O95671 · ASML_HUMAN
- ProteinProbable bifunctional dTTP/UTP pyrophosphatase/methyltransferase protein
- GeneASMTL
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids621 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Nucleoside triphosphate pyrophosphatase that hydrolyzes dTTP and UTP. Can also hydrolyze CTP and the modified nucleotides pseudo-UTP, 5-methyl-UTP (m5UTP) and 5-methyl-CTP (m5CTP). Has weak activity with dCTP, 8-oxo-GTP and N4-methyl-dCTP (PubMed:24210219).
May have a dual role in cell division arrest and in preventing the incorporation of modified nucleotides into cellular nucleic acids (PubMed:24210219).
In addition, the presence of the putative catalytic domain of S-adenosyl-L-methionine binding in the C-terminal region argues for a methyltransferase activity (Probable)
May have a dual role in cell division arrest and in preventing the incorporation of modified nucleotides into cellular nucleic acids (PubMed:24210219).
In addition, the presence of the putative catalytic domain of S-adenosyl-L-methionine binding in the C-terminal region argues for a methyltransferase activity (Probable)
Miscellaneous
The gene coding for this protein is located in the pseudoautosomal region 1 (PAR1) of X and Y chromosomes. It represents a unique fusion product of 2 different genes of different evolutionary origin and function. The N-terminus is homologous to the bacterial maf/orfE genes and the C-terminus is homologous to ASMT. Exon duplication, exon shuffling and gene fusion seem to be common characteristics of the PAR1 region.
Catalytic activity
- dTTP + H2O = diphosphate + dTMP + H+
- H2O + psi-UTP = diphosphate + H+ + psi-UMP
- H2O + TTP = 5-methyl-UMP + diphosphate + H+
- 5-methyl-CTP + H2O = 5-methyl-CMP + diphosphate + H+
Cofactor
Note: Pyrophosphatase activity requires a divalent metal cation.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
32.7 μM | dTTP | |||||
41.2 μM | UTP | |||||
17.4 μM | CTP | |||||
22.8 μM | dCTP | |||||
16.1 μM | m5UTP | |||||
39.4 μM | m5CTP | |||||
18.7 μM | pseudo-UTP | |||||
10.7 μM | 8-oxo-GTP | |||||
10.3 μM | N4-methyl-dCTP |
kcat is 0.7 sec-1 with dTTP as substrate. kcat is 0.7 sec-1 with UTP as substrate. kcat is 0.8 sec-1 with CTP as substrate. kcat is 0.3 sec-1 with dCTP as substrate. kcat is 1.5 sec-1 with m5UTP as substrate. kcat is 3.7 sec-1 with m5CTP as substrate. kcat is 2.5 sec-1 with pseudo-UTP as substrate. kcat is 0.2 sec-1 with 8-oxo-GTP as substrate. kcat is 0.3 sec-1 with N4-methyl-dCTP as substrate.
