O70372 (TERT_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified April 16, 2014. Version 107. History...
Names and origin
|Protein names||Recommended name:|
Telomerase reverse transcriptase
Telomerase catalytic subunit
|Organism||Mus musculus (Mouse) [Reference proteome]|
|Taxonomic identifier||10090 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus|
|Sequence length||1122 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes. Active in progenitor and cancer cells. Inactive, or very low activity, in normal somatic cells. Catalytic component of the teleromerase holoenzyme complex whose main activity is the elongation of telomeres by acting as a reverse transcriptase that adds simple sequence repeats to chromosome ends by copying a template sequence within the RNA component of the enzyme. Catalyzes the RNA-dependent extension of 3'-chromosomal termini with the 6-nucleotide telomeric repeat unit, 5'-TTAGGG-3'. The catalytic cycle involves primer binding, primer extension and release of product once the template boundary has been reached or nascent product translocation followed by further extension. More active on substrates containing 2 or 3 telomeric repeats. Telomerase activity is regulated by a number of factors including telomerase complex-associated proteins, chaperones and polypeptide modifiers. Modulates Wnt signaling. Plays important roles in aging and antiapoptosis By similarity. Ref.1 Ref.5 Ref.7
Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).
Homodimer; dimerization is required to produce a functional complex. Oligomer; can form oligomers in the absence of the telomerase RNA template component (TERC). Catalytic subunit of the telomerase holoenzyme complex composed minimally of TERT and TERC. The telomerase complex is composed of TERT, DKC1, WDR79/TCAB1, NOP10, NHP2, GAR1, TEP1, EST1A, POT1 and a telomerase RNA template component (TERC). The molecular chaperone HSP90/P23 complex is required for correct assembly and stabilization of the active telomerase. Interacts directly with HSP90A and PTGES3. Interacts with HSPA1A; the interaction occurs in the absence of TERC and dissociates once the complex has formed. Interacts with RAN; the interaction promotes nuclear export of TERT. Interacts with XPO1. Interacts with PTPN11; the interaction retains TERT in the nucleus. Interacts with NCL (via RRM1 and C-terminal RRM4/Arg/Gly-rich domains); the interaction is important for nucleolar localization of TERT. Interacts with SMARCA4 (via the bromodomain); the interaction regulates Wnt-mediated signaling By similarity. Interacts with MCRS1 (isoform MCRS2);the interaction inhibits in vitro telomerase activity. Interacts with PIF1; the interaction has no effect on the elongation activity of TERT. Interacts with PML; the interaction recruits TERT to PML bodies and inhibits telomerase activity By similarity. Interacts with GNL3L. Ref.5 Ref.6 Ref.7
Nucleus › nucleolus By similarity. Nucleus › nucleoplasm By similarity. Nucleus. Chromosome › telomere. Cytoplasm By similarity. Nucleus › PML body By similarity. Note: Shuttling between nuclear and cytoplasm depends on cell cycle, phosphorylation states, transformation and DNA damage. Diffuse localization in the nucleoplasm. Enriched in nucleoli of certain cell types. Translocated to the cytoplasm via nuclear pores in a CRM1/RAN-dependent manner involving oxidative stress-mediated phosphorylation at Tyr-697. Dephosphorylation at this site by SHP2 retains TERT in the nucleus. Translocated to the nucleus by phosphorylation by AKT By similarity.
Highest levels in midgestational stages, E9.5 to E15.5. Ref.1
The primer grip sequence in the RT domain is required for telomerase activity and for stable association with short telomeric primers By similarity.
The RNA-interacting domain 1 (RD1)/N-terminal extension (NTE) is required for interaction with the pseudoknot-template domain of each of TERC dimers. It contains anchor sites that bind primer nucleotides upstream of the RNA-DNA hybrid and is thus an essential determinant of repeat addition processivity By similarity.
The RNA-interacting domain 2 (RD2) is essential for both interaction with the CR4-CR5 domain of TERC and for DNA sythesis By similarity.
Phosphorylation at Tyr-697 under oxidative stress leads to translocation of TERT to the cytoplasm and reduces its antiapoptotic activity. Dephosphorylated by SHP2/PTPN11 leading to nuclear retention. Phosphorylation by the AKT pathway promotes nuclear location. Phosphorylation at the G2/M phase at Ser-447 by DYRK2 promotes ubiquitination by the EDVP complex and degradation By similarity.
Ubiquitinated by the EDVP complex, a E3 ligase complex following phosphorylation at Ser-447 by DYRK2. Ubiquitinated leads to proteasomal degradation By similarity.
Contains 1 reverse transcriptase domain.
