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Protein

Phylloquinone omega-hydroxylase CYP4F11

Gene

CYP4F11

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

Functioni

Omega-hydroxylase that oxidizes a variety of structurally unrelated compounds, including fatty acids and xenobiotics. Plays a key role in vitamin K catabolism by mediating omega-hydroxylation of vitamin K1 (phylloquinone), and menaquinone-4 (MK-4), a form of vitamin K2. Hydroxylation of phylloquinone and MK-4 probably regulates blood coagulation (PubMed:24138531). Catalyzes omega-hydroxylation of 3-hydroxy fatty acids, such as 3-hydroxypalmitate, 3-hydroxyoleate, 3-hydroxyarachidonate, and 3-hydroxystearate (PubMed:18065749, PubMed:19932081). Oxidizes drugs such as erythromycin, benzphetamine, ethylmorphine, chlorpromazine and imipramine (PubMed:15364545).4 Publications

Catalytic activityi

Phylloquinone + NADPH + O2 = omega-hydroxyphylloquinone + NADP+ + H2O.1 Publication

Cofactori

hemeBy similarity

Kineticsi

kcat is 0.088 min(-1) with menaquinone-4 (MK-4) as substrate.1 Publication

  1. KM=53.5 mM for 3-hydroxystearate1 Publication
  2. KM=105.8 mM for 3-hydroxypalmitate1 Publication
  3. KM=2.4 µM for menaquinone-4 (MK-4)1 Publication
  4. KM=125 µM for erythromycin1 Publication
  1. Vmax=830 pmol/min/ng enzyme with erythromycin as substrate1 Publication

Pathway: phylloquinone degradation

This protein is involved in the pathway phylloquinone degradation, which is part of Cofactor degradation.1 Publication
View all proteins of this organism that are known to be involved in the pathway phylloquinone degradation and in Cofactor degradation.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei328 – 3281Heme (covalent; via 1 link)By similarity
Metal bindingi468 – 4681Iron (heme axial ligand)By similarity

GO - Molecular functioni

GO - Biological processi

  • blood coagulation Source: UniProtKB
  • inflammatory response Source: UniProtKB
  • menaquinone catabolic process Source: UniProtKB
  • oxidation-reduction process Source: UniProtKB
  • phylloquinone catabolic process Source: UniProtKB
  • small molecule metabolic process Source: Reactome
  • vitamin K catabolic process Source: UniProtKB
  • xenobiotic metabolic process Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Monooxygenase, Oxidoreductase

Keywords - Ligandi

Heme, Iron, Metal-binding, NADP

Enzyme and pathway databases

ReactomeiREACT_13425. Miscellaneous substrates.
REACT_13645. Eicosanoids.
REACT_13814. Fatty acids.
REACT_150420. Synthesis of Leukotrienes (LT) and Eoxins (EX).
UniPathwayiUPA01054.

Names & Taxonomyi

Protein namesi
Recommended name:
Phylloquinone omega-hydroxylase CYP4F11Curated (EC:1.14.13.1941 Publication)
Alternative name(s):
3-hydroxy fatty acids omega-hydroxylase CYP4F11Curated (EC:1.14.13.-Curated)
Cytochrome P450 4F11
Short name:
CYPIVF11
Gene namesi
Name:CYP4F11Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:13265. CYP4F11.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei15 – 3723HelicalSequence AnalysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA27120.

Polymorphism and mutation databases

BioMutaiCYP4F11.
DMDMi296439388.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 524524Phylloquinone omega-hydroxylase CYP4F11PRO_0000051856Add
BLAST

Proteomic databases

MaxQBiQ9HBI6.
PaxDbiQ9HBI6.
PRIDEiQ9HBI6.

PTM databases

PhosphoSiteiQ9HBI6.

Expressioni

Tissue specificityi

Expressed mainly in human liver, followed by kidney, heart, and skeletal muscle.2 Publications

Gene expression databases

BgeeiQ9HBI6.
CleanExiHS_CYP4F11.
ExpressionAtlasiQ9HBI6. baseline and differential.
GenevisibleiQ9HBI6. HS.

Organism-specific databases

HPAiCAB033648.
HPA017265.
HPA058960.

Interactioni

Protein-protein interaction databases

BioGridi121790. 2 interactions.
IntActiQ9HBI6. 1 interaction.
STRINGi9606.ENSP00000248041.

