Histidine triad nucleotide-binding protein 1 (HINT1)
The protein contains 126 amino acids for an estimated molecular weight of 13802 Da.
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. (updated: Sept. 12, 2018)
Protein identification was indicated in the following studies:
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology.
Biological Process
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
The reference OMIM entry for this protein is 137200
Neuromyotonia and axonal neuropathy, autosomal recessive; nman
Gamstorp-wohlfart syndrome
Myokymia, myotonia, and muscle wasting
A number sign (#) is used with this entry because autosomal recessive neuromyotonia and axonal neuropathy (NMAN) is caused by homozygous or compound heterozygous mutation in the HINT1 gene (601314) on chromosome 5q31.
DESCRIPTION
NMAN is an autosomal recessive neurologic disorder characterized by onset in the first or second decade of a peripheral axonal neuropathy predominantly affecting motor more than sensory nerves. The axonal neuropathy is reminiscent of Charcot-Marie-Tooth disease type 2 (see, e.g.,CMT
2A1, 118210) and distal hereditary motor neuropathy (see, e.g., HMN1, 182960). Individuals with NMAN also have delayed muscle relaxation and action myotonia associated with neuromyotonic discharges on needle EMG resulting from hyperexcitability of the peripheral nerves (summary by Zimon et al., 2012).CLINICAL FEATURES
Hahn et al. (1991) reported a Canadian brother and sister of Chinese origin with childhood-onset neuromyotonia and progressive motor neuropathy. The boy developed generalized muscle stiffening at age 10 years. He had difficulty in releasing his grip, his fingers tended to cramp on writing, and he had involuntary twitching of his fingers, forearm muscles, and thighs at rest. A few years later, he had gait difficulties due to foot drop and weakness of the hands. Physical examination showed distal wasting and weakness of the muscles of the upper and lower limbs with hyporeflexia and absent ankle jerks. Myokymia and fasciculations were observed at rest. He also showed action myotonia and percussion of the tongue resulting in tonic contractions, although percussion of the thenar eminence showed no abnormalities. There were no sensory abnormalities. His younger sister was less severely affected, with no spontaneous muscle activity at rest, but she showed weakness in the distal muscles of the upper and lower limbs. There was percussion myotonia of the tongue, but grip release was not delayed. Reflexes and sensory examination were normal. Electrophysiologic studies in both patients showed a chronic motor neuropathy with partial denervation of muscle and collateral reinnervation and evidence of abnormal spontaneous nerve activity due to hyperexcitability of peripheral nerve fibers. Muscle biopsy in the brother showed chronic partial denervation. The neuromyotonic symptoms improved with diphenylhydantoin, carbamazepine, and tocainide. In the sibs reported by Hahn et al. (1991), Zimon et al. (2012) identified compound heterozygous mutations in the HINT1 gene (601314.0006 and 601314.0007). Zimon et al. (2012) reported 50 patients from 33 families with NMAN. Disease onset was typically in the first decade, and most patients presented with gait impairment due to distal leg weakness, although several presented with cramps in the hands and legs and muscle stiffness. The upper and lower limbs were affected. Some patients had foot deformities; most remained ambulatory in their thirties. Distal sensory impairment was present to a mild degree in about half of patients. Most patients showed delayed muscle relaxation of the hands after strong finger flexion, consistent with action myotonia. Nerve conduction studies showed an axonal neuropathy, which was pure motor in some and mixed motor and sensory in others. Sural nerve biopsy of some patients showed axonal neuropathy, even in the absence of clinical sensory abnormalities. Needle EMG showed spontaneous high-frequency motor unit action potentials consisten ... More on the omim web site
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 137200 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).