P49773 · HINT1_HUMAN
- ProteinAdenosine 5'-monophosphoramidase HINT1
- GeneHINT1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids126 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Exhibits adenosine 5'-monophosphoramidase activity, hydrolyzing purine nucleotide phosphoramidates with a single phosphate group such as adenosine 5'monophosphoramidate (AMP-NH2) to yield AMP and NH2 (PubMed:15703176, PubMed:16835243, PubMed:17217311, PubMed:17337452, PubMed:22329685, PubMed:23614568, PubMed:28691797, PubMed:29787766, PubMed:31990367).
Hydrolyzes adenosine 5'monophosphomorpholidate (AMP-morpholidate) and guanosine 5'monophosphomorpholidate (GMP-morpholidate) (PubMed:15703176, PubMed:16835243).
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 (PubMed:15703176, PubMed:17337452, PubMed:22329685).
Hydrolyzes 3-indolepropionic acyl-adenylate, tryptamine adenosine phosphoramidate monoester and other fluorogenic purine nucleoside tryptamine phosphoramidates in vitro (PubMed:17217311, PubMed:17337452, PubMed:23614568, PubMed:28691797, PubMed:29787766, PubMed:31990367).
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 (PubMed:30772266).
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 (PubMed:16014379, PubMed:22647378).
Modulates p53/TP53 levels and p53/TP53-mediated apoptosis (PubMed:16835243).
Modulates proteasomal degradation of target proteins by the SCF (SKP2-CUL1-F-box protein) E3 ubiquitin-protein ligase complex (PubMed:19112177).
Also exhibits SUMO-specific isopeptidase activity, deconjugating SUMO1 from RGS17 (PubMed:31088288).
Deconjugates SUMO1 from RANGAP1 (By similarity).
Hydrolyzes adenosine 5'monophosphomorpholidate (AMP-morpholidate) and guanosine 5'monophosphomorpholidate (GMP-morpholidate) (PubMed:15703176, PubMed:16835243).
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 (PubMed:15703176, PubMed:17337452, PubMed:22329685).
Hydrolyzes 3-indolepropionic acyl-adenylate, tryptamine adenosine phosphoramidate monoester and other fluorogenic purine nucleoside tryptamine phosphoramidates in vitro (PubMed:17217311, PubMed:17337452, PubMed:23614568, PubMed:28691797, PubMed:29787766, PubMed:31990367).
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 (PubMed:30772266).
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 (PubMed:16014379, PubMed:22647378).
Modulates p53/TP53 levels and p53/TP53-mediated apoptosis (PubMed:16835243).
Modulates proteasomal degradation of target proteins by the SCF (SKP2-CUL1-F-box protein) E3 ubiquitin-protein ligase complex (PubMed:19112177).
Also exhibits SUMO-specific isopeptidase activity, deconjugating SUMO1 from RGS17 (PubMed:31088288).
Deconjugates SUMO1 from RANGAP1 (By similarity).
Catalytic activity
- adenosine 5'-phosphoramidate + H2O = AMP + NH4+
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
0.04 μM | 3-indolepropionic acyl-adenylate | |||||
0.13 μM | tryptamine adenosine phosphoramidate | |||||
0.1 μM | tryptamine adenosine phosphoramidate |
Features
Showing features for binding site, active site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | cytoskeleton | |
Cellular Component | cytosol | |
Cellular Component | extracellular exosome | |
Cellular Component | histone deacetylase complex | |
Cellular Component | nucleoplasm | |
Cellular Component | nucleus | |
Cellular Component | plasma membrane | |
Molecular Function | adenosine 5'-monophosphoramidase activity | |
Molecular Function | deSUMOylase activity | |
Molecular Function | hydrolase activity | |
Molecular Function | nucleotide binding | |
Molecular Function | protein kinase C binding | |
Biological Process | intrinsic apoptotic signaling pathway by p53 class mediator | |
Biological Process | positive regulation of calcium-mediated signaling | |
Biological Process | protein desumoylation | |
Biological Process | proteolysis | |
Biological Process | purine ribonucleotide catabolic process | |
Biological Process | regulation of DNA-templated transcription | |
Biological Process | signal transduction |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameAdenosine 5'-monophosphoramidase HINT1
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP49773
- Secondary accessions
Proteomes
Organism-specific databases
Disease & Variants
Involvement in disease
Neuromyotonia and axonal neuropathy, autosomal recessive (NMAN)
- Note
- DescriptionAn 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 and distal hereditary motor neuropathy. 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.
