[1]	NUCLEOTIDE SEQUENCE [MRNA]. DOI=10.1038/354159a0; PubMed=1944596 [NCBI, ExPASy, EBI, Israel, Japan] Andersson S., Berman D.M., Jenkins E.P., Russell D.W.; "Deletion of steroid 5 alpha-reductase 2 gene in male pseudohermaphroditism."; Nature 354:159-161(1991).
[2]	NUCLEOTIDE SEQUENCE [GENOMIC DNA]. DOI=10.1210/en.131.3.1571; PubMed=1505484 [NCBI, ExPASy, EBI, Israel, Japan] Labrie F., Sugimoto Y., Luu-The V., Simard J., Lachance Y., Bachvarov D., Leblanc G., Durocher F., Paquet N.; "Structure of human type II 5 alpha-reductase gene."; Endocrinology 131:1571-1573(1992).
[3]	NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT LEU-89. TISSUE=Liver tumor; Schupp I.; Submitted (APR-2007) to the EMBL/GenBank/DDBJ databases.
[4]	NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS THR-49; LEU-89 AND VAL-113. Livingston R.J., Rieder M.J., Chung M.-W., Downing T.K., Olson A.N., Nguyen C.P., Gildersleeve H., Cassidy C.M., Johnson E.J., Swanson J.E., McFarland I., Yool B., Park C., Nickerson D.A.; "NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu)."; Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
[5]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LEU-89. DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team; "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."; Genome Res. 14:2121-2127(2004).
[6]	NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-67. TISSUE=Placenta; Nakanishi J., Hibino T.; "Transcription of type II 5 alpha-reductase is up-regulated by SRY in human dermal papilla cells."; Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases.
[7]	VARIANT PPSH TRP-246. PubMed=1522235 [NCBI, ExPASy, EBI, Israel, Japan] Thigpen A.E., Davis D.L., Milatovich A., Mendonca B.B., Imperato-Mcginley J., Griffin J.E., Francke U., Wilson J.D., Russell D.W.; "Molecular genetics of steroid 5 alpha-reductase 2 deficiency."; J. Clin. Invest. 90:799-809(1992).
[8]	VARIANT PPSH MET-157 DEL. PubMed=7554313 [NCBI, ExPASy, EBI, Israel, Japan] Boudon C., Lobaccaro J.-M., Lumbroso S., Ogur G., Ocal G., Belon C., Sultan C.; "A new deletion of the 5-alpha-reductase type 2 gene in a Turkish family with 5-alpha-reductase deficiency."; Clin. Endocrinol. (Oxf.) 43:183-188(1995).
[9]	VARIANTS PPSH ASP-115; SER-183 AND TRP-246. DOI=10.1210/jc.81.5.1730; PubMed=8626825 [NCBI, ExPASy, EBI, Israel, Japan] Cai L.-Q., Zhu Y.-S., Katz M.D., Herrera C., Baez J., DeFillo-Ricart M., Shackleton C.H.L., Imperato-McGinley J.; "5-alpha-reductase-2 gene mutations in the Dominican Republic."; J. Clin. Endocrinol. Metab. 81:1730-1735(1996).
[10]	VARIANT PPSH GLN-55. DOI=10.1210/jc.81.8.2821; PubMed=8768837 [NCBI, ExPASy, EBI, Israel, Japan] Hochberg Z., Chayen R., Reiss N., Falik Z., Makler A., Munichor M., Farkas A., Goldfarb H., Ohana N., Hiort O.; "Clinical, biochemical, and genetic findings in a large pedigree of male and female patients with 5-alpha-reductase 2 deficiency."; J. Clin. Endocrinol. Metab. 81:2821-2827(1996).
[11]	VARIANT PPSH LYS-200. PubMed=9208814 [NCBI, ExPASy, EBI, Israel, Japan] Anwar R., Gilbey S.G., New J.P., Markham A.F.; "Male pseudohermaphroditism resulting from a novel mutation in the human steroid 5 alpha-reductase type 2 gene (SRD5A2)."; Mol. Pathol. 50:51-52(1997).
[12]	VARIANT PPSH THR-228. DOI=10.1002/(SICI)1096-8628(19981116)80:3<269::AID-AJMG18>3.3.CO;2-K; PubMed=9843052 [NCBI, ExPASy, EBI, Israel, Japan] Nordenskjold A., Magnus O., Aagenaes O., Knudtzon J.; "Homozygous mutation (A228T) in the 5-alpha-reductase type 2 gene in a boy with 5-alpha-reductase deficiency: genotype-phenotype correlations."; Am. J. Med. Genet. 80:269-272(1998).
[13]	VARIANTS PPSH SER-196 AND ARG-231. DOI=10.1210/jc.83.9.3236; PubMed=9745434 [NCBI, ExPASy, EBI, Israel, Japan] Nordenskjold A., Ivarsson S.-A.; "Molecular characterization of 5-alpha-reductase type 2 deficiency and fertility in a Swedish family."; J. Clin. Endocrinol. Metab. 83:3236-3238(1998).
