3u88

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<StructureSection load='3u88' size='340' side='right'caption='[[3u88]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
<StructureSection load='3u88' size='340' side='right'caption='[[3u88]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3u88]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3U88 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3U88 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3u88]] 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=3U88 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3U88 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0BR:(4BETA,8ALPHA,9R)-6-METHOXY-10,11-DIHYDROCINCHONAN-9-OL'>0BR</scene>, <scene name='pdbligand=CHD:CHOLIC+ACID'>CHD</scene>, <scene name='pdbligand=GGB:L-CANAVANINE'>GGB</scene>, <scene name='pdbligand=GLV:GLYOXYLIC+ACID'>GLV</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3u84|3u84]], [[3u85|3u85]], [[3u86|3u86]]</div></td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0BR:(4BETA,8ALPHA,9R)-6-METHOXY-10,11-DIHYDROCINCHONAN-9-OL'>0BR</scene>, <scene name='pdbligand=CHD:CHOLIC+ACID'>CHD</scene>, <scene name='pdbligand=GGB:L-CANAVANINE'>GGB</scene>, <scene name='pdbligand=GLV:GLYOXYLIC+ACID'>GLV</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Histone-lysine_N-methyltransferase Histone-lysine N-methyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.43 2.1.1.43] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3u88 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3u88 OCA], [https://pdbe.org/3u88 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3u88 RCSB], [https://www.ebi.ac.uk/pdbsum/3u88 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3u88 ProSAT]</span></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=3u88 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3u88 OCA], [https://pdbe.org/3u88 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3u88 RCSB], [https://www.ebi.ac.uk/pdbsum/3u88 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3u88 ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
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[[https://www.uniprot.org/uniprot/MEN1_HUMAN MEN1_HUMAN]] Defects in MEN1 are the cause of familial multiple endocrine neoplasia type I (MEN1) [MIM:[https://omim.org/entry/131100 131100]]. Autosomal dominant disorder characterized by tumors of the parathyroid glands, gastro-intestinal endocrine tissue, the anterior pituitary and other tissues. Cutaneous lesions and nervous-tissue tumors can exist. Prognosis in MEN1 patients is related to hormonal hypersecretion by tumors, such as hypergastrinemia causing severe peptic ulcer disease (Zollinger-Ellison syndrome, ZES), primary hyperparathyroidism, and acute forms of hyperinsulinemia.<ref>PMID:14992727</ref> <ref>PMID:9989505</ref> <ref>PMID:9103196</ref> <ref>PMID:17555499</ref> <ref>PMID:9215689</ref> <ref>PMID:9215690</ref> <ref>PMID:9463336</ref> <ref>PMID:9683585</ref> <ref>PMID:9820618</ref> <ref>PMID:9671267</ref> <ref>PMID:10660339</ref> <ref>PMID:9506756</ref> <ref>PMID:9709921</ref> <ref>PMID:9709976</ref> <ref>PMID:9709985</ref> <ref>PMID:9740255</ref> <ref>PMID:9747036</ref> <ref>PMID:9832038</ref> <ref>PMID:10617276</ref> <ref>PMID:10229909</ref> <ref>PMID:10576763</ref> <ref>PMID:9888389</ref> <ref>PMID:10090472</ref> <ref>PMID:10534569</ref> <ref>PMID:10993647</ref> <ref>PMID:10849016</ref> <ref>PMID:10664520</ref> <ref>PMID:11102994</ref> <ref>PMID:11134142</ref> <ref>PMID:11241849</ref> <ref>PMID:12112656</ref> <ref>PMID:12417605</ref> <ref>PMID:12050235</ref> <ref>PMID:12699448</ref> <ref>PMID:12791038</ref> <ref>PMID:12652570</ref> <ref>PMID:14686752</ref> <ref>PMID:12746426</ref> <ref>PMID:15730416</ref> <ref>PMID:15714081</ref> Defects in MEN1 are the cause of familial isolated hyperparathyroidism (FIHP) [MIM:[https://omim.org/entry/145000 145000]]; also known as hyperparathyroidism type 1 (HRPT1). FIHP is an autosomal dominant disorder characterized by hypercalcemia, elevated parathyroid hormone (PTH) levels, and uniglandular or multiglandular parathyroid tumors.