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Showing HINT1 — HINT is a alias.

HINT1

Adenosine 5'-monophosphoramidase HINT1 · UniProt P49773

Length
126 aa
Mass
13.8 kDa
Annotated
2026-06-10
100 papers in source corpus 30 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HINT1 is a universally conserved, dimeric purine nucleotide-binding enzyme of the HIT superfamily that doubles as a redox-regulated signaling scaffold and transcriptional co-repressor (PMID:9164465, PMID:11805111). Its active site—built on the HIT phosphate-binding loop with Ser107 in acid-base catalysis and Trp123 anchoring substrate across the dimer interface—hydrolyzes adenosine 5'-monophosphoramidate, AMP-lysine, aminoacyl-adenylates, and nucleoside phosphorothioate/selenophosphate substrates, the latter releasing H2S or cytotoxic H2Se (PMID:11805111, PMID:14982931, PMID:20940308, PMID:22329685, PMID:35054788). Independently of catalysis, HINT1 acts as a tumor suppressor by binding and co-repressing oncogenic transcription factors including β-catenin/TCF (via Pontin/Reptin), MITF, AP-1/JNK2, USF2, and NF-κB, recruiting mSIN3a/HDAC1 and Tip60 repressor/acetyltransferase complexes to target promoters such as cyclin D1, BCL2, and Bax; catalytically dead H112N mutants retain this activity (PMID:16014379, PMID:16835243, PMID:17510397, PMID:22647378). This repressive function is tuned by post-translational control: SIRT1-mediated deacetylation at K21/K30 strengthens factor binding, while Ap4A-driven HINT1 polymerization competitively displaces MITF to relieve repression (PMID:31604935, PMID:32636443). In neurons, HINT1 scaffolds the C-terminus of GPCRs—particularly the mu-opioid receptor—recruiting RGSZ proteins, PKCγ, Raf-1, and σ1R through a NO/zinc redox switch to govern GPCR-NMDAR cross-regulation, opioid analgesia, and neuropathic pain (PMID:18652891, PMID:21235400, PMID:25557043, PMID:26461475). HINT1 also restrains cardiac hypertrophy by blocking PKCβ1 membrane translocation and the downstream MEK/ERK/YY1/HOXA5 axis (PMID:34098726). Loss-of-function mutations in HINT1 cause autosomal recessive axonal neuropathy with neuromyotonia (PMID:22961002).

Mechanistic history

Synthesis pass · year-by-year structured walk · 27 steps
  1. 1997 High

    Established the structural basis of HINT as a nucleotide-binding protein, defining the HIT motif's role and an unexpected fold relationship to GalT.

    Evidence X-ray crystallography of HINT-nucleotide complexes

    PMID:9164465

    Open questions at the time
    • Did not identify the physiological substrate
    • Catalytic mechanism not resolved from binding alone
  2. 2002 High

    Identified the natural enzymatic activity (AMP-phosphoramidate hydrolysis) and placed HINT in a transcription-kinase regulatory pathway via yeast genetics.

    Evidence In vitro kinetics with AMP-NH2 plus yeast epistasis with TFIIK/Cak1 alleles and rabbit Hint complementation

    PMID:11805111

    Open questions at the time
    • Direct enzymatic substrate in transcription pathway not pinpointed
    • Mechanism linking hydrolase activity to kinase regulation unresolved
  3. 2000 High

    Linked HINT physically to the cell-cycle/transcription kinase Cdk7, showing a kinase-activity-independent interaction conserved to yeast Kin28.

    Evidence Yeast two-hybrid, reciprocal Co-IP, localization, and yeast double-mutant analysis

    PMID:10958787

    Open questions at the time
    • Functional consequence of Cdk7 binding for HINT unclear
    • Mechanism of Cdk7-driven nuclear relocalization unknown
  4. 2004 High

    Defined the catalytic machinery for AMP-lysine/phosphoramidate hydrolysis, assigning Ser107 to acid-base catalysis and Trp123 to substrate binding.

    Evidence 1.8-Å co-crystal structure, S107A mutagenesis, and kinetics with novel substrates/inhibitors

    PMID:14982931

    Open questions at the time
    • In vivo substrate of the AMP-lysine activity not established
    • Physiological context of catalysis unaddressed
  5. 2005 High

    Revealed HINT1's enzyme-independent role as a transcriptional repressor of β-catenin/TCF signaling through Pontin/Reptin binding.

    Evidence Pull-down/Co-IP with domain mapping, TCF-luciferase reporters, and RNAi with target qPCR

    PMID:16014379

    Open questions at the time
    • Whether repression requires the catalytic site untested here
    • Recruitment of corepressor machinery not yet defined
  6. 2006 High

    Demonstrated catalysis-independent pro-apoptotic/tumor-suppressor function through Bax promoter occupancy and Tip60 complex association.

    Evidence ChIP, Co-IP with Tip60, apoptosis assays, shRNA, and H112N catalytic mutant in cancer cells

    PMID:16835243

    Open questions at the time
    • How HINT1 is recruited to the Bax promoter unknown
    • Relationship between p53 induction and direct chromatin binding unclear
  7. 2007 High

    Extended HINT1 repression to AP-1 by showing it forms a POSH-JNK2 complex blocking c-Jun phosphorylation, JNK2-specifically.

    Evidence Endogenous Co-IP, AP-1 reporters, JNK1/JNK2 KO MEF epistasis, and H112N mutant

    PMID:17510397

    Open questions at the time
    • Structural basis of HINT1-POSH-JNK2 assembly unknown
    • Why JNK2 but not JNK1 is targeted unexplained
  8. 2008 High

    Placed HINT1 in the DNA damage response, showing it is needed for γ-H2AX/ATM acetylation and efficient repair.

    Evidence IRIF immunofluorescence, Co-IP with γ-H2AX/ATM, acetylation and repair kinetics in Hint1-/- cells

    PMID:18852295

    Open questions at the time
    • Direct enzymatic contribution to acetylation events unclear
    • Mechanism of HINT1 recruitment to damage foci unknown
  9. 2008 High

    Defined HINT1 as a scaffold at the mu-opioid receptor C-terminus that recruits PKCγ via RGSZ proteins in a zinc/NMDAR-dependent manner.

    Evidence Brain Co-IP, ICV pharmacology, HINT1 siRNA, zinc chelation, and NOS/NMDAR inhibitors

    PMID:18652891

    Open questions at the time
    • Direct structural map of the MOR-HINT1-RGSZ interface absent
    • Source/handling of recruited zinc not fully resolved
  10. 2009 Medium

    Generalized HINT1 transcriptional repression to USF2 and NF-κB, including blockade of p65 nuclear translocation.

    Evidence Co-IP, multiple reporter assays, and nuclear fractionation in hepatoma cells

    PMID:19089909

    Open questions at the time
    • Single-lab Co-IP/reporter without domain mapping
    • Mechanism of p65 nuclear-translocation block undefined
  11. 2010 High

    Expanded the substrate repertoire to nucleoside phosphorothioates, showing HINT1 catalyzes desulfuration with H2S release.

    Evidence HPLC enzymatic assays, mutagenesis, and high-resolution crystallography of mutants

    PMID:20940308

    Open questions at the time
    • Physiological relevance of phosphorothioate desulfuration unknown
    • In vivo H2S generation not demonstrated
  12. 2011 Medium

    Showed NO-released zinc recruits the Ras/Raf-1/ERK cassette to HINT1 at MOR alongside PKCγ, integrating two CRD-bearing effectors.

    Evidence Brain Co-IP with NOS inhibitors and zinc chelation, ICV paradigms

    PMID:21235400

    Open questions at the time
    • Single-lab pharmacological dissection
    • Stoichiometry of simultaneous Raf-1/PKCγ binding unresolved
  13. 2012 High

    Identified HINT1 as a melanoma tumor suppressor co-repressing MITF and β-catenin via mSIN3a/HDAC1 recruitment at BCL2 and cyclin D1 promoters.

    Evidence Co-IP, ChIP, reporters, xenograft, and rescue by target overexpression

    PMID:22647378

    Open questions at the time
    • Determinants of promoter selectivity unclear
    • Whether the same complex operates on all repressed factors untested
  14. 2012 High

    Defined the structural basis for broad aminoacyl-adenylate hydrolysis, showing Trp123 cation-π anchoring of the α-amino group.

    Evidence Crystal structures with aa-AMP analogues and in vitro hydrolysis assays

    PMID:22329685

    Open questions at the time
    • Cellular substrate among aminoacyl-adenylates not identified
    • Link to translation/aaRS biology not tested
  15. 2012 High

    Established HINT1 as the causative gene for autosomal recessive axonal neuropathy with neuromyotonia.

    Evidence Linkage analysis and NGS across 33 families identifying 8 mutations

    PMID:22961002

    Open questions at the time
    • Which HINT1 molecular function underlies neuropathy not resolved by genetics
    • Cell-type-specific disease mechanism unknown
  16. 2013 High

    Showed HINT1 functionally constrains NMDAR activity in concert with GPCRs in neurons, with viral rescue restoring control.

    Evidence HINT1-/- and CNR1-/- cortical neurons, lentiviral rescue, excitotoxicity and electrophysiology

    PMID:24093505

    Open questions at the time
    • Molecular bridge between GPCR-HINT1 and NMDAR not fully mapped
    • Generalizability across GPCR types untested here
  17. 2015 High

    Defined a redox/zinc switch by which σ1R is recruited to MOR-HINT1 complexes to restrain opioid signaling and NMDAR coupling.

    Evidence Brain Co-IP, ICV pharmacology, σ1R-/- and HINT1-/- mice, NOS inhibition

    PMID:25557043 PMID:26461475

    Open questions at the time
    • Atomic-level interface of σ1R-HINT1-NR1 unknown
    • Quantitative thresholds of the zinc switch undefined
  18. 2015 Medium

    Identified teneurin-1 ICD as a HINT1-binding partner that titrates HINT1 away from MITF to derepress targets like GPNMB.

    Evidence Yeast two-hybrid, Co-IP in human cells, transcriptomics, and promoter reporters

    PMID:25648896

    Open questions at the time
    • Single-lab interaction without structural mapping
    • Physiological contexts of teneurin-HINT1 competition unclear
  19. 2015 Medium

    Linked HINT1 enzymatic active site to opioid pharmacology, showing an active-site inhibitor enhances analgesia and prevents tolerance.

    Evidence In vivo pharmacology with HINT1 inhibitor TpGc, antinociception and neuropathic pain assays

    PMID:25445489

    Open questions at the time
    • Enzymatic dependency inferred from inhibitor, not genetic active-site mutant in vivo
    • Single lab
  20. 2017 Medium

    Connected HINT1 PTMs (K21 acetylation, Y109 phosphorylation) and Ap4A signaling to switching MITF oncogenic activity on.

    Evidence Mass spectrometry of PTMs in mast cells, mutagenesis, and melanoma reporter assays

    PMID:28394346

    Open questions at the time
    • Writers/erasers for Y109 not identified
    • In vivo relevance of PTM switch untested
  21. 2019 Medium

    Proposed a SUMO isopeptidase activity for HINT1 gated by zinc/NO/CaM and altered in all tested ARAN-NM mutants.

    Evidence In vitro sumoylase assay, catalytic-triad mutagenesis, pharmacological gating, and disease-mutant panel

    PMID:31088288

    Open questions at the time
    • Novel activity from a single lab awaits independent confirmation
    • In vivo SUMO substrates not identified
  22. 2019 High

    Demonstrated structurally that Ap4A drives HINT1 polymerization through an interface overlapping the MITF-binding surface, providing a competitive derepression mechanism.

    Evidence Eight crystal structures, negative-stain EM, polymerization assays, and RBL cell experiments

    PMID:31604935

    Open questions at the time
    • Cellular triggers of Ap4A accumulation for polymerization not delineated
    • Reversibility kinetics in vivo unclear
  23. 2019 Medium

    Showed distinct HINT1 active-site inhibitors yield different effects on opioid tolerance versus NMDAR cross-talk, tied to differential binding surfaces.

    Evidence Crystallography of HINT1-inhibitor complexes, ITC, and spinal in vivo pharmacology

    PMID:31503445

    Open questions at the time
    • Structural basis for divergent behavioral outcomes incompletely defined
    • Single lab
  24. 2020 High

    Identified CBP/SIRT1 as writer/eraser at K21/K30 controlling HINT1's affinity for β-catenin/MITF and its tumor-suppressive output.

