HINT1
HINT1 (histidine triad nucleotide binding protein 1) is a member of the HINT family that hydrolyses purine nucleotide phosphoramidates and also acts as a scaffolding protein in transcriptional regulation. It is also known as PKCI-1, PRKCNH1 and HINT. Browse Assay Genie's current range of HINT1 research reagents below, or read on for the biology behind the target.
HINT1 exhibits adenosine 5'-monophosphoramidase activity, hydrolysing purine nucleotide phosphoramidates that carry a single phosphate group. Its substrates include adenosine 5'-monophosphoramidate (AMP-NH2), which is cleaved to AMP and NH2, as well as AMP-morpholidate, GMP-morpholidate and AMP-N-alanine methyl ester. It also hydrolyses lysyl-AMP generated by lysine tRNA ligase, along with Met-AMP, His-AMP and Asp-AMP. The enzyme engages its substrates through a histidine triad motif, and it can convert adenosine and guanosine 5'-O-phosphorothioate to the corresponding nucleoside 5'-O-phosphates with release of hydrogen sulfide.
Beyond catalysis, HINT1 functions as a scaffolding protein. It modulates transcriptional activation by the LEF1/TCF1-CTNNB1 complex and by the complex formed by MITF and CTNNB1. It modulates p53/TP53 levels and p53-mediated apoptosis, and it influences proteasomal degradation of target proteins by the SCF (SKP2-CUL1-F-box protein) E3 ubiquitin-protein ligase complex. HINT1 also shows SUMO-specific isopeptidase activity, deconjugating SUMO1 from RGS17 and RANGAP1. The protein is found in the cytoplasm and the nucleus.
The HINT1 gene belongs to the histidine triad superfamily and the HINT family, and its previous name was histidine triad nucleotide-binding protein. NCBI Gene describes it as a tumour suppressor gene, and mutations in it can cause autosomal recessive neuromyotonia and axonal neuropathy. Several related pseudogenes lie on chromosome 7, and several transcript variants have been observed. Mouse and rat both carry a Hint1 ortholog.
HINT1 is considered a tumour suppressor gene and modulates p53 levels and p53-mediated apoptosis, making it relevant to studies of cell death control.
As a scaffold for the LEF1/TCF1-CTNNB1 and MITF-CTNNB1 complexes, HINT1 is studied in transcriptional regulation downstream of beta-catenin.
HINT1 hydrolyses purine nucleotide phosphoramidates and aminoacyl-adenylates such as lysyl-AMP, giving a model for histidine triad enzyme activity.
Mutations in HINT1 cause autosomal recessive neuromyotonia and axonal neuropathy, linking the gene to inherited neuromuscular disease research.
HINT1 is an adenosine 5'-monophosphoramidase that hydrolyses purine nucleotide phosphoramidates such as AMP-NH2 and lysyl-AMP. It also acts as a scaffold in transcription by LEF1/TCF1-CTNNB1 complexes, modulates p53 levels and apoptosis, and has SUMO-specific isopeptidase activity toward RGS17 and RANGAP1.
HINT1 is also called PKCI-1, PRKCNH1 and HINT, and its UniProt protein name is adenosine 5'-monophosphoramidase HINT1. The previous HGNC name was histidine triad nucleotide-binding protein. NCBI Gene notes that several transcript variants have been observed.
NCBI Gene describes HINT1 as a tumour suppressor gene, and mutations in it can cause autosomal recessive neuromyotonia and axonal neuropathy. Mouse and rat each have a Hint1 ortholog. Check the datasheet of any product for its validated reactivity.
Binding partners and pathway components linked to HINT1 in transcription, p53 signalling and SUMO regulation.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P49773; product specifications from Assay Genie datasheets.