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AGMATINASE; AGMAT

AGMATINASE; AGMAT

Alternative titles; symbolsAGMATINE UREOHYDROLASE; AUHHGNC Approved Gene Symbol: AGMATCytogenetic location: 1p36.21 Genomic coordinates (GRCh38): 1:15,571,69...

Alternative titles; symbols

  • AGMATINE UREOHYDROLASE; AUH

HGNC Approved Gene Symbol: AGMAT

Cytogenetic location: 1p36.21 Genomic coordinates (GRCh38): 1:15,571,698-15,585,050 (from NCBI)

▼ Description
Agmatinase (EC 3.5.3.11) belongs to the arginase (see ARG1, 608313) superfamily of enzymes and hydrolyzes agmatine to putrescine and urea. This activity downregulates the biologic effects of agmatine and represents an alternative to ornithine decarboxylase (see ODC1, 165640) for polyamine biosynthesis (Mistry et al., 2002). In brain, agmatinase is predicted to have a major role in inactivating agmatine rather than fueling the alternative pathway of polyamine synthesis (Bernstein et al., 2011).

▼ Cloning and Expression
By database analysis to identify sequences similar to those of arginases and bacterial agmatinases, followed by screening of a human kidney cDNA library, Mistry et al. (2002) cloned AGMAT. The deduced 352-amino acid protein has a calculated molecular mass of 37.7 kD. It has a putative N-terminal mitochondrial targeting signal, followed by residues conserved in the arginase superfamily, including 6 aspartic acids and histidines that bind divalent manganese ions required for activity. AGMAT shares approximately 30% identity with bacterial agmatinases, but less than 20% identity with human ARG1 or ARG2 (107830). Northern blot analysis of human liver detected AGMAT transcripts of 3.9 and 1.9 kb. Real-time RT-PCR of human tissues found most abundant AGMAT expression in adult liver and kidney, with lower expression in skeletal muscle, fetal liver, brain, testis, skin, and gastrointestinal tract. In situ hybridization and immunohistochemical analysis of human liver detected AGMAT expression primarily in parenchymal cells. Database analysis identified orthologs of AGMAT in vertebrates.

Iyer et al. (2002) independently cloned human AGMAT, which encodes a deduced 352-amino acid protein with all 6 domains conserved in the arginase superfamily, including those required for binding to manganese ions and catalytic activity. Northern blot analysis detected AGMAT transcripts of 1.4 and 2.7 kb that were highly expressed in human liver and kidney, followed by muscle, colon, small intestine, and brain. AGMAT was detected in several specific human brain regions, with highest content in cerebral cortex. A single mouse Agmat transcript equivalent to the smaller human transcript was expressed in liver only.

Bernstein et al. (2011) stated that rat Agmat has a calculated molecular mass of 38 kD. Western blot analysis of rat liver detected Agmat at an apparent molecular mass of approximately 32 kD, suggesting loss of a predicted N-terminal mitochondrial localization signal. Immunohistochemical analysis of human brain detected AGMAT in distinct populations of neurons, especially cortical interneurons. AGMAT was also detected in principal neurons in limbic regions such as habenula and in cerebellum. A similar distribution of Agmat was detected in rat brain.

▼ Gene Function
Mistry et al. (2002) found that expression of human AGMAT complemented ornithine decarboxylase deficiency in yeast. Hepatitis B virus induced AGMAT expression in infected liver and HepG2 cells.

By colorimetric detection of the urea product, Iyer et al. (2002) confirmed that recombinant human AGMAT showed agmatinase activity in vitro.

▼ Gene Structure
Mistry et al. (2002) determined that the AGMAT gene has 8 exons that span 12.6 kb.

▼ Mapping
By genomic sequence analysis, Mistry et al. (2002) and Iyer et al. (2002) independently mapped the AGMAT gene to chromosome 1.

Hartz (2018) mapped the AGMAT gene to chromosome 1p36.21 based on an alignment of the AGMAT sequence (GenBank BC005090) with the genomic sequence (GRCh38).

Tags: 1p36.21