S5A2_HUMAN
ID S5A2_HUMAN Reviewed; 254 AA.
AC P31213; B2RE87; Q2M1R4; Q9BYE6;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1993, sequence version 1.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=3-oxo-5-alpha-steroid 4-dehydrogenase 2;
DE EC=1.3.1.22 {ECO:0000269|PubMed:10898110};
DE AltName: Full=5 alpha-SR2;
DE AltName: Full=SR type 2;
DE AltName: Full=Steroid 5-alpha-reductase 2;
DE Short=S5AR 2;
DE AltName: Full=Type II 5-alpha reductase;
GN Name=SRD5A2;
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 [MRNA].
RX PubMed=1944596; DOI=10.1038/354159a0;
RA Andersson S., Berman D.M., Jenkins E.P., Russell D.W.;
RT "Deletion of steroid 5 alpha-reductase 2 gene in male
RT pseudohermaphroditism.";
RL Nature 354:159-161(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1505484; DOI=10.1210/endo.131.3.1505484;
RA Labrie F., Sugimoto Y., Luu-The V., Simard J., Lachance Y., Bachvarov D.,
RA Leblanc G., Durocher F., Paquet N.;
RT "Structure of human type II 5 alpha-reductase gene.";
RL Endocrinology 131:1571-1573(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT LEU-89.
RC TISSUE=Liver tumor;
RA Schupp I.;
RL Submitted (APR-2007) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS THR-49; LEU-89 AND VAL-113.
RG NIEHS SNPs program;
RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LEU-89.
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 [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-67.
RC TISSUE=Placenta;
RA Nakanishi J., Hibino T.;
RT "Transcription of type II 5 alpha-reductase is up-regulated by SRY in human
RT dermal papilla cells.";
RL Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP VARIANT PPSH TRP-246.
RX PubMed=1522235; DOI=10.1172/jci115954;
RA Thigpen A.E., Davis D.L., Milatovich A., Mendonca B.B.,
RA Imperato-Mcginley J., Griffin J.E., Francke U., Wilson J.D., Russell D.W.;
RT "Molecular genetics of steroid 5 alpha-reductase 2 deficiency.";
RL J. Clin. Invest. 90:799-809(1992).
RN [10]
RP VARIANT PPSH MET-157 DEL.
RX PubMed=7554313; DOI=10.1111/j.1365-2265.1995.tb01913.x;
RA Boudon C., Lobaccaro J.-M., Lumbroso S., Ogur G., Ocal G., Belon C.,
RA Sultan C.;
RT "A new deletion of the 5-alpha-reductase type 2 gene in a Turkish family
RT with 5-alpha-reductase deficiency.";
RL Clin. Endocrinol. (Oxf.) 43:183-188(1995).
RN [11]
RP VARIANTS PPSH ASP-115; SER-183 AND TRP-246.
RX PubMed=8626825; DOI=10.1210/jcem.81.5.8626825;
RA Cai L.-Q., Zhu Y.-S., Katz M.D., Herrera C., Baez J., DeFillo-Ricart M.,
RA Shackleton C.H.L., Imperato-McGinley J.;
RT "5-alpha-reductase-2 gene mutations in the Dominican Republic.";
RL J. Clin. Endocrinol. Metab. 81:1730-1735(1996).
RN [12]
RP VARIANT PPSH GLN-55.
RX PubMed=8768837; DOI=10.1210/jcem.81.8.8768837;
RA Hochberg Z., Chayen R., Reiss N., Falik Z., Makler A., Munichor M.,
RA Farkas A., Goldfarb H., Ohana N., Hiort O.;
RT "Clinical, biochemical, and genetic findings in a large pedigree of male
RT and female patients with 5-alpha-reductase 2 deficiency.";
RL J. Clin. Endocrinol. Metab. 81:2821-2827(1996).
RN [13]
RP VARIANT PPSH LYS-200.
RX PubMed=9208814; DOI=10.1136/mp.50.1.51;
RA Anwar R., Gilbey S.G., New J.P., Markham A.F.;
RT "Male pseudohermaphroditism resulting from a novel mutation in the human
RT steroid 5 alpha-reductase type 2 gene (SRD5A2).";
RL Mol. Pathol. 50:51-52(1997).
