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Protein

Cytochrome P450 4F12

Gene

CYP4F12

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

Functioni

Catalyzes leukotriene B4 omega-hydroxylation and arachidonic acid omega-hydroxylation but with an activity much lower than that of CYP4F2. Catalyzes the hydroxylation of the antihistamine ebastine.

Catalytic activityi

RH + reduced flavoprotein + O2 = ROH + oxidized flavoprotein + H2O.

Cofactori

hemeBy similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi468 – 4681Iron (heme axial ligand)By similarity

GO - Molecular functioni

  1. alkane 1-monooxygenase activity Source: UniProtKB
  2. arachidonic acid epoxygenase activity Source: UniProtKB
  3. aromatase activity Source: UniProtKB-EC
  4. heme binding Source: InterPro
  5. iron ion binding Source: InterPro
  6. leukotriene-B4 20-monooxygenase activity Source: UniProtKB
  7. vitamin-K-epoxide reductase (warfarin-sensitive) activity Source: UniProtKB

GO - Biological processi

  1. arachidonic acid metabolic process Source: UniProtKB
  2. drug metabolic process Source: UniProtKB
  3. epoxygenase P450 pathway Source: UniProtKB
  4. leukotriene B4 catabolic process Source: UniProtKB
  5. long-chain fatty acid metabolic process Source: UniProtKB
  6. negative regulation of blood coagulation Source: UniProtKB
  7. oxidation-reduction process Source: UniProtKB
  8. pressure natriuresis Source: UniProtKB
  9. renal water homeostasis Source: UniProtKB
  10. small molecule metabolic process Source: Reactome
  11. sodium ion homeostasis Source: UniProtKB
  12. very long-chain fatty acid metabolic process Source: UniProtKB
  13. vitamin E metabolic process Source: UniProtKB
  14. vitamin K biosynthetic process 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_13645. Eicosanoids.
REACT_13814. Fatty acids.

Names & Taxonomyi

Protein namesi
Recommended name:
Cytochrome P450 4F12 (EC:1.14.14.1)
Alternative name(s):
CYPIVF12
Gene namesi
Name:CYP4F12
ORF Names:UNQ568/PRO1129
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 19

Organism-specific databases

HGNCiHGNC:18857. CYP4F12.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei19 – 3921HelicalSequence AnalysisAdd
BLAST
Transmembranei87 – 10721HelicalSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. apical plasma membrane Source: UniProtKB
  2. cytoplasm Source: UniProtKB
  3. endoplasmic reticulum membrane Source: Reactome
  4. integral component of membrane Source: UniProtKB-KW
  5. intracellular membrane-bounded organelle Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA38717.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 524524Cytochrome P450 4F12PRO_0000051857Add
BLAST

Proteomic databases

MaxQBiQ9HCS2.
PaxDbiQ9HCS2.
PRIDEiQ9HCS2.

PTM databases

PhosphoSiteiQ9HCS2.

Expressioni

Tissue specificityi

Expressed in small intestine, liver, colon and heart.2 Publications

Gene expression databases

BgeeiQ9HCS2.
CleanExiHS_CYP4F12.
ExpressionAtlasiQ9HCS2. baseline and differential.
GenevestigatoriQ9HCS2.

Interactioni

Protein-protein interaction databases

BioGridi122449. 3 interactions.
IntActiQ9HCS2. 3 interactions.
STRINGi9606.ENSP00000321821.

