1ee4 | pdb_00001ee4

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Template:STRUCTURE 1ee4

CRYSTAL STRUCTURE OF YEAST KARYOPHERIN (IMPORTIN) ALPHA IN A COMPLEX WITH A C-MYC NLS PEPTIDE

Template:ABSTRACT PUBMED 10745017

Disease

[MYC_HUMAN] Note=Overexpression of MYC is implicated in the etiology of a variety of hematopoietic tumors. Note=A chromosomal aberration involving MYC may be a cause of a form of B-cell chronic lymphocytic leukemia. Translocation t(8;12)(q24;q22) with BTG1. Defects in MYC are a cause of Burkitt lymphoma (BL) [MIM:113970]. A form of undifferentiated malignant lymphoma commonly manifested as a large osteolytic lesion in the jaw or as an abdominal mass. Note=Chromosomal aberrations involving MYC are usually found in Burkitt lymphoma. Translocations t(8;14), t(8;22) or t(2;8) which juxtapose MYC to one of the heavy or light chain immunoglobulin gene loci.

Function

[IMA1_YEAST] Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Promotes docking of import substrates to the nuclear envelope. Seems to act as a cytosolic receptor for both simple and bipartite NLS motifs (By similarity).[1][2][3] [MYC_HUMAN] Participates in the regulation of gene transcription. Binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. Seems to activate the transcription of growth-related genes.

About this Structure

1ee4 is a 6 chain structure with sequence from Homo sapiens and Saccharomyces cerevisiae. Full crystallographic information is available from OCA.

Reference

  1. Conti E, Kuriyan J. Crystallographic analysis of the specific yet versatile recognition of distinct nuclear localization signals by karyopherin alpha. Structure. 2000 Mar 15;8(3):329-38. PMID:10745017
  1. ↑ Kussel P, Frasch M. Yeast Srp1, a nuclear protein related to Drosophila and mouse pendulin, is required for normal migration, division, and integrity of nuclei during mitosis. Mol Gen Genet. 1995 Aug 21;248(3):351-63. PMID:7565597
  2. ↑ Tabb MM, Tongaonkar P, Vu L, Nomura M. Evidence for separable functions of Srp1p, the yeast homolog of importin alpha (Karyopherin alpha): role for Srp1p and Sts1p in protein degradation. Mol Cell Biol. 2000 Aug;20(16):6062-73. PMID:10913188
  3. ↑ Chen L, Romero L, Chuang SM, Tournier V, Joshi KK, Lee JA, Kovvali G, Madura K. Sts1 plays a key role in targeting proteasomes to the nucleus. J Biol Chem. 2011 Jan 28;286(4):3104-18. doi: 10.1074/jbc.M110.135863. Epub 2010 , Nov 12. PMID:21075847 doi:10.1074/jbc.M110.135863

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