CP21A_PIG
ID CP21A_PIG Reviewed; 492 AA.
AC P15540; A5A8W6; Q02390;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 2.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Steroid 21-hydroxylase {ECO:0000303|PubMed:2109953};
DE EC=1.14.14.16 {ECO:0000250|UniProtKB:P00191, ECO:0000250|UniProtKB:P08686};
DE AltName: Full=21-OHase;
DE AltName: Full=Cytochrome P-450c21;
DE AltName: Full=Cytochrome P450 21;
DE AltName: Full=Cytochrome P450 XXI;
DE AltName: Full=Cytochrome P450-C21;
GN Name=CYP21; Synonyms=CYP21A1, CYP21A3;
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 PROTEIN SEQUENCE.
RC TISSUE=Adrenal gland;
RX PubMed=3495238; DOI=10.1016/0003-9861(87)90115-9;
RA Haniu M., Yanagibashi K., Hall P.F., Shively J.E.;
RT "Complete amino acid sequence of 21-hydroxylase cytochrome P-450 from
RT porcine adrenal microsomes.";
RL Arch. Biochem. Biophys. 254:380-384(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1482677; DOI=10.1016/0167-4781(92)90115-g;
RA Burghelle-Mayeur C., Geffrotin C., Vaiman M.;
RT "Sequences of the swine 21-hydroxylase gene (CYP21) and a portion of the
RT opposite-strand overlapping gene of unknown function previously described
RT in human.";
RL Biochim. Biophys. Acta 1171:153-161(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Meishan;
RX PubMed=12643481; DOI=10.2527/2003.812385x;
RA Quintanilla R., Demeure O., Bidanel J.P., Milan D., Iannuccelli N.,
RA Amigues Y., Gruand J., Renard C., Chevalet C., Bonneau M.;
RT "Detection of quantitative trait loci for fat androstenone levels in
RT pigs.";
RL J. Anim. Sci. 81:385-394(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RG Porcine genome sequencing project;
RL Submitted (MAY-2007) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-99.
RX PubMed=2109953; DOI=10.1111/j.1365-2052.1990.tb03202.x;
RA Geffrotin C., Chardon P., de Andres-Cara D.F., Feil R., Renard C.,
RA Vaiman M.;
RT "The swine steroid 21-hydroxylase gene (CYP21): cloning and mapping within
RT the swine leucocyte antigen complex.";
RL Anim. Genet. 21:1-13(1990).
CC -!- FUNCTION: A cytochrome P450 monooxygenase that plays a major role in
CC adrenal steroidogenesis. Catalyzes the hydroxylation at C-21 of
CC progesterone and 17alpha-hydroxyprogesterone to respectively form 11-
CC deoxycorticosterone and 11-deoxycortisol, intermediate metabolites in
CC the biosynthetic pathway of mineralocorticoids and glucocorticoids.
CC Mechanistically, uses molecular oxygen inserting one oxygen atom into a
CC substrate, and reducing the second into a water molecule, with two
CC electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-
CC ferrihemoprotein reductase). {ECO:0000250|UniProtKB:P00191,
CC ECO:0000250|UniProtKB:P08686}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=O2 + progesterone + reduced [NADPH--hemoprotein reductase] =
CC 21-hydroxyprogesterone + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:50304, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16973, ChEBI:CHEBI:17026, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; EC=1.14.14.16;
CC Evidence={ECO:0000250|UniProtKB:P00191,
CC ECO:0000250|UniProtKB:P08686};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50305;
CC Evidence={ECO:0000250|UniProtKB:P00191,
CC ECO:0000250|UniProtKB:P08686};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17alpha-hydroxyprogesterone + O2 + reduced [NADPH--hemoprotein
CC reductase] = 11-deoxycortisol + H(+) + H2O + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:50308, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17252, ChEBI:CHEBI:28324,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; EC=1.14.14.16;
CC Evidence={ECO:0000250|UniProtKB:P00191,
CC ECO:0000250|UniProtKB:P08686};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50309;
CC Evidence={ECO:0000250|UniProtKB:P00191,
CC ECO:0000250|UniProtKB:P08686};
CC -!- COFACTOR:
CC Name=heme b; Xref=ChEBI:CHEBI:60344;
CC Evidence={ECO:0000250|UniProtKB:P00191,
CC ECO:0000250|UniProtKB:P08686};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P08686}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P08686}. Microsome membrane
CC {ECO:0000250|UniProtKB:P08686}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P08686}.
CC -!- DOMAIN: The leucine-rich hydrophobic amino acid N-terminal region
CC probably helps to anchor the protein to the microsomal membrane.
CC {ECO:0000250|UniProtKB:P08686}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; M83939; AAA31080.1; -; Genomic_DNA.
DR EMBL; AF490410; AAM11646.1; -; Genomic_DNA.
DR EMBL; AL773560; CAN59658.1; -; Genomic_DNA.
DR PIR; S28169; A32525.
DR RefSeq; NP_999598.1; NM_214433.1.
DR AlphaFoldDB; P15540; -.
DR SMR; P15540; -.
