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Q5TCH4

- CP4AM_HUMAN

UniProt

Q5TCH4 - CP4AM_HUMAN

Protein

Cytochrome P450 4A22

Gene

CYP4A22

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 93 (01 Oct 2014)
      Sequence version 1 (21 Dec 2004)
      Previous versions | rss
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    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

    Octane + reduced rubredoxin + O2 = 1-octanol + oxidized rubredoxin + H2O.

    Kineticsi

    Vmax:15.2 µmol/min/µmol enzyme.

    1. KM=56.7 µM for laurate1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei321 – 3211Heme (covalent; via 1 link)By similarity
    Metal bindingi457 – 4571Iron (heme axial ligand)By similarity

    GO - Molecular functioni

    1. alkane 1-monooxygenase activity Source: UniProtKB-EC
    2. arachidonic acid omega-hydroxylase activity Source: UniProtKB-EC
    3. heme binding Source: InterPro
    4. iron ion binding Source: InterPro

    Keywords - Molecular functioni

    Monooxygenase, Oxidoreductase

    Keywords - Ligandi

    Heme, Iron, Metal-binding

    Enzyme and pathway databases

    ReactomeiREACT_13425. Miscellaneous substrates.
    REACT_13645. Eicosanoids.
    REACT_13814. Fatty acids.
    REACT_150420. 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 (EC:1.14.15.3)
    Gene namesi
    Name:CYP4A22
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:20575. CYP4A22.

    Subcellular locationi

    GO - Cellular componenti

    1. endoplasmic reticulum membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane, Microsome

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA134979692.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Propeptidei1 – 44By similarityPRO_0000343408
    Chaini5 – 519515Cytochrome P450 4A22PRO_0000343409Add
    BLAST

    Proteomic databases

    PaxDbiQ5TCH4.
    PRIDEiQ5TCH4.

    PTM databases

    PhosphoSiteiQ5TCH4.

    Expressioni

    Gene expression databases

    BgeeiQ5TCH4.
    GenevestigatoriQ5TCH4.

    Interactioni

    Protein-protein interaction databases

    STRINGi9606.ENSP00000360958.

    Structurei

    3D structure databases

    ProteinModelPortaliQ5TCH4.
    SMRiQ5TCH4. Positions 61-508.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi24 – 318Poly-Leu
    Compositional biasi131 – 1344Poly-Leu

    Sequence similaritiesi

    Belongs to the cytochrome P450 family.Curated

    Phylogenomic databases

    eggNOGiCOG2124.
    HOGENOMiHOG000233833.
    HOVERGENiHBG000182.
    InParanoidiQ5TCH4.
    KOiK17688.
    OMAiKSAFSHQ.
    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. Align

