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Q02928 (CP4AB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 133. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
EC=1.14.15.3
Gene names
Name:CYP4A11
Synonyms:CYP4A2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length519 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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). Ref.12

Catalytic activity

Octane + reduced rubredoxin + O2 = 1-octanol + oxidized rubredoxin + H2O.

Cofactor

Heme group By similarity.

Subcellular location

Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral membrane protein.

Tissue specificity

Kidney and liver.

Polymorphism

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

Sequence similarities

Belongs to the cytochrome P450 family.

Ontologies

Keywords
   Cellular componentEndoplasmic reticulum
Membrane
Microsome
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandHeme
Iron
Metal-binding
   Molecular functionMonooxygenase
Oxidoreductase
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processarachidonic acid metabolic process

Inferred from direct assay PubMed 10660572. Source: UniProtKB

cellular lipid metabolic process

Traceable author statement. Source: Reactome

epoxygenase P450 pathway

Inferred from direct assay PubMed 9618440. Source: UniProtKB

fatty acid metabolic process

Traceable author statement Ref.1. Source: ProtInc

leukotriene B4 catabolic process

Inferred from direct assay PubMed 9799565. Source: GOC

leukotriene metabolic process

Inferred from direct assay PubMed 9799565. Source: UniProtKB

long-chain fatty acid metabolic process

Inferred from direct assay PubMed 18433732. Source: BHF-UCL

omega-hydroxylase P450 pathway

Traceable author statement. Source: Reactome

oxidation-reduction process

Inferred from direct assay PubMed 9618440PubMed 9799565. Source: UniProtKB

positive regulation of icosanoid secretion

Inferred from mutant phenotype PubMed 18391101. Source: UniProtKB

pressure natriuresis

Inferred from expression pattern PubMed 10660572. Source: UniProtKB

renal water homeostasis

Inferred from expression pattern PubMed 10660572. Source: UniProtKB

small molecule metabolic process

Traceable author statement. Source: Reactome

sodium ion homeostasis

Inferred from expression pattern PubMed 10660572. Source: UniProtKB

xenobiotic metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentapical plasma membrane

Inferred from direct assay PubMed 10660572. Source: UniProtKB

cytoplasm

Inferred from direct assay PubMed 10660572. Source: UniProtKB

endoplasmic reticulum membrane

Traceable author statement. Source: Reactome

intracellular membrane-bounded organelle

Inferred from direct assay PubMed 10660572PubMed 9618440PubMed 9799565. Source: UniProtKB

   Molecular_functionalkane 1-monooxygenase activity

Inferred from direct assay PubMed 18433732. Source: BHF-UCL

arachidonic acid epoxygenase activity

Inferred from direct assay PubMed 9618440. Source: UniProtKB

arachidonic acid omega-hydroxylase activity

Inferred from electronic annotation. Source: UniProtKB-EC

heme binding

Inferred from electronic annotation. Source: InterPro

iron ion binding

Inferred from electronic annotation. Source: InterPro

leukotriene-B4 20-monooxygenase activity

Inferred from direct assay PubMed 9799565. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: 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.
Isoform 2 (identifier: Q02928-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Propeptide1 – 44
PRO_0000003579
Chain5 – 519515Cytochrome P450 4A11
PRO_0000003580

Regions

Compositional bias24 – 318Poly-Leu
Compositional bias131 – 1344Poly-Leu

Sites

Metal binding4571Iron (heme axial ligand)
Binding site3211Heme (covalent; via 1 link)

Natural variations

Alternative sequence356 – 519164Missing in isoform 2.
VSP_034595
Natural variant2261N → S.
Corresponds to variant rs12759923 [ dbSNP | Ensembl ].
VAR_048452
Natural variant3531S → G. Ref.9 Ref.13
VAR_044377
Natural variant4341F → S Associated with hypertension; significantly reduced arachidonic acid and lauric acid metabolizing activity. Ref.3 Ref.5 Ref.9 Ref.12 Ref.13
Corresponds to variant rs1126742 [ dbSNP | Ensembl ].
VAR_019160
Natural variant500 – 51920NGIHL…DKDQL → MESTCVSGGSLTLVKTRTSF EGLHLPSCLPDPRFCPLPVC PYPVFCLPTFPSSHLPAVPQ SACPSLSHLSPGLPTCLSTC LLPTCISCWEKS in CYP4A11V.
VAR_001257

