View source for 9dhf


==The Retinoblastoma Protein with Mutation E554K==
<StructureSection load='9dhf' size='340' side='right'caption='[[9dhf]], [[Resolution|resolution]] 2.26&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9dhf]] is a 2 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=9DHF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9DHF FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.26&#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=9dhf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9dhf OCA], [https://pdbe.org/9dhf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9dhf RCSB], [https://www.ebi.ac.uk/pdbsum/9dhf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9dhf ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/RB_HUMAN RB_HUMAN] Defects in RB1 are the cause of childhood cancer retinoblastoma (RB) [MIM:[https://omim.org/entry/180200 180200]. RB is a congenital malignant tumor that arises from the nuclear layers of the retina. It occurs in about 1:20'000 live births and represents about 2% of childhood malignancies. It is bilateral in about 30% of cases. Although most RB appear sporadically, about 20% are transmitted as an autosomal dominant trait with incomplete penetrance. The diagnosis is usually made before the age of 2 years when strabismus or a gray to yellow reflex from pupil ('cat eye') is investigated.<ref>PMID:2594029</ref> <ref>PMID:1352883</ref> <ref>PMID:8346255</ref> <ref>PMID:7704558</ref> <ref>PMID:7927327</ref> <ref>PMID:8605116</ref> <ref>PMID:7795591</ref> <ref>PMID:8776589</ref> <ref>PMID:9311732</ref> <ref>PMID:9140452</ref> <ref>PMID:10671068</ref> <ref>PMID:9973307</ref> <ref>PMID:11524739</ref>   Defects in RB1 are a cause of susceptibility to bladder cancer (BLC) [MIM:[https://omim.org/entry/109800 109800]. A malignancy originating in tissues of the urinary bladder. It often presents with multiple tumors appearing at different times and at different sites in the bladder. Most bladder cancers are transitional cell carcinomas. They begin in cells that normally make up the inner lining of the bladder. Other types of bladder cancer include squamous cell carcinoma (cancer that begins in thin, flat cells) and adenocarcinoma (cancer that begins in cells that make and release mucus and other fluids). Bladder cancer is a complex disorder with both genetic and environmental influences.  Defects in RB1 are a cause of osteogenic sarcoma (OSRC) [MIM:[https://omim.org/entry/259500 259500].
== Function ==
[https://www.uniprot.org/uniprot/RB_HUMAN RB_HUMAN] Key regulator of entry into cell division that acts as a tumor suppressor. Promotes G0-G1 transition when phosphorylated by CDK3/cyclin-C. Acts as a transcription repressor of E2F1 target genes. The underphosphorylated, active form of RB1 interacts with E2F1 and represses its transcription activity, leading to cell cycle arrest. Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransferases SUV39H1, SUV420H1 and SUV420H2, leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation. Inhibits the intrinsic kinase activity of TAF1. Mediates transcriptional repression by SMARCA4/BRG1 by recruiting a histone deacetylase (HDAC) complex to the c-FOS promoter. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex (By similarity). In case of viral infections, interactions with SV40 large T antigen, HPV E7 protein or adenovirus E1A protein induce the disassembly of RB1-E2F1 complex thereby disrupting RB1's activity.<ref>PMID:15084261</ref> 
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Burke JR]]
[[Category: Castro A]]
[[Category: Ruiz-Rivera A]]