Q9NUW8 · TYDP1_HUMAN
- ProteinTyrosyl-DNA phosphodiesterase 1
- GeneTDP1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids608 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
0.08 μM | 14-mer single-stranded oligo with a 3'-phosphotyrosine |
Features
Showing features for active site, binding site, site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 263 | Nucleophile | ||||
Sequence: H | ||||||
Binding site | 265 | substrate | ||||
Sequence: K | ||||||
Active site | 493 | Proton donor/acceptor | ||||
Sequence: H | ||||||
Binding site | 495 | substrate | ||||
Sequence: K | ||||||
Site | 518 | Interaction with DNA | ||||
Sequence: S |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | intracellular membrane-bounded organelle | |
Cellular Component | nucleoplasm | |
Cellular Component | nucleus | |
Cellular Component | plasma membrane | |
Molecular Function | 3'-tyrosyl-DNA phosphodiesterase activity | |
Molecular Function | double-stranded DNA binding | |
Molecular Function | exonuclease activity | |
Molecular Function | single-stranded DNA binding | |
Biological Process | DNA repair | |
Biological Process | double-strand break repair | |
Biological Process | single strand break repair |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameTyrosyl-DNA phosphodiesterase 1
- EC number
- Short namesTyr-DNA phosphodiesterase 1
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9NUW8
- Secondary accessions
Proteomes
Organism-specific databases
Disease & Variants
Involvement in disease
Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1 (SCAN1)
- Note
- DescriptionA form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAN1 is an autosomal recessive cerebellar ataxia (ARCA) associated with peripheral axonal motor and sensory neuropathy, distal muscular atrophy, pes cavus and steppage gait as seen in Charcot-Marie-Tooth neuropathy. All affected individuals have normal intelligence.
- See alsoMIM:607250
Natural variants in SCAN1
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_017144 | 493 | H>R | in SCAN1; reduces enzyme activity and leads to the accumulation of covalent complexes between TDP1 and DNA; dbSNP:rs119467003 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_025817 | 95 | in dbSNP:rs35114462 | |||
Sequence: E → D | ||||||
Natural variant | VAR_025818 | 101 | in dbSNP:rs35455108 | |||
Sequence: P → L | ||||||
Natural variant | VAR_025819 | 134 | in dbSNP:rs28365054 | |||
Sequence: A → T | ||||||
Natural variant | VAR_025820 | 187 | in dbSNP:rs35271143 | |||
Sequence: D → G | ||||||
Mutagenesis | 263 | Loss of activity. | ||||
Sequence: H → A | ||||||
Mutagenesis | 265 | Abolishes hydrolysis of the covalent intermediate between the active site nucleophile and DNA. | ||||
Sequence: K → A | ||||||
Mutagenesis | 265 | Reduces the activity to nearly undetectable levels. | ||||
Sequence: K → S | ||||||
Mutagenesis | 283 | No effect. | ||||
Sequence: N → A | ||||||
Mutagenesis | 294 | Slightly reduced hydrolysis of the covalent intermediate between the active site nucleophile and DNA. | ||||
Sequence: Q → A | ||||||
Natural variant | VAR_025821 | 304 | in dbSNP:rs34452707 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_017144 | 493 | in SCAN1; reduces enzyme activity and leads to the accumulation of covalent complexes between TDP1 and DNA; dbSNP:rs119467003 | |||
Sequence: H → R | ||||||
Mutagenesis | 493 | 3000-fold reduction in activity; abolishes hydrolysis of the covalent intermediate between the active site nucleophile and DNA. | ||||
Sequence: H → A | ||||||
Mutagenesis | 493 | 15000-fold reduction in activity. | ||||
Sequence: H → N | ||||||
Mutagenesis | 495 | Abolishes hydrolysis of the covalent intermediate between the active site nucleophile and DNA. | ||||
Sequence: K → A | ||||||
Mutagenesis | 495 | 125-fold reduction in activity. | ||||
Sequence: K → S | ||||||
Mutagenesis | 516 | Reduced hydrolysis of the covalent intermediate between the active site nucleophile and DNA. | ||||
Sequence: N → A | ||||||
Mutagenesis | 538 | Abolishes hydrolysis of the covalent intermediate between the active site nucleophile and DNA. | ||||
Sequence: E → A | ||||||
Natural variant | VAR_017145 | 566 | in autosomal recessive or sporadic spinocerebellar ataxia affected Japanese individuals; dbSNP:rs767298655 | |||
Sequence: P → L | ||||||
Natural variant | VAR_025822 | 569 | in dbSNP:rs35973343 | |||
Sequence: T → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 772 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 chain, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000212486 | 1-608 | UniProt | Tyrosyl-DNA phosphodiesterase 1 | |||
