Adenosine 5'-monophosphoramidase HINT1

Definition:

Exhibits adenosine 5'-monophosphoramidase activity, hydrolyzing purine nucleotide phosphoramidates with a single phosphate group such as adenosine 5'monophosphoramidate (AMP-NH2) to yield AMP and NH2. Hydrolyzes adenosine 5'monophosphomorpholidate (AMP-morpholidate) and guanosine 5'monophosphomorpholidate (GMP-morpholidate). Hydrolyzes lysyl-AMP (AMP-N-epsilon-(N-alpha-acetyl lysine methyl ester)) generated by lysine tRNA ligase, as well as Met-AMP, His-AMP and Asp-AMP, lysyl-GMP (GMP-N-epsilon-(N-alpha-acetyl lysine methyl ester)) and AMP-N-alanine methyl ester. Hydrolyzes 3-indolepropionic acyl-adenylate, tryptamine adenosine phosphoramidate monoester and other fluorogenic purine nucleoside tryptamine phosphoramidates in vitro. Can also convert adenosine 5'-O-phosphorothioate and guanosine 5'-O-phosphorothioate to the corresponding nucleoside 5'-O-phosphates with concomitant release of hydrogen sulfide. In addition, functions as scaffolding protein that modulates transcriptional activation by the LEF1/TCF1-CTNNB1 complex and by the complex formed with MITF and CTNNB1. Modulates p53/TP53 levels and p53/TP53-mediated apoptosis. Modulates proteasomal degradation of target proteins by the SCF (SKP2-CUL1-F-box protein) E3 ubiquitin-protein ligase complex. Also exhibits SUMO-specific isopeptidase activity, deconjugating SUMO1 from RGS17. Deconjugates SUMO1 from RANGAP1 (By similarity).

References:

[1]. Xin Zhou, et al. Kinetic mechanism of human histidine triad nucleotide binding protein 1. Biochemistry. 2013 May 21;52(20):3588-600. [Content Brief]

[2]. Jörg Weiske, et al. The histidine triad protein Hint1 triggers apoptosis independent of its enzymatic activity. J Biol Chem. 2006 Sep 15;281(37):27356-66. [Content Brief]

[3]. Jing Wang, et al. Side chain independent recognition of aminoacyl adenylates by the Hint1 transcription suppressor. J Phys Chem B. 2012 Jun 14;116(23):6798-805. [Content Brief]

[4]. Giannicola Genovese, et al. The tumor suppressor HINT1 regulates MITF and β-catenin transcriptional activity in melanoma cells. Cell Cycle. 2012 Jun 1;11(11):2206-15. [Content Brief]

[5]. Jörg Weiske, et al. The histidine triad protein Hint1 interacts with Pontin and Reptin and inhibits TCF-beta-catenin-mediated transcription. J Cell Sci. 2005 Jul 15;118(Pt 14):3117-29. [Content Brief]

[6]. Bo Cen, et al. Histidine triad nucleotide-binding protein 1 up-regulates cellular levels of p27KIP1 by targeting ScfSKP2 ubiquitin ligase and Src. J Biol Chem. 2009 Feb 20;284(8):5265-76. [Content Brief]

[7]. Elsa Cortés-Montero, et al. The Axonal Motor Neuropathy-Related HINT1 Protein Is a Zinc- and Calmodulin-Regulated Cysteine SUMO Protease. Antioxid Redox Signal. 2019 Sep 1;31(7):503-520. [Content Brief]

[8]. Alexander Strom, et al. Histidine triad nucleotide-binding proteins HINT1 and HINT2 share similar substrate specificities and little affinity for the signaling dinucleotide Ap4A. FEBS Lett. 2020 May;594(10):1497-1505. [Content Brief]

[9]. Agnieszka Krakowiak, et al. The role of the Hint1 protein in the metabolism of phosphorothioate oligonucleotides drugs and prodrugs, and the release of H2S under cellular conditions. Biochem Pharmacol. 2019 May;163:250-259. [Content Brief]

[10]. Tsui-Fen Chou, et al. Phosphoramidate pronucleotides: a comparison of the phosphoramidase substrate specificity of human and Escherichia coli histidine triad nucleotide binding proteins. Mol Pharm. 2007 Mar-Apr;4(2):208-17. [Content Brief]

[11]. Tsui-Fen Chou, et al. 31P NMR and genetic analysis establish hinT as the only Escherchia coli purine nucleoside phosphoramidase and as essential for growth under high salt conditions. J Biol Chem. 2005 Apr 15;280(15):15356-61. [Content Brief]

[12]. Tsui-Fen Chou, et al. Engineered monomeric human histidine triad nucleotide-binding protein 1 hydrolyzes fluorogenic acyl-adenylate and lysyl-tRNA synthetase-generated lysyl-adenylate. J Biol Chem. 2007 May 18;282(20):15137-47. [Content Brief]

[13]. Rachit Shah, et al. Caught before Released: Structural Mapping of the Reaction Trajectory for the Sofosbuvir Activating Enzyme, Human Histidine Triad Nucleotide Binding Protein 1 (hHint1). Biochemistry. 2017 Jul 18;56(28):3559-3570. [Content Brief]

[14]. Rachit M Shah, et al. Structure and Functional Characterization of Human Histidine Triad Nucleotide-Binding Protein 1 Mutations Associated with Inherited Axonal Neuropathy with Neuromyotonia. J Mol Biol. 2018 Aug 17;430(17):2709-2721. [Content Brief]

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