LOCUS       NP_937983               1132 aa            linear   PRI 12-NOV-2024
DEFINITION  telomerase reverse transcriptase isoform 1 [Homo sapiens].
ACCESSION   NP_937983 NP_003210
VERSION     NP_937983.2
DBSOURCE    REFSEQ: accession NM_198253.3
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 1132)
  AUTHORS   Karna,D., Liang,L., Sharma,G., Mandal,S., Asamitsu,S., Kawamoto,Y.,
            Hashiya,K., Bando,T., Sugiyama,H. and Mao,H.
  TITLE     Modulation of dynamic DNA G-quadruplex structures in the hTERT
            promoter region by ligands
  JOURNAL   Nucleic Acids Res 52 (18), 10775-10787 (2024)
   PUBMED   39217470
  REMARK    GeneRIF: Modulation of dynamic DNA G-quadruplex structures in the
            hTERT promoter region by ligands.
REFERENCE   2  (residues 1 to 1132)
  AUTHORS   Sergeeva,S.V., Loshchenova,P.S., Oshchepkov,D.Y. and
            Orishchenko,K.E.
  TITLE     Crosstalk between BER and NHEJ in XRCC4-Deficient Cells Depending
            on hTERT Overexpression
  JOURNAL   Int J Mol Sci 25 (19), 10405 (2024)
   PUBMED   39408734
  REMARK    GeneRIF: Crosstalk between BER and NHEJ in XRCC4-Deficient Cells
            Depending on hTERT Overexpression.
            Publication Status: Online-Only
REFERENCE   3  (residues 1 to 1132)
  AUTHORS   Song,Y., Xu,J., Geng,W., Yin,L., Wang,J. and Zhao,J.
  TITLE     Association and causal impact of TERT genetic variants on
            peripheral blood leukocyte telomere length and cerebral small
            vessel disease risk in a Chinese Han population: a mendelian
            randomization analysis
  JOURNAL   Orphanet J Rare Dis 19 (1), 309 (2024)
   PUBMED   39180127
  REMARK    GeneRIF: Association and causal impact of TERT genetic variants on
            peripheral blood leukocyte telomere length and cerebral small
            vessel disease risk in a Chinese Han population: a mendelian
            randomization analysis.
            Publication Status: Online-Only
REFERENCE   4  (residues 1 to 1132)
  AUTHORS   Marczyk,V.R., Maia,A.L. and Goemann,I.M.
  TITLE     Distinct transcriptional and prognostic impacts of TERT promoter
            mutations C228T and C250T in papillary thyroid carcinoma
  JOURNAL   Endocr Relat Cancer 31 (9), e240058 (2024)
   PUBMED   38973620
  REMARK    GeneRIF: Distinct transcriptional and prognostic impacts of TERT
            promoter mutations C228T and C250T in papillary thyroid carcinoma.
            Publication Status: Online-Only
REFERENCE   5  (residues 1 to 1132)
  AUTHORS   Meyerson,M., Counter,C.M., Eaton,E.N., Ellisen,L.W., Steiner,P.,
            Caddle,S.D., Ziaugra,L., Beijersbergen,R.L., Davidoff,M.J., Liu,Q.,
            Bacchetti,S., Haber,D.A. and Weinberg,R.A.
  TITLE     hEST2, the putative human telomerase catalytic subunit gene, is
            up-regulated in tumor cells and during immortalization
  JOURNAL   Cell 90 (4), 785-795 (1997)
   PUBMED   9288757
REFERENCE   6  (residues 1 to 1132)
  AUTHORS   Nakamura,T.M., Morin,G.B., Chapman,K.B., Weinrich,S.L.,
            Andrews,W.H., Lingner,J., Harley,C.B. and Cech,T.R.
  TITLE     Telomerase catalytic subunit homologs from fission yeast and human
  JOURNAL   Science 277 (5328), 955-959 (1997)
   PUBMED   9252327
REFERENCE   7  (residues 1 to 1132)
  AUTHORS   Lingner,J., Hughes,T.R., Shevchenko,A., Mann,M., Lundblad,V. and
            Cech,T.R.
  TITLE     Reverse transcriptase motifs in the catalytic subunit of telomerase
  JOURNAL   Science 276 (5312), 561-567 (1997)
   PUBMED   9110970
REFERENCE   8  (residues 1 to 1132)
  AUTHORS   Savage,S.A. and Niewisch,M.R.
  TITLE     Dyskeratosis Congenita and Related Telomere Biology Disorders
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301779
REFERENCE   9  (residues 1 to 1132)
  AUTHORS   Garcia,C.K. and Talbert,J.L.
  TITLE     Pulmonary Fibrosis Predisposition Overview
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301408
REFERENCE   10 (residues 1 to 1132)
  AUTHORS   Morin,G.B.
  TITLE     The human telomere terminal transferase enzyme is a
            ribonucleoprotein that synthesizes TTAGGG repeats
  JOURNAL   Cell 59 (3), 521-529 (1989)
   PUBMED   2805070
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC114291.2, AF018167.1 and
            AF015950.1.
            
            On or before Jun 23, 2006 this sequence version replaced
            NP_003210.1, NP_937983.1.
            
            Summary: 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].
            
            Transcript Variant: This variant (1) represents the longest
            transcript and encodes the longer isoform (1).
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: AF015950.1, AF018167.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000310581.10/ ENSP00000309572.5
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..1132
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="5"
                     /map="5p15.33"
     Protein         1..1132
                     /product="telomerase reverse transcriptase isoform 1"
                     /EC_number="2.7.7.49"
                     /note="telomerase catalytic subunit; telomerase-associated
                     protein 2"
                     /calculated_mol_wt=126866
     Region          1..230
                     /region_name="RNA-interacting domain 1"
                     /note="propagated from UniProtKB/Swiss-Prot (O14746.1)"
     Region          <22..482
                     /region_name="PksD"
                     /note="Acyl transferase domain in polyketide synthase
                     (PKS) enzymes [Secondary metabolites biosynthesis,
                     transport and catabolism]; COG3321"
                     /db_xref="CDD:442550"
     Region          58..197
                     /region_name="GQ motif"
                     /note="propagated from UniProtKB/Swiss-Prot (O14746.1)"
     Region          137..141
                     /region_name="Required for regulating specificity for
                     telomeric DNA and for processivity for primer elongation"
                     /note="propagated from UniProtKB/Swiss-Prot (O14746.1)"
     Site            169
                     /site_type="other"
                     /note="Required for optimal binding of telomeric ssDNA and
                     incorporation of nucleotides at the second position of the
                     template; propagated from UniProtKB/Swiss-Prot (O14746.1)"
     Region          210..320
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (O14746.1)"
     Region          222..240
                     /region_name="Bipartite nuclear localization signal"
                     /note="propagated from UniProtKB/Swiss-Prot (O14746.1)"
     Site            227
                     /site_type="phosphorylation"
                     /note="Phosphoserine, by PKB/AKT1.
                     /evidence=ECO:0000269|PubMed:22366458; propagated from
                     UniProtKB/Swiss-Prot (O14746.1)"
     Region          231..324
                     /region_name="Linker"
                     /note="propagated from UniProtKB/Swiss-Prot (O14746.1)"
     Region          301..538
                     /region_name="Required for oligomerization"
                     /note="propagated from UniProtKB/Swiss-Prot (O14746.1)"
     Region          325..550
                     /region_name="RNA-interacting domain 2"
                     /note="propagated from UniProtKB/Swiss-Prot (O14746.1)"
     Region          328..333
                     /region_name="TFLY, involved in RNA binding.
                     /evidence=ECO:0000250|UniProtKB:Q4KTA7"
                     /note="propagated from UniProtKB/Swiss-Prot (O14746.1)"
     Region          376..521
                     /region_name="QFP motif"
                     /note="propagated from UniProtKB/Swiss-Prot (O14746.1)"
     Region          397..417
                     /region_name="CP motif"
                     /note="propagated from UniProtKB/Swiss-Prot (O14746.1)"
     Site            457
                     /site_type="phosphorylation"
                     /note="Phosphoserine, by DYRK2.
                     /evidence=ECO:0000269|PubMed:23362280; propagated from
                     UniProtKB/Swiss-Prot (O14746.1)"
     Region          460..592
                     /region_name="Telomerase_RBD"
                     /note="Telomerase ribonucleoprotein complex - RNA binding
                     domain; pfam12009"
                     /db_xref="CDD:463428"
     Region          618..>729
                     /region_name="ps-ssRNAv_RdRp-like"
                     /note="conserved catalytic core domain of RNA-dependent
                     RNA polymerase (RdRp) from the positive-sense
                     single-stranded RNA [(+)ssRNA] viruses and closely related
                     viruses; cl40470"
                     /db_xref="CDD:477363"
     Site            707
                     /site_type="phosphorylation"
                     /note="Phosphotyrosine, by SRC-type Tyr-kinases.
                     /evidence=ECO:0000269|PubMed:12808100,
                     ECO:0000269|PubMed:18829466; propagated from
                     UniProtKB/Swiss-Prot (O14746.1)"
     Region          825..936
                     /region_name="TERT"
                     /note="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...; cd01648"
                     /db_xref="CDD:238826"
     Site            834
                     /site_type="other"
                     /note="putative nucleic acid binding site [nucleotide
                     binding]"
                     /db_xref="CDD:238826"
     Site            867
                     /site_type="other"
                     /note="Required for nucleotide incorporation and primer
                     extension rate; propagated from UniProtKB/Swiss-Prot
                     (O14746.1)"
     Region          914..928
                     /region_name="Required for oligomerization"
                     /note="propagated from UniProtKB/Swiss-Prot (O14746.1)"
     Region          930..934
                     /region_name="Primer grip sequence"
                     /note="propagated from UniProtKB/Swiss-Prot (O14746.1)"
     Region          936..1132
                     /region_name="CTE"
                     /note="propagated from UniProtKB/Swiss-Prot (O14746.1)"
     CDS             1..1132
                     /gene="TERT"
                     /gene_synonym="CMM9; DKCA2; DKCB4; EST2; hEST2; hTRT;
                     PFBMFT1; TCS1; TP2; TRT"
                     /coded_by="NM_198253.3:80..3478"
                     /note="isoform 1 is encoded by transcript variant 1"
                     /db_xref="CCDS:CCDS3861.2"
                     /db_xref="GeneID:7015"
                     /db_xref="HGNC:HGNC:11730"
                     /db_xref="MIM:187270"
ORIGIN      
        1 mpraprcrav rsllrshyre vlplatfvrr lgpqgwrlvq rgdpaafral vaqclvcvpw
       61 darpppaaps frqvsclkel varvlqrlce rgaknvlafg falldgargg ppeafttsvr
      121 sylpntvtda lrgsgawgll lrrvgddvlv hllarcalfv lvapscayqv cgpplyqlga
      181 atqarpppha sgprrrlgce rawnhsvrea gvplglpapg arrrggsasr slplpkrprr
      241 gaapepertp vgqgswahpg rtrgpsdrgf cvvsparpae eatslegals gtrhshpsvg
      301 rqhhagppst srpprpwdtp cppvyaetkh flyssgdkeq lrpsfllssl rpsltgarrl
      361 vetiflgsrp wmpgtprrlp rlpqrywqmr plflellgnh aqcpygvllk thcplraavt
      421 paagvcarek pqgsvaapee edtdprrlvq llrqhsspwq vygfvraclr rlvppglwgs
      481 rhnerrflrn tkkfislgkh aklslqeltw kmsvrdcawl rrspgvgcvp aaehrlreei
      541 lakflhwlms vyvvellrsf fyvtettfqk nrlffyrksv wsklqsigir qhlkrvqlre
      601 lseaevrqhr earpalltsr lrfipkpdgl rpivnmdyvv gartfrrekr aerltsrvka
      661 lfsvlnyera rrpgllgasv lglddihraw rtfvlrvraq dpppelyfvk vdvtgaydti
      721 pqdrltevia siikpqntyc vrryavvqka ahghvrkafk shvstltdlq pymrqfvahl
      781 qetsplrdav vieqssslne assglfdvfl rfmchhavri rgksyvqcqg ipqgsilstl
      841 lcslcygdme nklfagirrd glllrlvddf llvtphltha ktflrtlvrg vpeygcvvnl
      901 rktvvnfpve dealggtafv qmpahglfpw cgllldtrtl evqsdyssya rtsirasltf
      961 nrgfkagrnm rrklfgvlrl kchslfldlq vnslqtvctn iykilllqay rfhacvlqlp
     1021 fhqqvwknpt fflrvisdta slcysilkak nagmslgakg aagplpseav qwlchqafll
     1081 kltrhrvtyv pllgslrtaq tqlsrklpgt tltaleaaan palpsdfkti ld
//