    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

    MSVSVLSPSR RLGGVSGILQ VTSLLILLLL LIKAAQLYLH RQWLLKALQQ    50
    FPCPPSHWLF GHIQEFQHDQ ELQRIQERVK TFPSACPYWI WGGKVRVQLY 100
    DPDYMKVILG RSDPKSHGSY KFLAPRIGYG LLLLNGQTWF QHRRMLTPAF 150
    HNDILKPYVG LMADSVRVML DKWEELLGQD SPLEVFQHVS LMTLDTIMKS 200
    AFSHQGSIQV DRNSQSYIQA ISDLNSLVFC CMRNAFHEND TIYSLTSAGR 250
    WTHRACQLAH QHTDQVIQLR KAQLQKEGEL EKIKRKRHLD FLDILLLAKM 300
    ENGSILSDKD LRAEVDTFMF EGHDTTASGI SWILYALATH PKHQERCREE 350
    IHGLLGDGAS ITWNHLDQMP YTTMCIKEAL RLYPPVPGIG RELSTPVTFP 400
    DGRSLPKGIM VLLSIYGLHH NPKVWPNLEV FDPSRFAPGS AQHSHAFLPF 450
    SGGSRNCIGK QFAMNQLKVA RALTLLRFEL LPDPTRIPIP MARLVLKSKN 500
    GIHLRLRRLP NPCEDKDQL 519
    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)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti2 – 21S → A in AAQ21368. (PubMed:15611369)Curated
    Sequence conflicti114 – 1141P → S in AAQ21368. (PubMed:15611369)Curated
    Sequence conflicti225 – 2251N → S in AAQ21368. (PubMed:15611369)Curated
    Sequence conflicti232 – 2321M → V in AAQ21367. (PubMed:15611369)Curated
    Sequence conflicti238 – 2381E → Q in AAQ21367. (PubMed:15611369)Curated
    Sequence conflicti241 – 2411T → A in AAQ21368. (PubMed:15611369)Curated
    Sequence conflicti353 – 3531G → S in AAQ21367. (PubMed:15611369)Curated
    Sequence conflicti434 – 4341S → F in AAQ21367. (PubMed:15611369)Curated
    Sequence conflicti487 – 4871I → T in AAQ21367. (PubMed:15611369)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti11 – 111R → C in allele CYP4A22*2 and CYP4A22*3. 1 Publication
    Corresponds to variant rs76011927 [ dbSNP | Ensembl ].
    VAR_044349
    Natural varianti104 – 1041Y → F.
    Corresponds to variant rs61507155 [ dbSNP | Ensembl ].
    VAR_061045
    Natural varianti121 – 1211K → R.1 Publication
    Corresponds to variant rs2758717 [ dbSNP | Ensembl ].
    VAR_044350
    Natural varianti126 – 1261R → 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 Publications
    Corresponds to variant rs12564525 [ dbSNP | Ensembl ].
    VAR_044351
    Natural varianti130 – 1301G → S in allele CYP4A22*4, allele CYP4A22*10, allele CYP4A22*12, allele CYP4A22*13, allele CYP4A22*14 and allele CYP4A22*15. 2 Publications
    Corresponds to variant rs2056900 [ dbSNP | Ensembl ].
    VAR_044352
    Natural varianti152 – 1521N → 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 Publications
    Corresponds to variant rs2056899 [ dbSNP | Ensembl ].
    VAR_044353
    Natural varianti185 – 1851V → F in allele CYP4A22*10, allele CYP4A22*11, allele CYP4A22*12, allele CYP4A22*13, allele CYP4A22*14 and allele CYP4A22*15. 1 Publication
    Corresponds to variant rs113777592 [ dbSNP | Ensembl ].
    VAR_044354
    Natural varianti226 – 2261S → N.1 Publication
    Corresponds to variant rs35202523 [ dbSNP | Ensembl ].
    VAR_044355
    Natural varianti230 – 2301C → S.1 Publication
    Corresponds to variant rs35156123 [ dbSNP | Ensembl ].
    VAR_044356
    Natural varianti231 – 2311C → 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 Publications
    Corresponds to variant rs10789501 [ dbSNP | Ensembl ].
    VAR_044357
    Natural varianti276 – 2761K → T in allele CYP4A22*8, allele CYP4A22*11, allele CYP4A22*14 and allele CYP4A22*15. 1 Publication
    Corresponds to variant rs149718343 [ dbSNP | Ensembl ].
    VAR_044358
    Natural varianti428 – 4281L → P in allele CYP4A22*6, allele CYP4A22*9, allele CYP4A22*10, allele CYP4A22*12, allele CYP4A22*13 and allele CYP4A22*15. 2 Publications
    Corresponds to variant rs2405599 [ dbSNP | Ensembl ].
    VAR_044359
    Natural varianti491 – 4911M → I.1 Publication
    Corresponds to variant rs2758714 [ dbSNP | Ensembl ].
    VAR_044360
    Natural varianti509 – 5091L → F in allele CYP4A22*7, allele CYP4A22*10, allele CYP4A22*11, allele CYP4A22*13, allele CYP4A22*14 and allele CYP4A22*15. 2 Publications
    Corresponds to variant rs4926600 [ dbSNP | Ensembl ].
    VAR_044361

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei356 – 519164Missing in isoform 2. CuratedVSP_034584Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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_001010969.2. [Q5TCH4-1]
    UniGeneiHs.726474.

    Genome annotation databases

    EnsembliENST00000294337; ENSP00000294337; ENSG00000162365.
    ENST00000371891; ENSP00000360958; ENSG00000162365. [Q5TCH4-1]
    GeneIDi284541.
    KEGGihsa:284541.
    UCSCiuc001cqv.1. human. [Q5TCH4-1]

    Polymorphism databases

    DMDMi74746067.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Cytochrome P450 Allele Nomenclature Committee

    CYP4A22 alleles

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS30707.1. [Q5TCH4-1 ]
    RefSeqi NP_001010969.2. NM_001010969.2. [Q5TCH4-1 ]
    UniGenei Hs.726474.

