ID M3YBZ0_MUSPF Unreviewed; 1113 AA.
AC M3YBZ0;
DT 01-MAY-2013, integrated into UniProtKB/TrEMBL.
DT 01-MAY-2013, sequence version 1.
DT 24-JAN-2024, entry version 61.
DE RecName: Full=Telomerase reverse transcriptase {ECO:0000256|ARBA:ARBA00016182, ECO:0000256|RuleBase:RU365061};
DE EC=2.7.7.49 {ECO:0000256|ARBA:ARBA00012493, ECO:0000256|RuleBase:RU365061};
DE AltName: Full=Telomerase catalytic subunit {ECO:0000256|ARBA:ARBA00032044, ECO:0000256|RuleBase:RU365061};
GN Name=TERT {ECO:0000313|Ensembl:ENSMPUP00000008847.1};
OS Mustela putorius furo (European domestic ferret) (Mustela furo).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Musteloidea; Mustelidae;
OC Mustelinae; Mustela.
OX NCBI_TaxID=9669 {ECO:0000313|Ensembl:ENSMPUP00000008847.1};
RN [1] {ECO:0000313|Ensembl:ENSMPUP00000008847.1}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (MAR-2023) to UniProtKB.
CC -!- FUNCTION: Telomerase is a ribonucleoprotein enzyme essential for the
CC replication of chromosome termini in most eukaryotes. Active in
CC progenitor and cancer cells. Inactive, or very low activity, in normal
CC somatic cells. Catalytic component of the teleromerase holoenzyme
CC complex whose main activity is the elongation of telomeres by acting as
CC a reverse transcriptase that adds simple sequence repeats to chromosome
CC ends by copying a template sequence within the RNA component of the
CC enzyme. Catalyzes the RNA-dependent extension of 3'-chromosomal termini
CC with the 6-nucleotide telomeric repeat unit, 5'-TTAGGG-3'. The
CC catalytic cycle involves primer binding, primer extension and release
CC of product once the template boundary has been reached or nascent
CC product translocation followed by further extension. More active on
CC substrates containing 2 or 3 telomeric repeats. Telomerase activity is
CC regulated by a number of factors including telomerase complex-
CC associated proteins, chaperones and polypeptide modifiers. Modulates
CC Wnt signaling. Plays important roles in aging and antiapoptosis.
CC {ECO:0000256|RuleBase:RU365061}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) =
CC diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339,
CC Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560,
CC ChEBI:CHEBI:173112; EC=2.7.7.49;
CC Evidence={ECO:0000256|ARBA:ARBA00024557,
CC ECO:0000256|RuleBase:RU365061};
CC -!- SUBCELLULAR LOCATION: Chromosome, telomere
CC {ECO:0000256|ARBA:ARBA00004574, ECO:0000256|RuleBase:RU365061}.
CC Nucleus, PML body {ECO:0000256|ARBA:ARBA00004322,
CC ECO:0000256|RuleBase:RU365061}. Nucleus, nucleolus
CC {ECO:0000256|RuleBase:RU365061}. Nucleus, nucleoplasm
CC {ECO:0000256|RuleBase:RU365061}. Nucleus
CC {ECO:0000256|RuleBase:RU365061}. Cytoplasm
CC {ECO:0000256|RuleBase:RU365061}. Note=Shuttling between nuclear and
CC cytoplasm depends on cell cycle, phosphorylation states, transformation
CC and DNA damage. Diffuse localization in the nucleoplasm. Enriched in
CC nucleoli of certain cell types. Translocated to the cytoplasm via
CC nuclear pores in a CRM1/RAN-dependent manner involving oxidative
CC stress-mediated phosphorylation at Tyr. Dephosphorylation at this site
CC by SHP2 retains TERT in the nucleus. Translocated to the nucleus by
CC phosphorylation by AKT. {ECO:0000256|RuleBase:RU365061}.
CC -!- DOMAIN: The RNA-interacting domain 1 (RD1)/N-terminal extension (NTE)
CC is required for interaction with the pseudoknot-template domain of each
CC of TERC dimers. It contains anchor sites that bind primer nucleotides
CC upstream of the RNA-DNA hybrid and is thus an essential determinant of
CC repeat addition processivity. {ECO:0000256|RuleBase:RU365061}.
CC -!- DOMAIN: The RNA-interacting domain 2 (RD2) is essential for both
CC interaction with the CR4-CR5 domain of TERC and for DNA synthesis.