Experimental info

Mutagenesis1301G → S: Loss of activity. Ref.12
Mutagenesis3211E → A: Loss of covalent heme binding. Ref.11
Sequence conflict51V → A AA sequence Ref.8
Sequence conflict3831Y → F in AAO16078. Ref.4
Sequence conflict3901G → S in CAA50586. Ref.9
Sequence conflict410 – 4123MVL → TVM in CAA50586. Ref.9

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1997. Version 1.
Checksum: A8D3073EEFF48AE9

FASTA51959,348
        10         20         30         40         50         60 
MSVSVLSPSR LLGDVSGILQ AASLLILLLL LIKAVQLYLH RQWLLKALQQ FPCPPSHWLF 

        70         80         90        100        110        120 
GHIQELQQDQ ELQRIQKWVE TFPSACPHWL WGGKVRVQLY DPDYMKVILG RSDPKSHGSY 

       130        140        150        160        170        180 
RFLAPWIGYG LLLLNGQTWF QHRRMLTPAF HYDILKPYVG LMADSVRVML DKWEELLGQD 

       190        200        210        220        230        240 
SPLEVFQHVS LMTLDTIMKC AFSHQGSIQV DRNSQSYIQA ISDLNNLVFS RVRNAFHQND 

       250        260        270        280        290        300 
TIYSLTSAGR WTHRACQLAH QHTDQVIQLR KAQLQKEGEL EKIKRKRHLD FLDILLLAKM 

       310        320        330        340        350        360 
ENGSILSDKD LRAEVDTFMF EGHDTTASGI SWILYALATH PKHQERCREE IHSLLGDGAS 

       370        380        390        400        410        420 
ITWNHLDQMP YTTMCIKEAL RLYPPVPGIG RELSTPVTFP DGRSLPKGIM VLLSIYGLHH 

       430        440        450        460        470        480 
NPKVWPNPEV FDPFRFAPGS AQHSHAFLPF SGGSRNCIGK QFAMNELKVA TALTLLRFEL 

       490        500        510 
LPDPTRIPIP IARLVLKSKN GIHLRLRRLP NPCEDKDQL 

« Hide

Isoform 2 [UniParc].

Checksum: A108E4661ACF9824
Show »

