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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O14746: Variant p.Thr726Met

Telomerase reverse transcriptase
Gene: TERT
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Variant information Variant position: help 726 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 Threonine (T) to Methionine (M) at position 726 (T726M, p.Thr726Met). 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 polar (T) to medium size and hydrophobic (M) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -1 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 AA; very severe; no effect on telomerase catalytic activity but shortened telomeres. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 726 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 LYFVKVDVTGAYDTIPQDRL T EVIASIIKPQNTYCVRRYAV 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                         LYFVKVDVTGAYDTIPQDRLTEVIASIIKPQNT-YCVRRYAV

                              LYFVKVDVTGAYDALPQDRLVEVIANVIRPQESTYCVRHYA

Mouse                         MYFVKADVTGAYDAIPQGKLVEVVANMIRHSESTYCIRQYA

Rat                           MYFVKADVTGAYDAIPQDKLVEIVANIIRRSESMYCIRQYA

Bovine                        LYFVKVDVVGAYDALPQDKLAEVIANVLQPQENTYCVRHCA

Baker's yeast                 LYFMKFDVKSCYDSIPRMECMRILKDALKNENGFFVRSQYF

Fission yeast                 KYFVRIDIKSCYDRIKQDLMFRIVKKKLKDPE--FVIRKYA
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
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.
Helix 722 – 733



Literature citations
Mutations in telomerase catalytic protein in Japanese children with aplastic anemia.
Liang J.; Yagasaki H.; Kamachi Y.; Hama A.; Matsumoto K.; Kato K.; Kudo K.; Kojima S.;
Haematologica 91:656-658(2006)
Cited for: VARIANTS AA ASP-682 AND MET-726; CHARACTERIZATION OF VARIANT AA MET-726; 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.