O70372 (TERT_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Telomerase reverse transcriptase
EC=2.7.7.49

Alternative name(s):
Telomerase catalytic subunit

Gene names

Name:

Tert

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1122 AA.
Sequence status	Complete.
Protein existence	Evidence at protein 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 Ref.5 Ref.7
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. Ref.5 Ref.6 Ref.7
Subcellular location	Nucleus › nucleolus By similarity. Nucleus › nucleoplasm By similarity. Nucleus. Chromosome › telomere. Cytoplasm By similarity. Nucleus › PML 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	High activity in intestine, liver and testis, moderate in lung, very low in muscle, heart and brain. Ref.1 Ref.2 Ref.3
Developmental stage	Highest levels in midgestational stages, E9.5 to E15.5. Ref.1
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	Ubiquitinated, leading to proteasomal degradation By similarity. 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 by the AKT pathway promotes nuclear location By similarity.
Sequence similarities	Belongs to the reverse transcriptase family. Telomerase subfamily. Contains 1 reverse transcriptase domain.
Caution	Was originally (Ref.3) thought to originate from rat.

Ontologies

Keywords
Cellular component	Chromosome Cytoplasm Nucleus Telomere
Ligand	DNA-binding Magnesium Metal-binding
Molecular function	Nucleotidyltransferase RNA-directed DNA polymerase Ribonucleoprotein Transferase
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA strand elongation Inferred from electronic annotation. Source: Compara negative regulation of apoptotic process Inferred from electronic annotation. Source: Compara replicative senescence Inferred from electronic annotation. Source: Compara telomere formation via telomerase Inferred from electronic annotation. Source: Compara telomere maintenance via telomerase Inferred from electronic annotation. Source: Compara
Cellular_component	PML body Inferred from electronic annotation. Source: UniProtKB-SubCell chromosome, telomeric region Inferred from electronic annotation. Source: UniProtKB-SubCell cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleolus Inferred from electronic annotation. Source: UniProtKB-SubCell telomerase holoenzyme complex Inferred from electronic annotation. Source: Compara
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW telomerase activity Inferred from direct assay PubMed 14701760. Source: MGI telomeric RNA binding Inferred from electronic annotation. Source: Compara telomeric template RNA reverse transcriptase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1122	1122	Telomerase reverse transcriptase		PRO_0000054926
Regions
	Domain	595 – 928	334	Reverse transcriptase
	Region	1 – 239	239	RNA-interacting domain 1 By similarity
	Region	58 – 205	148	GQ motif By similarity
	Region	137 – 141	5	Required for regulating specificity for telomeric DNA and for processivity for primer elongation By similarity
	Region	240 – 328	89	Linker By similarity
	Region	306 – 528	223	Required for oligomerization By similarity
	Region	329 – 540	212	RNA-interacting domain 2 By similarity
	Region	381 – 511	131	QFP motif By similarity
	Region	402 – 422	21	CP motif By similarity
	Region	907 – 921	15	Required for oligomerization By similarity
	Region	923 – 927	5	Primer grip sequence By similarity
	Region	929 – 1122	194	CTE By similarity
Sites
	Metal binding	702	1	Magnesium; catalytic By similarity
	Metal binding	861	1	Magnesium; catalytic By similarity
	Metal binding	862	1	Magnesium; catalytic By similarity
	Site	169	1	Required for optimal binding of telomeric ssDNA and incorporation of nucleotides at the second position of the template By similarity
	Site	860	1	Required for nucleotide incorporation and primer extension rate By similarity
Amino acid modifications
	Modified residue	697	1	Phosphotyrosine; by SRC-type Tyr-kinases By similarity
Experimental info
	Sequence conflict	553	1	I → V in AAB84200. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	O70372 [UniParc]. Last modified August 1, 1998. Version 1. Checksum: F85266905DD6558C	FASTA	1,122	127,978
	10 20 30 40 50 60 MTRAPRCPAV RSLLRSRYRE VWPLATFVRR LGPEGRRLVQ PGDPKIYRTL VAQCLVCMHW 70 80 90 100 110 120 GSQPPPADLS FHQVSSLKEL VARVVQRLCE RNERNVLAFG FELLNEARGG PPMAFTSSVR 130 140 150 160 170 180 SYLPNTVIET LRVSGAWMLL LSRVGDDLLV YLLAHCALYL LVPPSCAYQV CGSPLYQICA 190 200 210 220 230 240 TTDIWPSVSA SYRPTRPVGR NFTNLRFLQQ IKSSSRQEAP KPLALPSRGT KRHLSLTSTS 250 260 270 280 290 300 VPSAKKARCY PVPRVEEGPH RQVLPTPSGK SWVPSPARSP EVPTAEKDLS SKGKVSDLSL 310 320 330 340 350 360 SGSVCCKHKP SSTSLLSPPR QNAFQLRPFI ETRHFLYSRG DGQERLNPSF LLSNLQPNLT 370 380 390 400 410 420 GARRLVEIIF LGSRPRTSGP LCRTHRLSRR YWQMRPLFQQ LLVNHAECQY VRLLRSHCRF 430 440 450 460 470 480 RTANQQVTDA LNTSPPHLMD LLRLHSSPWQ VYGFLRACLC KVVSASLWGT RHNERRFFKN 490 500 510 520 530 540 LKKFISLGKY GKLSLQELMW KMKVEDCHWL RSSPGKDRVP AAEHRLRERI LATFLFWLMD 550 560 570 580 590 600 TYVVQLLRSF FYITESTFQK NRLFFYRKSV WSKLQSIGVR QHLERVRLRE LSQEEVRHHQ 610 620 630 640 650 660 DTWLAMPICR LRFIPKPNGL RPIVNMSYSM GTRALGRRKQ AQHFTQRLKT LFSMLNYERT 670 680 690 700 710 720 KHPHLMGSSV LGMNDIYRTW RAFVLRVRAL DQTPRMYFVK ADVTGAYDAI PQGKLVEVVA 730 740 750 760 770 780 NMIRHSESTY CIRQYAVVRR DSQGQVHKSF RRQVTTLSDL QPYMGQFLKH LQDSDASALR 790 800 810 820 830 840 NSVVIEQSIS MNESSSSLFD FFLHFLRHSV VKIGDRCYTQ CQGIPQGSSL STLLCSLCFG 850 860 870 880 890 900 DMENKLFAEV QRDGLLLRFV DDFLLVTPHL DQAKTFLSTL VHGVPEYGCM INLQKTVVNF 910 920 930 940 950 960 PVEPGTLGGA APYQLPAHCL FPWCGLLLDT QTLEVFCDYS GYAQTSIKTS LTFQSVFKAG 970 980 990 1000 1010 1020 KTMRNKLLSV LRLKCHGLFL DLQVNSLQTV CINIYKIFLL QAYRFHACVI QLPFDQRVRK 1030 1040 1050 1060 1070 1080 NLTFFLGIIS SQASCCYAIL KVKNPGMTLK ASGSFPPEAA HWLCYQAFLL KLAAHSVIYK 1090 1100 1110 1120 CLLGPLRTAQ KLLCRKLPEA TMTILKAAAD PALSTDFQTI LD