[14]	VARIANT THR-49. DOI=10.1016/S0140-6736(98)11282-5; PubMed=10501358 [NCBI, ExPASy, EBI, Israel, Japan] Makridakis N.M., Ross R.K., Pike M.C., Crocitto L.E., Kolonel L.N., Pearce C.L., Henderson B.E., Reichardt J.K.V.; "Association of mis-sense substitution in SRD5A2 gene with prostate cancer in African-American and Hispanic men in Los Angeles, USA."; Lancet 354:975-978(1999).
[15]	VARIANTS PPSH ASP-85; ASP-115; ARG-212; TYR-245 AND GLN-246. PubMed=10718838 [NCBI, ExPASy, EBI, Israel, Japan] Vilchis F., Mendez J.P., Canto P., Lieberman E., Chavez B.; "Identification of missense mutations in the SRD5A2 gene from patients with steroid 5alpha-reductase 2 deficiency."; Clin. Endocrinol. (Oxf.) 52:383-387(2000).
[16]	VARIANTS PPSH ASP-197 AND ARG-212. DOI=10.1210/jc.85.9.3147; PubMed=10999800 [NCBI, ExPASy, EBI, Israel, Japan] Chavez B., Valdez E., Vilchis F.; "Uniparental disomy in steroid 5-alpha-reductase 2 deficiency."; J. Clin. Endocrinol. Metab. 85:3147-3150(2000).
[17]	VARIANT LEU-89. PubMed=11927504 [NCBI, ExPASy, EBI, Israel, Japan] Pearce C.L., Makridakis N.M., Ross R.K., Pike M.C., Kolonel L.N., Henderson B.E., Reichardt J.K.V.; "Steroid 5-alpha reductase type II V89L substitution is not associated with risk of prostate cancer in a multiethnic population study."; Cancer Epidemiol. Biomarkers Prev. 11:417-418(2002).
[18]	VARIANT MICROPENIS GLN-227, AND VARIANT LEU-89. DOI=10.1210/jc.2002-021415; PubMed=12843198 [NCBI, ExPASy, EBI, Israel, Japan] Sasaki G., Ogata T., Ishii T., Kosaki K., Sato S., Homma K., Takahashi T., Hasegawa T., Matsuo N.; "Micropenis and the 5alpha-reductase-2 (SRD5A2) gene: mutation and V89L polymorphism analysis in 81 Japanese patients."; J. Clin. Endocrinol. Metab. 88:3431-3436(2003).
[19]	VARIANT THR-49, AND LACK OF ASSOCIATION WITH PROSTATE CANCER. DOI=10.1038/sj.ejhg.5201101; PubMed=14560315 [NCBI, ExPASy, EBI, Israel, Japan] Loukola A., Chadha M., Penn S.G., Rank D., Conti D.V., Thompson D., Cicek M., Love B., Bivolarevic V., Yang Q., Jiang Y., Hanzel D.K., Dains K., Paris P.L., Casey G., Witte J.S.; "Comprehensive evaluation of the association between prostate cancer and genotypes/haplotypes in CYP17A1, CYP3A4, and SRD5A2."; Eur. J. Hum. Genet. 12:321-332(2004).
[20]	VARIANTS PPSH ASP-115 AND TRP-246. DOI=10.1159/000081893; PubMed=15528927 [NCBI, ExPASy, EBI, Israel, Japan] Fernandez-Cancio M., Rodo J., Andaluz P., Martinez de Osaba M.J., Rodriguez-Hierro F., Esteban C., Carrascosa A., Audi L.; "Clinical, biochemical and morphologic diagnostic markers in an infant male pseudohermaphrodite patient with compound heterozygous mutations (G115D/R246W) in SRD5A2 gene."; Horm. Res. 62:259-264(2004).
[21]	VARIANTS PPSH TRP-145; LEU-181; SER-196; PHE-235 AND GLN-246, AND VARIANTS THR-49 AND LEU-89. DOI=10.1111/j.1365-2265.2005.02348.x; PubMed=16181229 [NCBI, ExPASy, EBI, Israel, Japan] Nicoletti A., Baldazzi L., Balsamo A., Barp L., Pirazzoli P., Gennari M., Radetti G., Cacciari E., Cicognani A.; "SRD5A2 gene analysis in an Italian population of under-masculinized 46,XY subjects."; Clin. Endocrinol. (Oxf.) 63:375-380(2005).
[22]	VARIANTS PPSH ARG-126; ARG-158; SER-183; SER-196; ASP-207 AND TRP-246, AND VARIANTS THR-49 AND LEU-89. DOI=10.1007/s00109-005-0651-7; PubMed=15770495 [NCBI, ExPASy, EBI, Israel, Japan] Hackel C., Oliveira L.E., Ferraz L.F., Tonini M.M., Silva D.N., Toralles M.B., Stuchi-Perez E.G., Guerra-Junior G.; "New mutations, hotspots, and founder effects in Brazilian patients with steroid 5alpha-reductase deficiency type 2."; J. Mol. Med. 83:569-576(2005).
[23]	VARIANT PPSH ARG-123. DOI=10.1016/j.urology.2005.02.021; PubMed=16098368 [NCBI, ExPASy, EBI, Israel, Japan] Bahceci M., Ersay A.R., Tuzcu A., Hiort O., Richter-Unruh A., Gokalp D.; "A novel missense mutation of 5-alpha reductase type 2 gene (SRD5A2) leads to severe male pseudohermaphroditism in a Turkish family."; Urology 66:407-410(2005).

