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{{Infobox_gene}}
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'''Histidine triad nucleotide-binding protein 1''' is a [[protein]] that in humans is encoded by the ''HINT1'' [[gene]].<ref name="pmid8812426">{{cite journal |vauthors=Brzoska PM, Chen H, Levin NA, Kuo WL, Collins C, Fu KK, Gray JW, Christman MF | title = Cloning, mapping, and in vivo localization of a human member of the PKCI-1 protein family (PRKCNH1) | journal = Genomics | volume = 36 | issue = 1 | pages = 151–6 |date=Feb 1997 | pmid = 8812426 | pmc =  | doi = 10.1006/geno.1996.0435 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: HINT1 histidine triad nucleotide binding protein 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3094| accessdate = }}</ref> It is a [[haploinsufficient]] tumor suppressor gene that inhibits the [[Wnt signaling pathway|Wnt/β-catenin pathway]] in colon cancer cells and [[microphthalmia-associated transcription factor]] (MITF) activity in human mast cells.<ref name="pmid19089909">{{cite journal |vauthors=Wang L, Li H, Zhang Y, Santella RM, Weinstein IB | title = HINT1 inhibits beta-catenin/TCF4, USF2 and NFkappaB activity in human hepatoma cells| journal = Int J Cancer | volume = 124 | issue = 7 | pages = 1526–34|date=Apr 2009 | pmid = 19089909 | pmc = 2667231 | doi = 10.1002/ijc.24072 }}</ref><ref name="pmid14975237">{{cite journal |vauthors=Lee YN, Nechushtan H, Figov N, Razin E | title = The function of lysyl-tRNA synthetase and Ap4A as signaling regulators of MITF activity in FcepsilonRI-activated mast cells | journal = Immunity| volume = 20 | issue = 2 | pages = 145–51 |date=Feb 2004 | pmid = 14975237 | pmc =  | doi =10.1016/S1074-7613(04)00020-2 }}</ref> 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 [[KARS (gene)|LysRS]].<ref name="pmid14975237"/><ref name="pmid19524539">{{cite journal |vauthors=Yannay-Cohen N, Carmi-Levy I, Kay G, Yang CM, Han JM, Kemeny DM, Kim S, Nechushtan H, Razin E | title = LysRS serves as a key signaling molecule in the immune response by regulating gene expression | journal = Mol Cell| volume = 34 | issue = 5 | pages = 603–11 |date=June 2009 | pmid = 19524539 | pmc =  | doi =10.1016/j.molcel.2009.05.019 }}</ref>
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{{GNF_Protein_box
| image = PBB_Protein_HINT1_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1av5.
| PDB = {{PDB2|1av5}}, {{PDB2|1kpa}}, {{PDB2|1kpb}}, {{PDB2|1kpc}}, {{PDB2|1kpe}}, {{PDB2|1kpf}}, {{PDB2|1rzy}}, {{PDB2|3rhn}}, {{PDB2|4rhn}}, {{PDB2|5rhn}}, {{PDB2|6rhn}}
| Name = Histidine triad nucleotide binding protein 1
| HGNCid = 4912
| Symbol = HINT1
| AltSymbols =; HINT; PKCI-1; PRKCNH1
| OMIM = 601314
| ECnumber =
| Homologene = 3904
| MGIid = 1321133
  | GeneAtlas_image1 = PBB_GE_HINT1_207721_x_at_tn.png
| GeneAtlas_image2 = PBB_GE_HINT1_208826_x_at_tn.png
| GeneAtlas_image3 = PBB_GE_HINT1_200093_s_at_tn.png
| Function = {{GNF_GO|id=GO:0005080 |text = protein kinase C binding}} {{GNF_GO|id=GO:0008270 |text = zinc ion binding}} {{GNF_GO|id=GO:0016787 |text = hydrolase activity}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}} {{GNF_GO|id=GO:0005856 |text = cytoskeleton}}
| Process = {{GNF_GO|id=GO:0007165 |text = signal transduction}}  
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 3094
    | Hs_Ensembl = ENSG00000169567
    | Hs_RefseqProtein = NP_005331
    | Hs_RefseqmRNA = NM_005340
    | Hs_GenLoc_db =
    | Hs_GenLoc_chr = 5
    | Hs_GenLoc_start = 130522883
    | Hs_GenLoc_end = 130528935
    | Hs_Uniprot = P49773
    | Mm_EntrezGene = 15254
    | Mm_Ensembl = ENSMUSG00000020267
    | Mm_RefseqmRNA = NM_008248
    | Mm_RefseqProtein = NP_032274
    | Mm_GenLoc_db =   
    | Mm_GenLoc_chr = 11
    | Mm_GenLoc_start = 54709816
    | Mm_GenLoc_end = 54713914
    | Mm_Uniprot = Q5SNR9
  }}
}}
'''Histidine triad nucleotide binding protein 1''', also known as '''HINT1''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: HINT1 histidine triad nucleotide binding protein 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3094| accessdate = }}</ref>


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| summary_text =  
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}}
==See also==
* [[Histidine triad nucleotide-binding protein 2]] (HINT2)