Sequence: MSQEGDYGRWTISSSDESEEEKPKPDKPSTSSLLCARQGAANEPRYTCSEAQKAAHKRKISPVKFSNTDSVLPPKRQKSGSQEDLGWCLSSSDDELQPEMPQKQAEKVVIKKEKDISAPNDGTAQRTENHGAPACHRLKEEEDEYETSGEGQDIWDMLDKGNPFQFYLTRVSGVKPKYNSGALHIKDILSPLFGTLVSSAQFNYCFDVDWLVKQYPPEFRKKPILLVHGDKREAKAHLHAQAKPYENISLCQAKLDIAFGTHHTKMMLLLYEEGLRVVIHTSNLIHADWHQKTQGIWLSPLYPRIADGTHKSGESPTHFKADLISYLMAYNAPSLKEWIDVIHKHDLSETNVYLIGSTPGRFQGSQKDNWGHFRLKKLLKDHASSMPNAESWPVVGQFSSVGSLGADESKWLCSEFKESMLTLGKESKTPGKSSVPLYLIYPSVENVRTSLEGYPAGGSLPYSIQTAEKQNWLHSYFHKWSAETSGRSNAMPHIKTYMRPSPDFSKIAWFLVTSANLSKAAWGALEKNGTQLMIRSYELGVLFLPSAFGLDSFKVKQKFFAGSQEPMATFPVPYDLPPELYGSKDRPWIWNIPYVKAPDTHGNMWVPS | |||||||
Modified residue | 61 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 147 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 147 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 148 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 148 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Gene expression databases
Organism-specific databases
Interaction
Subunit
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9NUW8 | BAG6 P46379-2 | 3 | EBI-2902553, EBI-10988864 | |
BINARY | Q9NUW8 | DCLRE1B Q9H816 | 3 | EBI-2902553, EBI-3508943 | |
BINARY | Q9NUW8 | KPNA2 P52292 | 2 | EBI-2902553, EBI-349938 | |
BINARY | Q9NUW8 | LDHAL6B Q9BYZ2 | 3 | EBI-2902553, EBI-1108377 | |
BINARY | Q9NUW8 | MKL1 A4FUJ8 | 3 | EBI-2902553, EBI-21250407 | |
BINARY | Q9NUW8 | PIAS1 O75925 | 3 | EBI-2902553, EBI-629434 | |
BINARY | Q9NUW8 | RASSF1 Q9NS23-4 | 3 | EBI-2902553, EBI-438710 | |
BINARY | Q9NUW8 | RNF111 Q6ZNA4-2 | 3 | EBI-2902553, EBI-21535400 | |
BINARY | Q9NUW8 | RYBP Q8N488 | 3 | EBI-2902553, EBI-752324 | |
BINARY | Q9NUW8 | SPATA2L Q8IUW3 | 3 | EBI-2902553, EBI-2510414 | |
BINARY | Q9NUW8 | TERF2 Q15554-4 | 3 | EBI-2902553, EBI-25840535 | |
BINARY | Q9NUW8 | VAC14 Q08AM6 | 3 | EBI-2902553, EBI-2107455 | |
BINARY | Q9NUW8 | XRCC1 P18887 | 3 | EBI-2902553, EBI-947466 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-101 | Disordered | ||||
Sequence: MSQEGDYGRWTISSSDESEEEKPKPDKPSTSSLLCARQGAANEPRYTCSEAQKAAHKRKISPVKFSNTDSVLPPKRQKSGSQEDLGWCLSSSDDELQPEMP | ||||||
Compositional bias | 13-27 | Basic and acidic residues | ||||
Sequence: SSSDESEEEKPKPDK | ||||||
Compositional bias | 64-88 | Polar residues | ||||
Sequence: KFSNTDSVLPPKRQKSGSQEDLGWC | ||||||
Region | 400-403 | Interaction with DNA | ||||
Sequence: SVGS |
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q9NUW8-1
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
- Length608
- Mass (Da)68,420
- Last updated2003-10-24 v2
- ChecksumF30202BD8329E5CE
Q9NUW8-2
- Name2
Computationally mapped potential isoform sequences
There are 13 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
E7EPD8 | E7EPD8_HUMAN | TDP1 | 589 | ||
H0YJL7 | H0YJL7_HUMAN | TDP1 | 51 | ||
H0YJ44 | H0YJ44_HUMAN | TDP1 | 281 | ||
G3V554 | G3V554_HUMAN | TDP1 | 161 | ||
G3V4W8 | G3V4W8_HUMAN | TDP1 | 191 | ||
G3V5B8 | G3V5B8_HUMAN | TDP1 | 151 | ||
G3V5F9 | G3V5F9_HUMAN | TDP1 | 147 | ||
G3V5H9 | G3V5H9_HUMAN | TDP1 | 259 | ||
G3V3Q0 | G3V3Q0_HUMAN | TDP1 | 146 | ||
G3V2U6 | G3V2U6_HUMAN | TDP1 | 279 | ||
G3V2F4 | G3V2F4_HUMAN | TDP1 | 578 | ||
G3V2J6 | G3V2J6_HUMAN | TDP1 | 219 | ||
Q9BRS7 | Q9BRS7_HUMAN | TDP1 | 298 |
Features
Showing features for alternative sequence, compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_055765 | 1-25 | in isoform 2 | |||
Sequence: MSQEGDYGRWTISSSDESEEEKPKP → MVISERLRLTSMPRPSLTRTSLSAR | ||||||
Compositional bias | 13-27 | Basic and acidic residues | ||||
Sequence: SSSDESEEEKPKPDK | ||||||
Alternative sequence | VSP_055766 | 26-264 | in isoform 2 | |||
Sequence: Missing | ||||||
Compositional bias | 64-88 | Polar residues | ||||
Sequence: KFSNTDSVLPPKRQKSGSQEDLGWC | ||||||
Sequence conflict | 389 | in Ref. 2; BAA91997 | ||||
Sequence: A → P | ||||||
Sequence conflict | 511 | in Ref. 6; AAF65624 | ||||
Sequence: L → R |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
BX161451 EMBL· GenBank· DDBJ | CAD61915.1 EMBL· GenBank· DDBJ | mRNA | ||
AK001952 EMBL· GenBank· DDBJ | BAA91997.1 EMBL· GenBank· DDBJ | mRNA | ||
DQ367843 EMBL· GenBank· DDBJ | ABC79301.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AL137128 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC015474 EMBL· GenBank· DDBJ | AAH15474.1 EMBL· GenBank· DDBJ | mRNA | ||
AF182002 EMBL· GenBank· DDBJ | AAF65623.1 EMBL· GenBank· DDBJ | mRNA | ||
AF182003 EMBL· GenBank· DDBJ | AAF65624.1 EMBL· GenBank· DDBJ | mRNA |