View source for 1a5e


==SOLUTION NMR STRUCTURE OF TUMOR SUPPRESSOR P16INK4A, 18 STRUCTURES==
<StructureSection load='1a5e' size='340' side='right'caption='[[1a5e]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1a5e]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1A5E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1A5E FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1a5e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1a5e OCA], [https://pdbe.org/1a5e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1a5e RCSB], [https://www.ebi.ac.uk/pdbsum/1a5e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1a5e ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/CDN2A_HUMAN CDN2A_HUMAN] Note=The association between cutaneous and uveal melanomas in some families suggests that mutations in CDKN2A may account for a proportion of uveal melanomas. However, CDKN2A mutations are rarely found in uveal melanoma patients.  Defects in CDKN2A are the cause of cutaneous malignant melanoma type 2 (CMM2) [MIM:[https://omim.org/entry/155601 155601]. Malignant melanoma is a malignant neoplasm of melanocytes, arising de novo or from a pre-existing benign nevus, which occurs most often in the skin but also may involve other sites.<ref>PMID:7987387</ref> <ref>PMID:8595405</ref> <ref>PMID:8653684</ref> <ref>PMID:8710906</ref> <ref>PMID:9328469</ref> <ref>PMID:9425228</ref> <ref>PMID:10651484</ref> <ref>PMID:11506491</ref> <ref>PMID:12019208</ref> <ref>PMID:10874641</ref> <ref>PMID:14646619</ref> <ref>PMID:19260062</ref>   Defects in CDKN2A are the cause of familial atypical multiple mole melanoma-pancreatic carcinoma syndrome (FAMMMPC) [MIM:[https://omim.org/entry/606719 606719].  Defects in CDKN2A are a cause of Li-Fraumeni syndrome (LFS) [MIM:[https://omim.org/entry/151623 151623]. LFS is a highly penetrant familial cancer phenotype usually associated with inherited mutations in TP53.<ref>PMID:10484981</ref>   Defects in CDKN2A are the cause of melanoma-astrocytoma syndrome (MASTS) [MIM:[https://omim.org/entry/155755 155755]. The melanoma-astrocytoma syndrome is characterized by a dual predisposition to melanoma and neural system tumors, commonly astrocytoma.<ref>PMID:11136714</ref> 
== Function ==
[https://www.uniprot.org/uniprot/CDN2A_HUMAN CDN2A_HUMAN] Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6. This inhibits their ability to interact with cyclins D and to phosphorylate the retinoblastoma protein.<ref>PMID:7972006</ref> <ref>PMID:16782892</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/a5/1a5e_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1a5e ConSurf].
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== Publication Abstract from PubMed ==
The solution structure of the tumor suppressor p16INK4A has been determined by NMR, and important recognition regions of both cdk4 and p16INK4A have been identified. The tertiary structure of p16INK4A contains four helix-turn-helix motifs linked by three loops. Twelve tumorigenic mutants of p16INK4A have been constructed and analyzed for their structure and activity, and new mutants have been designed rationally. A fragment of 58 residues at the N terminus of cdk4 important for p16INK4A binding has been identified. The importance of this region was further verified by mutational analysis of cdk4. These results and docking experiments have been used to assess possible modes of binding between p16INK4A and cdk4.

Tumor suppressor p16INK4A: determination of solution structure and analyses of its interaction with cyclin-dependent kinase 4.,Byeon IJ, Li J, Ericson K, Selby TL, Tevelev A, Kim HJ, O'Maille P, Tsai MD Mol Cell. 1998 Feb;1(3):421-31. PMID:9660926<ref>PMID:9660926</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Byeon I-JL]]
[[Category: Ericson K]]
[[Category: Kim H-J]]
[[Category: Li J]]
[[Category: O'Maille P]]
[[Category: Selby TL]]
[[Category: Tevelev A]]
[[Category: Tsai M-D]]