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UniProtKB/Swiss-Prot O14746: Variant p.Pro721Arg

Telomerase reverse transcriptase
Gene: TERT
Variant information

Variant position:  721
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LP/P [Disclaimer]
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 Proline (P) to Arginine (R) at position 721 (P721R, p.Pro721Arg).
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:  Change from medium size and hydrophobic (P) to large size and basic (R)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
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:  In DKCB4; no effect on telomerase catalytic activity and little effect on binding to TERC.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.

Sequence information

Variant position:  721
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1132
The length of the canonical sequence.

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.








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.

Chain 1 – 1132 Telomerase reverse transcriptase
Domain 605 – 935 Reverse transcriptase
Metal binding 712 – 712 Magnesium; catalytic
Modified residue 707 – 707 Phosphotyrosine; by SRC-type Tyr-kinases
Alternative sequence 711 – 722 Missing. In isoform 4.
Mutagenesis 707 – 707 Y -> F. Abolishes oxidative stress-induced phosphorylation and RAN binding. Impaired nuclear export and enhanced antiapoptotic activity against ROS-dependent apoptosis induction. Impaired interaction with PTPN11. No dephosphorylation by PTPN11.
Mutagenesis 712 – 712 D -> A. Loss of telomerase activity. In the absence of TR, no loss of binding to telomeric primers.

Literature citations

Mutations in dyskeratosis congenita: their impact on telomere length and the diversity of clinical presentation.
Vulliamy T.J.; Marrone A.; Knight S.W.; Walne A.; Mason P.J.; Dokal I.;
Blood 107:2680-2685(2006)
Cited for: VARIANT DKCB4 ARG-721;

Functional characterization of natural telomerase mutations found in patients with hematologic disorders.
Xin Z.T.; Beauchamp A.D.; Calado R.T.; Bradford J.W.; Regal J.A.; Shenoy A.; Liang Y.; Lansdorp P.M.; Young N.S.; Ly H.;
Blood 109:524-532(2007)
Cited for: VARIANT AA ASN-570; CHARACTERIZATION OF VARIANTS ASN-570; ASP-682; ARG-721; MET-726; ASN-902; TRP-979 AND LEU-1127;

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.