Dedicator of cytokinesis protein

From Proteopedia

Contents 1 Function 2 Disease 3 Structural highlights 4 3D structures of dedicator of cytokinesis protein Function Dedicator of cytokinesis proteins (DOCK) are guanine-nucleotide exchange factors for Rho-family GTPase. DOCKs are required in cell motility and phagocytosis. DOCK1 is a regulator of cancer metastasis[1]. DOCK2 is a regulator of various immune functions by activating Rac [2]. DOCK3 is highly expressed in neutrons and is essential for cell growth and migration[3]. DOCK5 has a role in regulating motile and invasive capacities of epithelial cells[4]. DOCK7 is a regulator of DNA replication stress by promoting replication protein A stability in chromatin[5]. DOCK8 is highly expressed in lymphocytes and regulates the actin cytoskeleton[6]. DOCK10 is a regulator of dendritic spine morphogenesis via a Cdc42-mediated pathway[7]. Disease Mutations in DOCK8 are found in patients diagnosed with an atypical form of hyper-IgE syndrome[8]. Structural highlights Human dedicator of cytokinesis protein 9 DHR-2 domain (DOCK9) complex with Cdc42 and GDP (PDB code 2wmn). GDP interacts with Cdc42 (GTP-binding protein). Water molecules shown as red spheres. DOCK9 has extensive contacts with Cdc42[9]. 3D structures of dedicator of cytokinesis protein Dedicator of cytokinesis protein 3D structures

spinqualitylabelsall models Human dedicator of cytokinesis protein 9 dimer DHR-2 domain (grey and aqua) complex with Cdc42 (green and olive) and GDP (PDB code 2wmn) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

References

1. ↑ Chiang SK, Chang WC, Chen SE, Chang LC. DOCK1 Regulates Growth and Motility through the RRP1B-Claudin-1 Pathway in Claudin-Low Breast Cancer Cells. Cancers (Basel). 2019 Nov 8;11(11):1762. PMID:31717460 doi:10.3390/cancers11111762
2. ↑ Guo X, Adeyanju O, Sunil C, Mandlem V, Olajuyin A, Huang S, Chen SY, Idell S, Tucker TA, Qian G. DOCK2 contributes to pulmonary fibrosis by promoting lung fibroblast to myofibroblast transition. Am J Physiol Cell Physiol. 2022 Jul 1;323(1):C133-C144. PMID:35584329 doi:10.1152/ajpcell.00067.2022
3. ↑ Alexander MS, Velinov M. DOCK3-Associated Neurodevelopmental Disorder-Clinical Features and Molecular Basis. Genes (Basel). 2023 Oct 14;14(10):1940. PMID:37895289 doi:10.3390/genes14101940
4. ↑ Frank SR, Köllmann CP, van Lidth de Jeude JF, Thiagarajah JR, Engelholm LH, Frödin M, Hansen SH. The focal adhesion-associated proteins DOCK5 and GIT2 comprise a rheostat in control of epithelial invasion. Oncogene. 2017 Mar 30;36(13):1816-1828. PMID:27669437 doi:10.1038/onc.2016.345
5. ↑ Gao M, Guo G, Huang J, Hou X, Ham H, Kim W, Zhao F, Tu X, Zhou Q, Zhang C, Zhu Q, Liu J, Yan Y, Xu Z, Yin P, Luo K, Weroha J, Deng M, Billadeau DD, Lou Z. DOCK7 protects against replication stress by promoting RPA stability on chromatin. Nucleic Acids Res. 2021 Apr 6;49(6):3322-3337. PMID:33704464 doi:10.1093/nar/gkab134
6. ↑ Biggs CM, Keles S, Chatila TA. DOCK8 deficiency: Insights into pathophysiology, clinical features and management. Clin Immunol. 2017 Aug;181:75-82. PMID:28625885 doi:10.1016/j.clim.2017.06.003
7. ↑ Jaudon F, Raynaud F, Wehrlé R, Bellanger JM, Doulazmi M, Vodjdani G, Gasman S, Fagni L, Dusart I, Debant A, Schmidt S. The RhoGEF DOCK10 is essential for dendritic spine morphogenesis. Mol Biol Cell. 2015 Jun 1;26(11):2112-27. PMID:25851601 doi:10.1091/mbc.E14-08-1310
8. ↑ Su HC. Dedicator of cytokinesis 8 (DOCK8) deficiency. Curr Opin Allergy Clin Immunol. 2010 Dec;10(6):515-20. doi:, 10.1097/ACI.0b013e32833fd718. PMID:20864884 doi:http://dx.doi.org/10.1097/ACI.0b013e32833fd718
9. ↑ Yang J, Zhang Z, Roe SM, Marshall CJ, Barford D. Activation of Rho GTPases by DOCK exchange factors is mediated by a nucleotide sensor. Science. 2009 Sep 11;325(5946):1398-402. PMID:19745154 doi:325/5946/1398