Sorbitol dehydrogenase (SORD)
The protein contains 357 amino acids for an estimated molecular weight of 38325 Da.
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). (updated: June 5, 2019)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is predicted to be membranous by TOPCONS.
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Biological Process
Flagellated sperm motility
Fructose biosynthetic process
Glucose metabolic process
Glucuronate catabolic process to xylulose 5-phosphate
L-xylitol catabolic process
L-xylitol metabolic process
Response to cadmium ion
Response to copper ion
Response to drug
Response to hormone
Response to nutrient levels
Response to osmotic stress
Sorbitol catabolic process
Cellular Component
Cytosol
Extracellular exosome
Extracellular space
Membrane
Mitochondrial membrane
Motile cilium
The reference OMIM entry for this protein is 182500
Sorbitol dehydrogenase; sord
Sorbitol dehydrogenase 1; sord1 sorbitol dehydrogenase 2, included; sord2, included
DESCRIPTION
Sorbitol dehydrogenase (SORD; EC 1.1.1.14) catalyzes the interconversion of polyols and their corresponding ketoses, and together with aldose reductase (ALDR1; 103880), makes up the sorbitol pathway that is believed to play an important role in the development of diabetic complications. The first reaction of the pathway (also called the polyol pathway) is the reduction of glucose to sorbitol by ALDR1 with NADPH as the cofactor. SORD then oxidizes the sorbitol to fructose using NAD(+) cofactor (summary by Carr and Markham, 1995).CLONING
Lee et al. (1994) cloned and sequenced cDNA for human SORD. They found that it translates into a peptide of 356 amino acid residues, 1 more than the sequence previously reported from peptide analysis. Iwata et al. (1995) cloned a human SORD cDNA as well as the gene. The promoter was shown to contain a CACCC box and 3 putative binding sites for the transcription factor Sp1 (SP1; 189906). Two alternative transcription initiation sites were identified. Northern blots demonstrated expression in most tissues and at particularly high levels in the kidney and lens of the eye.GENE FUNCTION
Carr and Markham (1995) noted that the polyol pathway is particularly active in hyperglycemic states. Although SORD is closely related to the class I long-chain alcohol dehydrogenases, it differs in substrate specificity, catalyzing polyols such as sorbitol and xylitol but having no activity towards primary alcohols.GENE STRUCTURE
Iwata et al. (1995) determined that the SORD gene is divided into 9 exons spanning approximately 30 kb. Carr and Markham (1995) defined the intron/exon boundaries of the SORD gene and identified a number of polymorphic variants.MAPPING
Donald et al. (1980) assigned the sorbitol dehydrogenase gene to chromosome 15pter-q21 by somatic cell hybridization. By fluorescence in situ hybridization (FISH), Lee et al. (1994) mapped the SORD gene to a single site on 15q15, indicating that it is a single-copy gene. The localization was confirmed by Southern blot hybridization in somatic cell hybrids. Iwata et al. (1995) mapped the SORD gene by FISH to 15q21.1. Carr and Markham (1995) confirmed the localization of SORD to chromosome 15 by screening somatic cell hybrid mapping panels by PCR and regionalized the gene to 15q15 by FISH. - SORD2 Carr et al. (1998) established that 2 very closely homologous SORD sequences lie within 0.5 Mb on chromosome 15. The SORD2 and SORD1 genes are oriented head-to-head in the order cen--SORD2--SORD1--tel. Thus the 2 genes appear to represent an inverted repeat with their 5-prime ends closest together. By fluorescence in situ hybridization, Carr et al. (1998) showed that both genes are located at 15q15.3.EVOLUTION
- SORD2 The duplicated human sequences SORD1 and SORD2 translate into proteins that differ by only 6 amino acid substitutions in their 335 residues, with a single-nucleotide deletion in exon 7 of SORD2, the apparent loss of exon 1 from SORD2, and an Alu insertion in intron 8 of SORD2 (Carr et al., 1997). To establish when the human SORD duplication occurred, Carr et al. (1998) sequenced the open reading frame of marmoset liver SORD. SORD appeared to be a single gene in this New World monkey. They found that marmoset SORD showed significantly less homology with either SORD1 or SORD2 than the 2 do with each other, suggesting that the human homologs represent a recent gene duplication event. Ca ... More on the omim web site
June 7, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 182500 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed