Homo sapiens L. (human) [HSA]

FULL NAME: Telomerase reverse transcriptase


DESCRIPTION:
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.

STRUCTURE SIMILARITY:
Contains 1 reverse transcriptase domain.
Belongs to the reverse transcriptase family. Telomerase subfamily.


CATALYTIC ACTIVITY:
Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).


POST-TRANSLATIONAL MODIFICATION:
Phosphorylation at Tyr-707 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.
Ubiquitinated, leading to proteasomal degradation.


PROTEIN TYPE(S):
RT polymerase


RELATED PATHWAY(S):
telomere maintenance


RELATED DISEASE(S):
aplastic anemia (AA)
dyskeratosis congenita autosomal dominant (ADDKC)
susceptibility to pulmonary fibrosis idiopathic (IPF)


Amino acids sequence

        10         20         30         40         50         60
MPRAPRCRAV RSLLRSHYRE VLPLATFVRR LGPQGWRLVQ RGDPAAFRAL VAQCLVCVPW
        70         80         90        100        110        120
DARPPPAAPS FRQVSCLKEL VARVLQRLCE RGAKNVLAFG FALLDGARGG PPEAFTTSVR
       130        140        150        160        170        180
SYLPNTVTDA LRGSGAWGLL LRRVGDDVLV HLLARCALFV LVAPSCAYQV CGPPLYQLGA
       190        200        210        220        230        240
ATQARPPPHA SGPRRRLGCE RAWNHSVREA GVPLGLPAPG ARRRGGSASR SLPLPKRPRR
       250        260        270        280        290        300
GAAPEPERTP VGQGSWAHPG RTRGPSDRGF CVVSPARPAE EATSLEGALS GTRHSHPSVG
       310        320        330        340        350        360
RQHHAGPPST SRPPRPWDTP CPPVYAETKH FLYSSGDKEQ LRPSFLLSSL RPSLTGARRL
       370        380        390        400        410        420
VETIFLGSRP WMPGTPRRLP RLPQRYWQMR PLFLELLGNH AQCPYGVLLK THCPLRAAVT
       430        440        450        460        470        480
PAAGVCAREK PQGSVAAPEE EDTDPRRLVQ LLRQHSSPWQ VYGFVRACLR RLVPPGLWGS
       490        500        510        520        530        540
RHNERRFLRN TKKFISLGKH AKLSLQELTW KMSVRDCAWL RRSPGVGCVP AAEHRLREEI
       550        560        570        580        590        600
LAKFLHWLMS VYVVELLRSF FYVTETTFQK NRLFFYRKSV WSKLQSIGIR QHLKRVQLRE
       610        620        630        640        650        660
LSEAEVRQHR EARPALLTSR LRFIPKPDGL RPIVNMDYVV GARTFRREKR AERLTSRVKA
       670        680        690        700        710        720
LFSVLNYERA RRPGLLGASV LGLDDIHRAW RTFVLRVRAQ DPPPELYFVK VDVTGAYDTI
       730        740        750        760        770        780
PQDRLTEVIA SIIKPQNTYC VRRYAVVQKA AHGHVRKAFK SHVSTLTDLQ PYMRQFVAHL
       790        800        810        820        830        840
QETSPLRDAV VIEQSSSLNE ASSGLFDVFL RFMCHHAVRI RGKSYVQCQG IPQGSILSTL
       850        860        870        880        890        900
LCSLCYGDME NKLFAGIRRD GLLLRLVDDF LLVTPHLTHA KTFLRTLVRG VPEYGCVVNL
       910        920        930        940        950        960
RKTVVNFPVE DEALGGTAFV QMPAHGLFPW CGLLLDTRTL EVQSDYSSYA RTSIRASLTF
       970        980        990       1000       1010       1020
NRGFKAGRNM RRKLFGVLRL KCHSLFLDLQ VNSLQTVCTN IYKILLLQAY RFHACVLQLP
      1030       1040       1050       1060       1070       1080
FHQQVWKNPT FFLRVISDTA SLCYSILKAK NAGMSLGAKG AAGPLPSEAV QWLCHQAFLL
      1090       1100       1110       1120       1130
KLTRHRVTYV PLLGSLRTAQ TQLSRKLPGT TLTALEAAAN PALPSDFKTI LD