    Evidence Co-IP, acetylation assays, K21R/K30R mutagenesis, binding assays, and xenografts

    PMID:32636443

    Open questions at the time
    • How acetylation alters the binding surface structurally unknown
    • Upstream signals regulating SIRT1/CBP on HINT1 undefined
  25. 2021 High

    Defined a cardioprotective HINT1 axis that blocks PKCβ1 membrane translocation to suppress MEK/ERK/YY1/HOXA5-driven hypertrophy.

    Evidence Co-IP, fractionation, Hint1 KO and AAV9-HINT1 mice with TAC, RNA-seq, and AAV9-shHoxa5 rescue

    PMID:34098726

    Open questions at the time
    • Direct HINT1-PKCβ1 binding interface not mapped
    • Whether enzymatic activity contributes untested
  26. 2021 Medium

    Showed HINT1/σ1R control α2δ1 incorporation into NMDAR complexes, linking the scaffold to neuropathic allodynia.

    Evidence PAG tissue Co-IP, σ1R-/- and HINT1-/- mice with constriction injury, and in vivo pharmacology

    PMID:34827679

    Open questions at the time
    • Single-lab series extension
    • Structural arrangement of the α2δ1-σ1R-NR1-HINT1 assembly unknown
  27. 2022 Medium

    Extended HINT1 catalysis to selenophosphate nucleotides, generating cytotoxic H2Se in cancer cells.

    Evidence HPLC/fluorescence enzymatic assays, viability assays, and intracellular H2Se detection

    PMID:35054788

    Open questions at the time
    • Endogenous selenophosphate substrate existence unknown
    • Therapeutic exploitation untested in vivo

Open questions

Synthesis pass · forward-looking unresolved questions
  • How HINT1's conserved enzymatic activities mechanistically connect to its scaffolding and transcriptional-repressor roles—and which function underlies ARAN-NM—remains unresolved.
  • No endogenous physiological substrate has been definitively assigned to the catalytic activity
  • The molecular basis by which loss-of-function mutations cause peripheral neuropathy is unestablished
  • Whether the proposed SUMO isopeptidase activity is independently reproducible is open

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 5 GO:0140110 transcription regulator activity 5 GO:0060090 molecular adaptor activity 4 GO:0003677 DNA binding 3 GO:0140098 catalytic activity, acting on RNA 2 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005634 nucleus 3 GO:0005886 plasma membrane 2 GO:0005829 cytosol 1 GO:0005856 cytoskeleton 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-112316 Neuronal System 3 R-HSA-1643685 Disease 1 R-HSA-5357801 Programmed Cell Death 1 R-HSA-73894 DNA Repair 1
Partners
CDK7CTNNB1MITFPKCGRAF1RGSZ2RUVBL1SIGMAR1
Complex memberships
MOR-HINT1-RGSZ scaffoldTip60 histone acetyltransferase complexmSIN3a/HDAC1 corepressor complex

