Telomerase ribonucleoprotein complex - RNA binding domain; Telomeres in most organisms are comprised of tandem simple sequence repeats. The total length of telomeric repeat sequence at each chromosome end is determined in a balance of sequence loss and sequence addition. One major influence on telomere length is the enzyme telomerase. It is a reverse transcriptase that adds these simple sequence repeats to chromosome ends by copying a template sequence within the RNA component of the enzyme. The RNA binding domain of telomerase - TRBD - is made up of twelve alpha helices and two short beta sheets. How telomerase and associated regulatory factors physically interact and function with each other to maintain appropriate telomere length is poorly understood. It is known however that TRBD is involved in formation of the holoenzyme (which performs the telomere extension) in addition to recognition and binding of RNA.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1012615172   434 RVYLFVRACLSAVIPRELWGSDHNRVHFFARARGFLLNGKFERLSLAELMWNMKVNDCDWLKISKSG--RIPPSELAYRT 511
Cdd:smart00975    1 QVVSFLRAILRKLFPLSLWGSRHNKRVFLKNLRRFLSLGRNEKFSLQELMWGIRVSDIPWLAGSKTTtqRVSKSEHEKRQ 80

                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|....*
gi 1012615172   512 QILGQFLAWLLDGFVAGLVRACFYATESMGQKNAVRFYRQDVWAKLQDLAFKGHL 566
Cdd:smart00975   81 ELLAQFVYWLFDCLVPPLLRSFFYVTESSGQKNKLLYFRHDVWKKLTRPALRRYL 135

conserved catalytic core domain of RNA-dependent RNA polymerase (RdRp) from the positive-sense single-stranded RNA [(+)ssRNA] viruses and closely related viruses; This family contains the catalytic core domain of RdRp of RNA viruses which belong to Group IV of the Baltimore classification system, and are a group of related viruses that have positive-sense (+), single-stranded (ss) genomes made of ribonucleic acid (RNA). RdRp (also known as RNA replicase) catalyzes the replication of RNA from an RNA template; specifically, it catalyzes the synthesis of the RNA strand complementary to a given RNA template. The Baltimore Classification is divided into 7 classes, 3 of which include RNA viruses: Group IV (+) RNA viruses, Group III double-stranded (ds) RNA viruses, and Group V negative-sense (-) RNA viruses. Baltimore groups of viruses differ with respect to the nature of their genome (i.e., the nucleic acid form that is packaged into virions) and correspond to distinct strategies of genome replication and expression. (+) viral RNA is similar to mRNA and thus can be immediately translated by the host cell. (+)ssRNA viruses can also produce (+) copies of the genome from (-) strands of an intermediate dsRNA genome. This acts as both a transcription and a replication process since the replicated RNA is also mRNA. RdRps belong to the expansive class of polymerases containing so-called palm catalytic domains along with the accessory fingers and thumb domains. All RdRps also have six conserved structural motifs (A-F), located in its majority in the palm subdomain (A-E motifs) and the F motif is located on the finger subdomain. All these motifs have been shown to be implicated in RdRp fidelity such as processes of correct incorporation and reorganization of nucleotides. In addition to Group IV viruses, this model also includes Picobirnaviruses (PBVs), members of the family Picobirnaviridae of dsRNA viruses (Baltimore classification Group III), which are bi-segmented dsRNA viruses. The phylogenetic tree of the RdRps of RNA viruses (realm Riboviria) showed that picobirnaviruses are embedded in the branch of diverse (+)RNA viruses; sometimes they are collectively referred to as the picornavirus supergroup. RdRps of members of the family Permutatetraviridae, a distinct group of RNA viruses that encompass a circular permutation within the RdRp palm domain, are not included in this model.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1012615172  589 SRLRFIPKTDGM------RPITrVVGTDPK--TRMFRARVRDLLDLLRVCV-------RSTpsllgstvwgMTDIHKVLS 653
Cdd:cd01650      2 ARIILIPKKGKPsdpknyRPIS-LLSVLYKllEKILANRLRPVLEENILPNqfgfrpgRST----------TDAILLLRE 70

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1012615172  654 SLAPAQKDKpQQLYFVKVDVSGAYESLPHSKLMEVIG--Q--ALSPIqdeLFT 702
Cdd:cd01650     71 VIEKAKEKK-KSLVLVFLDFEKAFDSVDHEFLLKALGvrQgdPLSPL---LFN 119

Telomerase ribonucleoprotein complex - RNA binding domain; Telomeres in most organisms are comprised of tandem simple sequence repeats. The total length of telomeric repeat sequence at each chromosome end is determined in a balance of sequence loss and sequence addition. One major influence on telomere length is the enzyme telomerase. It is a reverse transcriptase that adds these simple sequence repeats to chromosome ends by copying a template sequence within the RNA component of the enzyme. The RNA binding domain of telomerase - TRBD - is made up of twelve alpha helices and two short beta sheets. How telomerase and associated regulatory factors physically interact and function with each other to maintain appropriate telomere length is poorly understood. It is known however that TRBD is involved in formation of the holoenzyme (which performs the telomere extension) in addition to recognition and binding of RNA.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1012615172   434 RVYLFVRACLSAVIPRELWGSDHNRVHFFARARGFLLNGKFERLSLAELMWNMKVNDCDWLKISKSG--RIPPSELAYRT 511
Cdd:smart00975    1 QVVSFLRAILRKLFPLSLWGSRHNKRVFLKNLRRFLSLGRNEKFSLQELMWGIRVSDIPWLAGSKTTtqRVSKSEHEKRQ 80

                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|....*
gi 1012615172   512 QILGQFLAWLLDGFVAGLVRACFYATESMGQKNAVRFYRQDVWAKLQDLAFKGHL 566
Cdd:smart00975   81 ELLAQFVYWLFDCLVPPLLRSFFYVTESSGQKNKLLYFRHDVWKKLTRPALRRYL 135

TERT: Telomerase reverse transcriptase (TERT). Telomerase is a ribonucleoprotein (RNP) that synthesizes telomeric DNA repeats. The telomerase RNA subunit provides the template for synthesis of these repeats. The catalytic subunit of RNP is known as telomerase reverse transcriptase (TERT). The reverse transcriptase (RT) domain is located in the C-terminal region of the TERT polypeptide. Single amino acid substitutions in this region lead to telomere shortening and senescence. Telomerase is an enzyme that, in certain cells, maintains the physical ends of chromosomes (telomeres) during replication. In somatic cells, replication of the lagging strand requires the continual presence of an RNA primer approximately 200 nucleotides upstream, which is complementary to the template strand. Since there is a region of DNA less than 200 base pairs from the end of the chromosome where this is not possible, the chromosome is continually shortened. However, a surplus of repetitive DNA at the chromosome ends protects against the erosion of gene-encoding DNA. Telomerase is not normally expressed in somatic cells. It has been suggested that exogenous TERT may extend the lifespan of, or even immortalize, the cell. However, recent studies have shown that telomerase activity can be induced by a number of oncogenes. Conversely, the oncogene c-myc can be activated in human TERT immortalized cells. Sequence comparisons place the telomerase proteins in the RT family but reveal hallmarks that distinguish them from retroviral and retrotransposon relatives.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1012615172  779 GSVVQYgkktYRQCRGIPQGSVVSSLLCCLCYGHMENVLFKDVTENG--GCLMRMVDDFLLVTPDQHKAQTFLKILLAG- 855
Cdd:cd01648      8 DSIPQY----YRQKVGIPQGSPLSSLLCSLYYADLENKYLSFLDVIDkdSLLLRLVDDFLLITTSLDKAIKFLNLLLRGf 83

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 1012615172  856 VPQYGLVVNPQKVVVNFQvsgsvgscpgIRVLPPHCLFPWCGLLLD 901
Cdd:cd01648     84 INQYKTFVNFDKTQINFS----------FAQLDSSDLIPWCGLLIN 119

RT_nLTR: Non-LTR (long terminal repeat) retrotransposon and non-LTR retrovirus reverse transcriptase (RT). This subfamily contains both non-LTR retrotransposons and non-LTR retrovirus RTs. RTs catalyze the conversion of single-stranded RNA into double-stranded DNA for integration into host chromosomes. RT is a multifunctional enzyme with RNA-directed DNA polymerase, DNA directed DNA polymerase and ribonuclease hybrid (RNase H) activities.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1012615172  589 SRLRFIPKTDGM------RPITrVVGTDPK--TRMFRARVRDLLDLLRVCV-------RSTpsllgstvwgMTDIHKVLS 653
Cdd:cd01650      2 ARIILIPKKGKPsdpknyRPIS-LLSVLYKllEKILANRLRPVLEENILPNqfgfrpgRST----------TDAILLLRE 70

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1012615172  654 SLAPAQKDKpQQLYFVKVDVSGAYESLPHSKLMEVIG--Q--ALSPIqdeLFT 702
Cdd:cd01650     71 VIEKAKEKK-KSLVLVFLDFEKAFDSVDHEFLLKALGvrQgdPLSPL---LFN 119

Telomerase ribonucleoprotein complex - RNA binding domain; Telomeres in most organisms are comprised of tandem simple sequence repeats. The total length of telomeric repeat sequence at each chromosome end is determined in a balance of sequence loss and sequence addition. One major influence on telomere length is the enzyme telomerase. It is a reverse transcriptase that adds these simple sequence repeats to chromosome ends by copying a template sequence within the RNA component of the enzyme. The RNA binding domain of telomerase - TRBD - is made up of twelve alpha helices and two short beta sheets. How telomerase and associated regulatory factors physically interact and function with each other to maintain appropriate telomere length is poorly understood. It is known however that TRBD is involved in formation of the holoenzyme (which performs the telomere extension) in addition to recognition and binding of RNA.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1012615172   434 RVYLFVRACLSAVIPRELWGSDHNRVHFFARARGFLLNGKFERLSLAELMWNMKVNDCDWLKISKSG--RIPPSELAYRT 511
Cdd:smart00975    1 QVVSFLRAILRKLFPLSLWGSRHNKRVFLKNLRRFLSLGRNEKFSLQELMWGIRVSDIPWLAGSKTTtqRVSKSEHEKRQ 80

                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|....*
gi 1012615172   512 QILGQFLAWLLDGFVAGLVRACFYATESMGQKNAVRFYRQDVWAKLQDLAFKGHL 566
Cdd:smart00975   81 ELLAQFVYWLFDCLVPPLLRSFFYVTESSGQKNKLLYFRHDVWKKLTRPALRRYL 135

TERT: Telomerase reverse transcriptase (TERT). Telomerase is a ribonucleoprotein (RNP) that synthesizes telomeric DNA repeats. The telomerase RNA subunit provides the template for synthesis of these repeats. The catalytic subunit of RNP is known as telomerase reverse transcriptase (TERT). The reverse transcriptase (RT) domain is located in the C-terminal region of the TERT polypeptide. Single amino acid substitutions in this region lead to telomere shortening and senescence. Telomerase is an enzyme that, in certain cells, maintains the physical ends of chromosomes (telomeres) during replication. In somatic cells, replication of the lagging strand requires the continual presence of an RNA primer approximately 200 nucleotides upstream, which is complementary to the template strand. Since there is a region of DNA less than 200 base pairs from the end of the chromosome where this is not possible, the chromosome is continually shortened. However, a surplus of repetitive DNA at the chromosome ends protects against the erosion of gene-encoding DNA. Telomerase is not normally expressed in somatic cells. It has been suggested that exogenous TERT may extend the lifespan of, or even immortalize, the cell. However, recent studies have shown that telomerase activity can be induced by a number of oncogenes. Conversely, the oncogene c-myc can be activated in human TERT immortalized cells. Sequence comparisons place the telomerase proteins in the RT family but reveal hallmarks that distinguish them from retroviral and retrotransposon relatives.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1012615172  779 GSVVQYgkktYRQCRGIPQGSVVSSLLCCLCYGHMENVLFKDVTENG--GCLMRMVDDFLLVTPDQHKAQTFLKILLAG- 855
Cdd:cd01648      8 DSIPQY----YRQKVGIPQGSPLSSLLCSLYYADLENKYLSFLDVIDkdSLLLRLVDDFLLITTSLDKAIKFLNLLLRGf 83

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 1012615172  856 VPQYGLVVNPQKVVVNFQvsgsvgscpgIRVLPPHCLFPWCGLLLD 901
Cdd:cd01648     84 INQYKTFVNFDKTQINFS----------FAQLDSSDLIPWCGLLIN 119

RT_Bac_retron_I: Reverse transcriptases (RTs) in bacterial retrotransposons or retrons. The polymerase reaction of this enzyme leads to the production of a unique RNA-DNA complex called msDNA (multicopy single-stranded (ss)DNA) in which a small ssDNA branches out from a small ssRNA molecule via a 2'-5'phosphodiester linkage. Bacterial retron RTs produce cDNA corresponding to only a small portion of the retron genome.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1012615172  788 TYRQCRGIPQGSVVSSLLCclcyghmeNVLFKDVTE------NGGCLMRMVDDFLLVTPDQHKAQTFLKILLAGVPQYGL 861
Cdd:cd01646     47 QYGQTNGLPIGPLTSRFLA--------NIYLNDVDHelksklKGVDYVRYVDDIRIFADSKEEAEEILEELKEFLAELGL 118

                   ....*.
gi 1012615172  862 VVNPQK 867
Cdd:cd01646    119 SLNLSK 124

RT_nLTR: Non-LTR (long terminal repeat) retrotransposon and non-LTR retrovirus reverse transcriptase (RT). This subfamily contains both non-LTR retrotransposons and non-LTR retrovirus RTs. RTs catalyze the conversion of single-stranded RNA into double-stranded DNA for integration into host chromosomes. RT is a multifunctional enzyme with RNA-directed DNA polymerase, DNA directed DNA polymerase and ribonuclease hybrid (RNase H) activities.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1012615172  589 SRLRFIPKTDGM------RPITrVVGTDPK--TRMFRARVRDLLDLLRVCV-------RSTpsllgstvwgMTDIHKVLS 653
Cdd:cd01650      2 ARIILIPKKGKPsdpknyRPIS-LLSVLYKllEKILANRLRPVLEENILPNqfgfrpgRST----------TDAILLLRE 70

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1012615172  654 SLAPAQKDKpQQLYFVKVDVSGAYESLPHSKLMEVIG--Q--ALSPIqdeLFT 702
Cdd:cd01650     71 VIEKAKEKK-KSLVLVFLDFEKAFDSVDHEFLLKALGvrQgdPLSPL---LFN 119