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Protein

Telomerase reverse transcriptase

Gene

Tert

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

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)DescriptionActionsGraphical viewLength
Sitei169Required for optimal binding of telomeric ssDNA and incorporation of nucleotides at the second position of the templateBy similarity1
Metal bindingi702Magnesium; catalyticPROSITE-ProRule annotation1
Sitei860Required for nucleotide incorporation and primer extension rateBy similarity1
Metal bindingi861Magnesium; catalyticPROSITE-ProRule annotation1
Metal bindingi862Magnesium; catalyticPROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Nucleotidyltransferase, Ribonucleoprotein, RNA-directed DNA polymerase, Transferase

Keywords - Ligandi

DNA-binding, Magnesium, Metal-binding

Enzyme and pathway databases

ReactomeiR-RNO-171319. Telomere Extension By Telomerase.
R-RNO-201722. 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:TertImported
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 1

Organism-specific databases

RGDi70494. Tert.

Subcellular locationi

  • Nucleusnucleolus By similarity
  • Nucleusnucleoplasm By similarity
  • Nucleus Curated
  • 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

  • cytoplasm Source: RGD
  • mitochondrial nucleoid Source: Ensembl
  • mitochondrion Source: BHF-UCL
  • nuclear chromosome, telomeric region Source: Ensembl
  • nucleolus Source: UniProtKB
  • nucleus Source: RGD
  • plasma membrane Source: Ensembl
  • PML body Source: UniProtKB-SubCell
  • telomerase catalytic core complex Source: GO_Central
  • TERT-RMRP complex Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Cytoplasm, Nucleus, Telomere

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL3108654.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002451651 – 1125Telomerase reverse transcriptaseAdd BLAST1125

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei447Phosphoserine; by DYRK2By similarity1
Modified residuei697Phosphotyrosine; by SRC-type Tyr-kinasesBy similarity1

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 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

PaxDbiQ673L6.
PRIDEiQ673L6.

Expressioni

Tissue specificityi

Isoform 1 and isoform 2 expressed in thymus, liver, spleen, lung, kidney and testis. High level of inactive isoform 3 in adult hippocampus, low level in heart, cortex and cerebellum.2 Publications

Developmental stagei

High activity in cortex at embryonic stage 16 and postnatal day 2. Low activity in cortex from postnatal day 5.1 Publication

Inductioni

Down-regulated by TGFbeta in fibroblasts. This inhibition is mediated by SMAD3.1 Publication

Gene expression databases

BgeeiENSRNOG00000025327.

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. Interacts with NVL (By similarity).By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000022683.

Chemistry databases

BindingDBiQ673L6.

Structurei

3D structure databases

ProteinModelPortaliQ673L6.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini595 – 928Reverse transcriptasePROSITE-ProRule annotationAdd BLAST334

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 239RNA-interacting domain 1By similarityAdd BLAST239
Regioni58 – 205GQ motifBy similarityAdd BLAST148
Regioni137 – 141Required for regulating specificity for telomeric DNA and for processivity for primer elongationBy similarity5
Regioni240 – 328LinkerBy similarityAdd BLAST89
Regioni306 – 528Required for oligomerizationBy similarityAdd BLAST223
Regioni329 – 540RNA-interacting domain 2By similarityAdd BLAST212
Regioni381 – 511QFP motifBy similarityAdd BLAST131
Regioni402 – 422CP motifBy similarityAdd BLAST21
Regioni907 – 921Required for oligomerizationBy similarityAdd BLAST15
Regioni923 – 927Primer grip sequenceBy similarity5
Regioni929 – 1125CTEBy similarityAdd BLAST197

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi332 – 337TFLY; involved in RNA bindingBy similarity6

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

Belongs to the reverse transcriptase family. Telomerase subfamily.Sequence analysis
Contains 1 reverse transcriptase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG1005. Eukaryota.
ENOG410XQJH. LUCA.
GeneTreeiENSGT00390000018531.
HOGENOMiHOG000148780.
HOVERGENiHBG000460.
InParanoidiQ673L6.
KOiK11126.
OMAiGMRPITR.
OrthoDBiEOG091G04DO.
PhylomeDBiQ673L6.
TreeFamiTF329048.