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 Crystal structures of HINT in complex with nucleotides demonstrated that HINT is a dimeric purine nucleotide-binding protein; the HIT motif forms part of the phosphate-binding loop, and the most conserved residues mediate nucleotide binding. These structures revealed that HINT shares the same fold and mode of nucleotide binding as galactose-1-phosphate uridylyltransferase (GalT) despite no overall sequence similarity. X-ray crystallography of HINT-nucleotide complexes Nature structural biology High 9164465
2002 Rabbit HINT1 and yeast Hnt1 hydrolyze adenosine-5'-monophosphoramidate (AMP-NH2) as natural substrates in an active-site-dependent manner, with second-order rates exceeding 1,000,000 M−1 s−1. Loss of Hnt1 enzyme activity in yeast leads to failure to grow on galactose at elevated temperature and hypersensitivity to mutations in Kin28, Ccl1, and Tfb3 (the TFIIK kinase subcomplex of TFIIH), placing Hnt1 as a positive regulator of this transcription kinase pathway downstream of Cak1. In vitro enzymatic assay with AMP-NH2; yeast genetic epistasis with temperature-sensitive alleles and deletion strains; functional complementation with rabbit Hint The Journal of biological chemistry High 11805111
2002 HINT belongs to the adenosine 5'-monophosphoramide hydrolase branch of the HIT superfamily; a new enzyme mechanism was proposed for Hint and Fhit based on comparative structural and biochemical analysis of the three HIT branches (Hint, Fhit, GalT). Biochemical and structural comparative analysis; sequence/substrate specificity review with mechanistic inference Biochemistry Medium 12119013
2000 HINT/PKCI-1 physically interacts with Cdk7; this interaction was identified by yeast two-hybrid and confirmed by co-immunoprecipitation. Overexpression of Cdk7 leads to partial relocalization of Hint to the nucleus. The interaction is independent of cyclin H binding or Cdk7 kinase activity. The orthologous interaction between yeast Kin28 and Hnt1 is conserved, and genetic combination of hnt1 deletion with a kin28 temperature-sensitive allele causes elongated cell morphology and reduced colony formation. Yeast two-hybrid, co-immunoprecipitation, subcellular localization by fluorescence microscopy, yeast genetic interaction (double mutant analysis) The Journal of biological chemistry High 10958787
2004 Biochemical and structural characterization of HINT enzymatic activity as an AMP-lysine (adenosine phosphoramidate) hydrolase. The 1.8-Å co-crystal structure with N-ethylsulfamoyl adenosine revealed a binding site for the alkyl group against Trp-123 across the dimer interface. Ser-107 donates a hydrogen bond to the leaving-group nitrogen; the S107A mutant displays markedly depressed catalytic activity, confirming a role for Ser-107 in acid-base catalysis. A novel substrate AMP-pNA and inhibitors (AdoOSO2NH2, AdoOSO2NHCH2CH3) were characterized kinetically. X-ray crystallography (1.8 Å co-crystal), active-site mutagenesis (S107A), in vitro kinetic assay with novel substrates and inhibitors The Journal of biological chemistry High 14982931
2005 HINT1/PKCI-1 directly binds to Pontin and Reptin; pull-down and co-immunoprecipitation experiments mapped the HINT1 binding site to amino acids 214–295 of Pontin and 218–289 of Reptin, while Pontin and Reptin bind the N-terminus of HINT1. Through this interaction, HINT1 associates with the LEF-1/TCF–β-catenin transcription complex and acts as a negative regulator of TCF–β-catenin transcriptional activity, repressing cyclin D1 and axin2 expression. RNAi knockdown of HINT1 increases these target genes. Pull-down assay, co-immunoprecipitation, reporter gene assay (TCF-luciferase), RNAi knockdown with RT-PCR/qPCR Journal of cell science High 16014379
2006 HINT1 overexpression induces apoptosis in SW480 and MCF-7 cells via upregulation of p53 and proapoptotic Bax and downregulation of Bcl-2. HINT1 associates with the Bax promoter and is a component of the Tip60 histone acetyltransferase complex. A catalytically inactive mutant HINT1 (H112N) retains full pro-apoptotic activity, demonstrating that the apoptotic function is independent of AMP-NH2 hydrolase enzymatic activity. Transient transfection, caspase-3/PARP cleavage assay, cytochrome c release, DNA fragmentation ELISA, shRNA knockdown, chromatin immunoprecipitation (ChIP), co-immunoprecipitation with Tip60 complex, active-site mutant (H112N) The Journal of biological chemistry High 16835243
2007 HINT1 inhibits AP-1 transcriptional activity in colon cancer cells by forming an in vivo complex with POSH (plenty of SH3) and JNK2, thereby inhibiting phosphorylation of c-Jun. This pathway requires JNK2 but not JNK1, confirmed in JNK1-/- and JNK2-/- MEFs. Both wild-type HINT1 and the enzymatically inactive H112N mutant inhibit AP-1 activity equivalently, indicating the inhibition is independent of enzymatic function. Co-immunoprecipitation (HINT1-POSH-JNK complex), reporter gene assay (AP-1-luciferase), JNK1-/- and JNK2-/- MEF epistasis, phospho-c-Jun western blot, retroviral overexpression Cancer research High 17510397
2008 HINT1 participates in ionizing radiation (IR)-induced DNA damage responses: it is recruited to IR-induced foci (IRIF) and co-associates with γ-H2AX and ATM. HINT1 deficiency does not prevent γ-H2AX foci formation but impairs their removal and impairs acetylation of γ-H2AX. HINT1 deficiency also impairs acetylation and activation of ATM and retards DNA repair; HINT1-deficient cells resist IR-induced apoptosis and exhibit chromosomal abnormalities. Immunofluorescence (IRIF recruitment), co-immunoprecipitation (HINT1-γ-H2AX-ATM), acetylation assays, DNA repair kinetics, apoptosis assays in Hint1-/- cells vs. WT The Journal of cell biology High 18852295