RN [14]
RP VARIANT PPSH THR-228.
RX PubMed=9843052;
RX DOI=10.1002/(sici)1096-8628(19981116)80:3<269::aid-ajmg18>3.0.co;2-t;
RA Nordenskjold A., Magnus O., Aagenaes O., Knudtzon J.;
RT "Homozygous mutation (A228T) in the 5-alpha-reductase type 2 gene in a boy
RT with 5-alpha-reductase deficiency: genotype-phenotype correlations.";
RL Am. J. Med. Genet. 80:269-272(1998).
RN [15]
RP VARIANTS PPSH SER-196 AND ARG-231.
RX PubMed=9745434; DOI=10.1210/jcem.83.9.5125;
RA Nordenskjold A., Ivarsson S.-A.;
RT "Molecular characterization of 5-alpha-reductase type 2 deficiency and
RT fertility in a Swedish family.";
RL J. Clin. Endocrinol. Metab. 83:3236-3238(1998).
RN [16]
RP VARIANT THR-49, AND POLYMORPHISM.
RX PubMed=10501358; DOI=10.1016/s0140-6736(98)11282-5;
RA Makridakis N.M., Ross R.K., Pike M.C., Crocitto L.E., Kolonel L.N.,
RA Pearce C.L., Henderson B.E., Reichardt J.K.V.;
RT "Association of mis-sense substitution in SRD5A2 gene with prostate cancer
RT in African-American and Hispanic men in Los Angeles, USA.";
RL Lancet 354:975-978(1999).
RN [17]
RP VARIANTS PPSH ASP-85; ASP-115; ARG-212; TYR-245 AND GLN-246.
RX PubMed=10718838; DOI=10.1046/j.1365-2265.2000.00941.x;
RA Vilchis F., Mendez J.P., Canto P., Lieberman E., Chavez B.;
RT "Identification of missense mutations in the SRD5A2 gene from patients with
RT steroid 5alpha-reductase 2 deficiency.";
RL Clin. Endocrinol. (Oxf.) 52:383-387(2000).
RN [18]
RP VARIANTS PPSH ASP-197 AND ARG-212.
RX PubMed=10999800; DOI=10.1210/jcem.85.9.6786;
RA Chavez B., Valdez E., Vilchis F.;
RT "Uniparental disomy in steroid 5-alpha-reductase 2 deficiency.";
RL J. Clin. Endocrinol. Metab. 85:3147-3150(2000).
RN [19]
RP VARIANTS ARG-5; LEU-30; ARG-48; THR-49; THR-51; LEU-89; MET-187; LEU-194
RP AND LEU-234, VARIANT PPSH GLN-227, FUNCTION, CATALYTIC ACTIVITY, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=10898110; DOI=10.1097/00008571-200007000-00004;
RA Makridakis N.M., di Salle E., Reichardt J.K.;
RT "Biochemical and pharmacogenetic dissection of human steroid 5 alpha-
RT reductase type II.";
RL Pharmacogenetics 10:407-413(2000).
RN [20]
RP VARIANT LEU-89.
RX PubMed=11927504;
RA Pearce C.L., Makridakis N.M., Ross R.K., Pike M.C., Kolonel L.N.,
RA Henderson B.E., Reichardt J.K.V.;
RT "Steroid 5-alpha reductase type II V89L substitution is not associated with
RT risk of prostate cancer in a multiethnic population study.";
RL Cancer Epidemiol. Biomarkers Prev. 11:417-418(2002).
RN [21]
RP VARIANT PPSH GLN-227, AND VARIANT LEU-89.
RX PubMed=12843198; DOI=10.1210/jc.2002-021415;
RA Sasaki G., Ogata T., Ishii T., Kosaki K., Sato S., Homma K., Takahashi T.,
RA Hasegawa T., Matsuo N.;
RT "Micropenis and the 5alpha-reductase-2 (SRD5A2) gene: mutation and V89L
RT polymorphism analysis in 81 Japanese patients.";
RL J. Clin. Endocrinol. Metab. 88:3431-3436(2003).
RN [22]
RP VARIANT THR-49, AND LACK OF ASSOCIATION WITH PROSTATE CANCER.
