O43598 · DNPH1_HUMAN
- Protein5-hydroxymethyl-dUMP N-hydrolase
- GeneDNPH1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids174 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Part of a nucleotide salvage pathway that eliminates epigenetically modified 5-hydroxymethyl-dCMP (hmdCMP) in a two-step process entailing deamination to cytotoxic 5-hydroxymethyl-dUMP (hmdUMP), followed by its hydrolysis into 5-hydroxymethyluracil (hmU) and 2-deoxy-D-ribose 5-phosphate (deoxyribosephosphate) (PubMed:33833118).
Catalyzes the second step in that pathway, the hydrolysis of the N-glycosidic bond in hmdUMP, degrading this cytotoxic nucleotide to avoid its genomic integration (PubMed:33833118).
Catalyzes the second step in that pathway, the hydrolysis of the N-glycosidic bond in hmdUMP, degrading this cytotoxic nucleotide to avoid its genomic integration (PubMed:33833118).
Catalytic activity
- 5-hydroxymethyl-dUMP + H2O = 2-deoxy-D-ribose 5-phosphate + 5-hydroxymethyluracilThis reaction proceeds in the forward direction.
Activity regulation
Inhibited by AMP and GMP.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
6.3 μM | 5-hydroxymethyl-dUMP | 7.0 | 37 | |||
57 μM | dGMP | |||||
97 μM | dAMP | |||||
104 μM | dIMP | |||||
2500 μM | dCMP | |||||
7800 μM | dUMP | |||||
25000 μM | dTMP |
kcat is 0.33 sec-1 with 5-hydroxymethyl-dUMP as substrate (PubMed:37142196).
kcat is 0.014 sec-1 with dUMP as substrate (PubMed:37142196).
kcat is 0.014 sec-1 with dUMP as substrate (PubMed:37142196).
pH Dependence
Optimum pH is 6-7 at 37 degrees Celsius.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 27 | 5-hydroxymethyl-dUMP (UniProtKB | ChEBI); ligand shared between homodimeric partners | ||||
Sequence: G | ||||||
Binding site | 29 | 5-hydroxymethyl-dUMP (UniProtKB | ChEBI); ligand shared between homodimeric partners | ||||
Sequence: I | ||||||
Binding site | 30 | 5-hydroxymethyl-dUMP (UniProtKB | ChEBI); ligand shared between homodimeric partners | ||||
Sequence: R | ||||||
Binding site | 31 | 5-hydroxymethyl-dUMP (UniProtKB | ChEBI); ligand shared between homodimeric partners | ||||
Sequence: G | ||||||
Binding site | 98 | 5-hydroxymethyl-dUMP (UniProtKB | ChEBI); ligand shared between homodimeric partners | ||||
Sequence: S | ||||||
Binding site | 100 | 5-hydroxymethyl-dUMP (UniProtKB | ChEBI); ligand shared between homodimeric partners | ||||
Sequence: G | ||||||
Binding site | 104 | 5-hydroxymethyl-dUMP (UniProtKB | ChEBI); ligand shared between homodimeric partners | ||||
Sequence: E | ||||||
Binding site | 128 | 5-hydroxymethyl-dUMP (UniProtKB | ChEBI); ligand shared between homodimeric partners; in other chain | ||||
Sequence: S |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Cellular Component | extracellular exosome | |
Cellular Component | nucleus | |
Molecular Function | deoxyribonucleoside 5'-monophosphate N-glycosidase activity | |
Molecular Function | identical protein binding | |
Molecular Function | protein homodimerization activity | |
Biological Process | deoxyribonucleoside monophosphate catabolic process | |
Biological Process | epithelial cell differentiation | |
Biological Process | nucleoside salvage | |
Biological Process | positive regulation of cell growth | |
Biological Process | purine nucleotide catabolic process |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended name5-hydroxymethyl-dUMP N-hydrolase
- 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 accessionO43598
- Secondary accessions
Proteomes
Organism-specific databases
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 104 | Loss of deoxyribonucleoside 5'-monophosphate N-glycosidase activity. | ||||
Sequence: E → Q |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 241 variants from UniProt as well as other sources including ClinVar and dbSNP.
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_0000097200 | 2-174 | UniProt | 5-hydroxymethyl-dUMP N-hydrolase | |||
Sequence: AAAMVPGRSESWERGEPGRPALYFCGSIRGGREDRTLYERIVSRLRRFGTVLTEHVAAAELGARGEEAAGGDRLIHEQDLEWLQQADVVVAEVTQPSLGVGYELGRAVAFNKRILCLFRPQSGRVLSAMIRGAADGSRFQVWDYEEGEVEALLDRYFEADPPGQVAASPDPTT | |||||||
Modified residue (large scale data) | 10 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 12 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 28 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 28 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 51 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 98 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 123 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 123 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 128 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 138 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 169 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 169 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 174 | PRIDE | Phosphothreonine | ||||
Sequence: T |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed at low levels in brain, colon, lung, peripheral blood leukocytes, placenta, small intestine, and thymus. Expressed at high levels in heart, kidney, liver, skeletal muscle and spleen. Overexpressed in a significant proportion of breast cancers.
Induction
Expression is induced by ETV1.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Monomer and homodimer.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | O43598 | DDIT4L Q96D03 | 5 | EBI-748674, EBI-742054 | |
BINARY | O43598 | DNPH1 O43598 | 5 | EBI-748674, EBI-748674 | |
BINARY | O43598 | KAT5 Q92993 | 3 | EBI-748674, EBI-399080 | |
BINARY | O43598 | LMO3 Q8TAP4-4 | 3 | EBI-748674, EBI-11742507 | |
BINARY | O43598 | PRKCA P17252 | 3 | EBI-748674, EBI-1383528 | |
BINARY | O43598 | SETDB1 Q15047-2 | 3 | EBI-748674, EBI-9090795 | |
BINARY | O43598 | TERF1 P54274 | 2 | EBI-748674, EBI-710997 | |
BINARY | O43598 | YWHAG P61981 | 3 | EBI-748674, EBI-359832 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
O43598-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length174
- Mass (Da)19,108
- Last updated1998-06-01 v1
- ChecksumC148641A60F383A3
O43598-2
- Name2
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
H0Y8X4 | H0Y8X4_HUMAN | DNPH1 | 243 |
Features
Showing features for alternative sequence.
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF040105 EMBL· GenBank· DDBJ | AAB96766.1 EMBL· GenBank· DDBJ | mRNA | ||
EU585603 EMBL· GenBank· DDBJ | ACB87500.1 EMBL· GenBank· DDBJ | mRNA | ||
AL133375 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471081 EMBL· GenBank· DDBJ | EAX04166.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC011683 EMBL· GenBank· DDBJ | AAH11683.1 EMBL· GenBank· DDBJ | mRNA | ||
BQ052226 EMBL· GenBank· DDBJ | - | mRNA | No translation available. |