Encoded by TERT gene

FULL NAME: telomerase reverse transcriptase


OTHER NAME(S):
EST2
TCS1
TP2
TRT
hEST2
hTRT
DKCA2
DKCB4


DESCRIPTION:
Telomerase is a ribonucleoprotein polymerase that maintains telomere ends by addition of the telomere repeat TTAGGG. The enzyme consists of a protein component with reverse transcriptase activity, encoded by this gene, and an RNA component which serves as a template for the telomere repeat. Telomerase expression plays a role in cellular senescence, as it is normally repressed in postnatal somatic cells resulting in progressive shortening of telomeres. Deregulation of telomerase expression in somatic cells may be involved in oncogenesis. Studies in mouse suggest that telomerase also participates in chromosomal repair, since de novo synthesis of telomere repeats may occur at double-stranded breaks. Alternatively spliced variants encoding different isoforms of telomerase reverse transcriptase have been identified; the full-length sequence of some variants has not been determined. Alternative splicing at this locus is thought to be one mechanism of regulation of telomerase activity. [provided by RefSeq, Jul 2008]


Nucleic acid sequence

        10         20         30         40         50         60
atgccgcgcg ctccccgctg ccgagccgtg cgctccctgc tgcgcagcca ctaccgcgag
        70         80         90        100        110        120
gtgctgccgc tggccacgtt cgtgcggcgc ctggggcccc agggctggcg gctggtgcag
       130        140        150        160        170        180
cgcggggacc cggcggcttt ccgcgcgctg gtggcccagt gcctggtgtg cgtgccctgg
       190        200        210        220        230        240
gacgcacggc cgccccccgc cgccccctcc ttccgccagg tgtcctgcct gaaggagctg
       250        260        270        280        290        300
gtggcccgag tgctgcagag gctgtgcgag cgcggcgcga agaacgtgct ggccttcggc
       310        320        330        340        350        360
ttcgcgctgc tggacggggc ccgcgggggc ccccccgagg ccttcaccac cagcgtgcgc
       370        380        390        400        410        420
agctacctgc ccaacacggt gaccgacgca ctgcggggga gcggggcgtg ggggctgctg
       430        440        450        460        470        480
ctgcgccgcg tgggcgacga cgtgctggtt cacctgctgg cacgctgcgc gctctttgtg
       490        500        510        520        530        540
ctggtggctc ccagctgcgc ctaccaggtg tgcgggccgc cgctgtacca gctcggcgct
       550        560        570        580        590        600
gccactcagg cccggccccc gccacacgct agtggacccc gaaggcgtct gggatgcgaa
       610        620        630        640        650        660
cgggcctgga accatagcgt cagggaggcc ggggtccccc tgggcctgcc agccccgggt
       670        680        690        700        710        720
gcgaggaggc gcgggggcag tgccagccga agtctgccgt tgcccaagag gcccaggcgt
       730        740        750        760        770        780
ggcgctgccc ctgagccgga gcggacgccc gttgggcagg ggtcctgggc ccacccgggc
       790        800        810        820        830        840
aggacgcgtg gaccgagtga ccgtggtttc tgtgtggtgt cacctgccag acccgccgaa
       850        860        870        880        890        900
gaagccacct ctttggaggg tgcgctctct ggcacgcgcc actcccaccc atccgtgggc
       910        920        930        940        950        960
cgccagcacc acgcgggccc cccatccaca tcgcggccac cacgtccctg ggacacgcct
       970        980        990       1000       1010       1020
tgtcccccgg tgtacgccga gaccaagcac ttcctctact cctcaggcga caaggagcag
      1030       1040       1050       1060       1070       1080
ctgcggccct ccttcctact cagctctctg aggcccagcc tgactggcgc tcggaggctc
      1090       1100       1110       1120       1130       1140
gtggagacca tctttctggg ttccaggccc tggatgccag ggactccccg caggttgccc
      1150       1160       1170       1180       1190       1200
cgcctgcccc agcgctactg gcaaatgcgg cccctgtttc tggagctgct tgggaaccac
      1210       1220       1230       1240       1250       1260
gcgcagtgcc cctacggggt gctcctcaag acgcactgcc cgctgcgagc tgcggtcacc
      1270       1280       1290       1300       1310       1320
ccagcagccg gtgtctgtgc ccgggagaag ccccagggct ctgtggcggc ccccgaggag
      1330       1340       1350       1360       1370       1380
gaggacacag acccccgtcg cctggtgcag ctgctccgcc agcacagcag cccctggcag
      1390       1400       1410       1420       1430       1440
gtgtacggct tcgtgcgggc ctgcctgcgc cggctggtgc ccccaggcct ctggggctcc
      1450       1460       1470       1480       1490       1500
aggcacaacg aacgccgctt cctcaggaac accaagaagt tcatctccct ggggaagcat
      1510       1520       1530       1540       1550       1560
gccaagctct cgctgcagga gctgacgtgg aagatgagcg tgcgggactg cgcttggctg
      1570       1580       1590       1600       1610       1620
cgcaggagcc caggggttgg ctgtgttccg gccgcagagc accgtctgcg tgaggagatc
      1630       1640       1650       1660       1670       1680
ctggccaagt tcctgcactg gctgatgagt gtgtacgtcg tcgagctgct caggtctttc
      1690       1700       1710       1720       1730       1740
ttttatgtca cggagaccac gtttcaaaag aacaggctct ttttctaccg gaagagtgtc
      1750       1760       1770       1780       1790       1800
tggagcaagt tgcaaagcat tggaatcaga cagcacttga agagggtgca gctgcgggag
      1810       1820       1830       1840       1850       1860
ctgtcggaag cagaggtcag gcagcatcgg gaagccaggc ccgccctgct gacgtccaga
      1870       1880       1890       1900       1910       1920
ctccgcttca tccccaagcc tgacgggctg cggccgattg tgaacatgga ctacgtcgtg
      1930       1940       1950       1960       1970       1980
ggagccagaa cgttccgcag agaaaagagg gccgagcgtc tcacctcgag ggtgaaggca
      1990       2000       2010       2020       2030       2040
ctgttcagcg tgctcaacta cgagcgggcg cggcgccccg gcctcctggg cgcctctgtg
      2050       2060       2070       2080       2090       2100
ctgggcctgg acgatatcca cagggcctgg cgcaccttcg tgctgcgtgt gcgggcccag
      2110       2120       2130       2140       2150       2160
gacccgccgc ctgagctgta ctttgtcaag gtggatgtga cgggcgcgta cgacaccatc
      2170       2180       2190       2200       2210       2220
ccccaggaca ggctcacgga ggtcatcgcc agcatcatca aaccccagaa cacgtactgc
      2230       2240       2250       2260       2270       2280
gtgcgtcggt atgccgtggt ccagaaggcc gcccatgggc acgtccgcaa ggccttcaag
      2290       2300       2310       2320       2330       2340
agccacgtct ctaccttgac agacctccag ccgtacatgc gacagttcgt ggctcacctg
      2350       2360       2370       2380       2390       2400
caggagacca gcccgctgag ggatgccgtc gtcatcgagc agagctcctc cctgaatgag
      2410       2420       2430       2440       2450       2460
gccagcagtg gcctcttcga cgtcttccta cgcttcatgt gccaccacgc cgtgcgcatc
      2470       2480       2490       2500       2510       2520
aggggcaagt cctacgtcca gtgccagggg atcccgcagg gctccatcct ctccacgctg
      2530       2540       2550       2560       2570       2580
ctctgcagcc tgtgctacgg cgacatggag aacaagctgt ttgcggggat tcggcgggac
      2590       2600       2610       2620       2630       2640
gggctgctcc tgcgtttggt ggatgatttc ttgttggtga cacctcacct cacccacgcg
      2650       2660       2670       2680       2690       2700
aaaaccttcc tcagctatgc ccggacctcc atcagagcca gtctcacctt caaccgcggc
      2710       2720       2730       2740       2750       2760
ttcaaggctg ggaggaacat gcgtcgcaaa ctctttgggg tcttgcggct gaagtgtcac
      2770       2780       2790       2800       2810       2820
agcctgtttc tggatttgca ggtgaacagc ctccagacgg tgtgcaccaa catctacaag
      2830       2840       2850       2860       2870       2880
atcctcctgc tgcaggcgta caggtttcac gcatgtgtgc tgcagctccc atttcatcag
      2890       2900       2910       2920       2930       2940
caagtttgga agaaccccac atttttcctg cgcgtcatct ctgacacggc ctccctctgc
      2950       2960       2970       2980       2990       3000
tactccatcc tgaaagccaa gaacgcaggg atgtcgctgg gggccaaggg cgccgccggc
      3010       3020       3030       3040       3050       3060
cctctgccct ccgaggccgt gcagtggctg tgccaccaag cattcctgct caagctgact
      3070       3080       3090       3100       3110       3120
cgacaccgtg tcacctacgt gccactcctg gggtcactca ggacagccca gacgcagctg
      3130       3140       3150       3160       3170       3180
agtcggaagc tcccggggac gacgctgact gccctggagg ccgcagccaa cccggcactg
      3190       3200       3210
ccctcagact tcaagaccat cctggactga   

Last modification date: Oct. 2, 2011