<ref>PMID:9888389</ref> <ref>PMID:12699448</ref> <ref>PMID:9792884</ref> <ref>PMID:9843042</ref> <ref>PMID:10664521</ref> <ref>PMID:10634381</ref> <ref>PMID:12016470</ref> [[https://www.uniprot.org/uniprot/PSIP1_HUMAN PSIP1_HUMAN]] Note=A chromosomal aberration involving PSIP1 is associated with pediatric acute myeloid leukemia (AML) with intermediate characteristics between M2-M3 French-American-British (FAB) subtypes. Translocation t(9;11)(p22;p15) with NUP98. The chimeric transcript is an in-frame fusion of NUP98 exon 8 to PSIP1/LEDGF exon 4. [[https://www.uniprot.org/uniprot/KMT2A_HUMAN KMT2A_HUMAN]] Acute myeloid leukemia with 11q23 abnormalities;Precursor B-cell acute lymphoblastic leukemia;Wiedemann-Steiner syndrome;Acute biphenotypic leukemia;Acute undifferentiated leukemia;Bilineal acute leukemia. The disease is caused by mutations affecting the gene represented in this entry. Chromosomal aberrations involving KMT2A are a cause of acute leukemias. Translocation t(1;11)(q21;q23) with MLLT11/AF1Q; translocation t(3;11)(p21;q23) with NCKIPSD/AF3p21; translocation t(3,11)(q25,q23) with GMPS; translocation t(4;11)(q21;q23) with AFF1/MLLT2/AF4; insertion ins(5;11)(q31;q13q23) with AFF4/AF5Q31; translocation t(5;11)(q12;q23) with AF5-alpha/CENPK; translocation t(6;11)(q27;q23) with MLLT4/AF6; translocation t(9;11)(p22;q23) with MLLT3/AF9; translocation t(10;11)(p11.2;q23) with ABI1; translocation t(10;11)(p12;q23) with MLLT10/AF10; t(11;15)(q23;q14) with CASC5 and ZFYVE19; translocation t(11;17)(q23;q21) with MLLT6/AF17; translocation t(11;19)(q23;p13.3) with ELL; translocation t(11;19)(q23;p13.3) with MLLT1/ENL; translocation t(11;19)(q23;p23) with GAS7; translocation t(X;11)(q13;q23) with FOXO4/AFX1. Translocation t(3;11)(q28;q23) with LPP. Translocation t(10;11)(q22;q23) with TET1. Translocation t(9;11)(q34;q23) with DAB2IP. Translocation t(4;11)(p12;q23) with FRYL. Fusion proteins KMT2A-MLLT1, KMT2A-MLLT3 and KMT2A-ELL interact with PPP1R15A and, on the contrary to unfused KMT2A, inhibit PPP1R15A-induced apoptosis. A chromosomal aberration involving KMT2A may be a cause of chronic neutrophilic leukemia. Translocation t(4;11)(q21;q23) with SEPT11.
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[https://www.uniprot.org/uniprot/MEN1_HUMAN MEN1_HUMAN] Defects in MEN1 are the cause of familial multiple endocrine neoplasia type I (MEN1) [MIM:[https://omim.org/entry/131100 131100]. Autosomal dominant disorder characterized by tumors of the parathyroid glands, gastro-intestinal endocrine tissue, the anterior pituitary and other tissues. Cutaneous lesions and nervous-tissue tumors can exist. Prognosis in MEN1 patients is related to hormonal hypersecretion by tumors, such as hypergastrinemia causing severe peptic ulcer disease (Zollinger-Ellison syndrome, ZES), primary hyperparathyroidism, and acute forms of hyperinsulinemia.<ref>PMID:14992727</ref> <ref>PMID:9989505</ref> <ref>PMID:9103196</ref> <ref>PMID:17555499</ref> <ref>PMID:9215689</ref> <ref>PMID:9215690</ref> <ref>PMID:9463336</ref> <ref>PMID:9683585</ref> <ref>PMID:9820618</ref> <ref>PMID:9671267</ref> <ref>PMID:10660339</ref> <ref>PMID:9506756</ref> <ref>PMID:9709921</ref> <ref>PMID:9709976</ref> <ref>PMID:9709985</ref> <ref>PMID:9740255</ref> <ref>PMID:9747036</ref> <ref>PMID:9832038</ref> <ref>PMID:10617276</ref> <ref>PMID:10229909</ref> <ref>PMID:10576763</ref> <ref>PMID:9888389</ref> <ref>PMID:10090472</ref> <ref>PMID:10534569</ref> <ref>PMID:10993647</ref> <ref>PMID:10849016</ref> <ref>PMID:10664520</ref> <ref>PMID:11102994</ref> <ref>PMID:11134142</ref> <ref>PMID:11241849</ref> <ref>PMID:12112656</ref> <ref>PMID:12417605</ref> <ref>PMID:12050235</ref> <ref>PMID:12699448</ref> <ref>PMID:12791038</ref> <ref>PMID:12652570</ref> <ref>PMID:14686752</ref> <ref>PMID:12746426</ref> <ref>PMID:15730416</ref> <ref>PMID:15714081</ref> Defects in MEN1 are the cause of familial isolated hyperparathyroidism (FIHP) [MIM:[https://omim.org/entry/145000 145000]; also known as hyperparathyroidism type 1 (HRPT1). FIHP is an autosomal dominant disorder characterized by hypercalcemia, elevated parathyroid hormone (PTH) levels, and uniglandular or multiglandular parathyroid tumors.<ref>PMID:9888389</ref> <ref>PMID:12699448</ref> <ref>PMID:9792884</ref> <ref>PMID:9843042</ref> <ref>PMID:10664521</ref> <ref>PMID:10634381</ref> <ref>PMID:12016470</ref>
== Function ==
== Function ==
