CP4X1_HUMAN
ID CP4X1_HUMAN Reviewed; 509 AA.
AC Q8N118; G3V1U1; Q5VVE5; Q6ZN67; Q8NAZ3;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Cytochrome P450 4X1 {ECO:0000303|PubMed:18549450};
DE EC=1.14.14.- {ECO:0000269|PubMed:18549450};
DE AltName: Full=CYPIVX1;
GN Name=CYP4X1 {ECO:0000303|PubMed:18549450, ECO:0000312|HGNC:HGNC:20244};
GN ORFNames=UNQ1929/PRO4404;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Aorta;
RX PubMed=16478468; DOI=10.1111/j.1742-4658.2006.05119.x;
RA Al-Anizy M., Horley N.J., Kuo C.W., Gillett L.C., Laughton C.A.,
RA Kendall D., Barrett D.A., Parker T., Bell D.R.;
RT "Cytochrome P450 Cyp4x1 is a major P450 protein in mouse brain.";
RL FEBS J. 273:936-947(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Liver, Lung, and Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE
RP SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=18549450; DOI=10.1111/j.1742-4658.2008.06518.x;
RA Stark K., Dostalek M., Guengerich F.P.;
RT "Expression and purification of orphan cytochrome P450 4X1 and oxidation of
RT anandamide.";
RL FEBS J. 275:3706-3717(2008).
CC -!- FUNCTION: A cytochrome P450 monooxygenase that selectively catalyzes
CC the epoxidation of the last double bond of the arachidonoyl moiety of
CC anandamide, potentially modulating endocannabinoid signaling. Has no
CC hydroxylase activity toward various fatty acids, steroids and
CC prostaglandins. Mechanistically, uses molecular oxygen inserting one
CC oxygen atom into a substrate, and reducing the second into a water
CC molecule, with two electrons provided by NADPH via cytochrome P450
CC reductase (CPR; NADPH-ferrihemoprotein reductase).
CC {ECO:0000269|PubMed:18549450}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + O2 + reduced
CC [NADPH--hemoprotein reductase] = H(+) + H2O + N-(14,15-epoxy-
CC 5Z,8Z,11Z-eicosatrienoyl)-ethanolamine + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:53148, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:2700, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:136991; Evidence={ECO:0000269|PubMed:18549450};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53149;
CC Evidence={ECO:0000305|PubMed:18549450};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P51869};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=65 uM for N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine (14,15
CC epoxidation) {ECO:0000269|PubMed:18549450};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q6A152}; Single-pass membrane protein
CC {ECO:0000255}. Microsome membrane {ECO:0000250|UniProtKB:Q6A152};
CC Single-pass membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8N118-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8N118-2; Sequence=VSP_045890;
CC Name=3;
CC IsoId=Q8N118-3; Sequence=VSP_045889;
CC -!- TISSUE SPECIFICITY: Expressed in brain, heart, kidney and skin and, at
CC lower levels, in skeletal muscle and liver (PubMed:16478468,
CC PubMed:18549450). In the brain, high levels are detected in amygdala
CC and lower levels in globus pallidus and cerebellum (PubMed:18549450).
CC In the heart, very high levels in aorta, but very low levels in other
CC heart regions (PubMed:16478468, PubMed:18549450). Also expressed in
CC breast, prostate and colon (PubMed:18549450).
CC {ECO:0000269|PubMed:16478468, ECO:0000269|PubMed:18549450}.
CC -!- DEVELOPMENTAL STAGE: Expressed in fetal liver and aorta.
CC {ECO:0000269|PubMed:18549450}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; AM040940; CAJ13826.1; -; mRNA.
DR EMBL; AY358537; AAQ88901.1; -; mRNA.
DR EMBL; AK091806; BAC03751.1; -; mRNA.
DR EMBL; AK098065; BAC05226.1; -; mRNA.
DR EMBL; AK131355; BAD18508.1; -; mRNA.
DR EMBL; AL450996; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL731892; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471059; EAX06882.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06883.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06884.1; -; Genomic_DNA.
DR EMBL; BC028102; AAH28102.1; -; mRNA.
DR CCDS; CCDS544.1; -. [Q8N118-1]
DR RefSeq; NP_001307218.1; NM_001320289.1. [Q8N118-2]
DR RefSeq; NP_001307219.1; NM_001320290.1. [Q8N118-3]
DR RefSeq; NP_828847.1; NM_178033.1. [Q8N118-1]
DR AlphaFoldDB; Q8N118; -.
DR SMR; Q8N118; -.
DR BioGRID; 129254; 15.
DR IntAct; Q8N118; 1.
DR STRING; 9606.ENSP00000360968; -.
DR BindingDB; Q8N118; -.
DR ChEMBL; CHEMBL6048; -.
DR SwissLipids; SLP:000001715; -.
DR iPTMnet; Q8N118; -.
