Reviewed,
UniProtKB/Swiss-Prot P31213 (S5A2_HUMAN)
Last modified
January 19, 2010.
Version 99.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
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Names and origin
| Protein names | Recommended name: 3-oxo-5-alpha-steroid 4-dehydrogenase 2 EC=1.3.99.5 Alternative name(s): Steroid 5-alpha-reductase 2 5 alpha-SR2 Type II 5-alpha reductase SR type 2 | ||
| Gene names |
| ||
| Organism | Homo sapiens (Human) [Complete proteome] | ||
| Taxonomic identifier | 9606 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 254 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence 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 + acceptor = a 3-oxo-Delta(4)-steroid + reduced acceptor. |
| 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 | 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. 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. |
Ontologies
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 254 | 254 | 3-oxo-5-alpha-steroid 4-dehydrogenase 2 | PRO_0000213676 | |||||
Regions | |||||||||
| Transmembrane | 8 – 28 | 21 | Potential | ||||||
| Transmembrane | 72 – 92 | 21 | Potential | ||||||
| Transmembrane | 146 – 166 | 21 | Potential | ||||||
| Transmembrane | 206 – 226 | 21 | Potential | ||||||
Natural variations | |||||||||
| Natural variant | 49 | 1 | A → T: dbSNP rs9282858. Ref.23 Ref.24 Ref.4 Ref.16 Ref.21 | VAR_013104 | |||||
| Natural variant | 55 | 1 | L → Q in PPSH. Ref.12 | VAR_013105 | |||||
| Natural variant | 85 | 1 | G → D in PPSH. Ref.17 | VAR_013130 | |||||
| Natural variant | 89 | 1 | V → L: dbSNP rs523349. Ref.23 Ref.24 Ref.4 Ref.3 Ref.7 Ref.19 Ref.20 | VAR_013131 | |||||
| Natural variant | 113 | 1 | L → V: dbSNP rs28383048. Ref.4 | VAR_022302 | |||||
| Natural variant | 115 | 1 | G → D in PPSH. Ref.11 Ref.17 Ref.22 | VAR_013106 | |||||
| Natural variant | 123 | 1 | G → R in PPSH. Ref.25 | VAR_025854 | |||||
| Natural variant | 126 | 1 | Q → R in PPSH. Ref.24 | VAR_025855 | |||||
| Natural variant | 145 | 1 | R → W in PPSH. Ref.23 | VAR_025851 | |||||
| Natural variant | 157 | 1 | Missing in PPSH. | VAR_013107 | |||||
| Natural variant | 158 | 1 | G → R in PPSH. Ref.24 | VAR_025856 | |||||
| Natural variant | 181 | 1 | P → L in PPSH. Ref.23 | VAR_025852 | |||||
| Natural variant | 183 | 1 | G → S in PPSH. Ref.11 Ref.24 | VAR_013108 | |||||
| Natural variant | 196 | 1 | G → S in PPSH. Ref.15 Ref.23 Ref.24 | VAR_013109 | |||||
| Natural variant | 197 | 1 | E → D in PPSH. Ref.18 | VAR_013110 | |||||
| Natural variant | 200 | 1 | E → K in PPSH. Ref.13 | VAR_013132 | |||||
| Natural variant | 203 | 1 | G → S: dbSNP rs9332961. | VAR_059791 | |||||
| Natural variant | 207 | 1 | A → D in PPSH. Ref.24 | VAR_025857 | |||||
| Natural variant | 212 | 1 | P → R in PPSH. Ref.17 Ref.18 | VAR_013111 | |||||
| Natural variant | 224 | 1 | L → H: dbSNP rs9332963. | VAR_059792 | |||||
| Natural variant | 224 | 1 | L → M: dbSNP rs9332963. | VAR_037585 | |||||
| Natural variant | 227 | 1 | R → Q in micropenis. dbSNP rs9332964. Ref.20 | VAR_037586 | |||||
| Natural variant | 228 | 1 | A → T in PPSH. Ref.14 | VAR_013112 | |||||
| Natural variant | 231 | 1 | H → R in PPSH. Ref.15 | VAR_013113 | |||||
| Natural variant | 235 | 1 | Y → F in PPSH. Ref.23 | VAR_025853 | |||||
| Natural variant | 245 | 1 | S → Y in PPSH. Ref.17 | VAR_013133 | |||||
| Natural variant | 246 | 1 | R → Q in PPSH. dbSNP rs9332967. Ref.17 Ref.23 | VAR_013134 | |||||
| Natural variant | 246 | 1 | R → W in PPSH. Ref.9 Ref.11 Ref.22 Ref.24 | VAR_005609 | |||||
Sequences
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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: 1944596] [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: 1505484] [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. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [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. 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: 15489334] [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: 1522235] [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: 7554313] [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: 8626825] [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: 8768837] [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: 9208814] [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: 9843052] [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: 9745434] [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: 10501358] [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: 10718838] [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: 10999800] [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: 11927504] [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: 12843198] [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: 14560315] [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: 15528927] [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: 16181229] [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: 15770495] [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: 16098368] [Abstract] Cited for: VARIANT PPSH ARG-123. |
| + | Additional computationally mapped references. |
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. |
| IPI | IPI00010651. |
| PIR | A49169. |
| RefSeq | NP_000339.2. |
| UniGene | Hs.458345 |
3D structure databases | |
| ModBase | Search... |
Protein-protein interaction databases | |
| STRING | P31213. |
Proteomic databases | |
| PRIDE | P31213. |
Genome annotation databases | |
| Ensembl | ENST00000233139; ENSP00000233139; ENSG00000049319; Homo sapiens. [Genome view] |
| GeneID | 6716. |
| KEGG | hsa:6716. |
Organism-specific databases | |
| CTD | 6716. |
| GeneCards | GC02M031661. |
| H-InvDB | HIX0030017. |
| HGNC | HGNC:11285. SRD5A2. |
| MIM | 264600. phenotype. 607306. gene. |
| Orphanet | 753. 46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency. 1331. Prostate cancer, familial. |
| PharmGKB | PA36113. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | prNOG05314. |
| HOGENOM | HBG714186. |
| HOVERGEN | P31213. |
| InParanoid | P31213. |
Enzyme and pathway databases | |
| BRENDA | 1.3.99.5. 247. |
Gene expression databases | |
| ArrayExpress | P31213. |
| Bgee | P31213. |
| CleanEx | HS_SRD5A2. |
| Genevestigator | P31213. |
| GermOnline | ENSG00000049319. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR016636. 3-oxo-5-alpha-steroid_4-DH. IPR001104. 3-oxo-5_a-steroid_4-DH_C. [Graphical view] |
| Pfam | PF02544. Steroid_dh. 1 hit. [Graphical view] |
| PIRSF | PIRSF015596. 5_alpha-SR2. 1 hit. |
| PROSITE | PS50244. S5A_REDUCTASE. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| DrugBank | DB00548. Azelaic Acid. DB01126. Dutasteride. |
| NextBio | 26196. |
| SOURCE | Search... |
Entry information
| Entry name | S5A2_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P31213 Secondary accession number(s): B2RE87, Q2M1R4, Q9BYE6 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| Disclaimer | Any 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
| Human chromosome 2 Human chromosome 2: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with


