| IED ID | IndEnz0002003208 |
| Enzyme Type ID | protease003208 |
| Protein Name |
Adenosine 5'-monophosphoramidase HINT1 EC 3.9.1.- Desumoylating isopeptidase HINT1 EC 3.4.22.- Histidine triad nucleotide-binding protein 1 Protein kinase C inhibitor 1 Protein kinase C-interacting protein 1 PKCI-1 |
| Gene Name | HINT1 HINT PKCI1 PRKCNH1 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MADEIAKAQVARPGGDTIFGKIIRKEIPAKIIFEDDRCLAFHDISPQAPTHFLVIPKKHISQISVAEDDDESLLGHLMIVGKKCAADLGLNKGYRMVVNEGSDGGQSVYHVHLHVLGGRQMHWPPG |
| Enzyme Length | 126 |
| Uniprot Accession Number | P49773 |
| Absorption | |
| Active Site | ACT_SITE 112; /note=Tele-AMP-histidine intermediate; /evidence=ECO:0000269|PubMed:9323207 |
| Activity Regulation | |
| Binding Site | BINDING 99; /note="AMP"; /evidence="ECO:0000269|PubMed:22869114, ECO:0007744|PDB:3TW2" |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=adenosine 5'-phosphoramidate + H2O = AMP + NH4(+); Xref=Rhea:RHEA:67916, ChEBI:CHEBI:15377, ChEBI:CHEBI:28938, ChEBI:CHEBI:57890, ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:15703176, ECO:0000269|PubMed:16835243, ECO:0000269|PubMed:17217311, ECO:0000269|PubMed:17337452, ECO:0000269|PubMed:22329685, ECO:0000269|PubMed:23614568, ECO:0000269|PubMed:28691797, ECO:0000269|PubMed:29787766, ECO:0000269|PubMed:31990367}; |
| DNA Binding | |
| EC Number | 3.9.1.-; 3.4.22.- |
| Enzyme 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:17337452, PubMed:17217311, PubMed:23614568, PubMed:28691797, PubMed:29787766, PubMed:31990367, PubMed:22329685). 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:22329685, PubMed:17337452). Hydrolyzes 3-indolepropionic acyl-adenylate, tryptamine adenosine phosphoramidate monoester and other fluorogenic purine nucleoside tryptamine phosphoramidates in vitro (PubMed:17337452, PubMed:23614568, PubMed:29787766, PubMed:17217311, PubMed:28691797, 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). {ECO:0000250|UniProtKB:P80912, ECO:0000269|PubMed:15703176, ECO:0000269|PubMed:16014379, ECO:0000269|PubMed:16835243, ECO:0000269|PubMed:17217311, ECO:0000269|PubMed:17337452, ECO:0000269|PubMed:19112177, ECO:0000269|PubMed:22329685, ECO:0000269|PubMed:22647378, ECO:0000269|PubMed:23614568, ECO:0000269|PubMed:28691797, ECO:0000269|PubMed:29787766, ECO:0000269|PubMed:30772266, ECO:0000269|PubMed:31088288, ECO:0000269|PubMed:31990367}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 43..44; /note="AMP"; /evidence="ECO:0000269|PubMed:22869114, ECO:0007744|PDB:3TW2"; NP_BIND 105..107; /note="AMP"; /evidence="ECO:0000269|PubMed:22869114, ECO:0007744|PDB:3TW2"; NP_BIND 112..114; /note="AMP"; /evidence="ECO:0000269|PubMed:22869114, ECO:0007744|PDB:3TW2" |
| Features | Active site (1); Beta strand (6); Binding site (1); Chain (1); Domain (1); Helix (5); Initiator methionine (1); Modified residue (5); Motif (1); Mutagenesis (17); Natural variant (6); Nucleotide binding (3); Sequence conflict (1) |
| Keywords | 3D-structure;Acetylation;Apoptosis;Cytoplasm;Direct protein sequencing;Disease variant;Hydrolase;Neuropathy;Nucleotide-binding;Nucleus;Phosphoprotein;Protease;Reference proteome;Thiol protease;Transcription;Transcription regulation;Ubl conjugation pathway |
| Interact With | Q8N684-3 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10958787, ECO:0000269|PubMed:16014379, ECO:0000269|PubMed:19112177, ECO:0000269|PubMed:8812426}. Nucleus {ECO:0000269|PubMed:10958787, ECO:0000269|PubMed:16014379, ECO:0000269|PubMed:19112177, ECO:0000269|PubMed:9770345}. Note=Interaction with CDK7 leads to a more nuclear localization. {ECO:0000269|PubMed:10958787}. |
| Modified Residue | MOD_RES 2; /note=N-acetylalanine; /evidence=ECO:0007744|PubMed:22814378; MOD_RES 21; /note=N6-acetyllysine; /evidence=ECO:0007744|PubMed:19608861; MOD_RES 30; /note=N6-acetyllysine; /evidence=ECO:0007744|PubMed:19608861; MOD_RES 45; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P70349; MOD_RES 72; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P70349 |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (49) |
| Cross Reference PDB | 1AV5; 1KPA; 1KPB; 1KPC; 1KPE; 1KPF; 3TW2; 4EQE; 4EQG; 4EQH; 4ZKL; 4ZKV; 5ED3; 5ED6; 5EMT; 5I2E; 5I2F; 5IPB; 5IPC; 5IPD; 5IPE; 5KLY; 5KLZ; 5KM0; 5KM1; 5KM2; 5KM3; 5KM4; 5KM6; 5KMA; 5KMB; 5KMC; 5O8I; 5WA8; 5WA9; 5WAA; 6B42; 6G9Z; 6J53; 6J58; 6J5S; 6J5Z; 6J64; 6J65; 6N3V; 6N3W; 6N3X; 6N3Y; 6YQM; |
| Mapped Pubmed ID | 11771757; 11805111; 17126529; 17353931; 17939685; 17978999; 18593937; 18799291; 19081673; 19089909; 19240791; 20468064; 20499681; 20514075; 20711500; 21468541; 21553311; 21988832; 22104145; 23769013; 24105373; 24386364; 24447405; 25342199; 25648896; 26194197; 26520111; 26638075; 26905466; 27563403; 27623945; 28007994; 28739258; 28968488; 29125116; 30006059; 31400136; 31503445; 31604935; 31848916; 32636443; 33404983; 33663550; 34098726; 34329705; |
| Motif | MOTIF 110..114; /note=Histidine triad motif |
| Gene Encoded By | |
| Mass | 13,802 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=0.04 uM for 3-indolepropionic acyl-adenylate {ECO:0000269|PubMed:17337452, ECO:0000269|PubMed:23614568}; KM=0.13 uM for tryptamine adenosine phosphoramidate {ECO:0000269|PubMed:17337452, ECO:0000269|PubMed:23614568}; KM=0.10 uM for tryptamine adenosine phosphoramidate {ECO:0000269|PubMed:29787766}; |
| Metal Binding | |
| Rhea ID | RHEA:67916 |
| Cross Reference Brenda |