DR PhosphoSitePlus; Q8N118; -.
DR SwissPalm; Q8N118; -.
DR BioMuta; CYP4X1; -.
DR DMDM; 48428082; -.
DR EPD; Q8N118; -.
DR jPOST; Q8N118; -.
DR MassIVE; Q8N118; -.
DR MaxQB; Q8N118; -.
DR PaxDb; Q8N118; -.
DR PeptideAtlas; Q8N118; -.
DR PRIDE; Q8N118; -.
DR ProteomicsDB; 32441; -.
DR ProteomicsDB; 71519; -. [Q8N118-1]
DR Antibodypedia; 32842; 217 antibodies from 25 providers.
DR DNASU; 260293; -.
DR Ensembl; ENST00000371901.4; ENSP00000360968.3; ENSG00000186377.8. [Q8N118-1]
DR GeneID; 260293; -.
DR KEGG; hsa:260293; -.
DR MANE-Select; ENST00000371901.4; ENSP00000360968.3; NM_178033.2; NP_828847.1.
DR UCSC; uc001cqt.3; human. [Q8N118-1]
DR CTD; 260293; -.
DR DisGeNET; 260293; -.
DR GeneCards; CYP4X1; -.
DR HGNC; HGNC:20244; CYP4X1.
DR HPA; ENSG00000186377; Tissue enhanced (cervix, salivary gland).
DR MIM; 614999; gene.
DR neXtProt; NX_Q8N118; -.
DR OpenTargets; ENSG00000186377; -.
DR PharmGKB; PA134933184; -.
DR VEuPathDB; HostDB:ENSG00000186377; -.
DR eggNOG; KOG0157; Eukaryota.
DR GeneTree; ENSGT00940000160927; -.
DR HOGENOM; CLU_001570_5_1_1; -.
DR InParanoid; Q8N118; -.
DR OMA; SDQRHPY; -.
DR OrthoDB; 1247045at2759; -.
DR PhylomeDB; Q8N118; -.
DR TreeFam; TF105088; -.
DR PathwayCommons; Q8N118; -.
DR SignaLink; Q8N118; -.
DR BioGRID-ORCS; 260293; 23 hits in 1070 CRISPR screens.
DR ChiTaRS; CYP4X1; human.
DR GeneWiki; CYP4X1; -.
DR GenomeRNAi; 260293; -.
DR Pharos; Q8N118; Tbio.
DR PRO; PR:Q8N118; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q8N118; protein.
DR Bgee; ENSG00000186377; Expressed in palpebral conjunctiva and 173 other tissues.
DR Genevisible; Q8N118; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0062189; F:anandamide 14,15 epoxidase activity; IDA:UniProtKB.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Endoplasmic reticulum; Heme; Iron; Lipid metabolism;
KW Membrane; Metal-binding; Microsome; Monooxygenase; Oxidoreductase;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..509
FT /note="Cytochrome P450 4X1"
FT /id="PRO_0000051862"
FT TRANSMEM 14..34
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 454
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P51869"
FT VAR_SEQ 1..65
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045889"
FT VAR_SEQ 1..59
FT /note="MEFSWLETRWARPFYLAFVFCLALGLLQAIKLYLRRQRLLRDLRPFPAPPTH
FT WFLGHQK -> MMWGGGLDLCPMPGQLKFPPCLSRCLLWEPPSLYLTQPTSSLAEPQAL
FT ICMTSSSSGL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045890"
FT CONFLICT 192
FT /note="I -> V (in Ref. 3; BAD18508)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 509 AA; 58875 MW; 702470A76E814278 CRC64;
MEFSWLETRW ARPFYLAFVF CLALGLLQAI KLYLRRQRLL RDLRPFPAPP THWFLGHQKF
IQDDNMEKLE EIIEKYPRAF PFWIGPFQAF FCIYDPDYAK TLLSRTDPKS QYLQKFSPPL
LGKGLAALDG PKWFQHRRLL TPGFHFNILK AYIEVMAHSV KMMLDKWEKI CSTQDTSVEV
YEHINSMSLD IIMKCAFSKE TNCQTNSTHD PYAKAIFELS KIIFHRLYSL LYHSDIIFKL
SPQGYRFQKL SRVLNQYTDT IIQERKKSLQ AGVKQDNTPK RKYQDFLDIV LSAKDESGSS
FSDIDVHSEV STFLLAGHDT LAASISWILY CLALNPEHQE RCREEVRGIL GDGSSITWDQ
LGEMSYTTMC IKETCRLIPA VPSISRDLSK PLTFPDGCTL PAGITVVLSI WGLHHNPAVW
KNPKVFDPLR FSQENSDQRH PYAYLPFSAG SRNCIGQEFA MIELKVTIAL ILLHFRVTPD
PTRPLTFPNH FILKPKNGMY LHLKKLSEC