Comments

FUNCTION: Converts testosterone (T) into 5-alpha-dihydrotestosterone (DHT) and progesterone or corticosterone into their corresponding 5-alpha-3-oxosteroids. It plays a central role in sexual differentiation and androgen physiology.
CATALYTIC ACTIVITY: A 3-oxo-5-alpha-steroid + acceptor = a 3-oxo-Delta⁴-steroid + reduced acceptor.
BIOPHYSICOCHEMICAL PROPERTIES:

pH dependence: Optimally active at acidic pHs;
SUBCELLULAR LOCATION: Microsome membrane; Multi-pass membrane protein. Endoplasmic reticulum membrane; Multi-pass membrane protein (Potential).
TISSUE SPECIFICITY: Expressed in high levels in the prostate and many other androgen-sensitive tissues.
POLYMORPHISM: Individuals with Thr-49 have an increased risk of prostate cancer. The enzyme with Thr-49 has a higher in vitro V(max) than the Ala-49 enzyme.
DISEASE: Defects in SRD5A2 are the cause of pseudovaginal perineoscrotal hypospadias (PPSH) [MIM:264600]; also known as male pseudohermaphroditism due to 5-alpha-reductase deficiency or 5-ARD deficiency. PPSH is a rare form of male pseudohermaphroditism in which affected males develop normal internal urogenital tracts but fail to develop external male structures. Individuals with PPSH have testicles and tend to have a vagina and labia, but with a small penis capable of ejaculation instead of a clitoris (this penis, however, appears to be a clitoris at birth). These individuals are normally raised as girls. However at puberty their testes will descend, their voice will deepen and they often will develop a male sexual identity. They develop only limited facial hair and will not experience male-pattern baldness. Jeffrey Eugenides won a Pulitzer prize for his 2003 novel 'Middlesex' which describes the life an individual with such a deficiency.
SIMILARITY: Belongs to the steroid 5-alpha reductase family.
WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=SRD5A2";.
WEB RESOURCE: Name=Wikipedia; Note=5-alpha reductase entry; URL="http://en.wikipedia.org/wiki/5_alpha_reductase";.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

