ID S5A2_HUMAN Reviewed; 254 AA. AC P31213; B2RE87; Q2M1R4; Q9BYE6; DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot. DT 28-JUN-2023, sequence version 2. DT 27-MAR-2024, entry version 200. 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], AND VARIANT VAL-89. 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]. 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; VAL-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], AND VARIANT VAL-89. 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], AND VARIANT VAL-89. 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]. 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>3.3.co;2-k; 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; VAL-89; MET-187; LEU-194 RP AND LEU-234, VARIANT PPSH GLN-227, FUNCTION, CATALYTIC ACTIVITY, RP BIOPHYSICOCHEMICAL PROPERTIES, AND CHARACTERIZATION OF VARIANTS THR-49; RP VAL-89; MET-187 AND LEU-234. 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 VARIANTS MICROPENIS 26-TYR--PHE-254 DEL; ARG-34 AND GLN-227, AND VARIANT RP VAL-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 [21] 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 [22] 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 [23] 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 [24] RP VARIANTS PPSH TRP-145; LEU-181; SER-196; PHE-235 AND GLN-246, AND VARIANTS RP THR-49 AND VAL-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 [25] RP VARIANTS PPSH ARG-126; ARG-158; SER-183; SER-196; ASP-207 AND TRP-246, AND RP VARIANTS THR-49 AND VAL-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 [26] 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 -!- CATALYTIC ACTIVITY: CC Reaction=17beta-hydroxy-5alpha-androstan-3-one + NADP(+) = H(+) + NADPH CC + testosterone; Xref=Rhea:RHEA:50820, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:16330, ChEBI:CHEBI:17347, ChEBI:CHEBI:57783, CC ChEBI:CHEBI:58349; EC=1.3.1.22; CC Evidence={ECO:0000269|PubMed:10898110}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:50822; CC Evidence={ECO:0000305|PubMed:10898110}; CC -!- CATALYTIC ACTIVITY: CC Reaction=5alpha-pregnane-3,20-dione + NADP(+) = H(+) + NADPH + CC progesterone; Xref=Rhea:RHEA:21952, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:17026, ChEBI:CHEBI:28952, ChEBI:CHEBI:57783, CC ChEBI:CHEBI:58349; EC=1.3.1.22; CC Evidence={ECO:0000269|PubMed:10898110}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:21954; CC Evidence={ECO:0000305|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"; 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; 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 PaxDb; 9606-ENSP00000477587; -. DR PeptideAtlas; P31213; -. DR ProteomicsDB; 54764; -. DR Antibodypedia; 72759; 245 antibodies from 26 providers. DR DNASU; 6716; -. DR Ensembl; ENST00000622030.2; ENSP00000477587.1; ENSG00000277893.2. DR GeneID; 6716; -. DR KEGG; hsa:6716; -. DR MANE-Select; ENST00000622030.2; ENSP00000477587.1; NM_000348.4; NP_000339.2. DR UCSC; uc032nip.2; human. DR AGR; HGNC:11285; -. 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 OpenTargets; ENSG00000277893; -. DR Orphanet; 753; 46,XY difference 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 GeneTree; ENSGT00950000182886; -. DR HOGENOM; CLU_065395_1_1_1; -. DR InParanoid; P31213; -. DR OMA; SYGKHTE; -. DR OrthoDB; 152402at2759; -. DR PhylomeDB; P31213; -. DR BioCyc; MetaCyc:HS00619-MONOMER; -. 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 266 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 57 other cell types or tissues. DR GO; GO:0070852; C:cell body fiber; IEA:Ensembl. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. 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:0047751; F:3-oxo-5alpha-steroid 4-dehydrogenase (NADP+); IEA:UniProtKB-EC. DR GO; GO:0033218; F:amide binding; IEA:Ensembl. 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 Gene3D; 1.20.120.1630; -; 1. 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; 3-OXO-5-ALPHA-STEROID 4-DEHYDROGENASE; 1. DR PANTHER; PTHR10556:SF43; 3-OXO-5-ALPHA-STEROID 4-DEHYDROGENASE 2; 1. DR Pfam; PF02544; Steroid_dh; 1. DR PIRSF; PIRSF015596; 5_alpha-SR2; 1. DR PROSITE; PS50244; S5A_REDUCTASE; 1. DR Genevisible; P31213; HS. 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 26..254 FT /note="Missing (found in individual with micropenis; FT dbSNP:rs104893667)" FT /evidence="ECO:0000269|PubMed:12843198" FT /id="VAR_087980" 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 34 FT /note="G -> R (found in individual with micropenis; FT uncertain significance; dbSNP:rs782032018)" FT /evidence="ECO:0000269|PubMed:12843198" FT /id="VAR_087981" 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; FT 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="L -> V (no effect on affinity for testosterone; no FT effect on affinity for NADPH; increased Vmax; FT dbSNP:rs523349)" FT /evidence="ECO:0000269|PubMed:10898110, FT ECO:0000269|PubMed:12843198, ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15770495, ECO:0000269|PubMed:16181229, FT ECO:0000269|PubMed:1944596, ECO:0000269|Ref.4, FT ECO:0000269|Ref.6" 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; 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 found 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; FT dbSNP:rs9332966 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; 28407 MW; 34C9CBD55CF7BCA9 CRC64; MQVQCQQSPV LAGSATLVAL GALALYVAKP SGYGKHTESL KPAATRLPAR AAWFLQELPS FAVPAGILAR QPLSLFGPPG TVLLGLFCLH YFHRTFVYSL LNRGRPYPAI LILRGTAFCT GNGVLQGYYL IYCAEYPDGW YTDIRFSLGV FLFILGMGIN IHSDYILRQL RKPGEISYRI PQGGLFTYVS GANFLGEIIE WIGYALATWS LPALAFAFFS LCFLGLRAFH HHRFYLKMFE DYPKSRKALI PFIF //