Structurei

3D structure databases

ProteinModelPortaliQ9HBI6.
SMRiQ9HBI6. Positions 97-510.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the cytochrome P450 family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG2124.
GeneTreeiENSGT00760000118816.
HOGENOMiHOG000233833.
HOVERGENiHBG000182.
InParanoidiQ9HBI6.
KOiK17729.
OMAiPKGIVCL.
PhylomeDBiQ9HBI6.
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]

Sequencei

Sequence statusi: Complete.

Q9HBI6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPQLSLSWLG LGPVAASPWL LLLLVGGSWL LARVLAWTYT FYDNCRRLQC
60 70 80 90 100
FPQPPKQNWF WGHQGLVTPT EEGMKTLTQL VTTYPQGFKL WLGPTFPLLI
110 120 130 140 150
LCHPDIIRPI TSASAAVAPK DMIFYGFLKP WLGDGLLLSG GDKWSRHRRM
160 170 180 190 200
LTPAFHFNIL KPYMKIFNKS VNIMHDKWQR LASEGSARLD MFEHISLMTL
210 220 230 240 250
DSLQKCVFSF ESNCQEKPSE YIAAILELSA FVEKRNQQIL LHTDFLYYLT
260 270 280 290 300
PDGQRFRRAC HLVHDFTDAV IQERRCTLPT QGIDDFLKNK AKSKTLDFID
310 320 330 340 350
VLLLSKDEDG KELSDEDIRA EADTFMFEGH DTTASGLSWV LYHLAKHPEY
360 370 380 390 400
QEQCRQEVQE LLKDREPIEI EWDDLAQLPF LTMCIKESLR LHPPVPVISR
410 420 430 440 450
CCTQDFVLPD GRVIPKGIVC LINIIGIHYN PTVWPDPEVY DPFRFDQENI
460 470 480 490 500
KERSPLAFIP FSAGPRNCIG QAFAMAEMKV VLALTLLHFR ILPTHTEPRR
510 520
KPELILRAEG GLWLRVEPLG ANSQ
Length:524
Mass (Da):60,146
Last modified:May 18, 2010 - v3
Checksum:i8B0F14C52E657CB2
GO

Sequence cautioni

The sequence AAC27731.1 differs from that shown. Reason: Erroneous gene model prediction. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti458 – 4581F → L in BAF82113 (PubMed:14702039).Curated
Sequence conflicti496 – 4961T → I in AAG15889 (PubMed:10964514).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti146 – 1461R → C.
Corresponds to variant rs57519667 [ dbSNP | Ensembl ].
VAR_060265
Natural varianti276 – 2761C → R.4 Publications
Corresponds to variant rs8104361 [ dbSNP | Ensembl ].
VAR_060266
Natural varianti446 – 4461D → N Common polymorphism; does not affect enzyme activity. 4 Publications
Corresponds to variant rs1060463 [ dbSNP | Ensembl ].
VAR_071198

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF236085 mRNA. Translation: AAG15889.1.
AK289424 mRNA. Translation: BAF82113.1.
AC005336 Genomic DNA. Translation: AAC27731.1. Sequence problems.
AC020950 Genomic DNA. No translation available.
AC011517 Genomic DNA. No translation available.
CH471106 Genomic DNA. Translation: EAW84512.1.
CH471106 Genomic DNA. Translation: EAW84513.1.
BC016853 mRNA. Translation: AAH16853.1.
CCDSiCCDS12337.1.
RefSeqiNP_001122404.1. NM_001128932.1.
NP_067010.3. NM_021187.3.
UniGeneiHs.187393.

Genome annotation databases

EnsembliENST00000248041; ENSP00000248041; ENSG00000171903.
ENST00000402119; ENSP00000384588; ENSG00000171903.
GeneIDi57834.
KEGGihsa:57834.
UCSCiuc002nbt.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF236085 mRNA. Translation: AAG15889.1.
AK289424 mRNA. Translation: BAF82113.1.
AC005336 Genomic DNA. Translation: AAC27731.1. Sequence problems.
AC020950 Genomic DNA. No translation available.
AC011517 Genomic DNA. No translation available.
CH471106 Genomic DNA. Translation: EAW84512.1.
CH471106 Genomic DNA. Translation: EAW84513.1.
BC016853 mRNA. Translation: AAH16853.1.
CCDSiCCDS12337.1.
RefSeqiNP_001122404.1. NM_001128932.1.
NP_067010.3. NM_021187.3.
UniGeneiHs.187393.