M74047; AAA60586.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AB047857; BAB40419.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
EF560740; ABQ59050.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AY884245; AAW56942.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC112252; AAI12253.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC113641; AAI13642.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
L03843; -; NOT_ANNOTATED_CDS; Genomic_DNA.	[EMBL / GenBank / DDBJ]

A49169; A49169.

NP_000339.2; -.

3D structure databases

ModBase

P31213.

Polymorphism databases

NIEHS-SNPs

SRD5A2.

Organism-specific databases

HIX0030017; -.

HGNC:11285; SRD5A2.

264600; phenotype. [NCBI / EBI]
607306; gene. [NCBI / EBI]

Orphanet

753; Disorder of sexual developement 46,XY due to 5-alpha-reductase 2 deficiency.

PharmGKB

PA36113; -.

GeneCards

P31213.

Gene expression databases

ArrayExpress

P31213; -.

CleanEx

HS_SRD5A2; -.

GermOnline

ENSG00000049319; Homo sapiens.

Ontologies

GO:0005789;	Cellular component: endoplasmic reticulum membrane (inferred from electronic annotation from UniProtKB-SubCell).
GO:0016021;	Cellular component: integral to membrane (inferred from electronic annotation from InterPro).
GO:0005792;	Cellular component: microsome (inferred from electronic annotation from UniProtKB-KW).
GO:0003865;	Molecular function: 3-oxo-5-alpha-steroid 4-dehydrogenase activity (inferred from electronic annotation from InterPro).
GO:0009917;	Molecular function: sterol 5-alpha reductase activity (inferred from direct assay from UniProtKB).
GO:0030154;	Biological process: cell differentiation (inferred from electronic annotation from UniProtKB-KW).
GO:0007267;	Biological process: cell-cell signaling (traceable author statement from UniProtKB).
GO:0008584;	Biological process: male gonad development (inferred from mutant phenotype from UniProtKB).
GO:0055114;	Biological process: oxidation reduction (inferred from electronic annotation from UniProtKB-KW).
GO:0007530;	Biological process: sex determination (inferred from electronic annotation from UniProtKB-KW).
QuickGo view.

Family and domain databases

InterPro

IPR016636; 3-oxo-5-alpha-steroid_4-DH.
IPR001104; 3-oxo-5_a-steroid_4-DHase_C.
Graphical view of domain structure.

Pfam

PF02544; Steroid_dh; 1.
Pfam graphical view of domain structure.

PIRSF

PIRSF015596; 5_alpha-SR2; 1.

PROSITE

PS50244; S5A_REDUCTASE; 1.
PROSITE graphical view of domain structure (profiles).

Genome annotation databases

Ensembl

ENSG00000049319; Homo sapiens. [Contig view]

GeneID

6716; -.

KEGG

hsa:6716; -.

Phylogenomic databases

HOGENOM

P31213; -.

HOVERGEN

P31213; -.

Other

DrugBank

DB00548; Azelaic Acid.
DB01126; Dutasteride.

LinkHub

P31213; -.

NextBio

26196; -.

SOURCE

SRD5A2; Homo sapiens.

