CP21A_MOUSE
ID CP21A_MOUSE Reviewed; 487 AA.
AC P03940; A0JP50; O88304; Q64510; Q9QX14;
DT 23-OCT-1986, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 3.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Steroid 21-hydroxylase {ECO:0000303|Ref.3};
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=Cyp21a-1, Cyp21a1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3491986; DOI=10.1073/pnas.83.24.9601;
RA Chaplin D.D., Galbraith L.J., Seidman J.G., White P.C., Parker K.L.;
RT "Nucleotide sequence analysis of murine 21-hydroxylase genes: mutations
RT affecting gene expression.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:9601-9605(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=B10.WR;
RX PubMed=1918990;
RA Zepf N.E., Ogata R.T.;
RT "The murine Slp gene: additional evidence that sex-limited protein has no
RT biological function.";
RL J. Immunol. 147:2756-2763(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=C57BL/6 X CBA;
RA Matsumoto K., Ikuta T.;
RT "Mus musculus 5' truncated pseudogene of tenascin-X, steroid 21-hydroxylase
RT (Cyp21), and sex-limited protein (Slp) genes, partial cds and complete
RT sequences.";
RL Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=129;
RX PubMed=14656967; DOI=10.1101/gr.1736803;
RA Xie T., Rowen L., Aguado B., Ahearn M.E., Madan A., Qin S., Campbell R.D.,
RA Hood L.;
RT "Analysis of the gene-dense major histocompatibility complex class III
RT region and its comparison to mouse.";
RL Genome Res. 13:2621-2636(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 399-487.
RX PubMed=3874401; DOI=10.1073/pnas.82.13.4453;
RA Amor M., Tosi M., Duponchel C., Steinmetz M., Meo T.;
RT "Liver mRNA probes disclose two cytochrome P-450 genes duplicated in tandem
RT with the complement C4 loci of the mouse H-2S region.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:4453-4457(1985).
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; M15009; AAA37114.1; -; Genomic_DNA.
DR EMBL; M64933; AAA40118.1; -; Genomic_DNA.
DR EMBL; AB015623; BAA31153.1; -; Genomic_DNA.
DR EMBL; AF049850; AAC05278.1; -; Genomic_DNA.
DR EMBL; BC127167; AAI27168.1; -; mRNA.
DR CCDS; CCDS28658.1; -.
DR PIR; A26660; A26660.
DR PIR; S54785; S54785.
DR RefSeq; NP_034125.2; NM_009995.2.
DR AlphaFoldDB; P03940; -.
DR SMR; P03940; -.
DR BioGRID; 199004; 14.
DR STRING; 10090.ENSMUSP00000025223; -.
DR iPTMnet; P03940; -.
DR PhosphoSitePlus; P03940; -.
DR MaxQB; P03940; -.
DR PaxDb; P03940; -.
DR PRIDE; P03940; -.
DR ProteomicsDB; 283808; -.
DR GeneID; 13079; -.
DR KEGG; mmu:13079; -.
DR UCSC; uc008cdo.2; mouse.
DR CTD; 13079; -.
DR MGI; MGI:88591; Cyp21a1.
DR eggNOG; KOG0156; Eukaryota.
DR InParanoid; P03940; -.
DR OrthoDB; 702827at2759; -.
DR PhylomeDB; P03940; -.
DR TreeFam; TF105095; -.
DR Reactome; R-MMU-193993; Mineralocorticoid biosynthesis.
DR Reactome; R-MMU-194002; Glucocorticoid biosynthesis.
DR Reactome; R-MMU-211976; Endogenous sterols.
DR BioGRID-ORCS; 13079; 1 hit in 76 CRISPR screens.
DR PRO; PR:P03940; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; P03940; protein.
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; ISO:MGI.
DR GO; GO:0005496; F:steroid binding; IEA:UniProtKB-KW.
DR GO; GO:0008395; F:steroid hydroxylase activity; ISS:UniProtKB.
DR GO; GO:0006700; P:C21-steroid hormone biosynthetic process; ISO:MGI.
DR GO; GO:0006704; P:glucocorticoid biosynthetic process; IBA:GO_Central.
DR GO; GO:0006705; P:mineralocorticoid biosynthetic process; ISO:MGI.
DR GO; GO:0042448; P:progesterone metabolic process; ISO:MGI.
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 2: Evidence at transcript level;
KW Endoplasmic reticulum; Heme; Iron; Lipid-binding; Membrane; Metal-binding;
KW Microsome; Monooxygenase; Oxidoreductase; Reference proteome;
KW Steroid-binding; Steroidogenesis.
FT CHAIN 1..487
FT /note="Steroid 21-hydroxylase"
FT /id="PRO_0000051977"
FT BINDING 92
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /evidence="ECO:0000250|UniProtKB:P08686"
FT BINDING 117
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /evidence="ECO:0000250|UniProtKB:P08686"
FT BINDING 228
FT /ligand="17alpha-hydroxyprogesterone"
FT /ligand_id="ChEBI:CHEBI:17252"
FT /evidence="ECO:0000250|UniProtKB:P00191"
FT BINDING 228
FT /ligand="progesterone"
FT /ligand_id="ChEBI:CHEBI:17026"
FT /evidence="ECO:0000250|UniProtKB:P08686"
FT BINDING 357
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /evidence="ECO:0000250|UniProtKB:P08686"
FT BINDING 418
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /evidence="ECO:0000250|UniProtKB:P08686"
FT BINDING 420
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 31..32
FT /note="PP -> LR (in Ref. 1; AAA37114)"
FT /evidence="ECO:0000305"
FT CONFLICT 66
FT /note="M -> L (in Ref. 1; AAA37114)"
FT /evidence="ECO:0000305"
FT CONFLICT 218
FT /note="L -> F (in Ref. 3; BAA31153)"
FT /evidence="ECO:0000305"
FT CONFLICT 238
FT /note="Q -> R (in Ref. 3; BAA31153 and 4; AAC05278)"
FT /evidence="ECO:0000305"
FT CONFLICT 241
FT /note="D -> E (in Ref. 1; AAA37114)"
FT /evidence="ECO:0000305"
FT CONFLICT 314
FT /note="E -> A (in Ref. 1; AAA37114)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 487 AA; 55328 MW; CAD32B606004449F CRC64;
MLLPGLLLLL LLLAGTRWLW GQWKLRKLHL PPLAPGFLHF LQPNLPIYLL GLTQKLGPIY
RIRLGMQDVV VLNSNRTIEE ALIQKWVDFA GRPHMLNGKM DLDLSLGDYS LMWKAHKKLS
RSALMLGMRD SMEPLIEQLT QEFCERMRAQ AGTPVAIHKE FSFLTCSIIS CLTFGDKDST
LVQTLHDCVQ DLLQAWNHWS IQILTIIPLL RFLPNPGLQK LKQIQESRDH IVKQQLKQHK
DSLVAGQWKD MIDYMLQGVE KQRDGKDEER LHEGHVHMSV VDLFIGGTET TATTLSWAVA
FLLHHPEIQK RLQEELDLKL GPGSQLLYRN RMQLPLLMAT IAEVLRLRPV VPLALPHRAT
RASSISGYDI PKDMVIIPNI QGANLDEMVW ELPSKFWPDR FLEPGKNPRT PSFGCGARVC
LGEPLARLEL FVVLARLLQA FTLLPPPDGT LPSLQPQPYA GINLPIPPFQ VRLQPRNLAP
QDQGERP
