ID CP21A_HUMAN Reviewed; 495 AA.
AC P08686; A2BHY6; P04033; Q01204; Q08AG8; Q16749; Q16806; Q16874; Q5ST44;
AC Q96NU8;
DT 01-NOV-1986, integrated into UniProtKB/Swiss-Prot.
DT 24-JAN-2024, sequence version 2.
DT 24-JAN-2024, entry version 241.
DE RecName: Full=Steroid 21-hydroxylase {ECO:0000303|PubMed:25855791};
DE EC=1.14.14.16 {ECO:0000269|PubMed:16984992, ECO:0000269|PubMed:22014889, ECO:0000269|PubMed:25855791, ECO:0000269|PubMed:27721825};
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;
DE AltName: Full=Cytochrome P450-C21B;
GN Name=CYP21A2; Synonyms=CYP21, CYP21B;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE CYP21A2*1A), AND VARIANTS LEU-6
RP DEL; LYS-103 AND ASN-494.
RX PubMed=3486422; DOI=10.1073/pnas.83.9.2841;
RA Higashi Y., Yoshioka H., Yamane M., Gotoh O., Fujii-Kuriyama Y.;
RT "Complete nucleotide sequence of two steroid 21-hydroxylase genes tandemly
RT arranged in human chromosome: a pseudogene and a genuine gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:2841-2845(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ALLELE CYP21A2*1B) (ISOFORM 1),
RP AND VARIANTS LEU-6 DEL AND ASN-494.
RX PubMed=3487786; DOI=10.1073/pnas.83.14.5111;
RA White P.C., New M.I., Dupont B.;
RT "Structure of human steroid 21-hydroxylase genes.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:5111-5115(1986).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT AH3 THR-269, VARIANTS LYS-103
RP AND ASN-494, AND INVOLVEMENT IN AH3.
RX PubMed=3038528; DOI=10.1002/j.1460-2075.1987.tb02414.x;
RA Rodrigues N.R., Dunham I., Yu C.Y., Carroll M.C., Porter R.R.,
RA Campbell R.D.;
RT "Molecular characterization of the HLA-linked steroid 21-hydroxylase B gene
RT from an individual with congenital adrenal hyperplasia.";
RL EMBO J. 6:1653-1661(1987).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT AH3 LEU-282.
RX PubMed=3267225; DOI=10.1172/jci113562;
RA Globerman H., Amor M., Parker K.L., New M.I., White P.C.;
RT "Nonsense mutation causing steroid 21-hydroxylase deficiency.";
RL J. Clin. Invest. 82:139-144(1988).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS AH3 HIS-340 AND SER-454.
RC TISSUE=Peripheral blood;
RX PubMed=1406709; DOI=10.1210/mend.6.8.1406709;
RA Helmberg A., Tusie-Luna M.-T., Tabarelli M., Kofler R., White P.C.;
RT "R339H and P453S: CYP21 mutations associated with nonclassic steroid 21-
RT hydroxylase deficiency that are not apparent gene conversions.";
RL Mol. Endocrinol. 6:1318-1322(1992).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LEU-6 DEL; LYS-103 AND
RP ASN-494.
RX PubMed=19505723; DOI=10.1016/j.molimm.2009.04.033;
RA Blasko B., Banlaki Z., Gyapay G., Pozsonyi E., Sasvari-Szekely M.,
RA Rajczy K., Fust G., Szilagyi A.;
RT "Linkage analysis of the C4A/C4B copy number variation and polymorphisms of
RT the adjacent steroid 21-hydroxylase gene in a healthy population.";
RL Mol. Immunol. 46:2623-2629(2009).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=23241443; DOI=10.1093/gbe/evs121;
RA Banlaki Z., Szabo J.A., Szilagyi A., Patocs A., Prohaszka Z., Fust G.,
RA Doleschall M.;
RT "Intraspecific evolution of human RCCX copy number variation traced by
RT haplotypes of the CYP21A2 gene.";
RL Genome Biol. Evol. 5:98-112(2013).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=24312389; DOI=10.1371/journal.pone.0081977;
RA Szabo J.A., Szilagyi A., Doleschall Z., Patocs A., Farkas H., Prohaszka Z.,
RA Racz K., Fuest G., Doleschall M.;
RT "Both positive and negative selection pressures contribute to the
RT polymorphism pattern of the duplicated human CYP21A2 gene.";
RL PLoS ONE 8:e81977-e81977(2013).
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=28401898; DOI=10.1038/ejhg.2017.38;
RA Doleschall M., Luczay A., Koncz K., Hadzsiev K., Erhardt E., Szilagyi A.,
RA Doleschall Z., Nemeth K., Toeroek D., Prohaszka Z., Gereben B., Fekete G.,
RA Glaz E., Igaz P., Korbonits M., Toth M., Racz K., Patocs A.;
RT "A unique haplotype of RCCX copy number variation: from the clinics of
RT congenital adrenal hyperplasia to evolutionary genetics.";
RL Eur. J. Hum. Genet. 25:702-710(2017).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ALLELE CYP21A2*6) (ISOFORMS 1 AND
RP 2).
RC TISSUE=Adrenal gland;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [13]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [14]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT LYS-103.
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 [15]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 110-186, AND VARIANT AH3 ASN-173.
RX PubMed=8485582; DOI=10.1038/ng0393-260;
RA Collier S., Tassabehji M., Sinnott P., Strachan T.;
RT "A de novo pathological point mutation at the 21-hydroxylase locus:
RT implications for gene conversion in the human genome.";
RL Nat. Genet. 3:260-265(1993).
RN [16]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 150-183, AND VARIANT AH3 ASN-173.
RX PubMed=3871526; DOI=10.1073/pnas.82.2.521;
RA Carroll M.C., Campbell R.D., Porter R.R.;
RT "Mapping of steroid 21-hydroxylase genes adjacent to complement component
RT C4 genes in HLA, the major histocompatibility complex in man.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:521-525(1985).
RN [17]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 150-183, AND VARIANT AH3 ASN-173.
RX PubMed=3257825; DOI=10.1073/pnas.85.5.1600;
RA Amor M., Parker K.L., Globerman H., New M.I., White P.C.;
RT "Mutation in the CYP21B gene (Ile-172-->Asn) causes steroid 21-hydroxylase
RT deficiency.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:1600-1604(1988).
RN [18]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 266-495 (ISOFORM 1), VARIANT AH3 LEU-282, AND
RP VARIANT ASN-494.
RX PubMed=3497399; DOI=10.1073/pnas.84.16.5858;
RA Matteson K.J., Phillips J.A. III, Miller W.L., Chung B.C., Orlando P.J.,
RA Frisch H., Ferrandez A., Burr I.M.;
RT "P450XXI (steroid 21-hydroxylase) gene deletions are not found in family
RT studies of congenital adrenal hyperplasia.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:5858-5862(1987).
RN [19]
RP FUNCTION.
RX PubMed=10602386; DOI=10.1038/sj.gt.3301018;
RA Tajima T., Okada T., Ma X.M., Ramsey W., Bornstein S., Aguilera G.;
RT "Restoration of adrenal steroidogenesis by adenovirus-mediated transfer of
RT human cytochromeP450 21-hydroxylase into the adrenal gland of21-
RT hydroxylase-deficient mice.";
RL Gene Ther. 6:1898-1903(1999).
RN [20] {ECO:0007744|PDB:4Y8W}
RP X-RAY CRYSTALLOGRAPHY (2.64 ANGSTROMS) OF 30-495 IN COMPLEX WITH HEME AND
RP PROGESTERONE, FUNCTION, COFACTOR, CATALYTIC ACTIVITY, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=25855791; DOI=10.1074/jbc.m115.646307;
RA Pallan P.S., Wang C., Lei L., Yoshimoto F.K., Auchus R.J., Waterman M.R.,
RA Guengerich F.P., Egli M.;
RT "Human Cytochrome P450 21A2, the major steroid 21-hydroxylase: structure of
RT the enzyme-progesterone substrate complex and rate-limiting c-h bond
RT cleavage.";
RL J. Biol. Chem. 290:13128-13143(2015).
RN [21]
RP CHARACTERIZATION OF VARIANT AH3 LEU-282, AND MUTAGENESIS OF SER-269;
RP VAL-282 AND CYS-429.
RX PubMed=1864962; DOI=10.1172/jci115334;
RA Wu D.-A., Chung B.-C.;
RT "Mutations of P450c21 (steroid 21-hydroxylase) at Cys428, Val281, and
RT Ser268 result in complete, partial, or no loss of enzymatic activity,
RT respectively.";
RL J. Clin. Invest. 88:519-523(1991).
RN [22]
RP POLYMORPHISM.
RX PubMed=8081391; DOI=10.1002/humu.1380030408;
RA White P.C., Tusie-Luna M.-T., New M.I., Speiser P.W.;
RT "Mutations in steroid 21-hydroxylase (CYP21).";
RL Hum. Mutat. 3:373-378(1994).
RN [23]
RP VARIANTS AH3 LEU-212 AND LEU-282.
RX PubMed=3260007; DOI=10.1056/nejm198807073190104;
RA Speiser P.W., New M.I., White P.C.;
RT "Molecular genetic analysis of nonclassic steroid 21-hydroxylase deficiency
RT associated with HLA-B14,DR1.";
RL N. Engl. J. Med. 319:19-23(1988).
RN [24]
RP VARIANTS AH3 ASN-173 AND TRP-357.
RX PubMed=2303461; DOI=10.1016/s0021-9258(19)39804-7;
RA Chiou S.-H., Hu M.-C., Chung B.-C.;
RT "A missense mutation at Ile172-->Asn or Arg356-->Trp causes steroid 21-
RT hydroxylase deficiency.";
RL J. Biol. Chem. 265:3549-3552(1990).
RN [25]
RP VARIANT AH3 ASN-173.
RX PubMed=1937474; DOI=10.1007/bf00201731;
RA Partanen J., Campbell R.D.;
RT "Substitution of Ile-172 to Asn in the steroid 21-hydroxylase B (P450c21B)
RT gene in a Finnish patient with the simple virilizing form of congenital
RT adrenal hyperplasia.";
RL Hum. Genet. 87:716-720(1991).
RN [26]
RP VARIANT AH3 LEU-31, AND VARIANT THR-269.
RX PubMed=2072928; DOI=10.1210/mend-5-5-685;
RA Tusie-Luna M.T., Speiser P.W., Dumic M., New M.I., White P.C.;
RT "A mutation (Pro-30 to Leu) in CYP21 represents a potential nonclassic
RT steroid 21-hydroxylase deficiency allele.";
RL Mol. Endocrinol. 5:685-692(1991).