UniRef

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

Differentiation; Disease mutation; Endoplasmic reticulum; Membrane; Microsome; Oxidoreductase; Polymorphism; Pseudohermaphroditism; Sexual differentiation; Transmembrane.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 254`	`254`	`3-oxo-5-alpha-steroid 4-dehydrogenase 2.`	`PRO_0000213676`
`TRANSMEM`	`8 28`	`21`	`Potential.`
`TRANSMEM`	`72 92`	`21`	`Potential.`
`TRANSMEM`	`146 166`	`21`	`Potential.`
`TRANSMEM`	`206 226`	`21`	`Potential.`
`VARIANT`	`49 49`	`1`	`A -> T.`	`VAR_013104`
`VARIANT`	`55 55`	`1`	`L -> Q (in PPSH).`	`VAR_013105`
`VARIANT`	`85 85`	`1`	`G -> D (in PPSH).`	`VAR_013130`
`VARIANT`	`89 89`	`1`	`V -> L (in dbSNP:rs523349 [NCBI]).`	`VAR_013131`
`VARIANT`	`113 113`	`1`	`L -> V.`	`VAR_022302`
`VARIANT`	`115 115`	`1`	`G -> D (in PPSH).`	`VAR_013106`
`VARIANT`	`123 123`	`1`	`G -> R (in PPSH).`	`VAR_025854`
`VARIANT`	`126 126`	`1`	`Q -> R (in PPSH).`	`VAR_025855`
`VARIANT`	`145 145`	`1`	`R -> W (in PPSH).`	`VAR_025851`
`VARIANT`	`157 157`	`1`	`Missing (in PPSH).`	`VAR_013107`
`VARIANT`	`158 158`	`1`	`G -> R (in PPSH).`	`VAR_025856`
`VARIANT`	`181 181`	`1`	`P -> L (in PPSH).`	`VAR_025852`
`VARIANT`	`183 183`	`1`	`G -> S (in PPSH).`	`VAR_013108`
`VARIANT`	`196 196`	`1`	`G -> S (in PPSH).`	`VAR_013109`
`VARIANT`	`197 197`	`1`	`E -> D (in PPSH).`	`VAR_013110`
`VARIANT`	`200 200`	`1`	`E -> K (in PPSH).`	`VAR_013132`
`VARIANT`	`207 207`	`1`	`A -> D (in PPSH).`	`VAR_025857`
`VARIANT`	`212 212`	`1`	`P -> R (in PPSH).`	`VAR_013111`
`VARIANT`	`224 224`	`1`	`L -> M (in dbSNP:rs9332963 [NCBI]).`	`VAR_037585`
`VARIANT`	`227 227`	`1`	`R -> Q (in micropenis).`	`VAR_037586`
`VARIANT`	`228 228`	`1`	`A -> T (in PPSH).`	`VAR_013112`
`VARIANT`	`231 231`	`1`	`H -> R (in PPSH).`	`VAR_013113`
`VARIANT`	`235 235`	`1`	`Y -> F (in PPSH).`	`VAR_025853`
`VARIANT`	`245 245`	`1`	`S -> Y (in PPSH).`	`VAR_013133`
`VARIANT`	`246 246`	`1`	`R -> Q (in PPSH).`	`VAR_013134`
`VARIANT`	`246 246`	`1`	`R -> W (in PPSH).`	`VAR_005609`

Sequence information

Length: 254 AA [This is the length of the unprocessed precursor]

Molecular weight: 28393 Da [This is the MW of the unprocessed precursor]

CRC64: E65A19C8600DED05 [This is a checksum on the sequence]

        10         20         30         40         50         60 
MQVQCQQSPV LAGSATLVAL GALALYVAKP SGYGKHTESL KPAATRLPAR AAWFLQELPS 

        70         80         90        100        110        120 
FAVPAGILAR QPLSLFGPPG TVLLGLFCVH YFHRTFVYSL LNRGRPYPAI LILRGTAFCT 

       130        140        150        160        170        180 
GNGVLQGYYL IYCAEYPDGW YTDIRFSLGV FLFILGMGIN IHSDYILRQL RKPGEISYRI 

       190        200        210        220        230        240 
PQGGLFTYVS GANFLGEIIE WIGYALATWS LPALAFAFFS LCFLGLRAFH HHRFYLKMFE 

       250 
DYPKSRKALI PFIF

P31213 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools