AMPD3

AMPD3
Identifiers
Aliases	AMPD3
External IDs	MGI: 1096344 HomoloGene: 408 GeneCards: AMPD3
Gene ontology Molecular function • hydrolase activity • metal ion binding • deaminase activity • AMP deaminase activity Cellular component • cytosol Biological process • GTP metabolic process • purine ribonucleoside monophosphate biosynthetic process • erythrocyte homeostasis • nucleotide metabolic process • AMP metabolic process • ADP metabolic process • purine-containing compound salvage • IMP salvage • energy homeostasis • ATP metabolic process • AMP catabolic process • IMP biosynthetic process Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	272	11717
Ensembl	ENSG00000133805	ENSMUSG00000005686
UniProt	Q01432	O08739
RefSeq (mRNA)	NM_001172431 NM_000480 NM_001025389 NM_001025390 NM_001172430	NM_001276301 NM_009667
RefSeq (protein)	NP_000471.1 NP_001020560.1 NP_001020561.1 NP_001165901.1 NP_001165902.1	NP_001263230.1 NP_033797.2
Location (UCSC)	Chr 11: 10.31 – 10.51 Mb	Chr 7: 110.77 – 110.81 Mb
PubMed search	[1]	[2]
Wikidata

View/Edit Human

View/Edit Mouse

AMP deaminase 3 is an enzyme that in humans is encoded by the AMPD3 gene.^[3][4]

This gene encodes a member of the AMP deaminase gene family. The encoded protein is a highly regulated enzyme that catalyzes the hydrolytic deamination of adenosine monophosphate to inosine monophosphate, a branch point in the adenylate catabolic pathway. This gene encodes the erythrocyte (E) isoforms, whereas other family members encode isoforms that predominate in muscle (M) and liver (L) cells. Mutations in this gene lead to the clinically asymptomatic, autosomal recessive condition erythrocyte AMP deaminase deficiency. Alternatively spliced transcript variants encoding different isoforms of this gene have been described.^[4]

Model organisms

Ampd3 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Normal
Homozygous Fertility	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Plasma immunoglobulins	Abnormal
Haematology	Normal
Peripheral blood lymphocytes	Abnormal[5]
Micronucleus test	Normal
Heart weight	Normal
Tail epidermis wholemount	Normal
Skin Histopathology	Normal
Brain histopathology	Abnormal
Eye Histopathology	Normal
MicroCT & Quantitative Faxitron	Abnormal
Salmonella infection	Normal[6]
Citrobacter infection	Normal[7]
All tests and analysis from[8][9]

Model organisms have been used in the study of AMPD3 function. A conditional knockout mouse line, called Ampd3^{tm2a(KOMP)Wtsi[10][11]} 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.^[12][13][14]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.^[8][15] Twenty eight tests were carried out on mutant mice and four significant abnormalities were observed.^[8] Mutant animals had increased IgG1 levels, increased trabecular bone thickness, decreased B cell numbers / increased granulocyte number and unusual brain histopathology (the thickness of the stratum radiatum was reduced and the dorsal 3rd ventricle area was increased).^[8]

References

1. "Human PubMed Reference:".
2. "Mouse PubMed Reference:".
3. Mahnke-Zizelman DK, Sabina RL (Nov 1992). "Cloning of human AMP deaminase isoform E cDNAs. Evidence for a third AMPD gene exhibiting alternatively spliced 5'-exons". J Biol Chem. 267 (29): 20866–77. PMID 1400401.
4. "Entrez Gene: AMPD3 adenosine monophosphate deaminase (isoform E)".
5. "Peripheral blood lymphocytes data for Ampd3". Wellcome Trust Sanger Institute.
6. "Salmonella infection data for Ampd3". Wellcome Trust Sanger Institute.
7. "Citrobacter infection data for Ampd3". Wellcome Trust Sanger Institute.
8. 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.
9. Mouse Resources Portal, Wellcome Trust Sanger Institute.
10. "International Knockout Mouse Consortium".
11. "Mouse Genome Informatics".
12. Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
13. Dolgin E (2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
14. Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
15. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism.". Genome Biol. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

