KLHL15 (Xp22.11), HEL-S-305. DNA päätyjen trimmausproteiinin(CTIP) säätely

https://www.ncbi.nlm.nih.gov/pubmed/27561354/
 https://www.ncbi.nlm.nih.gov/gene/80311

Also known as HEL-S-305

Summary_This gene encodes a member of the kelch-like family of proteins that share a common domain structure consisting of an N-terminal broad-complex, tramtrack, bric-a-brac/poxvirus and zinc finger domain and C-terminal kelch repeat motifs. The encoded protein may be involved in protein ubiquitination and cytoskeletal organization. [provided by RefSeq, Apr 2009]

Expression Broad expression in bone marrow (RPKM 22.1), testis (RPKM 14.8) and 22 other tissues See more Orthologs mouse all

Preferred Names

kelch-like protein 15

Names

epididymis secretory protein Li 305

epididymis secretory sperm binding protein

kelch-like 15

https://www.nature.com/articles/ncomms12628 
 Figure!
 Cullin3-KLHL15 ubiquitin ligase mediates CtIP protein turnover to fine-tune DNA-end resection. Ferretti LP, et al. Nat Commun, 2016 Aug 26. PMID 27561354, Free PMC Article

Human CtIP (https://www.ncbi.nlm.nih.gov/gene/5932, DNA endonuclease RBBP8) )is a decisive factor in DNA double-strand break (DSB)repair pathway choice by enabling DNA-end resection, the first step that differentiates homologous recombination (HR) from non-homologous end-joining (NHEJ). To coordinate appropriate and timely execution of DNA-end resection, CtIP function is tightly controlled by multiple protein-protein interactions and post-translational modifications. Here, we identify the Cullin3 E3 ligase substrate adaptor Kelch-like protein 15 (KLHL15) as a new interaction partner of CtIP and show that KLHL15 promotes CtIP protein turnover via the ubiquitin-proteasome pathway. A tripeptide motif (FRY) conserved across vertebrate CtIP proteins is essential for KLHL15-binding; its mutation blocks KLHL15-dependent CtIP ubiquitination and degradation. Consequently, DNA-end resection is strongly attenuated in cells overexpressing KLHL15 but amplified in cells either expressing a CtIP-FRY mutant or lacking KLHL15, thus impacting the balance between HR and NHEJ. Collectively, our findings underline the key importance and high complexity of CtIP modulation for genome integrity.PMID: 27561354 PMCID: PMC5007465 DOI: 10.1038/ncomms12628 [Indexed for MEDLINE] Free PMC Article

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