CP4AL_PIG
ID CP4AL_PIG Reviewed; 504 AA.
AC Q9GJX5; Q70BW2; Q70BZ7;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=Taurochenodeoxycholic 6 alpha-hydroxylase;
DE EC=1.14.14.57 {ECO:0000269|PubMed:11113117, ECO:0000269|PubMed:3095476};
DE AltName: Full=CYPIVA21;
DE AltName: Full=Cytochrome P450 4A21;
GN Name=CYP4A21;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, FUNCTION, CATALYTIC
RP ACTIVITY, AND MUTAGENESIS OF 314-ALA--SER-319.
RC TISSUE=Liver;
RX PubMed=11113117; DOI=10.1074/jbc.m006584200;
RA Lundell K., Hansson R., Wikvall K.;
RT "Cloning and expression of a pig liver taurochenodeoxycholic acid 6alpha-
RT hydroxylase (CYP4A21): a novel member of the CYP4A subfamily.";
RL J. Biol. Chem. 276:9606-9612(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-42 AND 83-504.
RX PubMed=14641109; DOI=10.1042/bj20031657;
RA Lundell K.;
RT "The porcine taurochenodeoxycholic acid 6alpha-hydroxylase (CYP4A21) gene:
RT evolution by gene duplication and gene conversion.";
RL Biochem. J. 378:1053-1058(2004).
RN [3]
RP PROTEIN SEQUENCE OF 2-21; 59-71; 83-88; 228-238; 430-449 AND 472-480, AND
RP FUNCTION.
RX PubMed=7649186; DOI=10.1111/j.1432-1033.1995.0855d.x;
RA Araya Z., Hellman U., Hansson R.;
RT "Characterisation of taurochenodeoxycholic acid 6 alpha-hydroxylase from
RT pig liver microsomes.";
RL Eur. J. Biochem. 231:855-861(1995).
RN [4]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RC TISSUE=Liver;
RX PubMed=3095476;
RA Bostroem H.;
RT "Characterization of 6 alpha-hydroxylation of taurochenodeoxycholic acid in
RT pig liver.";
RL J. Lipid Res. 27:807-812(1986).
CC -!- FUNCTION: Catalyzes the 6 alpha hydroxylation oxidation of
CC taurodeoxycholate to produce the pig specific bile acid taurohyocholic
CC acid. {ECO:0000269|PubMed:11113117, ECO:0000269|PubMed:3095476,
CC ECO:0000269|PubMed:7649186}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=O2 + reduced [NADPH--hemoprotein reductase] +
CC taurochenodeoxycholate = H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase] + taurohyocholate; Xref=Rhea:RHEA:17857, Rhea:RHEA-
CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:9407,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:58874;
CC EC=1.14.14.57; Evidence={ECO:0000269|PubMed:11113117,
CC ECO:0000269|PubMed:3095476};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=lithocholate + O2 + reduced [NADPH--hemoprotein reductase] =
CC H(+) + H2O + hyodeoxycholate + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:23644, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:29744, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:58875; EC=1.14.14.57;
CC Evidence={ECO:0000269|PubMed:11113117, ECO:0000269|PubMed:3095476};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305};
CC Multi-pass membrane protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Primarily expressed in liver. Low expression in
CC kidney. {ECO:0000269|PubMed:11113117}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; AJ278474; CAC19358.1; -; mRNA.
DR EMBL; AJ586859; CAE52546.1; -; Genomic_DNA.
DR EMBL; AJ586618; CAE52532.1; -; Genomic_DNA.
DR RefSeq; NP_999590.1; NM_214425.1.
DR AlphaFoldDB; Q9GJX5; -.
DR SMR; Q9GJX5; -.
DR STRING; 9823.ENSSSCP00000004207; -.
DR PaxDb; Q9GJX5; -.
DR PeptideAtlas; Q9GJX5; -.
DR Ensembl; ENSSSCT00000004307; ENSSSCP00000004207; ENSSSCG00000003891.
DR GeneID; 403327; -.
DR KEGG; ssc:403327; -.
DR CTD; 403327; -.
DR eggNOG; KOG0157; Eukaryota.
DR GeneTree; ENSGT00940000155173; -.
DR InParanoid; Q9GJX5; -.
DR OrthoDB; 1247045at2759; -.
DR BRENDA; 1.14.14.57; 6170.
DR Proteomes; UP000008227; Chromosome 6.
DR Proteomes; UP000314985; Unplaced.
DR Bgee; ENSSSCG00000003891; Expressed in adult mammalian kidney and 20 other tissues.
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:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0033780; F:taurochenodeoxycholate 6alpha-hydroxylase activity; IEA:UniProtKB-EC.
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 Direct protein sequencing; Endoplasmic reticulum; Heme; Iron; Membrane;
KW Metal-binding; Monooxygenase; NADP; Oxidoreductase; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:7649186"
FT CHAIN 2..504
FT /note="Taurochenodeoxycholic 6 alpha-hydroxylase"
FT /id="PRO_0000280742"
FT TRANSMEM 6..26
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 110..130
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 451
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 MUTAGEN 314..319
FT /note="AAGHDS->FEGHDT: Complete loss of activity."
FT /evidence="ECO:0000269|PubMed:11113117"
FT CONFLICT 135
FT /note="Q -> P (in Ref. 2; CAE52532)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 504 AA; 57216 MW; 101DAF0494F1BF7D CRC64;
MTVPALASVS GLLQVASLLG LLLLLLKAAQ LYLRRQWLLK ALQQFPSPPS HWLYGHSREF
QEESELQPLL KRVEKYPSAC ARWLWGTRAM VLVYDPDYMK VVLARSEPKA PVLYRLLIPW
IGCGLLLLNG QMWFQRRRML TPAFHYDILK PYVGLMAKSV QVMLDKWEQL VAQDPRLEIV
GPVSLMTLDT IMKCAFSHQG SAQTDGDSQS YIQAIWDLKN LIFSRLRSAF LQNDIIYRLS
PEGRQCQRAC QKVHQHTDRV IQLRKTHLQK EGEMENVKKK RHLDFLDILL FARMENGNSL
SDTDVRAEVD TFMAAGHDST ASGISWVLYA LASNPEHQQR CREEIQGLLG DGTSITWDHL
DQMPYTTMCI KEALRLYPPV PSVGRELSKP ITFPDGRSLP AGIILSLSIY GLHHNPQVWP
NPEEFDPSRF APGSARHSHA FMPFSGGSRN CIGKQFAMNE MKVVVALTLL RFELAPDPSR
IPVPIQGIVL KSKNGIHLNL RKIP
