CP4AM_HUMAN
ID CP4AM_HUMAN Reviewed; 519 AA.
AC Q5TCH4; Q5TCH3; Q6JXK7; Q6JXK8; Q9NRM4;
DT 01-JUL-2008, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Cytochrome P450 4A22;
DE AltName: Full=CYPIVA22;
DE AltName: Full=Fatty acid omega-hydroxylase;
DE AltName: Full=Lauric acid omega-hydroxylase;
DE AltName: Full=Long-chain fatty acid omega-monooxygenase;
DE EC=1.14.14.80 {ECO:0000269|PubMed:10860550};
DE Flags: Precursor;
GN Name=CYP4A22;
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 [GENOMIC DNA] (ISOFORM 1), FUNCTION, CATALYTIC
RP ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND VARIANTS ARG-121 AND ILE-491.
RX PubMed=10860550; DOI=10.1006/abbi.2000.1831;
RA Kawashima H., Naganuma T., Kusunose E., Kono T., Yasumoto R., Sugimura K.,
RA Kishimoto T.;
RT "Human fatty acid omega-hydroxylase, CYP4A11: determination of complete
RT genomic sequence and characterization of purified recombinant protein.";
RL Arch. Biochem. Biophys. 378:333-339(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND VARIANTS TRP-126;
RP SER-130; TYR-152; ASN-226; SER-230; ARG-231; PRO-428 AND PHE-509.
RC TISSUE=Kidney, and Liver;
RX PubMed=15611369; DOI=10.1161/01.cir.0000151309.82473.59;
RA Gainer J.V., Bellamine A., Dawson E.P., Womble K.E., Grant S.W., Wang Y.,
RA Cupples L.A., Guo C.-Y., Demissie S., O'Donnell C.J., Brown N.J.,
RA Waterman M.R., Capdevila J.H.;
RT "Functional variant of CYP4A11 20-hydroxyeicosatetraenoic acid synthase is
RT associated with essential hypertension.";
RL Circulation 111:63-69(2005).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [5]
RP VARIANTS CYS-11; TRP-126; SER-130; TYR-152; PHE-185; ARG-231; THR-276;
RP PRO-428 AND PHE-509.
RX PubMed=16806293; DOI=10.1016/j.mrfmmm.2006.02.008;
RA Hiratsuka M., Nozawa H., Katsumoto Y., Moteki T., Sasaki T., Konno Y.,
RA Mizugaki M.;
RT "Genetic polymorphisms and haplotype structures of the CYP4A22 gene in a
RT Japanese population.";
RL Mutat. Res. 599:98-104(2006).
CC -!- FUNCTION: Catalyzes the omega- and (omega-1)-hydroxylation of various
CC fatty acids such as laurate and palmitate. Shows no activity towards
CC arachidonic acid and prostaglandin A1. Lacks functional activity in the
CC kidney and does not contribute to renal 20-hydroxyeicosatetraenoic acid
CC (20-HETE) biosynthesis. {ECO:0000269|PubMed:10860550,
CC ECO:0000269|PubMed:15611369}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an omega-methyl-long-chain fatty acid + O2 + reduced [NADPH--
CC hemoprotein reductase] = an omega-hydroxy-long-chain fatty acid +
CC H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:56748, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:140991,
CC ChEBI:CHEBI:140992; EC=1.14.14.80;
CC Evidence={ECO:0000269|PubMed:10860550};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=56.7 uM for laurate {ECO:0000269|PubMed:10860550};
CC Note=Vmax:15.2 umol/min/umol enzyme.;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250};
CC Peripheral membrane protein {ECO:0000250}. Microsome membrane
CC {ECO:0000250}; Peripheral membrane protein {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q5TCH4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5TCH4-2; Sequence=VSP_034584;
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC -!- CAUTION: Was originally termed CYP4A11. {ECO:0000305|PubMed:10860550}.
CC -!- WEB RESOURCE: Name=PharmVar Pharmacogen Variation Consortium;
CC Note=CYP4A22 alleles;
CC URL="https://www.pharmvar.org/gene/CYP4A22";
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DR EMBL; AF208532; AAF76722.1; -; Genomic_DNA.
DR EMBL; AY280371; AAQ21367.1; -; mRNA.
