DHRS4_BOVIN
ID DHRS4_BOVIN Reviewed; 279 AA.
AC Q8SPU8; Q2KHU6;
DT 10-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2010, sequence version 2.
DT 03-AUG-2022, entry version 99.
DE RecName: Full=Dehydrogenase/reductase SDR family member 4 {ECO:0000250|UniProtKB:Q8WNV7};
DE EC=1.1.1.184 {ECO:0000250|UniProtKB:Q8WNV7};
DE EC=1.1.1.300 {ECO:0000250|UniProtKB:Q8WNV7};
DE AltName: Full=NADPH-dependent carbonyl reductase {ECO:0000250|UniProtKB:Q8WNV7};
DE Short=CR {ECO:0000250|UniProtKB:Q8WNV7};
DE AltName: Full=NADPH-dependent retinol dehydrogenase/reductase {ECO:0000250|UniProtKB:Q8WNV7};
DE Short=NDRD {ECO:0000250|UniProtKB:Q8WNV7};
DE AltName: Full=Peroxisomal short-chain alcohol dehydrogenase;
DE Short=PSCD;
DE AltName: Full=Short chain dehydrogenase/reductase family 25C member 2 {ECO:0000250|UniProtKB:Q9BTZ2};
DE Short=Protein SDR25C2 {ECO:0000250|UniProtKB:Q9BTZ2};
GN Name=DHRS4; Synonyms=NDRD;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Heart ventricle;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 13-279.
RC TISSUE=Liver;
RA Wang G.L., Liu G.F., Du J., Xu X.L., Gasana V., Wang B., Zhu L.,
RA Huang D.Y.;
RT "Bos taurus NDRD mRNA for NADPH-dependent retinol
RT dehydrogenase/reductase.";
RL Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: NADPH-dependent oxidoreductase which catalyzes the reduction
CC of a variety of compounds bearing carbonyl groups including
CC ketosteroids, alpha-dicarbonyl compounds, aldehydes, aromatic ketones
CC and quinones. Reduces all-trans-retinal and 9-cis retinal. Reduces 3-
CC ketosteroids and benzil into 3alpha-hydroxysteroids and S-benzoin,
CC respectively, in contrast to the stereoselectivity of primates DHRS4s
CC which produce 3beta-hydroxysteroids and R-benzoin. In the reverse
CC reaction, catalyzes the NADP-dependent oxidation of 3alpha-
CC hydroxysteroids and alcohol, but with much lower efficiency. Involved
CC in the metabolism of 3alpha-hydroxysteroids, retinoid, isatin and
CC xenobiotic carbonyl compounds. {ECO:0000250|UniProtKB:Q8WNV7}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a secondary alcohol + NADP(+) = a ketone + H(+) + NADPH;
CC Xref=Rhea:RHEA:19257, ChEBI:CHEBI:15378, ChEBI:CHEBI:17087,
CC ChEBI:CHEBI:35681, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC EC=1.1.1.184; Evidence={ECO:0000250|UniProtKB:Q8WNV7};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:19259;
CC Evidence={ECO:0000250|UniProtKB:Q8WNV7};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3alpha-hydroxy-5beta-pregnan-20-one + NADP(+) = 5beta-pregnan-
CC 3,20-dione + H(+) + NADPH; Xref=Rhea:RHEA:69016, ChEBI:CHEBI:1712,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30154, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; Evidence={ECO:0000250|UniProtKB:Q8WNV7};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69017;
CC Evidence={ECO:0000250|UniProtKB:Q8WNV7};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5beta-dihydrotestosterone + H(+) + NADPH = 5beta-androstane-
CC 3alpha,17beta-diol + NADP(+); Xref=Rhea:RHEA:69028, ChEBI:CHEBI:2150,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:36714, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; Evidence={ECO:0000250|UniProtKB:Q8WNV7};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69029;
CC Evidence={ECO:0000250|UniProtKB:Q8WNV7};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=all-trans-retinol + NADP(+) = all-trans-retinal + H(+) +
CC NADPH; Xref=Rhea:RHEA:25033, ChEBI:CHEBI:15378, ChEBI:CHEBI:17336,
CC ChEBI:CHEBI:17898, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC EC=1.1.1.300; Evidence={ECO:0000250|UniProtKB:Q8WNV7};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:25035;
CC Evidence={ECO:0000250|UniProtKB:Q8WNV7};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + isatin + NADPH = 3-hydroxyindolin-2-one + NADP(+);
CC Xref=Rhea:RHEA:68608, ChEBI:CHEBI:15378, ChEBI:CHEBI:27539,
CC ChEBI:CHEBI:28536, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC Evidence={ECO:0000250|UniProtKB:Q8WNV7};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68609;
CC Evidence={ECO:0000250|UniProtKB:Q8WNV7};
CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:Q8WNV7}.
CC -!- SUBCELLULAR LOCATION: Peroxisome {ECO:0000250|UniProtKB:Q8WNV7}.