RN [27]
RP VARIANTS AH3 LEU-31; ASN-173; ASN-237; GLU-238; LYS-240; LEU-282 AND
RP TRP-357.
RX PubMed=1644925; DOI=10.1172/jci115897;
RA Speiser P.W., Dupont J., Zhu D., Serrat J., Buegeleisen M.,
RA Tusie-Luna M.-T., Lesser M., New M.I., White P.C.;
RT "Disease expression and molecular genotype in congenital adrenal
RT hyperplasia due to 21-hydroxylase deficiency.";
RL J. Clin. Invest. 90:584-595(1992).
RN [28]
RP VARIANT AH3 SER-454.
RX PubMed=1406699; DOI=10.1210/mend.6.8.1406699;
RA Owerbach D., Sherman L., Ballard A.L., Azziz R.;
RT "Pro-453 to Ser mutation in CYP21 is associated with nonclassic steroid 21-
RT hydroxylase deficiency.";
RL Mol. Endocrinol. 6:1211-1215(1992).
RN [29]
RP VARIANTS AH3 LEU-106; SER-292 AND SER-454.
RX PubMed=1496017; DOI=10.1073/pnas.89.15.7232;
RA Wedell A., Ritzen E.M., Haglund-Stengler B., Luthman H.;
RT "Steroid 21-hydroxylase deficiency: three additional mutated alleles and
RT establishment of phenotype-genotype relationships of common mutations.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:7232-7236(1992).
RN [30]
RP VARIANT AH3 PRO-484.
RX PubMed=8478006; DOI=10.1007/bf00218263;
RA Wedell A., Luthman H.;
RT "Steroid 21-hydroxylase (P450c21): a new allele and spread of mutations
RT through the pseudogene.";
RL Hum. Genet. 91:236-240(1993).
RN [31]
RP VARIANTS AH3 ASN-173; ASN-237; LEU-282 AND PRO-484.
RX PubMed=7749410; DOI=10.1002/humu.1380050205;
RA Barbat B., Bogyo A., Raux-Demay M.-C., Kuttenn F., Boue J., Simon-Bouy B.,
RA Serre J.-L., Boue A., Mornet E.;
RT "Screening of CYP21 gene mutations in 129 French patients affected by
RT steroid 21-hydroxylase deficiency.";
RL Hum. Mutat. 5:126-130(1995).
RN [32]
RP VARIANT AH3 ASP-381.
RX PubMed=9067760;
RX DOI=10.1002/(sici)1098-1004(1997)9:2<181::aid-humu12>3.0.co;2-z;
RA Kirby-Keyser L., Porter C.C., Donohoue P.A.;
RT "E380D: a novel point mutation of CYP21 in an HLA-homozygous patient with
RT salt-losing congenital adrenal hyperplasia due to 21-hydroxylase
RT deficiency.";
RL Hum. Mutat. 9:181-182(1997).
RN [33]
RP VARIANTS AH3 PRO-357 AND GLN-357.
RX PubMed=9187661; DOI=10.1007/s004390050436;
RA Lajic S., Levo A., Nikoshkov A., Lundberg Y., Partanen J., Wedell A.;
RT "A cluster of missense mutations at Arg356 of human steroid 21-hydroxylase
RT may impair redox partner interaction.";
RL Hum. Genet. 99:704-709(1997).
RN [34]
RP VARIANTS AH3 LEU-106 AND SER-454.
RX PubMed=8989258; DOI=10.1210/jcem.82.1.3678;
RA Nikoshkov A., Lajic S., Holst M., Wedell A., Luthman H.;
RT "Synergistic effect of partially inactivating mutations in steroid 21-
RT hydroxylase deficiency.";
RL J. Clin. Endocrinol. Metab. 82:194-199(1997).
RN [35]
RP VARIANTS ARG-99; LYS-103; GLU-184 AND ASN-494.
RX PubMed=9580109; DOI=10.1007/s004390050672;
RA Ordonez-Sanchez M.L., Ramirez-Jimenez S., Lopez-Gutierrez A.U., Riba L.,
RA Gamboa-Cardiel S., Cerrillo-Hinojosa M., Altamirano-Bustamante N.,
RA Calzada-Leon R., Robles-Valdes C., Mendoza-Morfin F., Tusie-Luna M.T.;
RT "Molecular genetic analysis of patients carrying steroid 21-hydroxylase
RT deficiency in the Mexican population: identification of possible new
RT mutations and high prevalence of apparent germ-line mutations.";
RL Hum. Genet. 102:170-177(1998).
RN [36]
RP VARIANTS AH3 GLU-197 DEL; SER-292 AND PRO-484.
RX PubMed=9497336; DOI=10.1074/jbc.273.11.6163;
RA Nikoshkov A., Lajic S., Vlamis-Gardikas A., Tranebjaerg L., Holst M.,
RA Wedell A., Luthman H.;
RT "Naturally occurring mutants of human steroid 21-hydroxylase (P450c21)
RT pinpoint residues important for enzyme activity and stability.";
RL J. Biol. Chem. 273:6163-6165(1998).
RN [37]
RP VARIANT AH3 GLN-31, CHARACTERIZATION OF VARIANT AH3 GLN-31, SUBCELLULAR
RP LOCATION, TOPOLOGY, AND DOMAIN.
RX PubMed=10198222; DOI=10.1006/bbrc.1999.0482;
RA Lajic S., Nikoshkov A., Holst M., Wedell A.;
RT "Effects of missense mutations and deletions on membrane anchoring and
RT enzyme function of human steroid 21-hydroxylase (P450c21).";
RL Biochem. Biophys. Res. Commun. 257:384-390(1999).
RN [38]
RP VARIANTS AH3 LEU-31; VAL-91; ASN-173; ALA-179; LEU-282; CYS-292; HIS-355;
RP TRP-357 AND SER-454.
RX PubMed=10364682; DOI=10.1159/000022866;
RA Lobato M.N., Ordonez-Sanchez M.L., Tusie-Luna M.T., Meseguer A.;
RT "Mutation analysis in patients with congenital adrenal hyperplasia in the
RT Spanish population: identification of putative novel steroid 21-hydroxylase
RT deficiency alleles associated with the classic form of the disease.";
RL Hum. Hered. 49:169-175(1999).
RN [39]
RP VARIANTS AH3 TYR-170; LEU-282 AND GLN-357.
RX PubMed=10094562;
RX DOI=10.1002/(sici)1098-1004(1999)13:2<172::aid-humu17>3.0.co;2-n;
RA Witchel S.F., Smith R., Suda-Hartman M.;
RT "Identification of CYP21 mutations, one novel, by single strand
RT conformational polymorphism (SSCP) analysis.";
RL Hum. Mutat. 13:172-172(1999).
RN [40]
RP VARIANTS AH3 LEU-31; GLU-65; ASN-173; ASN-237; LEU-282; SER-292; TRP-357
RP AND VAL-363.
RX PubMed=10408778;
RX DOI=10.1002/(sici)1098-1004(1999)13:6<482::aid-humu8>3.0.co;2-0;
RA Ohlsson G., Mueller J., Skakkebaek N.E., Schwartz M.;
RT "Steroid 21-hydroxylase deficiency: mutational spectrum in Denmark, three
RT novel mutations, and in vitro expression analysis.";
RL Hum. Mutat. 13:482-486(1999).
RN [41]
RP VARIANTS AH3 LEU-31; ASN-173; ASN-237; GLU-238; LYS-240; LEU-282 AND
RP TRP-357.
RX PubMed=10408786;
RX DOI=10.1002/(sici)1098-1004(1999)13:6<505::aid-humu16>3.0.co;2-0;
RA Kapelari K., Ghanaati Z., Wollmann H., Ventz M., Ranke M.B., Kofler R.,
RA Peters H.;
RT "A rapid screening for steroid 21-hydroxylase mutations in patients with
RT congenital adrenal hyperplasia.";
RL Hum. Mutat. 13:505-505(1999).
RN [42]
RP VARIANTS AH3 LEU-282; TRP-357 AND SER-425.
RX PubMed=10443693; DOI=10.1210/jcem.84.8.5937;
RA Billerbeck A.E.C., Bachega T.A.S.S., Frazatto E.T., Nishi M.Y.,
RA Goldberg A.C., Marin M.L.C., Madureira G., Monte O., Arnhold I.J.P.,
RA Mendonca B.B.;
RT "A novel missense mutation, GLY424SER, in Brazilian patients with 21-
RT hydroxylase deficiency.";
RL J. Clin. Endocrinol. Metab. 84:2870-2872(1999).
RN [43]
RP VARIANTS AH3 LEU-31; ASN-173; LEU-282 AND TRP-357, AND VARIANT THR-269.
RX PubMed=10496074; DOI=10.1007/s100380050167;
RA Asanuma A., Ohura T., Ogawa E., Sato S., Igarashi Y., Matsubara Y.,
RA Iinuma K.;
RT "Molecular analysis of Japanese patients with steroid 21-hydroxylase
RT deficiency.";
RL J. Hum. Genet. 44:312-317(1999).
RN [44]
RP VARIANTS AH3 ASN-173 AND TRP-357.
RX PubMed=10051010;
RA Lako M., Ramsden S., Campbell R.D., Strachan T.;
RT "Mutation screening in British 21-hydroxylase deficiency families and
RT development of novel microsatellite based approaches to prenatal
RT diagnosis.";
RL J. Med. Genet. 36:119-124(1999).
RN [45]
RP VARIANTS AH3 LEU-282 AND SER-454, AND VARIANT THR-269.
RX PubMed=10391209; DOI=10.1038/10290;
RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA Lander E.S.;
RT "Characterization of single-nucleotide polymorphisms in coding regions of
RT human genes.";
RL Nat. Genet. 22:231-238(1999).
RN [46]
RP ERRATUM OF PUBMED:10391209.
RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA Lander E.S.;
RL Nat. Genet. 23:373-373(1999).
RN [47]
RP VARIANTS AH3 LEU-31; ASN-173; LEU-282; GLY-282; PHE-301; CYS-355; TRP-357
RP AND SER-454.
RX PubMed=10720040; DOI=10.1210/jcem.85.3.6441;
RA Krone N., Braun A., Roscher A.A., Knorr D., Schwarz H.P.;
RT "Predicting phenotype in steroid 21-hydroxylase deficiency? Comprehensive
RT genotyping in 155 unrelated, well defined patients from southern Germany.";
RL J. Clin. Endocrinol. Metab. 85:1059-1065(2000).