Was originally (Ref.3) thought to originate from rat.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 1122||1122||Telomerase reverse transcriptase||PRO_0000054926|
|Domain||595 – 928||334||Reverse transcriptase|
|Region||1 – 239||239||RNA-interacting domain 1 By similarity|
|Region||58 – 205||148||GQ motif By similarity|
|Region||137 – 141||5||Required for regulating specificity for telomeric DNA and for processivity for primer elongation By similarity|
|Region||240 – 328||89||Linker By similarity|
|Region||306 – 528||223||Required for oligomerization By similarity|
|Region||329 – 540||212||RNA-interacting domain 2 By similarity|
|Region||381 – 511||131||QFP motif By similarity|
|Region||402 – 422||21||CP motif By similarity|
|Region||907 – 921||15||Required for oligomerization By similarity|
|Region||923 – 927||5||Primer grip sequence By similarity|
|Region||929 – 1122||194||CTE By similarity|
|Metal binding||702||1||Magnesium; catalytic By similarity|
|Metal binding||861||1||Magnesium; catalytic By similarity|
|Metal binding||862||1||Magnesium; catalytic By similarity|
|Site||169||1||Required for optimal binding of telomeric ssDNA and incorporation of nucleotides at the second position of the template By similarity|
|Site||860||1||Required for nucleotide incorporation and primer extension rate By similarity|
Amino acid modifications
|Modified residue||447||1||Phosphoserine; by DYRK2 By similarity|
|Modified residue||697||1||Phosphotyrosine; by SRC-type Tyr-kinases By similarity|
|Sequence conflict||553||1||I → V in AAB84200. Ref.4|
|||"Expression of mouse telomerase reverse transcriptase during development, differentiation and proliferation."|
Greenberg R.A., Allsopp R.C., Chin L., Morin G.B., DePinho R.A.
Oncogene 16:1723-1730(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DEVELOPMENTAL STAGE, INDUCTION, TISSUE SPECIFICITY.
|||"Expression of mouse telomerase catalytic subunit in embryos and adult tissues."|
Martin-Rivera L., Herrera E., Albar J.P., Blasco M.A.
Proc. Natl. Acad. Sci. U.S.A. 95:10471-10476(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
|||"Cloning of rat telomerase catalytic subunit functional domains, reconstitution of telomerase activity and enzymatic profile of pig and chicken tissues."|
Wong S.C., Ong L.L., Er C.P., Gao S., Yu H., So J.B.
Life Sci. 73:2749-2760(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 548-1122, TISSUE SPECIFICITY.
|||"Partial sequence of Mus musculus telomerase catalytic subunit homolog."|
Drissi R., Cleveland J.L.
Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 550-616.
|||"Murine Pif1 interacts with telomerase and is dispensable for telomere function in vivo."|
Snow B.E., Mateyak M., Paderova J., Wakeham A., Iorio C., Zakian V., Squire J., Harrington L.
Mol. Cell. Biol. 27:1017-1026(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PIF1, FUNCTION.
|||"GNL3L stabilizes the TRF1 complex and promotes mitotic transition."|
Zhu Q., Meng L., Hsu J.K., Lin T., Teishima J., Tsai R.Y.
J. Cell Biol. 185:827-839(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GNL3L.
|||"Telomerase modulates Wnt signalling by association with target gene chromatin."|
Park J.I., Venteicher A.S., Hong J.Y., Choi J., Jun S., Shkreli M., Chang W., Meng Z., Cheung P., Ji H., McLaughlin M., Veenstra T.D., Nusse R., McCrea P.D., Artandi S.E.
Nature 460:66-72(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SMARCA4, FUNCTION.
|+||Additional computationally mapped references.|
|AF051911 mRNA. Translation: AAC09323.1.|
AF073311 mRNA. Translation: AAC34821.1.
AF247818 mRNA. Translation: AAF62177.1.
AF029235 mRNA. Translation: AAB84200.1.
|RefSeq||NP_033380.1. NM_009354.1. |
3D structure databases
Protein-protein interaction databases
|BioGrid||204118. 1 interaction.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSMUST00000022104; ENSMUSP00000022104; ENSMUSG00000021611. |
|UCSC||uc007rdq.1. mouse. |
|MGI||MGI:1202709. Tert. |
Gene expression databases
Family and domain databases
|InterPro||IPR000477. RT_dom. |
|Pfam||PF00078. RVT_1. 1 hit. |
PF12009. Telomerase_RBD. 1 hit.
|PRINTS||PR01365. TELOMERASERT. |
|SMART||SM00975. Telomerase_RBD. 1 hit. |
|PROSITE||PS50878. RT_POL. 1 hit. |
|Accession||Primary (citable) accession number: O70372|
Secondary accession number(s): O35432, Q9JK99
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|