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DOCK1 (Dedicator of cytokinesis 1)

Written2015-03Ping Li, Fung Zhao, Annie N. Cheung
Departments of Pathology, the University of Hong Kong Shenzhen Hospital, Shenzhen (PL, ANC),, The University of Hong Kong, Hong Kong (FZ, AC), China

Abstract Dedicator of cytokinesis (DOCK) is a family of proteins with 11 members in mammal which can regulate cell motility, phagocytosis, myoblast fusion, tumor suppression, neuronal polarization and adhesion. They are classified into four subfamilies A to D. Dock1 (Dock180), the founding member of the family, is a large protein which includes an N-terminal SH3 domain and a flanking helical bundle that are vital to the formation of a functioning complex Dock1-ELMO1 (Gumienny et al.,2001; Grimsley et al.,2004; Komander et al., 2008). Genetic and biochemical studies show that DOCK1 acts as a guanine-nucleotide exchange factor (GEF) for the small GTPase Rac1 (Diyokawa et al., 1998; Nolan et al., 1998). Rac1 is a small GTPase required for myoblast fusion in organisms such as fruit flies, zebrafish and mice (Rochlin et al., 1998). In addition to playing an important role in a broad spectrum of biological processes, numerous studies have demonstrated contributions of DOCK members to the development of cancer. Deciphering the detailed mechanisms by which DOCK proteins participate in tumorigenesis will shed light on the design of new treatment strategies.

Keywords DOCK1

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Alias (NCBI)ced5
DOCK 180
HGNC Alias symbDOCK180
HGNC Alias nameDOwnstream of CrK
HGNC Previous namededicator of cyto-kinesis 1
LocusID (NCBI) 1793
Atlas_Id 40354
Location 10q26.13-q26.3  [Link to chromosome band 10q26]
Location_base_pair Starts at 126905428 and ends at 127452516 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping DOCK1.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
C3 (19p13.3)::DOCK1 (10q26.2)DOCK1 (10q26.2)::APBA1 (9q21.11)DOCK1 (10q26.2)::APBA1 (9q21.12)
DOCK1 (10q26.2)::DOCK1 (10q26.2)DOCK1 (10q26.2)::DPCD (10q24.32)DOCK1 (10q26.2)::MGMT (10q26.3)
DOCK1 (10q26.2)::PCDH15 (10q21.1)DOCK1 (10q26.2)::PLPP4 (10q26.12)DOCK1 (10q26.2)::TFDP2 (3q23)
FUOM (10q26.3)::DOCK1 (10q26.2)GALNT16 (14q24.1)::DOCK1 (10q26.2)TTC21B (2q24.3)::DOCK1 (10q26.2)


Description The DOCK1 gene is 6797 base pairs in length encoding a large protein (about 180kDa).
Transcription Variant (1) represents the longer transcript and encodes the longer isoform (1). Variant (2) uses an alternate splice site at an internal exon, compared to variant 1. The encoded isoform (2) is shorter, compared to isoform 1.


  "This research was originally published in Journal of Biological Chemistry. Premkumar L, et al. Structural basis of membrane targeting by the DOCK180 family of Rho family guanine exchange factors (Rho-GEFs). J Biol Chem. 2010, 23; 285(17):13211-22. copyright the American Society for Biochemistry and Molecular Biology." (Premkumar L et al., 2010)
Description Dock1 is a 180 kDa protein and largely responsible for regulating Rac-mediated polarization, migration, phagocytosis of apoptotic cells, myoblasts fusion and macrophages in vitro (Cte etal., 2005; Grimsley etal., 2004; Pajcini et al., 2008) DOCK1 and its homologues in Drosophila (Myoblast city) and C.elegans (CED-5) represent an evolutionarily conserved family of proteins which is called CDM (CED-5, DOCK180, MBC)-family (Wu and Horvitz, 1998). DOCK1 has 6 splice variants with two protein-coding transcripts generating products consisting of 1865 and 1886 amino acids respectively. The others are non-protein-coding transcripts. An SH3 domain at the A- terminus and two domain CRK-binding sequences at the carboxyl end have been identified in Dock1 (Hideki Hasegawa et al, 1996). There are two high sequence homology named DHR-1 and DHR-2 among Dock family members (Jean Francois Cote and Kristiina Vuori, 2002). DHR1 domain is 200-250 amino acids long that binds phospholipids, whereas DHR2 domain of 450-550 amino acids is responsible for the guanine nucleotide exchange activity (25022758). DHR domain DOCK1 and its homologues in Drosophila (Myoblast city) and C.elegans (CED-5) represent an evolutionarily conserved family of proteins which is called CDM (CED-5, DOCK180, MBC)-family(Wu and Horvitz, 1998). This family is one of the GEFs being identified as activators of Rho GTPases (Takai etal., 1996; Hasegawa et al., 1996; Erickson and Cerione, 2004). The other family is Db1 family (Hart et al., 1991) and all their members contain the Db1 Homology (DH) and the Pleckstrin Homology (PH) domains (Klinger et al., 2004; Srivastava et al., 1986; Worthylake te al., 2004; Feng et al.,2002; Baird et al., 2005). While DH domains directly catalyze GDP-GTP exchange, PH domains target proteins to membranes and mediate protein-protein interactions. DOCK 180-related proteins can catalyze nucleotide exchange without homology to DH/PH domains, which are characterized by two protein domains named DOCK homology regions 1 and 2 (DHR-1 and DHR-2, respectively) (Brugnera et al., 2002; Cote and Vuori, 2002). DOCK1 contains 1864 amino acids, a Src-homology 3 (SH3) domain at the amino terminus, a few proline-rich motifs at the carboxyl terminus and a potential phosphatidylinositol trisphosphate (PtdInsP3)-interacting motif near its C terminus (Hasegawa et al.m 1996; Kobayashi et al 2001). Inactivation of the DHR-2 (also known as CZH2 or DOCKER) in DOCK1 can inhibit Rac activation, cell migration and clearance of apoptotic cells. This demonstrates the necessity and sufficiency of DHR-2 to promote GDP/GTP exchange on various GTPases. DHR-2 has been suggested to consist of about 500 residues (Brugnera et al., 2002; Cote and Vuori, 2002). DHR-2 domains of these family members have been shown to interact with the nucleotide-free form of Rho GTPase leading to the exchange of GDP for GTP(Meller et al., 2004; Lin et al., 2006; Miyamoto et al., 2006; Nishikimi et al 2005). DHR-1 domain (also known as CZH1) is located upstream of DHR-2 domain (Meller et al., 2002) and is a novel PtdIns (3,4,5)P3-binding module which directly interacts with phosphoinositides (PI),playing an important role in Rac-mediated cell polarity and migration including myoblast fusion(Cote and Vuori, 2002).
SH3 domains src-homology3 (SH3) domains are protein-protein interaction modules in intracellular signal transduction. DOCK1 contains an SH3 domain at its N-terminus. SH3 domains have been reported to bind to a proline-finch motif at the C-terminus of ELMO (gumienny et al., 2001) which will be regulating the activation status of DOCK1. In DOCK1, SH3 domain interacts with DHR-2 domain directly which is dependent on a proline-rich region in DHR-2 domain, but inhibits some functions of the DHR-2 domain, such as binding to nucleotide-free Rac and facilitating GTP loading(Lu et al., 2005).
Interaction with ELMO ELMO is an evolutionarily conserved upstream regulator of Rac that takes effect at the same step as DOCK 1 in phagocytosis of apoptotic cells and cell migration (Gumienny et al., 2001). DOCK2-5 and DOCK 1 have an amino-terminal Src homology (SH)-3 domain which can interact with ELMO proteins and cooperate to activate Rac (Grimsley et al., 2004; Hiramoto et al., 2006). Other Dock-related proteins such as DOCK 6-8 and DOCK9-11 cannot physically interact with ELMO proteins due to the lack of a recognizable SH3 domain. Some studies showed that deletion mutants of DOCK 180 that fail to bind to ELMO could not efficiently activate Rac even when over-expressed in cells (Grimsley et al., 2004). Other studies suggested that owing to auto-inhibition, the isolated DHR-2 appears to have much higher GEF activity than total DOCK 180 (Lu et al., 2005; Cote et al., 2007). Co-expression of ELMO is required to relieve the auto-inhibited state (Lu et al., 2004; Santy et al., 2005). The ELMO-DOCK1 complex is located in the cytoplasm and will be translocated to the cell membrane, which is the key step for DOCK1 to activate Rac (Debakker et al., 2004; Katoh and Negishi et al., 2003; Hasegawa et al., 1996; Katoh et al., 2006). All three mammalian ELMO 1-3 proteins have no obvious catalytic activity. They have three recognizable features including armadillo repeats at the N-terminus, an atypical PH domain and a complex prolin-rich region at the C-terminus. In fact, the functions of ELMO proteins in mediating Rac signaling remain largely unknown, and the interaction between ELMO and DOCK is still unclear. Some data indicate that there are two contact regions between DOCK1 and ELMO1. The atypical ELMO1 PH domain and an uncharacterized region between the SH3 and DHR-1 domains primarily interact with each other. This interaction is sufficient to promote complex formation. N-terminal SH3 domain of DOCK1 and the C-terminal PxxP motifs of ELMO1 are involved in the second contact (Komander et al., 2008). The PH domain and proline-rich motifs are implicated in binding to DOCK protein (Manishha et al., 2011). It has been documented that the SH3 domain of DOCK1 binds to a proline-rich (pro-rich) motif at the C-terminus of ELMO, and this in turn would activate DOCK 1. This is the second interaction. So when either of these motifs is mutated, the interaction of ELMO and DOCK1 is completely interrupted (Gumienny et al., 2011; Lu et al., 2005). The PH domain of ELMO stabilizes the DOCK1-nucleotide-free Rac complex through binding "in trans" instead of interacting directly with either Rac or DOCK 180 (Lu et al, 2004). The atypical PH domain of ELMO plays a crucial role in increasing the catalytic activity of DOCK 180 towards Rac. ELMO1 or ELMO2, could coexpress with DOCK1, and overexpression of ELMO1 together with DOCK1 synergistically enhances phagocytosis(Zhou et al., 2001). ELMO PH domain could slightly enhance the catalytic activity of DOCK 1 toward Rac by about twofold in vitro. But this effect could be efficient in vivo because the Ced-12 PH domain mutations let Ced-12-null worms failed to rescue the migration defects (Lu et al., 2004). Therefore, the mechanism of action of Elmo remains inconclusive. Further studies are required to clarify the controversies.