RN [48]
RP VARIANTS AH3 LEU-31; ASN-173; PRO-262; TRP-357 AND PRO-484.
RX PubMed=11598371; DOI=10.1159/000049992;
RA Loke K.Y., Lee Y.S., Lee W.W.R., Poh L.K.S.;
RT "Molecular analysis of CYP-21 mutations for congenital adrenal hyperplasia
RT in Singapore.";
RL Horm. Res. 55:179-184(2001).
RN [49]
RP VARIANTS AH3 LEU-31; ASN-173; LEU-282; MET-318; TRP-357; CYS-436 AND
RP SER-454.
RX PubMed=11232002; DOI=10.1210/jcem.86.1.7131;
RA Deneux C., Tardy V., Dib A., Mornet E., Billaud L., Charron D., Morel Y.,
RA Kuttenn F.;
RT "Phenotype-genotype correlation in 56 women with nonclassical congenital
RT adrenal hyperplasia due to 21-hydroxylase deficiency.";
RL J. Clin. Endocrinol. Metab. 86:207-213(2001).
RN [50]
RP VARIANTS AH3 LEU-31; ASN-173; LEU-282; SER-292; TRP-357; SER-425; HIS-427;
RP SER-454 AND PRO-484, AND CHARACTERIZATION OF VARIANT AH3 HIS-427.
RX PubMed=11600539; DOI=10.1210/jcem.86.10.7898;
RA Baumgartner-Parzer S.M., Schulze E., Waldhaeusl W., Pauschenwein S.,
RA Rondot S., Nowotny P., Meyer K., Frisch H., Waldhauser F., Vierhapper H.;
RT "Mutational spectrum of the steroid 21-hydroxylase gene in Austria:
RT identification of a novel missense mutation.";
RL J. Clin. Endocrinol. Metab. 86:4771-4775(2001).
RN [51]
RP VARIANT AH3 TRP-364.
RX PubMed=11746135; DOI=10.1002/pd.167;
RA Levo A., Partanen J.;
RT "Novel mutations in the human CYP21 gene.";
RL Prenat. Diagn. 21:885-889(2001).
RN [52]
RP VARIANTS AH3 LEU-31; ASN-173; LEU-282; LEU-284; TRP-357 AND SER-454.
RX PubMed=12222711; DOI=10.1080/080352502760148595;
RA Ezquieta B., Cueva E., Varela J., Oliver A., Fernandez J., Jariego C.;
RT "Non-classical 21-hydroxylase deficiency in children: association of
RT adrenocorticotropic hormone-stimulated 17-hydroxyprogesterone with the risk
RT of compound heterozygosity with severe mutations.";
RL Acta Paediatr. 91:892-898(2002).
RN [53]
RP VARIANTS HYPERANDROGENISM MET-305; SER-376 AND SER-454, AND
RP CHARACTERIZATION OF VARIANTS HYPERANDROGENISM MET-305; SER-376 AND SER-454.
RX PubMed=12050257; DOI=10.1210/jcem.87.6.8525;
RA Lajic S., Clauin S., Robins T., Vexiau P., Blanche H.,
RA Bellanne-Chantelot C., Wedell A.;
RT "Novel mutations in CYP21 detected in individuals with hyperandrogenism.";
RL J. Clin. Endocrinol. Metab. 87:2824-2829(2002).
RN [54]
RP VARIANTS AH3 CYS-409 AND SER-425.
RX PubMed=12213891; DOI=10.1210/jc.2001-011939;
RA Billerbeck A.E.C., Mendonca B.B., Pinto E.M., Madureira G., Arnhold I.J.P.,
RA Bachega T.A.S.S.;
RT "Three novel mutations in CYP21 gene in Brazilian patients with the
RT classical form of 21-hydroxylase deficiency due to a founder effect.";
RL J. Clin. Endocrinol. Metab. 87:4314-4317(2002).
RN [55]
RP VARIANTS AH3 THR-16; LEU-31; ASN-173; LEU-282 AND SER-454.
RX PubMed=12887291; DOI=10.1530/eje.0.1490137;
RA Dolzan V., Stopar-Obreza M., Zerjav-Tansek M., Breskvar K., Krzisnik C.,
RA Battelino T.;
RT "Mutational spectrum of congenital adrenal hyperplasia in Slovenian
RT patients: a novel Ala15Thr mutation and Pro30Leu within a larger gene
RT conversion associated with a severe form of the disease.";
RL Eur. J. Endocrinol. 149:137-144(2003).
RN [56]
RP VARIANTS AH3 LEU-31; LEU-63; ASN-173; LEU-282; PRO-342; TRP-357; SER-454
RP AND PRO-484.
RX PubMed=12788866; DOI=10.1210/jc.2002-021433;
RA Pinto G., Tardy V., Trivin C., Thalassinos C., Lortat-Jacob S.,
RA Nihoul-Fekete C., Morel Y., Brauner R.;
RT "Follow-up of 68 children with congenital adrenal hyperplasia due to 21-
RT hydroxylase deficiency: relevance of genotype for management.";
RL J. Clin. Endocrinol. Metab. 88:2624-2633(2003).
RN [57]
RP VARIANTS AH3 ASN-173; LEU-282; ARG-292; TYR-302; TRP-357 AND GLN-484.
RX PubMed=12915679; DOI=10.1210/jc.2002-021681;
RA Stikkelbroeck N.M., Hoefsloot L.H., de Wijs I.J., Otten B.J., Hermus A.R.,
RA Sistermans E.A.;
RT "CYP21 gene mutation analysis in 198 patients with 21-hydroxylase
RT deficiency in The Netherlands: six novel mutations and a specific cluster
RT of four mutations.";
RL J. Clin. Endocrinol. Metab. 88:3852-3859(2003).
RN [58]
RP VARIANTS AH3 ASN-173; TRP-357 AND TRP-484.
RX PubMed=14715874; DOI=10.1210/jc.2003-031056;
RA Kharrat M., Tardy V., M'Rad R., Maazoul F., Jemaa L.B., Refai M., Morel Y.,
RA Chaabouni H.;
RT "Molecular genetic analysis of Tunisian patients with a classic form of 21-
RT hydroxylase deficiency: identification of four novel mutations and high
RT prevalence of Q318X mutation.";
RL J. Clin. Endocrinol. Metab. 89:368-374(2004).
RN [59]
RP VARIANT AH3 HIS-125.
RX PubMed=14676460; DOI=10.1159/000075587;
RA Usui T., Nishisho K., Kaji M., Ikuno N., Yorifuji T., Yasuda T., Kuzuya H.,
RA Shimatsu A.;
RT "Three novel mutations in Japanese patients with 21-hydroxylase
RT deficiency.";
RL Horm. Res. 61:126-132(2004).
RN [60]
RP VARIANTS AH3 THR-16; LEU-31; LEU-282 AND SER-483, AND CHARACTERIZATION OF
RP VARIANTS AH3 THR-16 AND SER-483.
RX PubMed=15126570; DOI=10.1210/jc.2003-031630;
RA Barbaro M., Lajic S., Baldazzi L., Balsamo A., Pirazzoli P., Cicognani A.,
RA Wedell A., Cacciari E.;
RT "Functional analysis of two recurrent amino acid substitutions in the CYP21
RT gene from Italian patients with congenital adrenal hyperplasia.";
RL J. Clin. Endocrinol. Metab. 89:2402-2407(2004).
RN [61]
RP VARIANTS AH3 LEU-31; ASN-173; ASN-237; GLU-238; LYS-240; LEU-282; SER-292;
RP GLN-357; TRP-357; TYR-366; SER-454; LEU-480 AND PRO-484.
RX PubMed=15110320; DOI=10.1016/j.ymgme.2004.02.006;
RA Zeng X., Witchel S.F., Dobrowolski S.F., Moulder P.V., Jarvik J.W.,
RA Telmer C.A.;
RT "Detection and assignment of CYP21 mutations using peptide mass signature
RT genotyping.";
RL Mol. Genet. Metab. 82:38-47(2004).
RN [62]
RP VARIANTS AH3 LEU-31; ASN-173 AND TRP-357.
RX PubMed=16046588; DOI=10.1210/jc.2005-0379;
RA Grigorescu Sido A., Weber M.M., Grigorescu Sido P., Clausmeyer S.,
RA Heinrich U., Schulze E.;
RT "21-Hydroxylase and 11beta-hydroxylase mutations in Romanian patients with
RT classic congenital adrenal hyperplasia.";
RL J. Clin. Endocrinol. Metab. 90:5769-5773(2005).
RN [63]
RP VARIANTS AH3 ARG-170; ARG-179; ARG-303 AND CYS-427, CHARACTERIZATION OF
RP VARIANTS AH3 ARG-170; ARG-179; ARG-303; CYS-427 AND HIS-427, FUNCTION, AND
RP CATALYTIC ACTIVITY.
RX PubMed=16984992; DOI=10.1210/jc.2006-0777;
RA Grischuk Y., Rubtsov P., Riepe F.G., Groetzinger J., Beljelarskaia S.,
RA Prassolov V., Kalintchenko N., Semitcheva T., Peterkova V., Tiulpakov A.,
RA Sippell W.G., Krone N.;
RT "Four novel missense mutations in the CYP21A2 gene detected in Russian
RT patients suffering from the classical form of congenital adrenal
RT hyperplasia: identification, functional characterization, and structural
RT analysis.";
RL J. Clin. Endocrinol. Metab. 91:4976-4980(2006).
RN [64]
RP VARIANTS AH3 LEU-31; LEU-63; ASN-173; TRP-357 AND SER-454, AND
RP CHARACTERIZATION OF VARIANTS AH3 LEU-63 AND SER-454.
RX PubMed=18319307; DOI=10.1210/jc.2007-2701;
RA Menassa R., Tardy V., Despert F., Bouvattier-Morel C., Brossier J.P.,
RA Cartigny M., Morel Y.;
RT "p.H62L, a rare mutation of the CYP21 gene identified in two forms of 21-
RT hydroxylase deficiency.";
RL J. Clin. Endocrinol. Metab. 93:1901-1908(2008).
RN [65]
RP VARIANTS AH3 ARG-57; LEU-63; ARG-108; PRO-143; ASN-173; TRP-357; CYS-409
RP AND SER-454, AND CHARACTERIZATION OF VARIANTS AH3 ARG-57; LEU-63; ARG-108;
RP PRO-143; CYS-409 AND SER-454.