    3D structure databases

    ProteinModelPortali Q5TCH4.
    SMRi Q5TCH4. Positions 61-508.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 9606.ENSP00000360958.

    PTM databases

    PhosphoSitei Q5TCH4.

    Polymorphism databases

    DMDMi 74746067.

    Proteomic databases

    PaxDbi Q5TCH4.
    PRIDEi Q5TCH4.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000294337 ; ENSP00000294337 ; ENSG00000162365 .
    ENST00000371891 ; ENSP00000360958 ; ENSG00000162365 . [Q5TCH4-1 ]
    GeneIDi 284541.
    KEGGi hsa:284541.
    UCSCi uc001cqv.1. human. [Q5TCH4-1 ]

    Organism-specific databases

    CTDi 284541.
    GeneCardsi GC01P047603.
    H-InvDB HIX0028676.
    HGNCi HGNC:20575. CYP4A22.
    MIMi 615341. gene.
    neXtProti NX_Q5TCH4.
    PharmGKBi PA134979692.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG2124.
    HOGENOMi HOG000233833.
    HOVERGENi HBG000182.
    InParanoidi Q5TCH4.
    KOi K17688.
    OMAi KSAFSHQ.
    PhylomeDBi Q5TCH4.
    TreeFami TF105088.

    Enzyme and pathway databases

    Reactomei REACT_13425. Miscellaneous substrates.
    REACT_13645. Eicosanoids.
    REACT_13814. Fatty acids.
    REACT_150420. Synthesis of Leukotrienes (LT) and Eoxins (EX).

    Miscellaneous databases

    GeneWikii CYP4A22.
    GenomeRNAii 284541.
    NextBioi 94950.
    PROi Q5TCH4.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q5TCH4.
    Genevestigatori Q5TCH4.

    Family and domain databases

    Gene3Di 1.10.630.10. 1 hit.
    InterProi IPR001128. Cyt_P450.
    IPR017972. Cyt_P450_CS.
    IPR002401. Cyt_P450_E_grp-I.
    [Graphical view ]
    Pfami PF00067. p450. 1 hit.
    [Graphical view ]
    PRINTSi PR00463. EP450I.
    PR00385. P450.
    SUPFAMi SSF48264. SSF48264. 1 hit.
    PROSITEi PS00086. CYTOCHROME_P450. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Human fatty acid omega-hydroxylase, CYP4A11: determination of complete genomic sequence and characterization of purified recombinant protein."
      Kawashima H., Naganuma T., Kusunose E., Kono T., Yasumoto R., Sugimura K., Kishimoto T.
      Arch. Biochem. Biophys. 378:333-339(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, VARIANTS ARG-121 AND ILE-491.
    2. "Functional variant of CYP4A11 20-hydroxyeicosatetraenoic acid synthase is associated with essential hypertension."
      Gainer J.V., Bellamine A., Dawson E.P., Womble K.E., Grant S.W., Wang Y., Cupples L.A., Guo C.-Y., Demissie S., O'Donnell C.J., Brown N.J., Waterman M.R., Capdevila J.H.
      Circulation 111:63-69(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, VARIANTS TRP-126; SER-130; TYR-152; ASN-226; SER-230; ARG-231; PRO-428 AND PHE-509.
      Tissue: Kidney and Liver.
    3. "The DNA sequence and biological annotation of human chromosome 1."
      Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
      , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
      Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. "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] (ISOFORM 1).
    5. "Genetic polymorphisms and haplotype structures of the CYP4A22 gene in a Japanese population."
      Hiratsuka M., Nozawa H., Katsumoto Y., Moteki T., Sasaki T., Konno Y., Mizugaki M.
      Mutat. Res. 599:98-104(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS CYS-11; TRP-126; SER-130; TYR-152; PHE-185; ARG-231; THR-276; PRO-428 AND PHE-509.

    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: October 1, 2014
    This is version 93 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

    External Data

    Dasty 3