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Protein

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

Gene

SRD5A2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.1 Publication

Catalytic activityi

A 3-oxo-5-alpha-steroid + NADP+ = a 3-oxo-Delta4-steroid + NADPH.1 Publication

Kineticsi

  1. KM=0.9 µM for testosterone (at pH 6.0)1 Publication
  2. KM=8 µM for NADPH (at pH 6.0)1 Publication
  1. Vmax=1.9 nmol/min/mg enzyme with testosterone as substrate with NADPH as cofactor (at pH 6.0)1 Publication

pH dependencei

Optimally active at acidic pHs.

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionOxidoreductase
Biological processDifferentiation, Sexual differentiation
LigandNADP

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:1.3.1.221 Publication)
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

EuPathDBiHostDB:ENSG00000277893.1
HGNCiHGNC:11285 SRD5A2
MIMi607306 gene
neXtProtiNX_P31213

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei8 – 28HelicalSequence analysisAdd BLAST21
Transmembranei72 – 92HelicalSequence analysisAdd BLAST21
Transmembranei146 – 166HelicalSequence analysisAdd BLAST21
Transmembranei206 – 226HelicalSequence analysisAdd BLAST21

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

Pathology & Biotechi

Involvement in diseasei

Pseudovaginal perineoscrotal hypospadias (PPSH)16 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)DescriptionActionsGraphical viewLength
Natural variantiVAR_01310555L → Q in PPSH. 1 Publication1
Natural variantiVAR_01313085G → D in PPSH. 1 Publication1
Natural variantiVAR_013106115G → D in PPSH. 3 Publications1
Natural variantiVAR_025854123G → R in PPSH. 1 Publication1
Natural variantiVAR_025855126Q → R in PPSH. 1 Publication1
Natural variantiVAR_025851145R → W in PPSH. 1 Publication1
Natural variantiVAR_013107157Missing in PPSH. 1 Publication1
Natural variantiVAR_025856158G → R in PPSH. 1 Publication1
Natural variantiVAR_025852181P → L in PPSH. 1 Publication1
Natural variantiVAR_013108183G → S in PPSH. 2 Publications1
Natural variantiVAR_013109196G → S in PPSH. 3 Publications1
Natural variantiVAR_013110197E → D in PPSH. 1 Publication1
Natural variantiVAR_013132200E → K in PPSH. 1 Publication1
Natural variantiVAR_025857207A → D in PPSH. 1 Publication1
Natural variantiVAR_013111212P → R in PPSH. 2 Publications1
Natural variantiVAR_037586227R → Q in PPSH; also in individuals with micropenis; increased affinity for testosterone; increased affinity for NADPH; decreased Vmax. 3 PublicationsCorresponds to variant dbSNP:rs9332964EnsemblClinVar.1
Natural variantiVAR_013112228A → T in PPSH. 1 Publication1
Natural variantiVAR_013113231H → R in PPSH. 1 Publication1
Natural variantiVAR_025853235Y → F in PPSH. 1 Publication1
Natural variantiVAR_013133245S → Y in PPSH. 1 Publication1
Natural variantiVAR_013134246R → Q in PPSH. 2 PublicationsCorresponds to variant dbSNP:rs9332967EnsemblClinVar.1
Natural variantiVAR_005609246R → W in PPSH. 4 Publications1

Keywords - Diseasei

Disease mutation, Pseudohermaphroditism

Organism-specific databases

DisGeNETi6716
MalaCardsiSRD5A2
MIMi264600 phenotype
Orphaneti753 46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency
1331 Familial prostate cancer
PharmGKBiPA36113

Chemistry databases

ChEMBLiCHEMBL1856
DrugBankiDB00548 Azelaic Acid
DB01126 Dutasteride
DB01216 Finasteride
DB00421 Spironolactone
GuidetoPHARMACOLOGYi2633

Polymorphism and mutation databases

BioMutaiSRD5A2
DMDMi401056

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002136761 – 2543-oxo-5-alpha-steroid 4-dehydrogenase 2Add BLAST254

Proteomic databases

PeptideAtlasiP31213
PRIDEiP31213
ProteomicsDBi54764

PTM databases

iPTMnetiP31213
PhosphoSitePlusiP31213

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000277893 Expressed in 51 organ(s), highest expression level in liver
CleanExiHS_SRD5A2
GenevisibleiP31213 HS

Interactioni

Protein-protein interaction databases

BioGridi112594, 1 interactor
IntActiP31213, 2 interactors

Chemistry databases

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

InterProiView protein in InterPro
IPR016636 3-oxo-5-alpha-steroid_4-DH
IPR001104 3-oxo-5_a-steroid_4-DH_C
IPR039357 SRD5A/TECR
PANTHERiPTHR10556 PTHR10556, 1 hit
PfamiView protein in Pfam
PF02544 Steroid_dh, 1 hit
PIRSFiPIRSF015596 5_alpha-SR2, 1 hit
PROSITEiView protein in PROSITE
PS50244 S5A_REDUCTASE, 1 hit

