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Protein

Docosahexaenoic acid omega-hydroxylase CYP4F3

Gene

CYP4F3

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

Functioni

Isoform CYP4F3A: Catalyzes the omega-hydroxylation of leukotriene-B4, a potent chemoattractant for polymorphonuclear leukocytes, it has low activity for arachidonic acid.2 Publications
Isoform CYP4F3B: Shows arachidonic acid omega-hydroxylase activity by mediating conversion of arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE) (PubMed:11461919, PubMed:16820285). Has a 30-fold higher Km for leukotriene-B4 compared with CYP4F3A (PubMed:11461919). Also converts eicosapentaenoate (EPA) to 20-hydroxyeicosapentaenoate (20-OH-EPA) (PubMed:16820285). Acts as a polyunsaturated omega-3 fatty acids hydroxylase: mediates conversion of docosahexaenoate (DHA) to 22-hydroxydocosahexaenoate (PubMed:16820285).3 Publications

Catalytic activityi

Docosahexaenoate + NADPH + O2 = 22-hydroxydocosahexaenoate + NADP+ + H2O.1 Publication
(5Z,8Z,11Z,14Z)-icosatetraenoate + NADPH + O2 = (5Z,8Z,11Z,14Z)-20-hydroxyicosa-5,8,11,14-tetraenoate + NADP+ + H2O.2 Publications
(6Z,8E,10E,14Z)-(5S,12R)-5,12-dihydroxyicosa-6,8,10,14-tetraenoate + NADPH + O2 = (6Z,8E,10E,14Z)-(5S,12R)-5,12,20-trihydroxyicosa-6,8,10,14-tetraenoate + NADP+ + H2O.1 Publication

Cofactori

hemeBy similarity

Enzyme regulationi

Inhibited by carbon monoxide (CO).

Pathwayi: leukotriene B4 degradation

This protein is involved in the pathway leukotriene B4 degradation, which is part of Lipid metabolism.
View all proteins of this organism that are known to be involved in the pathway leukotriene B4 degradation and in Lipid metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei328Heme (covalent; via 1 link)By similarity1
Metal bindingi468Iron (heme axial ligand)By similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionMonooxygenase, Oxidoreductase
Biological processLipid metabolism
LigandHeme, Iron, Metal-binding, NADP

Enzyme and pathway databases

ReactomeiR-HSA-211935 Fatty acids
R-HSA-211958 Miscellaneous substrates
R-HSA-211979 Eicosanoids
R-HSA-2142691 Synthesis of Leukotrienes (LT) and Eoxins (EX)
SABIO-RKiQ08477
UniPathwayiUPA00883

Chemistry databases

SwissLipidsiSLP:000000422 [Q08477-1]
SLP:000000423 [Q08477-2]

Names & Taxonomyi

Protein namesi
Recommended name:
Docosahexaenoic acid omega-hydroxylase CYP4F3Curated (EC:1.14.13.1991 Publication)
Alternative name(s):
20-hydroxyeicosatetraenoic acid synthase1 Publication (EC:1.14.13.-2 Publications)
Short name:
20-HETE synthase1 Publication
CYPIVF3
Cytochrome P450 4F3
Cytochrome P450-LTB-omega
Leukotriene-B(4) 20-monooxygenase 2
Leukotriene-B(4) omega-hydroxylase 2 (EC:1.14.13.301 Publication)
Gene namesi
Name:CYP4F3
Synonyms:LTB4H
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000186529.14
HGNCiHGNC:2646 CYP4F3
MIMi601270 gene
neXtProtiNX_Q08477

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei11 – 31HelicalSequence analysisAdd BLAST21

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

Pathology & Biotechi

Organism-specific databases

DisGeNETi4051
OpenTargetsiENSG00000186529
PharmGKBiPA234

Chemistry databases

ChEMBLiCHEMBL3508692

Polymorphism and mutation databases

BioMutaiCYP4F3
DMDMi56757430

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000518511 – 520Docosahexaenoic acid omega-hydroxylase CYP4F3Add BLAST520

Proteomic databases

MaxQBiQ08477
PaxDbiQ08477
PeptideAtlasiQ08477
PRIDEiQ08477
ProteomicsDBi58614

PTM databases

iPTMnetiQ08477
PhosphoSitePlusiQ08477

Expressioni

Tissue specificityi

Isoform CYP4F3A is expressed in the polymorphonuclear leukocytes as well as leukocytes and bone marrow. Isoform CYP4F3B is selectively expressed in liver and kidney and is also the predominant CYP4F isoform in trachea and tissues of the gastrointestinal tract.1 Publication

Gene expression databases

BgeeiENSG00000186529
CleanExiHS_CYP4F3
ExpressionAtlasiQ08477 baseline and differential
GenevisibleiQ08477 HS

Organism-specific databases

HPAiHPA058960

Interactioni

Protein-protein interaction databases

IntActiQ08477, 2 interactors
STRINGi9606.ENSP00000221307

Structurei

3D structure databases

ProteinModelPortaliQ08477
SMRiQ08477
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the cytochrome P450 family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0157 Eukaryota
COG2124 LUCA
GeneTreeiENSGT00900000140829
HOGENOMiHOG000233833
HOVERGENiHBG000182
InParanoidiQ08477
KOiK17726
OMAiYEKPWQS
PhylomeDBiQ08477
TreeFamiTF105088

Family and domain databases

Gene3Di1.10.630.10, 1 hit
InterProiView protein in InterPro
IPR001128 Cyt_P450
IPR017972 Cyt_P450_CS
IPR002401 Cyt_P450_E_grp-I
IPR036396 Cyt_P450_sf
PfamiView protein in Pfam
PF00067 p450, 1 hit
PRINTSiPR00463 EP450I
PR00385 P450
SUPFAMiSSF48264 SSF48264, 1 hit
PROSITEiView protein in PROSITE
PS00086 CYTOCHROME_P450, 1 hit

Sequences (2)i

Sequence statusi: Complete.