- See alsoMIM:137200
Natural variants in NMAN
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_069212 | 37 | R>P | in NMAN; negligible protein expression due to post-translational degradation; loss of homodimerization; significant decrease in adenosine 5'-monophosphoramidase activity; reduced SUMO-specific isopeptidase activity; dbSNP:rs149782619 | |
VAR_069213 | 51 | H>R | in NMAN; no mutant protein is detected due to post-translational degradation; no effect on SUMO-specific isopeptidase activity; dbSNP:rs397514491 | |
VAR_069214 | 84 | C>R | in NMAN; negligible protein expression due to post-translational degradation; no effect on homodimerization; no effect on adenosine 5'-monophosphoramidase; no effect on affinity for tryptamine adenosine phosphoramidate; loss of SUMO-specific isopeptidase activity; dbSNP:rs397514489 | |
VAR_069215 | 89 | G>V | in NMAN; no effect on homodimerization; no effect on adenosine 5'-monophosphoramidase activity; no effect on affinity for tryptamine adenosine phosphoramidate; loss of SUMO-specific isopeptidase activity; dbSNP:rs397514490 | |
VAR_069216 | 93 | G>D | in NMAN; loss of homodimerization; significant decrease in adenosine 5'-monophosphoramidase activity; approximately 40-fold increased affinity for tryptamine adenosine phosphoramidate; loss of SUMO-specific isopeptidase activity; dbSNP:rs397514493 | |
VAR_069217 | 112 | H>N | in NMAN; the enzyme has no residual activity although the mutant protein is expressed at normal levels; no effect on homodimerization; loss of SUMO-specific isopeptidase activity; dbSNP:rs373849532 |
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 33 | Loss of SUMO-specific isopeptidase activity. | ||||
Sequence: F → S | ||||||
Mutagenesis | 34 | Reduced SUMO-specific isopeptidase activity. | ||||
Sequence: E → K | ||||||
Natural variant | VAR_069212 | 37 | in NMAN; negligible protein expression due to post-translational degradation; loss of homodimerization; significant decrease in adenosine 5'-monophosphoramidase activity; reduced SUMO-specific isopeptidase activity; dbSNP:rs149782619 | |||
Sequence: R → P | ||||||
Mutagenesis | 38 | No effect on SUMO-specific isopeptidase activity. | ||||
Sequence: C → R | ||||||
Mutagenesis | 43 | Approximately 50-fold increased affinity for tryptamine adenosine phosphoramidate. | ||||
Sequence: D → N | ||||||
Mutagenesis | 44 | Approximately 10-fold increased affinity for tryptamine adenosine phosphoramidate. | ||||
Sequence: I → F | ||||||
Mutagenesis | 44 | Approximately 30-fold increased affinity for tryptamine adenosine phosphoramidate. | ||||
Sequence: I → W | ||||||
Natural variant | VAR_069213 | 51 | in NMAN; no mutant protein is detected due to post-translational degradation; no effect on SUMO-specific isopeptidase activity; dbSNP:rs397514491 | |||
Sequence: H → R | ||||||
Mutagenesis | 51 | No effect on affinity for 3-indolepropionic acyl-adenylate but a 13.8-fold increased affinity for tryptamine adenosine phosphoramidate monoester. | ||||
Sequence: H → A | ||||||
Mutagenesis | 57 | Loss of SUMO-specific isopeptidase activity. | ||||
Sequence: K → N | ||||||
Natural variant | VAR_069214 | 84 | in NMAN; negligible protein expression due to post-translational degradation; no effect on homodimerization; no effect on adenosine 5'-monophosphoramidase; no effect on affinity for tryptamine adenosine phosphoramidate; loss of SUMO-specific isopeptidase activity; dbSNP:rs397514489 | |||
Sequence: C → R | ||||||
Natural variant | VAR_069215 | 89 | in NMAN; no effect on homodimerization; no effect on adenosine 5'-monophosphoramidase activity; no effect on affinity for tryptamine adenosine phosphoramidate; loss of SUMO-specific isopeptidase activity; dbSNP:rs397514490 | |||
Sequence: G → V | ||||||
Natural variant | VAR_069216 | 93 | in NMAN; loss of homodimerization; significant decrease in adenosine 5'-monophosphoramidase activity; approximately 40-fold increased affinity for tryptamine adenosine phosphoramidate; loss of SUMO-specific isopeptidase activity; dbSNP:rs397514493 | |||
Sequence: G → D | ||||||
Mutagenesis | 97 | Loss of dimerization. Strongly reduced adenosine 5'-monophosphoramidase activity. A 110-fold increased affinity for 3-indolepropionic acyl-adenylate and a 100-fold increased affinity for tryptamine adenosine phosphoramidate monoester. | ||||
Sequence: V → D | ||||||
