = an omega-hydroxy-long-chain fatty acid + NADP+ + H2O.2 Publications

Cofactori

heme1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei321 – 3211Heme (covalent; via 1 link)1 Publication
Metal bindingi457 – 4571Iron (heme axial ligand)1 Publication

GO - Molecular functioni

  • alkane 1-monooxygenase activity Source: BHF-UCL
  • arachidonic acid epoxygenase activity Source: UniProtKB
  • heme binding Source: InterPro
  • iron ion binding Source: InterPro
  • leukotriene-B4 20-monooxygenase activity Source: UniProtKB
  • monooxygenase activity Source: Reactome
  • oxygen binding Source: Reactome

GO - Biological processi

  • arachidonic acid metabolic process Source: UniProtKB
  • epoxygenase P450 pathway Source: UniProtKB
  • fatty acid metabolic process Source: Reactome
  • leukotriene metabolic process Source: UniProtKB
  • long-chain fatty acid metabolic process Source: BHF-UCL
  • omega-hydroxylase P450 pathway Source: Reactome
  • oxidation-reduction process Source: UniProtKB
  • positive regulation of icosanoid secretion Source: UniProtKB
  • pressure natriuresis Source: UniProtKB
  • renal water homeostasis Source: UniProtKB
  • sodium ion homeostasis Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Monooxygenase, Oxidoreductase

Keywords - Ligandi

Heme, Iron, Metal-binding, NADP

Enzyme and pathway databases

ReactomeiR-HSA-1989781. PPARA activates gene expression.
R-HSA-211935. Fatty acids.
R-HSA-211958. Miscellaneous substrates.
R-HSA-211979. Eicosanoids.
R-HSA-2142691. Synthesis of Leukotrienes (LT) and Eoxins (EX).
R-HSA-2142816. Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE).

Chemistry

SwissLipidsiSLP:000000398.

Names & Taxonomyi

Protein namesi
Recommended name:
Cytochrome P450 4A11
Alternative name(s):
20-hydroxyeicosatetraenoic acid synthase
Short name:
20-HETE synthase
CYP4AII
CYPIVA11
Cytochrome P-450HK-omega
Cytochrome P450HL-omega
Fatty acid omega-hydroxylase
Lauric acid omega-hydroxylase
Long-chain fatty acid omega-monooxygenase (EC:1.14.13.2052 Publications)
Gene namesi
Name:CYP4A11
Synonyms:CYP4A2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:2642. CYP4A11.

Subcellular locationi

GO - Cellular componenti

  • apical plasma membrane Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • endoplasmic reticulum membrane Source: Reactome
  • extracellular exosome Source: UniProtKB
  • intracellular membrane-bounded organelle Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi130 – 1301G → S: Loss of activity. 1 Publication
Mutagenesisi321 – 3211E → A: Loss of covalent heme binding. 1 Publication

Organism-specific databases

PharmGKBiPA27118.

Chemistry

ChEMBLiCHEMBL3978.
DrugBankiDB00515. Cisplatin.
DB00636. Clofibrate.
DB01234. Dexamethasone.
DB00655. Estrone.
DB00898. Ethanol.
DB00448. Lansoprazole.
DB00082. Pegvisomant.
DB00738. Pentamidine.
DB01174. Phenobarbital.
DB01045. Rifampicin.
DB00755. Tretinoin.

Polymorphism and mutation databases

BioMutaiCYP4A11.
DMDMi2493371.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Propeptidei2 – 432 PublicationsPRO_0000003579
Chaini5 – 519515Cytochrome P450 4A11PRO_0000003580Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei440 – 4401PhosphoserineBy similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ02928.
PeptideAtlasiQ02928.
PRIDEiQ02928.

PTM databases

iPTMnetiQ02928.
PhosphoSiteiQ02928.

Expressioni

Tissue specificityi

Kidney and liver.1 Publication

Gene expression databases

BgeeiENSG00000187048.
CleanExiHS_CYP4A11.
ExpressionAtlasiQ02928. baseline and differential.
GenevisibleiQ02928. HS.

Interactioni

Protein-protein interaction databases

BioGridi107951. 4 interactions.
IntActiQ02928. 1 interaction.
STRINGi9606.ENSP00000311095.

