HINT1

Histidine triad nucleotide-binding protein 1 also known as adenosine 5'-monophosphoramidase is an enzyme that in humans is encoded by the HINT1 gene.[5][6]

HINT1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1AV5, 1KPA, 1KPB, 1KPC, 1KPE, 1KPF, 3TW2, 4EQE, 4EQG, 4EQH, 4ZKL, 4ZKV, 5I2E, 5I2F
Identifiers
Aliases	HINT1, HINT, NMAN, PKCI-1, PRKCNH1, histidine triad nucleotide binding protein 1
External IDs	OMIM: 601314 MGI: 1321133 HomoloGene: 3904 GeneCards: HINT1
Gene location (Human) Chr. Chromosome 5 (human)[1] Band 5q23.3 Start 131,159,027 bp[1] End 131,171,735 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11|11 B1.3 Start 54,866,383 bp[2] End 54,870,501 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • nucleotide binding • catalytic activity • hydrolase activity • protein kinase C binding Cellular component • histone deacetylase complex • cell membrane • extracellular exosome • cytoskeleton • cell nucleus • cytoplasm • cytosol Biological process • purine ribonucleotide catabolic process • positive regulation of calcium-mediated signaling • regulation of transcription, DNA-templated • transcription, DNA-templated • intrinsic apoptotic signaling pathway by p53 class mediator • signal transduction • apoptotic process Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	3094	15254
Ensembl	ENSG00000169567	ENSMUSG00000020267
UniProt	P49773	P70349
RefSeq (mRNA)	NM_005340	NM_008248
RefSeq (protein)	NP_005331	NP_032274
Location (UCSC)	Chr 5: 131.16 – 131.17 Mb	Chr 11: 54.87 – 54.87 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

HINT1 hydrolyzes purine nucleotide phosphoramidates with a single phosphate group.[7] In addition, functions as scaffolding protein that modulates transcriptional activation.[8]

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.[9][10] 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.[10][11]

See also

• Histidine triad nucleotide-binding protein 2 (HINT2)

References

1. GRCh38: Ensembl release 89: ENSG00000169567 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000020267 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Brzoska PM, Chen H, Levin NA, Kuo WL, Collins C, Fu KK, Gray JW, Christman MF (Feb 1997). "Cloning, mapping, and in vivo localization of a human member of the PKCI-1 protein family (PRKCNH1)". Genomics. 36 (1): 151–6. doi:10.1006/geno.1996.0435. PMID 8812426.
6. "Entrez Gene: HINT1 histidine triad nucleotide binding protein 1".
7. Strom A, Tong CL, Wagner CR (May 2020). "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. doi:10.1002/1873-3468.13745. PMID 31990367.
8. "P49773: HINT1 (human)". UniProt.
9. Wang L, Li H, Zhang Y, Santella RM, Weinstein IB (Apr 2009). "HINT1 inhibits beta-catenin/TCF4, USF2 and NFkappaB activity in human hepatoma cells". Int J Cancer. 124 (7): 1526–34. doi:10.1002/ijc.24072. PMC 2667231. PMID 19089909.
10. Lee YN, Nechushtan H, Figov N, Razin E (Feb 2004). "The function of lysyl-tRNA synthetase and Ap4A as signaling regulators of MITF activity in FcepsilonRI-activated mast cells". Immunity. 20 (2): 145–51. doi:10.1016/S1074-7613(04)00020-2. PMID 14975237.
11. Yannay-Cohen N, Carmi-Levy I, Kay G, Yang CM, Han JM, Kemeny DM, Kim S, Nechushtan H, Razin E (June 2009). "LysRS serves as a key signaling molecule in the immune response by regulating gene expression". Mol Cell. 34 (5): 603–11. doi:10.1016/j.molcel.2009.05.019. PMID 19524539.

Further reading

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