DR EMBL; AY280372; AAQ21368.1; -; mRNA.
DR EMBL; AL135960; CAI19737.1; -; Genomic_DNA.
DR EMBL; AL135960; CAI19738.1; -; Genomic_DNA.
DR EMBL; BC148248; AAI48249.1; -; mRNA.
DR CCDS; CCDS30707.1; -. [Q5TCH4-1]
DR RefSeq; NP_001010969.2; NM_001010969.3. [Q5TCH4-1]
DR RefSeq; NP_001295031.1; NM_001308102.1.
DR AlphaFoldDB; Q5TCH4; -.
DR SMR; Q5TCH4; -.
DR BioGRID; 129896; 2.
DR IntAct; Q5TCH4; 1.
DR STRING; 9606.ENSP00000360958; -.
DR BindingDB; Q5TCH4; -.
DR ChEMBL; CHEMBL4523986; -.
DR iPTMnet; Q5TCH4; -.
DR PhosphoSitePlus; Q5TCH4; -.
DR BioMuta; CYP4A22; -.
DR DMDM; 74746067; -.
DR MassIVE; Q5TCH4; -.
DR PaxDb; Q5TCH4; -.
DR PeptideAtlas; Q5TCH4; -.
DR PRIDE; Q5TCH4; -.
DR ProteomicsDB; 64954; -. [Q5TCH4-1]
DR ProteomicsDB; 64955; -. [Q5TCH4-2]
DR Antibodypedia; 18854; 94 antibodies from 18 providers.
DR DNASU; 284541; -.
DR Ensembl; ENST00000371891.8; ENSP00000360958.3; ENSG00000162365.13. [Q5TCH4-1]
DR GeneID; 284541; -.
DR KEGG; hsa:284541; -.
DR MANE-Select; ENST00000371891.8; ENSP00000360958.3; NM_001010969.4; NP_001010969.2.
DR UCSC; uc001cqv.2; human. [Q5TCH4-1]
DR CTD; 284541; -.
DR DisGeNET; 284541; -.
DR GeneCards; CYP4A22; -.
DR HGNC; HGNC:20575; CYP4A22.
DR HPA; ENSG00000162365; Tissue enriched (liver).
DR MIM; 615341; gene.
DR neXtProt; NX_Q5TCH4; -.
DR OpenTargets; ENSG00000162365; -.
DR PharmGKB; PA134979692; -.
DR VEuPathDB; HostDB:ENSG00000162365; -.
DR eggNOG; KOG0157; Eukaryota.
DR GeneTree; ENSGT00940000163504; -.
DR HOGENOM; CLU_001570_5_1_1; -.
DR InParanoid; Q5TCH4; -.
DR OMA; YGVQVCM; -.
DR OrthoDB; 825914at2759; -.
DR PhylomeDB; Q5TCH4; -.
DR TreeFam; TF105088; -.
DR PathwayCommons; Q5TCH4; -.
DR Reactome; R-HSA-211935; Fatty acids.
DR Reactome; R-HSA-211958; Miscellaneous substrates.
DR Reactome; R-HSA-211979; Eicosanoids.
DR Reactome; R-HSA-2142691; Synthesis of Leukotrienes (LT) and Eoxins (EX).
DR SignaLink; Q5TCH4; -.
DR BioGRID-ORCS; 284541; 5 hits in 1029 CRISPR screens.
DR ChiTaRS; CYP4A22; human.
DR GeneWiki; CYP4A22; -.
DR GenomeRNAi; 284541; -.
DR Pharos; Q5TCH4; Tbio.
DR PRO; PR:Q5TCH4; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q5TCH4; protein.
DR Bgee; ENSG00000162365; Expressed in right lobe of liver and 56 other tissues.
DR ExpressionAtlas; Q5TCH4; baseline and differential.
DR Genevisible; Q5TCH4; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0103002; F:16-hydroxypalmitate dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0018685; F:alkane 1-monooxygenase activity; IBA:GO_Central.
DR GO; GO:0008391; F:arachidonic acid monooxygenase activity; IBA:GO_Central.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0102116; F:laurate hydroxylase activity; IDA:UniProtKB.
DR GO; GO:0102033; F:long-chain fatty acid omega-hydroxylase activity; IEA:UniProtKB-EC.
DR GO; GO:0019369; P:arachidonic acid metabolic process; IBA:GO_Central.
DR GO; GO:0046456; P:icosanoid biosynthetic process; IBA:GO_Central.
DR GO; GO:0001822; P:kidney development; IBA:GO_Central.
DR GO; GO:0048252; P:lauric acid metabolic process; IBA:GO_Central.
DR GO; GO:0043651; P:linoleic acid metabolic process; IBA:GO_Central.
DR GO; GO:0002933; P:lipid hydroxylation; IDA:UniProtKB.
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; NADP; Oxidoreductase;
KW Phosphoprotein; Reference proteome.
FT PROPEP 1..4
FT /evidence="ECO:0000250"
FT /id="PRO_0000343408"
FT CHAIN 5..519
FT /note="Cytochrome P450 4A22"
FT /id="PRO_0000343409"
FT BINDING 321
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /note="covalent"
FT /evidence="ECO:0000250"
FT BINDING 457
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"
FT MOD_RES 440
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P20816"
FT VAR_SEQ 356..519
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_034584"
FT VARIANT 11
FT /note="R -> C (in allele CYP4A22*2 and CYP4A22*3;
FT dbSNP:rs76011927)"
FT /evidence="ECO:0000269|PubMed:16806293"
FT /id="VAR_044349"
FT VARIANT 104
FT /note="Y -> F (in dbSNP:rs61507155)"
FT /id="VAR_061045"
FT VARIANT 121
FT /note="K -> R (in dbSNP:rs2758717)"
FT /evidence="ECO:0000269|PubMed:10860550"
FT /id="VAR_044350"
FT VARIANT 126
FT /note="R -> W (in allele CYP4A22*8, allele CYP4A22*9,
FT allele CYP4A22*11, allele CYP4A22*12, allele CYP4A22*13,
FT allele CYP4A22*14 and allele CYP4A22*15; dbSNP:rs12564525)"
FT /evidence="ECO:0000269|PubMed:15611369,
FT ECO:0000269|PubMed:16806293"
FT /id="VAR_044351"
FT VARIANT 130
FT /note="G -> S (in allele CYP4A22*4, allele CYP4A22*10,
FT allele CYP4A22*12, allele CYP4A22*13, allele CYP4A22*14 and
FT allele CYP4A22*15; dbSNP:rs2056900)"
FT /evidence="ECO:0000269|PubMed:15611369,
FT ECO:0000269|PubMed:16806293"
FT /id="VAR_044352"
FT VARIANT 152
FT /note="N -> Y (in allele CYP4A22*2, allele CYP4A22*3,
FT allele CYP4A22*4, allele CYP4A22*5, allele CYP4A22*6,
FT allele CYP4A22*7, allele CYP4A22*8, allele CYP4A22*9,
FT allele CYP4A22*10, allele CYP4A22*11, allele CYP4A22*12,
FT allele CYP4A22*13, allele CYP4A22*14 and allele CYP4A22*15;
FT dbSNP:rs2056899)"
FT /evidence="ECO:0000269|PubMed:15611369,
FT ECO:0000269|PubMed:16806293"
FT /id="VAR_044353"
FT VARIANT 185
FT /note="V -> F (in allele CYP4A22*10, allele CYP4A22*11,
FT allele CYP4A22*12, allele CYP4A22*13, allele CYP4A22*14 and
FT allele CYP4A22*15; dbSNP:rs4926581)"
FT /evidence="ECO:0000269|PubMed:16806293"
FT /id="VAR_044354"
FT VARIANT 226
FT /note="S -> N (in dbSNP:rs35202523)"
FT /evidence="ECO:0000269|PubMed:15611369"
FT /id="VAR_044355"
FT VARIANT 230
FT /note="C -> S (in dbSNP:rs35156123)"