2008 In neurons, the C-terminus of the mu-opioid receptor (MOR) binds PKCI/HINT1, which in turn binds the regulator of G-protein signaling RGSZ1/Z2 proteins. Morphine administration recruits PKCγ (mostly) to the MOR via the HINT1/RGSZ complex. This recruitment requires zinc ions, HINT1, and RGSZ proteins, and specifically involves the cysteine-rich domains (CRDs) of PKCγ. NMDAR antagonist MK801 and NOS inhibition prevent PKCγ recruitment, implicating the NMDAR/nNOS cascade in providing zinc ions required for PKCγ to bind the HINT1/RGSZ complex at MOR. Co-immunoprecipitation from mouse brain; intracerebroventricular drug administration; siRNA knockdown of HINT1; zinc chelation (TPEN); phorbol ester and NO donor treatments Cellular signalling High 18652891
2009 HINT1 co-immunoprecipitates with USF2 in hepatoma cell extracts and inhibits transcriptional activities of β-catenin/TCF4, USF2, and NF-κB in HepG2 cells. HINT1 overexpression inhibits nuclear translocation of p65 (NF-κB subunit) and reduces expression of cyclin D1 and TGFβ2. Co-immunoprecipitation, reporter gene assays (β-catenin/TCF4, USF2, NF-κB luciferase), nuclear fractionation, western blot International journal of cancer Medium 19089909
2010 HINT1 (Hint-1) phosphoramidase catalyzes the desulfuration of nucleoside 5'-O-phosphorothioates ((d)NMPS) to the corresponding nucleoside 5'-O-phosphates with release of hydrogen sulfide. Crystallographic analysis (1.08–1.37 Å) of three engineered cysteine mutants confirmed minimal structural perturbation. Substrate specificity order was determined: GMPS > AMPS > dGMPS ≥ CMPS > UMPS > dAMPS >> dCMPS > TMPS. In vitro enzymatic assay (HPLC-based), active-site mutagenesis, X-ray crystallography (1.08–1.37 Å resolution) of mutant structures The Journal of biological chemistry High 20940308
2011 Morphine-generated nitric oxide (NO) causes release of endogenous zinc ions that recruit the Ras/Raf-1/ERK1/2 cassette to HINT1 at the MOR C-terminus; zinc bridges the Raf-1 cysteine-rich domain (CRD) with HINT1. Simultaneously, PKCγ is also recruited via NO/zinc to the MOR-HINT1 complex; Raf-1 and PKCγ CRDs bind simultaneously to HINT1, enabling PKCγ to enhance Raf-1 function and thereby MEK/ERK1/2 activation. A-Raf and B-Raf show little or no MOR association. Co-immunoprecipitation from mouse brain, pharmacological dissection (NOS inhibitors, zinc chelator TPEN), intracerebroventricular injection paradigms Antioxidants & redox signaling Medium 21235400
2012 HINT1 co-immunoprecipitates with MITF and β-catenin in melanoma cell lines. HINT1 inhibits MITF and β-catenin transcriptional activity, reduces cyclin D1 and BCL2 expression (known MITF and β-catenin targets), and ChIP assays demonstrate HINT1 occupancy at MITF and β-catenin binding sites in BCL2 and cyclin D1 promoters. HINT1 co-immunoprecipitates with mSIN3a and HDAC1, suggesting recruitment of a repressor complex. Co-immunoprecipitation, ChIP assay, reporter gene assay, stable HINT1 overexpression with xenograft, rescue by BCL2/cyclin D1 overexpression Cell cycle High 22647378
2012 Human HINT1 has broad specificity for aminoacyl adenylate (aa-AMP) hydrolysis, recognizing only the common main-chain of the aminoacyl moiety and having no contact with the amino acid side chain. High-resolution crystal structures of HINT1 with three different aa-AMP analogues revealed that the α-amino group is anchored by a cation-π interaction with Trp123 at the C-terminus. X-ray crystallography (HINT1 with aa-AMP analogues), in vitro hydrolysis assays The journal of physical chemistry B High 22329685
2012 Loss-of-function mutations in HINT1 cause autosomal recessive axonal neuropathy with neuromyotonia, identified by combining linkage analysis and next-generation sequencing in 33 families with 8 distinct mutations. Linkage analysis, next-generation sequencing, cohort mutation screening Nature genetics High 22961002
2013 HINT1 protein influences NMDAR activity in the presence of GPCRs: in CNR1+/+/HINT1-/- cortical neurons, NMDAR activation was enhanced and cannabinoid agonist WIN55,212-2 failed to protect against NMDA insult. Lentiviral re-expression of HINT1 normalized NMDAR activity and restored cannabinoid-mediated neuroprotection. In the absence of receptor activation, GPCRs collaborate with HINT1 to negatively control NMDAR activity. HINT1-/- and CNR1-/- mouse cortical neuron culture, lentiviral HINT1 rescue, NMDA excitotoxicity assay, electrophysiology Molecular brain High 24093505
2015 The teneurin-1 intracellular domain (ICD) binds HINT1 (identified by yeast two-hybrid and confirmed in human cells), disrupting HINT1-mediated repression of MITF transcriptional targets. Teneurin-1 ICD overexpression upregulates MITF target genes including GPNMB; promoter reporter assays showed the teneurin-1 ICD switches on MITF-dependent GPNMB transcription by binding and titrating HINT1 away from MITF. Yeast two-hybrid, co-immunoprecipitation in human cells, transcriptome analysis, RT-qPCR, promoter reporter assay The Journal of biological chemistry Medium 25648896
2015 The sigma 1 receptor (σ1R) engages HINT1 at the MOR C-terminus through a redox-regulated mechanism: activated MORs stimulate nitric oxide (NO) production; the RGSZ2 redox zinc switch converts this into free zinc ions that recruit PKCγ to HINT1 proteins, impairing HINT1-RGSZ2 association and enabling σ1R-NR1 interaction with MOR-HINT1 complexes to restrain opioid signaling. σ1R antagonists remove σ1R from NR1, facilitate Ca2+-CaM entry, and prevent NR1-HINT1 interaction, blocking the negative feedback on opioid analgesia. Co-immunoprecipitation from mouse brain, intracerebroventricular pharmacology, σ1R-/- and HINT1-/- mice, NOS inhibition, in vitro binding assays Antioxidants & redox signaling High 25557043
2015 HINT1 and σ1R coordinate GPCR-NMDAR interactions: HINT1 binds GPCRs and NMDAR NR1 subunits in a calcium-independent manner, while σ1R binding to these proteins increases with calcium. σ1R agonists retain HINT1 at the GPCR and promote GPCR-NMDAR interaction; σ1R antagonists transfer HINT1 to NR1 subunits and disengage GPCRs from NMDARs. In σ1R-/- mice, HINT1 proteins mostly associate with NMDARs and GPCRs are functionally disconnected from NMDARs. In HINT1-/- mice, ischemia produces reduced NMDAR-mediated brain damage. Co-immunoprecipitation, in vivo pharmacology, σ1R-/- and HINT1-/- mice, ischemia model, electrophysiology Oncotarget High 26461475
