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Protein

3-oxo-5-alpha-steroid 4-dehydrogenase 2

Gene

SRD5A2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 activityi

A 3-oxo-5-alpha-steroid + NADP+ = a 3-oxo-Delta(4)-steroid + NADPH.

pH dependencei

Optimally active at acidic pHs.

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Differentiation, Sexual differentiation

Keywords - Ligandi

NADP

Enzyme and pathway databases

BioCyciMetaCyc:HS00619-MONOMER.
BRENDAi1.3.1.22. 2681.
1.3.99.5. 2681.
ReactomeiR-HSA-193048. Androgen biosynthesis.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:SRD5A2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:11285. SRD5A2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei8 – 2821HelicalSequence analysisAdd
BLAST
Transmembranei72 – 9221HelicalSequence analysisAdd
BLAST
Transmembranei146 – 16621HelicalSequence analysisAdd
BLAST
Transmembranei206 – 22621HelicalSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

Pathology & Biotechi

Involvement in diseasei

Pseudovaginal perineoscrotal hypospadias (PPSH)13 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:264600
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti55 – 551L → Q in PPSH. 1 Publication
VAR_013105
Natural varianti85 – 851G → D in PPSH. 1 Publication
VAR_013130
Natural varianti115 – 1151G → D in PPSH. 3 Publications
VAR_013106
Natural varianti123 – 1231G → R in PPSH. 1 Publication
VAR_025854
Natural varianti126 – 1261Q → R in PPSH. 1 Publication
VAR_025855
Natural varianti145 – 1451R → W in PPSH. 1 Publication
VAR_025851
Natural varianti157 – 1571Missing in PPSH. 1 Publication
VAR_013107
Natural varianti158 – 1581G → R in PPSH. 1 Publication
VAR_025856
Natural varianti181 – 1811P → L in PPSH. 1 Publication
VAR_025852
Natural varianti183 – 1831G → S in PPSH. 2 Publications
VAR_013108
Natural varianti196 – 1961G → S in PPSH. 3 Publications
VAR_013109
Natural varianti197 – 1971E → D in PPSH. 1 Publication
VAR_013110
Natural varianti200 – 2001E → K in PPSH. 1 Publication
VAR_013132
Natural varianti207 – 2071A → D in PPSH. 1 Publication
VAR_025857
Natural varianti212 – 2121P → R in PPSH. 2 Publications
VAR_013111
Natural varianti228 – 2281A → T in PPSH. 1 Publication
VAR_013112
Natural varianti231 – 2311H → R in PPSH. 1 Publication
VAR_013113
Natural varianti235 – 2351Y → F in PPSH. 1 Publication
VAR_025853
Natural varianti245 – 2451S → Y in PPSH. 1 Publication
VAR_013133
Natural varianti246 – 2461R → Q in PPSH. 2 Publications
Corresponds to variant rs9332967 [ dbSNP | Ensembl ].
VAR_013134
Natural varianti246 – 2461R → W in PPSH. 4 Publications
VAR_005609

Keywords - Diseasei

Disease mutation, Pseudohermaphroditism

Organism-specific databases

MalaCardsiSRD5A2.
MIMi264600. phenotype.
Orphaneti753. 46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency.
1331. Familial prostate cancer.
PharmGKBiPA36113.

Chemistry

ChEMBLiCHEMBL2363075.
DrugBankiDB00548. Azelaic Acid.
DB01126. Dutasteride.
DB01216. Finasteride.
DB00421. Spironolactone.
GuidetoPHARMACOLOGYi2633.

Polymorphism and mutation databases

BioMutaiSRD5A2.
DMDMi401056.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 2542543-oxo-5-alpha-steroid 4-dehydrogenase 2PRO_0000213676Add
BLAST

Proteomic databases

PeptideAtlasiP31213.
PRIDEiP31213.

PTM databases

iPTMnetiP31213.
PhosphoSiteiP31213.

Expressioni

Tissue specificityi

Expressed in high levels in the prostate and many other androgen-sensitive tissues.

