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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O14746: Variant p.Pro721Arg

Telomerase reverse transcriptase
Gene: TERT
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Variant information Variant position: help 721 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help 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: help 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: help -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: help In DKCB4; no effect on telomerase catalytic activity and little effect on binding to TERC. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 721 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 1132 The length of the canonical sequence.
Location on the sequence: help DPPPELYFVKVDVTGAYDTI P QDRLTEVIASIIKPQNTYCV 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         DPPPELYFVKVDVTGAYDTIPQDRLTEVIASIIKPQNT-YCV

                              NPAPQLYFVKVDVTGAYDALPQDRLVEVIANVIRPQESTYC

Mouse                         DQTPRMYFVKADVTGAYDAIPQGKLVEVVANMIRHSESTYC

Rat                           DQTPRMYFVKADVTGAYDAIPQDKLVEIVANIIRRSESMYC

Bovine                        GPAPPLYFVKVDVVGAYDALPQDKLAEVIANVLQPQENTYC

Baker's yeast                 NVLPELYFMKFDVKSCYDSIPRMECMRILKDALKNENGFFV

Fission yeast                 GR--KKYFVRIDIKSCYDRIKQDLMFRIVKKKLKDPE--FV
Sequence annotation in neighborhood: help 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.
TypePositionsDescription
Chain 1 – 1132 Telomerase reverse transcriptase
Domain 605 – 935 Reverse transcriptase
Binding site 712 – 712
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.