CC -!- DOMAIN: The C-terminus peroxisomal targeting signal tripeptide is
CC important for peroxisomal import. Once in the peroxisome, it is
CC involved in intersubunit interactions. {ECO:0000250|UniProtKB:Q8WNV7}.
CC -!- DOMAIN: Three specific residues, Phe-177, Leu-180 and Asn-196 are
CC conserved between non-primate mammals whereas the respective residues
CC are serine, phenylalanine and threonine in primates. The two residues
CC at positions 177 and 180 are molecular determinants responsible for the
CC stereoselective reduction of 3-ketosteroids and benzil. The presence of
CC an asparagine at position 196 is important for the maintenance of the
CC quaternary structure resulting in stability at cold temperature and
CC improved catalytic activity toward retinal.
CC {ECO:0000250|UniProtKB:Q8WNV7}.
CC -!- MISCELLANEOUS: Primate DHRS4s display different stereoselectivity and
CC catalytic efficiency in the oxidoreduction of some substrates as
CC compared to other mammal DHRS4s due to a difference in conserved amino
CC acid residues. {ECO:0000250|UniProtKB:Q8WNV7}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAL93248.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; BC112878; AAI12879.1; -; mRNA.
DR EMBL; AF487454; AAL93248.1; ALT_INIT; mRNA.
DR RefSeq; NP_777247.2; NM_174822.3.
DR AlphaFoldDB; Q8SPU8; -.
DR SMR; Q8SPU8; -.
DR IntAct; Q8SPU8; 1.
DR STRING; 9913.ENSBTAP00000023493; -.
DR PaxDb; Q8SPU8; -.
DR PeptideAtlas; Q8SPU8; -.
DR PRIDE; Q8SPU8; -.
DR GeneID; 281360; -.
DR KEGG; bta:281360; -.
DR CTD; 10901; -.
DR eggNOG; KOG0725; Eukaryota.
DR InParanoid; Q8SPU8; -.
DR OrthoDB; 1194344at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005777; C:peroxisome; ISS:UniProtKB.
DR GO; GO:0004090; F:carbonyl reductase (NADPH) activity; IEA:UniProtKB-EC.
DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR GO; GO:0052650; F:NADP-retinol dehydrogenase activity; ISS:UniProtKB.
DR GO; GO:0042180; P:cellular ketone metabolic process; ISS:UniProtKB.
DR GO; GO:0001523; P:retinoid metabolic process; ISS:UniProtKB.
DR GO; GO:0008202; P:steroid metabolic process; ISS:UniProtKB.
DR InterPro; IPR029511; DHRS4-like.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR002347; SDR_fam.
DR PANTHER; PTHR43943:SF8; PTHR43943:SF8; 1.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 2: Evidence at transcript level;
KW Acetylation; NADP; Oxidoreductase; Peroxisome; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..279
FT /note="Dehydrogenase/reductase SDR family member 4"
FT /id="PRO_0000054646"
FT MOTIF 277..279
FT /note="Peroxisomal targeting signal"
FT ACT_SITE 183
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 37..61
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q8WNV7"
FT BINDING 170
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q99714"
FT BINDING 187
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q8WNV7"
FT SITE 177
FT /note="Responsible for the stereoselective reduction of 3-
FT ketosteroids into 3alpha-hydroxysteroids and benzil into S-
FT benzoin"
FT /evidence="ECO:0000250|UniProtKB:Q8WNV7"
FT SITE 180
FT /note="Responsible for the stereoselective reduction of 3-
FT ketosteroids into 3alpha-hydroxysteroids and benzil into S-
FT benzoin"
FT /evidence="ECO:0000250|UniProtKB:Q8WNV7"
FT SITE 196
FT /note="Important for the maintenance of the quaternary
FT structure, the catalytic activity and cold stability"
FT /evidence="ECO:0000250|UniProtKB:Q8WNV7"
FT MOD_RES 93
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99LB2"
FT MOD_RES 93
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99LB2"
FT MOD_RES 106
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99LB2"
FT MOD_RES 221
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99LB2"
FT MOD_RES 235
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99LB2"
FT CONFLICT 79
FT /note="G -> A (in Ref. 1; AAI12879)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 279 AA; 29440 MW; C0A92C9F0DC8DEF9 CRC64;
MLKVGLPLGA CARSWKSVRM ASCGMARRNP LDNKVALVTA STDGIGFAIA RRLAQDGAHV
VVSSRKQQNV DRAVATLKGE GLSVTGTVCH VGKAEDRERL VATAVKLHGG VDILISNAAV
SPFFGSLMDV PEEVWDKILD VNVKATALLT KAVVPEMAKR GGGSIVIVSS IAAYSPFPSL
GPYNVSKTAL LGLTKNLALE LAESNVRVNC LAPGLIRTSF SRVLWEDPAR QESIKATFQI
KRIGKPEECA GIVSFLCSED ASYITGETVV VAGGSLSHL