Structurei

3D structure databases

ProteinModelPortaliQ9HCS2.
SMRiQ9HCS2. Positions 97-524.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the cytochrome P450 family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG2124.
GeneTreeiENSGT00760000118816.
HOGENOMiHOG000233833.
HOVERGENiHBG000182.
InParanoidiQ9HCS2.
KOiK17730.
OMAiIICVINI.
OrthoDBiEOG7CNZFK.
PhylomeDBiQ9HCS2.
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.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q9HCS2-1) [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
MSLLSLPWLG LRPVATSPWL LLLLVVGSWL LARILAWTYA FYNNCRRLQC
60 70 80 90 100
FPQPPKRNWF WGHLGLITPT EEGLKNSTQM SATYSQGFTI WLGPIIPFIV
110 120 130 140 150
LCHPDTIRSI TNASAAIAPK DNLFIRFLKP WLGEGILLSG GDKWSRHRRM
160 170 180 190 200
LTPAFHFNIL KSYITIFNKS ANIMLDKWQH LASEGSSCLD MFEHISLMTL
210 220 230 240 250
DSLQKCIFSF DSHCQERPSE YIATILELSA LVEKRSQHIL QHMDFLYYLS
260 270 280 290 300
HDGRRFHRAC RLVHDFTDAV IRERRRTLPT QGIDDFFKDK AKSKTLDFID
310 320 330 340 350
VLLLSKDEDG KALSDEDIRA EADTFMFGGH DTTASGLSWV LYNLARHPEY
360 370 380 390 400
QERCRQEVQE LLKDRDPKEI EWDDLAQLPF LTMCVKESLR LHPPAPFISR
410 420 430 440 450
CCTQDIVLPD GRVIPKGITC LIDIIGVHHN PTVWPDPEVY DPFRFDPENS
460 470 480 490 500
KGRSPLAFIP FSAGPRNCIG QAFAMAEMKV VLALMLLHFR FLPDHTEPRR
510 520
KLELIMRAEG GLWLRVEPLN VSLQ
Length:524
Mass (Da):60,270
Last modified:November 30, 2010 - v2
Checksum:iF29C29BA8DB880FE
GO
Isoform 2 (identifier: Q9HCS2-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     90-102: IWLGPIIPFIVLC → LPLHPRIISSSGS
     103-524: Missing.

Note: No experimental confirmation available.

Show »
Length:102
Mass (Da):11,572
Checksum:i356BE81361CDE5A9
GO

Sequence cautioni

The sequence EAW84492.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti13 – 131P → L.1 Publication
Corresponds to variant rs16995376 [ dbSNP | Ensembl ].
VAR_013244
Natural varianti16 – 161T → M.6 Publications
Corresponds to variant rs16995378 [ dbSNP | Ensembl ].
VAR_048459
Natural varianti76 – 761N → D.6 Publications
Corresponds to variant rs609636 [ dbSNP | Ensembl ].
VAR_013245
Natural varianti90 – 901I → V.4 Publications
Corresponds to variant rs609290 [ dbSNP | Ensembl ].
VAR_013246
Natural varianti188 – 1881C → R.4 Publications
Corresponds to variant rs2285888 [ dbSNP | Ensembl ].
VAR_013247
Natural varianti522 – 5221S → G.4 Publications
Corresponds to variant rs593818 [ dbSNP | Ensembl ].
VAR_048460

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei90 – 10213IWLGP…FIVLC → LPLHPRIISSSGS in isoform 2. 2 PublicationsVSP_055581Add
BLAST
Alternative sequencei103 – 524422Missing in isoform 2. 2 PublicationsVSP_055582Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY008841 mRNA. Translation: AAG33247.1.
AB035130 mRNA. Translation: BAB18269.1.
AB035131 mRNA. Translation: BAB18270.1.
AY358977 mRNA. Translation: AAQ89336.1.
AK075435 mRNA. Translation: BAG52137.1.
AL832171 mRNA. Translation: CAI46131.1.
AC004523 Genomic DNA. Translation: AAC11543.1.
AC122702 Genomic DNA. No translation available.
CH471106 Genomic DNA. Translation: EAW84492.1. Different initiation.
CH471106 Genomic DNA. Translation: EAW84495.1.
CCDSiCCDS42517.1. [Q9HCS2-1]
PIRiJC7594.
JC7598.
RefSeqiNP_076433.3. NM_023944.3.
UniGeneiHs.131459.

Genome annotation databases

EnsembliENST00000517734; ENSP00000430849; ENSG00000186204. [Q9HCS2-2]
ENST00000548435; ENSP00000449703; ENSG00000186204. [Q9HCS2-2]
GeneIDi66002.
KEGGihsa:66002.
UCSCiuc002nbl.3. human. [Q9HCS2-1]

Polymorphism databases

DMDMi313104094.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY008841 mRNA. Translation: AAG33247.1.
AB035130 mRNA. Translation: BAB18269.1.
AB035131 mRNA. Translation: BAB18270.1.
AY358977 mRNA. Translation: AAQ89336.1.
AK075435 mRNA. Translation: BAG52137.1.
AL832171 mRNA. Translation: CAI46131.1.
AC004523 Genomic DNA. Translation: AAC11543.1.
AC122702 Genomic DNA. No translation available.
CH471106 Genomic DNA. Translation: EAW84492.1. Different initiation.
CH471106 Genomic DNA. Translation: EAW84495.1.
CCDSiCCDS42517.1. [Q9HCS2-1]
PIRiJC7594.
JC7598.
RefSeqiNP_076433.3. NM_023944.3.
UniGeneiHs.131459.

