TERT_CANLF
ID TERT_CANLF Reviewed; 1123 AA.
AC Q6A548;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2004, sequence version 1.
DT 03-AUG-2022, entry version 98.
DE RecName: Full=Telomerase reverse transcriptase;
DE EC=2.7.7.49;
DE AltName: Full=Telomerase catalytic subunit;
GN Name=TERT;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND FUNCTION.
RC TISSUE=Kidney;
RX PubMed=15225880; DOI=10.1016/j.gene.2004.03.032;
RA Nasir L., Gault E., Campbell S., Veeramalai M., Gilbert D., McFarlane R.,
RA Munro A., Argyle D.J.;
RT "Isolation and expression of the reverse transcriptase component of the
RT Canis familiaris telomerase ribonucleoprotein (dogTERT).";
RL Gene 336:105-113(2004).
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 (By
CC similarity). {ECO:0000250, ECO:0000269|PubMed:15225880}.
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; Evidence={ECO:0000255|PROSITE-
CC ProRule:PRU00405};
CC -!- SUBUNIT: Catalytic component of the telomerase holoenzyme complex
CC composed of one molecule of TERT, one molecule of WRAP53/TCAB1, two
CC molecules of H/ACA ribonucleoprotein complex subunits DKC1, NOP10, NHP2
CC and GAR1, and a telomerase RNA template component (TERC). The
CC telomerase holoenzyme complex is associated with TEP1, SMG6/EST1A and
CC POT1. The molecular chaperone HSP90/P23 complex is required for correct
CC assembly and stabilization of the active telomerase. Interacts directly
CC with HSP90A and PTGES3. Interacts with HSPA1A; the interaction occurs
CC in the absence of TERC and dissociates once the complex has formed.
CC Interacts with RAN; the interaction promotes nuclear export of TERT.
CC Interacts with XPO1. Interacts with PTPN11; the interaction retains
CC TERT in the nucleus. Interacts with NCL (via RRM1 and C-terminal
CC RRM4/Arg/Gly-rich domains); the interaction is important for nucleolar
CC localization of TERT (By similarity). Interacts with SMARCA4 (via the
CC bromodomain); the interaction regulates Wnt-mediated signaling (By
CC similarity). Interacts with MCRS1 (isoform MCRS2); the interaction
CC inhibits in vitro telomerase activity (By similarity). Interacts with
CC PIF1; the interaction has no effect on the elongation activity of TERT
CC (By similarity). Interacts with PML; the interaction recruits TERT to
CC PML bodies and inhibits telomerase activity (By similarity). Interacts
CC with GNL3L (By similarity). Interacts with isoform 1 and isoform 2 of
CC NVL (By similarity). Interacts with DHX36 (By similarity). Interacts
CC with ATF7 (By similarity). {ECO:0000250|UniProtKB:O14746,
CC ECO:0000250|UniProtKB:O70372}.
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus
CC {ECO:0000250|UniProtKB:O14746}. Nucleus, nucleoplasm {ECO:0000250}.
CC Nucleus. Chromosome, telomere. Cytoplasm {ECO:0000250}. Nucleus, PML
CC body {ECO:0000250}. Note=Shuttling between nuclear and cytoplasm
CC depends on cell cycle, phosphorylation states, transformation and DNA
CC damage. Diffuse localization in the nucleoplasm. Enriched in nucleoli
CC of certain cell types. Translocated to the cytoplasm via nuclear pores
CC in a CRM1/RAN-dependent manner involving oxidative stress-mediated
CC phosphorylation at Tyr-697. Dephosphorylation at this site by SHP2
CC retains TERT in the nucleus. Translocated to the nucleus by
CC phosphorylation by AKT (By similarity). {ECO:0000250}.
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:0000250}.
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 (By similarity). {ECO:0000250}.
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:0000250}.
CC -!- PTM: Phosphorylation at Tyr-697 under oxidative stress leads to
CC translocation of TERT to the cytoplasm and reduces its antiapoptotic
CC activity. Dephosphorylated by SHP2/PTPN11 leading to nuclear retention.
CC Phosphorylation at Ser-227 by the AKT pathway promotes nuclear
CC location. Phosphorylation at the G2/M phase at Ser-446 by DYRK2
CC promotes ubiquitination by the EDVP complex and degradation (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Ubiquitinated by the EDVP complex, a E3 ligase complex following
CC phosphorylation at Ser-446 by DYRK2. Ubiquitinated leads to proteasomal
CC degradation (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the reverse transcriptase family. Telomerase
CC subfamily. {ECO:0000305}.
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DR EMBL; AF380351; AAQ02791.1; -; mRNA.
DR RefSeq; NP_001026800.1; NM_001031630.1.
DR AlphaFoldDB; Q6A548; -.
DR SMR; Q6A548; -.
DR STRING; 9615.ENSCAFP00000048407; -.
DR PaxDb; Q6A548; -.
DR PRIDE; Q6A548; -.
DR GeneID; 403412; -.
DR KEGG; cfa:403412; -.
DR CTD; 7015; -.
DR eggNOG; KOG1005; Eukaryota.
DR InParanoid; Q6A548; -.
DR OrthoDB; 1297956at2759; -.
DR BRENDA; 2.7.7.49; 1153.
DR Proteomes; UP000002254; Unplaced.
DR GO; GO:0000781; C:chromosome, telomeric region; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005730; C:nucleolus; ISS:UniProtKB.
DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
DR GO; GO:0000333; C:telomerase catalytic core complex; IBA:GO_Central.
DR GO; GO:0005697; C:telomerase holoenzyme complex; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003720; F:telomerase activity; ISS:UniProtKB.
DR GO; GO:0070034; F:telomerase RNA binding; IBA:GO_Central.
DR GO; GO:0003721; F:telomerase RNA reverse transcriptase activity; IBA:GO_Central.
DR GO; GO:0042162; F:telomeric DNA binding; IBA:GO_Central.
DR GO; GO:0007004; P:telomere maintenance via telomerase; ISS:UniProtKB.
DR InterPro; IPR043502; DNA/RNA_pol_sf.
DR InterPro; IPR000477; RT_dom.
DR InterPro; IPR021891; Telomerase_RBD.
DR InterPro; IPR003545; Telomerase_RT.
DR PANTHER; PTHR12066; PTHR12066; 1.
DR Pfam; PF00078; RVT_1; 1.
DR Pfam; PF12009; Telomerase_RBD; 1.
DR PRINTS; PR01365; TELOMERASERT.
DR SMART; SM00975; Telomerase_RBD; 1.
DR SUPFAM; SSF56672; SSF56672; 1.
DR PROSITE; PS50878; RT_POL; 1.
PE 2: Evidence at transcript level;
KW Chromosome; Cytoplasm; DNA-binding; Magnesium; Metal-binding;
KW Nucleotidyltransferase; Nucleus; Phosphoprotein; Reference proteome;
KW Ribonucleoprotein; RNA-directed DNA polymerase; Telomere; Transferase;
KW Ubl conjugation.
FT CHAIN 1..1123
FT /note="Telomerase reverse transcriptase"
FT /id="PRO_0000054924"
FT DOMAIN 595..926
FT /note="Reverse transcriptase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00405"
FT REGION 1..230
FT /note="RNA-interacting domain 1"
FT /evidence="ECO:0000250"
FT REGION 58..197
FT /note="GQ motif"
FT /evidence="ECO:0000250"
FT REGION 137..141
FT /note="Required for regulating specificity for telomeric
FT DNA and for processivity for primer elongation"
FT /evidence="ECO:0000250"
FT REGION 202..311
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 231..308
FT /note="Linker"
FT /evidence="ECO:0000250"
FT REGION 309..539
FT /note="RNA-interacting domain 2"
FT /evidence="ECO:0000250"
FT REGION 360..510
FT /note="QFP motif"
FT /evidence="ECO:0000250"
FT REGION 381..401
FT /note="CP motif"
FT /evidence="ECO:0000250"
FT REGION 905..919
FT /note="Required for oligomerization"
FT /evidence="ECO:0000250"
FT REGION 921..925
FT /note="Primer grip sequence"
FT /evidence="ECO:0000250"
FT REGION 927..1123
FT /note="CTE"
FT /evidence="ECO:0000250"
FT MOTIF 222..240
FT /note="Bipartite nuclear localization signal"
FT /evidence="ECO:0000250"
FT MOTIF 312..317
FT /note="TFLY; involved in RNA binding"
FT /evidence="ECO:0000250|UniProtKB:Q4KTA7"
FT COMPBIAS 289..305
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 702
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00405"
FT BINDING 859
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00405"
FT BINDING 860
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00405"
FT SITE 169
FT /note="Required for optimal binding of telomeric ssDNA and
FT incorporation of nucleotides at the second position of the
FT template"
FT /evidence="ECO:0000250"
FT SITE 858
FT /note="Required for nucleotide incorporation and primer
FT extension rate"
FT /evidence="ECO:0000250"
FT MOD_RES 227
FT /note="Phosphoserine; by PKB/AKT1"
FT /evidence="ECO:0000250|UniProtKB:O14746"
FT MOD_RES 446
FT /note="Phosphoserine; by DYRK2"
FT /evidence="ECO:0000250|UniProtKB:O14746"
FT MOD_RES 697
FT /note="Phosphotyrosine; by SRC-type Tyr-kinases"
FT /evidence="ECO:0000250|UniProtKB:O14746"
SQ SEQUENCE 1123 AA; 124825 MW; F5F55D791106C1A3 CRC64;
MPRAPRCRAV RALLRGRYRE VLPLATFLRR LGPPGRLLVR RGDPAAFRAL VAQCLVCVPW
GARPPPAAPC FRQVSCLKEL VARVVQRLCE RGARNVLAFG FALLDGARGG PPVAFTTSVR
SYLPNTVTET LRGSGAWGLL LRRVGDDVLT HLLARCALYL LVAPSCAYQV CGPPLYDLCA
PASLPLPAPG LPGLPGLPGL GAGAGASADL RPTRQAQNSG ARRRRGSPGS GVPLAKRPRR
SVASEPERGA HRSFPRAQQP PVSEAPAVTP AVAASPAASW EGGPPGTRPT TPAWHPYPGP
QGVPHDPAHP ETKRFLYCSG GRERLRPSFL LSALPPTLSG ARKLVETIFL GSAPQKPGAA
RRMRRLPARY WRMRPLFQEL LGNHARCPYR ALLRTHCPLR AMAAKEGSGN QAHRGVGICP
LERPVAAPQE QTDSTRLVQL LRQHSSPWQV YAFLRACLCW LVPTGLWGSR HNQRRFLRNV
KKFISLGKHA KLSLQELTWK MKVRDCTWLH GNPGACCVPA AEHRRREEIL ARFLVLVDGH
IYVVKLLRSF FYVTETTFQK NRLFFYRKSV WSQLQSIGIR QLFNSVHLRE LSEAEVRRHR
EARPALLTSR LRFLPKPSGL RPIVNMDYIM GARTFHRDKK VQHLTSQLKT LFSVLNYERA
RRPSLLGASM LGMDDIHRAW RTFVLRIRAQ NPAPQLYFVK VDVTGAYDAL PQDRLVEVIA
NVIRPQESTY CVRHYAVVQR TARGHVRKAF KRHVSTFADL QPYMRQFVER LQETSLLRDA
VVIEQSSSLN EAGSSLFHLF LRLVHNHVVR IGGKSYIQCQ GVPQGSILST LLCSLCYGDM
ERRLFPGIEQ DGVLLRLVDD FLLVTPHLTQ AQAFLRTLVK GVPEYGCRAN LQKTAVNFPV
EDGALGSAAP LQLPAHCLFP WCGLLLDTRT LEVSCDYSSY AHTSIRASLT FSQGAKPGRN
MRRKLLAVLR LKCCALFLDL QVNGIHTVYM NVYKIFLLQA YRFHACVLQL PFNQPVRKNP
SFFLRVIADT ASCCYSLLKA RNAGLSLGAK GASGLFPSEA ARWLCLHAFL LKLAHHSGTY
RCLLGALQAA KAHLSRQLPR GTLAALEAAA DPSLTADFKT ILD
