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3-oxo-5-alpha-steroid 4-dehydrogenase 1 (EC 1.3.1.22) (SR type 1) (Steroid 5-alpha-reductase 1) (S5AR 1)

 S5A1_HUMAN              Reviewed;         259 AA.
P18405; B2R7Q1; Q9UHY4; Q9UP36; Q9UP37;
01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
01-NOV-1990, sequence version 1.
18-JUL-2018, entry version 167.
RecName: Full=3-oxo-5-alpha-steroid 4-dehydrogenase 1;
EC=1.3.1.22;
AltName: Full=SR type 1;
AltName: Full=Steroid 5-alpha-reductase 1;
Short=S5AR 1;
Name=SRD5A1;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=2339109; DOI=10.1073/pnas.87.10.3640;
Andersson S., Russell D.W.;
"Structural and biochemical properties of cloned and expressed human
and rat steroid 5 alpha-reductases.";
Proc. Natl. Acad. Sci. U.S.A. 87:3640-3644(1990).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=1686016; DOI=10.1016/0888-7543(91)90038-G;
Jenkins E.P., Hsieh C.L., Milatovich A., Normington K., Berman D.M.,
Francke U., Russell D.W.;
"Characterization and chromosomal mapping of a human steroid 5 alpha-
reductase gene and pseudogene and mapping of the mouse homologue.";
Genomics 11:1102-1112(1991).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Brain;
Yu W., Sarginson J., Gibbs R.A.;
Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Adrenal gland;
PubMed=10931946; DOI=10.1073/pnas.160270997;
Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X.,
Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H.,
Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J.,
Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M.,
Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L.;
"Gene expression profiling in the human hypothalamus-pituitary-adrenal
axis and full-length cDNA cloning.";
Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
Phelan M., Farmer A.;
"Cloning of human full-length CDSs in BD Creator(TM) system donor
vector.";
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
[6]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
NIEHS SNPs program;
Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
[7]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Hippocampus;
PubMed=14702039; DOI=10.1038/ng1285;
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.,
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.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[8]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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., 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.
[9]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Eye, and Urinary bladder;
PubMed=15489334; DOI=10.1101/gr.2596504;
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).
[10]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-98 AND 155-187.
PubMed=11678334; DOI=10.1007/s004240100019;
Eminovic I., Liovic M., Prezelj J., Kocijancic A., Rozman D.,
Komel R.;
"New steroid 5alpha-reductase type I (SRD5A1) homologous sequences on
human chromosomes 6 and 8.";
Pflugers Arch. 442:R187-R189(2001).
[11]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=22814378; DOI=10.1073/pnas.1210303109;
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
Aldabe R.;
"N-terminal acetylome analyses and functional insights of the N-
terminal acetyltransferase NatB.";
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
-!- FUNCTION: Converts testosterone into 5-alpha-dihydrotestosterone
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.
-!- BIOPHYSICOCHEMICAL PROPERTIES:
pH dependence:
Optimally active at alkaline pHs.;
-!- SUBCELLULAR LOCATION: Microsome membrane; Multi-pass membrane
protein. Endoplasmic reticulum membrane {ECO:0000305}; Multi-pass
membrane protein {ECO:0000305}.
-!- TISSUE SPECIFICITY: Liver and prostate (at a low level).
-!- INDUCTION: Its expression is regulated by androgens such as
testosterone.
-!- SIMILARITY: Belongs to the steroid 5-alpha reductase family.
{ECO:0000305}.
-!- WEB RESOURCE: Name=NIEHS-SNPs;
URL="http://egp.gs.washington.edu/data/srd5a1/";
-!- WEB RESOURCE: Name=Wikipedia; Note=5-alpha reductase entry;
URL="https://en.wikipedia.org/wiki/5_alpha_reductase";
-----------------------------------------------------------------------
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EMBL; M32313; AAA35490.1; -; mRNA.
EMBL; M68886; AAA60995.1; -; Genomic_DNA.
EMBL; M68882; AAA60995.1; JOINED; Genomic_DNA.
EMBL; M68883; AAA60995.1; JOINED; Genomic_DNA.
EMBL; M68884; AAA60995.1; JOINED; Genomic_DNA.
EMBL; M68885; AAA60995.1; JOINED; Genomic_DNA.
EMBL; AF052126; AAC28620.1; -; mRNA.
EMBL; AF113128; AAF14869.1; -; mRNA.
EMBL; BT006834; AAP35480.1; -; mRNA.
