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Q6A548 (TERT_CANFA) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 66. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
Telomerase reverse transcriptase

EC=2.7.7.49
Alternative name(s):
Telomerase catalytic subunit
Gene names
Name:TERT
OrganismCanis familiaris (Dog) (Canis lupus familiaris) [Reference proteome]
Taxonomic identifier9615 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis

Protein attributes

Sequence length1123 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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. Ref.1

Catalytic activity

Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).

Subunit structure

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 similarity.

Subcellular location

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.

Domain

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.

The RNA-interacting domain 2 (RD2) is essential for both interaction with the CR4-CR5 domain of TERC and for DNA sythesis By similarity.

Post-translational modification

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 Ser-227 by the AKT pathway promotes nuclear location. Phosphorylation at the G2/M phase at Ser-446 by DYRK2 promotes ubiquitination by the EDVP complex and degradation By similarity.

Ubiquitinated by the EDVP complex, a E3 ligase complex following phosphorylation at Ser-446 by DYRK2. Ubiquitinated leads to proteasomal degradation By similarity.

Sequence similarities

Belongs to the reverse transcriptase family. Telomerase subfamily.

Contains 1 reverse transcriptase domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11231123Telomerase reverse transcriptase
PRO_0000054924

Regions

Domain595 – 926332Reverse transcriptase
Region1 – 230230RNA-interacting domain 1 By similarity
Region58 – 197140GQ motif By similarity
Region137 – 1415Required for regulating specificity for telomeric DNA and for processivity for primer elongation By similarity
Region231 – 30878Linker By similarity
Region309 – 539231RNA-interacting domain 2 By similarity
Region360 – 510151QFP motif By similarity
Region381 – 40121CP motif By similarity
Region905 – 91915Required for oligomerization By similarity
Region921 – 9255Primer grip sequence By similarity
Region927 – 1123197CTE By similarity
Motif222 – 24019Bipartite nuclear localization signal By similarity

Sites

Metal binding7021Magnesium; catalytic By similarity
Metal binding8591Magnesium; catalytic By similarity
Metal binding8601Magnesium; catalytic By similarity
Site1691Required for optimal binding of telomeric ssDNA and incorporation of nucleotides at the second position of the template By similarity
Site8581Required for nucleotide incorporation and primer extension rate By similarity

Amino acid modifications

Modified residue2271Phosphoserine; by PKB/AKT1 By similarity
Modified residue4461Phosphoserine; by DYRK2 By similarity
Modified residue6971Phosphotyrosine; by SRC-type Tyr-kinases By similarity

Sequences

Sequence LengthMass (Da)Tools
Q6A548 [UniParc].

Last modified September 13, 2004. Version 1.
Checksum: F5F55D791106C1A3

FASTA1,123124,825
        10         20         30         40         50         60 
MPRAPRCRAV RALLRGRYRE VLPLATFLRR LGPPGRLLVR RGDPAAFRAL VAQCLVCVPW 

        70         80         90        100        110        120 
GARPPPAAPC FRQVSCLKEL VARVVQRLCE RGARNVLAFG FALLDGARGG PPVAFTTSVR 

       130        140        150        160        170        180 
SYLPNTVTET LRGSGAWGLL LRRVGDDVLT HLLARCALYL LVAPSCAYQV CGPPLYDLCA 

       190        200        210        220        230        240 
PASLPLPAPG LPGLPGLPGL GAGAGASADL RPTRQAQNSG ARRRRGSPGS GVPLAKRPRR 

       250        260        270        280        290        300 
SVASEPERGA HRSFPRAQQP PVSEAPAVTP AVAASPAASW EGGPPGTRPT TPAWHPYPGP 

       310        320        330        340        350        360 
QGVPHDPAHP ETKRFLYCSG GRERLRPSFL LSALPPTLSG ARKLVETIFL GSAPQKPGAA 