2015 The HINT1 enzymatic active site is critical for its regulatory role at the MOR-NMDAR interface; the HINT1 inhibitor guanosine-5'-tryptamine carbamate (TpGc) significantly enhances morphine antinociception, prevents tolerance development, and reduces MOR recruitment of NMDAR activity. Intracerebroventricular TpGc also attenuates NMDAR function and alleviates mechanical allodynia in chronic constriction injury mice. In vivo pharmacology with HINT1 active-site inhibitor, antinociception assays, mouse model of neuropathic pain, molecular interaction assays Neuropharmacology Medium 25445489
2017 HINT1 undergoes post-translational modifications in activated mast cells: K21 acetylation and Y109 phosphorylation. Mutational analysis confirmed that these modifications promote MITF transcriptional and oncogenic activity in melanoma cell lines, linked to the Ap4A-triggered dissociation of HINT1 from MITF. The LysRS-Ap4A-HINT1-MITF signaling pathway can be modulated through HINT1 PTMs to affect MITF-driven transcription. Mass spectrometry identification of PTMs in activated mast cells, site-directed mutagenesis (K21, Y109), reporter assays in melanoma cell lines Oncogene Medium 28394346
2019 HINT1 exhibits zinc- and redox-regulated cysteine SUMO isopeptidase (sumoylase) activity, removing SUMO from signaling proteins. The catalytic triad Cys84-Asp87-His114 in the C-terminal region and a SUMO-interacting motif (residues 110-116 HIHLHVL) were identified. HINT1 sumoylase activity is blocked by zinc and released by nitric oxide or calcium-activated calmodulin (CaM). All 15 human HINT1 mutants causing ARAN-NM showed altered sumoylase activity. In vitro sumoylase assay, site-directed mutagenesis of catalytic triad, zinc/NO/CaM pharmacological manipulation, analysis of 15 disease-causing mutants Antioxidants & redox signaling Medium 31088288
2019 Ap4A specifically polymerizes HINT1 in solution and in activated rat basophilic leukemia cells. Eight crystal structures revealed that Ap4A binding drives HINT1 polymerization; the polymerization interface overlaps with the HINT1-MITF interaction surface, suggesting a competitive mechanism to release MITF for transcriptional activation. The polymerization depends precisely on the length of the phosphodiester linkage of Ap4A. X-ray crystallography (8 structures), negative stain electron microscopy, biochemical polymerization assays, cellular experiments in RBL cells Nature communications High 31604935
2020 HINT1 is acetylated by CBP at K21 and K30 and deacetylated by SIRT1. Deacetylation of HINT1 by SIRT1 increases the binding capacity of HINT1 for β-catenin or MITF, enhancing its tumor-suppressive function. The deacetylation-mimetic double mutant HINT1-2KR (K21R/K30R) significantly reduced cellular proliferation in colon cancer and melanoma cells in both cell-based and xenograft assays. Co-immunoprecipitation (HINT1 with CBP/SIRT1), acetylation assays, site-directed mutagenesis (K21R, K30R), in vitro binding assays, xenograft tumor assays Experimental & molecular medicine High 32636443
2021 HINT1 inhibits PKCβ1 membrane translocation and phosphorylation via direct interaction, attenuating the MEK/ERK/YY1 signaling pathway and thereby downregulating HOXA5 expression. HOXA5, in turn, affects hypertrophy through the TGF-β signaling pathway. In Hint1-deficient mice, cardiac hypertrophy was exacerbated after pressure overload; cardiac-specific HINT1 overexpression (via AAV9) alleviated it. The cardioprotective role of HINT1 was abolished by HOXA5 knockdown in vivo. Co-immunoprecipitation (HINT1-PKCβ1), cellular fractionation (PKCβ1 membrane translocation assay), Hint1 KO and AAV9-HINT1 OE mice with transverse aortic constriction, RNA sequencing, PCR array, AAV9-shHoxa5 in vivo Circulation High 34098726
1996 Human PKCI-1 (HINT1/PRKCNH1) localizes to cytoskeletal structures in the cytoplasm of human fibroblast cell lines by indirect immunofluorescence and is largely excluded from the nucleus, consistent with a role in mediating membrane-derived signals. Indirect immunofluorescence in human fibroblast cell line Genomics Medium 8812426
2021 HINT1 and σ1R control α2δ1 binding to NMDAR NR1 subunits: α2δ1 peptides require σ1Rs to interact with the NMDAR NR1 C1 segment. σ1R antagonists or low calcium dissociate σ1R-NR1 C1 dimers. HINT1 removes α2δ1 from the δ1-σ1R-NR1 trimer, facilitating σ1R dissociation from NMDARs. In σ1R-/- mice, sciatic nerve injury does not promote NMDAR-α2δ1 complex formation and allodynia does not develop; in HINT1-/- mice, α2δ1-σ1R-NMDAR complexes are increased and allodynia is exacerbated. Co-immunoprecipitation from PAG tissue, σ1R-/- and HINT1-/- mice with chronic constriction injury model, in vivo pharmacology Biomolecules Medium 34827679
2019 Spinal inhibition of HINT1 enzymatic activity by active-site inhibitors (TrpGc vs. acyl-sulfamate analogues) differentially affects MOR-NMDAR cross-talk: TrpGc blocked both the development of opioid tolerance and the inhibitory effect of opioids on NMDA activation, while acyl-sulfamate analogues could only block the latter. X-ray crystallographic and thermodynamic binding studies revealed key differences between bound HINT1-inhibitor surfaces that may account for their distinct pharmacological profiles. X-ray crystallography of HINT1-inhibitor complexes, isothermal titration calorimetry, in vivo spinal pharmacology, opioid tolerance behavioral assay ACS chemical neuroscience Medium 31503445
2022 HINT1 catalyzes the hydrolysis of deoxyguanosine-5'-O-selenophosphate (dGMPSe) with similar kcat and Km to the corresponding thiophosphate (dGMPS), releasing hydrogen selenide (H2Se). This H2Se release is toxic to HeLa cancer cells, demonstrating that HINT1 enzymatic activity toward selenophosphate nucleotides can generate cytotoxic H2Se intracellularly. HPLC-based and fluorescence-based enzymatic assay, MTT viability assay, fluorescence detection of H2Se in living cells, electroporation of substrate International journal of molecular sciences Medium 35054788

