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O70372

- TERT_MOUSE

UniProt

O70372 - TERT_MOUSE

Protein

Telomerase reverse transcriptase

Gene

Tert

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 112 (01 Oct 2014)
      Sequence version 1 (01 Aug 1998)
      Previous versions | rss
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    Functioni

    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.By similarity

    Catalytic activityi

    Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).PROSITE-ProRule annotation

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei169 – 1691Required for optimal binding of telomeric ssDNA and incorporation of nucleotides at the second position of the templateBy similarity
    Metal bindingi702 – 7021Magnesium; catalyticPROSITE-ProRule annotation
    Sitei860 – 8601Required for nucleotide incorporation and primer extension rateBy similarity
    Metal bindingi861 – 8611Magnesium; catalyticPROSITE-ProRule annotation
    Metal bindingi862 – 8621Magnesium; catalyticPROSITE-ProRule annotation

    GO - Molecular functioni

    1. DNA binding Source: UniProtKB-KW
    2. metal ion binding Source: UniProtKB-KW
    3. protein binding Source: MGI
    4. telomerase activity Source: MGI
    5. telomeric RNA binding Source: Ensembl
    6. telomeric template RNA reverse transcriptase activity Source: InterPro

    GO - Biological processi

    1. DNA strand elongation Source: Ensembl
    2. negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: Ensembl
    3. replicative senescence Source: Ensembl
    4. telomere formation via telomerase Source: Ensembl
    5. telomere maintenance via telomerase Source: Ensembl

    Keywords - Molecular functioni

    Nucleotidyltransferase, Ribonucleoprotein, RNA-directed DNA polymerase, Transferase

    Keywords - Ligandi

    DNA-binding, Magnesium, Metal-binding

    Enzyme and pathway databases

    ReactomeiREACT_216539. formation of the beta-catenin:TCF transactivating complex.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Telomerase reverse transcriptase (EC:2.7.7.49)
    Alternative name(s):
    Telomerase catalytic subunit
    Gene namesi
    Name:Tert
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 13

    Organism-specific databases

    MGIiMGI:1202709. Tert.

    Subcellular locationi

    Nucleusnucleolus By similarity. Nucleusnucleoplasm By similarity. Nucleus. Chromosometelomere. Cytoplasm By similarity. NucleusPML 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.By similarity

    GO - Cellular componenti

    1. chromosome, telomeric region Source: UniProtKB-SubCell
    2. cytoplasm Source: UniProtKB-SubCell
    3. nucleolus Source: UniProtKB-SubCell
    4. PML body Source: UniProtKB-SubCell
    5. telomerase holoenzyme complex Source: Ensembl

    Keywords - Cellular componenti

    Chromosome, Cytoplasm, Nucleus, Telomere

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 11221122Telomerase reverse transcriptasePRO_0000054926Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei447 – 4471Phosphoserine; by DYRK2By similarity
    Modified residuei697 – 6971Phosphotyrosine; by SRC-type Tyr-kinasesBy similarity

    Post-translational modificationi

    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.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.By similarity

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Proteomic databases

    PaxDbiO70372.
    PRIDEiO70372.

    PTM databases

    PhosphoSiteiO70372.

    Expressioni

    Tissue specificityi

    High activity in intestine, liver and testis, moderate in lung, very low in muscle, heart and brain.3 Publications

    Developmental stagei

    Highest levels in midgestational stages, E9.5 to E15.5.1 Publication

    Gene expression databases

    ArrayExpressiO70372.
    BgeeiO70372.
    CleanExiMM_TERT.
    GenevestigatoriO70372.

    Interactioni

    Subunit structurei

    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.By similarity3 Publications

    Protein-protein interaction databases

    BioGridi204118. 1 interaction.
    DIPiDIP-60451N.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini595 – 928334Reverse transcriptasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 239239RNA-interacting domain 1By similarityAdd
    BLAST
    Regioni58 – 205148GQ motifBy similarityAdd
    BLAST
    Regioni137 – 1415Required for regulating specificity for telomeric DNA and for processivity for primer elongationBy similarity
    Regioni240 – 32889LinkerBy similarityAdd
    BLAST
    Regioni306 – 528223Required for oligomerizationBy similarityAdd
    BLAST
    Regioni329 – 540212RNA-interacting domain 2By similarityAdd
    BLAST
    Regioni381 – 511131QFP motifBy similarityAdd
    BLAST
    Regioni402 – 42221CP motifBy similarityAdd
    BLAST
    Regioni907 – 92115Required for oligomerizationBy similarityAdd
    BLAST
    Regioni923 – 9275Primer grip sequenceBy similarity
    Regioni929 – 1122194CTEBy similarityAdd
    BLAST

    Domaini

    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.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

    Sequence similaritiesi

    Contains 1 reverse transcriptase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiNOG276584.
    GeneTreeiENSGT00390000018531.
    HOGENOMiHOG000148780.
    HOVERGENiHBG000460.
    InParanoidiO70372.
    KOiK11126.
    OMAiRACFYAT.
    OrthoDBiEOG744TB3.
    PhylomeDBiO70372.
    TreeFamiTF329048.

    Family and domain databases

    InterProiIPR000477. RT_dom.
    IPR021891. Telomerase_RBD.
    IPR003545. Telomerase_RT.
    [Graphical view]
    PfamiPF00078. RVT_1. 1 hit.
    PF12009. Telomerase_RBD. 1 hit.
    [Graphical view]
    PRINTSiPR01365. TELOMERASERT.
    SMARTiSM00975. Telomerase_RBD. 1 hit.
    [Graphical view]
    PROSITEiPS50878. RT_POL. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    O70372-1 [UniParc]FASTAAdd to Basket

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    MTRAPRCPAV RSLLRSRYRE VWPLATFVRR LGPEGRRLVQ PGDPKIYRTL     50
    VAQCLVCMHW GSQPPPADLS FHQVSSLKEL VARVVQRLCE RNERNVLAFG 100
    FELLNEARGG PPMAFTSSVR SYLPNTVIET LRVSGAWMLL LSRVGDDLLV 150
    YLLAHCALYL LVPPSCAYQV CGSPLYQICA TTDIWPSVSA SYRPTRPVGR 200
    NFTNLRFLQQ IKSSSRQEAP KPLALPSRGT KRHLSLTSTS VPSAKKARCY 250
    PVPRVEEGPH RQVLPTPSGK SWVPSPARSP EVPTAEKDLS SKGKVSDLSL 300
    SGSVCCKHKP SSTSLLSPPR QNAFQLRPFI ETRHFLYSRG DGQERLNPSF 350
    LLSNLQPNLT GARRLVEIIF LGSRPRTSGP LCRTHRLSRR YWQMRPLFQQ 400
    LLVNHAECQY VRLLRSHCRF RTANQQVTDA LNTSPPHLMD LLRLHSSPWQ 450
    VYGFLRACLC KVVSASLWGT RHNERRFFKN LKKFISLGKY GKLSLQELMW 500
    KMKVEDCHWL RSSPGKDRVP AAEHRLRERI LATFLFWLMD TYVVQLLRSF 550
    FYITESTFQK NRLFFYRKSV WSKLQSIGVR QHLERVRLRE LSQEEVRHHQ 600
    DTWLAMPICR LRFIPKPNGL RPIVNMSYSM GTRALGRRKQ AQHFTQRLKT 650
    LFSMLNYERT KHPHLMGSSV LGMNDIYRTW RAFVLRVRAL DQTPRMYFVK 700
    ADVTGAYDAI PQGKLVEVVA NMIRHSESTY CIRQYAVVRR DSQGQVHKSF 750
    RRQVTTLSDL QPYMGQFLKH LQDSDASALR NSVVIEQSIS MNESSSSLFD 800
    FFLHFLRHSV VKIGDRCYTQ CQGIPQGSSL STLLCSLCFG DMENKLFAEV 850
    QRDGLLLRFV DDFLLVTPHL DQAKTFLSTL VHGVPEYGCM INLQKTVVNF 900
    PVEPGTLGGA APYQLPAHCL FPWCGLLLDT QTLEVFCDYS GYAQTSIKTS 950
    LTFQSVFKAG KTMRNKLLSV LRLKCHGLFL DLQVNSLQTV CINIYKIFLL 1000
    QAYRFHACVI QLPFDQRVRK NLTFFLGIIS SQASCCYAIL KVKNPGMTLK 1050
    ASGSFPPEAA HWLCYQAFLL KLAAHSVIYK CLLGPLRTAQ KLLCRKLPEA 1100
    TMTILKAAAD PALSTDFQTI LD 1122
    Length:1,122
    Mass (Da):127,978
    Last modified:August 1, 1998 - v1
    Checksum:iF85266905DD6558C
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti553 – 5531I → V in AAB84200. 1 PublicationCurated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF051911 mRNA. Translation: AAC09323.1.
    AF073311 mRNA. Translation: AAC34821.1.
    AF247818 mRNA. Translation: AAF62177.1.
    AF029235 mRNA. Translation: AAB84200.1.
    CCDSiCCDS26633.1.
    RefSeqiNP_033380.1. NM_009354.1.
    UniGeneiMm.10109.