3D structure databases

ProteinModelPortaliQ9HBI6.
SMRiQ9HBI6. Positions 97-510.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121790. 2 interactions.
IntActiQ9HBI6. 1 interaction.
STRINGi9606.ENSP00000248041.

PTM databases

PhosphoSiteiQ9HBI6.

Polymorphism and mutation databases

BioMutaiCYP4F11.
DMDMi296439388.

Proteomic databases

MaxQBiQ9HBI6.
PaxDbiQ9HBI6.
PRIDEiQ9HBI6.

Protocols and materials databases

DNASUi57834.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000248041; ENSP00000248041; ENSG00000171903.
ENST00000402119; ENSP00000384588; ENSG00000171903.
GeneIDi57834.
KEGGihsa:57834.
UCSCiuc002nbt.2. human.

Organism-specific databases

CTDi57834.
GeneCardsiGC19M016023.
H-InvDBHIX0014857.
HGNCiHGNC:13265. CYP4F11.
HPAiCAB033648.
HPA017265.
HPA058960.
MIMi611517. gene.
neXtProtiNX_Q9HBI6.
PharmGKBiPA27120.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG2124.
GeneTreeiENSGT00760000118816.
HOGENOMiHOG000233833.
HOVERGENiHBG000182.
InParanoidiQ9HBI6.
KOiK17729.
OMAiPKGIVCL.
PhylomeDBiQ9HBI6.
TreeFamiTF105088.

Enzyme and pathway databases

UniPathwayiUPA01054.
ReactomeiREACT_13425. Miscellaneous substrates.
REACT_13645. Eicosanoids.
REACT_13814. Fatty acids.
REACT_150420. Synthesis of Leukotrienes (LT) and Eoxins (EX).

Miscellaneous databases

GeneWikiiCYP4F11.
GenomeRNAii57834.
NextBioi35463709.
PROiQ9HBI6.
SOURCEiSearch...

Gene expression databases

BgeeiQ9HBI6.
CleanExiHS_CYP4F11.
ExpressionAtlasiQ9HBI6. baseline and differential.
GenevisibleiQ9HBI6. 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...

Publicationsi

« Hide 'large scale' publications
  1. "A novel human cytochrome P450 4F isoform (CYP4F11): cDNA cloning, expression, and genomic structural characterization."
    Cui X., Nelson D.R., Strobel H.W.
    Genomics 68:161-166(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, VARIANTS ARG-276 AND ASN-446.
    Tissue: Brain and Liver.
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS ARG-276 AND ASN-446.
    Tissue: Mammary glandImported.
  3. "The DNA sequence and biology of human chromosome 19."
    Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V.
    , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
    Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ARG-276.
  5. "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], VARIANTS ARG-276 AND ASN-446.
    Tissue: Colon.
  6. "Expression and characterization of human cytochrome P450 4F11: Putative role in the metabolism of therapeutic drugs and eicosanoids."
    Kalsotra A., Turman C.M., Kikuta Y., Strobel H.W.
    Toxicol. Appl. Pharmacol. 199:295-304(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES.
  7. "Omega oxidation of 3-hydroxy fatty acids by the human CYP4F gene subfamily enzyme CYP4F11."
    Dhar M., Sepkovic D.W., Hirani V., Magnusson R.P., Lasker J.M.
    J. Lipid Res. 49:612-624(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES.
  8. "Human cytochrome P450 4F11: heterologous expression in bacteria, purification, and characterization of catalytic function."
    Tang Z., Salamanca-Pinzon S.G., Wu Z.L., Xiao Y., Guengerich F.P.
    Arch. Biochem. Biophys. 494:86-93(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  9. "Cytochrome P450-dependent catabolism of vitamin K: omega-hydroxylation catalyzed by human CYP4F2 and CYP4F11."
    Edson K.Z., Prasad B., Unadkat J.D., Suhara Y., Okano T., Guengerich F.P., Rettie A.E.
    Biochemistry 52:8276-8285(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, IDENTIFICATION BY MASS SPECTROMETRY, PATHWAY, CHARACTERIZATION OF VARIANT ASN-446.
  10. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

Entry informationi

Entry nameiCP4FB_HUMAN
AccessioniPrimary (citable) accession number: Q9HBI6
Secondary accession number(s): A0A024R7G0
, A8K059, O75254, Q96AQ5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 10, 2002
Last sequence update: May 18, 2010
Last modified: June 24, 2015
This is version 134 of the entry and version 3 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, 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

External Data

Dasty 3

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 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.