UniProtKB/Swiss-Prot O95551: Variant p.Ile307Val

Tyrosyl-DNA phosphodiesterase 2
Gene: TDP2
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Variant information Variant position:

307 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Isoleucine (I) to Valine (V) at position 307 (I307V, p.Ile307Val). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties:

Similar physico-chemical property. Both residues are medium size and hydrophobic. The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

3 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:

Lowest score: -4 (low probability of substitution).
Highest score: 11 (high probability of substitution).

More information can be found on the following page
Variant description:

Slightly decreased phosphodiesterase activity. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs77273535 [ dbSNP | Ensembl ]

Sequence information Variant position:

307 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

362 The length of the canonical sequence.
Location on the sequence:

LGKPKHCQYTWDTQMNSNLG I TAACKLRFDRIFFRAAAEEG The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation:

The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         LGKPKHCQYTWDTQMNSNLGITAACKLRFDRIFFRAAAEEG

Mouse                         LGKPKHCQYTWDTKANNNLRIPAAYKHRFDRIFFR--AEEG

Rat                           LGKPKHCRYTWDTKANDNLRIPAACKHRFDRIFFR--AEEG

Bovine                        LGKPKHCQYTWDTQMNSNLGIAANCKLRFDRIFFRAAAEGG

Chicken                       LGKPQHCRYTWDTSSNTNLRIESKCKLRFDRLYFRPAAEGG

Xenopus laevis                LGKPEHCRYTWDTKLNNNLRACYTSRLRFDRILYRASMEGS

Xenopus tropicalis            LGKPEHCRYTWDTKVNKNLRAPYICRLRFDRIFFRASQEGS

Zebrafish                     LGKQEHCRYTWDTKANSNKTVPYVSRCRFDRIFLRSAKTAP

Caenorhabditis elegans        AGSDNKTKFTWDTFKNDNKQGFHGAKMRFDRLYWS-----G

Sequence annotation in neighborhood:

The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:

Type: the type of sequence feature.
Positions: endpoints of the sequence feature.
Description: contains additional information about the feature.

Type	Positions	Description
Chain	1 – 362	Tyrosyl-DNA phosphodiesterase 2
Site	297 – 297	Interaction with 5' end of substrate DNA
Site	315 – 315	Interaction with 5' end of substrate DNA
Mutagenesis	305 – 305	L -> AFW. Decreased phosphodiesterase activity.
Mutagenesis	316 – 316	D -> N. Strongly decreased phosphodiesterase activity.

Literature citations
TDP2 protects transcription from abortive topoisomerase activity and is required for normal neural function.
Gomez-Herreros F.; Schuurs-Hoeijmakers J.H.; McCormack M.; Greally M.T.; Rulten S.; Romero-Granados R.; Counihan T.J.; Chaila E.; Conroy J.; Ennis S.; Delanty N.; Cortes-Ledesma F.; de Brouwer A.P.; Cavalleri G.L.; El-Khamisy S.F.; de Vries B.B.; Caldecott K.W.;
Nat. Genet. 46:516-521(2014)
Cited for: FUNCTION; TISSUE SPECIFICITY; INVOLVEMENT IN SCAR23; VARIANT VAL-307; Reversal of DNA damage induced Topoisomerase 2 DNA-protein crosslinks by Tdp2.
Schellenberg M.J.; Perera L.; Strom C.N.; Waters C.A.; Monian B.; Appel C.D.; Vilas C.K.; Williams J.G.; Ramsden D.A.; Williams R.S.;
Nucleic Acids Res. 44:3829-3844(2016)
Cited for: X-RAY CRYSTALLOGRAPHY (3.21 ANGSTROMS) OF 108-362 IN COMPLEX WITH DNA; FUNCTION; CATALYTIC ACTIVITY; COFACTOR; ACTIVE SITE; CHARACTERIZATION OF VARIANT VAL-307; MUTAGENESIS OF TYR-178; ARG-206; ASP-262; LEU-305; ASP-316; ASP-350 AND HIS-351;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.