Expasy logo

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O14746: Variant p.Arg865His

Telomerase reverse transcriptase
Gene: TERT
Feedback?
Variant information Variant position: help 865 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 Arginine (R) to Histidine (H) at position 865 (R865H, p.Arg865His). 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 large size and basic (R) to medium size and polar (H) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 0 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 PFBMFT1. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 865 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 CYGDMENKLFAGIRRDGLLL R LVDDFLLVTPHLTHAKTFLR 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                         CYGDME---NKLFAGIRRDG-LLLRLVDDFLLVTPHLTHAKTFLR

                              CYGDME---RRLFPGIEQDG-VLLRLVDDFLLVTPHLTQAQ

Mouse                         CFGDME---NKLFAEVQRDG-LLLRFVDDFLLVTPHLDQAK

Rat                           CFGDME---NKLFAEVQQDG-LLLRFVDDFLLVTPHLAHAK

Bovine                        CYGDME---NKLFPGVQQDG-VLLRLVDDFLLVTPHLTRAR

Baker's yeast                 VYDDLLEFYSEFKASPSQDT-LILKLADDFLIISTDQQQVI

Fission yeast                 YMEDLI---DEYLSFTKKKGSVLLRVVDDFLFITVNKKDAK
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 868 – 868
Binding site 869 – 869
Site 867 – 867 Required for nucleotide incorporation and primer extension rate
Alternative sequence 808 – 1132 Missing. In isoform 2 and isoform 4.
Mutagenesis 866 – 866 L -> Y. Moderate reduction in telomerase activity, no change in repeat extension rate nor on nucleotide incorporation fidelity. Little further reduction in activity but 13.5-fold increase in nucleotide incorporation fidelity; when associated with M-867.
Mutagenesis 867 – 867 V -> A. About 75% reduction in telomerase activity, about 80% reduction in repeat reduction rate and 3.9-fold increase in nucleotide incorporation fidelity.
Mutagenesis 867 – 867 V -> M. About 75% reduction in telomerase activity, about 50% reduction in repeat extension rate and 5.2-fold increase in nucleotide incorporation fidelity. Little further reduction in activity and 13.5-fold increase in nucleotide incorporation fidelity; when associated with Y-866.
Mutagenesis 867 – 867 V -> T. Severe reduction in telomerase activity, about 50% reduction in repeat extension rate and 2.2-fold increase in nucleotide incorporation fidelity. No further reduction in activity but 2.8-fold increase in nucleotide incorporation fidelity; when associated with Y-866.
Mutagenesis 868 – 868 D -> A. Loss of telomerase activity.
Mutagenesis 869 – 869 D -> A. Loss of telomerase activity.
Beta strand 861 – 873



Literature citations
Adult-onset pulmonary fibrosis caused by mutations in telomerase.
Tsakiri K.D.; Cronkhite J.T.; Kuan P.J.; Xing C.; Raghu G.; Weissler J.C.; Rosenblatt R.L.; Shay J.W.; Garcia C.K.;
Proc. Natl. Acad. Sci. U.S.A. 104:7552-7557(2007)
Cited for: VARIANT PFBMFT1 HIS-865;
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.