DHSO_RAT
ID DHSO_RAT Reviewed; 357 AA.
AC P27867; A2VCV9; Q4FZY4; Q5I0F3;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 10-JUL-2007, sequence version 4.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Sorbitol dehydrogenase {ECO:0000303|PubMed:11306057, ECO:0000303|PubMed:6862079};
DE Short=SDH {ECO:0000303|PubMed:11306057};
DE EC=1.1.1.- {ECO:0000269|PubMed:6862079};
DE AltName: Full=L-iditol 2-dehydrogenase;
DE EC=1.1.1.14 {ECO:0000250|UniProtKB:P07846};
DE AltName: Full=Polyol dehydrogenase {ECO:0000305};
DE AltName: Full=Xylitol dehydrogenase;
DE Short=XDH;
DE EC=1.1.1.9 {ECO:0000250|UniProtKB:P07846};
GN Name=Sord; Synonyms=Sdh1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=2050152; DOI=10.1111/j.1432-1033.1991.tb16077.x;
RA Karlsson C., Joernvall H., Heoeog J.O.;
RT "Sorbitol dehydrogenase: cDNA coding for the rat enzyme. Variations within
RT the alcohol dehydrogenase family independent of quaternary structure and
RT metal content.";
RL Eur. J. Biochem. 198:761-765(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Testis;
RX PubMed=8223590; DOI=10.1111/j.1432-1033.1993.tb18221.x;
RA Wen Y., Bekhor I.;
RT "Sorbitol dehydrogenase. Full-length cDNA sequencing reveals a mRNA coding
RT for a protein containing an additional 42 amino acids at the N-terminal
RT end.";
RL Eur. J. Biochem. 217:83-87(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryonic liver, Liver, and Testis;
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 [4]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY
RP REGULATION, SUBUNIT, AND TISSUE SPECIFICITY.
RX PubMed=6862079; DOI=10.1016/0020-711x(83)90189-1;
RA Leissing N.C., McGuinness E.T.;
RT "Kinetic analysis of rat liver sorbitol dehydrogenase.";
RL Int. J. Biochem. 15:651-656(1983).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-169, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) IN COMPLEX WITH ZINC AND NAD(+),
RP COFACTOR, SUBUNIT, AND DOMAIN.
RX PubMed=11306057; DOI=10.1016/s0009-2797(00)00260-x;
RA Johansson K., El-Ahmad M., Kaiser C., Joernvall H., Eklund H., Hoeoeg J.,
RA Ramaswamy S.;
RT "Crystal structure of sorbitol dehydrogenase.";
RL Chem. Biol. Interact. 130:351-358(2001).
CC -!- FUNCTION: Polyol dehydrogenase that catalyzes the reversible NAD(+)-
CC dependent oxidation of various sugar alcohols (By similarity). Is
CC active with D-sorbitol (D-glucitol) leading to the C2-oxidized product
CC D-fructose (PubMed:6862079). Is a key enzyme in the polyol pathway that
CC interconverts glucose and fructose via sorbitol, which constitutes an
CC important alternate route for glucose metabolism. May play a role in
CC sperm motility by using sorbitol as an alternative energy source for
CC sperm motility (By similarity). {ECO:0000250|UniProtKB:Q00796,
CC ECO:0000269|PubMed:6862079}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + keto-D-fructose + NADH = D-sorbitol + NAD(+);
CC Xref=Rhea:RHEA:33031, ChEBI:CHEBI:15378, ChEBI:CHEBI:17924,
CC ChEBI:CHEBI:48095, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC Evidence={ECO:0000269|PubMed:6862079};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NAD(+) + xylitol = D-xylulose + H(+) + NADH;
CC Xref=Rhea:RHEA:20433, ChEBI:CHEBI:15378, ChEBI:CHEBI:17140,
CC ChEBI:CHEBI:17151, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.9;
CC Evidence={ECO:0000250|UniProtKB:P07846};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-iditol + NAD(+) = H(+) + keto-L-sorbose + NADH;