RX PubMed=14560315; DOI=10.1038/sj.ejhg.5201101;
RA Loukola A., Chadha M., Penn S.G., Rank D., Conti D.V., Thompson D.,
RA Cicek M., Love B., Bivolarevic V., Yang Q., Jiang Y., Hanzel D.K.,
RA Dains K., Paris P.L., Casey G., Witte J.S.;
RT "Comprehensive evaluation of the association between prostate cancer and
RT genotypes/haplotypes in CYP17A1, CYP3A4, and SRD5A2.";
RL Eur. J. Hum. Genet. 12:321-332(2004).
RN [23]
RP VARIANTS PPSH ASP-115 AND TRP-246.
RX PubMed=15528927; DOI=10.1159/000081893;
RA Fernandez-Cancio M., Rodo J., Andaluz P., Martinez de Osaba M.J.,
RA Rodriguez-Hierro F., Esteban C., Carrascosa A., Audi L.;
RT "Clinical, biochemical and morphologic diagnostic markers in an infant male
RT pseudohermaphrodite patient with compound heterozygous mutations
RT (G115D/R246W) in SRD5A2 gene.";
RL Horm. Res. 62:259-264(2004).
RN [24]
RP VARIANT PPSH GLN-227.
RX PubMed=15064320; DOI=10.1002/j.1939-4640.2004.tb02808.x;
RA Fernandez-Cancio M., Nistal M., Gracia R., Molina M.A., Tovar J.A.,
RA Esteban C., Carrascosa A., Audi L.;
RT "Compound heterozygous mutations in the SRD5A2 gene exon 4 in a male
RT pseudohermaphrodite patient of Chinese origin.";
RL J. Androl. 25:412-416(2004).
RN [25]
RP VARIANTS PPSH TRP-145; LEU-181; SER-196; PHE-235 AND GLN-246, AND VARIANTS
RP THR-49 AND LEU-89.
RX PubMed=16181229; DOI=10.1111/j.1365-2265.2005.02348.x;
RA Nicoletti A., Baldazzi L., Balsamo A., Barp L., Pirazzoli P., Gennari M.,
RA Radetti G., Cacciari E., Cicognani A.;
RT "SRD5A2 gene analysis in an Italian population of under-masculinized 46,XY
RT subjects.";
RL Clin. Endocrinol. (Oxf.) 63:375-380(2005).
RN [26]
RP VARIANTS PPSH ARG-126; ARG-158; SER-183; SER-196; ASP-207 AND TRP-246, AND
RP VARIANTS THR-49 AND LEU-89.
RX PubMed=15770495; DOI=10.1007/s00109-005-0651-7;
RA Hackel C., Oliveira L.E., Ferraz L.F., Tonini M.M., Silva D.N.,
RA Toralles M.B., Stuchi-Perez E.G., Guerra-Junior G.;
RT "New mutations, hotspots, and founder effects in Brazilian patients with
RT steroid 5alpha-reductase deficiency type 2.";
RL J. Mol. Med. 83:569-576(2005).
RN [27]
RP VARIANT PPSH ARG-123.
RX PubMed=16098368; DOI=10.1016/j.urology.2005.02.021;
RA Bahceci M., Ersay A.R., Tuzcu A., Hiort O., Richter-Unruh A., Gokalp D.;
RT "A novel missense mutation of 5-alpha reductase type 2 gene (SRD5A2) leads
RT to severe male pseudohermaphroditism in a Turkish family.";
RL Urology 66:407-410(2005).
CC -!- FUNCTION: Converts testosterone (T) into 5-alpha-dihydrotestosterone
CC (DHT) and progesterone or corticosterone into their corresponding 5-
CC alpha-3-oxosteroids. It plays a central role in sexual differentiation
CC and androgen physiology. {ECO:0000269|PubMed:10898110}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 3-oxo-5alpha-steroid + NADP(+) = a 3-oxo-Delta(4)-steroid +
CC H(+) + NADPH; Xref=Rhea:RHEA:54384, ChEBI:CHEBI:13601,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:47909, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; EC=1.3.1.22;
CC Evidence={ECO:0000269|PubMed:10898110};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.9 uM for testosterone (at pH 6.0) {ECO:0000269|PubMed:10898110};
CC KM=8 uM for NADPH (at pH 6.0) {ECO:0000269|PubMed:10898110};
CC Vmax=1.9 nmol/min/mg enzyme with testosterone as substrate with NADPH
CC as cofactor (at pH 6.0) {ECO:0000269|PubMed:10898110};
CC pH dependence:
CC Optimally active at acidic pHs.;
CC -!- INTERACTION:
CC P31213; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-13130472, EBI-3867333;
CC P31213; Q14749: GNMT; NbExp=3; IntAct=EBI-13130472, EBI-744239;
CC -!- SUBCELLULAR LOCATION: Microsome membrane; Multi-pass membrane protein.