Structurei

3D structure databases

ProteinModelPortaliQ02928.
SMRiQ02928. Positions 48-510.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi24 – 318Poly-Leu
Compositional biasi131 – 1344Poly-Leu

Sequence similaritiesi

Belongs to the cytochrome P450 family.Curated

Phylogenomic databases

eggNOGiKOG0157. Eukaryota.
COG2124. LUCA.
GeneTreeiENSGT00760000118816.
HOVERGENiHBG000182.
InParanoidiQ02928.
KOiK17687.
PhylomeDBiQ02928.
TreeFamiTF105088.

Family and domain databases

Gene3Di1.10.630.10. 1 hit.
InterProiIPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR002401. Cyt_P450_E_grp-I.
[Graphical view]
PfamiPF00067. p450. 1 hit.
[Graphical view]
PRINTSiPR00463. EP450I.
PR00385. P450.
SUPFAMiSSF48264. SSF48264. 1 hit.
PROSITEiPS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q02928-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MSVSVLSPSR LLGDVSGILQ AASLLILLLL LIKAVQLYLH RQWLLKALQQ
60 70 80 90 100
FPCPPSHWLF GHIQELQQDQ ELQRIQKWVE TFPSACPHWL WGGKVRVQLY
110 120 130 140 150
DPDYMKVILG RSDPKSHGSY RFLAPWIGYG LLLLNGQTWF QHRRMLTPAF
160 170 180 190 200
HYDILKPYVG LMADSVRVML DKWEELLGQD SPLEVFQHVS LMTLDTIMKC
210 220 230 240 250
AFSHQGSIQV DRNSQSYIQA ISDLNNLVFS RVRNAFHQND TIYSLTSAGR
260 270 280 290 300
WTHRACQLAH QHTDQVIQLR KAQLQKEGEL EKIKRKRHLD FLDILLLAKM
310 320 330 340 350
ENGSILSDKD LRAEVDTFMF EGHDTTASGI SWILYALATH PKHQERCREE
360 370 380 390 400
IHSLLGDGAS ITWNHLDQMP YTTMCIKEAL RLYPPVPGIG RELSTPVTFP
410 420 430 440 450
DGRSLPKGIM VLLSIYGLHH NPKVWPNPEV FDPFRFAPGS AQHSHAFLPF
460 470 480 490 500
SGGSRNCIGK QFAMNELKVA TALTLLRFEL LPDPTRIPIP IARLVLKSKN
510
GIHLRLRRLP NPCEDKDQL
Length:519
Mass (Da):59,348
Last modified:November 1, 1997 - v1
Checksum:iA8D3073EEFF48AE9
GO
Isoform 2 (identifier: Q02928-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     356-519: Missing.

Show »
Length:355
Mass (Da):41,052
Checksum:iA108E4661ACF9824
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti5 – 51V → A AA sequence (PubMed:1739747).Curated
Sequence conflicti383 – 3831Y → F in AAO16078 (PubMed:12464262).Curated
Sequence conflicti390 – 3901G → S in CAA50586 (PubMed:8363569).Curated
Sequence conflicti410 – 4123MVL → TVM in CAA50586 (PubMed:8363569).Curated

Polymorphismi

CYP4A11v seems to be a rare allelic variant of CYP4A11, it seems to be unstable and not to metabolize lauric acid.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti226 – 2261N → S.
Corresponds to variant rs12759923 [ dbSNP | Ensembl ].
VAR_048452
Natural varianti353 – 3531S → G.2 Publications
VAR_044377
Natural varianti434 – 4341F → S Associated with hypertension; significantly reduced arachidonic acid and lauric acid metabolizing activity. 5 Publications
Corresponds to variant rs1126742 [ dbSNP | Ensembl ].
VAR_019160
Natural varianti500 – 51920NGIHL…DKDQL → MESTCVSGGSLTLVKTRTSF EGLHLPSCLPDPRFCPLPVC PYPVFCLPTFPSSHLPAVPQ SACPSLSHLSPGLPTCLSTC LLPTCISCWEKS in CYP4A11V.
VAR_001257Add
BLAST

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei356 – 519164Missing in isoform 2. 1 PublicationVSP_034595Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L04751 mRNA. Translation: AAA58436.1.
D26481 mRNA. Translation: BAA05491.1.
S67580 mRNA. Translation: AAB29502.1.
S67581 mRNA. Translation: AAB29503.1.
AF525488 Genomic DNA. Translation: AAO16078.1.
AY369778 Genomic DNA. Translation: AAQ56847.1.
AL731892 Genomic DNA. Translation: CAH72778.1.
AL731892 Genomic DNA. Translation: CAH72779.1.
BC041158 mRNA. Translation: AAH41158.1.
X71480 mRNA. Translation: CAA50586.1.
CCDSiCCDS543.1. [Q02928-1]
PIRiA56859.
I53015.
I65981.
JX0331.
RefSeqiNP_000769.2. NM_000778.3. [Q02928-1]
NP_001306084.1. NM_001319155.1.
UniGeneiHs.1645.
Hs.726474.