Binding to Crk Crk is an adaptor protein consisting mostly of SH2 and SH3 domains which is also involved in signaling processes, such as cell adhesions, differentiation, migration, proliferation, and phagocytosis of apoptotic cells (Clark and Brugge, 1995; Juliano and Haskill, 1993; Richardson and Parsons, 1995). Crk gene can be translated into two proteins, Crk-I and Crk-II which are primarily isolated as oncogenic products (Mayer etal., 1988; Matsuda et al., 1992). DOCK180/DOCK1 can bind with the SH3 of the Crk through PxxP region in its C-termini (Matsuda et al., 1996). It has been shown that DOCK 1 has two C-terminal CRK-binding sequences. DOCK1 binds with Crk on the basis of a biochemical interaction. The complex will be transiently translocated to the membrane resulting in changes in cell morphology (Hasegawa et al., 1996).
Essential for myoblast fusion Mammalian myogenesis arises from the fusion of mononucleated myoblasts. Myogenic cells fuse with each other to form multinucleated myotubes (Horsley and Pavlath, 2004). Myoblast fusion is responsible for development during embryogenesis and postnatal maintenance, growth, and helps regenerate injured tissue (Cerletti et al.m 2008; Rudnicki et al., 2008). Proper regulation of myoblast fusion events determines myofiber length, appropriate contractile capacity and muscle function(Allen et al., 1999). In fact, the understanding of myoblast fusion of higher vertebrates remains poor. Current knowledge is largely derived from genetic analyses performed in Drosophila(Chen and Olson, 2004; Taylor, 2003) and in vivo experiments in vertebrates (Cote and Vuori, 2007). In Drosophila melanogaster, fusion-competent myoblasts and founder cells regulate the formation of multinucleate muscle fibers. At cellular level, the processes of myoblast fusion include alignment, actin cytoskeleton rearrangement at the contact sites and membrane fusion (Knudsen and Horwitz, 1977; Wakelam, 1985; Peckham, 2008; Duan and Gallagher, 2009). CDM superfamily consists of founding members such as MBC, human DOCK1, Caenorhabditis elegans CED-5 (Wu and Horvitz, 1998) and almost 20 additional members (Cote and Vuori, 2002). Myoblast city (mbc) is highly important in Drosophila melanogaster embryo for multinucleate fibers formation. It has been reported that Mbc together with ELMO, function as an atypical bipartite GEF to directly control Rac1 in vivo. Drosophila eye experiments show that Mbc and ELMO interaction will increase the activity of Ras (Gersbrecht et al., 2008).
Expression DOCK1 is predominantly located in the cytoplasm of cells. Nuclear localization of DOCK1 has also been reported (Zhao et al., 2011).
Function This family is one of the GEFs being identified as activators of Rho GTPases (Takai etal., 1996; Hasegawa et al., 1996; Erickson and Cerione, 2004). DOCK1 activates Rho GTPase through facilitating the exchange of bound GDP for GTP. GTPases can regulate actin cytoskeleton and be accountable for crucial biological functions, such as cell phagocytosis, cell migration, cell proliferation, cell survival, cell polarity, axonal guidance, transcription and intracellular trafficking (Iwasato et al., 2007; Schmidt and Hall, 2002). In addition to playing an important role in a broad spectrum of biological processes, numerous studies have demonstrated contribution of DOCK members to the development of cancer.
Homology In mammals, dedicator of cytokinesis (DOCK) represents a new family of proteins comprising 11 members named DOCK1 (also known as Dock180) to Dock11. They are classified into four subfamilies denoted Dock-A, -B, -C, -D. 11 members are classified as following: DOCK-A subfamily (DOCK1, DOCK2 and DOCK5); DOCK-B subfamily (DOCK3 and DOCK4); DOCK-C subfamily (DOCK6, DOCK7 and DOCK8); DOCK-D subfamily (DOCK9, DOCK10 and DOCK11) (Bridget Biersmith et al, 2011).

Implicated in

Entity Breast cancer
Note Expression of DOCK1 correlates with poor survival for HER2+ and basal breast cancer patients (Eckhardt et al., 2012; Perou et al., 2000). Dock1 protein interacts with HER2 and enhances HER2-induced Rac activation and cell migration (Laurin et al., 2013).
Entity Glioblastoma
Note EGFR8, a constitutively active EGFR mutant, promotes glioma tumorigenesis and invasion through protein kinase A-dependent phosphorylation of DOCK1 (Feng H et al, 2014).
Entity Ovarian cancer
Note Correlation of high Dock1 expression with poor survival for patients has been reported. Dock1 overexpression contributes to enhanced ovarian cancer cell migration and invasion (Zhao F et al, 2011).
Entity Lung cancer
Note Dock1 can upregulate PTTG which could play a role in actin cytoskeleton remodeling, cell migration and induction of epithelial mesenchymal transition in lung cancer. The integrin alpha(V)beta(3)-FAK (focal adhesion kinase) signaling pathway is involved. (Shah PP et al, 2012).
Entity Gastric cancer
Note Among genes involved in extracellular signal-regulated kinase (ERK) downstream signaling pathways activated by Cytotoxin-associated antigen (CagA), a H. pylori immunoprotein, single nucleotide polymorphism of Dock1 was found to be significantly associated with risk of developing gastric cancer with marginal gene dose effects. (Yang JJ et al, 2011).


Myonuclear domains in muscle adaptation and disease
Allen DL, Roy RR, Edgerton VR
Muscle Nerve 1999 Oct;22(10):1350-60
PMID 10487900
The Cool-2/alpha-Pix protein mediates a Cdc42-Rac signaling cascade
Baird D, Feng Q, Cerione RA
Curr Biol 2005 Jan 11;15(1):1-10
PMID 15649357
Unconventional Rac-GEF activity is mediated through the Dock180-ELMO complex
Brugnera E, Haney L, Grimsley C, Lu M, Walk SF, Tosello-Trampont AC, Macara IG, Madhani H, Fink GR, Ravichandran KS
Nat Cell Biol 2002 Aug;4(8):574-82
PMID 12134158
Rho and Rac take center stage
Burridge K, Wennerberg K
Cell 2004 Jan 23;116(2):167-79
PMID 14744429
GEF what? Dock180 and related proteins help Rac to polarize cells in new ways
Côté JF, Vuori K
Trends Cell Biol 2007 Aug;17(8):383-93
PMID 17765544
Regulation and function of skeletal muscle stem cells
Cerletti M, Shadrach JL, Jurga S, Sherwood R, Wagers AJ
Cold Spring Harb Symp Quant Biol 2008;73:317-22
PMID 19204065
Towards a molecular pathway for myoblast fusion in Drosophila
Chen EH, Olson EN
Trends Cell Biol 2004 Aug;14(8):452-60
PMID 15308212
Integrins and signal transduction pathways: the road taken
Clark EA, Brugge JS
Science 1995 Apr 14;268(5208):233-9
PMID 7716514
Genetic analysis of myoblast fusion: blown fuse is required for progression beyond the prefusion complex
Doberstein SK, Fetter RD, Mehta AY, Goodman CS
J Cell Biol 1997 Mar 24;136(6):1249-61
PMID 9087441
Dependence of myoblast fusion on a cortical actin wall and nonmuscle myosin IIA
Duan R, Gallagher PJ
Dev Biol 2009 Jan 15;325(2):374-85
PMID 19027000
Strategies for the discovery and development of therapies for metastatic breast cancer
Eckhardt BL, Francis PA, Parker BS, Anderson RL
Nat Rev Drug Discov 2012 Jun 1;11(6):479-97
PMID 22653217
Structural elements, mechanism, and evolutionary convergence of Rho protein-guanine nucleotide exchange factor complexes
Erickson JW, Cerione RA
Biochemistry 2004 Feb 3;43(4):837-42
PMID 14744125
EGFRvIII stimulates glioma growth and invasion through PKA-dependent serine phosphorylation of Dock180
Feng H, Hu B, Vuori K, Sarkaria JN, Furnari FB, Cavenee WK, Cheng SY
Oncogene 2014 May 8;33(19):2504-12
PMID 23728337
Regulation of the Cool/Pix proteins: key binding partners of the Cdc42/Rac targets, the p21-activated kinases
Feng Q, Albeck JG, Cerione RA, Yang W
J Biol Chem 2002 Feb 15;277(7):5644-50
PMID 11741931
Novel regulatory mechanisms for the Dbl family guanine nucleotide exchange factor Cool-2/alpha-Pix
Feng Q, Baird D, Cerione RA
EMBO J 2004 Sep 1;23(17):3492-504
PMID 15306850
Drosophila ELMO/CED-12 interacts with Myoblast city to direct myoblast fusion and ommatidial organization
Geisbrecht ER, Haralalka S, Swanson SK, Florens L, Washburn MP, Abmayr SM
Dev Biol 2008 Feb 1;314(1):137-49
PMID 18163987
Dock180 and ELMO1 proteins cooperate to promote evolutionarily conserved Rac-dependent cell migration
Grimsley CM, Kinchen JM, Tosello-Trampont AC, Brugnera E, Haney LB, Lu M, Chen Q, Klingele D, Hengartner MO, Ravichandran KS
J Biol Chem 2004 Feb 13;279(7):6087-97
PMID 14638695