Gene expression databases

CleanExiHS_SRD5A2.
GenevisibleiP31213. HS.

Interactioni

Chemistry

BindingDBiP31213.

Structurei

3D structure databases

ProteinModelPortaliP31213.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the steroid 5-alpha reductase family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

HOVERGENiHBG003402.
InParanoidiP31213.
KOiK12344.
OrthoDBiEOG091G0KU4.
PhylomeDBiP31213.

Family and domain databases

InterProiIPR016636. 3-oxo-5-alpha-steroid_4-DH.
IPR001104. 3-oxo-5_a-steroid_4-DH_C.
[Graphical view]
PfamiPF02544. Steroid_dh. 1 hit.
[Graphical view]
PIRSFiPIRSF015596. 5_alpha-SR2. 1 hit.
PROSITEiPS50244. S5A_REDUCTASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P31213-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQVQCQQSPV LAGSATLVAL GALALYVAKP SGYGKHTESL KPAATRLPAR
60 70 80 90 100
AAWFLQELPS FAVPAGILAR QPLSLFGPPG TVLLGLFCVH YFHRTFVYSL
110 120 130 140 150
LNRGRPYPAI LILRGTAFCT GNGVLQGYYL IYCAEYPDGW YTDIRFSLGV
160 170 180 190 200
FLFILGMGIN IHSDYILRQL RKPGEISYRI PQGGLFTYVS GANFLGEIIE
210 220 230 240 250
WIGYALATWS LPALAFAFFS LCFLGLRAFH HHRFYLKMFE DYPKSRKALI

PFIF
Length:254
Mass (Da):28,393
Last modified:July 1, 1993 - v1
Checksum:iE65A19C8600DED05
GO

Polymorphismi

Individuals with Thr-49 have an increased risk of prostate cancer (PubMed:10501358). The enzyme with Thr-49 has a higher in vitro V(max) than the Ala-49 enzyme (PubMed:10501358).1 Publication

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti49 – 491A → T.5 Publications
Corresponds to variant rs9282858 [ dbSNP | Ensembl ].
VAR_013104
Natural varianti55 – 551L → Q in PPSH. 1 Publication
VAR_013105
Natural varianti85 – 851G → D in PPSH. 1 Publication
VAR_013130
Natural varianti89 – 891V → L.7 Publications
Corresponds to variant rs523349 [ dbSNP | Ensembl ].
VAR_013131
Natural varianti113 – 1131L → V.1 Publication
Corresponds to variant rs28383048 [ dbSNP | Ensembl ].
VAR_022302
Natural varianti115 – 1151G → D in PPSH. 3 Publications
VAR_013106
Natural varianti123 – 1231G → R in PPSH. 1 Publication
VAR_025854
Natural varianti126 – 1261Q → R in PPSH. 1 Publication
VAR_025855
Natural varianti145 – 1451R → W in PPSH. 1 Publication
VAR_025851
Natural varianti157 – 1571Missing in PPSH. 1 Publication
VAR_013107
Natural varianti158 – 1581G → R in PPSH. 1 Publication
VAR_025856
Natural varianti181 – 1811P → L in PPSH. 1 Publication
VAR_025852
Natural varianti183 – 1831G → S in PPSH. 2 Publications
VAR_013108
Natural varianti196 – 1961G → S in PPSH. 3 Publications
VAR_013109
Natural varianti197 – 1971E → D in PPSH. 1 Publication
VAR_013110
Natural varianti200 – 2001E → K in PPSH. 1 Publication
VAR_013132
Natural varianti203 – 2031G → S.
Corresponds to variant rs9332961 [ dbSNP | Ensembl ].
VAR_059791
Natural varianti207 – 2071A → D in PPSH. 1 Publication
VAR_025857
Natural varianti212 – 2121P → R in PPSH. 2 Publications
VAR_013111
Natural varianti224 – 2241L → H.
Corresponds to variant rs9332963 [ dbSNP | Ensembl ].
VAR_059792
Natural varianti224 – 2241L → M.
Corresponds to variant rs9332963 [ dbSNP | Ensembl ].
VAR_037585
Natural varianti227 – 2271R → Q in micropenis. 1 Publication
Corresponds to variant rs9332964 [ dbSNP | Ensembl ].
VAR_037586
Natural varianti228 – 2281A → T in PPSH. 1 Publication
VAR_013112
Natural varianti231 – 2311H → R in PPSH. 1 Publication
VAR_013113
Natural varianti235 – 2351Y → F in PPSH. 1 Publication
VAR_025853
Natural varianti245 – 2451S → Y in PPSH. 1 Publication
VAR_013133
Natural varianti246 – 2461R → Q in PPSH. 2 Publications
Corresponds to variant rs9332967 [ dbSNP | Ensembl ].
VAR_013134
Natural varianti246 – 2461R → W in PPSH. 4 Publications
VAR_005609

