UniProtKB - Q00796 (DHSO_HUMAN)
Protein
Sorbitol dehydrogenase
Gene
SORD
Organism
Homo sapiens (Human)
Status
Functioni
Polyol dehydrogenase that catalyzes the reversible NAD+-dependent oxidation of various sugar alcohols. Is mostly active with D-sorbitol (D-glucitol), L-threitol, xylitol and ribitol as substrates, leading to the C2-oxidized products D-fructose, L-erythrulose, D-xylulose, and D-ribulose, respectively (PubMed:3365415). Is a key enzyme in the polyol pathway that interconverts glucose and fructose via sorbitol, which constitutes an important alternate route for glucose metabolism. The polyol pathway is believed to be involved in the etiology of diabetic complications, such as diabetic neuropathy and retinopathy, induced by hyperglycemia (PubMed:12962626, PubMed:29966615, PubMed:25105142). May play a role in sperm motility by using sorbitol as an alternative energy source for sperm motility (PubMed:16278369). May have a more general function in the metabolism of secondary alcohols since it also catalyzes the stereospecific oxidation of (2R,3R)-2,3-butanediol. To a lesser extent, can also oxidize L-arabinitol, galactitol and D-mannitol and glycerol in vitro. Oxidizes neither ethanol nor other primary alcohols. Cannot use NADP+ as the electron acceptor (PubMed:3365415).2 Publications1 Publication2 Publications
Catalytic activityi
- This reaction proceeds in the backward1 Publication direction.
- EC:1.1.1.91 Publication
- EC:1.1.1.561 Publication
- EC:1.1.1.41 Publication
- EC:1.1.1.14By similarity
Cofactori
Zn2+2 PublicationsNote: Binds 1 zinc ion per subunit.2 Publications
Activity regulationi
Inhibited by CP-166,572, an inhibitor that is competitive with fructose (PubMed:12962626). Also competitively inhibited by phenanthroline and 4-methylpyrazole in vitro (PubMed:3365415).2 Publications
Kineticsi
kcat is 1.7 sec(-1) for the oxidation of D-sorbitol at pH 7.1, and 5.2 sec(-1) at pH 10.0. kcat is 5.9 sec(-1) the oxidation of xylitol as substrate at pH 10.0. kcat is 5.3 sec(-1) the oxidation of L-threitol as substrate at pH 10.0. kcat is 4.2 sec(-1) the oxidation of (2R,3R)-2,3-butanediol as substrate at pH 10.0. kcat is 45 sec(-1) for the reduction of D-fructose at pH 7.1.1 Publication
- KM=1.5 mM for sorbitol1 Publication
- KM=225 µM for NAD+1 Publication
- KM=210 µM for NADH1 Publication
- KM=0.62 mM for D-sorbitol (at pH 7.1)1 Publication
- KM=0.67 mM for D-sorbitol (at pH 10.0)1 Publication
- KM=0.22 mM for xylitol (at pH 10.0)1 Publication
- KM=2.7 mM for L-threitol (at pH 10.0)1 Publication
- KM=9.5 mM for (2R,3R)-2,3-butanediol (at pH 10.0)1 Publication
- KM=0.14 M for D-fructose (at pH 7.1)1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 45 | Zinc; catalyticCombined sources1 Publication | 1 | |
Binding sitei | 51 | SubstrateBy similarity | 1 | |
Metal bindingi | 70 | Zinc; catalyticCombined sources1 Publication | 1 | |
Metal bindingi | 71 | Zinc; catalyticCombined sources1 Publication | 1 | |
Binding sitei | 156 | SubstrateBy similarity | 1 | |
Binding sitei | 184 | NAD; via amide nitrogenCombined sources1 Publication | 1 | |
Binding sitei | 204 | NADCombined sources1 Publication | 1 | |
Binding sitei | 209 | NADCombined sources1 Publication | 1 | |
Binding sitei | 299 | SubstrateBy similarity | 1 | |
Binding sitei | 300 | SubstrateBy similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 273 – 275 | NADCombined sources1 Publication | 3 | |
Nucleotide bindingi | 297 – 299 | NADCombined sources1 Publication | 3 |
GO - Molecular functioni
- (R,R)-butanediol dehydrogenase activity Source: UniProtKB-EC
- carbohydrate binding Source: UniProtKB
- D-xylulose reductase activity Source: UniProtKB-EC
- identical protein binding Source: IntAct
- L-iditol 2-dehydrogenase activity Source: UniProtKB
- NAD binding Source: UniProtKB