CED-12/ELMO, a novel member of the CrkII/Dock180/Rac pathway, is required for phagocytosis and cell migration
Gumienny TL, Brugnera E, Tosello-Trampont AC, Kinchen JM, Haney LB, Nishiwaki K, Walk SF, Nemergut ME, Macara IG, Francis R, Schedl T, Qin Y, Van Aelst L, Hengartner MO, Ravichandran KS
Cell 2001 Oct 5;107(1):27-41
PMID 11595183
Catalysis of guanine nucleotide exchange on the CDC42Hs protein by the dbl oncogene product
Hart MJ, Eva A, Evans T, Aaronson SA, Cerione RA
Nature 1991 Nov 28;354(6351):311-4
PMID 1956381
DOCK180, a major CRK-binding protein, alters cell morphology upon translocation to the cell membrane
Hasegawa H, Kiyokawa E, Tanaka S, Nagashima K, Gotoh N, Shibuya M, Kurata T, Matsuda M
Mol Cell Biol 1996 Apr;16(4):1770-6
PMID 8657152
Dock4 is regulated by RhoG and promotes Rac-dependent cell migration
Hiramoto K, Negishi M, Katoh H
Exp Cell Res 2006 Dec 10;312(20):4205-16
PMID 17027967
Forming a multinucleated cell: molecules that regulate myoblast fusion
Horsley V, Pavlath GK
Cells Tissues Organs 2004;176(1-3):67-78
Rac-GAP alpha-chimerin regulates motor-circuit formation as a key mediator of EphrinB3/EphA4 forward signaling
Iwasato T, Katoh H, Nishimaru H, Ishikawa Y, Inoue H, Saito YM, Ando R, Iwama M, Takahashi R, Negishi M, Itohara S
Cell 2007 Aug 24;130(4):742-53
PMID 17719550
Signal transduction from the extracellular matrix
Juliano RL, Haskill S
J Cell Biol 1993 Feb;120(3):577-85
PMID 8381117
Activation of Rac1 by RhoG regulates cell migration
Katoh H, Hiramoto K, Negishi M
J Cell Sci 2006 Jan 1;119(Pt 1):56-65
RhoG activates Rac1 by direct interaction with the Dock180-binding protein Elmo
Katoh H, Negishi M
Nature 2003 Jul 24;424(6947):461-4
PMID 12879077
Activation of Rac1 by a Crk SH3-binding protein, DOCK180
Kiyokawa E, Hashimoto Y, Kobayashi S, Sugimura H, Kurata T, Matsuda M
Genes Dev 1998 Nov 1;12(21):3331-6
PMID 9808620
The RhoA- and CDC42-specific exchange factor Dbs promotes expansion of immature thymocytes and deletion of double-positive and single-positive thymocytes
Klinger MB, Guilbault B, Kay RJ
Eur J Immunol 2004 Mar;34(3):806-16
PMID 14991610
Tandem events in myoblast fusion
Knudsen KA, Horwitz AF
Dev Biol 1977 Jul 15;58(2):328-38
PMID 885292
Membrane recruitment of DOCK180 by binding to PtdIns(3,4,5)P3
Kobayashi S, Shirai T, Kiyokawa E, Mochizuki N, Matsuda M, Fukui Y
Biochem J 2001 Feb 15;354(Pt 1):73-8
PMID 11171081
An alpha-helical extension of the ELMO1 pleckstrin homology domain mediates direct interaction to DOCK180 and is critical in Rac signaling
Komander D, Patel M, Laurin M, Fradet N, Pelletier A, Barford D, Côté JF
Mol Biol Cell 2008 Nov;19(11):4837-51
PMID 18768751
Rac-specific guanine nucleotide exchange factor DOCK1 is a critical regulator of HER2-mediated breast cancer metastasis
Laurin M, Huber J, Pelletier A, Houalla T, Park M, Fukui Y, Haibe-Kains B, Muller WJ, Côté JF
Proc Natl Acad Sci U S A 2013 Apr 30;110(18):7434-9
PMID 23592719
Identification of a DOCK180-related guanine nucleotide exchange factor that is capable of mediating a positive feedback activation of Cdc42
Lin Q, Yang W, Baird D, Feng Q, Cerione RA
J Biol Chem 2006 Nov 17;281(46):35253-62
PMID 16968698
A Steric-inhibition model for regulation of nucleotide exchange via the Dock180 family of GEFs
Lu M, Kinchen JM, Rossman KL, Grimsley C, Hall M, Sondek J, Hengartner MO, Yajnik V, Ravichandran KS
Curr Biol 2005 Feb 22;15(4):371-7
PMID 15723800
Interaction between the amino-terminal SH3 domain of CRK and its natural target proteins
Matsuda M, Ota S, Tanimura R, Nakamura H, Matuoka K, Takenawa T, Nagashima K, Kurata T
J Biol Chem 1996 Jun 14;271(24):14468-72
Two species of human CRK cDNA encode proteins with distinct biological activities
Matsuda M, Tanaka S, Nagata S, Kojima A, Kurata T, Shibuya M
Mol Cell Biol 1992 Aug;12(8):3482-9
PMID 1630456
A novel viral oncogene with structural similarity to phospholipase C
Mayer BJ, Hamaguchi M, Hanafusa H
Nature 1988 Mar 17;332(6161):272-5
