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1co1

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Revision as of 23:24, 22 December 2014

FOLD OF THE CBFA

Structural highlights

1co1 is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, RCSB, PDBsum

Disease

[RUNX1_HUMAN] Note=A chromosomal aberration involving RUNX1/AML1 is a cause of M2 type acute myeloid leukemia (AML-M2). Translocation t(8;21)(q22;q22) with RUNX1T1.^[1] ^[2] ^[3] ^[4] ^[5] Note=A chromosomal aberration involving RUNX1/AML1 is a cause of therapy-related myelodysplastic syndrome (T-MDS). Translocation t(3;21)(q26;q22) with EAP or MECOM. Note=A chromosomal aberration involving RUNX1/AML1 is a cause of chronic myelogenous leukemia (CML). Translocation t(3;21)(q26;q22) with EAP or MECOM. Note=A chromosomal aberration involving RUNX1/AML1 is found in childhood acute lymphoblastic leukemia (ALL). Translocation t(12;21)(p13;q22) with TEL. The translocation fuses the 3'-end of TEL to the alternate 5'-exon of AML-1H. Note=A chromosomal aberration involving RUNX1 is found in acute leukemia. Translocation t(11,21)(q13;q22) that forms a MACROD1-RUNX1 fusion protein. Defects in RUNX1 are the cause of familial platelet disorder with associated myeloid malignancy (FPDMM) [MIM:601399]. FPDMM is an autosomal dominant disease characterized by qualitative and quantitative platelet defects, and propensity to develop acute myelogenous leukemia.^[6] Note=A chromosomal aberration involving RUNX1/AML1 is found in therapy-related myeloid malignancies. Translocation t(16;21)(q24;q22) that forms a RUNX1-CBFA2T3 fusion protein. Note=A chromosomal aberration involving RUNX1/AML1 is a cause of chronic myelomonocytic leukemia. Inversion inv(21)(q21;q22) with USP16.

Function

[RUNX1_HUMAN] CBF binds to the core site, 5'-PYGPYGGT-3', of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, LCK, IL-3 and GM-CSF promoters. The alpha subunit binds DNA and appears to have a role in the development of normal hematopoiesis. Isoform AML-1L interferes with the transactivation activity of RUNX1. Acts synergistically with ELF4 to transactivate the IL-3 promoter and with ELF2 to transactivate the mouse BLK promoter. Inhibits KAT6B-dependent transcriptional activation.^[7] ^[8] ^[9] ^[10]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

BACKGROUND: CBFA is the DNA-binding subunit of the transcription factor complex called core binding factor, or CBF. Knockout of the Cbfa2 gene in mice leads to embryonic lethality and a profound block in hematopoietic development. Chromosomal disruptions of the human CBFA gene are associated with a large percentage of human leukemias. RESULTS: Utilizing nuclear magnetic resonance spectroscopy we have determined the three-dimensional fold of the CBFA Runt domain in its DNA-bound state, showing that it is an s-type immunoglobulin (Ig) fold. DNA binding by the Runt domain is shown to be mediated by loop regions located at both ends of the Runt domain Ig fold. A putative site for CBFB binding has been identified; the spatial location of this site provides a rationale for the ability of CBFB to modulate the affinity of the Runt domain for DNA. CONCLUSIONS: Structural comparisons demonstrate that the s-type Ig fold found in the Runt domain is conserved in the Ig folds found in the DNA-binding domains of NF-kappaB, NFAT, p53, STAT-1, and the T-domain. Thus, these proteins form a family of structurally and functionally related DNA-binding domains. Unlike the other members of this family, the Runt domain utilizes loops at both ends of the Ig fold for DNA recognition.