RX PubMed=18381579; DOI=10.1210/jc.2007-2594;
RA Soardi F.C., Barbaro M., Lau I.F., Lemos-Marini S.H., Baptista M.T.,
RA Guerra-Junior G., Wedell A., Lajic S., de Mello M.P.;
RT "Inhibition of CYP21A2 enzyme activity caused by novel missense mutations
RT identified in Brazilian and Scandinavian patients.";
RL J. Clin. Endocrinol. Metab. 93:2416-2420(2008).
RN [66]
RP VARIANTS AH3 GLN-122 AND SER-454, AND CHARACTERIZATION OF VARIANT AH3
RP GLN-122.
RX PubMed=18445671; DOI=10.1210/jc.2007-2646;
RA Riepe F.G., Hiort O., Grotzinger J., Sippell W.G., Krone N.,
RA Holterhus P.M.;
RT "Functional and structural consequences of a novel point mutation in the
RT CYP21A2 gene causing congenital adrenal hyperplasia: potential relevance of
RT helix C for P450 oxidoreductase-21-hydroxylase interaction.";
RL J. Clin. Endocrinol. Metab. 93:2891-2895(2008).
RN [67]
RP VARIANTS AH3 THR-78; PRO-168; ASN-173; THR-231; LYS-234; LEU-282; SER-292;
RP ASP-293; LYS-321; PRO-342; HIS-355; TRP-357; TRP-370; CYS-409; SER-425;
RP HIS-427 AND SER-454, AND CHARACTERIZATION OF VARIANTS AH3 PRO-168; ASN-173;
RP LEU-282; ASP-293; LYS-321; TRP-370 AND SER-425.
RX PubMed=20080860; DOI=10.1210/jc.2009-1202;
RA Tardy V., Menassa R., Sulmont V., Lienhardt-Roussie A., Lecointre C.,
RA Brauner R., David M., Morel Y.;
RT "Phenotype-genotype correlations of 13 rare CYP21A2 mutations detected in
RT 46 patients affected with 21-hydroxylase deficiency and in one carrier.";
RL J. Clin. Endocrinol. Metab. 95:1288-1300(2010).
RN [68]
RP VARIANT AH3 PHE-199.
RX PubMed=21169732; DOI=10.3275/7417;
RA Niceta M., Bono M., Fabiano C., Pojero F., Niceta F., Sammarco P.,
RA Corsello G., Garofalo P.;
RT "A large view of CYP21 locus among Sicilians and other populations:
RT identification of a novel CYP21A2 variant in Sicily.";
RL J. Endocrinol. Invest. 34:847-854(2011).
RN [69]
RP VARIANTS AH3 HIS-192 AND ASN-283, CHARACTERIZATION OF VARIANTS AH3 HIS-192
RP AND ASN-283, FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=22014889; DOI=10.1016/j.metabol.2011.08.008;
RA Concolino P., Mello E., Patrosso M.C., Penco S., Zuppi C., Capoluongo E.;
RT "p.H282N and p.Y191H: 2 novel CYP21A2 mutations in Italian congenital
RT adrenal hyperplasia patients.";
RL Metabolism 61:519-524(2012).
RN [70]
RP VARIANTS AH3 MET-13; PHE-114; 390-GLN--ALA-392 DEL AND PRO-451, VARIANTS
RP CYS-17; GLY-203; LEU-268 AND MET-451, CHARACTERIZATION OF VARIANTS AH3
RP MET-13; PHE-114; 390-GLN--ALA-392 DEL; PRO-451 AND SER-483,
RP CHARACTERIZATION OF VARIANTS CYS-17; GLY-203; LEU-268 AND MET-451,
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=27721825; DOI=10.1155/2016/4209670;
RA de Paula Michelatto D., Karlsson L., Lusa A.L., Silva C.D., Oestberg L.J.,
RA Persson B., Guerra-Junior G., de Lemos-Marini S.H., Barbaro M.,
RA de Mello M.P., Lajic S.;
RT "Functional and structural consequences of nine CYP21A2 mutations ranging
RT from very mild to severe effects.";
RL Int. J. Endocrinol. 2016:4209670-4209670(2016).
RN [71]
RP VARIANT AH3 TRP-342.
RX PubMed=29328376; DOI=10.3892/mmr.2018.8391;
RA Liu J., Zhang X., Zhang H., Fang L., Xu J., Guan Q., Xu C.;
RT "Identification of a novel compound heterozygous mutation of the CYP21A2
RT gene causing 21-hydroxylase deficiency in a Chinese pedigree.";
RL Mol. Med. Report. 17:4265-4272(2018).
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 (PubMed:25855791, PubMed:10602386, PubMed:16984992, PubMed:22014889,
CC PubMed:27721825). Mechanistically, uses molecular oxygen inserting one
CC oxygen atom into a substrate, and reducing the second into a water
CC molecule, with two electrons provided by NADPH via cytochrome P450
CC reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:25855791).
CC {ECO:0000269|PubMed:10602386, ECO:0000269|PubMed:16984992,
CC ECO:0000269|PubMed:22014889, ECO:0000269|PubMed:25855791,
CC ECO:0000269|PubMed:27721825}.
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:16984992, ECO:0000269|PubMed:22014889,
CC ECO:0000269|PubMed:25855791, ECO:0000269|PubMed:27721825};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50305;
CC Evidence={ECO:0000305|PubMed:16984992, ECO:0000305|PubMed:22014889,
CC ECO:0000305|PubMed:25855791, ECO:0000305|PubMed:27721825};
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:0000269|PubMed:16984992, ECO:0000269|PubMed:22014889,
CC ECO:0000269|PubMed:25855791, ECO:0000269|PubMed:27721825};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50309;
CC Evidence={ECO:0000305|PubMed:16984992, ECO:0000305|PubMed:22014889,
CC ECO:0000305|PubMed:25855791, ECO:0000305|PubMed:27721825};
CC -!- COFACTOR:
CC Name=heme b; Xref=ChEBI:CHEBI:60344;
CC Evidence={ECO:0000269|PubMed:25855791};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.59 uM for 17alpha-hydroxyprogesterone
CC {ECO:0000269|PubMed:22014889};
CC KM=12.5 uM for 17alpha-hydroxyprogesterone (at 37 degrees Celsius)
CC {ECO:0000269|PubMed:27721825};
CC KM=1.5 uM for 17alpha-hydroxyprogesterone
CC {ECO:0000269|PubMed:25855791};
CC KM=1.05 uM for progesterone {ECO:0000269|PubMed:22014889};
CC KM=0.21 uM for progesterone {ECO:0000269|PubMed:25855791};
CC Vmax=5.8 nmol/min/mg enzyme {ECO:0000269|PubMed:22014889};
CC Vmax=0.5 nmol/min/mg enzyme (at 37 degrees Celsius)
CC {ECO:0000269|PubMed:27721825};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral
CC membrane protein {ECO:0000269|PubMed:10198222}. Microsome membrane
CC {ECO:0000269|PubMed:10198222}; Peripheral membrane protein
CC {ECO:0000269|PubMed:10198222}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P08686-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P08686-2; Sequence=VSP_062040;
CC -!- DOMAIN: The leucine-rich hydrophobic amino acid N-terminal region
CC probably helps to anchor the protein to the microsomal membrane.
CC {ECO:0000269|PubMed:10198222}.
CC -!- POLYMORPHISM: Several non deleterious alleles have been described
CC including CYP21A2*1A, CYP21A2*1B, CYP21A2*2, CYP21A2*3, CYP21A2*4,
CC CYP21A2*5 and CYP21A2*6. Deleterious alleles are mostly generated by
CC recombinations between CYP21A2 and the pseudogene CYP21A1P through gene
CC conversion. This process consists of recombination events that either
CC delete CYP21A2 or transfer deleterious mutations from CYP21A1P to
CC CYP21A2. {ECO:0000303|PubMed:8081391}.
CC -!- DISEASE: Adrenal hyperplasia 3 (AH3) [MIM:201910]: A form of congenital
CC adrenal hyperplasia, a common recessive disease due to defective
CC synthesis of cortisol. Congenital adrenal hyperplasia is characterized
CC by androgen excess leading to ambiguous genitalia in affected females,
CC rapid somatic growth during childhood in both sexes with premature
CC closure of the epiphyses and short adult stature. Four clinical types:
CC 'salt wasting' (SW, the most severe type), 'simple virilizing' (SV,
CC less severely affected patients), with normal aldosterone biosynthesis,
CC 'non-classic form' or late-onset (NC or LOAH) and 'cryptic'
CC (asymptomatic). {ECO:0000269|PubMed:10051010,
CC ECO:0000269|PubMed:10094562, ECO:0000269|PubMed:10198222,
CC ECO:0000269|PubMed:10364682, ECO:0000269|PubMed:10391209,
CC ECO:0000269|PubMed:10408778, ECO:0000269|PubMed:10408786,
CC ECO:0000269|PubMed:10443693, ECO:0000269|PubMed:10496074,
CC ECO:0000269|PubMed:10720040, ECO:0000269|PubMed:11232002,
CC ECO:0000269|PubMed:11598371, ECO:0000269|PubMed:11600539,
CC ECO:0000269|PubMed:11746135, ECO:0000269|PubMed:12213891,
CC ECO:0000269|PubMed:12222711, ECO:0000269|PubMed:12788866,
CC ECO:0000269|PubMed:12887291, ECO:0000269|PubMed:12915679,
CC ECO:0000269|PubMed:1406699, ECO:0000269|PubMed:1406709,
CC ECO:0000269|PubMed:14676460, ECO:0000269|PubMed:14715874,
CC ECO:0000269|PubMed:1496017, ECO:0000269|PubMed:15110320,
CC ECO:0000269|PubMed:15126570, ECO:0000269|PubMed:16046588,
CC ECO:0000269|PubMed:1644925, ECO:0000269|PubMed:16984992,
CC ECO:0000269|PubMed:18319307, ECO:0000269|PubMed:18381579,
CC ECO:0000269|PubMed:18445671, ECO:0000269|PubMed:1864962,
CC ECO:0000269|PubMed:1937474, ECO:0000269|PubMed:20080860,
CC ECO:0000269|PubMed:2072928, ECO:0000269|PubMed:21169732,
CC ECO:0000269|PubMed:22014889, ECO:0000269|PubMed:2303461,
CC ECO:0000269|PubMed:27721825, ECO:0000269|PubMed:29328376,
CC ECO:0000269|PubMed:3038528, ECO:0000269|PubMed:3257825,
CC ECO:0000269|PubMed:3260007, ECO:0000269|PubMed:3267225,
CC ECO:0000269|PubMed:3497399, ECO:0000269|PubMed:3871526,
CC ECO:0000269|PubMed:7749410, ECO:0000269|PubMed:8478006,
CC ECO:0000269|PubMed:8485582, ECO:0000269|PubMed:8989258,
CC ECO:0000269|PubMed:9067760, ECO:0000269|PubMed:9187661,
CC ECO:0000269|PubMed:9497336}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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; M12792; AAB59440.1; -; Genomic_DNA.