- ribitol 2-dehydrogenase activity Source: UniProtKB-EC
- zinc ion binding Source: UniProtKB
GO - Biological processi
- flagellated sperm motility Source: UniProtKB
- fructose biosynthetic process Source: UniProtKB
- glucose metabolic process Source: UniProtKB
- glucuronate catabolic process to xylulose 5-phosphate Source: Reactome
- L-xylitol catabolic process Source: UniProtKB
- L-xylitol metabolic process Source: UniProtKB
- response to cadmium ion Source: Ensembl
- response to copper ion Source: Ensembl
- response to drug Source: Ensembl
- response to hormone Source: Ensembl
- response to nutrient levels Source: Ensembl
- response to osmotic stress Source: Ensembl
- sorbitol catabolic process Source: UniProtKB
Keywordsi
Molecular function | Oxidoreductase |
Ligand | Metal-binding, NAD, Zinc |
Enzyme and pathway databases
BRENDAi | 1.1.1.14, 2681 |
PathwayCommonsi | Q00796 |
Reactomei | R-HSA-5652227, Fructose biosynthesis R-HSA-5661270, Formation of xylulose-5-phosphate |
SABIO-RKi | Q00796 |
Names & Taxonomyi
Protein namesi | |
Gene namesi | Name:SORD |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:11184, SORD |
MIMi | 182500, gene |
neXtProti | NX_Q00796 |
VEuPathDBi | HostDB:ENSG00000140263.13 |
Subcellular locationi
Mitochondrion
- Mitochondrion membrane By similarity; Peripheral membrane protein By similarity
Other locations
- flagellum By similarity
Note: Associated with mitochondria of the midpiece and near the plasma membrane in the principal piece of the flagellum. Also found in the epididymosome, secreted by the epididymal epithelium and that transfers proteins from the epididymal fluid to the sperm surface.By similarity
Cytosol
- cytosol Source: Reactome
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
- extracellular space Source: UniProtKB
Mitochondrion
- mitochondrial membrane Source: UniProtKB-SubCell
Other locations
- membrane Source: UniProtKB
- motile cilium Source: UniProtKB
Keywords - Cellular componenti
Cell projection, Cilium, Flagellum, Membrane, MitochondrionPathology & Biotechi
Organism-specific databases
DisGeNETi | 6652 |
OpenTargetsi | ENSG00000140263 |
PharmGKBi | PA36021 |
Miscellaneous databases
Pharosi | Q00796, Tchem |
Chemistry databases
ChEMBLi | CHEMBL2275 |
DrugBanki | DB04478, Cp-166572, 2-Hydroxymethyl-4-(4-N,N-Dimethylaminosulfonyl-1-Piperazino)-Pyrimidine DB00157, NADH |
DrugCentrali | Q00796 |
Genetic variation databases
BioMutai | SORD |
DMDMi | 292495088 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedCombined sources2 Publications | |||
ChainiPRO_0000160817 | 2 – 357 | Sorbitol dehydrogenaseAdd BLAST | 356 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylalanineCombined sources | 1 | |
Modified residuei | 211 | PhosphoserineCombined sources | 1 | |
Modified residuei | 225 | PhosphoserineCombined sources | 1 |
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
EPDi | Q00796 |
jPOSTi | Q00796 |
MassIVEi | Q00796 |
MaxQBi | Q00796 |
PaxDbi | Q00796 |
PeptideAtlasi | Q00796 |
PRIDEi | Q00796 |
ProteomicsDBi | 57873 [Q00796-1] 6501 |
2D gel databases
REPRODUCTION-2DPAGEi | IPI00216057 |
PTM databases
iPTMneti | Q00796 |
MetOSitei | Q00796 |
PhosphoSitePlusi | Q00796 |
SwissPalmi | Q00796 |
Expressioni
Tissue specificityi
Expressed in liver (PubMed:3365415). Expressed in kidney and epithelial cells of both benign and malignant prostate tissue. Expressed in epididymis (at protein level).4 Publications
Inductioni
Up-regulated by androgens and down-regulated by castration.1 Publication
Gene expression databases
Bgeei | ENSG00000140263, Expressed in thyroid gland and 161 other tissues |
ExpressionAtlasi | Q00796, baseline and differential |
Genevisiblei | Q00796, HS |
Organism-specific databases
HPAi | ENSG00000140263, Tissue enhanced (cervix, uterine, liver, thyroid gland) |
Interactioni
Subunit structurei
Homotetramer.
2 PublicationsBinary interactionsi
Q00796
With | #Exp. | IntAct |
---|---|---|
itself | 6 | EBI-750068,EBI-750068 |
GO - Molecular functioni
- identical protein binding Source: IntAct
Protein-protein interaction databases
BioGRIDi | 112535, 75 interactors |
IntActi | Q00796, 13 interactors |
MINTi | Q00796 |
STRINGi | 9606.ENSP00000267814 |
Chemistry databases
BindingDBi | Q00796 |
Miscellaneous databases
RNActi | Q00796, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q00796 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q00796 |
Family & Domainsi
Sequence similaritiesi
Belongs to the zinc-containing alcohol dehydrogenase family.Curated
Phylogenomic databases
eggNOGi | KOG0024, Eukaryota |
GeneTreei | ENSGT00550000074781 |
HOGENOMi | CLU_168382_0_0_1 |
InParanoidi | Q00796 |
OMAi | ETWYAMS |
OrthoDBi | 1019156at2759 |
PhylomeDBi | Q00796 |
TreeFami | TF313060 |
Family and domain databases
InterProi | View protein in InterPro IPR013149, ADH_C IPR013154, ADH_N IPR002328, ADH_Zn_CS IPR011032, GroES-like_sf IPR036291, NAD(P)-bd_dom_sf IPR020843, PKS_ER |
Pfami | View protein in Pfam PF08240, ADH_N, 1 hit PF00107, ADH_zinc_N, 1 hit |
SMARTi | View protein in SMART SM00829, PKS_ER, 1 hit |
SUPFAMi | SSF50129, SSF50129, 1 hit SSF51735, SSF51735, 1 hit |
PROSITEi | View protein in PROSITE PS00059, ADH_ZINC, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q00796-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MAAAAKPNNL SLVVHGPGDL RLENYPIPEP GPNEVLLRMH SVGICGSDVH
60 70 80 90 100
YWEYGRIGNF IVKKPMVLGH EASGTVEKVG SSVKHLKPGD RVAIEPGAPR
110 120 130 140 150
ENDEFCKMGR YNLSPSIFFC ATPPDDGNLC RFYKHNAAFC YKLPDNVTFE
160 170 180 190 200
EGALIEPLSV GIHACRRGGV TLGHKVLVCG AGPIGMVTLL VAKAMGAAQV
210 220 230 240 250
VVTDLSATRL SKAKEIGADL VLQISKESPQ EIARKVEGQL GCKPEVTIEC
260 270 280 290 300
TGAEASIQAG IYATRSGGNL VLVGLGSEMT TVPLLHAAIR EVDIKGVFRY
310 320 330 340 350
CNTWPVAISM LASKSVNVKP LVTHRFPLEK ALEAFETFKK GLGLKIMLKC
DPSDQNP
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A6I8PIS1 | A0A6I8PIS1_HUMAN | Sorbitol dehydrogenase | SORD | 252 | Annotation score: | ||
H0YKB3 | H0YKB3_HUMAN | Sorbitol dehydrogenase | SORD | 117 | Annotation score: | ||
A0A6I8PRA7 | A0A6I8PRA7_HUMAN | Sorbitol dehydrogenase | SORD | 25 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 5 | Missing AA sequence (PubMed:2691249).Curated | 1 | |
Sequence conflicti | 59 | N → D AA sequence (PubMed:2691249).Curated | 1 | |
Sequence conflicti | 186 | M → E AA sequence (PubMed:2691249).Curated | 1 | |
Sequence conflicti | 281 | T → S AA sequence (PubMed:2691249).Curated | 1 | |
Sequence conflicti | 289 | I → T AA sequence (PubMed:2691249).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_000430 | 239 | Q → L1 PublicationCorresponds to variant dbSNP:rs1042079EnsemblClinVar. | 1 | |