CC Endoplasmic reticulum membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in high levels in the prostate and many
CC other androgen-sensitive tissues.
CC -!- POLYMORPHISM: Individuals with Thr-49 have an increased risk of
CC prostate cancer (PubMed:10501358). The enzyme with Thr-49 has a higher
CC in vitro V(max) than the Ala-49 enzyme (PubMed:10501358).
CC {ECO:0000269|PubMed:10501358}.
CC -!- DISEASE: Pseudovaginal perineoscrotal hypospadias (PPSH) [MIM:264600]:
CC A form of male pseudohermaphroditism in which 46,XY males show
CC ambiguous genitalia at birth, including perineal hypospadias and a
CC blind perineal pouch, and develop masculinization at puberty. The name
CC of the disorder stems from the finding of a blind-ending perineal
CC opening resembling a vagina and a severely hypospadiac penis with the
CC urethra opening onto the perineum. {ECO:0000269|PubMed:10718838,
CC ECO:0000269|PubMed:10898110, ECO:0000269|PubMed:10999800,
CC ECO:0000269|PubMed:12843198, ECO:0000269|PubMed:15064320,
CC ECO:0000269|PubMed:1522235, ECO:0000269|PubMed:15528927,
CC ECO:0000269|PubMed:15770495, ECO:0000269|PubMed:16098368,
CC ECO:0000269|PubMed:16181229, ECO:0000269|PubMed:7554313,
CC ECO:0000269|PubMed:8626825, ECO:0000269|PubMed:8768837,
CC ECO:0000269|PubMed:9208814, ECO:0000269|PubMed:9745434,
CC ECO:0000269|PubMed:9843052}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the steroid 5-alpha reductase family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/srd5a2/";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=5-alpha reductase entry;
CC URL="https://en.wikipedia.org/wiki/5_alpha_reductase";
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DR EMBL; M74047; AAA60586.1; -; mRNA.
DR EMBL; AB047857; BAB40419.1; -; Genomic_DNA.
DR EMBL; EF560740; ABQ59050.1; -; mRNA.
DR EMBL; AY884245; AAW56942.1; -; Genomic_DNA.
DR EMBL; AK316597; BAG38184.1; -; mRNA.
DR EMBL; CH471053; EAX00478.1; -; Genomic_DNA.
DR EMBL; BC112252; AAI12253.1; -; mRNA.
DR EMBL; BC113641; AAI13642.1; -; mRNA.
DR EMBL; L03843; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS74503.1; -.
DR PIR; A49169; A49169.
DR RefSeq; NP_000339.2; NM_000348.3.
DR PDB; 7BW1; X-ray; 2.80 A; A=1-254.
DR PDBsum; 7BW1; -.
DR AlphaFoldDB; P31213; -.
DR SMR; P31213; -.
DR BioGRID; 112594; 5.
DR IntAct; P31213; 2.
DR STRING; 9606.ENSP00000477587; -.
DR BindingDB; P31213; -.
DR ChEMBL; CHEMBL1856; -.
DR DrugBank; DB00548; Azelaic acid.
DR DrugBank; DB01126; Dutasteride.
DR DrugBank; DB01216; Finasteride.
DR DrugBank; DB00741; Hydrocortisone.
DR DrugBank; DB00717; Norethisterone.
DR DrugBank; DB00421; Spironolactone.
DR DrugBank; DB13943; Testosterone cypionate.
DR DrugBank; DB13944; Testosterone enanthate.
DR DrugBank; DB01420; Testosterone propionate.
DR DrugBank; DB13946; Testosterone undecanoate.
DR DrugCentral; P31213; -.
DR GuidetoPHARMACOLOGY; 2633; -.