==References==
==References==
{{reflist|2}}
{{reflist}}
 
==Further reading==
==Further reading==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading  
{{PBB_Further_reading  
| citations =  
| citations =  
*{{cite journal | author=Brzoska PM, Chen H, Zhu Y, ''et al.'' |title=The product of the ataxia-telangiectasia group D complementing gene, ATDC, interacts with a protein kinase C substrate and inhibitor. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=92 |issue= 17 |pages= 7824-8 |year= 1995 |pmid= 7644499 |doi=  }}
*{{cite journal   |vauthors=Brzoska PM, Chen H, Zhu Y, etal |title=The product of the ataxia-telangiectasia group D complementing gene, ATDC, interacts with a protein kinase C substrate and inhibitor. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=92 |issue= 17 |pages= 7824–8 |year= 1995 |pmid= 7644499 |doi=10.1073/pnas.92.17.7824  | pmc=41238 }}
*{{cite journal  | author=Lima CD, Klein MG, Weinstein IB, Hendrickson WA |title=Three-dimensional structure of human protein kinase C interacting protein 1, a member of the HIT family of proteins. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=93 |issue= 11 |pages= 5357-62 |year= 1996 |pmid= 8643579 |doi=  }}
*{{cite journal  |vauthors=Lima CD, Klein MG, Weinstein IB, Hendrickson WA |title=Three-dimensional structure of human protein kinase C interacting protein 1, a member of the HIT family of proteins. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=93 |issue= 11 |pages= 5357–62 |year= 1996 |pmid= 8643579 |doi=10.1073/pnas.93.11.5357  | pmc=39250  }}
*{{cite journal  | author=Brzoska PM, Chen H, Levin NA, ''et al.'' |title=Cloning, mapping, and in vivo localization of a human member of the PKCI-1 protein family (PRKCNH1). |journal=Genomics |volume=36 |issue= 1 |pages= 151-6 |year= 1997 |pmid= 8812426 |doi= 10.1006/geno.1996.0435 }}
*{{cite journal  |vauthors=Lima CD, Klein MG, Hendrickson WA |title=Structure-based analysis of catalysis and substrate definition in the HIT protein family. |journal=Science |volume=278 |issue= 5336 |pages= 286–90 |year= 1997 |pmid= 9323207 |doi=10.1126/science.278.5336.286 }}
*{{cite journal  | author=Lima CD, Klein MG, Hendrickson WA |title=Structure-based analysis of catalysis and substrate definition in the HIT protein family. |journal=Science |volume=278 |issue= 5336 |pages= 286-90 |year= 1997 |pmid= 9323207 |doi=  }}
*{{cite journal   |vauthors=Klein MG, Yao Y, Slosberg ED, etal |title=Characterization of PKCI and comparative studies with FHIT, related members of the HIT protein family. |journal=Exp. Cell Res. |volume=244 |issue= 1 |pages= 26–32 |year= 1998 |pmid= 9770345 |doi= 10.1006/excr.1998.4153 }}
*{{cite journal | author=Klein MG, Yao Y, Slosberg ED, ''et al.'' |title=Characterization of PKCI and comparative studies with FHIT, related members of the HIT protein family. |journal=Exp. Cell Res. |volume=244 |issue= 1 |pages= 26-32 |year= 1998 |pmid= 9770345 |doi= 10.1006/excr.1998.4153 }}
*{{cite journal   |vauthors=Weitzdoerfer R, Stolzlechner D, Dierssen M, etal |title=Reduction of nucleoside diphosphate kinase B, Rab GDP-dissociation inhibitor beta and histidine triad nucleotide-binding protein in fetal Down syndrome brain. |journal=J. Neural Transm. Suppl. |volume= |issue= 61 |pages= 347–59 |year= 2002 |pmid= 11771757 |doi=  10.1007/978-3-7091-6262-0_29}}
*{{cite journal | author=Weitzdoerfer R, Stolzlechner D, Dierssen M, ''et al.'' |title=Reduction of nucleoside diphosphate kinase B, Rab GDP-dissociation inhibitor beta and histidine triad nucleotide-binding protein in fetal Down syndrome brain. |journal=J. Neural Transm. Suppl. |volume= |issue= 61 |pages= 347-59 |year= 2002 |pmid= 11771757 |doi=  }}
*{{cite journal   |vauthors=Bieganowski P, Garrison PN, Hodawadekar SC, etal |title=Adenosine monophosphoramidase activity of Hint and Hnt1 supports function of Kin28, Ccl1, and Tfb3. |journal=J. Biol. Chem. |volume=277 |issue= 13 |pages= 10852–60 |year= 2002 |pmid= 11805111 |doi= 10.1074/jbc.M111480200 | pmc=2556056 }}
*{{cite journal | author=Bieganowski P, Garrison PN, Hodawadekar SC, ''et al.'' |title=Adenosine monophosphoramidase activity of Hint and Hnt1 supports function of Kin28, Ccl1, and Tfb3. |journal=J. Biol. Chem. |volume=277 |issue= 13 |pages= 10852-60 |year= 2002 |pmid= 11805111 |doi= 10.1074/jbc.M111480200 }}
*{{cite journal  | author=Brenner C |title=Hint, Fhit, and GalT: function, structure, evolution, and mechanism of three branches of the histidine triad superfamily of nucleotide hydrolases and transferases. |journal=Biochemistry |volume=41 |issue= 29 |pages= 9003–14 |year= 2002 |pmid= 12119013 |doi=10.1021/bi025942q  | pmc=2571077 }}