DR EMBL; M13936; AAA59695.1; -; Genomic_DNA.
DR EMBL; M26856; AAA52064.1; -; Genomic_DNA.
DR EMBL; X58906; CAA41709.1; -; Genomic_DNA.
DR EMBL; GQ222278; ACT35404.1; -; Genomic_DNA.
DR EMBL; GQ222283; ACT35409.1; -; Genomic_DNA.
DR EMBL; GQ222286; ACT35412.1; -; Genomic_DNA.
DR EMBL; GQ222289; ACT35415.1; -; Genomic_DNA.
DR EMBL; GQ222296; ACT35422.1; -; Genomic_DNA.
DR EMBL; GQ222301; ACT35427.1; -; Genomic_DNA.
DR EMBL; GQ222319; ACT35445.1; -; Genomic_DNA.
DR EMBL; GQ222295; ACT35421.1; -; Genomic_DNA.
DR EMBL; GQ222312; ACT35438.1; -; Genomic_DNA.
DR EMBL; GQ222297; ACT35423.1; -; Genomic_DNA.
DR EMBL; GQ222320; ACT35446.1; -; Genomic_DNA.
DR EMBL; GQ222321; ACT35447.1; -; Genomic_DNA.
DR EMBL; GQ222327; ACT35453.1; -; Genomic_DNA.
DR EMBL; GQ222323; ACT35449.1; -; Genomic_DNA.
DR EMBL; GQ222334; ACT35460.1; -; Genomic_DNA.
DR EMBL; GQ222340; ACT35466.1; -; Genomic_DNA.
DR EMBL; JN034391; AFK10114.1; -; Genomic_DNA.
DR EMBL; JN034393; AFK10116.1; -; Genomic_DNA.
DR EMBL; JN034394; AFK10117.1; -; Genomic_DNA.
DR EMBL; JN034395; AFK10118.1; -; Genomic_DNA.
DR EMBL; JN034396; AFK10119.1; -; Genomic_DNA.
DR EMBL; JN034397; AFK10120.1; -; Genomic_DNA.
DR EMBL; JN034398; AFK10121.1; -; Genomic_DNA.
DR EMBL; JN034401; AFK10124.1; -; Genomic_DNA.
DR EMBL; JN034403; AFK10126.1; -; Genomic_DNA.
DR EMBL; JN034402; AFK10125.1; -; Genomic_DNA.
DR EMBL; JN034410; AFK10133.1; -; Genomic_DNA.
DR EMBL; JN034411; AFK10134.1; -; Genomic_DNA.
DR EMBL; KC493622; AHA59281.1; -; Genomic_DNA.
DR EMBL; KU302773; APT40592.1; -; Genomic_DNA.
DR EMBL; KU302772; APT40591.1; -; Genomic_DNA.
DR EMBL; AK054616; BAB70774.1; -; mRNA.
DR EMBL; AK314651; BAG37212.1; -; mRNA.
DR EMBL; AF019413; AAB67982.1; -; Genomic_DNA.
DR EMBL; AL049547; CAB89301.1; -; Genomic_DNA.
DR EMBL; AL645922; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL662828; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL662849; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL844853; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL929593; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX679671; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR753845; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR936924; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471081; EAX03570.1; -; Genomic_DNA.
DR EMBL; CH471081; EAX03571.1; -; Genomic_DNA.
DR EMBL; BC125182; AAI25183.1; -; mRNA.
DR EMBL; K02771; AAA59706.1; -; Genomic_DNA.
DR EMBL; M19711; AAA83248.1; -; Genomic_DNA.
DR EMBL; M17252; AAA59985.1; -; mRNA.
DR CCDS; CCDS47406.1; -. [P08686-2]
DR PIR; A25446; O4HUC2.
DR RefSeq; NP_000491.4; NM_000500.7.
DR RefSeq; NP_001122062.3; NM_001128590.3.
DR PDB; 4Y8W; X-ray; 2.64 A; A/B/C=30-495.
DR PDB; 5VBU; X-ray; 3.31 A; A/B/C=30-495.
DR PDBsum; 4Y8W; -.
DR PDBsum; 5VBU; -.
DR AlphaFoldDB; P08686; -.
DR SMR; P08686; -.
DR BioGRID; 107961; 20.
DR IntAct; P08686; 2.
DR STRING; 9606.ENSP00000496625; -.
DR BindingDB; P08686; -.
DR ChEMBL; CHEMBL2759; -.
DR DrugBank; DB01026; Ketoconazole.
DR DrugBank; DB05667; Levoketoconazole.
DR DrugCentral; P08686; -.
DR SwissLipids; SLP:000001618; -.
DR iPTMnet; P08686; -.
DR PhosphoSitePlus; P08686; -.
DR BioMuta; CYP21A2; -.
DR DMDM; 117275; -.
DR MassIVE; P08686; -.
DR PaxDb; 9606-ENSP00000408860; -.
DR PeptideAtlas; P08686; -.
DR ProteomicsDB; 52155; -. [P08686-1]
DR ProteomicsDB; 63894; -.
DR Antibodypedia; 53182; 387 antibodies from 28 providers.
DR DNASU; 1589; -.
DR Ensembl; ENST00000383321.4; ENSP00000372811.4; ENSG00000206338.9.
DR Ensembl; ENST00000434026.2; ENSP00000392321.2; ENSG00000232414.6.
DR Ensembl; ENST00000435122.3; ENSP00000415043.2; ENSG00000231852.9.
DR Ensembl; ENST00000436607.6; ENSP00000403721.2; ENSG00000235134.7. [P08686-1]
DR Ensembl; ENST00000448314.6; ENSP00000398594.2; ENSG00000198457.13. [P08686-1]
DR Ensembl; ENST00000452386.2; ENSP00000403230.2; ENSG00000233151.6.
DR GeneID; 1589; -.
DR KEGG; hsa:1589; -.
DR MANE-Select; ENST00000644719.2; ENSP00000496625.1; NM_000500.9; NP_000491.4.
DR UCSC; uc003nzf.3; human. [P08686-1]
DR AGR; HGNC:2600; -.
DR CTD; 1589; -.
DR DisGeNET; 1589; -.
DR GeneCards; CYP21A2; -.
DR GeneReviews; CYP21A2; -.
DR HGNC; HGNC:2600; CYP21A2.
DR HPA; ENSG00000231852; Tissue enriched (adrenal).
DR MalaCards; CYP21A2; -.
DR MIM; 201910; phenotype.
DR MIM; 613815; gene.
DR neXtProt; NX_P08686; -.
DR Orphanet; 315306; Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency, salt wasting form.
DR Orphanet; 315311; Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency, simple virilizing form.
DR Orphanet; 95698; NON RARE IN EUROPE: Non-classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
DR PharmGKB; PA27096; -.
DR VEuPathDB; HostDB:ENSG00000231852; -.
DR eggNOG; KOG0156; Eukaryota.
DR GeneTree; ENSGT00940000158338; -.
DR HOGENOM; CLU_001570_22_0_1; -.
DR InParanoid; P08686; -.
DR OMA; PWKADIK; -.
DR OrthoDB; 2900138at2759; -.
DR PhylomeDB; P08686; -.
DR TreeFam; TF105095; -.
DR BioCyc; MetaCyc:HS09769-MONOMER; -.
DR BRENDA; 1.14.14.16; 2681.
DR PathwayCommons; P08686; -.
DR Reactome; R-HSA-193993; Mineralocorticoid biosynthesis.
DR Reactome; R-HSA-194002; Glucocorticoid biosynthesis.
DR Reactome; R-HSA-211976; Endogenous sterols.
DR Reactome; R-HSA-5579021; Defective CYP21A2 causes AH3.
DR SignaLink; P08686; -.
DR SIGNOR; P08686; -.
DR BioGRID-ORCS; 1589; 13 hits in 1141 CRISPR screens.
DR ChiTaRS; CYP21A2; human.
DR GeneWiki; 21-Hydroxylase; -.
DR GenomeRNAi; 1589; -.
DR Pharos; P08686; Tchem.
DR PRO; PR:P08686; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; P08686; Protein.
DR Bgee; ENSG00000231852; Expressed in right adrenal gland and 92 other cell types or tissues.
DR ExpressionAtlas; P08686; baseline and differential.
DR Genevisible; P08686; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0103069; F:17-hydroxyprogesterone 21-hydroxylase activity; IDA:UniProtKB.
DR GO; GO:0020037; F:heme binding; IDA:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0106309; F:progesterone 21-hydroxylase activity; IDA: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; IMP:UniProtKB.
DR GO; GO:0006704; P:glucocorticoid biosynthetic process; IBA:GO_Central.
DR GO; GO:0006705; P:mineralocorticoid biosynthetic process; TAS:Reactome.
DR GO; GO:0006694; P:steroid biosynthetic process; IDA:UniProtKB.
DR GO; GO:0008202; P:steroid metabolic process; IMP:UniProtKB.
DR GO; GO:0016125; P:sterol metabolic process; TAS:Reactome.
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:SF13; STEROID 17-ALPHA-HYDROXYLASE/17,20 LYASE; 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 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Congenital adrenal hyperplasia;
KW Disease variant; Endoplasmic reticulum; Heme; Iron; Lipid metabolism;
KW Lipid-binding; Membrane; Metal-binding; Microsome; Monooxygenase;
KW Oxidoreductase; Reference proteome; Steroid-binding; Steroidogenesis.