Further reading

• Zydowo MM (1994). "Regulatory effects of the lipid-cytosolic enzyme interaction: AMP deaminase.". Acta Biochim. Pol. 40 (4): 429–32. PMID 8140814.
• Yamada Y, Goto H, Ogasawara N (1992). "Cloning and nucleotide sequence of the cDNA encoding human erythrocyte-specific AMP deaminase.". Biochim. Biophys. Acta. 1171 (1): 125–8. doi:10.1016/0167-4781(92)90153-Q. PMID 1420359.
• Ogasawara N, Goto H, Yamada Y, et al. (1987). "Deficiency of AMP deaminase in erythrocytes.". Hum. Genet. 75 (1): 15–8. doi:10.1007/BF00273831. PMID 3804327.
• Yamada Y, Goto H, Murase T, Ogasawara N (1995). "Molecular basis for human erythrocyte AMP deaminase deficiency: screening for the major point mutation and identification of other mutations.". Hum. Mol. Genet. 3 (12): 2243–5. doi:10.1093/hmg/3.12.2243. PMID 7881427.
• Yamada Y, Goto H, Ogasawara N (1994). "A point mutation responsible for human erythrocyte AMP deaminase deficiency.". Hum. Mol. Genet. 3 (2): 331–4. doi:10.1093/hmg/3.2.331. PMID 8004104.
• Mahnke-Zizelman DK, Eddy R, Shows TB, Sabina RL (1996). "Characterization of the human AMPD3 gene reveals that 5' exon usage is subject to transcriptional control by three tandem promoters and alternative splicing.". Biochim. Biophys. Acta. 1306 (1): 75–92. doi:10.1016/0167-4781(95)00231-6. PMID 8611627.
• Fortuin FD, Morisaki T, Holmes EW (1997). "Subunit composition of AMPD varies in response to changes in AMPD1 and AMPD3 gene expression in skeletal muscle.". Proc. Assoc. Am. Physicians. 108 (4): 329–33. PMID 8863347.
• Mahnke-Zizelman DK, D'cunha J, Wojnar JM, et al. (1997). "Regulation of rat AMP deaminase 3 (isoform C) by development and skeletal muscle fibre type.". Biochem. J. 326 (2): 521–9. PMC 1218700. PMID 9291127.
• Yamada Y, Goto H, Wakamatsu N, Ogasawara N (2001). "A rare case of complete human erythrocyte AMP deaminase deficiency due to two novel missense mutations in AMPD3.". Hum. Mutat. 17 (1): 78. doi:10.1002/1098-1004(2001)17:1<78::AID-HUMU21>3.0.CO;2-B. PMID 11139257.
• Mahnke-Zizelman DK, Sabina RL (2003). "N-terminal sequence and distal histidine residues are responsible for pH-regulated cytoplasmic membrane binding of human AMP deaminase isoform E.". J. Biol. Chem. 277 (45): 42654–62. doi:10.1074/jbc.M203473200. PMID 12213808.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Tomikura Y, Hisatome I, Tsuboi M, et al. (2003). "Coordinate induction of AMP deaminase in human atrium with mitochondrial DNA deletion.". Biochem. Biophys. Res. Commun. 302 (2): 372–6. doi:10.1016/S0006-291X(03)00160-8. PMID 12604357.
• Mahnke DK, Sabina RL (2005). "Calcium activates erythrocyte AMP deaminase [isoform E (AMPD3)] through a protein-protein interaction between calmodulin and the N-terminal domain of the AMPD3 polypeptide.". Biochemistry. 44 (14): 5551–9. doi:10.1021/bi048121p. PMID 15807549.
• Sabina RL, Waldenström A, Ronquist G (2006). "The contribution of Ca+ calmodulin activation of human erythrocyte AMP deaminase (isoform E) to the erythrocyte metabolic dysregulation of familial phosphofructokinase deficiency.". Haematologica. 91 (5): 652–5. PMID 16670071.