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Q02928

- CP4AB_HUMAN

UniProt

Q02928 - CP4AB_HUMAN

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Protein
Cytochrome P450 4A11
Gene
CYP4A11, CYP4A2
Organism
Homo sapiens (Human)
Status
Reviewed - 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).1 Publication

Catalytic activityi

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

Cofactori

Heme group By similarity.

Sites

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

GO - Molecular functioni

  1. alkane 1-monooxygenase activity Source: BHF-UCL
  2. arachidonic acid epoxygenase activity Source: UniProtKB
  3. arachidonic acid omega-hydroxylase activity Source: UniProtKB-EC
  4. heme binding Source: InterPro
  5. iron ion binding Source: InterPro
  6. leukotriene-B4 20-monooxygenase activity Source: UniProtKB

GO - Biological processi

  1. arachidonic acid metabolic process Source: UniProtKB
  2. cellular lipid metabolic process Source: Reactome
  3. epoxygenase P450 pathway Source: UniProtKB
  4. fatty acid metabolic process Source: ProtInc
  5. leukotriene B4 catabolic process Source: GOC
  6. leukotriene metabolic process Source: UniProtKB
  7. long-chain fatty acid metabolic process Source: BHF-UCL
  8. omega-hydroxylase P450 pathway Source: Reactome
  9. oxidation-reduction process Source: UniProtKB
  10. positive regulation of icosanoid secretion Source: UniProtKB
  11. pressure natriuresis Source: UniProtKB
  12. renal water homeostasis Source: UniProtKB
  13. small molecule metabolic process Source: Reactome
  14. sodium ion homeostasis Source: UniProtKB
  15. xenobiotic metabolic process Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Monooxygenase, Oxidoreductase

Keywords - Ligandi

Heme, Iron, Metal-binding

Enzyme and pathway databases

ReactomeiREACT_116145. PPARA activates gene expression.
REACT_13425. Miscellaneous substrates.
REACT_13645. Eicosanoids.
REACT_13814. Fatty acids.
REACT_150134. Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE).
REACT_150420. Synthesis of Leukotrienes (LT) and Eoxins (EX).

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 (EC:1.14.15.3)
Gene namesi
Name:CYP4A11
Synonyms:CYP4A2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 1

Organism-specific databases

HGNCiHGNC:2642. CYP4A11.

Subcellular locationi

GO - Cellular componenti

  1. apical plasma membrane Source: UniProtKB
  2. cytoplasm Source: UniProtKB
  3. endoplasmic reticulum membrane Source: Reactome
  4. extracellular vesicular exosome Source: UniProt
  5. 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.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Propeptidei1 – 44
PRO_0000003579
Chaini5 – 519515Cytochrome P450 4A11
PRO_0000003580Add
BLAST

Proteomic databases

PaxDbiQ02928.
PRIDEiQ02928.

PTM databases

PhosphoSiteiQ02928.

Expressioni

Tissue specificityi

Kidney and liver.

Gene expression databases

ArrayExpressiQ02928.
BgeeiQ02928.
CleanExiHS_CYP4A11.
GenevestigatoriQ02928.

Interactioni

Protein-protein interaction databases

BioGridi107951. 3 interactions.
IntActiQ02928. 1 interaction.
STRINGi9606.ENSP00000311095.

Structurei

3D structure databases

ProteinModelPortaliQ02928.
SMRiQ02928. Positions 48-510.

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.

Phylogenomic databases

eggNOGiCOG2124.
HOVERGENiHBG000182.
KOiK17687.
OrthoDBiEOG7CNZFK.
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. Align