FASTA35541,052

References

« Hide 'large scale' references
[1]"Characterization of a cDNA encoding a human kidney, cytochrome P-450 4A fatty acid omega-hydroxylase and the cognate enzyme expressed in Escherichia coli."
Palmer C.N.A., Richardson T.H., Griffin K.J., Hsu M.-H., Muerhoff A.S., Clark J.E., Johnson E.F.
Biochim. Biophys. Acta 1172:161-166(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION.
Tissue: Kidney.
[2]"Purification and cDNA cloning of human liver CYP4A fatty acid omega-hydroxylase."
Kawashima H., Kusunose E., Kikuta Y., Kinoshita H., Tanaka S., Yamamoto S., Kishimoto T., Kusunose M.
J. Biochem. 116:74-80(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 5-24, CHARACTERIZATION.
Tissue: Liver.
[3]"Complete cDNA sequence and cDNA-directed expression of CYP4A11, a fatty acid omega-hydroxylase expressed in human kidney."
Imaoka S., Ogawa H., Kimura S., Gonzalez F.J.
DNA Cell Biol. 12:893-899(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT SER-434, CHARACTERIZATION.
Tissue: Kidney.
[4]"Characterization of the CYP4A11 gene, a second CYP4A gene in humans."
Bellamine A., Wang Y., Waterman M.R., Gainer J.V. III, Dawson E.P., Brown N.J., Capdevila J.H.
Arch. Biochem. Biophys. 409:221-227(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[5]SeattleSNPs variation discovery resource
Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), VARIANT SER-434.
[6]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Colon.
[8]"Purification and NH2-terminal amino acid sequences of human and rat kidney fatty acid omega-hydroxylases."
Kawashima H., Kusunose E., Kubota I., Maekawa M., Kusunose M.
Biochim. Biophys. Acta 1123:156-162(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 5-39, CHARACTERIZATION.
Tissue: Kidney.
[9]"Species-specific induction of cytochrome P-450 4A RNAs: PCR cloning of partial guinea-pig, human and mouse CYP4A cDNAs."
Bell D.R., Plant N.J., Rider C.G., Na L., Brown S., Ateitalla I., Acharya S.K., Davies M.H., Elias E.E., Jenkins N.A., Gilbert D.J., Copeland N.G., Elcombe C.R.
Biochem. J. 294:173-180(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 317-457, VARIANTS GLY-353 AND SER-434.
Tissue: Liver.
[10]"Covalently linked heme in cytochrome P4504A fatty acid hydroxylases."
Hoch U., Ortiz de Montellano P.R.
J. Biol. Chem. 276:11339-11346(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: COVALENT HEME ATTACHMENT.
[11]"Autocatalytic mechanism and consequences of covalent heme attachment in the cytochrome P4504A family."
LeBrun L.A., Hoch U., Ortiz de Montellano P.R.
J. Biol. Chem. 277:12755-12761(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: COVALENT HEME ATTACHMENT, MUTAGENESIS OF GLU-321.
[12]"Functional variant of CYP4A11 20-hydroxyeicosatetraenoic acid synthase is associated with essential hypertension."
Gainer J.V., Bellamine A., Dawson E.P., Womble K.E., Grant S.W., Wang Y., Cupples L.A., Guo C.-Y., Demissie S., O'Donnell C.J., Brown N.J., Waterman M.R., Capdevila J.H.
Circulation 111:63-69(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF GLY-130, VARIANT SER-434.
[13]"Highly polymorphic human CYP4A11 gene."
Cho B.H., Park B.L., Kim L.H., Chung H.S., Shin H.D.
J. Hum. Genet. 50:259-263(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GLY-353 AND SER-434.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRA56859.
I53015.
I65981.
JX0331.
RefSeqNP_000769.2. NM_000778.3.
UniGeneHs.1645.
Hs.726474.

3D structure databases

ProteinModelPortalQ02928.
SMRQ02928. Positions 48-505.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107951. 3 interactions.
IntActQ02928. 1 interaction.
STRING9606.ENSP00000311095.

Chemistry

BindingDBQ02928.
DrugBankDB00157. NADH.

PTM databases

PhosphoSiteQ02928.

Polymorphism databases

DMDM2493371.

Proteomic databases

PaxDbQ02928.
PRIDEQ02928.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000310638; ENSP00000311095; ENSG00000187048. [Q02928-1]
ENST00000371905; ENSP00000360972; ENSG00000187048.
GeneID1579.
KEGGhsa:1579.
UCSCuc001cqp.4. human. [Q02928-1]

Organism-specific databases

CTD1579.
GeneCardsGC01M047394.
HGNCHGNC:2642. CYP4A11.
MIM601310. gene.
neXtProtNX_Q02928.
PharmGKBPA27118.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2124.
HOVERGENHBG000182.
KOK17687.
OrthoDBEOG7CNZFK.
PhylomeDBQ02928.
TreeFamTF105088.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressQ02928.
BgeeQ02928.
CleanExHS_CYP4A11.
GenevestigatorQ02928.

Family and domain databases

Gene3D1.10.630.10. 1 hit.
InterProIPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR002401. Cyt_P450_E_grp-I.
[Graphical view]
PfamPF00067. p450. 1 hit.
[Graphical view]
PRINTSPR00463. EP450I.
PR00385. P450.
SUPFAMSSF48264. SSF48264. 1 hit.
PROSITEPS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCYP4A11. human.
GeneWikiCYP4A11.
GenomeRNAi1579.
NextBio6485.
PROQ02928.
SOURCESearch...

Entry information

Entry nameCP4AB_HUMAN
AccessionPrimary (citable) accession number: Q02928
Secondary accession number(s): Q06766 expand/collapse secondary AC list , Q16865, Q16866, Q5VSP8, Q86SU6, Q8IWY5
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: April 16, 2014
This is version 133 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM