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Protein

Cytochrome P450 4A22

Gene

CYP4A22

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

Functioni

Catalyzes the omega- and (omega-1)-hydroxylation of various fatty acids such as laurate and palmitate. Shows no activity towards arachidonic acid and prostaglandin A1. Lacks functional activity in the kidney and does not contribute to renal 20-hydroxyeicosatetraenoic acid (20-HETE) biosynthesis.2 Publications

Catalytic activityi

A long-chain fatty acid + NADPH + O2 = an omega-hydroxy-long-chain fatty acid + NADP+ + H2O.1 Publication

Kineticsi

Vmax:15.2 µmol/min/µmol enzyme.

  1. KM=56.7 µM for laurate1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei321Heme (covalent; via 1 link)By similarity1
    Metal bindingi457Iron (heme axial ligand)By similarity1

    GO - Molecular functioni

    Complete GO annotation...

    Keywords - Molecular functioni

    Monooxygenase, Oxidoreductase

    Keywords - Ligandi

    Heme, Iron, Metal-binding, NADP

    Enzyme and pathway databases

    BioCyciZFISH:HS08660-MONOMER.
    ReactomeiR-HSA-211935. Fatty acids.
    R-HSA-211958. Miscellaneous substrates.
    R-HSA-211979. Eicosanoids.
    R-HSA-2142691. Synthesis of Leukotrienes (LT) and Eoxins (EX).

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cytochrome P450 4A22
    Alternative name(s):
    CYPIVA22
    Fatty acid omega-hydroxylase
    Lauric acid omega-hydroxylase
    Long-chain fatty acid omega-monooxygenase (EC:1.14.13.2051 Publication)
    Gene namesi
    Name:CYP4A22
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:20575. CYP4A22.

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane, Microsome

    Pathology & Biotechi

    Organism-specific databases

    OpenTargetsiENSG00000162365.
    PharmGKBiPA134979692.

    Polymorphism and mutation databases

    BioMutaiCYP4A22.
    DMDMi74746067.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Initiator methionineiRemovedBy similarity
    PropeptideiPRO_00003434082 – 4By similarity3
    ChainiPRO_00003434095 – 519Cytochrome P450 4A22Add BLAST515

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei440PhosphoserineBy similarity1

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PaxDbiQ5TCH4.
    PeptideAtlasiQ5TCH4.
    PRIDEiQ5TCH4.

    PTM databases

    iPTMnetiQ5TCH4.
    PhosphoSitePlusiQ5TCH4.

    Expressioni

    Gene expression databases

    BgeeiENSG00000162365.
    ExpressionAtlasiQ5TCH4. baseline and differential.
    GenevisibleiQ5TCH4. HS.

    Interactioni

    Protein-protein interaction databases

    BioGridi129896. 1 interactor.
    STRINGi9606.ENSP00000360958.

    Structurei

    3D structure databases

    ProteinModelPortaliQ5TCH4.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Compositional bias

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Compositional biasi24 – 31Poly-Leu8
    Compositional biasi131 – 134Poly-Leu4

    Sequence similaritiesi

    Belongs to the cytochrome P450 family.Curated

    Phylogenomic databases

    eggNOGiKOG0157. Eukaryota.
    COG2124. LUCA.
    GeneTreeiENSGT00760000118816.
    HOGENOMiHOG000233833.
    HOVERGENiHBG000182.
    InParanoidiQ5TCH4.
    KOiK17688.
    PhylomeDBiQ5TCH4.
    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.

    Sequence processingi: The displayed sequence is further processed into a mature form.

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

    Isoform 1 (identifier: Q5TCH4-1) [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
    MSVSVLSPSR RLGGVSGILQ VTSLLILLLL LIKAAQLYLH RQWLLKALQQ
    60 70 80 90 100
    FPCPPSHWLF GHIQEFQHDQ ELQRIQERVK TFPSACPYWI WGGKVRVQLY
    110 120 130 140 150
    DPDYMKVILG RSDPKSHGSY KFLAPRIGYG LLLLNGQTWF QHRRMLTPAF
    160 170 180 190 200
    HNDILKPYVG LMADSVRVML DKWEELLGQD SPLEVFQHVS LMTLDTIMKS
    210 220 230 240 250
    AFSHQGSIQV DRNSQSYIQA ISDLNSLVFC CMRNAFHEND TIYSLTSAGR
    260 270 280 290 300
    WTHRACQLAH QHTDQVIQLR KAQLQKEGEL EKIKRKRHLD FLDILLLAKM
    310 320 330 340 350
    ENGSILSDKD LRAEVDTFMF EGHDTTASGI SWILYALATH PKHQERCREE
    360 370 380 390 400
    IHGLLGDGAS ITWNHLDQMP YTTMCIKEAL RLYPPVPGIG RELSTPVTFP
    410 420 430 440 450
    DGRSLPKGIM VLLSIYGLHH NPKVWPNLEV FDPSRFAPGS AQHSHAFLPF
    460 470 480 490 500
    SGGSRNCIGK QFAMNQLKVA RALTLLRFEL LPDPTRIPIP MARLVLKSKN
    510
    GIHLRLRRLP NPCEDKDQL
    Length:519
    Mass (Da):59,246
    Last modified:December 21, 2004 - v1
    Checksum:iAA96444A38EE79BC
    GO
    Isoform 2 (identifier: Q5TCH4-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         356-519: Missing.

    Show »
    Length:355
    Mass (Da):40,922
    Checksum:i392C812A7C120920
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti2S → A in AAQ21368 (PubMed:15611369).Curated1
    Sequence conflicti114P → S in AAQ21368 (PubMed:15611369).Curated1
    Sequence conflicti225N → S in AAQ21368 (PubMed:15611369).Curated1
    Sequence conflicti232M → V in AAQ21367 (PubMed:15611369).Curated1
    Sequence conflicti238E → Q in AAQ21367 (PubMed:15611369).Curated1
    Sequence conflicti241T → A in AAQ21368 (PubMed:15611369).Curated1
    Sequence conflicti353G → S in AAQ21367 (PubMed:15611369).Curated1
    Sequence conflicti434S → F in AAQ21367 (PubMed:15611369).Curated1
    Sequence conflicti487I → T in AAQ21367 (PubMed:15611369).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_04434911R → C in allele CYP4A22*2 and CYP4A22*3. 1 PublicationCorresponds to variant rs76011927dbSNPEnsembl.1
    Natural variantiVAR_061045104Y → F.Corresponds to variant rs61507155dbSNPEnsembl.1
    Natural variantiVAR_044350121K → R.1 PublicationCorresponds to variant rs2758717dbSNPEnsembl.1
    Natural variantiVAR_044351126R → W in allele CYP4A22*8, allele CYP4A22*9, allele CYP4A22*11, allele CYP4A22*12, allele CYP4A22*13, allele CYP4A22*14 and allele CYP4A22*15. 2 PublicationsCorresponds to variant rs12564525dbSNPEnsembl.1
    Natural variantiVAR_044352130G → S in allele CYP4A22*4, allele CYP4A22*10, allele CYP4A22*12, allele CYP4A22*13, allele CYP4A22*14 and allele CYP4A22*15. 2 PublicationsCorresponds to variant rs2056900dbSNPEnsembl.1
    Natural variantiVAR_044353152N → Y in allele CYP4A22*2, allele CYP4A22*3, allele CYP4A22*4, allele CYP4A22*5, allele CYP4A22*6, allele CYP4A22*7, allele CYP4A22*8, allele CYP4A22*9, allele CYP4A22*10, allele CYP4A22*11, allele CYP4A22*12, allele CYP4A22*13, allele CYP4A22*14 and allele CYP4A22*15. 2 PublicationsCorresponds to variant rs2056899dbSNPEnsembl.1
    Natural variantiVAR_044354185V → F in allele CYP4A22*10, allele CYP4A22*11, allele CYP4A22*12, allele CYP4A22*13, allele CYP4A22*14 and allele CYP4A22*15. 1 PublicationCorresponds to variant rs113777592dbSNPEnsembl.1
    Natural variantiVAR_044355226S → N.1 PublicationCorresponds to variant rs35202523dbSNPEnsembl.1
    Natural variantiVAR_044356230C → S.1 PublicationCorresponds to variant rs35156123dbSNPEnsembl.1
    Natural variantiVAR_044357231C → R Allele CYP4A22*2, allele CYP4A22*3, allele CYP4A22*4, allele CYP4A22*5, allele CYP4A22*6, allele CYP4A22*7, allele CYP4A22*8, allele CYP4A22*9, allele CYP4A22*10, allele CYP4A22*11, allele CYP4A22*12, allele CYP4A22*13, allele CYP4A22*14 and allele CYP4A22*15. 2 PublicationsCorresponds to variant rs10789501dbSNPEnsembl.1
    Natural variantiVAR_044358276K → T in allele CYP4A22*8, allele CYP4A22*11, allele CYP4A22*14 and allele CYP4A22*15. 1 PublicationCorresponds to variant rs149718343dbSNPEnsembl.1
    Natural variantiVAR_044359428L → P in allele CYP4A22*6, allele CYP4A22*9, allele CYP4A22*10, allele CYP4A22*12, allele CYP4A22*13 and allele CYP4A22*15. 2 PublicationsCorresponds to variant rs2405599dbSNPEnsembl.1
    Natural variantiVAR_044360491M → I.1 PublicationCorresponds to variant rs2758714dbSNPEnsembl.1
    Natural variantiVAR_044361509L → F in allele CYP4A22*7, allele CYP4A22*10, allele CYP4A22*11, allele CYP4A22*13, allele CYP4A22*14 and allele CYP4A22*15. 2 PublicationsCorresponds to variant rs4926600dbSNPEnsembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_034584356 – 519Missing in isoform 2. CuratedAdd BLAST164

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF208532 Genomic DNA. Translation: AAF76722.1.
    AY280371 mRNA. Translation: AAQ21367.1.
    AY280372 mRNA. Translation: AAQ21368.1.
    AL135960 Genomic DNA. Translation: CAI19737.1.
    AL135960 Genomic DNA. Translation: CAI19738.1.
    BC148248 mRNA. Translation: AAI48249.1.
    CCDSiCCDS30707.1. [Q5TCH4-1]
    RefSeqiNP_001010969.2. NM_001010969.3. [Q5TCH4-1]
    NP_001295031.1. NM_001308102.1.
    UniGeneiHs.726474.

    Genome annotation databases

    EnsembliENST00000371891; ENSP00000360958; ENSG00000162365. [Q5TCH4-1]
    GeneIDi284541.
    KEGGihsa:284541.
    UCSCiuc001cqv.2. human. [Q5TCH4-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Cytochrome P450 Allele Nomenclature Committee

    CYP4A22 alleles

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF208532 Genomic DNA. Translation: AAF76722.1.
    AY280371 mRNA. Translation: AAQ21367.1.
    AY280372 mRNA. Translation: AAQ21368.1.
    AL135960 Genomic DNA. Translation: CAI19737.1.
    AL135960 Genomic DNA. Translation: CAI19738.1.
    BC148248 mRNA. Translation: AAI48249.1.
    CCDSiCCDS30707.1. [Q5TCH4-1]
    RefSeqiNP_001010969.2. NM_001010969.3. [Q5TCH4-1]
    NP_001295031.1. NM_001308102.1.
    UniGeneiHs.726474.

    3D structure databases

    ProteinModelPortaliQ5TCH4.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi129896. 1 interactor.
    STRINGi9606.ENSP00000360958.

    PTM databases

    iPTMnetiQ5TCH4.
    PhosphoSitePlusiQ5TCH4.

    Polymorphism and mutation databases

    BioMutaiCYP4A22.
    DMDMi74746067.

    Proteomic databases

    PaxDbiQ5TCH4.
    PeptideAtlasiQ5TCH4.
    PRIDEiQ5TCH4.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000371891; ENSP00000360958; ENSG00000162365. [Q5TCH4-1]
    GeneIDi284541.
    KEGGihsa:284541.
    UCSCiuc001cqv.2. human. [Q5TCH4-1]

    Organism-specific databases

    CTDi284541.
    GeneCardsiCYP4A22.
    H-InvDBHIX0028676.
    HGNCiHGNC:20575. CYP4A22.
    MIMi615341. gene.
    neXtProtiNX_Q5TCH4.
    OpenTargetsiENSG00000162365.
    PharmGKBiPA134979692.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG0157. Eukaryota.
    COG2124. LUCA.
    GeneTreeiENSGT00760000118816.
    HOGENOMiHOG000233833.
    HOVERGENiHBG000182.
    InParanoidiQ5TCH4.
    KOiK17688.
    PhylomeDBiQ5TCH4.
    TreeFamiTF105088.

    Enzyme and pathway databases

    BioCyciZFISH:HS08660-MONOMER.
    ReactomeiR-HSA-211935. Fatty acids.
    R-HSA-211958. Miscellaneous substrates.
    R-HSA-211979. Eicosanoids.
    R-HSA-2142691. Synthesis of Leukotrienes (LT) and Eoxins (EX).

    Miscellaneous databases

    GeneWikiiCYP4A22.
    GenomeRNAii284541.
    PROiQ5TCH4.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000162365.
    ExpressionAtlasiQ5TCH4. baseline and differential.
    GenevisibleiQ5TCH4. 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...

    Entry informationi

    Entry nameiCP4AM_HUMAN
    AccessioniPrimary (citable) accession number: Q5TCH4
    Secondary accession number(s): Q5TCH3
    , Q6JXK7, Q6JXK8, Q9NRM4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 1, 2008
    Last sequence update: December 21, 2004
    Last modified: November 2, 2016
    This is version 112 of the entry and version 1 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

    Caution

    Was originally termed CYP4A11.1 Publication

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 1
      Human chromosome 1: 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

    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 one 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.