Family and domain databases

InterProiIPR000477. RT_dom.
IPR021891. Telomerase_RBD.
IPR003545. Telomerase_RT.
[Graphical view]
PANTHERiPTHR12066:SF0. PTHR12066:SF0. 1 hit.
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]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 11 Publication (identifier: Q673L6-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MPRAPRCPAV RSLLRSRYRE VWPLATFVRR LGLEGSRLVQ PGDPKVFRTL
60 70 80 90 100
VAQCLVCVPW GSQPPPADLS FHQVSSLKEL VSRVVQKLCE RGERNVLAFG
110 120 130 140 150
FALLNGARGG PPMAFTTSVH SYLPNSVTES LCVSGAWMLL LSRVGDDLLV
160 170 180 190 200
YLLSHCALYL LVPPSCAYQV CGSPLYQICA TTDTWSSVPA GYRPTRPVGG
210 220 230 240 250
NFTNLGSAHQ IKNSGHQEAP KPQALPSRGT KRLLSLTSTN VPSAKKARFE
260 270 280 290 300
PALRVDKGPH RQVVPTPSGK TWAPSPAASP KVPPAAKNLS LKGKASDPSL
310 320 330 340 350
SGSVCCKHKP SSSSLLSSPP QDAEKLRPFT ETRHFLYSRG GGQEELNPSF
360 370 380 390 400
LLNSLPPSLT GARRLVEIIF LGSRPRTSGP FCRTRRLPRR YWQMRPLFQQ
410 420 430 440 450
LLMNHAKCQY VRFLRSHCRF RTANQRVPDA MDTSPSHLTS LLRLHSSPWQ
460 470 480 490 500
VYGFLRACLR ELVPAGLWGT RHNERRFLKN VKKFISLGKY AKLSLQELMW
510 520 530 540 550
RVKVEDCHWL RSSPEKDTVP AAEHRLRERI LAMFLFWLMD TYVVQLLRSF
560 570 580 590 600
FYITETTFQK NRLFFYRKSV WSKLQSIGIR QQLERVQLRE LSQEEVKHHQ
610 620 630 640 650
DTWLAMPICR LRFIPKLNGL RPIVNMSYGM DTRAFGKKKQ TQCFTQSLKT
660 670 680 690 700
LFSVLNYERT KHPNLMGASV LGTSDSYRIW RTFVLRVRAL DQTPRMYFVK
710 720 730 740 750
ADVTGAYDAI PQDKLVEIVA NIIRRSESMY CIRQYAVVQK DSQGQVHKSF
760 770 780 790 800
RRQVSTLSDL QPYMGQFTKH LQDSDASALR NSVVIEQSIS MNETGSSLLH
810 820 830 840 850
FFLRFVRHSV VKIDGRFYVQ CQGIPQGSSL STLLCSLCFG DMENKLFAEV
860 870 880 890 900
QQDGLLLRFV DDFLLVTPHL AHAKAFLSTL VHGVPEYGCM INLQKTVVNF
910 920 930 940 950
PVETGALGGA APHQLPAHCL FPWCGLLLDT RTLEVFCDYS GYGRTSIKMS
960 970 980 990 1000
LTFQGVSRAG KTMRYKLLSV LRLKCHGLFL DLQVNSLQTV CINIYKIFLL
1010 1020 1030 1040 1050
QAYRFHACVI RLPFGQHVRK NHAFFLGIIS NLASCCYAIL KVKNPGVSLR
1060 1070 1080 1090 1100
AKGAPGSFPP EATRWLCYQA FLLKLAAHSV TYKCLLGPLR TAQKQLCRKL
1110 1120
PEATMTLLKT AADPALSTDF QTILD
Length:1,125
Mass (Da):126,934
Last modified:October 11, 2004 - v1
Checksum:iB8B2A11C914372DF
GO
Isoform 21 Publication (identifier: Q673L6-2) [UniParc]FASTAAdd to basket
Also known as: a1 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     641-646: Missing.

Show »
Length:1,119
Mass (Da):126,225
Checksum:i4CABB74D64E3F972
GO
Isoform 31 Publication (identifier: Q673L6-3) [UniParc]FASTAAdd to basket
Also known as: b1 Publication, c1 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     515-615: EKDTVPAAEH...MPICRLRFIP → ACTSFWDSPS...VPEEPPFLLP
     616-1125: Missing.