CC Xref=Rhea:RHEA:10160, ChEBI:CHEBI:13172, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:18202, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.14;
CC Evidence={ECO:0000250|UniProtKB:P07846};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:11306057};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:11306057};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.38 mM for sorbitol {ECO:0000269|PubMed:6862079};
CC KM=0.082 mM for NAD(+) {ECO:0000269|PubMed:6862079};
CC KM=136 mM for D-fructose {ECO:0000269|PubMed:6862079};
CC KM=67 uM for NADH {ECO:0000269|PubMed:6862079};
CC Vmax=0.229 umol/min/mg enzyme for sorbitol oxidation
CC {ECO:0000269|PubMed:6862079};
CC Vmax=5.84 umol/min/mg enzyme for D-fructose reduction
CC {ECO:0000269|PubMed:6862079};
CC Note=kcat is 8 sec(-1) for sorbitol oxidation and 190 sec(-1) for D-
CC fructose reduction.;
CC -!- SUBUNIT: Homotetramer; dimer of dimers. {ECO:0000269|PubMed:11306057}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion membrane
CC {ECO:0000250|UniProtKB:Q64442}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q64442}. Cell projection, cilium, flagellum
CC {ECO:0000250|UniProtKB:Q64442}. Note=Associated with mitochondria of
CC the midpiece and near the plasma membrane in the principal piece of the
CC flagellum. Also found in the epididymosome, secreted by the epididymal
CC epithelium and that transfers proteins from the epididymal fluid to the
CC sperm surface. {ECO:0000250|UniProtKB:Q64442}.
CC -!- TISSUE SPECIFICITY: Expressed in liver and testis.
CC {ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:2050152,
CC ECO:0000269|PubMed:6862079, ECO:0000269|PubMed:8223590}.
CC -!- DOMAIN: Consists of two distinct domains, a catalytic domain and a
CC coenzyme-binding domain. {ECO:0000269|PubMed:11306057}.
CC -!- SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase
CC family. {ECO:0000305}.
CC -!- CAUTION: PubMed:8223590 reports a cDNA predicted to encode a protein
CC with an extended N-terminus but there is no further evidence for the
CC existence of such a protein. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA52670.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; X59037; CAA41761.1; -; mRNA.
DR EMBL; X74593; CAA52670.1; ALT_INIT; mRNA.
DR EMBL; BC088398; AAH88398.2; -; mRNA.
DR EMBL; BC098919; AAH98919.2; -; mRNA.
DR EMBL; BC128707; AAI28708.2; -; mRNA.
DR PIR; S38363; S16132.
DR RefSeq; NP_058748.2; NM_017052.2.
DR AlphaFoldDB; P27867; -.
DR SMR; P27867; -.
DR STRING; 10116.ENSRNOP00000023350; -.
DR BindingDB; P27867; -.
DR ChEMBL; CHEMBL4038; -.
DR iPTMnet; P27867; -.
DR PhosphoSitePlus; P27867; -.
DR jPOST; P27867; -.
DR PaxDb; P27867; -.
DR PRIDE; P27867; -.
DR GeneID; 24788; -.
DR KEGG; rno:24788; -.
DR UCSC; RGD:3734; rat.
DR CTD; 6652; -.
DR RGD; 3734; Sord.
DR VEuPathDB; HostDB:ENSRNOG00000017291; -.
DR eggNOG; KOG0024; Eukaryota.
DR HOGENOM; CLU_026673_11_5_1; -.
DR InParanoid; P27867; -.
DR OMA; ETWYAMS; -.
DR OrthoDB; 1019156at2759; -.
DR PhylomeDB; P27867; -.
DR TreeFam; TF313060; -.
DR Reactome; R-RNO-5652227; Fructose biosynthesis.
DR Reactome; R-RNO-5661270; Formation of xylulose-5-phosphate.
DR SABIO-RK; P27867; -.
DR PRO; PR:P27867; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Bgee; ENSRNOG00000017291; Expressed in adult mammalian kidney and 19 other tissues.
DR Genevisible; P27867; RN.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular exosome; ISO:RGD.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; ISO:RGD.