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[[https://www.uniprot.org/uniprot/MEN1_HUMAN MEN1_HUMAN]] Essential component of a MLL/SET1 histone methyltransferase (HMT) complex, a complex that specifically methylates 'Lys-4' of histone H3 (H3K4). Functions as a transcriptional regulator. Binds to the TERT promoter and represses telomerase expression. Plays a role in TGFB1-mediated inhibition of cell-proliferation, possibly regulating SMAD3 transcriptional activity. Represses JUND-mediated transcriptional activation on AP1 sites, as well as that mediated by NFKB subunit RELA. Positively regulates HOXC8 and HOXC6 gene expression. May be involved in normal hematopoiesis through the activation of HOXA9 expression (By similarity). May be involved in DNA repair.<ref>PMID:11526476</ref> <ref>PMID:11274402</ref> <ref>PMID:12874027</ref> <ref>PMID:12837246</ref> <ref>PMID:14992727</ref> [[https://www.uniprot.org/uniprot/PSIP1_HUMAN PSIP1_HUMAN]] Transcriptional coactivator involved in neuroepithelial stem cell differentiation and neurogenesis. Involved in particular in lens epithelial cell gene regulation and stress responses. May play an important role in lens epithelial to fiber cell terminal differentiation. May play a protective role during stress-induced apoptosis. Isoform 2 is a more general and stronger transcriptional coactivator. Isoform 2 may also act as an adapter to coordinate pre-mRNA splicing. Cellular cofactor for lentiviral integration.<ref>PMID:15642333</ref> [[https://www.uniprot.org/uniprot/KMT2A_HUMAN KMT2A_HUMAN]] Histone methyltransferase that plays an essential role in early development and hematopoiesis. Catalytic subunit of the MLL1/MLL complex, a multiprotein complex that mediates both methylation of 'Lys-4' of histone H3 (H3K4me) complex and acetylation of 'Lys-16' of histone H4 (H4K16ac). In the MLL1/MLL complex, it specifically mediates H3K4me, a specific tag for epigenetic transcriptional activation. Has weak methyltransferase activity by itself, and requires other component of the MLL1/MLL complex to obtain full methyltransferase activity. Has no activity toward histone H3 phosphorylated on 'Thr-3', less activity toward H3 dimethylated on 'Arg-8' or 'Lys-9', while it has higher activity toward H3 acetylated on 'Lys-9'. Required for transcriptional activation of HOXA9. Promotes PPP1R15A-induced apoptosis.<ref>PMID:10490642</ref> <ref>PMID:12453419</ref> <ref>PMID:15960975</ref> <ref>PMID:19556245</ref>
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[https://www.uniprot.org/uniprot/MEN1_HUMAN MEN1_HUMAN] Essential component of a MLL/SET1 histone methyltransferase (HMT) complex, a complex that specifically methylates 'Lys-4' of histone H3 (H3K4). Functions as a transcriptional regulator. Binds to the TERT promoter and represses telomerase expression. Plays a role in TGFB1-mediated inhibition of cell-proliferation, possibly regulating SMAD3 transcriptional activity. Represses JUND-mediated transcriptional activation on AP1 sites, as well as that mediated by NFKB subunit RELA. Positively regulates HOXC8 and HOXC6 gene expression. May be involved in normal hematopoiesis through the activation of HOXA9 expression (By similarity). May be involved in DNA repair.<ref>PMID:11526476</ref> <ref>PMID:11274402</ref> <ref>PMID:12874027</ref> <ref>PMID:12837246</ref> <ref>PMID:14992727</ref>
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<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Histone-lysine N-methyltransferase]]
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Huang, J]]
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[[Category: Huang J]]
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[[Category: Lei, M]]
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[[Category: Lei M]]
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[[Category: Wan, B]]
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[[Category: Wan B]]
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[[Category: Jund]]
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[[Category: Ledgf]]
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[[Category: Men1]]
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[[Category: Menin]]
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[[Category: Mll]]
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[[Category: Tpr]]
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[[Category: Transcription]]
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Current revision

Crystal structure of human menin in complex with MLL1 and LEDGF

PDB ID 3u88

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