DR STRING; 9823.ENSSSCP00000001529; -.
DR PaxDb; P15540; -.
DR PRIDE; P15540; -.
DR Ensembl; ENSSSCT00000001571; ENSSSCP00000001529; ENSSSCG00000001428.
DR Ensembl; ENSSSCT00030070209; ENSSSCP00030032011; ENSSSCG00030050353.
DR Ensembl; ENSSSCT00035083801; ENSSSCP00035034843; ENSSSCG00035062342.
DR Ensembl; ENSSSCT00040073731; ENSSSCP00040031580; ENSSSCG00040054409.
DR GeneID; 403337; -.
DR KEGG; ssc:403337; -.
DR CTD; 13079; -.
DR VGNC; VGNC:103369; CYP21A1.
DR eggNOG; KOG0156; Eukaryota.
DR GeneTree; ENSGT00940000158338; -.
DR InParanoid; P15540; -.
DR OMA; ALADWAC; -.
DR OrthoDB; 702827at2759; -.
DR TreeFam; TF105095; -.
DR Reactome; R-SSC-193993; Mineralocorticoid biosynthesis.
DR Reactome; R-SSC-194002; Glucocorticoid biosynthesis.
DR Reactome; R-SSC-211976; Endogenous sterols.
DR Proteomes; UP000008227; Chromosome 7.
DR Proteomes; UP000314985; Unplaced.
DR Bgee; ENSSSCG00000001428; Expressed in semimembranosus muscle and 11 other tissues.
DR ExpressionAtlas; P15540; differential.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0103069; F:17-hydroxyprogesterone 21-hydroxylase activity; ISS:UniProtKB.
DR GO; GO:0020037; F:heme binding; ISS:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0106309; F:progesterone 21-hydroxylase activity; ISS:UniProtKB.
DR GO; GO:0004509; F:steroid 21-monooxygenase activity; IBA:GO_Central.
DR GO; GO:0005496; F:steroid binding; IEA:UniProtKB-KW.
DR GO; GO:0008395; F:steroid hydroxylase activity; ISS:UniProtKB.
DR GO; GO:0006704; P:glucocorticoid biosynthetic process; IBA:GO_Central.
DR GO; GO:0006694; P:steroid biosynthetic process; IBA:GO_Central.
DR GO; GO:0008202; P:steroid metabolic process; ISS: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 Direct protein sequencing; Endoplasmic reticulum; Heme; Iron;
KW Lipid-binding; Membrane; Metal-binding; Microsome; Monooxygenase;
KW Oxidoreductase; Reference proteome; Steroid-binding; Steroidogenesis.
FT CHAIN 1..492
FT /note="Steroid 21-hydroxylase"
FT /id="PRO_0000051978"
FT BINDING 92
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /evidence="ECO:0000250|UniProtKB:P08686"
FT BINDING 121
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /evidence="ECO:0000250|UniProtKB:P08686"
FT BINDING 232
FT /ligand="17alpha-hydroxyprogesterone"
FT /ligand_id="ChEBI:CHEBI:17252"
FT /evidence="ECO:0000250|UniProtKB:P00191"
FT BINDING 232
FT /ligand="progesterone"
FT /ligand_id="ChEBI:CHEBI:17026"
FT /evidence="ECO:0000250|UniProtKB:P08686"
FT BINDING 364
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /evidence="ECO:0000250|UniProtKB:P08686"
FT BINDING 425
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /evidence="ECO:0000250|UniProtKB:P08686"
FT BINDING 427
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P08686"
FT CONFLICT 10
FT /note="L -> T (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 13
FT /note="L -> K (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 55
FT /note="R -> K (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 141
FT /note="E -> C (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 201
FT /note="E -> D (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 391
FT /note="H -> I (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 463..465
FT /note="HPH -> VPY (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 492 AA; 55620 MW; 1FD5FFBFCA5A9E02 CRC64;
MVLVWLLLLL TLLAGARLLW GQWKLRNLHL PPLVPGFLHL LQPNLPIYLL GLTQRLGPIY
RLRLGLQDVV VLNSKRTIEE ALVRKWVDFA GRPQIPSYKL ASQHCPDISL GDYSLFWKAH
KKLTRSALLL GVRSSMEPRV EQLTQEFCER MRAQAGTPVT IQKEFSVLTC SIICCLTFGD
KEDTLVHALH DCVQDLMKTW EHWSIQILDM VPFLRFFPSP GLRRLKQAIE NRDHLVEKQL
RRHKESMVAG QWRDMLDYML QEAGRQRVEE GQGQLLEGHV HMSVVDLFIG GTETTANTLS
WAVVYLLHHP EIQWRLQEEL DRELGPGAAG SRVPYKDRAR LPLLNATIAE VLRLRPVVPL
ALPHRATRPS SIFGYDIPEG TVVIPNLQGA HLDETVWEQP HEFRPDRFLA PGANPSALAF
GCGARVCLGE PLARLELFVV LVQLLQAFTL LPPEGALPSL QPHPHSGINL KVQPFQVRLQ
PRGGRGEGPG PR
