HINT1 explained

Histidine triad nucleotide-binding protein 1 also known as adenosine 5'-monophosphoramidase is an enzyme that in humans is encoded by the HINT1 gene.^{[1] [2]}

HINT1 hydrolyzes purine nucleotide phosphoramidates with a single phosphate group.^[3] In addition, functions as scaffolding protein that modulates transcriptional activation.^[4]

It is a haploinsufficient tumor suppressor gene that inhibits the Wnt/β-catenin pathway in colon cancer cells and microphthalmia-associated transcription factor (MITF) activity in human mast cells.^{[5] [6]} In the LysRS-Ap4A-MITF signaling pathway, HINT1 inhibits the MITF transcriptional activity by direct association. Upon pathway activation, HINT1 is released from MITF by diadenosine tetraphosphate (Ap4A), produced by LysRS.^{[6] [7]}

See also

• Histidine triad nucleotide-binding protein 2 (HINT2)

Further reading

• Brzoska PM, Chen H, Zhu Y, etal . The product of the ataxia-telangiectasia group D complementing gene, ATDC, interacts with a protein kinase C substrate and inhibitor. . Proc. Natl. Acad. Sci. U.S.A. . 92 . 17 . 7824–8 . 1995 . 7644499 . 10.1073/pnas.92.17.7824 . 41238 . 1995PNAS...92.7824B . free .
• Lima CD, Klein MG, Weinstein IB, Hendrickson WA . Three-dimensional structure of human protein kinase C interacting protein 1, a member of the HIT family of proteins. . Proc. Natl. Acad. Sci. U.S.A. . 93 . 11 . 5357–62 . 1996 . 8643579 . 10.1073/pnas.93.11.5357 . 39250 . 1996PNAS...93.5357L . free .
• Lima CD, Klein MG, Hendrickson WA . Structure-based analysis of catalysis and substrate definition in the HIT protein family. . Science . 278 . 5336 . 286–90 . 1997 . 9323207 . 10.1126/science.278.5336.286 .
• Klein MG, Yao Y, Slosberg ED, etal . Characterization of PKCI and comparative studies with FHIT, related members of the HIT protein family. . Exp. Cell Res. . 244 . 1 . 26–32 . 1998 . 9770345 . 10.1006/excr.1998.4153 . free .
• Book: Weitzdoerfer R, Stolzlechner D, Dierssen M, etal . Reduction of nucleoside diphosphate kinase B, Rab GDP- dissociation inhibitor beta and histidine triad nucleotide-binding protein in fetal Down Syndrome brain . Protein Expression in Down Syndrome Brain . Journal of Neural Transmission. Supplementum . 61 . 347–59 . 2002 . 11771757 . 10.1007/978-3-7091-6262-0_29. 978-3-211-83704-7 .
• Bieganowski P, Garrison PN, Hodawadekar SC, etal . Adenosine monophosphoramidase activity of Hint and Hnt1 supports function of Kin28, Ccl1, and Tfb3. . J. Biol. Chem. . 277 . 13 . 10852–60 . 2002 . 11805111 . 10.1074/jbc.M111480200 . 2556056 . free .
• Brenner C . Hint, Fhit, and GalT: function, structure, evolution, and mechanism of three branches of the histidine triad superfamily of nucleotide hydrolases and transferases. . Biochemistry . 41 . 29 . 9003–14 . 2002 . 12119013 . 10.1021/bi025942q . 2571077 .
• Strausberg RL, Feingold EA, Grouse LH, etal . 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 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Gevaert K, Goethals M, Martens L, etal . Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. . Nat. Biotechnol. . 21 . 5 . 566–9 . 2004 . 12665801 . 10.1038/nbt810 . 23783563 .
• Galey D, Becker K, Haughey N, etal . Differential transcriptional regulation by human immunodeficiency virus type 1 and gp120 in human astrocytes. . J. Neurovirol. . 9 . 3 . 358–71 . 2003 . 12775419 . 10.1080/13550280390201119 . 22016092 .
• Ota T, Suzuki Y, Nishikawa T, etal . Complete sequencing and characterization of 21,243 full-length human cDNAs. . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . free .
• Gerhard DS, Wagner L, Feingold EA, etal . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
• Weiske J, Huber O . The histidine triad protein Hint1 triggers apoptosis independent of its enzymatic activity. . J. Biol. Chem. . 281 . 37 . 27356–66 . 2006 . 16835243 . 10.1074/jbc.M513452200 . free .
• Ajit SK, Ramineni S, Edris W, etal . RGSZ1 interacts with protein kinase C interacting protein PKCI-1 and modulates mu opioid receptor signaling. . Cell. Signal. . 19 . 4 . 723–30 . 2007 . 17126529 . 10.1016/j.cellsig.2006.09.008 .
• Symes AJ, Eilertsen M, Millar M. Quantitative Analysis of BTF3, HINT1, NDRG1 and ODC1 Protein Over-Expression in Human Prostate Cancer Tissue . PLOS ONE . 8 . 12 . e84295 . 2013 . 24386364. 10.1371/journal.pone.0084295 . 3874000. 2013PLoSO...884295S . etal. free .

Notes and References

1. Brzoska PM, Chen H, Levin NA, Kuo WL, Collins C, Fu KK, Gray JW, Christman MF . Cloning, mapping, and in vivo localization of a human member of the PKCI-1 protein family (PRKCNH1) . Genomics . 36 . 1 . 151–6 . Feb 1997 . 8812426 . 10.1006/geno.1996.0435 .
2. Web site: Entrez Gene: HINT1 histidine triad nucleotide binding protein 1.
3. Strom A, Tong CL, Wagner CR . Histidine triad nucleotide-binding proteins HINT1 and HINT2 share similar substrate specificities and little affinity for the signaling dinucleotide Ap4A . FEBS Letters . 594 . 10 . 1497–1505 . May 2020 . 31990367 . 10.1002/1873-3468.13745 . 210933742 . free .
4. Web site: P49773: HINT1 (human) . UniProt .
5. Wang L, Li H, Zhang Y, Santella RM, Weinstein IB . HINT1 inhibits beta-catenin/TCF4, USF2 and NFkappaB activity in human hepatoma cells. Int J Cancer . 124 . 7 . 1526–34. Apr 2009 . 19089909 . 2667231 . 10.1002/ijc.24072 .
6. Lee YN, Nechushtan H, Figov N, Razin E . The function of lysyl-tRNA synthetase and Ap4A as signaling regulators of MITF activity in FcepsilonRI-activated mast cells . Immunity. 20 . 2 . 145–51 . Feb 2004 . 14975237 . 10.1016/S1074-7613(04)00020-2 . free .
7. Yannay-Cohen N, Carmi-Levy I, Kay G, Yang CM, Han JM, Kemeny DM, Kim S, Nechushtan H, Razin E . LysRS serves as a key signaling molecule in the immune response by regulating gene expression . Mol Cell. 34 . 5 . 603–11 . June 2009 . 19524539 . 10.1016/j.molcel.2009.05.019 . free .