DHSO_MOUSE
ID DHSO_MOUSE Reviewed; 357 AA.
AC Q64442; Q569V5; Q9CPS0;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 10-JUL-2007, sequence version 3.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=Sorbitol dehydrogenase {ECO:0000303|PubMed:18799757, ECO:0000303|PubMed:6852349, ECO:0000303|PubMed:7601136};
DE Short=SDH;
DE Short=SORD {ECO:0000303|PubMed:18799757};
DE EC=1.1.1.- {ECO:0000269|PubMed:6852349};
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ; TISSUE=Liver;
RX PubMed=7601136; DOI=10.1111/j.1432-1033.1995.tb20656.x;
RA Lee F.K., Lee A.Y.W., Lin C.X.F., Chung S.S.-M., Chung S.K.;
RT "Cloning, sequencing, and determination of the sites of expression of mouse
RT sorbitol dehydrogenase cDNA.";
RL Eur. J. Biochem. 230:1059-1065(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Blastocyst, Lung, and Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney, and Liver;
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 [5]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY
RP REGULATION, SUBUNIT, AND TISSUE SPECIFICITY.
RX PubMed=6852349; DOI=10.1016/0020-711x(83)90124-6;
RA Burnell J.N., Holmes R.S.;
RT "Purification and properties of sorbitol dehydrogenase from mouse liver.";
RL Int. J. Biochem. 15:507-511(1983).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-169, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=18630941; DOI=10.1021/pr800223m;
RA Zhou H., Ye M., Dong J., Han G., Jiang X., Wu R., Zou H.;
RT "Specific phosphopeptide enrichment with immobilized titanium ion affinity
RT chromatography adsorbent for phosphoproteome analysis.";
RL J. Proteome Res. 7:3957-3967(2008).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=18799757; DOI=10.1095/biolreprod.108.068882;
RA Cao W., Aghajanian H.K., Haig-Ladewig L.A., Gerton G.L.;
RT "Sorbitol can fuel mouse sperm motility and protein tyrosine
RT phosphorylation via sorbitol dehydrogenase.";
RL Biol. Reprod. 80:124-133(2009).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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:6852349). 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 (By similarity). May
CC play a role in sperm motility by using sorbitol as an alternative
CC energy source for sperm motility and protein tyrosine phosphorylation
CC (PubMed:18799757). Has no activity on ethanol. Cannot use NADP(+) as
CC the electron acceptor (PubMed:6852349). {ECO:0000250|UniProtKB:Q00796,
CC ECO:0000269|PubMed:18799757, ECO:0000269|PubMed:6852349}.
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:6852349};
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:0000250|UniProtKB:P07846};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:P07846};
CC -!- ACTIVITY REGULATION: Inhibited in vitro by p-hydroxymercuribenzoate,
CC EDTA, l,l0-phenanthroline and N-ethylmaleimide.
CC {ECO:0000269|PubMed:6852349}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.54 mM for sorbitol {ECO:0000269|PubMed:6852349};
CC KM=58.8 uM for NAD(+) {ECO:0000269|PubMed:6852349};
CC KM=154 mM for fructose {ECO:0000269|PubMed:6852349};
CC KM=15 uM for NADH {ECO:0000269|PubMed:6852349};
CC pH dependence:
CC Optimum pH is 9.0 for sorbitol oxidation and 7.5 for D-fructose
CC reduction. {ECO:0000269|PubMed:6852349};
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:6852349}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion membrane
CC {ECO:0000269|PubMed:18799757}; Peripheral membrane protein
CC {ECO:0000269|PubMed:18799757}. Cell projection, cilium, flagellum
CC {ECO:0000269|PubMed:18799757}. Note=Associated with mitochondria of the
CC 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.
CC -!- TISSUE SPECIFICITY: Testis has the highest level of expression,
CC followed by kidney, liver, and lung. Low levels of expression are also
CC observed in lens, brain, and skeletal muscle. Expressed in sperm
CC flagellum and very low expression in the sperm head.
CC {ECO:0000269|PubMed:18799757, ECO:0000269|PubMed:6852349,
CC ECO:0000269|PubMed:7601136}.
CC -!- DEVELOPMENTAL STAGE: Detected early in spermatogenesis. Detected in
CC condensing spermatids (at protein level) and is up-regulated during
CC late spermatogenesis. {ECO:0000269|PubMed:18799757}.
CC -!- SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA79043.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; U27014; AAA79043.1; ALT_INIT; mRNA.
DR EMBL; AK004692; BAB23478.1; -; mRNA.
DR EMBL; AK015059; BAB29695.1; -; mRNA.
DR EMBL; AK166988; BAE39168.1; -; mRNA.
DR EMBL; AK166996; BAE39175.1; -; mRNA.
DR EMBL; AL844566; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL844573; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC024124; AAH24124.1; -; mRNA.
DR EMBL; BC030875; AAH30875.1; -; mRNA.
DR EMBL; BC092291; AAH92291.1; -; mRNA.
DR CCDS; CCDS16657.1; -.
DR PIR; S65956; S65956.
DR RefSeq; NP_666238.1; NM_146126.4.
DR AlphaFoldDB; Q64442; -.
DR SMR; Q64442; -.
