Identification and functional characterization of a bipartite nuclear localization signal in ANKRD11. 2023

Min Chen, and Xue Yang, and Haiyang Liu, and Jun Wan
Biomedical Research Institute, Shenzhen-Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, 518036, China.

ANKRD11 gene encodes for the large nuclear protein essential for multiple system development including the nervous system. However, the molecular basis for the proper nuclear localization of ANKRD11 has not yet been elucidated. In this study, we have identified a functional bipartite nuclear localization signal (bNLS) between residues 53 and 87 of ANKRD11. Using biochemical approaches, we discovered two major binding sites in this bipartite NLS for Importin α1. Through site-directed mutagenesis and functional analysis, we further found that this bipartite NLS is sufficient for nuclear import of overexpressing GFP in HeLa cells and necessary for nuclear localization of ANKRD11. Importantly, our study provides a possible pathogenic mechanism for certain clinical variants located within the bipartite nuclear localization signal of ANKRD11.

UI MeSH Term Description Entries
D012097 Repressor Proteins Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release. Repressor Molecules,Transcriptional Silencing Factors,Proteins, Repressor,Silencing Factors, Transcriptional
D002467 Cell Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed) Cell Nuclei,Nuclei, Cell,Nucleus, Cell
D006367 HeLa Cells The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for, among other things, VIRUS CULTIVATION and PRECLINICAL DRUG EVALUATION assays. Cell, HeLa,Cells, HeLa,HeLa Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D014157 Transcription Factors Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. Transcription Factor,Factor, Transcription,Factors, Transcription
D019913 Nuclear Localization Signals Short, predominantly basic amino acid sequences identified as nuclear import signals for some proteins. These sequences are believed to interact with specific receptors at the NUCLEAR PORE. Nuclear Localization Signal,NLS Peptide,Nuclear Localization Signal Peptide,NLS Peptides,Peptide, NLS,Peptides, NLS,Signal, Nuclear Localization,Signals, Nuclear Localization
D021581 Active Transport, Cell Nucleus Gated transport mechanisms by which proteins or RNA are moved across the NUCLEAR MEMBRANE. Nuclear Export,Nuclear Import,Nuclear Transport,Nucleocytoplasmic Transport,Nucleo-cytoplasmic Transport,Export, Nuclear,Import, Nuclear,Nucleo cytoplasmic Transport,Transport, Nuclear,Transport, Nucleo-cytoplasmic,Transport, Nucleocytoplasmic,Transports, Nucleo-cytoplasmic
D028901 alpha Karyopherins Nucleocytoplasmic transport molecules that bind to the NUCLEAR LOCALIZATION SIGNALS of cytoplasmic molecules destined to be imported into the CELL NUCLEUS. Once attached to their cargo they bind to BETA KARYOPHERINS and are transported through the NUCLEAR PORE COMPLEX. Inside the CELL NUCLEUS alpha karyopherins dissociate from beta karypherins and their cargo. They then form a complex with CELLULAR APOPTOSIS SUSCEPTIBILITY PROTEIN and RAN GTP-BINDING PROTEIN which is exported to the CYTOPLASM. Importin-alpha,Karyopherin alpha,NLS Receptor,NLS-Binding Protein,NLSBP,Nuclear Localization Sequence Receptor,Nuclear Localization Signal-Binding Protein,Karyopherins, alpha,receptor, NLS

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