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P31213 (S5A2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 137. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
3-oxo-5-alpha-steroid 4-dehydrogenase 2

EC=1.3.1.22
Alternative name(s):
5 alpha-SR2
SR type 2
Steroid 5-alpha-reductase 2
Short name=S5AR 2
Type II 5-alpha reductase
Gene names
Name:SRD5A2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length254 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (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 + NADP+ = a 3-oxo-Delta(4)-steroid + NADPH.

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.

Involvement in disease

Pseudovaginal perineoscrotal hypospadias (PPSH) [MIM:264600]: A form of male pseudohermaphroditism in which 46,XY males show ambiguous genitalia at birth, including perineal hypospadias and a blind perineal pouch, and develop masculinization at puberty. The name of the disorder stems from the finding of a blind-ending perineal opening resembling a vagina and a severely hypospadiac penis with the urethra opening onto the perineum.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.17 Ref.18 Ref.22 Ref.23 Ref.24 Ref.25

Sequence similarities

Belongs to the steroid 5-alpha reductase family.

Biophysicochemical properties

pH dependence:

Optimally active at acidic pHs.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 2542543-oxo-5-alpha-steroid 4-dehydrogenase 2
PRO_0000213676

Regions

Transmembrane8 – 2821Helical; Potential
Transmembrane72 – 9221Helical; Potential
Transmembrane146 – 16621Helical; Potential
Transmembrane206 – 22621Helical; Potential

Natural variations

Natural variant491A → T. Ref.4 Ref.16 Ref.21 Ref.23 Ref.24
Corresponds to variant rs9282858 [ dbSNP | Ensembl ].
VAR_013104
Natural variant551L → Q in PPSH. Ref.12
VAR_013105
Natural variant851G → D in PPSH. Ref.17
VAR_013130
Natural variant891V → L. Ref.3 Ref.4 Ref.7 Ref.19 Ref.20 Ref.23 Ref.24
Corresponds to variant rs523349 [ dbSNP | Ensembl ].
VAR_013131
Natural variant1131L → V. Ref.4
Corresponds to variant rs28383048 [ dbSNP | Ensembl ].
VAR_022302
Natural variant1151G → D in PPSH. Ref.11 Ref.17 Ref.22
VAR_013106
Natural variant1231G → R in PPSH. Ref.25
VAR_025854
Natural variant1261Q → R in PPSH. Ref.24
VAR_025855
Natural variant1451R → W in PPSH. Ref.23
VAR_025851
Natural variant1571Missing in PPSH. Ref.10
VAR_013107
Natural variant1581G → R in PPSH. Ref.24
VAR_025856
Natural variant1811P → L in PPSH. Ref.23
VAR_025852
Natural variant1831G → S in PPSH. Ref.11 Ref.24
VAR_013108
Natural variant1961G → S in PPSH. Ref.15 Ref.23 Ref.24
VAR_013109
Natural variant1971E → D in PPSH. Ref.18
VAR_013110
Natural variant2001E → K in PPSH. Ref.13
VAR_013132
Natural variant2031G → S.
Corresponds to variant rs9332961 [ dbSNP | Ensembl ].
VAR_059791
Natural variant2071A → D in PPSH. Ref.24
VAR_025857
Natural variant2121P → R in PPSH. Ref.17 Ref.18
VAR_013111
Natural variant2241L → H.
Corresponds to variant rs9332963 [ dbSNP | Ensembl ].
VAR_059792
Natural variant2241L → M.
Corresponds to variant rs9332963 [ dbSNP | Ensembl ].
VAR_037585
Natural variant2271R → Q in micropenis. Ref.20
Corresponds to variant rs9332964 [ dbSNP | Ensembl ].
VAR_037586
Natural variant2281A → T in PPSH. Ref.14
VAR_013112
Natural variant2311H → R in PPSH. Ref.15
VAR_013113
Natural variant2351Y → F in PPSH. Ref.23
VAR_025853
Natural variant2451S → Y in PPSH. Ref.17
VAR_013133
Natural variant2461R → Q in PPSH. Ref.17 Ref.23
Corresponds to variant rs9332967 [ dbSNP | Ensembl ].
VAR_013134
Natural variant2461R → W in PPSH. Ref.9 Ref.11 Ref.22 Ref.24
VAR_005609

Sequences

Sequence LengthMass (Da)Tools
P31213 [UniParc].

Last modified July 1, 1993. Version 1.
Checksum: E65A19C8600DED05

FASTA25428,393
        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 

« Hide

References

« Hide 'large scale' references
[1]"Deletion of steroid 5 alpha-reductase 2 gene in male pseudohermaphroditism."
Andersson S., Berman D.M., Jenkins E.P., Russell D.W.
Nature 354:159-161(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Structure of human type II 5 alpha-reductase gene."
Labrie F., Sugimoto Y., Luu-The V., Simard J., Lachance Y., Bachvarov D., Leblanc G., Durocher F., Paquet N.
Endocrinology 131:1571-1573(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]Schupp I.
Submitted (APR-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT LEU-89.
Tissue: Liver tumor.
[4]NIEHS SNPs program
Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-49; LEU-89 AND VAL-113.
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT LEU-89.
[8]"Transcription of type II 5 alpha-reductase is up-regulated by SRY in human dermal papilla cells."
Nakanishi J., Hibino T.
Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-67.
Tissue: Placenta.
[9]"Molecular genetics of steroid 5 alpha-reductase 2 deficiency."
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.
J. Clin. Invest. 90:799-809(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PPSH TRP-246.
[10]"A new deletion of the 5-alpha-reductase type 2 gene in a Turkish family with 5-alpha-reductase deficiency."
Boudon C., Lobaccaro J.-M., Lumbroso S., Ogur G., Ocal G., Belon C., Sultan C.
Clin. Endocrinol. (Oxf.) 43:183-188(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PPSH MET-157 DEL.
[11]"5-alpha-reductase-2 gene mutations in the Dominican Republic."
Cai L.-Q., Zhu Y.-S., Katz M.D., Herrera C., Baez J., DeFillo-Ricart M., Shackleton C.H.L., Imperato-McGinley J.
J. Clin. Endocrinol. Metab. 81:1730-1735(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PPSH ASP-115; SER-183 AND TRP-246.
[12]"Clinical, biochemical, and genetic findings in a large pedigree of male and female patients with 5-alpha-reductase 2 deficiency."
Hochberg Z., Chayen R., Reiss N., Falik Z., Makler A., Munichor M., Farkas A., Goldfarb H., Ohana N., Hiort O.
J. Clin. Endocrinol. Metab. 81:2821-2827(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PPSH GLN-55.
[13]"Male pseudohermaphroditism resulting from a novel mutation in the human steroid 5 alpha-reductase type 2 gene (SRD5A2)."
Anwar R., Gilbey S.G., New J.P., Markham A.F.
Mol. Pathol. 50:51-52(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PPSH LYS-200.
[14]"Homozygous mutation (A228T) in the 5-alpha-reductase type 2 gene in a boy with 5-alpha-reductase deficiency: genotype-phenotype correlations."
Nordenskjold A., Magnus O., Aagenaes O., Knudtzon J.
Am. J. Med. Genet. 80:269-272(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PPSH THR-228.
[15]"Molecular characterization of 5-alpha-reductase type 2 deficiency and fertility in a Swedish family."
Nordenskjold A., Ivarsson S.-A.
J. Clin. Endocrinol. Metab. 83:3236-3238(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PPSH SER-196 AND ARG-231.
[16]"Association of mis-sense substitution in SRD5A2 gene with prostate cancer in African-American and Hispanic men in Los Angeles, USA."
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.
Lancet 354:975-978(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT THR-49.
[17]"Identification of missense mutations in the SRD5A2 gene from patients with steroid 5alpha-reductase 2 deficiency."
Vilchis F., Mendez J.P., Canto P., Lieberman E., Chavez B.
Clin. Endocrinol. (Oxf.) 52:383-387(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PPSH ASP-85; ASP-115; ARG-212; TYR-245 AND GLN-246.
[18]"Uniparental disomy in steroid 5-alpha-reductase 2 deficiency."
Chavez B., Valdez E., Vilchis F.
J. Clin. Endocrinol. Metab. 85:3147-3150(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PPSH ASP-197 AND ARG-212.
[19]"Steroid 5-alpha reductase type II V89L substitution is not associated with risk of prostate cancer in a multiethnic population study."
Pearce C.L., Makridakis N.M., Ross R.K., Pike M.C., Kolonel L.N., Henderson B.E., Reichardt J.K.V.
Cancer Epidemiol. Biomarkers Prev. 11:417-418(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LEU-89.
[20]"Micropenis and the 5alpha-reductase-2 (SRD5A2) gene: mutation and V89L polymorphism analysis in 81 Japanese patients."
Sasaki G., Ogata T., Ishii T., Kosaki K., Sato S., Homma K., Takahashi T., Hasegawa T., Matsuo N.
J. Clin. Endocrinol. Metab. 88:3431-3436(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MICROPENIS GLN-227, VARIANT LEU-89.
[21]"Comprehensive evaluation of the association between prostate cancer and genotypes/haplotypes in CYP17A1, CYP3A4, and SRD5A2."
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.
Eur. J. Hum. Genet. 12:321-332(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT THR-49, LACK OF ASSOCIATION WITH PROSTATE CANCER.
[22]"Clinical, biochemical and morphologic diagnostic markers in an infant male pseudohermaphrodite patient with compound heterozygous mutations (G115D/R246W) in SRD5A2 gene."
Fernandez-Cancio M., Rodo J., Andaluz P., Martinez de Osaba M.J., Rodriguez-Hierro F., Esteban C., Carrascosa A., Audi L.
Horm. Res. 62:259-264(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PPSH ASP-115 AND TRP-246.
[23]"SRD5A2 gene analysis in an Italian population of under-masculinized 46,XY subjects."
Nicoletti A., Baldazzi L., Balsamo A., Barp L., Pirazzoli P., Gennari M., Radetti G., Cacciari E., Cicognani A.
Clin. Endocrinol. (Oxf.) 63:375-380(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PPSH TRP-145; LEU-181; SER-196; PHE-235 AND GLN-246, VARIANTS THR-49 AND LEU-89.
[24]"New mutations, hotspots, and founder effects in Brazilian patients with steroid 5alpha-reductase deficiency type 2."
Hackel C., Oliveira L.E., Ferraz L.F., Tonini M.M., Silva D.N., Toralles M.B., Stuchi-Perez E.G., Guerra-Junior G.
J. Mol. Med. 83:569-576(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PPSH ARG-126; ARG-158; SER-183; SER-196; ASP-207 AND TRP-246, VARIANTS THR-49 AND LEU-89.
[25]"A novel missense mutation of 5-alpha reductase type 2 gene (SRD5A2) leads to severe male pseudohermaphroditism in a Turkish family."
Bahceci M., Ersay A.R., Tuzcu A., Hiort O., Richter-Unruh A., Gokalp D.
Urology 66:407-410(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PPSH ARG-123.
+Additional computationally mapped references.