Features
Showing features for site, active site, binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 23 | Important for substrate specificity; for pyrophosphatase activity | ||||
Sequence: R | ||||||
Active site | 88 | Proton acceptor; for pyrophosphatase activity | ||||
Sequence: D | ||||||
Site | 89 | Important for substrate specificity; for pyrophosphatase activity | ||||
Sequence: T | ||||||
Site | 179 | Important for substrate specificity; for pyrophosphatase activity | ||||
Sequence: Q | ||||||
Binding site | 482 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 508-510 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: GDF | ||||||
Binding site | 525 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: R |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Molecular Function | dTTP diphosphatase activity | |
Molecular Function | nucleoside triphosphate diphosphatase activity | |
Molecular Function | O-methyltransferase activity | |
Molecular Function | UTP diphosphatase activity | |
Biological Process | methylation | |
Biological Process | nucleotide metabolic process |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameProbable bifunctional dTTP/UTP pyrophosphatase/methyltransferase protein
Including 2 domains:
- Recommended namedTTP/UTP pyrophosphatase
- EC number
- Short namesdTTPase/UTPase
- Alternative names
- Recommended nameN-acetylserotonin O-methyltransferase-like protein
- EC number
- Short namesASMTL
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionO95671
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Disease & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 19 | Loss of pyrophosphatase activity. | ||||
Sequence: S → A | ||||||
Mutagenesis | 21 | Loss of pyrophosphatase activity. | ||||
Sequence: S → A | ||||||
Mutagenesis | 23 | Decrease in pyrophosphatase activity. | ||||
Sequence: R → A | ||||||
Mutagenesis | 24 | Loss of pyrophosphatase activity. | ||||
Sequence: R → A | ||||||
Mutagenesis | 44 | Loss of pyrophosphatase activity. | ||||
Sequence: E → A | ||||||
Mutagenesis | 57 | Loss of pyrophosphatase activity. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 65 | Loss of pyrophosphatase activity. | ||||
Sequence: K → A | ||||||
Mutagenesis | 88 | Loss of pyrophosphatase activity. | ||||
Sequence: D → A or N | ||||||
Mutagenesis | 99 | Loss of pyrophosphatase activity. | ||||
Sequence: E → A | ||||||
Mutagenesis | 179 | Loss of pyrophosphatase activity. | ||||
Sequence: Q → A | ||||||
Mutagenesis | 179 | Strong decrease in pyrophosphatase activity. | ||||
Sequence: Q → E | ||||||
Natural variant | VAR_054802 | 458 | in dbSNP:rs4503285 | |||
Sequence: V → M | ||||||
Natural variant | VAR_054803 | 541 | in dbSNP:rs1127297 | |||
Sequence: R → K |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 837 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data), modified residue.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000064702 | 1-621 | UniProt | Probable bifunctional dTTP/UTP pyrophosphatase/methyltransferase protein | |||
Sequence: MVLCPVIGKLLHKRVVLASASPRRQEILSNAGLRFEVVPSKFKEKLDKASFATPYGYAMETAKQKALEVANRLYQKDLRAPDVVIGADTIVTVGGLILEKPVDKQDAYRMLSRLSGREHSVFTGVAIVHCSSKDHQLDTRVSEFYEETKVKFSELSEELLWEYVHSGEPMDKAGGYGIQALGGMLVESVHGDFLNVVGFPLNHFCKQLVKLYYPPRPEDLRRSVKHDSIPAADTFEDLSDVEGGGSEPTQRDAGSRDEKAEAGEAGQATAEAECHRTRETLPPFPTRLLELIEGFMLSKGLLTACKLKVFDLLKDEAPQKAADIASKVDASACGMERLLDICAAMGLLEKTEQGYSNTETANVYLASDGEYSLHGFIMHNNDLTWNLFTYLEFAIREGTNQHHRALGKKAEDLFQDAYYQSPETRLRFMRAMHGMTKLTACQVATAFNLSRFSSACDVGGCTGALARELAREYPRMQVTVFDLPDIIELAAHFQPPGPQAVQIHFAAGDFFRDPLPSAELYVLCRILHDWPDDKVHKLLSRVAESCKPGAGLLLVETLLDEEKRVAQRALMQSLNMLVQTEGKERSLGEYQCLLELHGFHQVQVVHLGGVLDAILATKVAP | |||||||
