DHB2_HUMAN
ID DHB2_HUMAN Reviewed; 387 AA.
AC P37059; B2R7T4;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 195.
DE RecName: Full=17-beta-hydroxysteroid dehydrogenase type 2 {ECO:0000305};
DE Short=17-beta-HSD 2;
DE AltName: Full=20 alpha-hydroxysteroid dehydrogenase;
DE Short=20-alpha-HSD;
DE AltName: Full=E2DH;
DE AltName: Full=Estradiol 17-beta-dehydrogenase 2;
DE EC=1.1.1.62 {ECO:0000269|PubMed:10385431, ECO:0000269|PubMed:11940569, ECO:0000269|PubMed:8099587};
DE AltName: Full=Microsomal 17-beta-hydroxysteroid dehydrogenase;
DE AltName: Full=Short chain dehydrogenase/reductase family 9C member 2;
DE AltName: Full=Testosterone 17-beta-dehydrogenase;
DE EC=1.1.1.239 {ECO:0000269|PubMed:10385431, ECO:0000269|PubMed:11940569, ECO:0000269|PubMed:8099587};
GN Name=HSD17B2 {ECO:0000312|HGNC:HGNC:5211}; Synonyms=EDH17B2, SDR9C2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], BIOPHYSICOCHEMICAL PROPERTIES, CATALYTIC
RP ACTIVITY, AND FUNCTION.
RC TISSUE=Prostate;
RX PubMed=8099587; DOI=10.1016/s0021-9258(18)31480-7;
RA Wu L., Einstein M., Geissler W.M., Chan H.K., Elliston K.O., Andersson S.;
RT "Expression cloning and characterization of human 17 beta-hydroxysteroid
RT dehydrogenase type 2, a microsomal enzyme possessing 20 alpha-
RT hydroxysteroid dehydrogenase activity.";
RL J. Biol. Chem. 268:12964-12969(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7546291; DOI=10.1089/dna.1995.14.849;
RA Labrie Y., Durocher F., Lachance Y., Turgeon C., Simard J., Labrie C.,
RA Labrie F.;
RT "The human type II 17 beta-hydroxysteroid dehydrogenase gene encodes two
RT alternatively spliced mRNA species.";
RL DNA Cell Biol. 14:849-862(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT THR-121.
RG NIEHS SNPs program;
RL Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Bone marrow;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP SUBCELLULAR LOCATION, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=10385431; DOI=10.1210/endo.140.7.6861;
RA Puranen T.J., Kurkela R.M., Lakkakorpi J.T., Poutanen M.H., Itaeranta P.V.,
RA Melis J.P., Ghosh D., Vihko R.K., Vihko P.T.;
RT "Characterization of molecular and catalytic properties of intact and
RT truncated human 17beta-hydroxysteroid dehydrogenase type 2 enzymes:
RT intracellular localization of the wild-type enzyme in the endoplasmic
RT reticulum.";
RL Endocrinology 140:3334-3341(1999).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RX PubMed=11940569; DOI=10.1074/jbc.m111726200;
RA Lu M.L., Huang Y.W., Lin S.X.;
RT "Purification, reconstitution, and steady-state kinetics of the trans-
RT membrane 17 beta-hydroxysteroid dehydrogenase 2.";
RL J. Biol. Chem. 277:22123-22130(2002).
CC -!- FUNCTION: Catalyzes the NAD-dependent oxidation of the highly active
CC 17beta-hydroxysteroids, such as estradiol (E2), testosterone (T), and
CC dihydrotestosterone (DHT), to their less active forms and thus
CC regulates the biological potency of these steroids. Oxidizes estradiol
CC to estrone, testosterone to androstenedione, and dihydrotestosterone to
CC 5alpha-androstan-3,17-dione. Also has 20-alpha-HSD activity.
