ID CP21A_CANLU Reviewed; 492 AA. AC Q2LCM1; DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot. DT 21-FEB-2006, sequence version 1. DT 27-MAR-2024, entry version 77. DE RecName: Full=Steroid 21-hydroxylase; DE EC=1.14.14.16 {ECO:0000250|UniProtKB:P00191}; 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; OS Canis lupus (Gray wolf). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis. OX NCBI_TaxID=9612; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC TISSUE=Muscle; RA Kosowska B., Brzezinska K., Dobosz T., Moska M., Strzala T., Marszalek B., RA Schmidt K.; RT "Phylogenetic analysis of a steroid 21-hydroxylase gene in some species of RT animals and a man."; RL Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Specifically catalyzes the 21-hydroxylation of steroids. CC Required for the adrenal synthesis of mineralocorticoids and CC glucocorticoids. {ECO:0000250|UniProtKB:P00191}. CC -!- CATALYTIC ACTIVITY: CC Reaction=17alpha-hydroxyprogesterone + O2 + reduced [NADPH--hemoprotein CC reductase] = 11-deoxycortisol + H(+) + H2O + oxidized CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:50308, Rhea:RHEA- CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17252, CC ChEBI:CHEBI:28324, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; CC EC=1.14.14.16; Evidence={ECO:0000250|UniProtKB:P00191}; 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 -!- COFACTOR: CC Name=heme b; Xref=ChEBI:CHEBI:60344; CC Evidence={ECO:0000250|UniProtKB:P00191}; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral CC membrane protein. Microsome membrane; Peripheral membrane protein. CC -!- DOMAIN: The leucine-rich hydrophobic amino acid N-terminal region CC probably helps to anchor the protein to the microsomal membrane. CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; DQ336566; ABC67289.1; -; Genomic_DNA. DR AlphaFoldDB; Q2LCM1; -. DR SMR; Q2LCM1; -. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0103069; F:17-hydroxyprogesterone 21-hydroxylase activity; IEA:RHEA. DR GO; GO:0020037; F:heme binding; IEA:InterPro. DR GO; GO:0005506; F:iron ion binding; IEA:InterPro. DR GO; GO:0106309; F:progesterone 21-hydroxylase activity; IEA:RHEA. DR GO; GO:0005496; F:steroid binding; IEA:UniProtKB-KW. DR GO; GO:0008395; F:steroid hydroxylase activity; ISS:UniProtKB. DR GO; GO:0006694; P:steroid biosynthetic process; IEA:UniProtKB-KW. DR GO; GO:0008202; P:steroid metabolic process; ISS:UniProtKB. DR CDD; cd20674; CYP21; 1. DR Gene3D; 1.10.630.10; Cytochrome P450; 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 PANTHER; PTHR24289; STEROID 17-ALPHA-HYDROXYLASE/17,20 LYASE; 1. DR PANTHER; PTHR24289:SF14; STEROID 21-HYDROXYLASE-LIKE; 1. DR Pfam; PF00067; p450; 1. DR PRINTS; PR00463; EP450I. DR PRINTS; PR00385; P450. DR SUPFAM; SSF48264; Cytochrome P450; 1. DR PROSITE; PS00086; CYTOCHROME_P450; 1. PE 3: Inferred from homology; KW Endoplasmic reticulum; Heme; Iron; Lipid-binding; Membrane; Metal-binding; KW Microsome; Monooxygenase; Oxidoreductase; Steroid-binding; Steroidogenesis. FT CHAIN 1..492 FT /note="Steroid 21-hydroxylase" FT /id="PRO_0000269709" FT BINDING 91 FT /ligand="heme b" FT /ligand_id="ChEBI:CHEBI:60344" FT /evidence="ECO:0000250|UniProtKB:P08686" FT BINDING 120 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 363 FT /ligand="heme b" FT /ligand_id="ChEBI:CHEBI:60344" FT /evidence="ECO:0000250|UniProtKB:P08686" FT BINDING 424 FT /ligand="heme b" FT /ligand_id="ChEBI:CHEBI:60344" FT /evidence="ECO:0000250|UniProtKB:P08686" FT BINDING 426 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 492 AA; 55366 MW; 8151F79FF0484A54 CRC64; MLLLGVLLLT VLAGARLLWG KWKLRGLHLP PLVPGCLHLL QPDLPLHLLG LTQKLGPIYR LRLGLQDVVV LNSKRTIEEA MVRKWVDFAG RPQTPSYKLV SLHHQDLSLG DYSLLWKAHK KLTRSALLLG IRSSMEPLVE QLTQEFCERM RAQAGTPVAI QKEFSLLTCA IICHLTFGDK EDTLVHTFHD CVQDLMRTWE HWSIQMLDII PFLRFFPNPG LWRLKRALEN RDHIVEKQLR QHKESMVAGQ WRDMTDYMLQ RVGRLRAEEG CGQLLEGHVH MSVVDLFIGG TETTATTLSW AVAFLLHHPE IQQRLQEELD RELGPGASGS RIPYRDPTRL PLLSATVAEV LRLRPVVPLA LPHCTTRPSS ISGYDIPEGM VVIPNLQGAH LDETVWERPQ EFRPDRFLVP GASPRVLAFG CGARVCLGEP LARLELLVVL AQLLRAFTLM PAAGTLPSLR PRARCGVNLS MQPFQVQLQP RGAGVLGRGQ HP //