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS74503.1.
PIRiA49169.
RefSeqiNP_000339.2. NM_000348.3.
UniGeneiHs.458345.

Genome annotation databases

EnsembliENST00000622030; ENSP00000477587; ENSG00000277893.
GeneIDi6716.
KEGGihsa:6716.
UCSCiuc032nip.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs
Wikipedia

5-alpha reductase entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS74503.1.
PIRiA49169.
RefSeqiNP_000339.2. NM_000348.3.
UniGeneiHs.458345.

3D structure databases

ProteinModelPortaliP31213.
ModBaseiSearch...
MobiDBiSearch...

Chemistry

BindingDBiP31213.
ChEMBLiCHEMBL2363075.
DrugBankiDB00548. Azelaic Acid.
DB01126. Dutasteride.
DB01216. Finasteride.
DB00421. Spironolactone.
GuidetoPHARMACOLOGYi2633.

PTM databases

iPTMnetiP31213.
PhosphoSiteiP31213.

Polymorphism and mutation databases

BioMutaiSRD5A2.
DMDMi401056.

Proteomic databases

PeptideAtlasiP31213.
PRIDEiP31213.

Protocols and materials databases

DNASUi6716.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000622030; ENSP00000477587; ENSG00000277893.
GeneIDi6716.
KEGGihsa:6716.
UCSCiuc032nip.2. human.

Organism-specific databases

CTDi6716.
GeneCardsiSRD5A2.
H-InvDBHIX0030017.
HGNCiHGNC:11285. SRD5A2.
MalaCardsiSRD5A2.
MIMi264600. phenotype.
607306. gene.
neXtProtiNX_P31213.
Orphaneti753. 46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency.
1331. Familial prostate cancer.
PharmGKBiPA36113.
GenAtlasiSearch...

Phylogenomic databases

HOVERGENiHBG003402.
InParanoidiP31213.
KOiK12344.
OrthoDBiEOG091G0KU4.
PhylomeDBiP31213.

Enzyme and pathway databases

BioCyciMetaCyc:HS00619-MONOMER.
BRENDAi1.3.1.22. 2681.
1.3.99.5. 2681.
ReactomeiR-HSA-193048. Androgen biosynthesis.

Miscellaneous databases

ChiTaRSiSRD5A2. human.
GeneWikiiSRD5A2.
GenomeRNAii6716.
PROiP31213.
SOURCEiSearch...

Gene expression databases

CleanExiHS_SRD5A2.
GenevisibleiP31213. HS.

Family and domain databases

InterProiIPR016636. 3-oxo-5-alpha-steroid_4-DH.
IPR001104. 3-oxo-5_a-steroid_4-DH_C.
[Graphical view]
PfamiPF02544. Steroid_dh. 1 hit.
[Graphical view]
PIRSFiPIRSF015596. 5_alpha-SR2. 1 hit.
PROSITEiPS50244. S5A_REDUCTASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiS5A2_HUMAN
AccessioniPrimary (citable) accession number: P31213
Secondary accession number(s): B2RE87, Q2M1R4, Q9BYE6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 1, 1993
Last modified: September 7, 2016
This is version 157 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.