DR GO; GO:0031514; C:motile cilium; ISS:UniProtKB.
DR GO; GO:0047833; F:D-sorbitol dehydrogenase (acceptor) activity; IEA:Ensembl.
DR GO; GO:0046526; F:D-xylulose reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0042802; F:identical protein binding; IDA:RGD.
DR GO; GO:0003939; F:L-iditol 2-dehydrogenase activity; ISO:RGD.
DR GO; GO:0051287; F:NAD binding; ISO:RGD.
DR GO; GO:0008270; F:zinc ion binding; IDA:RGD.
DR GO; GO:0030317; P:flagellated sperm motility; ISS:UniProtKB.
DR GO; GO:0046370; P:fructose biosynthetic process; ISO:RGD.
DR GO; GO:0051160; P:L-xylitol catabolic process; ISO:RGD.
DR GO; GO:0051164; P:L-xylitol metabolic process; ISO:RGD.
DR GO; GO:0046686; P:response to cadmium ion; IDA:RGD.
DR GO; GO:0046688; P:response to copper ion; IDA:RGD.
DR GO; GO:0009725; P:response to hormone; IDA:RGD.
DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
DR GO; GO:0006970; P:response to osmotic stress; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0006062; P:sorbitol catabolic process; ISO:RGD.
DR GO; GO:0006060; P:sorbitol metabolic process; ISO:RGD.
DR CDD; cd05285; sorbitol_DH; 1.
DR InterPro; IPR013149; ADH-like_C.
DR InterPro; IPR013154; ADH_N.
DR InterPro; IPR002328; ADH_Zn_CS.
DR InterPro; IPR011032; GroES-like_sf.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020843; PKS_ER.
DR InterPro; IPR045306; SDH-like.
DR Pfam; PF08240; ADH_N; 1.
DR Pfam; PF00107; ADH_zinc_N; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SUPFAM; SSF50129; SSF50129; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00059; ADH_ZINC; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cell projection; Cilium; Flagellum; Membrane; Metal-binding;
KW Mitochondrion; NAD; Oxidoreductase; Phosphoprotein; Reference proteome;
KW Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q00796"
FT CHAIN 2..357
FT /note="Sorbitol dehydrogenase"
FT /id="PRO_0000000884"
FT BINDING 45
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:11306057"
FT BINDING 51
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P07846,
FT ECO:0000305|PubMed:11306057"
FT BINDING 70
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:11306057"
FT BINDING 71
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:11306057"
FT BINDING 156
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P07846,
FT ECO:0000305|PubMed:11306057"
FT BINDING 156
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:11306057"
FT BINDING 184
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q00796"
FT BINDING 204
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:11306057"
FT BINDING 209
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:11306057"
FT BINDING 273..275
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:11306057"
FT BINDING 297..299
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:11306057"
FT BINDING 299
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P07846,
FT ECO:0000305|PubMed:11306057"
FT BINDING 300
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P07846,
FT ECO:0000305|PubMed:11306057"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q00796"
FT MOD_RES 169
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CONFLICT 259
FT /note="T -> D (in Ref. 1; CAA41761)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 357 AA; 38235 MW; E6F535775EF73D36 CRC64;
MAAPAKGENL SLVVHGPGDI RLENYPIPEL GPNDVLLKMH SVGICGSDVH YWEHGRIGDF
VVKKPMVLGH EAAGTVTKVG PMVKHLKPGD RVAIEPGVPR EIDEFCKIGR YNLTPSIFFC
ATPPDDGNLC RFYKHSADFC YKLPDSVTFE EGALIEPLSV GIYACRRGSV SLGNKVLVCG
AGPIGIVTLL VAKAMGASQV VVIDLSASRL AKAKEVGADF TIQVAKETPH DIAKKVESVL
GSKPEVTIEC TGAESSVQTG IYATHSGGTL VVVGMGPEMI NLPLVHAAVR EVDIKGVFRY
CNTWPMAVSM LASKTLNVKP LVTHRFPLEK AVEAFETAKK GLGLKVMIKC DPNDQNP