DR BioGRID; 203145; 6.
DR STRING; 10090.ENSMUSP00000106180; -.
DR iPTMnet; Q64442; -.
DR MetOSite; Q64442; -.
DR PhosphoSitePlus; Q64442; -.
DR SwissPalm; Q64442; -.
DR REPRODUCTION-2DPAGE; IPI00753038; -.
DR REPRODUCTION-2DPAGE; Q64442; -.
DR CPTAC; non-CPTAC-3910; -.
DR EPD; Q64442; -.
DR jPOST; Q64442; -.
DR MaxQB; Q64442; -.
DR PaxDb; Q64442; -.
DR PeptideAtlas; Q64442; -.
DR PRIDE; Q64442; -.
DR ProteomicsDB; 279648; -.
DR Antibodypedia; 24307; 573 antibodies from 32 providers.
DR DNASU; 20322; -.
DR Ensembl; ENSMUST00000110551; ENSMUSP00000106180; ENSMUSG00000027227.
DR GeneID; 20322; -.
DR KEGG; mmu:20322; -.
DR UCSC; uc008maj.1; mouse.
DR CTD; 6652; -.
DR MGI; MGI:98266; Sord.
DR VEuPathDB; HostDB:ENSMUSG00000027227; -.
DR eggNOG; KOG0024; Eukaryota.
DR GeneTree; ENSGT00550000074781; -.
DR HOGENOM; CLU_026673_11_5_1; -.
DR InParanoid; Q64442; -.
DR OMA; ETWYAMS; -.
DR OrthoDB; 1019156at2759; -.
DR PhylomeDB; Q64442; -.
DR TreeFam; TF313060; -.
DR Reactome; R-MMU-5652227; Fructose biosynthesis.
DR Reactome; R-MMU-5661270; Formation of xylulose-5-phosphate.
DR BioGRID-ORCS; 20322; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Sord; mouse.
DR PRO; PR:Q64442; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q64442; protein.
DR Bgee; ENSMUSG00000027227; Expressed in seminiferous tubule of testis and 222 other tissues.
DR Genevisible; Q64442; MM.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0070062; C:extracellular exosome; ISO:MGI.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0031514; C:motile cilium; IDA:UniProtKB.
DR GO; GO:0047833; F:D-sorbitol dehydrogenase (acceptor) activity; IDA:MGI.
DR GO; GO:0046526; F:D-xylulose reductase activity; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0003939; F:L-iditol 2-dehydrogenase activity; IDA:MGI.
DR GO; GO:0051287; F:NAD binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; ISO:MGI.
DR GO; GO:0030317; P:flagellated sperm motility; IDA:UniProtKB.
DR GO; GO:0046370; P:fructose biosynthetic process; IDA:MGI.
DR GO; GO:0019640; P:glucuronate catabolic process to xylulose 5-phosphate; IDA:MGI.
DR GO; GO:0051160; P:L-xylitol catabolic process; ISO:MGI.
DR GO; GO:0051164; P:L-xylitol metabolic process; ISO:MGI.
DR GO; GO:0046686; P:response to cadmium ion; ISO:MGI.
DR GO; GO:0046688; P:response to copper ion; ISO:MGI.
DR GO; GO:0009725; P:response to hormone; ISO:MGI.
DR GO; GO:0031667; P:response to nutrient levels; IEA:Ensembl.
DR GO; GO:0006970; P:response to osmotic stress; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0006062; P:sorbitol catabolic process; ISO:MGI.
DR GO; GO:0006060; P:sorbitol metabolic process; IDA:MGI.
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_0000000882"
FT BINDING 45
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P07846"
FT BINDING 51
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P07846"
FT BINDING 70
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P07846"
FT BINDING 71
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P07846"
FT BINDING 156
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P07846"
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:0000250|UniProtKB:Q00796"
FT BINDING 209
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q00796"
FT BINDING 273..275
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q00796"
FT BINDING 297..299
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q00796"
FT BINDING 299
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P07846"
FT BINDING 300
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P07846"
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:18630941"
FT CONFLICT 49
FT /note="V -> L (in Ref. 1; AAA79043)"
FT /evidence="ECO:0000305"
FT CONFLICT 259
FT /note="T -> S (in Ref. 1; AAA79043)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 357 AA; 38249 MW; FDAA462EF1EB6C21 CRC64;
MAAPAKGENL SLVVHGPGDI RLENYPIPEL GPNDVLLKMH SVGICGSDVH YWEHGRIGDF
VVKKPMVLGH EAAGTVTKVG ELVKHLKPGD RVAIEPGVPR EVDEYCKIGR YNLTPTIFFC
ATPPDDGNLC RFYKHNADFC YKLPDSVTFE EGALIEPLSV GIYACRRGSV SLGNKVLVCG
AGPVGMVTLL VAKAMGAAQV VVTDLSASRL TKAKEVGADF TIQVGKETPQ EIASKVESLL
GSKPEVTIEC TGAESSVQTG IYATHSGGTL VIVGMGAEMV NLPLVHAAIR EVDIKGVFRY
CNTWPMAISM LASKTLNVKP LVTHRFPLEK AVEAFETAKK GVGLKVMIKC DPNDQNP
