View source for 9q12


==Human telomerase catalytic core with shelterin protein TPP1 and DNA primer ending in TTAG==
<StructureSection load='9q12' size='340' side='right'caption='[[9q12]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9q12]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9Q12 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9Q12 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9q12 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9q12 OCA], [https://pdbe.org/9q12 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9q12 RCSB], [https://www.ebi.ac.uk/pdbsum/9q12 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9q12 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/TERT_HUMAN TERT_HUMAN] Note=Activation of telomerase has been implicated in cell immortalization and cancer cell pathogenesis.  Defects in TERT are associated with susceptibilty to aplastic anemia (AA) [MIM:[https://omim.org/entry/609135 609135]. AA is a rare disease in which the reduction of the circulating blood cells results from damage to the stem cell pool in bone marrow. In most patients, the stem cell lesion is caused by an autoimmune attack. T-lymphocytes, activated by an endogenous or exogenous, and most often unknown antigenic stimulus, secrete cytokines, including IFN-gamma, which would in turn be able to suppress hematopoiesis.<ref>PMID:15885610</ref> <ref>PMID:16627250</ref> <ref>PMID:16990594</ref> <ref>PMID:19760749</ref>   Note=Genetic variations in TERT are associated with coronary artery disease (CAD).<ref>PMID:16890917</ref>   Defects in TERT are the cause of dyskeratosis congenita autosomal dominant type 2 (DKCA2) [MIM:[https://omim.org/entry/613989 613989]. A rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy.<ref>PMID:15885610</ref> <ref>PMID:16247010</ref>   Defects in TERT are the cause of pulmonary fibrosis, and/or bone marrow failure, telomere-related, type 1 (PFBMFT1) [MIM:[https://omim.org/entry/614742 614742]. A disease associated with shortened telomeres. Pulmonary fibrosis is the most common manifestation. Other manifestations include aplastic anemia due to bone marrow failure, hepatic fibrosis, and increased cancer risk, particularly myelodysplastic syndrome and acute myeloid leukemia. Phenotype, age at onset, and severity are determined by telomere length. infections, fatal pulmonary complications, or malignancy.<ref>PMID:15814878</ref> <ref>PMID:17460043</ref> <ref>PMID:21436073</ref> <ref>PMID:21483807</ref> <ref>PMID:22512499</ref>   Defects in TERT are the cause of dyskeratosis congenita autosomal recessive type 4 (DKCB4) [MIM:[https://omim.org/entry/613989 613989]. A rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy.  Defects in TERT are a cause of susceptibility to pulmonary fibrosis idiopathic (IPF) [MIM:[https://omim.org/entry/178500 178500]. Pulmonary fibrosis is a lung disease characterized by shortness of breath, radiographically evident diffuse pulmonary infiltrates, and varying degrees of inflammation and fibrosis on biopsy. It results in acute lung injury with subsequent scarring and endstage lung disease.
== Function ==
[https://www.uniprot.org/uniprot/TERT_HUMAN TERT_HUMAN] 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.<ref>PMID:9389643</ref> <ref>PMID:14963003</ref> <ref>PMID:15082768</ref> <ref>PMID:15857955</ref> <ref>PMID:17026956</ref> <ref>PMID:17548608</ref> <ref>PMID:17296728</ref> <ref>PMID:17264120</ref> <ref>PMID:19188162</ref> <ref>PMID:19567472</ref> <ref>PMID:19571879</ref> <ref>PMID:19777057</ref> 
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Feigon J]]
[[Category: He Y]]
[[Category: Liu B]]
[[Category: Wang Y]]