Histidine triad nucleotide-binding protein 1

Details

Name
Histidine triad nucleotide-binding protein 1
Synonyms
  • 3.-.-.-
  • Adenosine 5'-monophosphoramidase
  • HINT
  • PKCI-1
  • PKCI1
  • PRKCNH1
  • Protein kinase C inhibitor 1
  • Protein kinase C-interacting protein 1
Gene Name
HINT1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0016443|Histidine triad nucleotide-binding protein 1
MADEIAKAQVARPGGDTIFGKIIRKEIPAKIIFEDDRCLAFHDISPQAPTHFLVIPKKHI
SQISVAEDDDESLLGHLMIVGKKCAADLGLNKGYRMVVNEGSDGGQSVYHVHLHVLGGRQ
MHWPPG
Number of residues
126
Molecular Weight
13801.815
Theoretical pI
6.96
GO Classification
Functions
hydrolase activity / nucleotide binding / protein kinase C binding
Processes
intrinsic apoptotic signaling pathway by p53 class mediator / positive regulation of calcium-mediated signaling / purine ribonucleotide catabolic process / regulation of transcription, DNA-templated / signal transduction / transcription, DNA-templated
Components
cytoplasm / cytoskeleton / extracellular exosome / histone deacetylase complex / nucleus / plasma membrane
General Function
Protein kinase c binding
Specific Function
Hydrolyzes purine nucleotide phosphoramidates with a single phosphate group, including adenosine 5'monophosphoramidate (AMP-NH2), adenosine 5'monophosphomorpholidate (AMP-morpholidate) and guanosine 5'monophosphomorpholidate (GMP-morpholidate). Hydrolyzes lysyl-AMP (AMP-N-epsilon-(N-alpha-acetyl lysine methyl ester)) generated by lysine tRNA ligase, as well as Met-AMP, His-AMP and Asp-AMP, lysyl-GMP (GMP-N-epsilon-(N-alpha-acetyl lysine methyl ester)) and AMP-N-alanine methyl ester. Can also convert adenosine 5'-O-phosphorothioate and guanosine 5'-O-phosphorothioate to the corresponding nucleoside 5'-O-phosphates with concomitant release of hydrogen sulfide. In addition, functions as scaffolding protein that modulates transcriptional activation by the LEF1/TCF1-CTNNB1 complex and by the complex formed with MITF and CTNNB1. Modulates p53/TP53 levels and p53/TP53-mediated apoptosis. Modulates proteasomal degradation of target proteins by the SCF (SKP2-CUL1-F-box protein) E3 ubiquitin-protein ligase complex.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0016444|Histidine triad nucleotide-binding protein 1 (HINT1)
ATGGCAGATGAGATTGCCAAGGCTCAGGTCGCTCGGCCTGGTGGCGACACGATCTTTGGG
AAGATCATCCGCAAGGAAATACCAGCCAAAATCATTTTTGAGGATGACCGGTGCCTTGCT
TTCCATGACATTTCCCCTCAAGCACCAACACATTTTCTGGTGATACCCAAGAAACATATA
TCCCAGATTTCTGTGGCAGAAGATGATGATGAAAGTCTTCTTGGACACTTAATGATTGTT
GGCAAGAAATGTGCTGCTGATCTGGGCCTGAATAAGGGTTATCGAATGGTGGTGAATGAA
GGTTCAGATGGTGGACAGTCTGTCTATCACGTTCATCTCCATGTTCTTGGAGGTCGGCAA
ATGCATTGGCCTCCTGGTTAA
Chromosome Location
5
Locus
5q31.2
External Identifiers
ResourceLink
UniProtKB IDP49773
UniProtKB Entry NameHINT1_HUMAN
GenBank Protein ID862933
GenBank Gene IDU27143
GenAtlas IDHINT1
HGNC IDHGNC:4912
General References
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  5. 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. 1996 May 28;93(11):5357-62. [PubMed:8643579]
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  7. Chou TF, Bieganowski P, Shilinski K, Cheng J, Brenner C, Wagner CR: 31P NMR and genetic analysis establish hinT as the only Escherchia coli purine nucleoside phosphoramidase and as essential for growth under high salt conditions. J Biol Chem. 2005 Apr 15;280(15):15356-61. Epub 2005 Feb 9. [PubMed:15703176]
  8. Weiske J, Huber O: The histidine triad protein Hint1 interacts with Pontin and Reptin and inhibits TCF-beta-catenin-mediated transcription. J Cell Sci. 2005 Jul 15;118(Pt 14):3117-29. [PubMed:16014379]
  9. Weiske J, Huber O: The histidine triad protein Hint1 triggers apoptosis independent of its enzymatic activity. J Biol Chem. 2006 Sep 15;281(37):27356-66. Epub 2006 Jul 11. [PubMed:16835243]
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  11. Cen B, Li H, Weinstein IB: Histidine triad nucleotide-binding protein 1 up-regulates cellular levels of p27KIP1 by targeting ScfSKP2 ubiquitin ligase and Src. J Biol Chem. 2009 Feb 20;284(8):5265-76. doi: 10.1074/jbc.M804531200. Epub 2008 Dec 27. [PubMed:19112177]
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  17. Lima CD, Klein MG, Hendrickson WA: Structure-based analysis of catalysis and substrate definition in the HIT protein family. Science. 1997 Oct 10;278(5336):286-90. [PubMed:9323207]
  18. Dolot R, Ozga M, Wlodarczyk A, Krakowiak A, Nawrot B: A new crystal form of human histidine triad nucleotide-binding protein 1 (hHINT1) in complex with adenosine 5'-monophosphate at 1.38 A resolution. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012 Aug 1;68(Pt 8):883-8. doi: 10.1107/S1744309112029491. Epub 2012 Jul 27. [PubMed:22869114]
  19. Wang J, Fang P, Schimmel P, Guo M: Side chain independent recognition of aminoacyl adenylates by the Hint1 transcription suppressor. J Phys Chem B. 2012 Jun 14;116(23):6798-805. doi: 10.1021/jp212457w. Epub 2012 Mar 2. [PubMed:22329685]
  20. Zimon M, Baets J, Almeida-Souza L, De Vriendt E, Nikodinovic J, Parman Y, Battaloglu E, Matur Z, Guergueltcheva V, Tournev I, Auer-Grumbach M, De Rijk P, Petersen BS, Muller T, Fransen E, Van Damme P, Loscher WN, Barisic N, Mitrovic Z, Previtali SC, Topaloglu H, Bernert G, Beleza-Meireles A, Todorovic S, Savic-Pavicevic D, Ishpekova B, Lechner S, Peeters K, Ooms T, Hahn AF, Zuchner S, Timmerman V, Van Dijck P, Rasic VM, Janecke AR, De Jonghe P, Jordanova A: Loss-of-function mutations in HINT1 cause axonal neuropathy with neuromyotonia. Nat Genet. 2012 Oct;44(10):1080-3. doi: 10.1038/ng.2406. Epub 2012 Sep 9. [PubMed:22961002]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00131Adenosine phosphateapproved, investigational, nutraceuticalunknownproduct ofDetails
DB01972Guanosine-5'-MonophosphateexperimentalunknownDetails
DB021625'-O-(N-Ethyl-Sulfamoyl)AdenosineexperimentalunknownDetails
DB02183Adenosine-5'-DitungstateexperimentalunknownDetails
DB033498-Bromo-Adenosine-5'-MonophosphateexperimentalunknownDetails
DB08934SofosbuvirapprovedunknownsubstrateDetails