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

Isoform CYP4F3A (identifier: Q08477-1) [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
MPQLSLSSLG LWPMAASPWL LLLLVGASWL LARILAWTYT FYDNCCRLRC
60 70 80 90 100
FPQPPKRNWF LGHLGLIHSS EEGLLYTQSL ACTFGDMCCW WVGPWHAIVR
110 120 130 140 150
IFHPTYIKPV LFAPAAIVPK DKVFYSFLKP WLGDGLLLSA GEKWSRHRRM
160 170 180 190 200
LTPAFHFNIL KPYMKIFNES VNIMHAKWQL LASEGSARLD MFEHISLMTL
210 220 230 240 250
DSLQKCVFSF DSHCQEKPSE YIAAILELSA LVTKRHQQIL LYIDFLYYLT
260 270 280 290 300
PDGQRFRRAC RLVHDFTDAV IQERRRTLPS QGVDDFLQAK AKSKTLDFID
310 320 330 340 350
VLLLSKDEDG KKLSDEDIRA EADTFMFEGH DTTASGLSWV LYHLAKHPEY
360 370 380 390 400
QERCRQEVQE LLKDREPKEI EWDDLAQLPF LTMCIKESLR LHPPVPAVSR
410 420 430 440 450
CCTQDIVLPD GRVIPKGIIC LISVFGTHHN PAVWPDPEVY DPFRFDPKNI
460 470 480 490 500
KERSPLAFIP FSAGPRNCIG QAFAMAEMKV VLGLTLLRFR VLPDHTEPRR
510 520
KPELVLRAEG GLWLRVEPLS
Length:520
Mass (Da):59,847
Last modified:December 21, 2004 - v2
Checksum:i2519D875280CF9DC
GO
Isoform CYP4F3B (identifier: Q08477-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     67-114: IHSSEEGLLY...TYIKPVLFAP → VTPTEQGMRV...NIIRSVINAS

Show »
Length:520
Mass (Da):59,739
Checksum:iEA737D889AD662C2
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti184 – 186EGS → KGY in AAC08589 (Ref. 3) Curated3
Sequence conflicti488R → A in BAA02144 (PubMed:8486631).Curated1
Sequence conflicti488R → A in BAA25990 (PubMed:9539102).Curated1
Sequence conflicti488R → A in BAA25991 (PubMed:9539102).Curated1
Sequence conflicti512L → I in AAC08589 (Ref. 3) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04845796H → Q. Corresponds to variant dbSNP:rs34923393Ensembl.1
Natural variantiVAR_048458106Y → C. Corresponds to variant dbSNP:rs35888783Ensembl.1
Natural variantiVAR_001258269A → D3 PublicationsCorresponds to variant dbSNP:rs1805040Ensembl.1
Natural variantiVAR_020664270V → I1 PublicationCorresponds to variant dbSNP:rs28371536Ensembl.1
Natural variantiVAR_020665271I → T1 PublicationCorresponds to variant dbSNP:rs28371479Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04719367 – 114IHSSE…VLFAP → VTPTEQGMRVLTQLVATYPQ GFKVWMGPIFPVIRFCHPNI IRSVINAS in isoform CYP4F3B. 3 PublicationsAdd BLAST48

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D12620 mRNA Translation: BAA02144.1
D12621 mRNA Translation: BAA02145.1
AB002454 mRNA Translation: BAA25990.1
AB002461 Genomic DNA Translation: BAA25991.1
AF054821 mRNA Translation: AAC08589.1
AK304200 mRNA Translation: BAH14129.1
AK316136 mRNA Translation: BAH14507.1
AY792513 Genomic DNA Translation: AAV40834.1
AD000685 Genomic DNA No translation available.
CH471106 Genomic DNA Translation: EAW84489.1
BC136299 mRNA Translation: AAI36300.1
CCDSiCCDS12332.1 [Q08477-1]
CCDS59362.1 [Q08477-2]
PIRiA46661
RefSeqiNP_000887.2, NM_000896.2 [Q08477-1]
NP_001186137.1, NM_001199208.1 [Q08477-2]
NP_001186138.1, NM_001199209.1 [Q08477-2]
XP_016882303.1, XM_017026814.1 [Q08477-2]
UniGeneiHs.106242

Genome annotation databases

EnsembliENST00000221307; ENSP00000221307; ENSG00000186529 [Q08477-1]
ENST00000585846; ENSP00000468105; ENSG00000186529 [Q08477-2]
ENST00000586182; ENSP00000466395; ENSG00000186529 [Q08477-2]
ENST00000591058; ENSP00000466988; ENSG00000186529 [Q08477-2]
GeneIDi4051
KEGGihsa:4051
UCSCiuc002nbj.4 human [Q08477-1]

Keywords - Coding sequence diversityi

Alternative promoter usage, Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCP4F3_HUMAN
AccessioniPrimary (citable) accession number: Q08477
Secondary accession number(s): B7Z8Z3, O60634, Q5U740
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: December 21, 2004
Last modified: June 20, 2018
This is version 175 of the entry and version 2 of the sequence. See 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, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: 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. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. SIMILARITY comments
    Index of protein domains and families

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