EMBL; AY341029; AAP88935.1; -; Genomic_DNA.
EMBL; AK313070; BAG35898.1; -; mRNA.
EMBL; CH471102; EAX08104.1; -; Genomic_DNA.
EMBL; BC007033; AAH07033.1; -; mRNA.
EMBL; BC008673; AAH08673.1; -; mRNA.
EMBL; AF073301; AAC26862.1; -; Genomic_DNA.
EMBL; AF073302; AAC26863.1; -; Genomic_DNA.
EMBL; AF073303; AAC26864.1; -; Genomic_DNA.
EMBL; AF073304; AAC26865.1; -; Genomic_DNA.
CCDS; CCDS3870.1; -.
PIR; A55274; A55274.
RefSeq; NP_001038.1; NM_001047.3.
RefSeq; NP_001311251.1; NM_001324322.1.
RefSeq; NP_001311252.1; NM_001324323.1.
UniGene; Hs.552; -.
ProteinModelPortal; P18405; -.
BioGrid; 112593; 3.
STRING; 9606.ENSP00000274192; -.
BindingDB; P18405; -.
ChEMBL; CHEMBL1787; -.
DrugBank; DB01126; Dutasteride.
DrugBank; DB01216; Finasteride.
DrugBank; DB00367; Levonorgestrel.
DrugBank; DB09389; Norgestrel.
DrugBank; DB06412; Oxymetholone.
DrugBank; DB00421; Spironolactone.
SwissLipids; SLP:000001636; -.
PhosphoSitePlus; P18405; -.
BioMuta; SRD5A1; -.
DMDM; 134151; -.
EPD; P18405; -.
MaxQB; P18405; -.
PaxDb; P18405; -.
PeptideAtlas; P18405; -.
PRIDE; P18405; -.
ProteomicsDB; 53557; -.
DNASU; 6715; -.
Ensembl; ENST00000274192; ENSP00000274192; ENSG00000145545.
GeneID; 6715; -.
KEGG; hsa:6715; -.
UCSC; uc003jdw.4; human.
CTD; 6715; -.
DisGeNET; 6715; -.
EuPathDB; HostDB:ENSG00000145545.11; -.
GeneCards; SRD5A1; -.
HGNC; HGNC:11284; SRD5A1.
HPA; HPA051402; -.
MIM; 184753; gene.
neXtProt; NX_P18405; -.
OpenTargets; ENSG00000145545; -.
PharmGKB; PA36112; -.
eggNOG; KOG1638; Eukaryota.
eggNOG; ENOG410XS6P; LUCA.
GeneTree; ENSGT00510000046634; -.
HOGENOM; HOG000050133; -.
HOVERGEN; HBG003402; -.
InParanoid; P18405; -.
KO; K12343; -.
OMA; VEWCGFA; -.
OrthoDB; EOG091G0KU4; -.
PhylomeDB; P18405; -.
TreeFam; TF314668; -.
BioCyc; MetaCyc:HS07261-MONOMER; -.
BRENDA; 1.3.1.22; 2681.
BRENDA; 1.3.99.5; 2681.
Reactome; R-HSA-193048; Androgen biosynthesis.
SIGNOR; P18405; -.
GeneWiki; SRD5A1; -.
GenomeRNAi; 6715; -.
PRO; PR:P18405; -.
Proteomes; UP000005640; Chromosome 5.
Bgee; ENSG00000145545; -.
CleanEx; HS_SRD5A1; -.
ExpressionAtlas; P18405; baseline and differential.
Genevisible; P18405; HS.
GO; GO:0070852; C:cell body fiber; IEA:Ensembl.
GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
GO; GO:0043209; C:myelin sheath; IEA:Ensembl.
GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
GO; GO:0031090; C:organelle membrane; IEA:UniProtKB-SubCell.
GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
GO; GO:0003865; F:3-oxo-5-alpha-steroid 4-dehydrogenase activity; IDA:UniProtKB.
GO; GO:0033218; F:amide binding; IEA:Ensembl.
GO; GO:0047751; F:cholestenone 5-alpha-reductase activity; IEA:UniProtKB-EC.
GO; GO:0009055; F:electron transfer activity; TAS:UniProtKB.
GO; GO:0070402; F:NADPH binding; IEA:Ensembl.
GO; GO:0006702; P:androgen biosynthetic process; IBA:GO_Central.