Genome annotation databases

EnsembliENST00000310638; ENSP00000311095; ENSG00000187048. [Q02928-1]
GeneIDi1579.
KEGGihsa:1579.
UCSCiuc001cqp.5. human. [Q02928-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Cytochrome P450 Allele Nomenclature Committee

CYP4A11 alleles

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L04751 mRNA. Translation: AAA58436.1.
D26481 mRNA. Translation: BAA05491.1.
S67580 mRNA. Translation: AAB29502.1.
S67581 mRNA. Translation: AAB29503.1.
AF525488 Genomic DNA. Translation: AAO16078.1.
AY369778 Genomic DNA. Translation: AAQ56847.1.
AL731892 Genomic DNA. Translation: CAH72778.1.
AL731892 Genomic DNA. Translation: CAH72779.1.
BC041158 mRNA. Translation: AAH41158.1.
X71480 mRNA. Translation: CAA50586.1.
CCDSiCCDS543.1. [Q02928-1]
PIRiA56859.
I53015.
I65981.
JX0331.
RefSeqiNP_000769.2. NM_000778.3. [Q02928-1]
NP_001306084.1. NM_001319155.1.
UniGeneiHs.1645.
Hs.726474.

3D structure databases

ProteinModelPortaliQ02928.
SMRiQ02928. Positions 48-510.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107951. 4 interactions.
IntActiQ02928. 1 interaction.
STRINGi9606.ENSP00000311095.

Chemistry

ChEMBLiCHEMBL3978.
DrugBankiDB00515. Cisplatin.
DB00636. Clofibrate.
DB01234. Dexamethasone.
DB00655. Estrone.
DB00898. Ethanol.
DB00448. Lansoprazole.
DB00082. Pegvisomant.
DB00738. Pentamidine.
DB01174. Phenobarbital.
DB01045. Rifampicin.
DB00755. Tretinoin.
SwissLipidsiSLP:000000398.

PTM databases

iPTMnetiQ02928.
PhosphoSiteiQ02928.

Polymorphism and mutation databases

BioMutaiCYP4A11.
DMDMi2493371.

Proteomic databases

PaxDbiQ02928.
PeptideAtlasiQ02928.
PRIDEiQ02928.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000310638; ENSP00000311095; ENSG00000187048. [Q02928-1]
GeneIDi1579.
KEGGihsa:1579.
UCSCiuc001cqp.5. human. [Q02928-1]

Organism-specific databases

CTDi1579.
GeneCardsiCYP4A11.
HGNCiHGNC:2642. CYP4A11.
MIMi601310. gene.
neXtProtiNX_Q02928.
PharmGKBiPA27118.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0157. Eukaryota.
COG2124. LUCA.
GeneTreeiENSGT00760000118816.
HOVERGENiHBG000182.
InParanoidiQ02928.
KOiK17687.
PhylomeDBiQ02928.
TreeFamiTF105088.

Enzyme and pathway databases

ReactomeiR-HSA-1989781. PPARA activates gene expression.
R-HSA-211935. Fatty acids.
R-HSA-211958. Miscellaneous substrates.
R-HSA-211979. Eicosanoids.
R-HSA-2142691. Synthesis of Leukotrienes (LT) and Eoxins (EX).
R-HSA-2142816. Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE).

Miscellaneous databases

ChiTaRSiCYP4A11. human.
GeneWikiiCYP4A11.
GenomeRNAii1579.
PROiQ02928.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000187048.
CleanExiHS_CYP4A11.
ExpressionAtlasiQ02928. baseline and differential.
GenevisibleiQ02928. HS.

Family and domain databases

Gene3Di1.10.630.10. 1 hit.
InterProiIPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR002401. Cyt_P450_E_grp-I.
[Graphical view]
PfamiPF00067. p450. 1 hit.
[Graphical view]
PRINTSiPR00463. EP450I.
PR00385. P450.
SUPFAMiSSF48264. SSF48264. 1 hit.
PROSITEiPS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCP4AB_HUMAN
AccessioniPrimary (citable) accession number: Q02928
Secondary accession number(s): Q06766
, Q16865, Q16866, Q5VSP8, Q86SU6, Q8IWY5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: September 7, 2016
This is version 156 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.