FT CHAIN 1..495
FT /note="Steroid 21-hydroxylase"
FT /id="PRO_0000051976"
FT BINDING 92
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /evidence="ECO:0000269|PubMed:25855791,
FT ECO:0007744|PDB:4Y8W"
FT BINDING 121
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /evidence="ECO:0000269|PubMed:25855791,
FT ECO:0007744|PDB:4Y8W"
FT BINDING 234
FT /ligand="17alpha-hydroxyprogesterone"
FT /ligand_id="ChEBI:CHEBI:17252"
FT /evidence="ECO:0000250|UniProtKB:P00191"
FT BINDING 234
FT /ligand="progesterone"
FT /ligand_id="ChEBI:CHEBI:17026"
FT /evidence="ECO:0000269|PubMed:25855791,
FT ECO:0007744|PDB:4Y8W"
FT BINDING 366
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /evidence="ECO:0000269|PubMed:25855791,
FT ECO:0007744|PDB:4Y8W"
FT BINDING 427
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /evidence="ECO:0000269|PubMed:25855791,
FT ECO:0007744|PDB:4Y8W"
FT BINDING 429
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:0000269|PubMed:25855791,
FT ECO:0007744|PDB:4Y8W"
FT VAR_SEQ 69..98
FT /note="Missing (in isoform 2)"
FT /id="VSP_062040"
FT VARIANT 6
FT /note="Missing"
FT /evidence="ECO:0000269|PubMed:19505723,
FT ECO:0000269|PubMed:3486422, ECO:0000269|PubMed:3487786"
FT /id="VAR_088451"
FT VARIANT 13
FT /note="L -> M (in AH3; uncertain significance; non-classic
FT form; no effect on steroid 21-monooxygenase activity)"
FT /evidence="ECO:0000269|PubMed:27721825"
FT /id="VAR_077582"
FT VARIANT 16
FT /note="A -> T (in AH3; uncertain significance; salt wasting
FT form; no significant difference in steroid 21-monooxygenase
FT activity; dbSNP:rs63749090)"
FT /evidence="ECO:0000269|PubMed:12887291,
FT ECO:0000269|PubMed:15126570"
FT /id="VAR_026059"
FT VARIANT 17
FT /note="R -> C (decreased steroid 21-monooxygenase activity;
FT dbSNP:rs757608533)"
FT /evidence="ECO:0000269|PubMed:27721825"
FT /id="VAR_077583"
FT VARIANT 31
FT /note="P -> L (in AH3; non-classic form; 50% steroid 21-
FT monooxygenase activity; dbSNP:rs9378251)"
FT /evidence="ECO:0000269|PubMed:10364682,
FT ECO:0000269|PubMed:10408778, ECO:0000269|PubMed:10408786,
FT ECO:0000269|PubMed:10496074, ECO:0000269|PubMed:10720040,
FT ECO:0000269|PubMed:11232002, ECO:0000269|PubMed:11598371,
FT ECO:0000269|PubMed:11600539, ECO:0000269|PubMed:12222711,
FT ECO:0000269|PubMed:12788866, ECO:0000269|PubMed:12887291,
FT ECO:0000269|PubMed:15110320, ECO:0000269|PubMed:15126570,
FT ECO:0000269|PubMed:16046588, ECO:0000269|PubMed:1644925,
FT ECO:0000269|PubMed:18319307, ECO:0000269|PubMed:2072928"
FT /id="VAR_001281"
FT VARIANT 31
FT /note="P -> Q (in AH3; does not affect membrane binding;
FT enzyme function abolished)"
FT /evidence="ECO:0000269|PubMed:10198222"
FT /id="VAR_026060"
FT VARIANT 57
FT /note="G -> R (in AH3; loss of activity;
FT dbSNP:rs1413433421)"
FT /evidence="ECO:0000269|PubMed:18381579"
FT /id="VAR_065668"
FT VARIANT 63
FT /note="H -> L (in AH3; non-classic form; simple virilizing
FT form when associated with a second mild mutation such as S-
FT 453 or L-30; activity is significantly reduced in
FT association with S-453; dbSNP:rs9378252)"
FT /evidence="ECO:0000269|PubMed:12788866,
FT ECO:0000269|PubMed:18319307, ECO:0000269|PubMed:18381579"
FT /id="VAR_018364"
FT VARIANT 65
FT /note="G -> E (in AH3; no activity)"
FT /evidence="ECO:0000269|PubMed:10408778"
FT /id="VAR_007923"
FT VARIANT 78
FT /note="I -> T (in AH3; simple virilizing form;
FT dbSNP:rs1333278223)"
FT /evidence="ECO:0000269|PubMed:20080860"
FT /id="VAR_065669"
FT VARIANT 91
FT /note="G -> V (in AH3)"
FT /evidence="ECO:0000269|PubMed:10364682"
FT /id="VAR_026061"
FT VARIANT 99
FT /note="K -> R (in dbSNP:rs1268071078)"
FT /evidence="ECO:0000269|PubMed:9580109"
FT /id="VAR_001282"
FT VARIANT 103
FT /note="R -> K (in dbSNP:rs6474)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:19505723, ECO:0000269|PubMed:3038528,
FT ECO:0000269|PubMed:3486422, ECO:0000269|PubMed:9580109"
FT /id="VAR_001283"
FT VARIANT 106
FT /note="P -> L (in AH3; dbSNP:rs550051210)"
FT /evidence="ECO:0000269|PubMed:1496017,
FT ECO:0000269|PubMed:8989258"
FT /id="VAR_001284"
FT VARIANT 108
FT /note="L -> R (in AH3; loss of activity;
FT dbSNP:rs957886272)"
FT /evidence="ECO:0000269|PubMed:18381579"
FT /id="VAR_065670"
FT VARIANT 114
FT /note="S -> F (in AH3; non-classic form; loss of steroid
FT 21-monooxygenase activity; dbSNP:rs1296268275)"
FT /evidence="ECO:0000269|PubMed:27721825"
FT /id="VAR_077584"
FT VARIANT 122
FT /note="K -> Q (in AH3; non-classic form; reduced activity;
FT decreased affinity for 17-hydroxyprogesterone and
FT progesterone; dbSNP:rs547552654)"
FT /evidence="ECO:0000269|PubMed:18445671"
FT /id="VAR_065671"
FT VARIANT 125
FT /note="R -> H (in AH3; dbSNP:rs72552750)"
FT /evidence="ECO:0000269|PubMed:14676460"
FT /id="VAR_026062"
FT VARIANT 143
FT /note="L -> P (in AH3; loss of activity;
FT dbSNP:rs755020999)"
FT /evidence="ECO:0000269|PubMed:18381579"
FT /id="VAR_065672"
FT VARIANT 168
FT /note="L -> P (in AH3; salt wasting form; loss of
FT activity)"
FT /evidence="ECO:0000269|PubMed:20080860"
FT /id="VAR_065673"
FT VARIANT 170
FT /note="C -> R (in AH3; loss of hydroxylase activity toward
FT 17-hydroxyprogesterone and progesterone)"
FT /evidence="ECO:0000269|PubMed:16984992"
FT /id="VAR_075372"
FT VARIANT 170
FT /note="C -> Y (in AH3)"
FT /evidence="ECO:0000269|PubMed:10094562"
FT /id="VAR_001285"
FT VARIANT 173
FT /note="I -> N (in AH3; simple virilizing form; 1-4%
FT activity; dbSNP:rs6475)"
FT /evidence="ECO:0000269|PubMed:10051010,
FT ECO:0000269|PubMed:10364682, ECO:0000269|PubMed:10408778,
FT ECO:0000269|PubMed:10408786, ECO:0000269|PubMed:10496074,
FT ECO:0000269|PubMed:10720040, ECO:0000269|PubMed:11232002,
FT ECO:0000269|PubMed:11598371, ECO:0000269|PubMed:11600539,
FT ECO:0000269|PubMed:12222711, ECO:0000269|PubMed:12788866,
FT ECO:0000269|PubMed:12887291, ECO:0000269|PubMed:12915679,
FT ECO:0000269|PubMed:14715874, ECO:0000269|PubMed:15110320,
FT ECO:0000269|PubMed:16046588, ECO:0000269|PubMed:1644925,
FT ECO:0000269|PubMed:18319307, ECO:0000269|PubMed:18381579,
FT ECO:0000269|PubMed:1937474, ECO:0000269|PubMed:20080860,
FT ECO:0000269|PubMed:2303461, ECO:0000269|PubMed:3257825,
FT ECO:0000269|PubMed:3871526, ECO:0000269|PubMed:7749410,
FT ECO:0000269|PubMed:8485582"
FT /id="VAR_001286"
FT VARIANT 179
FT /note="G -> A (in AH3; dbSNP:rs72552751)"
FT /evidence="ECO:0000269|PubMed:10364682"
FT /id="VAR_026063"
FT VARIANT 179
FT /note="G -> R (in AH3; loss of enzymatic activity toward
FT 17-hydroxyprogesterone and progesterone;
FT dbSNP:rs772317717)"
FT /evidence="ECO:0000269|PubMed:16984992"
FT /id="VAR_075373"
FT VARIANT 184
FT /note="D -> E (in allele CYP21A2*4; dbSNP:rs397515531)"
FT /evidence="ECO:0000269|PubMed:9580109"
FT /id="VAR_001287"
FT VARIANT 192
FT /note="Y -> H (in AH3; exhibits low enzymatic activity
FT toward 17-hydroxyprogesterone and progesterone)"
FT /evidence="ECO:0000269|PubMed:22014889"
FT /id="VAR_075374"
FT VARIANT 197
FT /note="Missing (in AH3; moderate)"
FT /evidence="ECO:0000269|PubMed:9497336"
FT /id="VAR_008688"
FT VARIANT 199
FT /note="L -> F (in AH3; dbSNP:rs143240527)"
FT /evidence="ECO:0000269|PubMed:21169732"
FT /id="VAR_075375"
FT VARIANT 203
FT /note="S -> G (decreased steroid 21-monooxygenase activity;
FT dbSNP:rs372964292)"
FT /evidence="ECO:0000269|PubMed:27721825"
FT /id="VAR_077585"
FT VARIANT 212
FT /note="V -> L (in AH3; uncertain significance; non-classic
FT form)"
FT /evidence="ECO:0000269|PubMed:3260007"
FT /id="VAR_026064"
FT VARIANT 231
FT /note="I -> T (in AH3)"
FT /evidence="ECO:0000269|PubMed:20080860"
FT /id="VAR_065674"
FT VARIANT 234
FT /note="R -> K (in AH3)"
FT /evidence="ECO:0000269|PubMed:20080860"
FT /id="VAR_065675"
FT VARIANT 237
FT /note="I -> N (in AH3; salt wasting form;
FT dbSNP:rs111647200)"
FT /evidence="ECO:0000269|PubMed:10408778,
FT ECO:0000269|PubMed:10408786, ECO:0000269|PubMed:15110320,
FT ECO:0000269|PubMed:1644925, ECO:0000269|PubMed:7749410"
FT /id="VAR_001288"
FT VARIANT 238
FT /note="V -> E (in AH3; salt wasting form;
FT dbSNP:rs12530380)"
FT /evidence="ECO:0000269|PubMed:10408786,
FT ECO:0000269|PubMed:15110320, ECO:0000269|PubMed:1644925"
FT /id="VAR_001289"
FT VARIANT 240
FT /note="M -> K (in AH3; salt wasting form; dbSNP:rs6476)"
FT /evidence="ECO:0000269|PubMed:10408786,
FT ECO:0000269|PubMed:15110320, ECO:0000269|PubMed:1644925"
FT /id="VAR_001290"
FT VARIANT 262
FT /note="L -> P (in AH3; dbSNP:rs750337015)"
FT /evidence="ECO:0000269|PubMed:11598371"
FT /id="VAR_026065"
FT VARIANT 268
FT /note="P -> L (decreased steroid 21-monooxygenase activity;
FT dbSNP:rs61732108 and dbSNP:rs142028935)"
FT /evidence="ECO:0000269|PubMed:27721825"
FT /id="VAR_077586"
FT VARIANT 269
FT /note="S -> T (in allele CYP21A2*5; dbSNP:rs6472)"
FT /evidence="ECO:0000269|PubMed:10391209,
FT ECO:0000269|PubMed:10496074, ECO:0000269|PubMed:2072928,
FT ECO:0000269|PubMed:3038528"
FT /id="VAR_001291"
FT VARIANT 282
FT /note="V -> G (in AH3; salt wasting form)"
FT /evidence="ECO:0000269|PubMed:10720040"
FT /id="VAR_026066"
FT VARIANT 282
FT /note="V -> L (in AH3; non-classic form; 50% activity; most
FT common variant; normal KM but 20% reduced Vmax;
FT dbSNP:rs6471)"
FT /evidence="ECO:0000269|PubMed:10094562,
FT ECO:0000269|PubMed:10364682, ECO:0000269|PubMed:10391209,
FT ECO:0000269|PubMed:10408778, ECO:0000269|PubMed:10408786,
FT ECO:0000269|PubMed:10443693, ECO:0000269|PubMed:10496074,
FT ECO:0000269|PubMed:10720040, ECO:0000269|PubMed:11232002,
FT ECO:0000269|PubMed:11600539, ECO:0000269|PubMed:12222711,
FT ECO:0000269|PubMed:12788866, ECO:0000269|PubMed:12887291,
FT ECO:0000269|PubMed:12915679, ECO:0000269|PubMed:15110320,
FT ECO:0000269|PubMed:15126570, ECO:0000269|PubMed:1644925,
FT ECO:0000269|PubMed:1864962, ECO:0000269|PubMed:20080860,
FT ECO:0000269|PubMed:3260007, ECO:0000269|PubMed:3267225,
FT ECO:0000269|PubMed:3497399, ECO:0000269|PubMed:7749410"
FT /id="VAR_001292"
FT VARIANT 283
FT /note="H -> N (in AH3; exhibits low enzymatic activity
FT toward 17-hydroxyprogesterone and progesterone)"
FT /evidence="ECO:0000269|PubMed:22014889"
FT /id="VAR_075376"
FT VARIANT 284
FT /note="M -> L (in AH3)"
FT /evidence="ECO:0000269|PubMed:12222711"
FT /id="VAR_026067"
FT VARIANT 292
FT /note="G -> C (in AH3)"
FT /evidence="ECO:0000269|PubMed:10364682"
FT /id="VAR_026068"
FT VARIANT 292
FT /note="G -> R (in AH3; dbSNP:rs201552310)"
FT /evidence="ECO:0000269|PubMed:12915679"
FT /id="VAR_018365"
FT VARIANT 292
FT /note="G -> S (in AH3; salt wasting form; less then 1%
FT activity; dbSNP:rs201552310)"
FT /evidence="ECO:0000269|PubMed:10408778,
FT ECO:0000269|PubMed:11600539, ECO:0000269|PubMed:1496017,
FT ECO:0000269|PubMed:15110320, ECO:0000269|PubMed:20080860,
FT ECO:0000269|PubMed:9497336"
FT /id="VAR_001293"
FT VARIANT 293
FT /note="G -> D (in AH3; salt wasting form; less then 1%
FT activity)"
FT /evidence="ECO:0000269|PubMed:20080860"
FT /id="VAR_065676"
FT VARIANT 301
FT /note="L -> F (in AH3; salt wasting form;
FT dbSNP:rs765001985)"
FT /evidence="ECO:0000269|PubMed:10720040"
FT /id="VAR_026069"
FT VARIANT 302
FT /note="S -> Y (in AH3)"
FT /evidence="ECO:0000269|PubMed:12915679"
FT /id="VAR_018366"
FT VARIANT 303
FT /note="W -> R (in AH3; loss of enzymatic activity toward
FT 17-hydroxyprogesterone and progesterone)"
FT /evidence="ECO:0000269|PubMed:16984992"
FT /id="VAR_075377"
FT VARIANT 305
FT /note="V -> M (in hyperandrogenism; due to 21-hydroxylase
FT deficiency; non-classic type; residual activity of 46% for
FT conversion of 17-hydroxyprogesterone and 26% for conversion
FT of progesterone compared with the normal enzyme;
FT dbSNP:rs151344505)"
FT /evidence="ECO:0000269|PubMed:12050257"
FT /id="VAR_026070"
FT VARIANT 318
FT /note="L -> M (in AH3)"
FT /evidence="ECO:0000269|PubMed:11232002"
FT /id="VAR_026071"
FT VARIANT 321
FT /note="E -> K (in AH3; simple virilizing form; 4%
FT activity)"
FT /evidence="ECO:0000269|PubMed:20080860"
FT /id="VAR_065677"
FT VARIANT 340
FT /note="R -> H (in AH3; non-classic form; 50% activity;
FT dbSNP:rs72552754)"
FT /evidence="ECO:0000269|PubMed:1406709"
FT /id="VAR_001294"
FT VARIANT 342
FT /note="R -> P (in AH3; simple virilizing form;
FT dbSNP:rs747079101)"
FT /evidence="ECO:0000269|PubMed:12788866,
FT ECO:0000269|PubMed:20080860"
FT /id="VAR_018367"
FT VARIANT 342
FT /note="R -> W (in AH3; non-classic form; mild;
FT dbSNP:rs72552755)"
FT /evidence="ECO:0000269|PubMed:29328376"
FT /id="VAR_001295"
FT VARIANT 355
FT /note="R -> C (in AH3; salt wasting form;
FT dbSNP:rs772900496)"
FT /evidence="ECO:0000269|PubMed:10720040"
FT /id="VAR_026072"
FT VARIANT 355
FT /note="R -> H (in AH3; salt wasting form;
FT dbSNP:rs760216630)"
FT /evidence="ECO:0000269|PubMed:10364682,
FT ECO:0000269|PubMed:20080860"
FT /id="VAR_026073"
FT VARIANT 357
FT /note="R -> P (in AH3; salt wasting form; 0.15% activity)"
FT /evidence="ECO:0000269|PubMed:9187661"
FT /id="VAR_001296"
FT VARIANT 357
FT /note="R -> Q (in AH3; simple virilizing form; mild; 0.65%
FT activity; dbSNP:rs574370139)"
FT /evidence="ECO:0000269|PubMed:10094562,
FT ECO:0000269|PubMed:15110320, ECO:0000269|PubMed:9187661"
FT /id="VAR_001297"
FT VARIANT 357
FT /note="R -> W (in AH3; salt wasting form; dbSNP:rs7769409)"
FT /evidence="ECO:0000269|PubMed:10051010,
FT ECO:0000269|PubMed:10364682, ECO:0000269|PubMed:10408778,
FT ECO:0000269|PubMed:10408786, ECO:0000269|PubMed:10443693,
FT ECO:0000269|PubMed:10496074, ECO:0000269|PubMed:10720040,
FT ECO:0000269|PubMed:11232002, ECO:0000269|PubMed:11598371,
FT ECO:0000269|PubMed:11600539, ECO:0000269|PubMed:12222711,
FT ECO:0000269|PubMed:12788866, ECO:0000269|PubMed:12915679,
FT ECO:0000269|PubMed:14715874, ECO:0000269|PubMed:15110320,
FT ECO:0000269|PubMed:16046588, ECO:0000269|PubMed:1644925,
FT ECO:0000269|PubMed:18319307, ECO:0000269|PubMed:18381579,
FT ECO:0000269|PubMed:20080860, ECO:0000269|PubMed:2303461"
FT /id="VAR_001298"
FT VARIANT 363
FT /note="A -> V (in AH3; no activity)"
FT /evidence="ECO:0000269|PubMed:10408778"
FT /id="VAR_007924"
FT VARIANT 364
FT /note="L -> W (in AH3)"
FT /evidence="ECO:0000269|PubMed:11746135"
FT /id="VAR_026074"
FT VARIANT 366
FT /note="H -> Y (in AH3; dbSNP:rs1330554738)"
FT /evidence="ECO:0000269|PubMed:15110320"
FT /id="VAR_026075"
FT VARIANT 370
FT /note="R -> W (in AH3; dbSNP:rs781074931)"
FT /evidence="ECO:0000269|PubMed:20080860"
FT /id="VAR_065678"
FT VARIANT 376
FT /note="G -> S (in hyperandrogenism; due to 21-hydroxylase
FT deficiency; almost completely abolished enzyme activity;
FT dbSNP:rs151344506)"
FT /evidence="ECO:0000269|PubMed:12050257"
FT /id="VAR_026076"
FT VARIANT 381
FT /note="E -> D (in AH3; salt wasting form;