Note: Inactive form.
Show »
Length:615
Mass (Da):68,614
Checksum:i2892840D86620B63
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti521A → V in DAA01427 (PubMed:15057822).Curated1
Sequence conflicti528E → V in DAA01427 (PubMed:15057822).Curated1
Sequence conflicti550 – 551FF → LL in DAA01427 (PubMed:15057822).Curated2
Sequence conflicti583L → P in DAA01427 (PubMed:15057822).Curated1
Sequence conflicti630M → L in DAA01427 (PubMed:15057822).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_052081515 – 615EKDTV…LRFIP → ACTSFWDSPSPSQVSFIFIT AGKPSFPWIRRPLRYLETHR VELTHPAWQEGHCPCRRAPS EGEDPCHVPVLANGHICGTA AEVILLHHRDHVPEEPPFLL P in isoform 3. 1 PublicationAdd BLAST101
Alternative sequenceiVSP_052082616 – 1125Missing in isoform 3. 1 PublicationAdd BLAST510
Alternative sequenceiVSP_052083641 – 646Missing in isoform 2. 1 Publication6

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY539717 mRNA. Translation: AAT09124.1.
AY539718 mRNA. Translation: AAT09125.1.
AY539719 mRNA. Translation: AAT09126.1.
AY539720 mRNA. Translation: AAT09127.1.
AC123569 Genomic DNA. No translation available.
DQ021473 Genomic DNA. Translation: AAY40300.1.
AJ440965 mRNA. Translation: CAD29524.1.
AJ440966 Genomic DNA. Translation: CAD29525.2.
BK000660 mRNA. Translation: DAA01427.1.
RefSeqiNP_445875.1. NM_053423.1. [Q673L6-1]
UniGeneiRn.48802.

Genome annotation databases

EnsembliENSRNOT00000022683; ENSRNOP00000022683; ENSRNOG00000025327. [Q673L6-1]
GeneIDi301965.
KEGGirno:301965.
UCSCiRGD:70494. rat. [Q673L6-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY539717 mRNA. Translation: AAT09124.1.
AY539718 mRNA. Translation: AAT09125.1.
AY539719 mRNA. Translation: AAT09126.1.
AY539720 mRNA. Translation: AAT09127.1.
AC123569 Genomic DNA. No translation available.
DQ021473 Genomic DNA. Translation: AAY40300.1.
AJ440965 mRNA. Translation: CAD29524.1.
AJ440966 Genomic DNA. Translation: CAD29525.2.
BK000660 mRNA. Translation: DAA01427.1.
RefSeqiNP_445875.1. NM_053423.1. [Q673L6-1]
UniGeneiRn.48802.

3D structure databases

ProteinModelPortaliQ673L6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000022683.

Chemistry databases

BindingDBiQ673L6.
ChEMBLiCHEMBL3108654.

Proteomic databases

PaxDbiQ673L6.
PRIDEiQ673L6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000022683; ENSRNOP00000022683; ENSRNOG00000025327. [Q673L6-1]
GeneIDi301965.
KEGGirno:301965.
UCSCiRGD:70494. rat. [Q673L6-1]

Organism-specific databases

CTDi7015.
RGDi70494. Tert.

Phylogenomic databases

eggNOGiKOG1005. Eukaryota.
ENOG410XQJH. LUCA.
GeneTreeiENSGT00390000018531.
HOGENOMiHOG000148780.
HOVERGENiHBG000460.
InParanoidiQ673L6.
KOiK11126.
OMAiGMRPITR.
OrthoDBiEOG091G04DO.
PhylomeDBiQ673L6.
TreeFamiTF329048.

Enzyme and pathway databases

ReactomeiR-RNO-171319. Telomere Extension By Telomerase.
R-RNO-201722. Formation of the beta-catenin:TCF transactivating complex.

Miscellaneous databases

PROiQ673L6.

Gene expression databases

BgeeiENSRNOG00000025327.

Family and domain databases

InterProiIPR000477. RT_dom.
IPR021891. Telomerase_RBD.
IPR003545. Telomerase_RT.
[Graphical view]
PANTHERiPTHR12066:SF0. PTHR12066:SF0. 1 hit.
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]
ProtoNetiSearch...

Entry informationi

Entry nameiTERT_RAT
AccessioniPrimary (citable) accession number: Q673L6
Secondary accession number(s): Q1LZ57
, Q4U0V7, Q673L3, Q673L5, Q80SU5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 11, 2006
Last sequence update: October 11, 2004
Last modified: November 2, 2016
This is version 98 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.