Reactome: A Curated Pathway Database
THIS SITE IS USED FOR CURATION AND TESTING
IT IS NOT STABLE, IS LINKED TO AN INCOMPLETE DATA SET, AND IS NOT MONITORED FOR PERFORMANCE. WE STRONGLY RECOMMEND THE USE OF OUR PUBLIC SITE

Query author contributions in Reactome

Reactome depends on collaboration between our curation team and outside experts to assemble and peer-review its pathway modules. The integration of ORCID within Reactome enables us to meet a key challenge with authoring, curating and reviewing biological information by incentivizing and crediting the external experts that contribute their expertise and time to the Reactome curation process. More information is available at ORCID and Reactome.

If you have an ORCID ID that is not listed on this page, please forward this information to us and we will update your Reactome pathway records.

Name Email address

Details on Person UniProt:P49773 HINT1

Class:IdReferenceGeneProduct:56624
_chainChangeLoginitiator methionine:1 added on Sat February 7 2015;chain:2-126 added on Sat February 7 2015;initiator methionine:1 for 56624 removed on Fri Nov 03 2023;initiator methionine: for 56624 added on Fri Nov 03 2023;initiator methionine: for 56624 removed on Fri Aug 15 2025;initiator methionine:1 for 56624 added on Fri Aug 15 2025
_displayNameUniProt:P49773 HINT1
_timestamp2026-02-20 22:44:09
chaininitiator methionine:1
chain:2-126
checksum6C2B0119370384AA
commentFUNCTION 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).CATALYTIC ACTIVITY adenosine 5'-phosphoramidate + H2O = NH4(+) + AMPBIOPHYSICOCHEMICAL PROPERTIES 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).INTERACTION Interaction with CDK7 leads to a more nuclear localization.TISSUE SPECIFICITY Widely expressed.PTM Deubiquitinated by USP40, leading to stabilization.DISEASE The disease is caused by variants affecting the gene represented in this entry.MISCELLANEOUS Involved in the activation pathway of bemnifosbuvir (AT-527) and its epimer, AT-752 (PubMed:39190717). AT-527 and AT-752 are two guanosine analogs tested in clinical trials against several RNA viruses, which are activated into their common 5'-triphosphate AT-9010 in human cells (PubMed:39190717). Mediates the second activation step by catalyzing transformation of AT-551 into AT-8003 (PubMed:39190717).SIMILARITY Belongs to the HINT family.CAUTION Was originally thought to be a protein kinase C inhibitor and to bind zinc in solution. Both seem to be incorrect.
descriptionrecommendedName: fullName evidence="28"Adenosine 5'-monophosphoramidase HINT1 ecNumber evidence="6 8 9 10 16 17"3.9.1.- alternativeName: fullName evidence="29"Desumoylating isopeptidase HINT1 ecNumber evidence="20"3.4.22.- alternativeName: Histidine triad nucleotide-binding protein 1 alternativeName: Protein kinase C inhibitor 1 alternativeName: Protein kinase C-interacting protein 1 shortName: PKCI-1
geneNameHINT1
HINT
PKCI1
PRKCNH1
identifierP49773
isSequenceChangedFALSE
keyword3D-structure
Acetylation
Apoptosis
Cytoplasm
Direct protein sequencing
Disease variant
Hydrolase
Neuropathy
Nucleotide-binding
Nucleus
Phosphoprotein
Protease
Proteomics identification
Reference proteome
Thiol protease
Transcription
Transcription regulation
Ubl conjugation pathway
modified[InstanceEdit:9836292] Weiser, Joel, 2023-05-25
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9917590] Weiser, Joel, 2024-08-09
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
[InstanceEdit:9963647] Weiser, Joel, 2025-08-15
[InstanceEdit:9983091] Weiser, Joel, 2026-02-20
nameHINT1
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:8960107] ENSEMBL:ENSG00000169567 HINT1 [Homo sapiens]
secondaryIdentifierHINT1_HUMAN
Q9H5W8
sequenceLength126
species[Species:48887] Homo sapiens
(referenceEntity)[EntityWithAccessionedSequence:8960713] HINT1 [extracellular region] [Homo sapiens]
[EntityWithAccessionedSequence:9825679] HINT1 [nucleoplasm] [Homo sapiens]
[EntityWithAccessionedSequence:9825685] Ac-K21,K30 HINT1 [nucleoplasm] [Homo sapiens]
(referenceSequence)[ModifiedResidue:9825682] N6-acetyl-L-lysine at 30
[ModifiedResidue:9825683] N6-acetyl-L-lysine at 21
[Change default viewing format]
No pathways have been reviewed or authored by UniProt:P49773 HINT1 (56624)