The Ig fold of the core binding factor alpha Runt domain is a member of a family of structurally and functionally related Ig-fold DNA-binding domains.,Berardi MJ, Sun C, Zehr M, Abildgaard F, Peng J, Speck NA, Bushweller JH Structure. 1999 Oct 15;7(10):1247-56. PMID:10545320^[11]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Nisson PE, Watkins PC, Sacchi N. Transcriptionally active chimeric gene derived from the fusion of the AML1 gene and a novel gene on chromosome 8 in t(8;21) leukemic cells. Cancer Genet Cytogenet. 1992 Oct 15;63(2):81-8. PMID:1423235
↑ Kozu T, Miyoshi H, Shimizu K, Maseki N, Kaneko Y, Asou H, Kamada N, Ohki M. Junctions of the AML1/MTG8(ETO) fusion are constant in t(8;21) acute myeloid leukemia detected by reverse transcription polymerase chain reaction. Blood. 1993 Aug 15;82(4):1270-6. PMID:8353289
↑ Miyoshi H, Kozu T, Shimizu K, Enomoto K, Maseki N, Kaneko Y, Kamada N, Ohki M. The t(8;21) translocation in acute myeloid leukemia results in production of an AML1-MTG8 fusion transcript. EMBO J. 1993 Jul;12(7):2715-21. PMID:8334990
↑ Tighe JE, Calabi F. Alternative, out-of-frame runt/MTG8 transcripts are encoded by the derivative (8) chromosome in the t(8;21) of acute myeloid leukemia M2. Blood. 1994 Oct 1;84(7):2115-21. PMID:7919324
↑ Era T, Asou N, Kunisada T, Yamasaki H, Asou H, Kamada N, Nishikawa S, Yamaguchi K, Takatsuki K. Identification of two transcripts of AML1/ETO-fused gene in t(8;21) leukemic cells and expression of wild-type ETO gene in hematopoietic cells. Genes Chromosomes Cancer. 1995 May;13(1):25-33. PMID:7541640
↑ Song WJ, Sullivan MG, Legare RD, Hutchings S, Tan X, Kufrin D, Ratajczak J, Resende IC, Haworth C, Hock R, Loh M, Felix C, Roy DC, Busque L, Kurnit D, Willman C, Gewirtz AM, Speck NA, Bushweller JH, Li FP, Gardiner K, Poncz M, Maris JM, Gilliland DG. Haploinsufficiency of CBFA2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemia. Nat Genet. 1999 Oct;23(2):166-75. PMID:10508512 doi:10.1038/13793
↑ Mao S, Frank RC, Zhang J, Miyazaki Y, Nimer SD. Functional and physical interactions between AML1 proteins and an ETS protein, MEF: implications for the pathogenesis of t(8;21)-positive leukemias. Mol Cell Biol. 1999 May;19(5):3635-44. PMID:10207087
↑ Pelletier N, Champagne N, Stifani S, Yang XJ. MOZ and MORF histone acetyltransferases interact with the Runt-domain transcription factor Runx2. Oncogene. 2002 Apr 18;21(17):2729-40. PMID:11965546 doi:10.1038/sj.onc.1205367
↑ Cho JY, Akbarali Y, Zerbini LF, Gu X, Boltax J, Wang Y, Oettgen P, Zhang DE, Libermann TA. Isoforms of the Ets transcription factor NERF/ELF-2 physically interact with AML1 and mediate opposing effects on AML1-mediated transcription of the B cell-specific blk gene. J Biol Chem. 2004 May 7;279(19):19512-22. Epub 2004 Feb 17. PMID:14970218 doi:10.1074/jbc.M309074200
↑ Fujimoto T, Anderson K, Jacobsen SE, Nishikawa SI, Nerlov C. Cdk6 blocks myeloid differentiation by interfering with Runx1 DNA binding and Runx1-C/EBPalpha interaction. EMBO J. 2007 May 2;26(9):2361-70. Epub 2007 Apr 12. PMID:17431401 doi:10.1038/sj.emboj.7601675
↑ Berardi MJ, Sun C, Zehr M, Abildgaard F, Peng J, Speck NA, Bushweller JH. The Ig fold of the core binding factor alpha Runt domain is a member of a family of structurally and functionally related Ig-fold DNA-binding domains. Structure. 1999 Oct 15;7(10):1247-56. PMID:10545320

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1co1"

Categories: Homo sapiens | Berardi, M J | Bushweller, J H | Cbfa runt aml-1 runt domain | Gene regulation

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1co1]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CO1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1CO1 FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1co1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1co1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1co1 RCSB], [http://www.ebi.ac.uk/pdbsum/1co1 PDBsum]</span></td></tr>
+</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=1co1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1co1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1co1 RCSB], [http://www.ebi.ac.uk/pdbsum/1co1 PDBsum]</span></td></tr>
-<table>
+</table>
 == Disease ==
 [[http://www.uniprot.org/uniprot/RUNX1_HUMAN RUNX1_HUMAN]] Note=A chromosomal aberration involving RUNX1/AML1 is a cause of M2 type acute myeloid leukemia (AML-M2). Translocation t(8;21)(q22;q22) with RUNX1T1.<ref>PMID:1423235</ref> <ref>PMID:8353289</ref> <ref>PMID:8334990</ref> <ref>PMID:7919324</ref> <ref>PMID:7541640</ref>   Note=A chromosomal aberration involving RUNX1/AML1 is a cause of therapy-related myelodysplastic syndrome (T-MDS). Translocation t(3;21)(q26;q22) with EAP or MECOM.  Note=A chromosomal aberration involving RUNX1/AML1 is a cause of chronic myelogenous leukemia (CML). Translocation t(3;21)(q26;q22) with EAP or MECOM.  Note=A chromosomal aberration involving RUNX1/AML1 is found in childhood acute lymphoblastic leukemia (ALL). Translocation t(12;21)(p13;q22) with TEL. The translocation fuses the 3'-end of TEL to the alternate 5'-exon of AML-1H.  Note=A chromosomal aberration involving RUNX1 is found in acute leukemia. Translocation t(11,21)(q13;q22) that forms a MACROD1-RUNX1 fusion protein.  Defects in RUNX1 are the cause of familial platelet disorder with associated myeloid malignancy (FPDMM) [MIM:[http://omim.org/entry/601399 601399]]. FPDMM is an autosomal dominant disease characterized by qualitative and quantitative platelet defects, and propensity to develop acute myelogenous leukemia.<ref>PMID:10508512</ref>   Note=A chromosomal aberration involving RUNX1/AML1 is found in therapy-related myeloid malignancies. Translocation t(16;21)(q24;q22) that forms a RUNX1-CBFA2T3 fusion protein.  Note=A chromosomal aberration involving RUNX1/AML1 is a cause of chronic myelomonocytic leukemia. Inversion inv(21)(q21;q22) with USP16.
@@ Line 32: / Line 32: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Berardi, M J.]]
+[[Category: Berardi, M J]]
-[[Category: Bushweller, J H.]]
+[[Category: Bushweller, J H]]
 [[Category: Cbfa runt aml-1 runt domain]]
 [[Category: Gene regulation]]

1co1

From Proteopedia

Revision as of 23:24, 22 December 2014

FOLD OF THE CBFA

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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