    Genome annotation databases

    EnsembliENSMUST00000022104; ENSMUSP00000022104; ENSMUSG00000021611.
    GeneIDi21752.
    KEGGimmu:21752.
    UCSCiuc007rdq.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF051911 mRNA. Translation: AAC09323.1 .
    AF073311 mRNA. Translation: AAC34821.1 .
    AF247818 mRNA. Translation: AAF62177.1 .
    AF029235 mRNA. Translation: AAB84200.1 .
    CCDSi CCDS26633.1.
    RefSeqi NP_033380.1. NM_009354.1.
    UniGenei Mm.10109.

    3D structure databases

    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 204118. 1 interaction.
    DIPi DIP-60451N.

    PTM databases

    PhosphoSitei O70372.

    Proteomic databases

    PaxDbi O70372.
    PRIDEi O70372.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000022104 ; ENSMUSP00000022104 ; ENSMUSG00000021611 .
    GeneIDi 21752.
    KEGGi mmu:21752.
    UCSCi uc007rdq.1. mouse.

    Organism-specific databases

    CTDi 7015.
    MGIi MGI:1202709. Tert.

    Phylogenomic databases

    eggNOGi NOG276584.
    GeneTreei ENSGT00390000018531.
    HOGENOMi HOG000148780.
    HOVERGENi HBG000460.
    InParanoidi O70372.
    KOi K11126.
    OMAi RACFYAT.
    OrthoDBi EOG744TB3.
    PhylomeDBi O70372.
    TreeFami TF329048.

    Enzyme and pathway databases

    Reactomei REACT_216539. formation of the beta-catenin:TCF transactivating complex.

    Miscellaneous databases

    NextBioi 301049.
    PROi O70372.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O70372.
    Bgeei O70372.
    CleanExi MM_TERT.
    Genevestigatori O70372.

    Family and domain databases

    InterProi IPR000477. RT_dom.
    IPR021891. Telomerase_RBD.
    IPR003545. Telomerase_RT.
    [Graphical view ]
    Pfami PF00078. RVT_1. 1 hit.
    PF12009. Telomerase_RBD. 1 hit.
    [Graphical view ]
    PRINTSi PR01365. TELOMERASERT.
    SMARTi SM00975. Telomerase_RBD. 1 hit.
    [Graphical view ]
    PROSITEi PS50878. RT_POL. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "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.
    2. "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.
    3. "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.
    4. "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.
    5. "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.
    6. "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.
    7. Cited for: INTERACTION WITH SMARCA4, FUNCTION.

    Entry informationi

    Entry nameiTERT_MOUSE
    AccessioniPrimary (citable) accession number: O70372
    Secondary accession number(s): O35432, Q9JK99
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 30, 2000
    Last sequence update: August 1, 1998
    Last modified: October 1, 2014
    This is version 112 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Caution

    Was originally thought to originate from rat.1 Publication

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3