Proteopedia

Histidine triad nucleotide-binding protein


Function

Histidine triad nucleotide-binding protein (HINT) or protein kinase C interacting protein or adenosine 5'-monophosphoamidase hydrolyzes purine nucleotide monophosphoamidates and some amino acid-AMPs[1]. HINT contain the His-X-His-X-His-X motif where X is a hydrophobic amino acid.

  • HINT1 is a tumor suppressor and has a role in neuropsychiatric diseases[2].
  • HINT2 is a mitochondrial hydrolase whose overexpression sensitizes cells to apoptosis[3].
  • Fragile histidine triad (FHIT) cleave diadenosine polyphosphates like ApppA.

Disease

FHIT gene abnormalities are seen in gallbladder carcinoma[4] and lung cancer[5].

Relevance

HINT is a tumor suppressor. FHIT-Ap(n)A complex functions in proapoptotic tumor suppression pathway. FHIT is overexpressed in inflammatory bowel disease[6] and in colorectal cancer[7].

Structural highlights

The [8]. Water molecules shown as red spheres.

3D structures of histidine triad nucleotide-binding protein

Histidine triad nucleotide-binding protein 3D structures


Structure of rabbit HINT1 complex with GMP (PDB code 3rhn).

Drag the structure with the mouse to rotate

ReferencesReferences

  1. ↑ Linde CI, Feng B, Wang JB, Golovina VA. Histidine triad nucleotide-binding protein 1 (HINT1) regulates Ca(2+) signaling in mouse fibroblasts and neuronal cells via store-operated Ca(2+) entry pathway. Am J Physiol Cell Physiol. 2013 Jun 1;304(11):C1098-104. doi:, 10.1152/ajpcell.00073.2013. Epub 2013 Apr 10. PMID:23576580 doi:http://dx.doi.org/10.1152/ajpcell.00073.2013
  2. ↑ Zhang Y, Da Q, Cao S, Yan K, Shi Z, Miao Q, Li C, Hu L, Sun S, Wu W, Wu L, Chen F, Wang L, Gao Y, Huang Z, Shao Y, Chen H, Wei Y, Chen F, Han Y, Xie L, Ji Y. HINT1 (Histidine Triad Nucleotide-Binding Protein 1) Attenuates Cardiac Hypertrophy Via Suppressing HOXA5 (Homeobox A5) Expression. Circulation. 2021 Aug 24;144(8):638-654. PMID:34098726 doi:10.1161/CIRCULATIONAHA.120.051094
  3. ↑ Martin J, Magnino F, Schmidt K, Piguet AC, Lee JS, Semela D, St-Pierre MV, Ziemiecki A, Cassio D, Brenner C, Thorgeirsson SS, Dufour JF. Hint2, a mitochondrial apoptotic sensitizer down-regulated in hepatocellular carcinoma. Gastroenterology. 2006 Jun;130(7):2179-88. PMID:16762638 doi:10.1053/j.gastro.2006.03.024
  4. ↑ Wistuba II, Ashfaq R, Maitra A, Alvarez H, Riquelme E, Gazdar AF. Fragile histidine triad gene abnormalities in the pathogenesis of gallbladder carcinoma. Am J Pathol. 2002 Jun;160(6):2073-9. PMID:12057912 doi:http://dx.doi.org/10.1016/S0002-9440(10)61157-1
  5. ↑ Zochbauer-Muller S, Wistuba II, Minna JD, Gazdar AF. Fragile histidine triad (FHIT) gene abnormalities in lung cancer. Clin Lung Cancer. 2000 Nov;2(2):141-5. PMID:14731325
  6. ↑ Wierzbicki PM, Adrych K, Kartanowicz D, Wypych J, Stanislawowski M, Zwolinska-Wcislo M, Celinski K, Skrodzka D, Godlewski J, Korybalski B, Smoczynski M, Kmiec Z. Overexpression of the fragile histidine triad (FHIT) gene in inflammatory bowel disease. J Physiol Pharmacol. 2009 Oct;60 Suppl 4:57-62. PMID:20083852
  7. ↑ Wierzbicki PM, Adrych K, Kartanowicz D, Dobrowolski S, Stanislawowski M, Chybicki J, Godlewski J, Korybalski B, Smoczynski M, Kmiec Z. Fragile histidine triad (FHIT) gene is overexpressed in colorectal cancer. J Physiol Pharmacol. 2009 Oct;60 Suppl 4:63-70. PMID:20083853
  8. ↑ Brenner C, Garrison P, Gilmour J, Peisach D, Ringe D, Petsko GA, Lowenstein JM. Crystal structures of HINT demonstrate that histidine triad proteins are GalT-related nucleotide-binding proteins. Nat Struct Biol. 1997 Mar;4(3):231-8. PMID:9164465

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