Mitochondrial 2-oxodicarboxylate carrier

SLC25A21
Identifiers
Aliases	SLC25A21 , ODC, ODC1, solute carrier family 25 member 21, MTDPS18
External IDs	OMIM: 607571 MGI: 2445059 HomoloGene: 6988 GeneCards: SLC25A21
Gene location (Human) Chr. Chromosome 14 (human) [1] Band 14q13.3 Start 36,677,921 bp [1] End 37,172,606 bp [1]
Gene location (Mouse) Chr. Chromosome 12 (mouse) [2] Band 12|12 C1 Start 56,759,419 bp [2] End 57,244,257 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in stromal cell of endometrium gastric mucosa popliteal artery bone marrow Achilles tendon smooth muscle tissue islet of Langerhans body of stomach right coronary artery gastrocnemius muscle Top expressed in proximal tubule bone marrow hepatobiliary system liver kidney spermatocyte lobe of liver morula yolk sac placenta More reference expression data BioGPS n/a
Gene ontology Molecular function alpha-ketoglutarate transmembrane transporter activity dicarboxylic acid transmembrane transporter activity transmembrane transporter activity Cellular component membrane mitochondrion mitochondrial inner membrane integral component of membrane Biological process transmembrane transport lysine catabolic process alpha-ketoglutarate transport dicarboxylic acid transport mitochondrial transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 89874 217593 Ensembl ENSG00000183032 ENSMUSG00000035472 UniProt Q9BQT8 Q8BZ09 RefSeq (mRNA) NM_001171170 NM_030631 NM_001167976 NM_172577 RefSeq (protein) NP_001164641 NP_085134 NP_001161448 NP_766165 Location (UCSC) Chr 14: 36.68 – 37.17 Mb Chr 12: 56.76 – 57.24 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Mitochondrial 2-oxodicarboxylate carrier also known as solute carrier family 25 member 21 (SLC25A21) is a protein that in humans is encoded by the SLC25A21 gene. ^[5]

It is a homolog of the S. cerevisiae ODC proteins, mitochondrial carriers that transport C5-C7 oxodicarboxylates across inner mitochondrial membranes. One of the species transported by ODC is 2-oxoadipate, a common intermediate in the catabolism of lysine, tryptophan, and hydroxylysine in mammals. Within mitochondria, 2-oxoadipate is converted into acetyl-CoA. ^[5]

Model organisms

Slc25a21 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Abnormal
Recessive lethal study	Normal
Fertility	Normal
Body weight	Abnormal [6]
Anxiety	Normal
Neurological assessment	Abnormal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Abnormal [7]
Indirect calorimetry	Abnormal [8]
Glucose tolerance test	Normal
Auditory brainstem response	Abnormal
DEXA	Abnormal [9]
Radiography	Abnormal [10]
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Abnormal [11]
Haematology	Abnormal [12]
Micronucleus test	Normal
Heart weight	Normal
Brain histopathology	Normal
All tests and analysis from [13] [14]

Model organisms have been used in the study of SLC25A21 function. A conditional knockout mouse line, called Slc25a21^{tm1a(KOMP)Wtsi [15] [16]} was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists. ^{[17] [18] [19]}

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. ^{[13] [20]} Twenty one tests were carried out on homozygous mutant mice and ten significant abnormalities were observed, including sub-viability at weaning, decreased body weight, absent pinna reflex, abnormal snout, skull, spine and tooth morphology, atypical indirect calorimetry, body composition and plasma chemistry data, increased mean platelet volume and moderate elevations in auditory thresholds. ^[13]

References

1. GRCh38: Ensembl release 89: ENSG00000183032 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000035472 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Solute carrier family 25 (mitochondrial oxodicarboxylate carrier), member 21" . Retrieved 2011-12-04.
6. "Body weight data for Slc25a21". Wellcome Trust Sanger Institute.
7. "Dysmorphology data for Slc25a21". Wellcome Trust Sanger Institute.
8. "Indirect calorimetry data for Slc25a21". Wellcome Trust Sanger Institute.
9. "DEXA data for Slc25a21". Wellcome Trust Sanger Institute.
10. "Radiography data for Slc25a21". Wellcome Trust Sanger Institute.
11. "Clinical chemistry data for Slc25a21". Wellcome Trust Sanger Institute.
12. "Haematology data for Slc25a21". Wellcome Trust Sanger Institute.
13. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. S2CID   85911512.
14. Mouse Resources Portal, Wellcome Trust Sanger Institute.
15. "International Knockout Mouse Consortium".
16. "Mouse Genome Informatics".
17. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (June 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC   3572410 . PMID   21677750.
18. Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi: 10.1038/474262a . PMID   21677718.
19. Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi: 10.1016/j.cell.2006.12.018 . PMID   17218247. S2CID   18872015.
20. van der Weyden L, White JK, Adams DJ, Logan DW (June 2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi: 10.1186/gb-2011-12-6-224 . PMC   3218837 . PMID   21722353.

Further reading

• Fiermonte G, Dolce V, Palmieri L, Ventura M, Runswick MJ, Palmieri F, Walker JE (March 2001). "Identification of the human mitochondrial oxodicarboxylate carrier. Bacterial expression, reconstitution, functional characterization, tissue distribution, and chromosomal location". The Journal of Biological Chemistry. 276 (11): 8225–30. doi: 10.1074/jbc.M009607200 . PMID   11083877.
• Trynka G, Zhernakova A, Romanos J, Franke L, Hunt KA, Turner G, Bruinenberg M, Heap GA, Platteel M, Ryan AW, de Kovel C, Holmes GK, Howdle PD, Walters JR, Sanders DS, Mulder CJ, Mearin ML, Verbeek WH, Trimble V, Stevens FM, Kelleher D, Barisani D, Bardella MT, McManus R, van Heel DA, Wijmenga C (August 2009). "Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling". Gut. 58 (8): 1078–83. doi:10.1136/gut.2008.169052. PMID   19240061. S2CID   17111427.
• Talmud PJ, Drenos F, Shah S, Shah T, Palmen J, Verzilli C, Gaunt TR, Pallas J, Lovering R, Li K, Casas JP, Sofat R, Kumari M, Rodriguez S, Johnson T, Newhouse SJ, Dominiczak A, Samani NJ, Caulfield M, Sever P, Stanton A, Shields DC, Padmanabhan S, Melander O, Hastie C, Delles C, Ebrahim S, Marmot MG, Smith GD, Lawlor DA, Munroe PB, Day IN, Kivimaki M, Whittaker J, Humphries SE, Hingorani AD (November 2009). "Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip". American Journal of Human Genetics. 85 (5): 628–42. doi:10.1016/j.ajhg.2009.10.014. PMC   2775832 . PMID   19913121.