References

[1]	"Expression of mouse telomerase reverse transcriptase during development, differentiation and proliferation." Greenberg R.A., Allsopp R.C., Chin L., Morin G.B., DePinho R.A. Oncogene 16:1723-1730(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DEVELOPMENTAL STAGE, INDUCTION, TISSUE SPECIFICITY.
[2]	"Expression of mouse telomerase catalytic subunit in embryos and adult tissues." Martin-Rivera L., Herrera E., Albar J.P., Blasco M.A. Proc. Natl. Acad. Sci. U.S.A. 95:10471-10476(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[3]	"Cloning of rat telomerase catalytic subunit functional domains, reconstitution of telomerase activity and enzymatic profile of pig and chicken tissues." Wong S.C., Ong L.L., Er C.P., Gao S., Yu H., So J.B. Life Sci. 73:2749-2760(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 548-1122, TISSUE SPECIFICITY.
[4]	"Partial sequence of Mus musculus telomerase catalytic subunit homolog." Drissi R., Cleveland J.L. Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 550-616.
[5]	"Murine Pif1 interacts with telomerase and is dispensable for telomere function in vivo." Snow B.E., Mateyak M., Paderova J., Wakeham A., Iorio C., Zakian V., Squire J., Harrington L. Mol. Cell. Biol. 27:1017-1026(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PIF1, FUNCTION.
[6]	"GNL3L stabilizes the TRF1 complex and promotes mitotic transition." Zhu Q., Meng L., Hsu J.K., Lin T., Teishima J., Tsai R.Y. J. Cell Biol. 185:827-839(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GNL3L.
[7]	"Telomerase modulates Wnt signalling by association with target gene chromatin." Park J.I., Venteicher A.S., Hong J.Y., Choi J., Jun S., Shkreli M., Chang W., Meng Z., Cheung P., Ji H., McLaughlin M., Veenstra T.D., Nusse R., McCrea P.D., Artandi S.E. Nature 460:66-72(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SMARCA4, FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF051911 mRNA. Translation: AAC09323.1. AF073311 mRNA. Translation: AAC34821.1. AF247818 mRNA. Translation: AAF62177.1. AF029235 mRNA. Translation: AAB84200.1.
IPI	IPI00117405.
RefSeq	NP_033380.1. NM_009354.1.
UniGene	Mm.10109.
3D structure databases
ProteinModelPortal	O70372.
SMR	O70372. Positions 423-579, 787-1092.
ModBase	Search...
PTM databases
PhosphoSite	O70372.
Proteomic databases
PaxDb	O70372.
PRIDE	O70372.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000022104; ENSMUSP00000022104; ENSMUSG00000021611.
GeneID	21752.
KEGG	mmu:21752.
UCSC	uc007rdq.1. mouse.
Organism-specific databases
CTD	7015.
MGI	MGI:1202709. Tert.
Phylogenomic databases
eggNOG	NOG276584.
GeneTree	ENSGT00390000018531.
HOGENOM	HOG000148780.
HOVERGEN	HBG000460.
InParanoid	O70372.
KO	K11126.
OMA	EQSCSLN.
OrthoDB	EOG4J117F.
Gene expression databases
ArrayExpress	O70372.
Bgee	O70372.
CleanEx	MM_TERT.
Genevestigator	O70372.
GermOnline	ENSMUSG00000021611. Mus musculus.
Family and domain databases
InterPro	IPR000477. RVT. IPR021891. Telomerase_RBD. IPR003545. Telomerase_RT. [Graphical view]
Pfam	PF00078. RVT_1. 1 hit. PF12009. Telomerase_RBD. 1 hit. [Graphical view]
PRINTS	PR01365. TELOMERASERT.
SMART	SM00975. Telomerase_RBD. 1 hit. [Graphical view]
PROSITE	PS50878. RT_POL. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	301049.
SOURCE	Search...

Entry information

Entry name

TERT_MOUSE

Accession

Primary (citable) accession number: O70372
Secondary accession number(s): O35432, Q9JK99

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	August 1, 1998
Last modified:	May 1, 2013
This is version 98 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program