Disease relevance of MAP2

• Angiogenesis inhibitors specific for methionine aminopeptidase 2 as drugs for malaria and leishmaniasis [1].

High impact information on MAP2

• Fission yeast genes that confer resistance to staurosporine encode an AP-1-like transcription factor and a protein kinase related to the mammalian ERK1/MAP2 and budding yeast FUS3 and KSS1 kinases [2].
• We demonstrate that fumagillin selectively inhibits the S. cerevisiae MetAP-2 protein in vivo [3].
• This fumagillin binding protein was found to be a metalloprotease, methionine aminopeptidase (MetAP-2), that is highly conserved between human and Saccharomyces cerevisiae [3].
• The map2 null strain, like the map1 null strain, is viable but with a slower growth rate [4].
• TNP-470, the first anti-angiogenic small molecule to enter clinical trials, targets methionine aminopeptidase-2 (MetAP-2), a metalloprotease that cleaves the N-terminal methionine of proteins [5].

Biological context of MAP2

• Phylogenetic relationships of methionine aminopeptidase 2 among Encephalitozoon species and genotypes of microsporidia [6].
• The targeted downregulation of either methionine aminopeptidase MetAP-1 or MetAP-2 protein expression by small interfering RNA (siRNA) significantly inhibited the proliferation of human umbilical vein endothelial cells (HUVEC) (70%-80%), while A549 human lung carcinoma cell proliferation was less inhibited (20%-30%) [7].
• Methionine aminopeptidase 2 (MetAP2) is responsible for the hydrolysis of the initiator methionine molecule from the majority of newly synthesized proteins [1].

Anatomical context of MAP2

• In neurones, a limited number of mRNAs is found in dendrites, including transcripts encoding the microtubule-associated protein 2 (MAP2) [8].
• The purified enzyme also used a number of mammalian proteins as phosphoacceptors, including myelin basic protein (MBP), microtubule-associated protein 2 (MAP-2), and tau protein [9].

Associations of MAP2 with chemical compounds

• Eukaryotic methionine aminopeptidase type 2 (MetAP2, MetAP2 gene (MAP2)), together with eukaryotic MetAP1, cotranslationally hydrolyzes initiator methionine from nascent polypeptides when the side chain of the second residue is small and uncharged [10].
• Hence, these results identify MetAP-2 as an important target of study in the analysis of the potent biological activities of fumagillin [3].
• Some of the pyridine-2-carboxylic acid derivatives (compound 2 and 3) had selective inhibition of the growth of map2 deletion yeast and weak inhibition on wild-type yeast growth, while no inhibition on map1 deletion yeast [11].

References