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Q673L6 (TERT_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 75. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Telomerase reverse transcriptase

EC=2.7.7.49
Alternative name(s):
Telomerase catalytic subunit
Gene names
Name:Tert
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length1125 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. UniProtKB O14746

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.

Tissue specificity

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. Ref.1 Ref.4

Developmental stage

High activity in cortex at embryonic stage 16 and postnatal day 2. Low activity in cortex from postnatal day 5. Ref.1

Induction

Down-regulated by TGFbeta in fibroblasts. This inhibition is mediated by SMAD3. Ref.3

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 the G2/M phase at Ser-447 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-447 by DYRK2. Ubiquitinated leads to proteasomal degradation By similarity.

Sequence similarities

Belongs to the reverse transcriptase family. Telomerase subfamily.

Contains 1 reverse transcriptase domain.

Ontologies

Keywords
   Cellular componentChromosome
Cytoplasm
Nucleus
Telomere
   Coding sequence diversityAlternative splicing
   LigandDNA-binding
Magnesium
Metal-binding
   Molecular functionNucleotidyltransferase
Ribonucleoprotein
RNA-directed DNA polymerase
Transferase
   PTMPhosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA strand elongation

Inferred from electronic annotation. Source: Ensembl

negative regulation of extrinsic apoptotic signaling pathway in absence of ligand

Inferred from electronic annotation. Source: Ensembl

replicative senescence

Inferred from electronic annotation. Source: Ensembl

telomere formation via telomerase

Inferred from electronic annotation. Source: Ensembl

telomere maintenance via telomerase

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentPML body

Inferred from electronic annotation. Source: UniProtKB-SubCell

chromosome, telomeric region

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytoplasm

Inferred from direct assay PubMed 11485973. Source: RGD

nucleolus

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from direct assay PubMed 11485973. Source: RGD

telomerase holoenzyme complex

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionDNA binding

Inferred from electronic annotation. Source: UniProtKB-KW

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

telomeric RNA binding

Inferred from electronic annotation. Source: Ensembl

telomeric template RNA reverse transcriptase activity

Traceable author statement PubMed 11517337. Source: RGD

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 Ref.1 (identifier: Q673L6-1)

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.
Isoform 2 Ref.1 (identifier: Q673L6-2)

Also known as: a;

The sequence of this isoform differs from the canonical sequence as follows:
     641-646: Missing.
Isoform 3 Ref.1 (identifier: Q673L6-3)

Also known as: b; c;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11251125Telomerase reverse transcriptase
PRO_0000245165

Regions

Domain595 – 928334Reverse transcriptase
Region1 – 239239RNA-interacting domain 1 By similarity
Region58 – 205148GQ motif By similarity
Region137 – 1415Required for regulating specificity for telomeric DNA and for processivity for primer elongation By similarity
Region240 – 32889Linker By similarity
Region306 – 528223Required for oligomerization By similarity
Region329 – 540212RNA-interacting domain 2 By similarity
Region381 – 511131QFP motif By similarity
Region402 – 42221CP motif By similarity
Region907 – 92115Required for oligomerization By similarity
Region923 – 9275Primer grip sequence By similarity
Region929 – 1125197CTE By similarity

Sites

Metal binding7021Magnesium; catalytic By similarity
Metal binding8611Magnesium; catalytic By similarity
Metal binding8621Magnesium; catalytic By similarity
Site1691Required for optimal binding of telomeric ssDNA and incorporation of nucleotides at the second position of the template By similarity
Site8601Required for nucleotide incorporation and primer extension rate By similarity

Amino acid modifications

Modified residue4471Phosphoserine; by DYRK2 By similarity
Modified residue6971Phosphotyrosine; by SRC-type Tyr-kinases By similarity

Natural variations

Alternative sequence515 – 615101EKDTV…LRFIP → ACTSFWDSPSPSQVSFIFIT AGKPSFPWIRRPLRYLETHR VELTHPAWQEGHCPCRRAPS EGEDPCHVPVLANGHICGTA AEVILLHHRDHVPEEPPFLL P in isoform 3. Ref.1
VSP_052081
Alternative sequence616 – 1125510Missing in isoform 3. Ref.1
VSP_052082
Alternative sequence641 – 6466Missing in isoform 2. Ref.1
VSP_052083

Experimental info

Sequence conflict5211A → V in DAA01427. Ref.2
Sequence conflict5281E → V in DAA01427. Ref.2
Sequence conflict550 – 5512FF → LL in DAA01427. Ref.2
Sequence conflict5831L → P in DAA01427. Ref.2
Sequence conflict6301M → L in DAA01427. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 11, 2004. Version 1.
Checksum: B8B2A11C914372DF

FASTA1,125126,934
        10         20         30         40         50         60 
MPRAPRCPAV RSLLRSRYRE VWPLATFVRR LGLEGSRLVQ PGDPKVFRTL VAQCLVCVPW 

        70         80         90        100        110        120 
GSQPPPADLS FHQVSSLKEL VSRVVQKLCE RGERNVLAFG FALLNGARGG PPMAFTTSVH 

       130        140        150        160        170        180 
SYLPNSVTES LCVSGAWMLL LSRVGDDLLV YLLSHCALYL LVPPSCAYQV CGSPLYQICA 

       190        200        210        220        230        240 
TTDTWSSVPA GYRPTRPVGG NFTNLGSAHQ IKNSGHQEAP KPQALPSRGT KRLLSLTSTN 

       250        260        270        280        290        300 
VPSAKKARFE PALRVDKGPH RQVVPTPSGK TWAPSPAASP KVPPAAKNLS LKGKASDPSL 

       310        320        330        340        350        360 
SGSVCCKHKP SSSSLLSSPP QDAEKLRPFT ETRHFLYSRG GGQEELNPSF LLNSLPPSLT 

       370        380        390        400        410        420 
GARRLVEIIF LGSRPRTSGP FCRTRRLPRR YWQMRPLFQQ LLMNHAKCQY VRFLRSHCRF 

       430        440        450        460        470        480 
RTANQRVPDA MDTSPSHLTS LLRLHSSPWQ VYGFLRACLR ELVPAGLWGT RHNERRFLKN 

       490        500        510        520        530        540 
VKKFISLGKY AKLSLQELMW RVKVEDCHWL RSSPEKDTVP AAEHRLRERI LAMFLFWLMD 

       550        560        570        580        590        600 
TYVVQLLRSF FYITETTFQK NRLFFYRKSV WSKLQSIGIR QQLERVQLRE LSQEEVKHHQ 

       610        620        630        640        650        660 
DTWLAMPICR LRFIPKLNGL RPIVNMSYGM DTRAFGKKKQ TQCFTQSLKT LFSVLNYERT 

       670        680        690        700        710        720 
KHPNLMGASV LGTSDSYRIW RTFVLRVRAL DQTPRMYFVK ADVTGAYDAI PQDKLVEIVA 

       730        740        750        760        770        780 
NIIRRSESMY CIRQYAVVQK DSQGQVHKSF RRQVSTLSDL QPYMGQFTKH LQDSDASALR 

       790        800        810        820        830        840 
NSVVIEQSIS MNETGSSLLH FFLRFVRHSV VKIDGRFYVQ CQGIPQGSSL STLLCSLCFG 

       850        860        870        880        890        900 
DMENKLFAEV QQDGLLLRFV DDFLLVTPHL AHAKAFLSTL VHGVPEYGCM INLQKTVVNF 

       910        920        930        940        950        960 
PVETGALGGA APHQLPAHCL FPWCGLLLDT RTLEVFCDYS GYGRTSIKMS LTFQGVSRAG 

       970        980        990       1000       1010       1020 
KTMRYKLLSV LRLKCHGLFL DLQVNSLQTV CINIYKIFLL QAYRFHACVI RLPFGQHVRK 

      1030       1040       1050       1060       1070       1080 
NHAFFLGIIS NLASCCYAIL KVKNPGVSLR AKGAPGSFPP EATRWLCYQA FLLKLAAHSV 

      1090       1100       1110       1120 
TYKCLLGPLR TAQKQLCRKL PEATMTLLKT AADPALSTDF QTILD 

« Hide

Isoform 2 (a) [UniParc].

Checksum: 4CABB74D64E3F972
Show »

FASTA1,119126,225
Isoform 3 (b) (c) [UniParc].

Checksum: 2892840D86620B63
Show »

FASTA61568,614

References

« Hide 'large scale' references
[1]"Predominant expression of rTERTb, an inactive TERT variant, in the adult rat brain."
Kaneko R., Esumi S., Yagi T., Hirabayashi T.
Protein Pept. Lett. 13:59-65(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
Strain: Brown Norway.
[2]"Genome sequence of the Brown Norway rat yields insights into mammalian evolution."
Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., Morgan M. expand/collapse author list , Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S., Collins F.S.
Nature 428:493-521(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: Brown Norway.
[3]"Role of Smad3 in the regulation of rat telomerase reverse transcriptase by TGFbeta."
Hu B., Tack D.C., Liu T., Wu Z., Ullenbruch M.R., Phan S.H.
Oncogene 25:1030-1041(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-58, INDUCTION.
[4]"Detection and quantification of transcripts for the catalytic subunit TERT and the RNA component of telomerase in rat tissue."
Holzmann K., Berger W., Mejri D., Cerni C., Sasgary S.
Anal. Biochem. 317:120-123(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 46-161, TISSUE SPECIFICITY.
Strain: Fischer.
[5]"The identification and characterization of rat telomerase catalytic subunit rTERT mRNA from rat genomic sequence."
Kim M.H., Choi C.
Chonnam Med. J. 41:1-13(2005)
Cited for: IDENTIFICATION.
Strain: Brown Norway.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_445875.1. NM_053423.1.
UniGeneRn.48802.

3D structure databases

ProteinModelPortalQ673L6.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10116.ENSRNOP00000022683.

Proteomic databases

PaxDbQ673L6.
PRIDEQ673L6.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000022683; ENSRNOP00000022683; ENSRNOG00000025327. [Q673L6-1]
ENSRNOT00000034937; ENSRNOP00000033885; ENSRNOG00000025327. [Q673L6-3]
GeneID301965.
KEGGrno:301965.
UCSCRGD:70494. rat. [Q673L6-1]

Organism-specific databases

CTD7015.
RGD70494. Tert.

Phylogenomic databases

eggNOGNOG276584.
GeneTreeENSGT00390000018531.
HOGENOMHOG000148780.
HOVERGENHBG000460.
InParanoidQ673L6.
KOK11126.
OMADTASCCY.
OrthoDBEOG744TB3.
PhylomeDBQ673L6.
TreeFamTF329048.

Gene expression databases

GenevestigatorQ673L6.

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

NextBio649227.
PROQ673L6.

Entry information

Entry nameTERT_RAT
AccessionPrimary (citable) accession number: Q673L6
Secondary accession number(s): Q1LZ57 expand/collapse secondary AC list , Q4U0V7, Q673L3, Q673L5, Q80SU5
Entry history
Integrated into UniProtKB/Swiss-Prot: July 11, 2006
Last sequence update: October 11, 2004
Last modified: April 16, 2014
This is version 75 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