*{{cite journal  | author=Brenner C |title=Hint, Fhit, and GalT: function, structure, evolution, and mechanism of three branches of the histidine triad superfamily of nucleotide hydrolases and transferases. |journal=Biochemistry |volume=41 |issue= 29 |pages= 9003-14 |year= 2002 |pmid= 12119013 |doi=  }}
*{{cite journal   |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 }}
*{{cite journal | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{cite journal   |vauthors=Gevaert K, Goethals M, Martens L, etal |title=Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. |journal=Nat. Biotechnol. |volume=21 |issue= 5 |pages= 566–9 |year= 2004 |pmid= 12665801 |doi= 10.1038/nbt810 }}
*{{cite journal | author=Gevaert K, Goethals M, Martens L, ''et al.'' |title=Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. |journal=Nat. Biotechnol. |volume=21 |issue= 5 |pages= 566-9 |year= 2004 |pmid= 12665801 |doi= 10.1038/nbt810 }}
*{{cite journal   |vauthors=Galey D, Becker K, Haughey N, etal |title=Differential transcriptional regulation by human immunodeficiency virus type 1 and gp120 in human astrocytes. |journal=J. Neurovirol. |volume=9 |issue= 3 |pages= 358–71 |year= 2003 |pmid= 12775419 |doi=10.1080/13550280390201119 }}
*{{cite journal | author=Galey D, Becker K, Haughey N, ''et al.'' |title=Differential transcriptional regulation by human immunodeficiency virus type 1 and gp120 in human astrocytes. |journal=J. Neurovirol. |volume=9 |issue= 3 |pages= 358-71 |year= 2003 |pmid= 12775419 |doi=  }}
*{{cite journal   |vauthors=Ota T, Suzuki Y, Nishikawa T, etal |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40–5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
*{{cite journal | author=Ota T, Suzuki Y, Nishikawa T, ''et al.'' |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40-5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
*{{cite journal   |vauthors=Gerhard DS, Wagner L, Feingold EA, etal |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 | pmc=528928 }}
*{{cite journal | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
*{{cite journal  |vauthors=Weiske J, Huber O |title=The histidine triad protein Hint1 triggers apoptosis independent of its enzymatic activity. |journal=J. Biol. Chem. |volume=281 |issue= 37 |pages= 27356–66 |year= 2006 |pmid= 16835243 |doi= 10.1074/jbc.M513452200 }}
*{{cite journal  | author=Weiske J, Huber O |title=The histidine triad protein Hint1 triggers apoptosis independent of its enzymatic activity. |journal=J. Biol. Chem. |volume=281 |issue= 37 |pages= 27356-66 |year= 2006 |pmid= 16835243 |doi= 10.1074/jbc.M513452200 }}
*{{cite journal   |vauthors=Ajit SK, Ramineni S, Edris W, etal |title=RGSZ1 interacts with protein kinase C interacting protein PKCI-1 and modulates mu opioid receptor signaling. |journal=Cell. Signal. |volume=19 |issue= 4 |pages= 723–30 |year= 2007 |pmid= 17126529 |doi= 10.1016/j.cellsig.2006.09.008 }}
*{{cite journal | author=Ajit SK, Ramineni S, Edris W, ''et al.'' |title=RGSZ1 interacts with protein kinase C interacting protein PKCI-1 and modulates mu opioid receptor signaling. |journal=Cell. Signal. |volume=19 |issue= 4 |pages= 723-30 |year= 2007 |pmid= 17126529 |doi= 10.1016/j.cellsig.2006.09.008 }}
*{{cite journal  | vauthors= Symes AJ, Eilertsen M, Millar M| last-author-amp= yes|title=Quantitative Analysis of BTF3, HINT1, NDRG1 and ODC1 Protein Over-Expression in Human Prostate Cancer Tissue  |journal=PLoS ONE |volume=8 |issue=12 |pages=  e84295 |year= 2013 |pmid=  24386364|doi= 10.1371/journal.pone.0084295 |pmc=3874000|display-authors=etal}}
}}
}}
{{refend}}
{{refend}}
{{PDB Gallery|geneid=3094}}
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Latest revision as of 13:38, 31 August 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

n/a

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Histidine triad nucleotide-binding protein 1 is a protein that in humans is encoded by the HINT1 gene.[1][2] 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.[3][4] 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.[4][5]


See also

References

  1. 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.
  2. "Entrez Gene: HINT1 histidine triad nucleotide binding protein 1".
  3. 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.
  4. 4.0 4.1 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.
  5. 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