Natural variantiVAR_060351 | 269 | N → T5 PublicationsCorresponds to variant dbSNP:rs930337Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_056353 | 90 – 99 | DRVAIEPGAP → FLTMSPLRKA in isoform 2. 1 Publication | 10 | |
Alternative sequenceiVSP_056354 | 100 – 356 | Missing in isoform 2. 1 PublicationAdd BLAST | 257 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U07361 mRNA Translation: AAA66064.1 L29008 mRNA Translation: AAA80565.1 L29254 , L29249, L29250, L29251, L29252, L29253 Genomic DNA Translation: AAA80566.1 U67243 , U67236, U67237, U67238, U67239, U67240, U67241, U67242 Genomic DNA Translation: AAB61898.1 AK295656 mRNA Translation: BAH12142.1 AK312444 mRNA Translation: BAG35352.1 AC090888 Genomic DNA No translation available. AC091117 Genomic DNA No translation available. BC021085 mRNA Translation: AAH21085.1 BC025295 mRNA Translation: AAH25295.1 |
CCDSi | CCDS10116.1 [Q00796-1] |
PIRi | A54674 |
RefSeqi | NP_003095.2, NM_003104.5 [Q00796-1] |
Genome annotation databases
Ensembli | ENST00000267814; ENSP00000267814; ENSG00000140263 [Q00796-1] ENST00000558789; ENSP00000453904; ENSG00000140263 [Q00796-2] |
GeneIDi | 6652 |
KEGGi | hsa:6652 |
UCSCi | uc001zul.5, human [Q00796-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U07361 mRNA Translation: AAA66064.1 L29008 mRNA Translation: AAA80565.1 L29254 , L29249, L29250, L29251, L29252, L29253 Genomic DNA Translation: AAA80566.1 U67243 , U67236, U67237, U67238, U67239, U67240, U67241, U67242 Genomic DNA Translation: AAB61898.1 AK295656 mRNA Translation: BAH12142.1 AK312444 mRNA Translation: BAG35352.1 AC090888 Genomic DNA No translation available. AC091117 Genomic DNA No translation available. BC021085 mRNA Translation: AAH21085.1 BC025295 mRNA Translation: AAH25295.1 |
CCDSi | CCDS10116.1 [Q00796-1] |
PIRi | A54674 |
RefSeqi | NP_003095.2, NM_003104.5 [Q00796-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1PL6 | X-ray | 2.00 | A/B/C/D | 2-357 | [»] | |
1PL7 | X-ray | 2.20 | A/B/C/D | 2-357 | [»] | |
1PL8 | X-ray | 1.90 | A/B/C/D | 2-357 | [»] | |
SMRi | Q00796 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 112535, 75 interactors |
IntActi | Q00796, 13 interactors |
MINTi | Q00796 |
STRINGi | 9606.ENSP00000267814 |
Chemistry databases
BindingDBi | Q00796 |
ChEMBLi | CHEMBL2275 |
DrugBanki | DB04478, Cp-166572, 2-Hydroxymethyl-4-(4-N,N-Dimethylaminosulfonyl-1-Piperazino)-Pyrimidine DB00157, NADH |
DrugCentrali | Q00796 |
PTM databases
iPTMneti | Q00796 |
MetOSitei | Q00796 |
PhosphoSitePlusi | Q00796 |
SwissPalmi | Q00796 |
Genetic variation databases
BioMutai | SORD |
DMDMi | 292495088 |
2D gel databases
