2ckk
From Proteopedia
High resolution crystal structure of the human kin17 C-terminal domain containing a kow motif
Structural highlights
FunctionKIN17_HUMAN Involved in DNA replication and the cellular response to DNA damage. May participate in DNA replication factories and create a bridge between DNA replication and repair mediated by high molecular weight complexes. May play a role in illegitimate recombination and regulation of gene expression. May participate in mRNA processing. Binds, in vitro, to double-stranded DNA. Also shown to bind preferentially to curved DNA in vitro and in vivo (By similarity). Binds via its C-terminal domain to RNA in vitro.[UniProtKB:Q8K339][1] [2] [3] [4] [5] [6] 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 PubMedThe human KIN17 protein is an essential nuclear protein conserved from yeast to human and expressed ubiquitously in mammals. Suppression of Rts2, the yeast equivalent of gene KIN17, renders the cells unviable, and silencing the human KIN17 gene slows cell growth dramatically. Moreover, the human gene KIN17 is up-regulated following exposure to ionizing radiations and UV light, depending on the integrity of the human global genome repair machinery. Its ectopic over-expression blocks S-phase progression by inhibiting DNA synthesis. The C-terminal region of human KIN17 is crucial for this anti-proliferation effect. Its high-resolution structure, presented here, reveals a tandem of SH3-like subdomains. This domain binds to ribonucleotide homopolymers with the same preferences as the whole protein. Analysis of its structure complexed with tungstate shows structural variability within the domain. The interaction with tungstate is mediated by several lysine residues located within a positively charged groove at the interface between the two subdomains. This groove could be the site of interaction with RNA, since mutagenesis of two of these highly conserved lysine residue weakens RNA binding. A tandem of SH3-like domains participates in RNA binding in KIN17, a human protein activated in response to genotoxics.,le Maire A, Schiltz M, Stura EA, Pinon-Lataillade G, Couprie J, Moutiez M, Gondry M, Angulo JF, Zinn-Justin S J Mol Biol. 2006 Dec 8;364(4):764-76. Epub 2006 Sep 16. PMID:17045609[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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