TERT_BOVIN
ID TERT_BOVIN Reviewed; 1125 AA.
AC Q27ID4;
DT 11-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 02-MAY-2006, sequence version 2.
DT 03-AUG-2022, entry version 85.
DE RecName: Full=Telomerase reverse transcriptase;
DE EC=2.7.7.49;
DE AltName: Full=Telomerase catalytic subunit;
GN Name=TERT;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Zhao D., Du Z., Li N.;
RT "Cloning and expression of the reverse transcriptase component of Bos
RT taurus telomerase.";
RL Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases.
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}.
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-700. 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-700 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-231 by the AKT pathway promotes nuclear
CC location. Phosphorylation at the G2/M phase at Ser-450 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-450 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; DQ399842; ABD61652.2; -; Genomic_DNA.
DR RefSeq; NP_001039707.1; NM_001046242.1.
DR AlphaFoldDB; Q27ID4; -.
DR SMR; Q27ID4; -.
DR STRING; 9913.ENSBTAP00000016685; -.
DR PaxDb; Q27ID4; -.
DR PRIDE; Q27ID4; -.
DR GeneID; 518884; -.
DR KEGG; bta:518884; -.
DR CTD; 7015; -.
DR eggNOG; KOG1005; Eukaryota.
DR InParanoid; Q27ID4; -.
DR OrthoDB; 1297956at2759; -.
DR Proteomes; UP000009136; 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:0005697; C:telomerase holoenzyme complex; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003720; F:telomerase activity; ISS:UniProtKB.
DR GO; GO:0003721; F:telomerase RNA reverse transcriptase activity; IEA:InterPro.
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 3: Inferred from homology;
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..1125
FT /note="Telomerase reverse transcriptase"
FT /id="PRO_0000245166"
FT DOMAIN 598..928
FT /note="Reverse transcriptase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00405"
FT REGION 1..234
FT /note="RNA-interacting domain 1"
FT /evidence="ECO:0000250"
FT REGION 58..199
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 186..308
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 235..312
FT /note="Linker"
FT /evidence="ECO:0000250"
FT REGION 290..531
FT /note="Required for oligomerization"
FT /evidence="ECO:0000250"
FT REGION 313..543
FT /note="RNA-interacting domain 2"
FT /evidence="ECO:0000250"
FT REGION 364..514
FT /note="QFP motif"
FT /evidence="ECO:0000250"
FT REGION 385..405
FT /note="CP motif"
FT /evidence="ECO:0000250"
FT REGION 907..921
FT /note="Required for oligomerization"
FT /evidence="ECO:0000250"
FT REGION 923..927
FT /note="Primer grip sequence"
FT /evidence="ECO:0000250"
FT REGION 929..1125
FT /note="CTE"
FT /evidence="ECO:0000250"
FT MOTIF 226..244
FT /note="Bipartite nuclear localization signal"
FT /evidence="ECO:0000250"
FT MOTIF 316..321
FT /note="TFLY; involved in RNA binding"
FT /evidence="ECO:0000250|UniProtKB:Q4KTA7"
FT BINDING 705
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00405"
FT BINDING 861
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00405"
FT BINDING 862
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 860
FT /note="Required for nucleotide incorporation and primer
FT extension rate"
FT /evidence="ECO:0000250"
FT MOD_RES 231
FT /note="Phosphoserine; by PKB/AKT1"
FT /evidence="ECO:0000250|UniProtKB:O14746"
FT MOD_RES 450
FT /note="Phosphoserine; by DYRK2"
FT /evidence="ECO:0000250|UniProtKB:O14746"
FT MOD_RES 700
FT /note="Phosphotyrosine; by SRC-type Tyr-kinases"
FT /evidence="ECO:0000250|UniProtKB:O14746"
SQ SEQUENCE 1125 AA; 124447 MW; 717F437B50BB747B CRC64;
MPRAPRCRAV RALLRASYRQ VLPLAAFVRR LRPQGHRLVR RGDPAAFRAL VAQCLVCVPW
DAQPPPAAPS FRQVSCLKEL VARVVQRLCE RGARNVLAFG FTLLAGARGG PPVAFTTSVR
SYLPNTVTDT LRGSGAWGLL LHRVGDDVLT HLLSRCALYL LVPPTCAYQV CGPPLYDLRA
AAAAARRPTR QVGGTRAGFG LPRPASSNGG HGEAEGLLEA RAQGARRRRS SARGRLPPAK
RPRRGLEPGR DLEGQVARSP PRVVTPTRDA AEAKSRKGDV PGPCRLFPGG ERGVGSASWR
LSPSEGEPGA GACAETKRFL YCSGGGEQLR RSFLLCSLPP SLAGARTLVE TIFLDSKPGP
PGAPRRPRRL PARYWQMRPL FRKLLGNHAR SPYGALLRAH CPLPASAPRA GPDHQKCPGV
GGCPSERPAA APEGEANSGR LVQLLRQHSS PWQVYGLLRA CLRRLVPAGL WGSRHNERRF
LRNVKKLLSL GKHGRLSQQE LTWKMKVQDC AWLRASPGAR CVPAAEHRQR EAVLGRFLHW
LMGAYVVELL RSFFYVTETT FQKNRLFFFR KRIWSQLQRL GVRQHLDRVR LRELSEAEVR
QHQEARPALL TSRLRFVPKP GGLRPIVNVG CVEGAPAPPR DKKVQHLSSR VKTLFAVLNY
ERARRPGLLG ASVLGMDDIH RAWRAFVLPL RARGPAPPLY FVKVDVVGAY DALPQDKLAE
VIANVLQPQE NTYCVRHCAM VRTARGRMRK SFKRHVSTFS DFQPYLRQLV EHLQAMGSLR
DAVVIEQSCS LNEPGSSLFN LFLHLVRSHV IRIGGRSYIQ CQGIPQGSIL STLLCSFCYG
DMENKLFPGV QQDGVLLRLV DDFLLVTPHL TRARDFLRTL VRGVPEYGCQ VNLRKTVVNF
PVEPGALGGA APLQLPAHCL FPWCGLLLDT RTLEVHGDHS SYARTSIRAS LTFTQGFKPG
RNMRRKLLAV LQLKCHGLFL DLQVNSLQTV FTNVYKIFLL QAYRFHACVL QLPFSQPVRS
SPAFFLQVIA DTASRGYALL KARNAGASLG ARGAAGLFPS EAAQWLCLHA FLLKLARHRV
TYSRLLGALR TARARLHRQL PGPTRAALEA AADPALTADF KTILD