DR TCDB; 2.A.90.3.6; the vitamin a receptor/transporter (stra6) family.
DR iPTMnet; P31213; -.
DR PhosphoSitePlus; P31213; -.
DR BioMuta; SRD5A2; -.
DR DMDM; 401056; -.
DR MassIVE; P31213; -.
DR PeptideAtlas; P31213; -.
DR PRIDE; P31213; -.
DR ProteomicsDB; 54764; -.
DR Antibodypedia; 72759; 236 antibodies from 26 providers.
DR DNASU; 6716; -.
DR Ensembl; ENST00000622030.2; ENSP00000477587.1; ENSG00000277893.2.
DR GeneID; 6716; -.
DR KEGG; hsa:6716; -.
DR UCSC; uc032nip.2; human.
DR CTD; 6716; -.
DR DisGeNET; 6716; -.
DR GeneCards; SRD5A2; -.
DR HGNC; HGNC:11285; SRD5A2.
DR HPA; ENSG00000277893; Group enriched (epididymis, fallopian tube, liver, prostate, seminal vesicle).
DR MalaCards; SRD5A2; -.
DR MIM; 264600; phenotype.
DR MIM; 607306; gene.
DR neXtProt; NX_P31213; -.
DR Orphanet; 753; 46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency.
DR Orphanet; 1331; Familial prostate cancer.
DR PharmGKB; PA36113; -.
DR VEuPathDB; HostDB:ENSG00000277893; -.
DR eggNOG; KOG1638; Eukaryota.
DR HOGENOM; CLU_065395_1_1_1; -.
DR InParanoid; P31213; -.
DR OrthoDB; 1574389at2759; -.
DR PhylomeDB; P31213; -.
DR BioCyc; MetaCyc:HS00619-MON; -.
DR BRENDA; 1.3.1.22; 2681.
DR BRENDA; 1.3.99.5; 2681.
DR PathwayCommons; P31213; -.
DR Reactome; R-HSA-193048; Androgen biosynthesis.
DR SignaLink; P31213; -.
DR BioGRID-ORCS; 6716; 8 hits in 204 CRISPR screens.
DR ChiTaRS; SRD5A2; human.
DR GeneWiki; SRD5A2; -.
DR GenomeRNAi; 6716; -.
DR Pharos; P31213; Tclin.
DR PRO; PR:P31213; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P31213; protein.
DR Bgee; ENSG00000277893; Expressed in corpus epididymis and 55 other tissues.
DR Genevisible; P31213; HS.
DR GO; GO:0070852; C:cell body fiber; IEA:Ensembl.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0003865; F:3-oxo-5-alpha-steroid 4-dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0033218; F:amide binding; IEA:Ensembl.
DR GO; GO:0047751; F:cholestenone 5-alpha-reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0009917; F:sterol 5-alpha reductase activity; IDA:UniProtKB.
DR GO; GO:0030283; F:testosterone dehydrogenase [NAD(P)] activity; IDA:UniProtKB.
DR GO; GO:0006702; P:androgen biosynthetic process; TAS:Reactome.
DR GO; GO:0008209; P:androgen metabolic process; IDA:UniProtKB.
DR GO; GO:0018879; P:biphenyl metabolic process; IEA:Ensembl.
DR GO; GO:0060348; P:bone development; IEA:Ensembl.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0007267; P:cell-cell signaling; TAS:UniProtKB.
DR GO; GO:0018894; P:dibenzo-p-dioxin metabolic process; IEA:Ensembl.
DR GO; GO:0030540; P:female genitalia development; IEA:Ensembl.
DR GO; GO:0021766; P:hippocampus development; IEA:Ensembl.
DR GO; GO:0021854; P:hypothalamus development; IEA:Ensembl.
DR GO; GO:0030539; P:male genitalia development; IEA:Ensembl.
DR GO; GO:0008584; P:male gonad development; IMP:UniProtKB.
DR GO; GO:0018963; P:phthalate metabolic process; IEA:Ensembl.
DR GO; GO:0032354; P:response to follicle-stimulating hormone; IEA:Ensembl.
DR GO; GO:0031667; P:response to nutrient levels; IEA:Ensembl.
DR GO; GO:0043434; P:response to peptide hormone; IEA:Ensembl.
