DHRS4_PONAB
ID DHRS4_PONAB Reviewed; 278 AA.
AC Q5RCF8; Q5RAT3;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2010, sequence version 3.
DT 03-AUG-2022, entry version 84.
DE RecName: Full=Dehydrogenase/reductase SDR family member 4 {ECO:0000250|UniProtKB:Q9BTZ2};
DE EC=1.1.1.184 {ECO:0000250|UniProtKB:Q9BTZ2};
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;
DE Short=NDRD;
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;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-2004) 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 3-ketosteroids and benzil into 3beta-
CC hydroxysteroids and R-benzoin, respectively, in contrast to the
CC stereoselectivity of non-primate DHRS4s which produce 3alpha-
CC hydroxysteroids and S-benzoin. Diplays low activity toward all-trans-
CC retinal and no activity toward 9-cis-retinal as compared to non-primate
CC mammals. In the reverse reaction, catalyze the NAD-dependent oxidation
CC of 3beta-hydroxysteroids and alcohol, but with much lower efficiency.
CC Involved in the metabolism of 3beta-hydroxysteroids, isatin and
CC xenobiotic carbonyl compounds. {ECO:0000250|UniProtKB:Q9BTZ2}.
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:Q9BTZ2};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:19259;
CC Evidence={ECO:0000250|UniProtKB:Q9BTZ2};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3beta-hydroxy-5beta-pregnane-20-one + NADP(+) = 5beta-pregnan-
CC 3,20-dione + H(+) + NADPH; Xref=Rhea:RHEA:22944, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16229, ChEBI:CHEBI:30154, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; Evidence={ECO:0000250|UniProtKB:Q9BTZ2};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:22946;
CC Evidence={ECO:0000250|UniProtKB:Q9BTZ2};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5beta-dihydrotestosterone + H(+) + NADPH = 5beta-androstane-
CC 3beta,17beta-diol + NADP(+); Xref=Rhea:RHEA:69012, ChEBI:CHEBI:2150,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:36715, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; Evidence={ECO:0000250|UniProtKB:Q9BTZ2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69013;
CC Evidence={ECO:0000250|UniProtKB:Q9BTZ2};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5beta-androstane-3,17-dione + H(+) + NADPH = 3beta-hydroxy-
CC 5beta-androstane-17-one + NADP(+); Xref=Rhea:RHEA:69036,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16985, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:89524;
CC Evidence={ECO:0000250|UniProtKB:Q9BTZ2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69037;
CC Evidence={ECO:0000250|UniProtKB:Q9BTZ2};
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:Q9BTZ2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68609;
CC Evidence={ECO:0000250|UniProtKB:Q9BTZ2};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=lithocholate + NADP(+) = 3-oxo-5beta-cholan-24-oate + H(+) +
CC NADPH; Xref=Rhea:RHEA:47496, ChEBI:CHEBI:11867, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29744, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC Evidence={ECO:0000250|UniProtKB:Q9BTZ2};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:47498;
CC Evidence={ECO:0000250|UniProtKB:Q9BTZ2};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-oxo-5beta-cholan-24-oate + H(+) + NADPH = isolithocholate +
CC NADP(+); Xref=Rhea:RHEA:47520, ChEBI:CHEBI:11867, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:87728;
CC Evidence={ECO:0000250|UniProtKB:Q9BTZ2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47521;
CC Evidence={ECO:0000250|UniProtKB:Q9BTZ2};
CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:Q9GKX2}.
CC -!- SUBCELLULAR LOCATION: Peroxisome {ECO:0000250|UniProtKB:Q9BTZ2}.
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, Ser-176, Phe-179 and Thr-195 are
CC conserved between primates whereas the respective residues are
CC phenylalanine, leucine, and asparagine in the other mammal enzymes. The
CC two residues at positions 176 and 179 are molecular determinants
CC responsible for the stereoselective reduction of 3-ketosteroids and
CC benzil. The presence of an asparagine at position 195 is important for
CC the maintenance of the quaternary structure and stability at cold
CC temperature. The absence of an asparagine at position 195 destabilizes
CC the quaternary structure, thereby affecting catalytic efficiency toward
CC some substrates and decreasing stability at cold temperature.
