HINT1

Histidine triad nucleotide-binding protein 1 also known as adenosine 5'-monophosphoramidase is an enzyme that in humans is encoded by the HINT1 gene.[5][6]

HINT1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesHINT1, HINT, NMAN, PKCI-1, PRKCNH1, histidine triad nucleotide binding protein 1
External IDsOMIM: 601314 MGI: 1321133 HomoloGene: 3904 GeneCards: HINT1
Orthologs
SpeciesHumanMouse
Entrez

3094

15254

Ensembl

ENSG00000169567

ENSMUSG00000020267

UniProt

P49773

P70349

RefSeq (mRNA)

NM_005340

NM_008248

RefSeq (protein)

NP_005331

NP_032274

Location (UCSC)Chr 5: 131.16 – 131.22 MbChr 11: 54.76 – 54.76 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

HINT1 hydrolyzes purine nucleotide phosphoramidates with a single phosphate group.[7] In addition, functions as scaffolding protein that modulates transcriptional activation.[8]

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.[9][10] 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.[10][11]

See also

References

  1. GRCh38: Ensembl release 89: ENSG00000169567 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000020267 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 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.
  6. "Entrez Gene: HINT1 histidine triad nucleotide binding protein 1".
  7. Strom A, Tong CL, Wagner CR (May 2020). "Histidine triad nucleotide-binding proteins HINT1 and HINT2 share similar substrate specificities and little affinity for the signaling dinucleotide Ap4A". FEBS Letters. 594 (10): 1497–1505. doi:10.1002/1873-3468.13745. PMID 31990367. S2CID 210933742.
  8. "P49773: HINT1 (human)". UniProt.
  9. 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.
  10. 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.
  11. 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


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