Histidine triad nucleotide-binding protein 1

NameHistidine 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 NameHINT1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0016443|Histidine triad nucleotide-binding protein 1
MADEIAKAQVARPGGDTIFGKIIRKEIPAKIIFEDDRCLAFHDISPQAPTHFLVIPKKHI
SQISVAEDDDESLLGHLMIVGKKCAADLGLNKGYRMVVNEGSDGGQSVYHVHLHVLGGRQ
MHWPPG
Number of residues126
Molecular Weight13801.815
Theoretical pI6.96
GO Classification
Functions
  • protein kinase C binding
  • hydrolase activity
  • nucleotide binding
Processes
  • signal transduction
  • regulation of transcription, DNA-templated
  • positive regulation of calcium-mediated signaling
  • transcription, DNA-templated
  • intrinsic apoptotic signaling pathway by p53 class mediator
  • purine ribonucleotide catabolic process
Components
  • cytoplasm
  • cytoskeleton
  • nucleus
  • plasma membrane
  • extracellular exosome
  • histone deacetylase complex
General FunctionProtein kinase c binding
Specific FunctionHydrolyzes 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 RegionsNot Available
GenBank Protein ID862933
UniProtKB IDP49773
UniProtKB Entry NameHINT1_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0016444|Histidine triad nucleotide-binding protein 1 (HINT1)
ATGGCAGATGAGATTGCCAAGGCTCAGGTCGCTCGGCCTGGTGGCGACACGATCTTTGGG
AAGATCATCCGCAAGGAAATACCAGCCAAAATCATTTTTGAGGATGACCGGTGCCTTGCT
TTCCATGACATTTCCCCTCAAGCACCAACACATTTTCTGGTGATACCCAAGAAACATATA
TCCCAGATTTCTGTGGCAGAAGATGATGATGAAAGTCTTCTTGGACACTTAATGATTGTT
GGCAAGAAATGTGCTGCTGATCTGGGCCTGAATAAGGGTTATCGAATGGTGGTGAATGAA
GGTTCAGATGGTGGACAGTCTGTCTATCACGTTCATCTCCATGTTCTTGGAGGTCGGCAA
ATGCATTGGCCTCCTGGTTAA
GenBank Gene IDU27143
GeneCard IDNot Available
GenAtlas IDHINT1
HGNC IDHGNC:4912
Chromosome Location5
Locus5q31.2
References
  1. Brzoska PM, Chen H, Levin NA, Kuo WL, Collins C, Fu KK, Gray JW, Christman MF: Cloning, mapping, and in vivo localization of a human member of the PKCI-1 protein family (PRKCNH1). Genomics. 1996 Aug 15;36(1):151-6. 8812426
  2. Brzoska PM, Chen H, Zhu Y, Levin NA, Disatnik MH, Mochly-Rosen D, Murnane JP, Christman MF: 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. 1995 Aug 15;92(17):7824-8. 7644499
  3. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  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. 8643579
  6. Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J: Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nat Biotechnol. 2003 May;21(5):566-9. Epub 2003 Mar 31. 12665801
  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. 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. 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. 16835243
  10. Chou TF, Tikh IB, Horta BA, Ghosh B, De Alencastro RB, Wagner CR: Engineered monomeric human histidine triad nucleotide-binding protein 1 hydrolyzes fluorogenic acyl-adenylate and lysyl-tRNA synthetase-generated lysyl-adenylate. J Biol Chem. 2007 May 18;282(20):15137-47. Epub 2007 Mar 2. 17337452
  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. 19112177
  12. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. 19608861
  13. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. 21269460
  14. Genovese G, Ghosh P, Li H, Rettino A, Sioletic S, Cittadini A, Sgambato A: The tumor suppressor HINT1 regulates MITF and beta-catenin transcriptional activity in melanoma cells. Cell Cycle. 2012 Jun 1;11(11):2206-15. doi: 10.4161/cc.20765. Epub 2012 Jun 1. 22647378
  15. Van Damme P, Lasa M, Polevoda B, Gazquez C, Elosegui-Artola A, Kim DS, De Juan-Pardo E, Demeyer K, Hole K, Larrea E, Timmerman E, Prieto J, Arnesen T, Sherman F, Gevaert K, Aldabe R: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12449-54. doi: 10.1073/pnas.1210303109. Epub 2012 Jul 18. 22814378
  16. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. 24275569
  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. 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. 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. 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. 22961002