CC {ECO:0000250|UniProtKB:Q9BTZ2}.
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:Q9BTZ2}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; CR858312; CAH90549.1; -; mRNA.
DR EMBL; CR858929; CAH91127.1; -; mRNA.
DR RefSeq; NP_001125292.1; NM_001131820.2.
DR RefSeq; XP_009247234.1; XM_009248959.1.
DR AlphaFoldDB; Q5RCF8; -.
DR SMR; Q5RCF8; -.
DR STRING; 9601.ENSPPYP00000006452; -.
DR Ensembl; ENSPPYT00000006707; ENSPPYP00000006452; ENSPPYG00000005675.
DR GeneID; 100172190; -.
DR KEGG; pon:100172190; -.
DR CTD; 10901; -.
DR eggNOG; KOG0725; Eukaryota.
DR GeneTree; ENSGT00940000158919; -.
DR InParanoid; Q5RCF8; -.
DR OrthoDB; 1194344at2759; -.
DR Proteomes; UP000001595; Chromosome 14.
DR GO; GO:0005778; C:peroxisomal membrane; IEA:Ensembl.
DR GO; GO:0000253; F:3-keto sterol reductase activity; IEA:Ensembl.
DR GO; GO:0033703; F:3beta-hydroxy-5beta-steroid dehydrogenase activity; IEA:RHEA.
DR GO; GO:0018455; F:alcohol dehydrogenase [NAD(P)+] activity; IEA:Ensembl.
DR GO; GO:0004090; F:carbonyl reductase (NADPH) activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR GO; GO:0016655; F:oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor; IEA:Ensembl.
DR GO; GO:0006066; P:alcohol metabolic process; IEA:Ensembl.
DR GO; GO:0042180; P:cellular ketone metabolic process; ISS:UniProtKB.
DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; IEA:Ensembl.
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..278
FT /note="Dehydrogenase/reductase SDR family member 4"
FT /id="PRO_0000054650"
FT MOTIF 276..278
FT /note="Peroxisomal targeting signal"
FT ACT_SITE 182
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 36..60
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q8WNV7"
FT BINDING 169
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q99714"
FT BINDING 186
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q8WNV7"
FT SITE 176
FT /note="Responsible for the stereoselective reduction of 3-
FT ketosteroids into 3beta-hydroxysteroids and benzil into R-
FT benzoin"
FT /evidence="ECO:0000250|UniProtKB:Q9BTZ2"
FT SITE 179
FT /note="Responsible for the stereoselective reduction of 3-
FT ketosteroids into 3beta-hydroxysteroids and benzil into R-
FT benzoin"
FT /evidence="ECO:0000250|UniProtKB:Q9BTZ2"
FT MOD_RES 92
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99LB2"
FT MOD_RES 92
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99LB2"
FT MOD_RES 105
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99LB2"
FT MOD_RES 216
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99LB2"
FT MOD_RES 216
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99LB2"
FT MOD_RES 220
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99LB2"
FT MOD_RES 227
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99LB2"
FT MOD_RES 234
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99LB2"
SQ SEQUENCE 278 AA; 29552 MW; 4C15BCF9BDB01C2B CRC64;
MHKAGQLGLC ARAWNSVRMA SSGMTRRDPL ANKVALVTAS TDGIGFAIAR RLAQDGAHVV
VSSRKQQNVD QAVATLQGEG LSVTGTVCHV GKAEDRERLV ATAVKLHGGI DILVSNAAVN
PFFGSLMDVT EEVWDKTLDI NVKAPALMTK AVVPEMEKRG GGSVVIVSSI AAFSPSPGFS
PYNVSKTALL GLTKTLAIEL APRNIRVNCL APGLIKTSFS RMLWMDKEKE ESMKETLRIR
RLGEPEDCAG IVSFLCSEDA SYITGETVVV GGGTPSRL