FT dbSNP:rs72552756)"
FT /evidence="ECO:0000269|PubMed:9067760"
FT /id="VAR_001299"
FT VARIANT 390..392
FT /note="Missing (in AH3; salt wasting form; loss of steroid
FT 21-monooxygenase activity)"
FT /evidence="ECO:0000269|PubMed:27721825"
FT /id="VAR_077587"
FT VARIANT 409
FT /note="R -> C (in AH3; very low residual activity;
FT dbSNP:rs72552757)"
FT /evidence="ECO:0000269|PubMed:12213891,
FT ECO:0000269|PubMed:18381579, ECO:0000269|PubMed:20080860"
FT /id="VAR_026077"
FT VARIANT 425
FT /note="G -> S (in AH3; very low activity;
FT dbSNP:rs72552758)"
FT /evidence="ECO:0000269|PubMed:10443693,
FT ECO:0000269|PubMed:11600539, ECO:0000269|PubMed:12213891,
FT ECO:0000269|PubMed:20080860"
FT /id="VAR_026078"
FT VARIANT 427
FT /note="R -> C (in AH3; loss of enzymatic activity toward
FT 17-hydroxyprogesterone and progesterone;
FT dbSNP:rs1370167869)"
FT /evidence="ECO:0000269|PubMed:16984992"
FT /id="VAR_075378"
FT VARIANT 427
FT /note="R -> H (in AH3; loss of enzymatic activity toward
FT 17-hydroxyprogesterone; dbSNP:rs151344504)"
FT /evidence="ECO:0000269|PubMed:11600539,
FT ECO:0000269|PubMed:16984992, ECO:0000269|PubMed:20080860"
FT /id="VAR_026079"
FT VARIANT 436
FT /note="R -> C (in AH3; dbSNP:rs767333157)"
FT /evidence="ECO:0000269|PubMed:11232002"
FT /id="VAR_026080"
FT VARIANT 451
FT /note="T -> M (decreased steroid 21-monooxygenase activity;
FT dbSNP:rs1319651744)"
FT /evidence="ECO:0000269|PubMed:27721825"
FT /id="VAR_077588"
FT VARIANT 451
FT /note="T -> P (in AH3; salt wasting form; loss of steroid
FT 21-monooxygenase activity)"
FT /evidence="ECO:0000269|PubMed:27721825"
FT /id="VAR_077589"
FT VARIANT 454
FT /note="P -> S (in AH3; non-classic form; simple virilizing
FT form when associated with L-62; 50% of activity; almost
FT completely abolished enzyme activity when associated with
FT S-375; dbSNP:rs6445)"
FT /evidence="ECO:0000269|PubMed:10364682,
FT ECO:0000269|PubMed:10391209, ECO:0000269|PubMed:10720040,
FT ECO:0000269|PubMed:11232002, ECO:0000269|PubMed:11600539,
FT ECO:0000269|PubMed:12050257, ECO:0000269|PubMed:12222711,
FT ECO:0000269|PubMed:12788866, ECO:0000269|PubMed:12887291,
FT ECO:0000269|PubMed:1406699, ECO:0000269|PubMed:1406709,
FT ECO:0000269|PubMed:1496017, ECO:0000269|PubMed:15110320,
FT ECO:0000269|PubMed:18319307, ECO:0000269|PubMed:18381579,
FT ECO:0000269|PubMed:18445671, ECO:0000269|PubMed:20080860,
FT ECO:0000269|PubMed:8989258"
FT /id="VAR_001300"
FT VARIANT 480
FT /note="R -> L (in AH3; dbSNP:rs184649564)"
FT /evidence="ECO:0000269|PubMed:15110320"
FT /id="VAR_026081"
FT VARIANT 483
FT /note="P -> S (in AH3; reduced enzyme activity to 70% of
FT normal; dbSNP:rs776989258)"
FT /evidence="ECO:0000269|PubMed:15126570,
FT ECO:0000269|PubMed:27721825"
FT /id="VAR_026082"
FT VARIANT 484
FT /note="R -> P (in AH3; moderate; 1-2% of activity;
FT dbSNP:rs200005406)"
FT /evidence="ECO:0000269|PubMed:11598371,
FT ECO:0000269|PubMed:11600539, ECO:0000269|PubMed:12788866,
FT ECO:0000269|PubMed:15110320, ECO:0000269|PubMed:7749410,
FT ECO:0000269|PubMed:8478006, ECO:0000269|PubMed:9497336"
FT /id="VAR_001301"
FT VARIANT 484
FT /note="R -> Q (in AH3; dbSNP:rs200005406)"
FT /evidence="ECO:0000269|PubMed:12915679"
FT /id="VAR_018368"
FT VARIANT 484
FT /note="R -> W (in AH3; salt wasting form;
FT dbSNP:rs759736443)"
FT /evidence="ECO:0000269|PubMed:14715874"
FT /id="VAR_026083"
FT VARIANT 494
FT /note="S -> N (in dbSNP:rs6473)"
FT /evidence="ECO:0000269|PubMed:19505723,
FT ECO:0000269|PubMed:3038528, ECO:0000269|PubMed:3486422,
FT ECO:0000269|PubMed:3487786, ECO:0000269|PubMed:3497399,
FT ECO:0000269|PubMed:9580109"
FT /id="VAR_001302"
FT MUTAGEN 269
FT /note="S->C,M,T: No effect on progesterone 21-hydroxylase
FT activity."
FT /evidence="ECO:0000269|PubMed:1864962"
FT MUTAGEN 282
FT /note="V->I: Decreased 21-hydroxylase activity. Normal KM
FT but 50% reduced Vmax."
FT /evidence="ECO:0000269|PubMed:1864962"
FT MUTAGEN 282
FT /note="V->T: Decreased 21-hydroxylase activity. Normal KM
FT but 10% reduced Vmax."
FT /evidence="ECO:0000269|PubMed:1864962"
FT MUTAGEN 429
FT /note="C->M,S,T: Loss of progesterone 21-hydroxylase
FT activity and loss of P450 absorption."
FT /evidence="ECO:0000269|PubMed:1864962"
FT CONFLICT 156
FT /note="G -> D (in Ref. 10; BAB70774)"
FT /evidence="ECO:0000305"
FT CONFLICT 243
FT /note="R -> G (in Ref. 10; BAB70774)"
FT /evidence="ECO:0000305"
FT CONFLICT 278
FT /note="L -> Q (in Ref. 10; BAB70774)"
FT /evidence="ECO:0000305"
FT CONFLICT 305
FT /note="V -> A (in Ref. 10; BAB70774)"
FT /evidence="ECO:0000305"
FT CONFLICT 312
FT /note="P -> L (in Ref. 18; AAA59985)"
FT /evidence="ECO:0000305"
FT CONFLICT 347
FT /note="N -> I (in Ref. 18; AAA59985)"
FT /evidence="ECO:0000305"
FT CONFLICT 427
FT /note="R -> P (in Ref. 1; AAB59440)"
FT /evidence="ECO:0000305"
FT CONFLICT 438
FT /note="E -> D (in Ref. 1; AAB59440)"
FT /evidence="ECO:0000305"
FT HELIX 39..41
FT /evidence="ECO:0007829|PDB:4Y8W"
FT HELIX 45..51
FT /evidence="ECO:0007829|PDB:4Y8W"
FT HELIX 53..56
FT /evidence="ECO:0007829|PDB:4Y8W"
FT STRAND 58..64
FT /evidence="ECO:0007829|PDB:4Y8W"
FT STRAND 67..72
FT /evidence="ECO:0007829|PDB:4Y8W"
FT HELIX 75..82
FT /evidence="ECO:0007829|PDB:4Y8W"
FT TURN 83..85
FT /evidence="ECO:0007829|PDB:4Y8W"
FT HELIX 86..89
FT /evidence="ECO:0007829|PDB:4Y8W"
FT HELIX 96..100
FT /evidence="ECO:0007829|PDB:4Y8W"
FT HELIX 115..129
FT /evidence="ECO:0007829|PDB:4Y8W"
FT TURN 130..135
FT /evidence="ECO:0007829|PDB:4Y8W"
FT HELIX 136..151
FT /evidence="ECO:0007829|PDB:4Y8W"
FT HELIX 161..178
FT /evidence="ECO:0007829|PDB:4Y8W"
FT HELIX 180..183
FT /evidence="ECO:0007829|PDB:4Y8W"
FT TURN 184..186
FT /evidence="ECO:0007829|PDB:4Y8W"
FT HELIX 188..202
FT /evidence="ECO:0007829|PDB:4Y8W"
FT HELIX 205..212
FT /evidence="ECO:0007829|PDB:4Y8W"
FT HELIX 214..217
FT /evidence="ECO:0007829|PDB:4Y8W"
FT HELIX 224..246
FT /evidence="ECO:0007829|PDB:4Y8W"
FT HELIX 257..262
FT /evidence="ECO:0007829|PDB:4Y8W"
FT HELIX 279..310
FT /evidence="ECO:0007829|PDB:4Y8W"
FT HELIX 312..325
FT /evidence="ECO:0007829|PDB:4Y8W"
FT TURN 337..339
FT /evidence="ECO:0007829|PDB:4Y8W"
FT HELIX 344..356
FT /evidence="ECO:0007829|PDB:4Y8W"
FT STRAND 370..374
FT /evidence="ECO:0007829|PDB:4Y8W"
FT STRAND 377..379
FT /evidence="ECO:0007829|PDB:4Y8W"
FT STRAND 384..387
FT /evidence="ECO:0007829|PDB:4Y8W"
FT HELIX 389..393
FT /evidence="ECO:0007829|PDB:4Y8W"
FT TURN 396..398
FT /evidence="ECO:0007829|PDB:4Y8W"
FT STRAND 399..401
FT /evidence="ECO:0007829|PDB:4Y8W"
FT HELIX 407..410
FT /evidence="ECO:0007829|PDB:4Y8W"
FT HELIX 432..447
FT /evidence="ECO:0007829|PDB:4Y8W"
FT STRAND 450..458
FT /evidence="ECO:0007829|PDB:4Y8W"
FT STRAND 479..483
FT /evidence="ECO:0007829|PDB:4Y8W"
SQ SEQUENCE 495 AA; 56001 MW; CE5C4EE9D3A0851C CRC64;
MLLLGLLLLL PLLAGARLLW NWWKLRSLHL PPLAPGFLHL LQPDLPIYLL GLTQKFGPIY
RLHLGLQDVV VLNSKRTIEE AMVKKWADFA GRPEPLTYKL VSRNYPDLSL GDYSLLWKAH
KKLTRSALLL GIRDSMEPVV EQLTQEFCER MRAQPGTPVA IEEEFSLLTC SIICYLTFGD
KIKDDNLMPA YYKCIQEVLK TWSHWSIQIV DVIPFLRFFP NPGLRRLKQA IEKRDHIVEM
QLRQHKESLV AGQWRDMMDY MLQGVAQPSM EEGSGQLLEG HVHMAAVDLL IGGTETTANT
LSWAVVFLLH HPEIQQRLQE ELDHELGPGA SSSRVPYKDR ARLPLLNATI AEVLRLRPVV
PLALPHRTTR PSSISGYDIP EGTVIIPNLQ GAHLDETVWE RPHEFWPDRF LEPGKNSRAL
AFGCGARVCL GEPLARLELF VVLTRLLQAF TLLPSGDALP SLQPLPHCSV ILKMQPFQVR
LQPRGMGAHS PGQSQ
//