3D structure databases

ProteinModelPortaliQ9HCS2.
SMRiQ9HCS2. Positions 97-524.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122449. 3 interactions.
IntActiQ9HCS2. 3 interactions.
STRINGi9606.ENSP00000321821.

Chemistry

DrugBankiDB08868. Fingolimod.

PTM databases

PhosphoSiteiQ9HCS2.

Polymorphism databases

DMDMi313104094.

Proteomic databases

MaxQBiQ9HCS2.
PaxDbiQ9HCS2.
PRIDEiQ9HCS2.

Protocols and materials databases

DNASUi66002.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000517734; ENSP00000430849; ENSG00000186204. [Q9HCS2-2]
ENST00000548435; ENSP00000449703; ENSG00000186204. [Q9HCS2-2]
GeneIDi66002.
KEGGihsa:66002.
UCSCiuc002nbl.3. human. [Q9HCS2-1]

Organism-specific databases

CTDi66002.
GeneCardsiGC19P015783.
HGNCiHGNC:18857. CYP4F12.
MIMi611485. gene.
neXtProtiNX_Q9HCS2.
PharmGKBiPA38717.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG2124.
GeneTreeiENSGT00760000118816.
HOGENOMiHOG000233833.
HOVERGENiHBG000182.
InParanoidiQ9HCS2.
KOiK17730.
OMAiIICVINI.
OrthoDBiEOG7CNZFK.
PhylomeDBiQ9HCS2.
TreeFamiTF105088.

Enzyme and pathway databases

ReactomeiREACT_13645. Eicosanoids.
REACT_13814. Fatty acids.

Miscellaneous databases

GeneWikiiCYP4F12.
GenomeRNAii66002.
NextBioi35500284.
PROiQ9HCS2.
SOURCEiSearch...

Gene expression databases

BgeeiQ9HCS2.
CleanExiHS_CYP4F12.
ExpressionAtlasiQ9HCS2. baseline and differential.
GenevestigatoriQ9HCS2.

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. "cDNA cloning and expression of CYP4F12, a novel human cytochrome P450."
    Bylund J., Bylund M., Oliw E.H.
    Biochem. Biophys. Res. Commun. 280:892-897(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, CHARACTERIZATION, VARIANTS MET-16; ASP-76; VAL-90; ARG-188 AND GLY-522.
    Tissue: Liver.
  2. "cDNA cloning and expression of a novel cytochrome p450 (cyp4f12) from human small intestine."
    Hashizume T., Imaoka S., Hiroi T., Terauchi Y., Fujii T., Miyazaki H., Kamataki T., Funae Y.
    Biochem. Biophys. Res. Commun. 280:1135-1141(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, CHARACTERIZATION, VARIANTS LEU-13; MET-16; ASP-76; VAL-90; ARG-188 AND GLY-522.
    Tissue: Small intestine.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANTS MET-16; ASP-76; VAL-90; ARG-188 AND GLY-522.
  4. "Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries."
    Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J., Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S., Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.
    , Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S., Isogai T.
    DNA Res. 12:117-126(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANTS MET-16 AND ASP-76.
    Tissue: Placenta.
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANTS MET-16 AND ASP-76.
    Tissue: Cervix.
  6. "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].
  7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANTS MET-16; ASP-76; VAL-90; ARG-188 AND GLY-522.

Entry informationi

Entry nameiCP4FC_HUMAN
AccessioniPrimary (citable) accession number: Q9HCS2
Secondary accession number(s): E7ET51
, O60389, Q5JPJ7, Q9HCS1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 10, 2002
Last sequence update: November 30, 2010
Last modified: January 7, 2015
This is version 125 of the entry and version 2 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. 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.