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)DescriptionActionsGraphical viewLength
Natural variantiVAR_0775465C → R No effect on affinity for testosterone; no effect on affinity for NADPH; no effect on Vmax. 1 Publication1
Natural variantiVAR_07754730P → L Increased affinity for testosterone; increased affinity for NADPH; decreased Vmax. 1 Publication1
Natural variantiVAR_07754848P → R Increased affinity for testosterone; increased affinity for NADPH; decreased Vmax. 1 Publication1
Natural variantiVAR_01310449A → T Increased affinity for testosterone; no effect on affinity for NADPH; increased Vmax; no effect on affinity for testosterone when associated with L-89; no effect on affinity for NADPH when associated with L-89; increased Vmax when associated with L-89. 6 PublicationsCorresponds to variant dbSNP:rs9282858EnsemblClinVar.1
Natural variantiVAR_07754951A → T No effect on affinity for testosterone; increased affinity for NADPH; decreased Vmax. 1 Publication1
Natural variantiVAR_01310555L → Q in PPSH. 1 Publication1
Natural variantiVAR_01313085G → D in PPSH. 1 Publication1
Natural variantiVAR_01313189V → L No effect on affinity for testosterone; no effect on affinity for NADPH; decreased Vmax; no effect on affinity for testosterone when associated with T-49; no effect on affinity for NADPH when associated with T-49; increased Vmax when associated with T-49; decreased affinity for testosterone when associated with M-187; increased affinity for NADPH when associated with M-187; decreased Vmax when associated with M-187; no effect on affinity for testosterone when associated with L-234; increased affinity for NADPH when associated with L-234; decreased Vmax when associated with L-234. 8 PublicationsCorresponds to variant dbSNP:rs523349Ensembl.1
Natural variantiVAR_022302113L → V1 PublicationCorresponds to variant dbSNP:rs28383048EnsemblClinVar.1
Natural variantiVAR_013106115G → D in PPSH. 3 Publications1
Natural variantiVAR_025854123G → R in PPSH. 1 Publication1
Natural variantiVAR_025855126Q → R in PPSH. 1 Publication1
Natural variantiVAR_025851145R → W in PPSH. 1 Publication1
Natural variantiVAR_013107157Missing in PPSH. 1 Publication1
Natural variantiVAR_025856158G → R in PPSH. 1 Publication1
Natural variantiVAR_025852181P → L in PPSH. 1 Publication1
Natural variantiVAR_013108183G → S in PPSH. 2 Publications1
Natural variantiVAR_077550187T → M No effect on affinity for testosterone; increased affinity for NADPH; decreased Vmax; decreased affinity for testosterone when associated with L-89; increased affinity for NADPH when associated with L-89; decreased Vmax when associated with L-89. 1 Publication1
Natural variantiVAR_077551194F → L No effect on affinity for testosterone; increased affinity for NADPH; increased Vmax. 1 Publication1
Natural variantiVAR_013109196G → S in PPSH. 3 Publications1
Natural variantiVAR_013110197E → D in PPSH. 1 Publication1
Natural variantiVAR_013132200E → K in PPSH. 1 Publication1
Natural variantiVAR_059791203G → S. Corresponds to variant dbSNP:rs9332961EnsemblClinVar.1
Natural variantiVAR_025857207A → D in PPSH. 1 Publication1
Natural variantiVAR_013111212P → R in PPSH. 2 Publications1
Natural variantiVAR_059792224L → H. Corresponds to variant dbSNP:rs9332963Ensembl.1
Natural variantiVAR_037585224L → M. Corresponds to variant dbSNP:rs9332963Ensembl.1
Natural variantiVAR_037586227R → Q in PPSH; also in individuals with micropenis; increased affinity for testosterone; increased affinity for NADPH; decreased Vmax. 3 PublicationsCorresponds to variant dbSNP:rs9332964EnsemblClinVar.1
Natural variantiVAR_013112228A → T in PPSH. 1 Publication1
Natural variantiVAR_013113231H → R in PPSH. 1 Publication1
Natural variantiVAR_077552234F → L Increased affinity for testosterone; increased affinity for NADPH; decreased Vmax; no effect on affinity for testosterone when associated with L-89; increased affinity for NADPH when associated with L-89; decreased Vmax when associated with L-89. 1 Publication1
Natural variantiVAR_025853235Y → F in PPSH. 1 Publication1
Natural variantiVAR_013133245S → Y in PPSH. 1 Publication1
Natural variantiVAR_013134246R → Q in PPSH. 2 PublicationsCorresponds to variant dbSNP:rs9332967EnsemblClinVar.1
Natural variantiVAR_005609246R → W in PPSH. 4 Publications1

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

Similar proteinsi

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...

Protein-protein interaction databases

BioGridi112594, 1 interactor
IntActiP31213, 2 interactors

Chemistry databases

BindingDBiP31213
ChEMBLiCHEMBL1856
DrugBankiDB00548 Azelaic Acid
DB01126 Dutasteride
DB01216 Finasteride
DB00421 Spironolactone
GuidetoPHARMACOLOGYi2633

PTM databases

iPTMnetiP31213
PhosphoSitePlusiP31213

Polymorphism and mutation databases

BioMutaiSRD5A2
DMDMi401056

Proteomic databases

PeptideAtlasiP31213
PRIDEiP31213
ProteomicsDBi54764

Protocols and materials databases

DNASUi6716
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi6716
DisGeNETi6716
EuPathDBiHostDB:ENSG00000277893.1
GeneCardsiSRD5A2
H-InvDBiHIX0030017
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
PROiPR:P31213
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000277893 Expressed in 51 organ(s), highest expression level in liver
CleanExiHS_SRD5A2
GenevisibleiP31213 HS

Family and domain databases

InterProiView protein in InterPro
IPR016636 3-oxo-5-alpha-steroid_4-DH
IPR001104 3-oxo-5_a-steroid_4-DH_C
IPR039357 SRD5A/TECR
PANTHERiPTHR10556 PTHR10556, 1 hit
PfamiView protein in Pfam
PF02544 Steroid_dh, 1 hit
PIRSFiPIRSF015596 5_alpha-SR2, 1 hit
PROSITEiView protein in PROSITE
PS50244 S5A_REDUCTASE, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiS5A2_HUMAN
AccessioniPrimary (citable) accession number: P31213
Secondary accession number(s): B2RE87, Q2M1R4, Q9BYE6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 1, 1993
Last modified: September 12, 2018
This is version 168 of the entry and version 1 of the sequence. See 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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