DR GO; GO:0048545; P:response to steroid hormone; IEA:Ensembl.
DR GO; GO:0033574; P:response to testosterone; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0006694; P:steroid biosynthetic process; IBA:GO_Central.
DR GO; GO:0006706; P:steroid catabolic process; IEA:Ensembl.
DR GO; GO:0061370; P:testosterone biosynthetic process; IDA:UniProtKB.
DR InterPro; IPR016636; 3-oxo-5-alpha-steroid_4-DH.
DR InterPro; IPR001104; 3-oxo-5_a-steroid_4-DH_C.
DR InterPro; IPR039357; SRD5A/TECR.
DR PANTHER; PTHR10556; PTHR10556; 1.
DR Pfam; PF02544; Steroid_dh; 1.
DR PIRSF; PIRSF015596; 5_alpha-SR2; 1.
DR PROSITE; PS50244; S5A_REDUCTASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Differentiation; Disease variant; Endoplasmic reticulum;
KW Lipid metabolism; Membrane; Microsome; NADP; Oxidoreductase;
KW Pseudohermaphroditism; Reference proteome; Sexual differentiation;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..254
FT /note="3-oxo-5-alpha-steroid 4-dehydrogenase 2"
FT /id="PRO_0000213676"
FT TRANSMEM 8..28
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 72..92
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 146..166
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 206..226
FT /note="Helical"
FT /evidence="ECO:0000255"
FT VARIANT 5
FT /note="C -> R (no effect on affinity for testosterone; no
FT effect on affinity for NADPH; no effect on Vmax;
FT dbSNP:rs61748120)"
FT /evidence="ECO:0000269|PubMed:10898110"
FT /id="VAR_077546"
FT VARIANT 30
FT /note="P -> L (increased affinity for testosterone;
FT increased affinity for NADPH; decreased Vmax)"
FT /evidence="ECO:0000269|PubMed:10898110"
FT /id="VAR_077547"
FT VARIANT 48
FT /note="P -> R (increased affinity for testosterone;
FT increased affinity for NADPH; decreased Vmax;
FT dbSNP:rs61748122)"
FT /evidence="ECO:0000269|PubMed:10898110"
FT /id="VAR_077548"
FT VARIANT 49
FT /note="A -> T (increased affinity for testosterone; no
FT effect on affinity for NADPH; increased Vmax; no effect on
FT affinity for testosterone when associated with L-89; no
FT effect on affinity for NADPH when associated with L-89;
FT increased Vmax when associated with L-89; dbSNP:rs9282858)"
FT /evidence="ECO:0000269|PubMed:10501358,
FT ECO:0000269|PubMed:10898110, ECO:0000269|PubMed:14560315,
FT ECO:0000269|PubMed:15770495, ECO:0000269|PubMed:16181229,
FT ECO:0000269|Ref.4"
FT /id="VAR_013104"
FT VARIANT 51
FT /note="A -> T (no effect on affinity for testosterone;
FT increased affinity for NADPH; decreased Vmax;
FT dbSNP:rs61748123)"
FT /evidence="ECO:0000269|PubMed:10898110"
FT /id="VAR_077549"
FT VARIANT 55
FT /note="L -> Q (in PPSH; dbSNP:rs121434245)"
FT /evidence="ECO:0000269|PubMed:8768837"
FT /id="VAR_013105"
FT VARIANT 85
FT /note="G -> D (in PPSH; dbSNP:rs1351269392)"
FT /evidence="ECO:0000269|PubMed:10718838"
FT /id="VAR_013130"
FT VARIANT 89
FT /note="V -> L (no effect on affinity for testosterone; no
FT effect on affinity for NADPH; decreased Vmax; no effect on
FT affinity for testosterone when associated with T-49; no