REPRODUCTION-2DPAGEi | IPI00216057 |
Proteomic databases
EPDi | Q00796 |
jPOSTi | Q00796 |
MassIVEi | Q00796 |
MaxQBi | Q00796 |
PaxDbi | Q00796 |
PeptideAtlasi | Q00796 |
PRIDEi | Q00796 |
ProteomicsDBi | 57873 [Q00796-1] 6501 |
Protocols and materials databases
Antibodypediai | 24307, 530 antibodies |
DNASUi | 6652 |
Genome annotation databases
Ensembli | ENST00000267814; ENSP00000267814; ENSG00000140263 [Q00796-1] ENST00000558789; ENSP00000453904; ENSG00000140263 [Q00796-2] |
GeneIDi | 6652 |
KEGGi | hsa:6652 |
UCSCi | uc001zul.5, human [Q00796-1] |
Organism-specific databases
CTDi | 6652 |
DisGeNETi | 6652 |
GeneCardsi | SORD |
HGNCi | HGNC:11184, SORD |
HPAi | ENSG00000140263, Tissue enhanced (cervix, uterine, liver, thyroid gland) |
MIMi | 182500, gene |
neXtProti | NX_Q00796 |
OpenTargetsi | ENSG00000140263 |
PharmGKBi | PA36021 |
VEuPathDBi | HostDB:ENSG00000140263.13 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0024, Eukaryota |
GeneTreei | ENSGT00550000074781 |
HOGENOMi | CLU_168382_0_0_1 |
InParanoidi | Q00796 |
OMAi | ETWYAMS |
OrthoDBi | 1019156at2759 |
PhylomeDBi | Q00796 |
TreeFami | TF313060 |
Enzyme and pathway databases
BRENDAi | 1.1.1.14, 2681 |
PathwayCommonsi | Q00796 |
Reactomei | R-HSA-5652227, Fructose biosynthesis R-HSA-5661270, Formation of xylulose-5-phosphate |
SABIO-RKi | Q00796 |
Miscellaneous databases
BioGRID-ORCSi | 6652, 6 hits in 875 CRISPR screens |
ChiTaRSi | SORD, human |
EvolutionaryTracei | Q00796 |
GeneWikii | SORD |
GenomeRNAii | 6652 |
Pharosi | Q00796, Tchem |
PROi | PR:Q00796 |
RNActi | Q00796, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000140263, Expressed in thyroid gland and 161 other tissues |
ExpressionAtlasi | Q00796, baseline and differential |
Genevisiblei | Q00796, HS |
Family and domain databases
InterProi | View protein in InterPro IPR013149, ADH_C IPR013154, ADH_N IPR002328, ADH_Zn_CS IPR011032, GroES-like_sf IPR036291, NAD(P)-bd_dom_sf IPR020843, PKS_ER |
Pfami | View protein in Pfam PF08240, ADH_N, 1 hit PF00107, ADH_zinc_N, 1 hit |
SMARTi | View protein in SMART SM00829, PKS_ER, 1 hit |
SUPFAMi | SSF50129, SSF50129, 1 hit SSF51735, SSF51735, 1 hit |
PROSITEi | View protein in PROSITE PS00059, ADH_ZINC, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | DHSO_HUMAN | |
Accessioni | Q00796Primary (citable) accession number: Q00796 Secondary accession number(s): B2R655 Q9UMD6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 1, 1993 |
Last sequence update: | March 23, 2010 | |
Last modified: | February 10, 2021 | |
This is version 216 of the entry and version 4 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 15
Human chromosome 15: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families