DOCK10

Last update 08 May 2025

Basic Info

Synonyms

dedicator of cytokinesis 10, Dedicator of cytokinesis protein 10, DOCK10

+ [3]

Introduction

Guanine nucleotide-exchange factor (GEF) that activates CDC42 and RAC1 by exchanging bound GDP for free GTP. Essential for dendritic spine morphogenesis in Purkinje cells and in hippocampal neurons, via a CDC42-mediated pathway. Sustains B-cell lymphopoiesis in secondary lymphoid tissues and regulates FCER2/CD23 expression.

100 Clinical Results associated with DOCK10

100 Translational Medicine associated with DOCK10

0 Patents (Medical) associated with DOCK10

Literatures (Medical) associated with DOCK10

01 May 2024·Cancer Genomics - Proteomics

Identification of a Gene Expression Signature to Predict the Risk of Early Recurrence and the Degree of Immune Cell Infiltration in Triple-negative Breast Cancer

Article

Author: Miura, Kentaro ; Sato, Keiko ; Akimoto, Kazunori ; Tamori, Shoma

BACKGROUND/AIMPatients with triple-negative breast cancer (TNBC) have a high rate of recurrence within 3 years of diagnosis and a high rate of death within 5 years compared to other subtypes. The number of clinical trials investigating various new agents and combination therapies has recently increased; however, current strategies benefit only a minority of patients. This study aimed to identify specific genes that predict patients at high risk of recurrence and the immune status of the tumor microenvironment at an early stage, thereby providing insight into potential therapeutic targets to improve clinical outcomes in TNBC patients.MATERIALS AND METHODSWe evaluated the prognostic significance of microarray mRNA expression of 20,603 genes in 233 TNBC patients from the METABRIC dataset and further validated the results using RNA-seq mRNA expression data in 143 TNBC patients from the GSE96058 dataset.RESULTSEighteen differentially expressed genes (AKNA, ARHGAP30, CA9, CD3D, CD3G, CD6, CXCR6, CYSLTR1, DOCK10, ENO1, FLT3LG, IFNG, IL2RB, LPXN, PRKCB, PVRIG, RASSF5, and STAT4) identified in both datasets were found to be reliable biomarkers for predicting TNBC recurrence and progression. Notably, the genes whose low expression was associated with increased risk of recurrence and death were immune-related genes, with significant differences in levels of immune cell infiltration in the tumor microenvironment between high- and low- expression groups.CONCLUSIONGenes reported herein may be effective biomarkers to identify TNBC patients who will and will not benefit from immunotherapy and may be particularly important genes for developing future treatment strategies, including immunotherapy.

02 Apr 2024·Genetics, selection, evolution : GSE

Whole-genome resequencing of Chinese indigenous sheep provides insight into the genetic basis underlying climate adaptation.

Article

Author: Wang, Huihua ; Liu, Gang ; Yuan, Zehu ; Jin, Meilin ; Lu, Jian ; Lu, Zengkui ; Li, Taotao ; Liu, Engming ; Wei, Caihong ; Du, Lixin

BACKGROUNDChinese indigenous sheep are valuable resources with unique features and characteristics. They are distributed across regions with different climates in mainland China; however, few reports have analyzed the environmental adaptability of sheep based on their genome. We examined the variants and signatures of selection involved in adaptation to extreme humidity, altitude, and temperature conditions in 173 sheep genomes from 41 phenotypically and geographically representative Chinese indigenous sheep breeds to characterize the genetic basis underlying environmental adaptation in these populations.RESULTSBased on the analysis of population structure, we inferred that Chinese indigenous sheep are divided into four groups: Kazakh (KAZ), Mongolian (MON), Tibetan (TIB), and Yunnan (YUN). We also detected a set of candidate genes that are relevant to adaptation to extreme environmental conditions, such as drought-prone regions (TBXT, TG, and HOXA1), high-altitude regions (DYSF, EPAS1, JAZF1, PDGFD, and NF1) and warm-temperature regions (TSHR, ABCD4, and TEX11). Among all these candidate genes, eight ABCD4, CNTN4, DOCK10, LOC105608545, LOC121816479, SEM3A, SVIL, and TSHR overlap between extreme environmental conditions. The TSHR gene shows a strong signature for positive selection in the warm-temperature group and harbors a single nucleotide polymorphism (SNP) missense mutation located between positions 90,600,001 and 90,650,001 on chromosome 7, which leads to a change in the protein structure of TSHR and influences its stability.CONCLUSIONSAnalysis of the signatures of selection uncovered genes that are likely related to environmental adaptation and a SNP missense mutation in the TSHR gene that affects the protein structure and stability. It also provides information on the evolution of the phylogeographic structure of Chinese indigenous sheep populations. These results provide important genetic resources for future breeding studies and new perspectives on how animals can adapt to climate change.

01 Apr 2023·Biochemical and Biophysical Research Communications

Structural basis for the dual GTPase specificity of the DOCK10 guanine nucleotide exchange factor

Article

Author: Ihara, Kentaro ; Yokoyama, Shigeyuki ; Kukimoto-Niino, Mutsuko ; Fukui, Yoshinori ; Mishima-Tsumagari, Chiemi ; Inoue, Mio ; Shirouzu, Mikako

Dedicator of cytokinesis 10 (DOCK10), an evolutionarily conserved guanine nucleotide exchange factor (GEF) for Rho GTPases, has the unique specificity within the DOCK-D subfamily to activate both Cdc42 and Rac, but the structural bases for these activities remained unknown. Here we present the crystal structures of the catalytic DHR2 domain of mouse DOCK10, complexed with either Cdc42 or Rac1. The structures revealed that DOCK10^DHR2 binds to Cdc42 or Rac1 by slightly changing the arrangement of its two catalytic lobes. DOCK10 also has a flexible binding pocket for the 56th GTPase residue, allowing a novel interaction with Trp56^Rac1. The conserved residues in switch 1 of Cdc42 and Rac1 showed common interactions with the unique Lys-His sequence in the β5/β6 loop of DOCK10^DHR2. However, the interaction of switch 1 in Rac1 was less stable than that of switch 1 in Cdc42, due to amino acid differences at positions 27 and 30. Structure-based mutagenesis identified the DOCK10 residues that determine the Cdc42/Rac1 dual specificity.

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DOCK10

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