CC {ECO:0000269|PubMed:10385431, ECO:0000269|PubMed:11940569,
CC ECO:0000269|PubMed:8099587}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-estradiol + NAD(+) = estrone + H(+) + NADH;
CC Xref=Rhea:RHEA:24612, ChEBI:CHEBI:15378, ChEBI:CHEBI:16469,
CC ChEBI:CHEBI:17263, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.62;
CC Evidence={ECO:0000269|PubMed:10385431, ECO:0000269|PubMed:11940569,
CC ECO:0000269|PubMed:8099587};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24613;
CC Evidence={ECO:0000305|PubMed:10385431, ECO:0000305|PubMed:8099587};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NAD(+) + testosterone = androst-4-ene-3,17-dione + H(+) +
CC NADH; Xref=Rhea:RHEA:14929, ChEBI:CHEBI:15378, ChEBI:CHEBI:16422,
CC ChEBI:CHEBI:17347, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC EC=1.1.1.239; Evidence={ECO:0000269|PubMed:10385431,
CC ECO:0000269|PubMed:11940569, ECO:0000269|PubMed:8099587};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14930;
CC Evidence={ECO:0000305|PubMed:8099587};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-hydroxy-5alpha-androstan-3-one + NAD(+) = 5alpha-
CC androstan-3,17-dione + H(+) + NADH; Xref=Rhea:RHEA:41992,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15994, ChEBI:CHEBI:16330,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC Evidence={ECO:0000269|PubMed:10385431, ECO:0000269|PubMed:11940569,
CC ECO:0000269|PubMed:8099587};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(20S)-hydroxypregn-4-en-3-one + NAD(+) = H(+) + NADH +
CC progesterone; Xref=Rhea:RHEA:42108, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17026, ChEBI:CHEBI:28453, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; Evidence={ECO:0000269|PubMed:10385431,
CC ECO:0000269|PubMed:11940569, ECO:0000269|PubMed:8099587};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.21 uM for estradiol {ECO:0000269|PubMed:8099587};
CC KM=0.39 uM for testosterone {ECO:0000269|PubMed:8099587};
CC KM=0.31 uM for dihydrotestosterone {ECO:0000269|PubMed:8099587};
CC KM=0.71 uM for 20-alpha-dihydroprogesterone
CC {ECO:0000269|PubMed:8099587};
CC KM=2.63 uM for androstenedione {ECO:0000269|PubMed:8099587};
CC KM=0.78 uM for estrone {ECO:0000269|PubMed:8099587};
CC KM=110 uM for NAD {ECO:0000269|PubMed:11940569};
CC KM=9600 uM for NADP {ECO:0000269|PubMed:11940569};
CC KM=0.35 uM for estradiol {ECO:0000269|PubMed:11940569};
CC KM=0.61 uM for testosterone {ECO:0000269|PubMed:11940569};
CC KM=0.25 uM for dihydrotestosterone {ECO:0000269|PubMed:11940569};
CC KM=0.53 uM for 20-alpha-dihydroprogesterone
CC {ECO:0000269|PubMed:11940569};
CC Vmax=38 nmol/min/mg enzyme with estradiol as substrate
CC {ECO:0000269|PubMed:8099587};
CC Vmax=45 nmol/min/mg enzyme with testosterone as substrate
CC {ECO:0000269|PubMed:8099587};
CC Vmax=38 nmol/min/mg enzyme with dihydrotestosterone as substrate
CC {ECO:0000269|PubMed:8099587};
CC Vmax=5.6 nmol/min/mg enzyme with 20-alpha-dihydroprogesterone as
CC substrate {ECO:0000269|PubMed:8099587};
CC Vmax=6.6 nmol/min/mg enzyme with estrone as substrate
CC {ECO:0000269|PubMed:8099587};
CC Vmax=11.5 nmol/min/mg enzyme with androstenedione as substrate
CC {ECO:0000269|PubMed:8099587};
CC pH dependence:
CC Optimum pH is 9 with testosterone and estradiol as substrates and 5.5
CC with androstenedione and estrone as substrates.
CC {ECO:0000269|PubMed:8099587};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:11940569}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:10385431}; Single-pass type II membrane protein
CC {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in placenta.
CC {ECO:0000269|PubMed:8099587}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/hsd17b2/";
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DR EMBL; L11708; AAA03562.1; -; mRNA.
DR EMBL; L40802; AAC41917.1; -; Genomic_DNA.
DR EMBL; L40796; AAC41917.1; JOINED; Genomic_DNA.
DR EMBL; L40797; AAC41917.1; JOINED; Genomic_DNA.
DR EMBL; L40798; AAC41917.1; JOINED; Genomic_DNA.
DR EMBL; L40801; AAC41917.1; JOINED; Genomic_DNA.
DR EMBL; AY325910; AAP78485.1; -; Genomic_DNA.
DR EMBL; AK313109; BAG35931.1; -; mRNA.
DR EMBL; CH471114; EAW95519.1; -; Genomic_DNA.
DR EMBL; BC009581; AAH09581.1; -; mRNA.
DR EMBL; BC059170; AAH59170.1; -; mRNA.
DR CCDS; CCDS10936.1; -.
DR PIR; A47287; A47287.
DR RefSeq; NP_002144.1; NM_002153.2.
DR AlphaFoldDB; P37059; -.
DR SMR; P37059; -.
DR BioGRID; 109527; 10.
DR IntAct; P37059; 2.
DR MINT; P37059; -.
DR STRING; 9606.ENSP00000199936; -.
DR BindingDB; P37059; -.
DR ChEMBL; CHEMBL2789; -.
DR DrugBank; DB13952; Estradiol acetate.
DR DrugBank; DB13953; Estradiol benzoate.
DR DrugBank; DB13954; Estradiol cypionate.
DR DrugBank; DB13955; Estradiol dienanthate.
DR DrugBank; DB13956; Estradiol valerate.
DR DrugBank; DB00157; NADH.
DR DrugCentral; P37059; -.
DR GuidetoPHARMACOLOGY; 3094; -.
DR SwissLipids; SLP:000001217; -.
DR iPTMnet; P37059; -.
DR PhosphoSitePlus; P37059; -.
DR BioMuta; HSD17B2; -.
