The reference OMIM entry for this protein is 102771

Adenosine monophosphate deaminase 2; ampd2

DESCRIPTION

The AMPD2 gene encodes adenosine monophosphate deaminase-2 (EC 3.5.4.6), an enzyme that catalyzes the deamination of AMP to IMP and plays an important role in the purine nucleotide cycle (summary by Akizu et al., 2013).

CLONING

By screening a human spleen cDNA library with a previously cloned partial rat AMPD2 cDNA, followed by the use of PCR techniques, Bausch-Jurken et al. (1992) isolated cDNA clones for human AMPD2 from T-lymphoblast and placenta libraries. The deduced 760-amino acid polypeptide has a predicted molecular mass of 88.1 kD and shares significant homology in the C-terminal region with AMPD1 (102770). AMPD2 encodes isoform L (liver). Morisaki et al. (1990) found that whereas AMPD1 is expressed at high levels in skeletal muscle of the adult rat, AMPD2, which they cloned from an adult rat brain cDNA library, is the predominant gene expressed in nonmuscle tissues and smooth muscle of the adult rat and is also the predominant gene expressed in embryonic muscle and undifferentiated myoblasts. Both genes are expressed in cardiac muscle of the adult rat. The peptides encoded by these 2 genes have distinct immunologic properties. Human isoform L corresponds to rat isoform B (liver and kidney). Akizu et al. (2013) found high expression of AMPD2 in human cerebellum.

MAPPING

By Southern blot analysis, Moseley et al. (1990) demonstrated that distinct restriction fragments in the rat and human genome hybridized to AMPD1 and AMPD2 cDNAs. Indirect evidence suggested that the 2 genes are linked; L6 myoblasts resistant to coformycin coamplified both genes while expressing only AMPD2. Moseley et al. (1990) demonstrated further that Ampd1 and Ampd2 are closely linked on distal mouse chromosome 3. By studies of human/mouse somatic cell hybrids, Eddy et al. (1993) demonstrated that the AMPD2 gene is localized to 1p, as is AMPD1. Mahnke-Zizelman et al. (1996) refined the map location of AMPD2 to chromosome 1p13.3 using somatic cell hybrids and fluorescence in situ hybridization.

GENE STRUCTURE

Mahnke-Zizelman et al. (1996) showed that the AMPD2 gene contains 19 exons and spans 14 kb of genomic DNA. Alternatively spliced forms arise from the use of either exon 1A or exon 1B, both of which have promoter activity and contain an initiation codon.

GENE FUNCTION

Van den Berghe and Hers (1980) noted that AMP deaminase is normally about 95% inhibited by guanosine triphosphate (GTP) and may be the limiting step in adenine nucleotide catabolism. They studied the liver from a man with familial primary gout and found defective inhibition of AMP deaminase by GTP. The authors suggested that a genetically determined reduction in sensitivity of AMP deaminase to inhibition might be a basis for primary gout.

MOLECULAR GENETICS

- Spastic Paraplegia 63 In affected members of a consanguineous family segregating spastic paraplegia-63 (SPG63; 615686), Novarino et al. (2014) identified a homozygous frameshift mutation in the AMPD2 gene (102771.0001). - Pontocerebellar Hypoplasia Type 9 In 8 patients from 5 families with pontocerebellar hypoplasia type 9 (PCH9; 615809), Akizu et al. (2013) identified 5 different homozygous mutations in the AMPD2 gene (102771.0002-102771.0006). Two mutations resulted in premature termination, whereas 3 were missense mutations at highly conserved residues. The mutations were found by whole-exome sequencing of 30 probands with PCH. The AMPD2 protein was nearly ... More on the omim web site

Subscribe to this protein entry history

Feb. 22, 2019: Protein entry updated
Automatic update: model status changed

Nov. 16, 2018: Protein entry updated
Automatic update: OMIM entry 102771 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).