CC {ECO:0000256|RuleBase:RU365061}.
CC -!- DOMAIN: The primer grip sequence in the RT domain is required for
CC telomerase activity and for stable association with short telomeric
CC primers. {ECO:0000256|RuleBase:RU365061}.
CC -!- SIMILARITY: Belongs to the reverse transcriptase family. Telomerase
CC subfamily. {ECO:0000256|ARBA:ARBA00008001,
CC ECO:0000256|RuleBase:RU365061}.
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DR EMBL; AEYP01069882; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_004768446.1; XM_004768389.2.
DR AlphaFoldDB; M3YBZ0; -.
DR STRING; 9669.ENSMPUP00000008847; -.
DR Ensembl; ENSMPUT00000008991.1; ENSMPUP00000008847.1; ENSMPUG00000008917.1.
DR GeneID; 101689866; -.
DR KEGG; mpuf:101689866; -.
DR CTD; 7015; -.
DR eggNOG; KOG1005; Eukaryota.
DR GeneTree; ENSGT00390000018531; -.
DR HOGENOM; CLU_001996_2_0_1; -.
DR InParanoid; M3YBZ0; -.
DR OMA; LAAMKFH; -.
DR OrthoDB; 55913at2759; -.
DR GO; GO:0000781; C:chromosome, telomeric region; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0042645; C:mitochondrial nucleoid; IEA:Ensembl.
DR GO; GO:0016607; C:nuclear speck; IEA:Ensembl.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
DR GO; GO:0000333; C:telomerase catalytic core complex; IEA:Ensembl.
DR GO; GO:1990572; C:TERT-RMRP complex; IEA:Ensembl.
DR GO; GO:0003677; F:DNA binding; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
DR GO; GO:0051087; F:protein-folding chaperone binding; IEA:Ensembl.
DR GO; GO:0003968; F:RNA-dependent RNA polymerase activity; IEA:Ensembl.
DR GO; GO:0070034; F:telomerase RNA binding; IEA:Ensembl.
DR GO; GO:0003721; F:telomerase RNA reverse transcriptase activity; IEA:Ensembl.
DR GO; GO:0098680; F:template-free RNA nucleotidyltransferase; IEA:Ensembl.
DR GO; GO:0001223; F:transcription coactivator binding; IEA:Ensembl.
DR GO; GO:0000049; F:tRNA binding; IEA:Ensembl.
DR GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl.
DR GO; GO:0022616; P:DNA strand elongation; IEA:Ensembl.
DR GO; GO:0070200; P:establishment of protein localization to telomere; IEA:Ensembl.
DR GO; GO:0007005; P:mitochondrion organization; IEA:Ensembl.
DR GO; GO:2000773; P:negative regulation of cellular senescence; IEA:Ensembl.
DR GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; IEA:Ensembl.
DR GO; GO:0046326; P:positive regulation of glucose import; IEA:Ensembl.
DR GO; GO:0042635; P:positive regulation of hair cycle; IEA:Ensembl.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; IEA:Ensembl.
DR GO; GO:1904751; P:positive regulation of protein localization to nucleolus; IEA:Ensembl.
DR GO; GO:2000648; P:positive regulation of stem cell proliferation; IEA:Ensembl.
DR GO; GO:0030177; P:positive regulation of Wnt signaling pathway; IEA:Ensembl.
DR GO; GO:0031647; P:regulation of protein stability; IEA:Ensembl.
DR GO; GO:0090399; P:replicative senescence; IEA:Ensembl.
DR GO; GO:0030422; P:siRNA processing; IEA:Ensembl.
DR GO; GO:0140745; P:siRNA transcription; IEA:Ensembl.
DR GO; GO:0007004; P:telomere maintenance via telomerase; IEA:Ensembl.
DR CDD; cd01648; TERT; 1.
DR Gene3D; 1.10.132.70; -; 1.
DR Gene3D; 1.10.357.90; -; 1.
DR Gene3D; 3.30.70.2630; -; 1.
DR InterPro; IPR043502; DNA/RNA_pol_sf.
DR InterPro; IPR000477; RT_dom.
DR InterPro; IPR021891; Telomerase_RBD.
DR InterPro; IPR003545; Telomerase_RT.
DR InterPro; IPR049139; TERT_C.
DR PANTHER; PTHR12066; TELOMERASE REVERSE TRANSCRIPTASE; 1.
DR PANTHER; PTHR12066:SF0; TELOMERASE REVERSE TRANSCRIPTASE; 1.