Mutagenesis | 97 | Loss of dimerization. Strongly reduced adenosine 5'-monophosphoramidase activity. A 128-fold increased affinity for 3-indolepropionic acyl-adenylate and a 1000-fold increased affinity for tryptamine adenosine phosphoramidate monoester. | ||||
Sequence: V → E | ||||||
Mutagenesis | 97 | Loss of SUMO-specific isopeptidase activity. | ||||
Sequence: V → M | ||||||
Mutagenesis | 105 | Reduces adenosine 5'-monophosphoramidase activity. | ||||
Sequence: G → A | ||||||
Mutagenesis | 107 | Reduces adenosine 5'-monophosphoramidase activity. | ||||
Sequence: S → A | ||||||
Mutagenesis | 110 | No significant effect on affinity for 3-indolepropionic acyl-adenylate and tryptamine adenosine phosphoramidate monoester. | ||||
Sequence: H → A | ||||||
Natural variant | VAR_069217 | 112 | in NMAN; the enzyme has no residual activity although the mutant protein is expressed at normal levels; no effect on homodimerization; loss of SUMO-specific isopeptidase activity; dbSNP:rs373849532 | |||
Sequence: H → N | ||||||
Mutagenesis | 114 | Nearly abolishes adenosine 5'-monophosphoramidase activity. A 3-fold increased affinity for 3-indolepropionic acyl-adenylate and a 2-fold increased affinity for tryptamine adenosine phosphoramidate monoester. | ||||
Sequence: H → A | ||||||
Mutagenesis | 114 | Loss of SUMO-specific isopeptidase activity. | ||||
Sequence: H → R | ||||||
Mutagenesis | 123 | Nearly abolishes adenosine 5'-monophosphoramidase activity. | ||||
Sequence: W → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 152 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Initiator methionine | 1 | UniProt | Removed | ||||
Sequence: M | |||||||
Modified residue | 2 | UniProt | N-acetylalanine | ||||
Sequence: A | |||||||
Chain | PRO_0000109781 | 2-126 | UniProt | Adenosine 5'-monophosphoramidase HINT1 | |||
Sequence: ADEIAKAQVARPGGDTIFGKIIRKEIPAKIIFEDDRCLAFHDISPQAPTHFLVIPKKHISQISVAEDDDESLLGHLMIVGKKCAADLGLNKGYRMVVNEGSDGGQSVYHVHLHVLGGRQMHWPPG | |||||||
Modified residue | 21 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 30 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 45 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 45 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 72 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 72 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 102 | PRIDE | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
2D gel databases
PTM databases
Expression
Tissue specificity
Widely expressed.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Homodimer. Interacts with CDK7. Interacts with RUVBL1 and RUVBL2 and is associated with the LEF1/TCF1-CTNNB1 complex and with a KAT5 histone acetyltransferase complex. Identified in a complex with MITF and CTNNB1. Interacts with CDC34 and RBX1, and is part of a SCF (SKP2-CUL1-F-box protein) E3 ubiquitin-protein ligase complex (PubMed:19112177).
Interacts with SUMO1, SUMO2 and RGS17 (By similarity).
Interacts with the Ten-1 ICD form of TENM1 (By similarity).
Interacts with CALM1; interaction increases in the presence of calcium ions (By similarity).
Interacts with SUMO1, SUMO2 and RGS17 (By similarity).
Interacts with the Ten-1 ICD form of TENM1 (By similarity).
Interacts with CALM1; interaction increases in the presence of calcium ions (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P49773 | CPSF7 Q8N684-3 | 3 | EBI-1054330, EBI-11523759 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 18-126 | HIT | ||||
Sequence: IFGKIIRKEIPAKIIFEDDRCLAFHDISPQAPTHFLVIPKKHISQISVAEDDDESLLGHLMIVGKKCAADLGLNKGYRMVVNEGSDGGQSVYHVHLHVLGGRQMHWPPG | ||||||
Motif | 110-114 | Histidine triad motif | ||||
Sequence: HVHLH |
Sequence similarities
Belongs to the HINT family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length126
- Mass (Da)13,802
- Last updated2007-01-23 v2
- Checksum6C2B0119370384AA
Computationally mapped potential isoform sequences
There are 6 potential isoforms mapped to this entry
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 25 | in Ref. 3; BAB15500 | ||||
Sequence: K → E |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U27143 EMBL· GenBank· DDBJ | AAA82926.1 EMBL· GenBank· DDBJ | mRNA | ||
U51004 EMBL· GenBank· DDBJ | AAC71077.1 EMBL· GenBank· DDBJ | mRNA | ||
AK026557 EMBL· GenBank· DDBJ | BAB15500.1 EMBL· GenBank· DDBJ | mRNA | ||
CR457048 EMBL· GenBank· DDBJ | CAG33329.1 EMBL· GenBank· DDBJ | mRNA | ||
BC001287 EMBL· GenBank· DDBJ | AAH01287.1 EMBL· GenBank· DDBJ | mRNA | ||
BC007090 EMBL· GenBank· DDBJ | AAH07090.1 EMBL· GenBank· DDBJ | mRNA |