       370        380        390        400        410        420 
RRMRRLPARY WRMRPLFQEL LGNHARCPYR ALLRTHCPLR AMAAKEGSGN QAHRGVGICP 

       430        440        450        460        470        480 
LERPVAAPQE QTDSTRLVQL LRQHSSPWQV YAFLRACLCW LVPTGLWGSR HNQRRFLRNV 

       490        500        510        520        530        540 
KKFISLGKHA KLSLQELTWK MKVRDCTWLH GNPGACCVPA AEHRRREEIL ARFLVLVDGH 

       550        560        570        580        590        600 
IYVVKLLRSF FYVTETTFQK NRLFFYRKSV WSQLQSIGIR QLFNSVHLRE LSEAEVRRHR 

       610        620        630        640        650        660 
EARPALLTSR LRFLPKPSGL RPIVNMDYIM GARTFHRDKK VQHLTSQLKT LFSVLNYERA 

       670        680        690        700        710        720 
RRPSLLGASM LGMDDIHRAW RTFVLRIRAQ NPAPQLYFVK VDVTGAYDAL PQDRLVEVIA 

       730        740        750        760        770        780 
NVIRPQESTY CVRHYAVVQR TARGHVRKAF KRHVSTFADL QPYMRQFVER LQETSLLRDA 

       790        800        810        820        830        840 
VVIEQSSSLN EAGSSLFHLF LRLVHNHVVR IGGKSYIQCQ GVPQGSILST LLCSLCYGDM 

       850        860        870        880        890        900 
ERRLFPGIEQ DGVLLRLVDD FLLVTPHLTQ AQAFLRTLVK GVPEYGCRAN LQKTAVNFPV 

       910        920        930        940        950        960 
EDGALGSAAP LQLPAHCLFP WCGLLLDTRT LEVSCDYSSY AHTSIRASLT FSQGAKPGRN 

       970        980        990       1000       1010       1020 
MRRKLLAVLR LKCCALFLDL QVNGIHTVYM NVYKIFLLQA YRFHACVLQL PFNQPVRKNP 

      1030       1040       1050       1060       1070       1080 
SFFLRVIADT ASCCYSLLKA RNAGLSLGAK GASGLFPSEA ARWLCLHAFL LKLAHHSGTY 

      1090       1100       1110       1120 
RCLLGALQAA KAHLSRQLPR GTLAALEAAA DPSLTADFKT ILD 

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References

[1]"Isolation and expression of the reverse transcriptase component of the Canis familiaris telomerase ribonucleoprotein (dogTERT)."
Nasir L., Gault E., Campbell S., Veeramalai M., Gilbert D., McFarlane R., Munro A., Argyle D.J.
Gene 336:105-113(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, FUNCTION.
Tissue: Kidney.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF380351 mRNA. Translation: AAQ02791.1.
RefSeqNP_001026800.1. NM_001031630.1.
UniGeneCfa.114.

3D structure databases

ProteinModelPortalQ6A548.
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID403412.
KEGGcfa:403412.

Organism-specific databases

CTD7015.

Phylogenomic databases

eggNOGNOG276584.
HOGENOMHOG000148780.
HOVERGENHBG000460.
InParanoidQ6A548.
KOK11126.

Family and domain databases

InterProIPR000477. RT_dom.
IPR021891. Telomerase_RBD.
IPR003545. Telomerase_RT.
[Graphical view]
PfamPF00078. RVT_1. 1 hit.
PF12009. Telomerase_RBD. 1 hit.
[Graphical view]
PRINTSPR01365. TELOMERASERT.
SMARTSM00975. Telomerase_RBD. 1 hit.
[Graphical view]
PROSITEPS50878. RT_POL. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio20816932.

Entry information

Entry nameTERT_CANFA
AccessionPrimary (citable) accession number: Q6A548
Entry history
Integrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: September 13, 2004
Last modified: March 19, 2014
This is version 66 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families