The novel Cdc42 guanine nucleotide exchange factor, zizimin1, dimerizes via the Cdc42-binding CZH2 domain
Meller N, Irani-Tehrani M, Ratnikov BI, Paschal BM, Schwartz MA
J Biol Chem 2004 Sep 3;279(36):37470-6
PMID 15247287
Dock6, a Dock-C subfamily guanine nucleotide exchanger, has the dual specificity for Rac1 and Cdc42 and regulates neurite outgrowth
Miyamoto Y, Yamauchi J, Sanbe A, Tanoue A
Exp Cell Res 2007 Feb 15;313(4):791-804
PMID 17196961
MOCA induces membrane spreading by activating Rac1
Namekata K, Enokido Y, Iwasawa K, Kimura H
J Biol Chem 2004 Apr 2;279(14):14331-7
PMID 14718541
Molecular and immunohistochemical analysis of signaling adaptor protein Crk in human cancers
Nishihara H, Tanaka S, Tsuda M, Oikawa S, Maeda M, Shimizu M, Shinomiya H, Tanigami A, Sawa H, Nagashima K
Cancer Lett 2002 Jun 6;180(1):55-61
PMID 11911970
Zizimin2: a novel, DOCK180-related Cdc42 guanine nucleotide exchange factor expressed predominantly in lymphocytes
Nishikimi A, Meller N, Uekawa N, Isobe K, Schwartz MA, Maruyama M
FEBS Lett 2005 Feb 14;579(5):1039-46
PMID 15710388
Myoblast city, the Drosophila homolog of DOCK180/CED-5, is required in a Rac signaling pathway utilized for multiple developmental processes
Nolan KM, Barrett K, Lu Y, Hu KQ, Vincent S, Settleman J
Genes Dev 1998 Nov 1;12(21):3337-42
PMID 9808621
Myoblasts and macrophages share molecular components that contribute to cell-cell fusion
Pajcini KV, Pomerantz JH, Alkan O, Doyonnas R, Blau HM
J Cell Biol 2008 Mar 10;180(5):1005-19
PMID 18332221
Opening up on ELMO regulation: New insights into the control of Rac signaling by the DOCK180/ELMO complex
Patel M, Pelletier A, Côté JF
Small GTPases 2011 Sep;2(5):268-275
PMID 22292130
Engineering a multi-nucleated myotube, the role of the actin cytoskeleton
Peckham M
J Microsc 2008 Sep;231(3):486-93
PMID 18755004
Molecular portraits of human breast tumours
Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lønning PE, Børresen-Dale AL, Brown PO, Botstein D
Nature 2000 Aug 17;406(6797):747-52
PMID 10963602
Structural basis of membrane targeting by the Dock180 family of Rho family guanine exchange factors (Rho-GEFs)
Premkumar L, Bobkov AA, Patel M, Jaroszewski L, Bankston LA, Stec B, Vuori K, Côté JF, Liddington RC
J Biol Chem 2010 Apr 23;285(17):13211-22
PMID 20167601
Signal transduction through integrins: a central role for focal adhesion kinase? Bioessays
Richardson A, Parsons JT
1995 Mar;17(3):229-36 Review
PMID 7748177
Myoblast fusion: when it takes more to make one
Rochlin K, Yu S, Roy S, Baylies MK
Dev Biol 2010 May 1;341(1):66-83
PMID 19932206
GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors
Rossman KL, Der CJ, Sondek J
Nat Rev Mol Cell Biol 2005 Feb;6(2):167-80
PMID 15688002
The molecular regulation of muscle stem cell function
Rudnicki MA, Le Grand F, McKinnell I, Kuang S
Cold Spring Harb Symp Quant Biol 2008;73:323-31
PMID 19329572
The DOCK180/Elmo complex couples ARNO-mediated Arf6 activation to the downstream activation of Rac1
Santy LC, Ravichandran KS, Casanova JE
Curr Biol 2005 Oct 11;15(19):1749-54
PMID 16213822
Guanine nucleotide exchange factors for Rho GTPases: turning on the switch
Schmidt A, Hall A
Genes Dev 2002 Jul 1;16(13):1587-609
PMID 12101119
PTTG induces EMT through integrin αVβ3-focal adhesion kinase signaling in lung cancer cells
Shah PP, Fong MY, Kakar SS
Oncogene 2012 Jun 28;31(26):3124-35
PMID 22081074
Identification of the protein encoded by the human diffuse B-cell lymphoma (dbl) oncogene
Srivastava SK, Wheelock RH, Aaronson SA, Eva A
Proc Natl Acad Sci U S A 1986 Dec;83(23):8868-72
PMID 3491366
Chromosomal mapping of the gene encoding DOCK180, a major Crk-binding protein, to 10q26
Takai S, Hasegawa H, Kiyokawa E, Yamada K, Kurata T, Matsuda M
13-q26 3 by fluorescence in situ hybridization
PMID 8661160
Muscle differentiation: signalling cell fusion
Taylor MV
Curr Biol 2003 Dec 16;13(24):R964-6
PMID 14680655
The fusion of myoblasts
Wakelam MJ
Biochem J 1985 May 15;228(1):1-12
PMID 3890835
Crystal structure of the DH/PH fragment of Dbs without bound GTPase
Worthylake DK, Rossman KL, Sondek J
Structure 2004 Jun;12(6):1078-86
PMID 15274927
Wu YC, Horvitz HR
elegans phagocytosis and cell-migration protein CED-5 is similar to human DOCK180 Nature
PMID 9548255
DOCK4, a GTPase activator, is disrupted during tumorigenesis
Yajnik V, Paulding C, Sordella R, McClatchey AI, Saito M, Wahrer DC, Reynolds P, Bell DW, Lake R, van den Heuvel S, Settleman J, Haber DA
Cell 2003 Mar 7;112(5):673-84
PMID 12628187
Oncogenic CagA promotes gastric cancer risk via activating ERK signaling pathways: a nested case-control study
Yang JJ, Cho LY, Ma SH, Ko KP, Shin A, Choi BY, Han DS, Song KS, Kim YS, Chang SH, Shin HR, Kang D, Yoo KY, Park SK
PLoS One 2011;6(6):e21155
PMID 21698158
Overexpression of dedicator of cytokinesis I (Dock180) in ovarian cancer correlated with aggressive phenotype and poor patient survival
Zhao F, Siu MK, Jiang L, Tam KF, Ngan HY, Le XF, Wong OG, Wong ES, Chan HY, Cheung AN
Histopathology 2011 Dec;59(6):1163-72
PMID 22175896
The C
Zhou Z, Caron E, Hartwieg E, Hall A, Horvitz HR
elegans PH domain protein CED-12 regulates cytoskeletal reorganization via a Rho/Rac GTPase signaling pathway Dev Cell
PMID 11703939
Phagocytosis of apoptotic cells is regulated by a UNC-73/TRIO-MIG-2/RhoG signaling module and armadillo repeats of CED-12/ELMO
deBakker CD, Haney LB, Kinchen JM, Grimsley C, Lu M, Klingele D, Hsu PK, Chou BK, Cheng LC, Blangy A, Sondek J, Hengartner MO, Wu YC, Ravichandran KS
Curr Biol 2004 Dec 29;14(24):2208-16
PMID 15620647


This paper should be referenced as such :
Ping Li, Fung Zhao, Annie N Cheung
DOCK1 (Dedicator of cytokinesis 1)
Atlas Genet Cytogenet Oncol Haematol. 2016;20(3):115-120.
Free journal version : [ pdf ]   [ DOI ]

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  t(3;11)(p25;p15) ANKRD28::NUP98

External links


HGNC (Hugo)DOCK1   2987
Entrez_Gene (NCBI)DOCK1    dedicator of cytokinesis 1
AliasesDOCK180; ced5
GeneCards (Weizmann)DOCK1
Ensembl hg19 (Hinxton)ENSG00000150760 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000150760 [Gene_View]  ENSG00000150760 [Sequence]  chr10:126905428-127452516 [Contig_View]  DOCK1 [Vega]
ICGC DataPortalENSG00000150760
TCGA cBioPortalDOCK1
Genatlas (Paris)DOCK1
SOURCE (Princeton)DOCK1
Genetics Home Reference (NIH)DOCK1
Genomic and cartography
GoldenPath hg38 (UCSC)DOCK1  -     chr10:126905428-127452516 +  10q26.2   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)DOCK1  -     10q26.2   [Description]    (hg19-Feb_2009)
GoldenPathDOCK1 - 10q26.2 [CytoView hg19]  DOCK1 - 10q26.2 [CytoView hg38]
Genome Data Viewer NCBIDOCK1 [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AI951513 AK091673 AL157538 AW298149 BC084559
RefSeq transcript (Entrez)NM_001290223 NM_001377543 NM_001377544 NM_001377546 NM_001377547 NM_001377548 NM_001377550 NM_001377553 NM_001377554 NM_001377556 NM_001377558 NM_001377560 NM_001377561 NM_001380
Consensus coding sequences : CCDS (NCBI)DOCK1
Gene ExpressionDOCK1 [ NCBI-GEO ]   DOCK1 [ EBI - ARRAY_EXPRESS ]   DOCK1 [ SEEK ]   DOCK1 [ MEM ]
Gene Expression Viewer (FireBrowse)DOCK1 [ Firebrowse - Broad ]
GenevisibleExpression of DOCK1 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)1793
GTEX Portal (Tissue expression)DOCK1
Human Protein AtlasENSG00000150760-DOCK1 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ14185   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ14185  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ14185
Domaine pattern : Prosite (Expaxy)C2_DOCK (PS51650)    DOCKER (PS51651)    SH3 (PS50002)   
Domains : Interpro (EBI)ARM-type_fold    C2_domain_sf    DHR-1_domain    DHR-2    DOCK    DOCK_C    DOCK_C_lobe_A    DOCK_C_lobe_C    DOCK_N    DOCK_N_sub1    SH3-like_dom_sf    SH3_domain   
Domain families : Pfam (Sanger)DHR-2 (PF06920)    DOCK-C2 (PF14429)    DOCK_N (PF16172)    SH3_1 (PF00018)   
Domain families : Pfam (NCBI)pfam06920    pfam14429    pfam16172    pfam00018   
Domain families : Smart (EMBL)SH3 (SM00326)  
Conserved Domain (NCBI)DOCK1
PDB Europe3L4C   
PDB (PDBSum)3L4C   
PDB (IMB)3L4C   
Structural Biology KnowledgeBase3L4C   
SCOP (Structural Classification of Proteins)3L4C   
CATH (Classification of proteins structures)3L4C   
AlphaFold pdb e-kbQ14185   
Human Protein Atlas [tissue]ENSG00000150760-DOCK1 [tissue]
Protein Interaction databases
IntAct (EBI)Q14185
Ontologies - Pathways
Ontology : AmiGOguanyl-nucleotide exchange factor activity  GTPase activator activity  protein binding  nucleoplasm  cytoplasm  cytosol  cytosol  phagocytosis, engulfment  apoptotic process  signal transduction  integrin-mediated signaling pathway  small GTPase mediated signal transduction  blood coagulation  positive regulation of epithelial cell migration  membrane  nuclear speck  SH3 domain binding  guanyl-nucleotide exchange factor complex  Fc-gamma receptor signaling pathway involved in phagocytosis  vascular endothelial growth factor receptor signaling pathway  regulation of catalytic activity  positive regulation of substrate adhesion-dependent cell spreading  
Ontology : EGO-EBIguanyl-nucleotide exchange factor activity  GTPase activator activity  protein binding  nucleoplasm  cytoplasm  cytosol  cytosol  phagocytosis, engulfment  apoptotic process  signal transduction  integrin-mediated signaling pathway  small GTPase mediated signal transduction  blood coagulation  positive regulation of epithelial cell migration  membrane  nuclear speck  SH3 domain binding  guanyl-nucleotide exchange factor complex  Fc-gamma receptor signaling pathway involved in phagocytosis  vascular endothelial growth factor receptor signaling pathway  regulation of catalytic activity  positive regulation of substrate adhesion-dependent cell spreading  
Pathways : BIOCARTASignaling of Hepatocyte Growth Factor Receptor [Genes]   
Pathways : KEGGFocal adhesion    Regulation of actin cytoskeleton    Bacterial invasion of epithelial cells    Shigellosis   
REACTOMEQ14185 [protein]
REACTOME PathwaysR-HSA-983231 [pathway]   
NDEx NetworkDOCK1
Atlas of Cancer Signalling NetworkDOCK1
Wikipedia pathwaysDOCK1
Orthology - Evolution
GeneTree (enSembl)ENSG00000150760
Phylogenetic Trees/Animal Genes : TreeFamDOCK1
Homologs : HomoloGeneDOCK1
Homology/Alignments : Family Browser (UCSC)DOCK1
Gene fusions - Rearrangements
Fusion : MitelmanDOCK1::APBA1 [10q26.2/9q21.11]  
Fusion : MitelmanDOCK1::DPCD [10q26.2/10q24.32]  
Fusion : MitelmanDOCK1::MGMT [10q26.2/10q26.3]  
Fusion : MitelmanDOCK1::PCDH15 [10q26.2/10q21.1]  
Fusion : MitelmanDOCK1::PPAPDC1A [10q26.2/10q26.12]  
Fusion : MitelmanFUOM::DOCK1 [10q26.3/10q26.2]  
Fusion : MitelmanGALNT16::DOCK1 [14q24.1/10q26.2]  
Fusion : QuiverDOCK1
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerDOCK1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)DOCK1
Exome Variant ServerDOCK1
GNOMAD BrowserENSG00000150760
Varsome BrowserDOCK1
ACMGDOCK1 variants
Genomic Variants (DGV)DOCK1 [DGVbeta]
DECIPHERDOCK1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisDOCK1 
ICGC Data PortalDOCK1 
TCGA Data PortalDOCK1 
Broad Tumor PortalDOCK1
OASIS PortalDOCK1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICDOCK1  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DDOCK1
Mutations and Diseases : HGMDDOCK1
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)DOCK1
DoCM (Curated mutations)DOCK1
CIViC (Clinical Interpretations of Variants in Cancer)DOCK1
NCG (London)DOCK1
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry DOCK1
NextProtQ14185 [Medical]
Target ValidationDOCK1
Huge Navigator DOCK1 [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTDDOCK1
Pharm GKB GenePA27453
Clinical trialDOCK1
DataMed IndexDOCK1
PubMed103 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Oct 8 21:16:26 CEST 2021

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