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 HINT: High-quality protein interactomes and their applications in understanding human disease. BMC systems biology 315 22846459
2002 Hint, Fhit, and GalT: function, structure, evolution, and mechanism of three branches of the histidine triad superfamily of nucleotide hydrolases and transferases. Biochemistry 247 12119013
1997 Crystal structures of HINT demonstrate that histidine triad proteins are GalT-related nucleotide-binding proteins. Nature structural biology 125 9164465
2002 Stability of a PKCI-1-related mRNA is controlled by the splicing factor ASF/SF2: a novel function for SR proteins. Genes & development 120 11877379
2006 The histidine triad protein Hint1 triggers apoptosis independent of its enzymatic activity. The Journal of biological chemistry 116 16835243
2005 The histidine triad protein Hint1 interacts with Pontin and Reptin and inhibits TCF-beta-catenin-mediated transcription. Journal of cell science 100 16014379
2002 Adenosine monophosphoramidase activity of Hint and Hnt1 supports function of Kin28, Ccl1, and Tfb3. The Journal of biological chemistry 96 11805111
2006 Hint1 is a haplo-insufficient tumor suppressor in mice. Oncogene 93 16186798
2012 Loss-of-function mutations in HINT1 cause axonal neuropathy with neuromyotonia. Nature genetics 92 22961002
2004 A hint to search for metalloproteins in gene banks. Bioinformatics (Oxford, England) 90 14962940
2006 A hint for the function of human Sco1 from different structures. Proceedings of the National Academy of Sciences of the United States of America 83 16735468
2015 The σ1 receptor engages the redox-regulated HINT1 protein to bring opioid analgesia under NMDA receptor negative control. Antioxidants & redox signaling 73 25557043
2006 Mapping the energetics of water-protein and water-ligand interactions with the "natural" HINT forcefield: predictive tools for characterizing the roles of water in biomolecules. Journal of molecular biology 64 16497327
2007 Hint1 inhibits growth and activator protein-1 activity in human colon cancer cells. Cancer research 61 17510397
2009 Anti-depressant and anxiolytic like behaviors in PKCI/HINT1 knockout mice associated with elevated plasma corticosterone level. BMC neuroscience 54 19912621
2021 HINT1 (Histidine Triad Nucleotide-Binding Protein 1) Attenuates Cardiac Hypertrophy Via Suppressing HOXA5 (Homeobox A5) Expression. Circulation 53 34098726
2008 NMDAR-nNOS generated zinc recruits PKCgamma to the HINT1-RGS17 complex bound to the C terminus of Mu-opioid receptors. Cellular signalling 53 18652891
2015 The ON:OFF switch, σ1R-HINT1 protein, controls GPCR-NMDA receptor cross-regulation: implications in neurological disorders. Oncotarget 52 26461475
2009 Atypical p-ANCA in PSC and AIH: a hint toward a "leaky gut"? Clinical reviews in allergy & immunology 52 18626795
2006 RGSZ1 interacts with protein kinase C interacting protein PKCI-1 and modulates mu opioid receptor signaling. Cellular signalling 52 17126529
2004 Biochemical, crystallographic, and mutagenic characterization of hint, the AMP-lysine hydrolase, with novel substrates and inhibitors. The Journal of biological chemistry 52 14982931
2000 Interactions of Cdk7 and Kin28 with Hint/PKCI-1 and Hnt1 histidine triad proteins. The Journal of biological chemistry 52 10958787
2005 31P NMR and genetic analysis establish hinT as the only Escherchia coli purine nucleoside phosphoramidase and as essential for growth under high salt conditions. The Journal of biological chemistry 50 15703176
2013 HINT1 protein cooperates with cannabinoid 1 receptor to negatively regulate glutamate NMDA receptor activity. Molecular brain 48 24093505
2007 Supersensitivity to amphetamine in protein kinase-C interacting protein/HINT1 knockout mice. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 48 17203012
2018 Taraxasterol suppresses the growth of human liver cancer by upregulating Hint1 expression. Journal of molecular medicine (Berlin, Germany) 46 29806073
2013 Quantitative analysis of BTF3, HINT1, NDRG1 and ODC1 protein over-expression in human prostate cancer tissue. PloS one 44 24386364
2008 Evolution of hedgehog and hedgehog-related genes, their origin from Hog proteins in ancestral eukaryotes and discovery of a novel Hint motif. BMC genomics 44 18334026
2012 The tumor suppressor HINT1 regulates MITF and β-catenin transcriptional activity in melanoma cells. Cell cycle (Georgetown, Tex.) 43 22647378
2011 Increased anxiety-related behaviour in Hint1 knockout mice. Behavioural brain research 43 21316396
2008 Is the histidine triad nucleotide-binding protein 1 (HINT1) gene a candidate for schizophrenia? Schizophrenia research 42 18799291
2008 Distribution and expression of protein kinase C interactive protein (PKCI/HINT1) in mouse central nervous system (CNS). Neurochemical research 41 18270824
2009 HINT1 inhibits beta-catenin/TCF4, USF2 and NFkappaB activity in human hepatoma cells. International journal of cancer 38 19089909
2008 Silencing of Hint1, a novel tumor suppressor gene, by promoter hypermethylation in hepatocellular carcinoma. Cancer letters 38 19081673
2017 Post-translational modification of HINT1 mediates activation of MITF transcriptional activity in human melanoma cells. Oncogene 37 28394346
2017 Social isolation induces schizophrenia-like behavior potentially associated with HINT1, NMDA receptor 1, and dopamine receptor 2. Neuroreport 36 28410269
2015 HINT1 protein: a new therapeutic target to enhance opioid antinociception and block mechanical allodynia. Neuropharmacology 35 25445489
2010 Histidine triad nucleotide-binding protein 1 (HINT-1) phosphoramidase transforms nucleoside 5'-O-phosphorothioates to nucleoside 5'-O-phosphates. The Journal of biological chemistry 34 20940308
2009 Computational chemistry study of 3D-structure-function relationships for enzymes based on Markov models for protein electrostatic, HINT, and van der Waals potentials. Journal of computational chemistry 34 19086060
2008 The HINT1 tumor suppressor regulates both gamma-H2AX and ATM in response to DNA damage. The Journal of cell biology 33 18852295
2003 Coordinate expression of NADPH-dependent flavin reductase, Fre-1, and Hint-related 7meGMP-directed hydrolase, DCS-1. The Journal of biological chemistry 33 12871939
2017 Axonal neuropathy with neuromyotonia: there is a HINT. Brain : a journal of neurology 31 28007994
2014 Mutations in HINT1 are one of the most frequent causes of hereditary neuropathy among Czech patients and neuromyotonia is rather an underdiagnosed symptom. Neurogenetics 31 25342199
2011 NO-released zinc supports the simultaneous binding of Raf-1 and PKCγ cysteine-rich domains to HINT1 protein at the mu-opioid receptor. Antioxidants & redox signaling 29 21235400
2003 Feminizing chicks: a model for avian sex determination based on titration of Hint enzyme activity and the predicted structure of an Asw-Hint heterodimer. Genome biology 29 12620103
2018 Altered Light Conditions Contribute to Abnormalities in Emotion and Cognition Through HINT1 Dysfunction in C57BL/6 Mice. Frontiers in behavioral neuroscience 28 29937721
2013 Exome sequencing reveals HINT1 mutations as a cause of distal hereditary motor neuropathy. European journal of human genetics : EJHG 28 24105373
2020 Pharmacological Targets of Kaempferol Within Inflammatory Pathways-A Hint Towards the Central Role of Tryptophan Metabolism. Antioxidants (Basel, Switzerland) 27 32098277
2015 The intracellular domain of teneurin-1 induces the activity of microphthalmia-associated transcription factor (MITF) by binding to transcriptional repressor HINT1. The Journal of biological chemistry 27 25648896
2024 DLM-DTI: a dual language model for the prediction of drug-target interaction with hint-based learning. Journal of cheminformatics 26 38297330
2021 Enriched Opportunistic Pathogens Revealed by Metagenomic Sequencing Hint Potential Linkages between Pharyngeal Microbiota and COVID-19. Virologica Sinica 25 33978940
