ID   3BHS_VAR67              Reviewed;         210 AA.
AC   Q89187;
DT   21-SEP-2011, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   03-AUG-2022, entry version 94.
DE   RecName: Full=3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase;
DE            Short=3-beta-HSD;
DE   Includes:
DE     RecName: Full=3-beta-hydroxy-Delta(5)-steroid dehydrogenase;
DE              EC=1.1.1.145;
DE     AltName: Full=3-beta-hydroxy-5-ene steroid dehydrogenase;
DE     AltName: Full=Progesterone reductase;
DE   Includes:
DE     RecName: Full=Steroid Delta-isomerase;
DE              EC=5.3.3.1;
DE     AltName: Full=Delta-5-3-ketosteroid isomerase;
GN   Name=A49L;
OS   Variola virus (isolate Human/India/Ind3/1967) (VARV) (Smallpox virus).
OC   Viruses; Varidnaviria; Bamfordvirae; Nucleocytoviricota; Pokkesviricetes;
OC   Chitovirales; Poxviridae; Chordopoxvirinae; Orthopoxvirus.
OX   NCBI_TaxID=587200;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=8384129; DOI=10.1016/0014-5793(93)80041-r;
RA   Shchelkunov S.N., Blinov V.M., Sandakhchiev L.S.;
RT   "Genes of variola and vaccinia viruses necessary to overcome the host
RT   protective mechanisms.";
RL   FEBS Lett. 319:80-83(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=7856312; DOI=10.1016/0168-1702(94)90125-2;
RA   Shchelkunov S.N., Blinov V.M., Resenchuk S.M., Totmenin A.V., Olenina L.V.,
RA   Chirikova G.B., Sandakhchiev L.S.;
RT   "Analysis of the nucleotide sequence of 53 kbp from the right terminus of
RT   the genome of variola major virus strain India-1967.";
RL   Virus Res. 34:207-236(1994).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=7597802; DOI=10.1007/bf01702879;
RA   Shchelkunov S.N., Totmenin A.V.;
RT   "Two types of deletions in orthopoxvirus genomes.";
RL   Virus Genes 9:231-245(1995).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=8725113; DOI=10.1016/0168-1702(95)01269-9;
RA   Shchelkunov S.N., Totmenin A.V., Sandakhchiev L.S.;
RT   "Analysis of the nucleotide sequence of 23.8 kbp from the left terminus of
RT   the genome of variola major virus strain India-1967.";
RL   Virus Res. 40:169-183(1996).
CC   -!- FUNCTION: Catalyzes the oxidative conversion of Delta(5)-ene-3-beta-
CC       hydroxy steroid, and the oxidative conversion of ketosteroids. The 3-
CC       beta-HSD enzymatic system plays a crucial role in the biosynthesis of
CC       all classes of hormonal steroids. During viral infection, steroid
CC       production contributes to virulence by inhibiting the host inflammatory
CC       response (By similarity). {ECO:0000250}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a 3beta-hydroxy-Delta(5)-steroid + NAD(+) = a 3-oxo-Delta(5)-
CC         steroid + H(+) + NADH; Xref=Rhea:RHEA:24076, ChEBI:CHEBI:1722,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:47907, ChEBI:CHEBI:57540,
CC         ChEBI:CHEBI:57945; EC=1.1.1.145;
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a 3-oxo-Delta(5)-steroid = a 3-oxo-Delta(4)-steroid;
CC         Xref=Rhea:RHEA:14709, ChEBI:CHEBI:47907, ChEBI:CHEBI:47909;
CC         EC=5.3.3.1;
CC   -!- PATHWAY: Lipid metabolism; steroid biosynthesis.
CC   -!- SIMILARITY: Belongs to the 3-beta-HSD family. {ECO:0000305}.
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DR   EMBL; X69198; CAA49096.1; -; Genomic_DNA.
DR   PIR; E36853; E36853.
DR   PIR; JQ1850; JQ1850.
DR   RefSeq; NP_042199.1; NC_001611.1.
DR   PRIDE; Q89187; -.
DR   GeneID; 1486530; -.
DR   KEGG; vg:1486530; -.
DR   UniPathway; UPA00062; -.
DR   Proteomes; UP000002060; Genome.
DR   GO; GO:0003854; F:3-beta-hydroxy-delta5-steroid dehydrogenase activity; IEA:UniProtKB-EC.
DR   GO; GO:0102294; F:cholesterol dehydrogenase activity; IEA:UniProtKB-EC.
DR   GO; GO:0004769; F:steroid delta-isomerase activity; IEA:UniProtKB-EC.
DR   GO; GO:0006694; P:steroid biosynthetic process; IEA:UniProtKB-UniPathway.
DR   InterPro; IPR002225; 3Beta_OHSteriod_DH/Estase.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   Pfam; PF01073; 3Beta_HSD; 1.
DR   SUPFAM; SSF51735; SSF51735; 1.
PE   3: Inferred from homology;
KW   Host-virus interaction; Isomerase; Multifunctional enzyme; NAD;
KW   Oxidoreductase; Reference proteome; Steroidogenesis; Viral immunoevasion.
FT   CHAIN           1..210
FT                   /note="3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-
FT                   isomerase"
FT                   /id="PRO_0000412627"
FT   ACT_SITE        29
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250"
FT   BINDING         33
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   210 AA;  24163 MW;  AAAEEB99C00AF08A CRC64;
     MEAIGPNKHG NPFIGHEHTL YDISPGHVYA KSKRMVEQLV TKANNSVIMN GAKLYTCCLR
     PTGIYGGGDK LTKVFYEQCT QHGNIMYRTV DDDAVHSRVY VGNVAWMHVL AVKYIQYPGS
     EIKGNAYFCY GYSPSCSYDM FNLLLMKPLG IEQGSRIPRW MLKMYTCKND MKRILFRKPS
     LLNNYTLKIS NTTFEARQQC RTRFQLLPYL