CP21A_RAT
ID CP21A_RAT Reviewed; 493 AA.
AC Q64562;
DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=Steroid 21-hydroxylase;
DE EC=1.14.14.16 {ECO:0000269|PubMed:9408081};
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;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND TISSUE
RP SPECIFICITY.
RC STRAIN=Sprague-Dawley;
RX PubMed=9408081; DOI=10.1016/s0960-0760(97)00040-x;
RA Zhou M.Y., del Carmen Vila M., Gomez-Sanchez E.P., Gomez-Sanchez C.E.;
RT "Cloning of two alternatively spliced 21-hydroxylase cDNAs from rat
RT adrenal.";
RL J. Steroid Biochem. Mol. Biol. 62:277-286(1997).
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:P08686,
CC ECO:0000269|PubMed:9408081}.
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:0000269|PubMed:9408081};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50305;
CC Evidence={ECO:0000305|PubMed:9408081};
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 -!- TISSUE SPECIFICITY: Expressed in the adrenal gland, kidney, aorta,
CC liver, cerebellum, hypothalamus and brain stem.
CC {ECO:0000269|PubMed:9408081}.
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; U56853; AAD05573.1; -; mRNA.
DR AlphaFoldDB; Q64562; -.
DR SMR; Q64562; -.
DR STRING; 10116.ENSRNOP00000037516; -.
DR PaxDb; Q64562; -.
DR UCSC; RGD:2461; rat.
DR RGD; 2461; Cyp21a1.
DR eggNOG; KOG0156; Eukaryota.
DR InParanoid; Q64562; -.
DR PhylomeDB; Q64562; -.
DR Reactome; R-RNO-193993; Mineralocorticoid biosynthesis.
DR Reactome; R-RNO-194002; Glucocorticoid biosynthesis.
DR Reactome; R-RNO-211976; Endogenous sterols.
DR PRO; PR:Q64562; -.
DR Proteomes; UP000002494; Unplaced.
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; IDA:RGD.
DR GO; GO:0005496; F:steroid binding; IEA:UniProtKB-KW.
DR GO; GO:0008395; F:steroid hydroxylase activity; IBA:GO_Central.
DR GO; GO:0006700; P:C21-steroid hormone biosynthetic process; IMP:RGD.
DR GO; GO:0071375; P:cellular response to peptide hormone stimulus; IEP:RGD.
DR GO; GO:0006704; P:glucocorticoid biosynthetic process; IBA:GO_Central.
DR GO; GO:0006705; P:mineralocorticoid biosynthetic process; IDA:RGD.
DR GO; GO:0042448; P:progesterone metabolic process; IDA:RGD.
DR GO; GO:0046677; P:response to antibiotic; IEP:RGD.
DR GO; GO:0006694; P:steroid biosynthetic process; IBA:GO_Central.
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 Endoplasmic reticulum; Heme; Iron; Lipid-binding; Membrane; Metal-binding;
KW Microsome; Monooxygenase; Oxidoreductase; Reference proteome;
KW Steroid-binding; Steroidogenesis.
FT CHAIN 1..493
FT /note="Steroid 21-hydroxylase"
FT /id="PRO_0000051979"
FT BINDING 94
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /evidence="ECO:0000250|UniProtKB:P08686"
FT BINDING 119
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /evidence="ECO:0000250|UniProtKB:P08686"
FT BINDING 231
FT /ligand="17alpha-hydroxyprogesterone"
FT /ligand_id="ChEBI:CHEBI:17252"
FT /evidence="ECO:0000250|UniProtKB:P00191"
FT BINDING 231
FT /ligand="progesterone"
FT /ligand_id="ChEBI:CHEBI:17026"
FT /evidence="ECO:0000250|UniProtKB:P08686"
FT BINDING 360
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /evidence="ECO:0000250|UniProtKB:P08686"
FT BINDING 421
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /evidence="ECO:0000250|UniProtKB:P08686"
FT BINDING 423
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"
SQ SEQUENCE 493 AA; 55946 MW; FF6CC5E993B8B133 CRC64;
MLLPGLLLLL LLLLLAGTRW LWGQWKLWKL RLPPLAPGFL HFLQPNLPVY LFGLAQKLGP
IYRIRLGLQD VVVLNSNKTI EEALIQKWVD FAGRPQILDG KMNFDLSMGD YSLTWKAHKK
LSRSALVLGM RDSMEPLVEQ LTQEFCERMR AQAGASVAIH KEFSLLTCSI ISCLTFGDKQ
DSTLLNATHS CVRDLLKAWN HWSVQILDII PFLRFFPNPG LWKLKQFQES RDHIVMQELK
RHKDSLVAGQ WKDMIDYMLQ GVEKQRDARD PGQLHERHVH MSVVDLFVGG TETTAATLSW
AVAFLLHHPE IQKRLQEELD LKLAPSSQLL YKNRMQLPLL MATIAEVLRL RPVVPMALPH
RATKASSISG YDIPKDTIII PNIQGANLDE MVWELPSKFW PDRFLESGKS PRIPTFGCGA
RVCLGEPLAR LEFFVVLARL LQTFTLLPPP DGTLPSLQPL PYTGINLLIP PFQVRLQPRN
LAPQDQGQKS STG