FT /evidence="ECO:0000269|PubMed:15611369"
FT /id="VAR_044356"
FT VARIANT 231
FT /note="C -> R (allele CYP4A22*2, allele CYP4A22*3, allele
FT CYP4A22*4, allele CYP4A22*5, allele CYP4A22*6, allele
FT CYP4A22*7, allele CYP4A22*8, allele CYP4A22*9, allele
FT CYP4A22*10, allele CYP4A22*11, allele CYP4A22*12, allele
FT CYP4A22*13, allele CYP4A22*14 and allele CYP4A22*15;
FT dbSNP:rs10789501)"
FT /evidence="ECO:0000269|PubMed:15611369,
FT ECO:0000269|PubMed:16806293"
FT /id="VAR_044357"
FT VARIANT 276
FT /note="K -> T (in allele CYP4A22*8, allele CYP4A22*11,
FT allele CYP4A22*14 and allele CYP4A22*15; dbSNP:rs6661132)"
FT /evidence="ECO:0000269|PubMed:16806293"
FT /id="VAR_044358"
FT VARIANT 428
FT /note="L -> P (in allele CYP4A22*6, allele CYP4A22*9,
FT allele CYP4A22*10, allele CYP4A22*12, allele CYP4A22*13 and
FT allele CYP4A22*15; dbSNP:rs2405599)"
FT /evidence="ECO:0000269|PubMed:15611369,
FT ECO:0000269|PubMed:16806293"
FT /id="VAR_044359"
FT VARIANT 491
FT /note="M -> I (in dbSNP:rs2758714)"
FT /evidence="ECO:0000269|PubMed:10860550"
FT /id="VAR_044360"
FT VARIANT 509
FT /note="L -> F (in allele CYP4A22*7, allele CYP4A22*10,
FT allele CYP4A22*11, allele CYP4A22*13, allele CYP4A22*14 and
FT allele CYP4A22*15; dbSNP:rs4926600)"
FT /evidence="ECO:0000269|PubMed:15611369,
FT ECO:0000269|PubMed:16806293"
FT /id="VAR_044361"
FT CONFLICT 2
FT /note="S -> A (in Ref. 2; AAQ21368)"
FT /evidence="ECO:0000305"
FT CONFLICT 114
FT /note="P -> S (in Ref. 2; AAQ21368)"
FT /evidence="ECO:0000305"
FT CONFLICT 225
FT /note="N -> S (in Ref. 2; AAQ21368)"
FT /evidence="ECO:0000305"
FT CONFLICT 232
FT /note="M -> V (in Ref. 2; AAQ21367)"
FT /evidence="ECO:0000305"
FT CONFLICT 238
FT /note="E -> Q (in Ref. 2; AAQ21367)"
FT /evidence="ECO:0000305"
FT CONFLICT 241
FT /note="T -> A (in Ref. 2; AAQ21368)"
FT /evidence="ECO:0000305"
FT CONFLICT 353
FT /note="G -> S (in Ref. 2; AAQ21367)"
FT /evidence="ECO:0000305"
FT CONFLICT 434
FT /note="S -> F (in Ref. 2; AAQ21367)"
FT /evidence="ECO:0000305"
FT CONFLICT 487
FT /note="I -> T (in Ref. 2; AAQ21367)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 519 AA; 59246 MW; AA96444A38EE79BC CRC64;
MSVSVLSPSR RLGGVSGILQ VTSLLILLLL LIKAAQLYLH RQWLLKALQQ FPCPPSHWLF
GHIQEFQHDQ ELQRIQERVK TFPSACPYWI WGGKVRVQLY DPDYMKVILG RSDPKSHGSY
KFLAPRIGYG LLLLNGQTWF QHRRMLTPAF HNDILKPYVG LMADSVRVML DKWEELLGQD
SPLEVFQHVS LMTLDTIMKS AFSHQGSIQV DRNSQSYIQA ISDLNSLVFC CMRNAFHEND
TIYSLTSAGR WTHRACQLAH QHTDQVIQLR KAQLQKEGEL EKIKRKRHLD FLDILLLAKM
ENGSILSDKD LRAEVDTFMF EGHDTTASGI SWILYALATH PKHQERCREE IHGLLGDGAS
ITWNHLDQMP YTTMCIKEAL RLYPPVPGIG RELSTPVTFP DGRSLPKGIM VLLSIYGLHH
NPKVWPNLEV FDPSRFAPGS AQHSHAFLPF SGGSRNCIGK QFAMNQLKVA RALTLLRFEL
LPDPTRIPIP MARLVLKSKN GIHLRLRRLP NPCEDKDQL