Modified residue (large scale data) | 19 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 21 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 21 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 223 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 228 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 228 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 234 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 234 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 239 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 239 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 246 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 255 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 421 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 421 | PRIDE | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Widely expressed. In adult, highly expressed in pancreas, placenta, fibroblast, thymus, prostate, testis, ovary and colon. Expressed at lower levels in spleen, small intestine and leukocytes. In fetus, expressed at high levels in the lung and kidney and at lower level in brain and liver.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Homodimer.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | O95671 | DCTN1 Q14203-5 | 3 | EBI-743231, EBI-25840379 | |
BINARY | O95671 | GORASP2 Q9H8Y8 | 3 | EBI-743231, EBI-739467 | |
BINARY | O95671 | KRT31 Q15323 | 6 | EBI-743231, EBI-948001 | |
BINARY | O95671 | KRT34 O76011 | 3 | EBI-743231, EBI-1047093 | |
BINARY | O95671 | KRT40 Q6A162 | 3 | EBI-743231, EBI-10171697 | |
BINARY | O95671 | OPTN Q96CV9 | 3 | EBI-743231, EBI-748974 | |
BINARY | O95671 | PNMA1 Q8ND90 | 3 | EBI-743231, EBI-302345 | |
BINARY | O95671 | REL Q04864-2 | 3 | EBI-743231, EBI-10829018 | |
BINARY | O95671 | TDO2 P48775 | 12 | EBI-743231, EBI-743494 | |
BINARY | O95671 | ZNF655 Q8N720 | 3 | EBI-743231, EBI-625509 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 11-223 | MAF-like | ||||
Sequence: LHKRVVLASASPRRQEILSNAGLRFEVVPSKFKEKLDKASFATPYGYAMETAKQKALEVANRLYQKDLRAPDVVIGADTIVTVGGLILEKPVDKQDAYRMLSRLSGREHSVFTGVAIVHCSSKDHQLDTRVSEFYEETKVKFSELSEELLWEYVHSGEPMDKAGGYGIQALGGMLVESVHGDFLNVVGFPLNHFCKQLVKLYYPPRPEDLRRS | ||||||
Region | 235-279 | Disordered | ||||
Sequence: FEDLSDVEGGGSEPTQRDAGSRDEKAEAGEAGQATAEAECHRTRE | ||||||
Region | 277-621 | ASMT-like | ||||
Sequence: TRETLPPFPTRLLELIEGFMLSKGLLTACKLKVFDLLKDEAPQKAADIASKVDASACGMERLLDICAAMGLLEKTEQGYSNTETANVYLASDGEYSLHGFIMHNNDLTWNLFTYLEFAIREGTNQHHRALGKKAEDLFQDAYYQSPETRLRFMRAMHGMTKLTACQVATAFNLSRFSSACDVGGCTGALARELAREYPRMQVTVFDLPDIIELAAHFQPPGPQAVQIHFAAGDFFRDPLPSAELYVLCRILHDWPDDKVHKLLSRVAESCKPGAGLLLVETLLDEEKRVAQRALMQSLNMLVQTEGKERSLGEYQCLLELHGFHQVQVVHLGGVLDAILATKVAP |
Sequence similarities
In the N-terminal section; belongs to the Maf family. YhdE subfamily.
In the C-terminal section; belongs to the class I-like SAM-binding methyltransferase superfamily. Cation-independent O-methyltransferase family.
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 3 isoforms produced by Alternative splicing.
O95671-1
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
- Length621
- Mass (Da)68,857
- Last updated2006-10-03 v3
- Checksum564C2D538F4919EC
O95671-2
- Name2
- Differences from canonical
- 76-91: Missing
O95671-3
- Name3
- Differences from canonical
- 1-58: Missing
Sequence caution
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_047412 | 1-58 | in isoform 3 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_007213 | 76-91 | in isoform 2 | |||
Sequence: Missing | ||||||
Sequence conflict | 228 | in Ref. 2; BAG63287 | ||||
Sequence: S → P | ||||||
Sequence conflict | 364 | in Ref. 2; BAG63287 | ||||
Sequence: Y → H | ||||||
Sequence conflict | 434 | in Ref. 2; BAG63287 | ||||
Sequence: G → S |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
Y15521 EMBL· GenBank· DDBJ | CAA75675.1 EMBL· GenBank· DDBJ | Genomic DNA | Frameshift | |
Y15521 EMBL· GenBank· DDBJ | CAA75676.1 EMBL· GenBank· DDBJ | Genomic DNA | Frameshift | |
AK090498 EMBL· GenBank· DDBJ | BAC03468.1 EMBL· GenBank· DDBJ | mRNA | ||
AK301844 EMBL· GenBank· DDBJ | BAG63287.1 EMBL· GenBank· DDBJ | mRNA | ||
AL683870 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC002508 EMBL· GenBank· DDBJ | AAH02508.1 EMBL· GenBank· DDBJ | mRNA | ||
BC010089 EMBL· GenBank· DDBJ | AAH10089.1 EMBL· GenBank· DDBJ | mRNA |