GO; GO:0060348; P:bone development; IEA:Ensembl.
GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
GO; GO:0071320; P:cellular response to cAMP; IEA:Ensembl.
GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEA:Ensembl.
GO; GO:0071872; P:cellular response to epinephrine stimulus; IEA:Ensembl.
GO; GO:0071392; P:cellular response to estradiol stimulus; IEA:Ensembl.
GO; GO:0071363; P:cellular response to growth factor stimulus; IEA:Ensembl.
GO; GO:0032869; P:cellular response to insulin stimulus; IEA:Ensembl.
GO; GO:0009267; P:cellular response to starvation; IEA:Ensembl.
GO; GO:0071394; P:cellular response to testosterone stimulus; IEA:Ensembl.
GO; GO:0021987; P:cerebral cortex development; IEA:Ensembl.
GO; GO:0042747; P:circadian sleep/wake cycle, REM sleep; IEA:Ensembl.
GO; GO:0016101; P:diterpenoid metabolic process; IEA:Ensembl.
GO; GO:0030540; P:female genitalia development; IBA:GO_Central.
GO; GO:0021766; P:hippocampus development; IEA:Ensembl.
GO; GO:0021854; P:hypothalamus development; IEA:Ensembl.
GO; GO:0001889; P:liver development; IEA:Ensembl.
GO; GO:0030539; P:male genitalia development; IBA:GO_Central.
GO; GO:0008584; P:male gonad development; IEA:Ensembl.
GO; GO:0021983; P:pituitary gland development; IEA:Ensembl.
GO; GO:0042448; P:progesterone metabolic process; IBA:GO_Central.
GO; GO:0043627; P:response to estrogen; IEA:Ensembl.
GO; GO:0032354; P:response to follicle-stimulating hormone; IEA:Ensembl.
GO; GO:0060992; P:response to fungicide; IEA:Ensembl.
GO; GO:0060416; P:response to growth hormone; IEA:Ensembl.
GO; GO:0014850; P:response to muscle activity; IEA:Ensembl.
GO; GO:0042428; P:serotonin metabolic process; IEA:Ensembl.
GO; GO:0007530; P:sex determination; NAS:ProtInc.
GO; GO:0021510; P:spinal cord development; IEA:Ensembl.
GO; GO:0021794; P:thalamus development; IEA:Ensembl.
GO; GO:0001655; P:urogenital system development; IEA:Ensembl.
InterPro; IPR016636; 3-oxo-5-alpha-steroid_4-DH.
InterPro; IPR001104; 3-oxo-5_a-steroid_4-DH_C.
InterPro; IPR039357; SRD5A/TECR.
PANTHER; PTHR10556; PTHR10556; 1.
Pfam; PF02544; Steroid_dh; 1.
PIRSF; PIRSF015596; 5_alpha-SR2; 1.
PROSITE; PS50244; S5A_REDUCTASE; 1.
1: Evidence at protein level;
Complete proteome; Differentiation; Endoplasmic reticulum; Membrane;
Microsome; NADP; Oxidoreductase; Reference proteome;
Sexual differentiation; Transmembrane; Transmembrane helix.
CHAIN 1 259 3-oxo-5-alpha-steroid 4-dehydrogenase 1.
/FTId=PRO_0000213674.
TRANSMEM 12 29 Helical. {ECO:0000255}.
TRANSMEM 86 106 Helical. {ECO:0000255}.
TRANSMEM 111 131 Helical. {ECO:0000255}.
TRANSMEM 151 171 Helical. {ECO:0000255}.
TRANSMEM 209 229 Helical. {ECO:0000255}.
CONFLICT 29 76 Missing (in Ref. 4; AAF14869).
{ECO:0000305}.
SEQUENCE 259 AA; 29459 MW; AEF9FD5521E43AC4 CRC64;
MATATGVAEE RLLAALAYLQ CAVGCAVFAR NRQTNSVYGR HALPSHRLRV PARAAWVVQE
LPSLALPLYQ YASESAPRLR SAPNCILLAM FLVHYGHRCL IYPFLMRGGK PMPLLACTMA
IMFCTCNGYL QSRYLSHCAV YADDWVTDPR FLIGFGLWLT GMLINIHSDH ILRNLRKPGD
TGYKIPRGGL FEYVTAANYF GEIMEWCGYA LASWSVQGAA FAFFTFCFLS GRAKEHHEWY
LRKFEEYPKF RKIIIPFLF


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