DR DMDM; 544152; -.
DR EPD; P37059; -.
DR jPOST; P37059; -.
DR MassIVE; P37059; -.
DR MaxQB; P37059; -.
DR PaxDb; P37059; -.
DR PeptideAtlas; P37059; -.
DR PRIDE; P37059; -.
DR ProteomicsDB; 55256; -.
DR Antibodypedia; 16980; 322 antibodies from 32 providers.
DR DNASU; 3294; -.
DR Ensembl; ENST00000199936.9; ENSP00000199936.4; ENSG00000086696.11.
DR GeneID; 3294; -.
DR KEGG; hsa:3294; -.
DR MANE-Select; ENST00000199936.9; ENSP00000199936.4; NM_002153.3; NP_002144.1.
DR UCSC; uc002fgv.4; human.
DR CTD; 3294; -.
DR DisGeNET; 3294; -.
DR GeneCards; HSD17B2; -.
DR HGNC; HGNC:5211; HSD17B2.
DR HPA; ENSG00000086696; Group enriched (intestine, liver, placenta).
DR MIM; 109685; gene.
DR neXtProt; NX_P37059; -.
DR OpenTargets; ENSG00000086696; -.
DR PharmGKB; PA29479; -.
DR VEuPathDB; HostDB:ENSG00000086696; -.
DR eggNOG; KOG1610; Eukaryota.
DR GeneTree; ENSGT00940000160204; -.
DR InParanoid; P37059; -.
DR OMA; KKCMAVN; -.
DR OrthoDB; 1313182at2759; -.
DR PhylomeDB; P37059; -.
DR TreeFam; TF325617; -.
DR BioCyc; MetaCyc:HS01540-MON; -.
DR BRENDA; 1.1.1.62; 2681.
DR PathwayCommons; P37059; -.
DR Reactome; R-HSA-193144; Estrogen biosynthesis.
DR SABIO-RK; P37059; -.
DR SignaLink; P37059; -.
DR BioGRID-ORCS; 3294; 6 hits in 1072 CRISPR screens.
DR ChiTaRS; HSD17B2; human.
DR GeneWiki; HSD17B2; -.
DR GenomeRNAi; 3294; -.
DR Pharos; P37059; Tchem.
DR PRO; PR:P37059; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; P37059; protein.
DR Bgee; ENSG00000086696; Expressed in jejunal mucosa and 101 other tissues.
DR ExpressionAtlas; P37059; baseline and differential.
DR Genevisible; P37059; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0047006; F:17-alpha,20-alpha-dihydroxypregn-4-en-3-one dehydrogenase activity; TAS:BHF-UCL.
DR GO; GO:0044594; F:17-beta-hydroxysteroid dehydrogenase (NAD+) activity; IEA:RHEA.
DR GO; GO:0004303; F:estradiol 17-beta-dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0016229; F:steroid dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0047035; F:testosterone dehydrogenase (NAD+) activity; IDA:UniProtKB.
DR GO; GO:0008209; P:androgen metabolic process; IDA:UniProtKB.
DR GO; GO:0006703; P:estrogen biosynthetic process; IDA:UniProtKB.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0001890; P:placenta development; IEA:Ensembl.
DR GO; GO:0032526; P:response to retinoic acid; IDA:BHF-UCL.
DR GO; GO:0008202; P:steroid metabolic process; IBA:GO_Central.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR002347; SDR_fam.
DR Pfam; PF00106; adh_short; 1.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Lipid biosynthesis; Lipid metabolism; Membrane; NAD;
KW Oxidoreductase; Reference proteome; Signal-anchor; Steroid biosynthesis;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..387
FT /note="17-beta-hydroxysteroid dehydrogenase type 2"
FT /id="PRO_0000054570"
FT TRANSMEM 4..24
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT ACT_SITE 232
FT /evidence="ECO:0000250"
FT BINDING 82..111
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 219
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT VARIANT 121
FT /note="A -> T (in dbSNP:rs8191136)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_018852"
SQ SEQUENCE 387 AA; 42785 MW; EDE5606EA041042B CRC64;
MSTFFSDTAW ICLAVPTVLC GTVFCKYKKS SGQLWSWMVC LAGLCAVCLL ILSPFWGLIL
FSVSCFLMYT YLSGQELLPV DQKAVLVTGG DCGLGHALCK YLDELGFTVF AGVLNENGPG
AEELRRTCSP RLSVLQMDIT KPVQIKDAYS KVAAMLQDRG LWAVINNAGV LGFPTDGELL
LMTDYKQCMA VNFFGTVEVT KTFLPLLRKS KGRLVNVSSM GGGAPMERLA SYGSSKAAVT
MFSSVMRLEL SKWGIKVASI QPGGFLTNIA GTSDKWEKLE KDILDHLPAE VQEDYGQDYI
LAQRNFLLLI NSLASKDFSP VLRDIQHAIL AKSPFAYYTP GKGAYLWICL AHYLPIGIYD
YFAKRHFGQD KPMPRALRMP NYKKKAT
