Histidine triad nucleotide-binding protein

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<StructureSection load='3rhn' size='350' side='right' caption='Structure of rabbit HINT1 complex with GMP (PDB code [[3rhn]]).' scene='59/593304/Cv/1'>
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<StructureSection load='' size='350' side='right' caption='Structure of rabbit HINT1 complex with GMP (PDB code [[3rhn]]).' scene='59/593304/Cv/1'>
== Function ==
== Function ==
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'''Histidine triad nucleotide-binding protein''' (HINT) or '''protein kinase C interacting protein''' hydrolyzes purine nucleotide monophosphoamidates and some amino acid-AMPs<ref>PMID:23576580</ref>. '''Fragile histidine triad''' (FHIT) cleave diadenosine polyphosphates like ApppA.
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'''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<ref>PMID:23576580</ref>. HINT contain the His-X-His-X-His-X motif where X is a hydrophobic amino acid.
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*'''HINT1''' is a tumor suppressor and has a role in neuropsychiatric diseases<ref>PMID:34098726</ref>.
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*'''HINT2''' is a mitochondrial hydrolase whose overexpression sensitizes cells to apoptosis<ref>PMID:16762638</ref>.
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* '''Fragile histidine triad''' (FHIT) cleave diadenosine polyphosphates like ApppA.
== Disease ==
== Disease ==
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== Relevance ==
== Relevance ==
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HINT is a tumor suppressor. FHIT-Ap(n)A complex functions in proapoptotic tumor suppression pathway. FHIT is overexpressed in inflammatory bowel disease<ref>PMID:20083852</ref> and in colorectal cancer<ref>PMID:20083853</ref>.
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HINT is a tumor suppressor. FHIT-Ap(n)A complex functions in proapoptotic tumor suppression pathway. FHIT is overexpressed in inflammatory bowel disease<ref>PMID:20083852</ref> and in colorectal cancer<ref>PMID:20083853</ref>.
== Structural highlights ==
== Structural highlights ==
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The <scene name='59/593304/Cv/4'>HINT nucleotide-binding cleft is at the top of the β sheet</scene><ref>PMID:9164465</ref>. Water molecules shown as red spheres.
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The <scene name='59/593304/Cv/5'>HINT nucleotide-binding cleft is at the top of the β sheet</scene><ref>PMID:9164465</ref>. Water molecules shown as red spheres.
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</StructureSection>
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==3D structures of histidine triad nucleotide-binding protein==
==3D structures of histidine triad nucleotide-binding protein==
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[[Histidine triad nucleotide-binding protein 3D structures]]
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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</StructureSection>
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{{#tree:id=OrganizedByTopic|openlevels=0|
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*HINT1
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**[[1kpa]], [[1kpb]], [[1kpc]] – hHINT – human<br />
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**[[6rhn]] – rHINT - rabbit<br />
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**[[3o1z]] – rHINT (mutant) <br />
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*HINT1 complexes
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**[[3rhn]] – rHINT + GMP <br />
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**[[4rhn]], [[3qgz]] – rHINT + adenosine<br />
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**[[5rhn]] – rHINT + 8-Br-AMP <br />
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**[[1av5]], [[1kpe]] – hHINT + adenosine derivative<br />
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**[[1kpf]], [[3tw2]] – hHINT + AMP <br />
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**[[1rzy]] – rHINT + adenosine derivative<br />
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**[[3o1c]], [[3o1x]] – rHINT (mutant) + adenosine <br />
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**[[4eqe]] – hHINT + Lys-AMS <br />
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**[[4eqg]] – hHINT + Ala-AMS <br />
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**[[4eqh]] – hHINT + Trp-AMS <br />
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*HINT2
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**[[4inc]], [[4njx]], [[4njy]], [[4njz]], [[4nk0]] – hHINT <br />
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**[[4ini]] – hHINT + AMP <br />
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*FHIT
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**[[1fit]], [[2fit]], [[4fit]] – hFHIT <br />
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**[[3fit]] – hFHIT + AMP <br />
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**[[5fit]], [[6fit]] – hFHIT + adenosine derivative<br />
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**[[1fhi]] – hFHIT + ApppA derivative<br />
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**[[2fhi]] – hFHIT (mutant) + ApppA derivative<br />
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}}
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== References ==
== References ==

Current revision

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

Drag the structure with the mouse to rotate

References

  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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