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

MSVSVLSPSR LLGDVSGILQ AASLLILLLL LIKAVQLYLH RQWLLKALQQ    50
FPCPPSHWLF GHIQELQQDQ ELQRIQKWVE TFPSACPHWL WGGKVRVQLY 100
DPDYMKVILG RSDPKSHGSY RFLAPWIGYG LLLLNGQTWF QHRRMLTPAF 150
HYDILKPYVG LMADSVRVML DKWEELLGQD SPLEVFQHVS LMTLDTIMKC 200
AFSHQGSIQV DRNSQSYIQA ISDLNNLVFS RVRNAFHQND TIYSLTSAGR 250
WTHRACQLAH QHTDQVIQLR KAQLQKEGEL EKIKRKRHLD FLDILLLAKM 300
ENGSILSDKD LRAEVDTFMF EGHDTTASGI SWILYALATH PKHQERCREE 350
IHSLLGDGAS ITWNHLDQMP YTTMCIKEAL RLYPPVPGIG RELSTPVTFP 400
DGRSLPKGIM VLLSIYGLHH NPKVWPNPEV FDPFRFAPGS AQHSHAFLPF 450
SGGSRNCIGK QFAMNELKVA TALTLLRFEL LPDPTRIPIP IARLVLKSKN 500
GIHLRLRRLP NPCEDKDQL 519
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

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.
VSP_034595Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti5 – 51V → A AA sequence 1 Publication
Sequence conflicti383 – 3831Y → F in AAO16078. 1 Publication
Sequence conflicti390 – 3901G → S in CAA50586. 1 Publication
Sequence conflicti410 – 4123MVL → TVM in CAA50586. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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]
UniGeneiHs.1645.
Hs.726474.

Genome annotation databases

EnsembliENST00000310638; ENSP00000311095; ENSG00000187048. [Q02928-1]
ENST00000371905; ENSP00000360972; ENSG00000187048.
GeneIDi1579.
KEGGihsa:1579.
UCSCiuc001cqp.4. human. [Q02928-1]

Polymorphism databases

DMDMi2493371.

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:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS543.1. [Q02928-1 ]
PIRi A56859.
I53015.
I65981.
JX0331.
RefSeqi NP_000769.2. NM_000778.3. [Q02928-1 ]
UniGenei Hs.1645.
Hs.726474.

3D structure databases

ProteinModelPortali Q02928.
SMRi Q02928. Positions 48-510.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 107951. 3 interactions.
IntActi Q02928. 1 interaction.
STRINGi 9606.ENSP00000311095.

Chemistry

BindingDBi Q02928.
DrugBanki DB00157. NADH.

PTM databases

PhosphoSitei Q02928.

Polymorphism databases

DMDMi 2493371.

Proteomic databases

PaxDbi Q02928.
PRIDEi Q02928.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000310638 ; ENSP00000311095 ; ENSG00000187048 . [Q02928-1 ]
ENST00000371905 ; ENSP00000360972 ; ENSG00000187048 .
GeneIDi 1579.
KEGGi hsa:1579.
UCSCi uc001cqp.4. human. [Q02928-1 ]

Organism-specific databases

CTDi 1579.
GeneCardsi GC01M047394.
HGNCi HGNC:2642. CYP4A11.
MIMi 601310. gene.
neXtProti NX_Q02928.
PharmGKBi PA27118.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG2124.
HOVERGENi HBG000182.
KOi K17687.
OrthoDBi EOG7CNZFK.
PhylomeDBi Q02928.
TreeFami TF105088.

Enzyme and pathway databases

Reactomei REACT_116145. PPARA activates gene expression.
REACT_13425. Miscellaneous substrates.
REACT_13645. Eicosanoids.
REACT_13814. Fatty acids.
REACT_150134. Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE).
REACT_150420. Synthesis of Leukotrienes (LT) and Eoxins (EX).

Miscellaneous databases

ChiTaRSi CYP4A11. human.
GeneWikii CYP4A11.
GenomeRNAii 1579.
NextBioi 6485.
PROi Q02928.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q02928.
Bgeei Q02928.
CleanExi HS_CYP4A11.
Genevestigatori Q02928.

Family and domain databases

Gene3Di 1.10.630.10. 1 hit.
InterProi IPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR002401. Cyt_P450_E_grp-I.
[Graphical view ]
Pfami PF00067. p450. 1 hit.
[Graphical view ]
PRINTSi PR00463. EP450I.
PR00385. P450.
SUPFAMi SSF48264. SSF48264. 1 hit.
PROSITEi PS00086. CYTOCHROME_P450. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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.
    , 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. Cited for: VARIANTS GLY-353 AND SER-434.

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 3, 2014
This is version 137 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

External Data

Dasty 3

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