FT effect on affinity for NADPH when associated with T-49;
FT increased Vmax when associated with T-49; decreased
FT affinity for testosterone when associated with M-187;
FT increased affinity for NADPH when associated with M-187;
FT decreased Vmax when associated with M-187; no effect on
FT affinity for testosterone when associated with L-234;
FT increased affinity for NADPH when associated with L-234;
FT decreased Vmax when associated with L-234; dbSNP:rs523349)"
FT /evidence="ECO:0000269|PubMed:10898110,
FT ECO:0000269|PubMed:11927504, ECO:0000269|PubMed:12843198,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:15770495,
FT ECO:0000269|PubMed:16181229, ECO:0000269|Ref.3,
FT ECO:0000269|Ref.4"
FT /id="VAR_013131"
FT VARIANT 113
FT /note="L -> V (in dbSNP:rs28383048)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_022302"
FT VARIANT 115
FT /note="G -> D (in PPSH; dbSNP:rs121434246)"
FT /evidence="ECO:0000269|PubMed:10718838,
FT ECO:0000269|PubMed:15528927, ECO:0000269|PubMed:8626825"
FT /id="VAR_013106"
FT VARIANT 123
FT /note="G -> R (in PPSH; dbSNP:rs1331249320)"
FT /evidence="ECO:0000269|PubMed:16098368"
FT /id="VAR_025854"
FT VARIANT 126
FT /note="Q -> R (in PPSH; dbSNP:rs368386747)"
FT /evidence="ECO:0000269|PubMed:15770495"
FT /id="VAR_025855"
FT VARIANT 145
FT /note="R -> W (in PPSH; dbSNP:rs759561106)"
FT /evidence="ECO:0000269|PubMed:16181229"
FT /id="VAR_025851"
FT VARIANT 157
FT /note="Missing (in PPSH)"
FT /evidence="ECO:0000269|PubMed:7554313"
FT /id="VAR_013107"
FT VARIANT 158
FT /note="G -> R (in PPSH)"
FT /evidence="ECO:0000269|PubMed:15770495"
FT /id="VAR_025856"
FT VARIANT 181
FT /note="P -> L (in PPSH; dbSNP:rs1057517829)"
FT /evidence="ECO:0000269|PubMed:16181229"
FT /id="VAR_025852"
FT VARIANT 183
FT /note="G -> S (in PPSH; dbSNP:rs121434247)"
FT /evidence="ECO:0000269|PubMed:15770495,
FT ECO:0000269|PubMed:8626825"
FT /id="VAR_013108"
FT VARIANT 187
FT /note="T -> M (no effect on affinity for testosterone;
FT increased affinity for NADPH; decreased Vmax; decreased
FT affinity for testosterone when associated with L-89;
FT increased affinity for NADPH when associated with L-89;
FT decreased Vmax when associated with L-89;
FT dbSNP:rs61748125)"
FT /evidence="ECO:0000269|PubMed:10898110"
FT /id="VAR_077550"
FT VARIANT 194
FT /note="F -> L (no effect on affinity for testosterone;
FT increased affinity for NADPH; increased Vmax;
FT dbSNP:rs61748126)"
FT /evidence="ECO:0000269|PubMed:10898110"
FT /id="VAR_077551"
FT VARIANT 196
FT /note="G -> S (in PPSH; dbSNP:rs121434250)"
FT /evidence="ECO:0000269|PubMed:15770495,
FT ECO:0000269|PubMed:16181229, ECO:0000269|PubMed:9745434"
FT /id="VAR_013109"
FT VARIANT 197
FT /note="E -> D (in PPSH; dbSNP:rs121434253)"
FT /evidence="ECO:0000269|PubMed:10999800"
FT /id="VAR_013110"
FT VARIANT 200
FT /note="E -> K (in PPSH; dbSNP:rs756853742)"
FT /evidence="ECO:0000269|PubMed:9208814"
FT /id="VAR_013132"
FT VARIANT 203
FT /note="G -> S (in dbSNP:rs9332961)"
FT /id="VAR_059791"
FT VARIANT 207
FT /note="A -> D (in PPSH; dbSNP:rs767564684)"