2011 Differential expression of HINT1 in schizophrenia brain tissue. European archives of psychiatry and clinical neuroscience 25 21553311
2004 P80, the HinT interacting membrane protein, is a secreted antigen of Mycoplasma hominis. BMC microbiology 25 15579213
2022 Endogenous reparative pluripotent Muse cells with a unique immune privilege system: Hint at a new strategy for controlling acute and chronic inflammation. Frontiers in pharmacology 24 36339573
2017 A novel relationship for schizophrenia, bipolar and major depressive disorder Part 5: a hint from chromosome 5 high density association screen. American journal of translational research 24 28559998
2003 The histidine triad protein Hint is not required for murine development or Cdk7 function. Molecular and cellular biology 24 12748294
1996 Cloning, mapping, and in vivo localization of a human member of the PKCI-1 protein family (PRKCNH1). Genomics 24 8812426
2020 Signal multi-amplified electrochemical biosensor for voltammetric determination of tau-441 protein in biological samples using carbon nanomaterials and gold nanoparticles to hint dementia. Mikrochimica acta 23 32350619
2010 Association of the histidine-triad nucleotide-binding protein-1 (HINT1) gene variants with nicotine dependence. The pharmacogenomics journal 23 20514075
2005 HINT: a database of annotated protein-protein interactions and their homologs. Biophysics (Nagoya-shi, Japan) 23 27857549
2018 Novel mutations in HINT1 gene cause the autosomal recessive axonal neuropathy with neuromyotonia. European journal of medical genetics 22 30006059
2017 HINT1 in Neuropsychiatric Diseases: A Potential Neuroplastic Mediator. Neural plasticity 22 29214080
2011 Increased human defensine levels hint at an inflammatory etiology of bisphosphonate-associated osteonecrosis of the jaw: an immunohistological study. Journal of translational medicine 22 21843332
2004 Altered specificity of Hint-W123Q supports a role for Hint inhibition by ASW in avian sex determination. Physiological genomics 22 15507519
2014 Lack of neuropathy-related phenotypes in hint1 knockout mice. Journal of neuropathology and experimental neurology 21 24918641
2013 Myofibroblasts, regeneration or renal fibrosis--is there a decisive hint? Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 21 23975753
2010 Turner syndrome and schizophrenia: a further hint for the role of the X-chromosome in the pathogenesis of schizophrenic disorders. The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry 21 20218787
2005 Histone acetylation, chromatin remodelling and nucleotide excision repair: hint from the study on MFA2 in Saccharomyces cerevisiae. Cell cycle (Georgetown, Tex.) 21 16082210
2019 Second messenger Ap4A polymerizes target protein HINT1 to transduce signals in FcεRI-activated mast cells. Nature communications 20 31604935
2017 Increased PKC activity and altered GSK3β/NMDAR function drive behavior cycling in HINT1-deficient mice: bipolarity or opposing forces. Scientific reports 20 28240305
2016 A Novel Relationship for Schizophrenia, Bipolar, and Major Depressive Disorder. Part 8: a Hint from Chromosome 8 High Density Association Screen. Molecular neurobiology 20 27660274
2020 Deacetylation by SIRT1 promotes the tumor-suppressive activity of HINT1 by enhancing its binding capacity for β-catenin or MITF in colon cancer and melanoma cells. Experimental & molecular medicine 19 32636443
2015 A case of neuromyotonia and axonal motor neuropathy: A report of a HINT1 mutation in the United States. Muscle & nerve 19 26182879
2015 HINT1 is involved in the behavioral abnormalities induced by social isolation rearing. Neuroscience letters 19 26300541
2012 Side chain independent recognition of aminoacyl adenylates by the Hint1 transcription suppressor. The journal of physical chemistry. B 19 22329685
2010 Design and structure of an equilibrium protein folding intermediate: a hint into dynamical regions of proteins. Journal of molecular biology 19 20553732
2014 HINT1 peptide/Hsp70 complex induces NK-cell-dependent immunoregulation in a model of autoimmune demyelination. European journal of immunology 18 25092109
2012 Acute behavioral effects of nicotine in male and female HINT1 knockout mice. Genes, brain, and behavior 18 22827509
2019 The Axonal Motor Neuropathy-Related HINT1 Protein Is a Zinc- and Calmodulin-Regulated Cysteine SUMO Protease. Antioxidants & redox signaling 17 31088288
2016 DO SYMPTOMS OF ILLNESS SERVE SIGNALING FUNCTIONS? (HINT: YES). The Quarterly review of biology 17 27405223
2012 The role of insulin C-peptide in the coevolution analyses of the insulin signaling pathway: a hint for its functions. PloS one 17 23300796
2009 Web application for studying the free energy of binding and protonation states of protein-ligand complexes based on HINT. Journal of computer-aided molecular design 17 19554265
2003 Familial Parkinson's disease: a hint to elucidate the mechanisms of nigral degeneration. Journal of neurology 17 14579118
2018 The histidine triad nucleotide-binding protein 2 (HINT-2) positively regulates hepatocellular energy metabolism. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 16 29913563
2015 Membrane Hydration: A Hint to a New Model for Biomembranes. Sub-cellular biochemistry 16 26438259
2001 Characterization of Cre-loxP interaction in the major groove: hint for structural distortion of mutant Cre and possible strategy for HIV-1 therapy. Journal of cellular biochemistry 16 11135361
1979 RNA synthesis in isolated bovine thyroid nuclei and nucleoli. alpha-Amanitin effect, a hint to the existence of a specific regulatory system. Hoppe-Seyler's Zeitschrift fur physiologische Chemie 16 511117
2019 HINT1 gene pathogenic variants: the most common cause of recessive hereditary motor and sensory neuropathies in Russian patients. Molecular biology reports 15 31848916
2016 Hint1 suppresses migration and invasion of hepatocellular carcinoma cells in vitro by modulating girdin activity. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 15 27623945
2023 Hint from an Enzymatic Reaction: Superoxide Dismutase Models Efficiently Suppress Colorectal Cancer Cell Proliferation. Journal of the American Chemical Society 14 37441741
2022 Intracellular HINT1-Assisted Hydrolysis of Nucleoside 5'-O-Selenophosphate Leads to the Release of Hydrogen Selenide That Exhibits Toxic Effects in Human Cervical Cancer Cells. International journal of molecular sciences 14 35054788
2020 The role of HINT1 protein in morphine addiction: An animal model-based study. Addiction biology 14 32171181
2019 Inhibition of HINT1 Modulates Spinal Nociception and NMDA Evoked Behavior in Mice. ACS chemical neuroscience 14 31503445
2013 The Bmi-1/NF-κB/VEGF story: another hint for proteasome involvement in glioma angiogenesis? Journal of cell communication and signaling 14 23494769
2011 Clinical significance of expression of Hint1 and potential epigenetic mechanism in gastric cancer. International journal of oncology 14 21468541
2021 The σ1 Receptor and the HINT1 Protein Control α2δ1 Binding to Glutamate NMDA Receptors: Implications in Neuropathic Pain. Biomolecules 13 34827679
2020 Histidine triad nucleotide-binding proteins HINT1 and HINT2 share similar substrate specificities and little affinity for the signaling dinucleotide Ap4A. FEBS letters 13 31990367
2018 Novel mutations in HINT1 gene cause autosomal recessive axonal neuropathy with neuromyotonia in two cases of sensorimotor neuropathy and one case of motor neuropathy. Neuromuscular disorders : NMD 13 30001929
2004 Hypergravity stimulates osteoblast phenotype expression: a therapeutic hint for disuse bone atrophy. Annals of the New York Academy of Sciences 13 15659793
2003 Hypoxia-inducible factor-1: a molecular hint of physiological changes in the carotid body during long-term hypoxemia? Current drug targets. Cardiovascular & haematological disorders 13 12871043

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