DR Pfam; PF00078; RVT_1; 1.
DR Pfam; PF12009; Telomerase_RBD; 1.
DR Pfam; PF21399; TERT_C; 1.
DR PRINTS; PR01365; TELOMERASERT.
DR SMART; SM00975; Telomerase_RBD; 1.
DR SUPFAM; SSF56672; DNA/RNA polymerases; 1.
DR PROSITE; PS50878; RT_POL; 1.
PE 3: Inferred from homology;
KW Chromosome {ECO:0000256|ARBA:ARBA00022454, ECO:0000256|RuleBase:RU365061};
KW Magnesium {ECO:0000256|ARBA:ARBA00022842, ECO:0000256|RuleBase:RU365061};
KW Metal-binding {ECO:0000256|ARBA:ARBA00022723,
KW ECO:0000256|RuleBase:RU365061};
KW Nucleotidyltransferase {ECO:0000256|ARBA:ARBA00022695,
KW ECO:0000256|RuleBase:RU365061};
KW Nucleus {ECO:0000256|ARBA:ARBA00023242, ECO:0000256|RuleBase:RU365061};
KW RNA-directed DNA polymerase {ECO:0000256|RuleBase:RU365061};
KW Telomere {ECO:0000256|ARBA:ARBA00022895, ECO:0000256|RuleBase:RU365061};
KW Transferase {ECO:0000256|ARBA:ARBA00022679, ECO:0000256|RuleBase:RU365061}.
FT DOMAIN 585..916
FT /note="Reverse transcriptase"
FT /evidence="ECO:0000259|PROSITE:PS50878"
FT REGION 190..302
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 232..251
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 276..293
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 1113 AA; 124632 MW; 3473093EDA608911 CRC64;
MPRAPRCRAV RALLRSRYRE VLPLASFLRR LGPQGRRLVR RGDPAAFRAL VAQCLVCVPW
DARPPPVAPS FRQVSCLKEL VARVVQRLCE RGARNVLAFG FALLDGARGG PPLAFTTSVR
SYLPNTVTET LRGSGAWGLL LRRVGDDVLA HLLTCCALYV LVAPSCAYQV CGPPLYDLCV
PAAVARPLGS PGHSPGTWKD LRPTRQAWKS GARRRRQGRS GSSPPLAKRP RRSVTPEPEQ
GTHRPSNQAH RGDSKPHAVT PARVAAEAAS WEGGPLGTRL SSTTAQPSQG PQGVPHQPAH
PETKHFLYCS GGRERLRPSF LLSALPPSLT GARKLVETVF LGSGPQRAGA SHRTRRLPAR
YWRMRPLFQE LLGNHARCPY RALLRTHCPL RAQAPGEASS KQAHGGVGVC PLERPVAAPE
ENTDPRRLVR LLRQHSSPWQ VYTFLRACLC RLVPPALWGS RHNQRRFLRN VKKFISLGKH
AKLSPQELTW KMKVQDCAWL RGSPGACSVP AAEHRRREGV LARLLCWLMG TYVVELLRSF
FYVTETTFQK NRLFFYRKSV WSPLQTLGVR QHCTSVRLRE LSAAEVRRQH EARATLLTSR
LRFLPKPGGL RPIVNMDYVA GARALCRDKK IQHLTSQVKT LFSVLNYERA RRPRLLGASV
LGMDDIHRAW HDFVLRVRAQ DPAPRLYFVK VDVTGAYDAL PQDRLAEVVA NVLRPHENTY
CLRRYAVVRR TAQGHVRRSF KRHVSTFTDL PPYMRQFVER LQETTSLRDS VVIEQSYSLN
EASSGLFQLF LSLVYSHVIR IGGKSYLQCQ GIPQGSVLST LLCSLCYGDM ERRLFPGIQQ
DGLLLRLVDD FLLITPHLKR AQAFLRTLVR GVPEYGCSAN LQKTAVNFPV EDMALGSTAP
LQLPAHCLFP WCGLLLDTQT LEVSCDYSSY ARTSIRSSLT FSQGTRPGRS LRHKLFALLR
LKCCALFLDL QVNSVRTVYA NMYKIFLLQA YRFHACVLQF PFDQPVRKNP AFFLRIISDT
ASRCYSLLKA RNTGMSLGAK GASGLFPSEA ARWLCLQAFW LKLARHSGTY RCLLGALRAA
QGHLCRQLPR ATLAALEAAA DPSLTADFKT ILD
//