FT /evidence="ECO:0000269|PubMed:15770495"
FT /id="VAR_025857"
FT VARIANT 212
FT /note="P -> R (in PPSH; dbSNP:rs121434252)"
FT /evidence="ECO:0000269|PubMed:10718838,
FT ECO:0000269|PubMed:10999800"
FT /id="VAR_013111"
FT VARIANT 224
FT /note="L -> H (in dbSNP:rs9332963)"
FT /id="VAR_059792"
FT VARIANT 224
FT /note="L -> M (in dbSNP:rs9332963)"
FT /id="VAR_037585"
FT VARIANT 227
FT /note="R -> Q (in PPSH; also in individuals with
FT micropenis; increased affinity for testosterone; increased
FT affinity for NADPH; decreased Vmax; dbSNP:rs9332964)"
FT /evidence="ECO:0000269|PubMed:10898110,
FT ECO:0000269|PubMed:12843198, ECO:0000269|PubMed:15064320"
FT /id="VAR_037586"
FT VARIANT 228
FT /note="A -> T (in PPSH; dbSNP:rs121434249)"
FT /evidence="ECO:0000269|PubMed:9843052"
FT /id="VAR_013112"
FT VARIANT 231
FT /note="H -> R (in PPSH; dbSNP:rs121434251)"
FT /evidence="ECO:0000269|PubMed:9745434"
FT /id="VAR_013113"
FT VARIANT 234
FT /note="F -> L (increased affinity for testosterone;
FT increased affinity for NADPH; decreased Vmax; no effect on
FT affinity for testosterone when associated with L-89;
FT increased affinity for NADPH when associated with L-89;
FT decreased Vmax when associated with L-89; dbSNP:rs9332966
FT and dbSNP:rs1378704759)"
FT /evidence="ECO:0000269|PubMed:10898110"
FT /id="VAR_077552"
FT VARIANT 235
FT /note="Y -> F (in PPSH; dbSNP:rs772283403)"
FT /evidence="ECO:0000269|PubMed:16181229"
FT /id="VAR_025853"
FT VARIANT 245
FT /note="S -> Y (in PPSH; dbSNP:rs145712014)"
FT /evidence="ECO:0000269|PubMed:10718838"
FT /id="VAR_013133"
FT VARIANT 246
FT /note="R -> Q (in PPSH; dbSNP:rs9332967)"
FT /evidence="ECO:0000269|PubMed:10718838,
FT ECO:0000269|PubMed:16181229"
FT /id="VAR_013134"
FT VARIANT 246
FT /note="R -> W (in PPSH; dbSNP:rs121434244)"
FT /evidence="ECO:0000269|PubMed:1522235,
FT ECO:0000269|PubMed:15528927, ECO:0000269|PubMed:15770495,
FT ECO:0000269|PubMed:8626825"
FT /id="VAR_005609"
FT HELIX 8..27
FT /evidence="ECO:0007829|PDB:7BW1"
FT STRAND 33..35
FT /evidence="ECO:0007829|PDB:7BW1"
FT HELIX 49..57
FT /evidence="ECO:0007829|PDB:7BW1"
FT HELIX 59..68
FT /evidence="ECO:0007829|PDB:7BW1"
FT STRAND 75..77
FT /evidence="ECO:0007829|PDB:7BW1"
FT HELIX 79..96
FT /evidence="ECO:0007829|PDB:7BW1"
FT HELIX 99..101
FT /evidence="ECO:0007829|PDB:7BW1"
FT HELIX 109..132
FT /evidence="ECO:0007829|PDB:7BW1"
FT HELIX 144..168
FT /evidence="ECO:0007829|PDB:7BW1"
FT TURN 184..188
FT /evidence="ECO:0007829|PDB:7BW1"
FT HELIX 192..208
FT /evidence="ECO:0007829|PDB:7BW1"
FT HELIX 211..238
FT /evidence="ECO:0007829|PDB:7BW1"
FT STRAND 247..250
FT /evidence="ECO:0007829|PDB:7BW1"
FT TURN 251..253
FT /evidence="ECO:0007829|PDB:7BW1"
SQ SEQUENCE 254 AA; 28393 MW; E65A19C8600DED05 CRC64;
MQVQCQQSPV LAGSATLVAL GALALYVAKP SGYGKHTESL KPAATRLPAR AAWFLQELPS
FAVPAGILAR QPLSLFGPPG TVLLGLFCVH YFHRTFVYSL LNRGRPYPAI LILRGTAFCT
GNGVLQGYYL IYCAEYPDGW YTDIRFSLGV FLFILGMGIN IHSDYILRQL RKPGEISYRI
PQGGLFTYVS GANFLGEIIE WIGYALATWS LPALAFAFFS LCFLGLRAFH HHRFYLKMFE
DYPKSRKALI PFIF