Web resources

GeneReviews
NIEHS-SNPs
Wikipedia

5-alpha reductase entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M74047 mRNA. Translation: AAA60586.1.
AB047857 Genomic DNA. Translation: BAB40419.1.
EF560740 mRNA. Translation: ABQ59050.1.
AY884245 Genomic DNA. Translation: AAW56942.1.
AK316597 mRNA. Translation: BAG38184.1.
CH471053 Genomic DNA. Translation: EAX00478.1.
BC112252 mRNA. Translation: AAI12253.1.
BC113641 mRNA. Translation: AAI13642.1.
L03843 Genomic DNA. No translation available.
PIRA49169.
RefSeqNP_000339.2. NM_000348.3.
UniGeneHs.458345.

3D structure databases

ProteinModelPortalP31213.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000233139.

Chemistry

BindingDBP31213.
ChEMBLCHEMBL1856.
DrugBankDB00548. Azelaic Acid.
DB01126. Dutasteride.
GuidetoPHARMACOLOGY2633.

PTM databases

PhosphoSiteP31213.

Polymorphism databases

DMDM401056.

Proteomic databases

PaxDbP31213.
PRIDEP31213.

Protocols and materials databases

DNASU6716.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID6716.
KEGGhsa:6716.
UCSCuc002rnw.1. human.

Organism-specific databases

CTD6716.
GeneCardsGC02M031661.
H-InvDBHIX0030017.
HGNCHGNC:11285. SRD5A2.
MIM264600. phenotype.
607306. gene.
neXtProtNX_P31213.
Orphanet753. 46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency.
1331. Familial prostate cancer.
PharmGKBPA36113.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG282706.
HOVERGENHBG003402.
InParanoidP31213.
KOK12344.
PhylomeDBP31213.

Enzyme and pathway databases

BioCycMetaCyc:HS00619-MONOMER.
ReactomeREACT_111217. Metabolism.
REACT_15493. Steroid hormones.

Gene expression databases

CleanExHS_SRD5A2.
GenevestigatorP31213.

Family and domain databases

InterProIPR016636. 3-oxo-5-alpha-steroid_4-DH.
IPR001104. 3-oxo-5_a-steroid_4-DH_C.
[Graphical view]
PfamPF02544. Steroid_dh. 1 hit.
[Graphical view]
PIRSFPIRSF015596. 5_alpha-SR2. 1 hit.
PROSITEPS50244. S5A_REDUCTASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSRD5A2. human.
GeneWikiSRD5A2.
GenomeRNAi6716.
NextBio26196.
PROP31213.
SOURCESearch...

Entry information

Entry nameS5A2_HUMAN
AccessionPrimary (citable) accession number: P31213
Secondary accession number(s): B2RE87, Q2M1R4, Q9BYE6
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 1, 1993
Last modified: April 16, 2014
This is version 137 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM