4b18

<StructureSection load='4b18' size='340' side='right' caption='[[4b18]], [[Resolution|resolution]] 2.52&Aring;' scene=''>

<table><tr><td colspan='2'>[[4b18]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4B18 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4B18 FirstGlance]. <br>

</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2bck|2bck]], [[2jdq|2jdq]]</td></tr>

<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_DNA_polymerase RNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.49 2.7.7.49] </span></td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4b18 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4b18 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4b18 RCSB], [http://www.ebi.ac.uk/pdbsum/4b18 PDBsum]</span></td></tr>

== Disease ==

[[http://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:[http://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:[http://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:[http://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:[http://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:[http://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.

[[http://www.uniprot.org/uniprot/IMA1_HUMAN IMA1_HUMAN]] Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. [[http://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>

*[[Importin|Importin]]

[[Category: Human]]

[[Category: RNA-directed DNA polymerase]]

[[Category: Cho, H S]]

[[Category: Kim, K L]]

[[Category: Yoo, J H]]

[[Category: Transport protein - peptide complex]]