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FLASH GENE

Symbol

DOCK2

contributors: mct/pgu - updated : 06-09-2017

HGNC name	dedicator of cyto-kinesis 2
HGNC id	2988

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	IMD40 Immunodeficiency 40
Location	5q35.1      Physical location : 169.064.250 - 169.510.384
Synonym name	dedicator of cyto-kinesis 2
Synonym symbol(s)	KIAA0209, FLJ46592

DNA

TYPE	functioning gene
STRUCTURE	446.13 kb     52 Exon(s)

10 Kb 5' upstream gene genomic sequence study

motif	Viral sequence   long terminal repeat
text structure	specific HERV-K LTR within intron 30

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_004946 52 - 6117 NP_004937 211.8 1830 - 2010 20350533

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Lymphoid/Immune spleen       highly Homo sapiens   thymus       highly Homo sapiens Nervous brain         Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic       predominantly Homo sapiens Blood / hematopoietic plasma       Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic leukocyte Homo sapiens Blood/Hematopoietic mature hematopoietic Homo sapiens Blood/Hematopoietic progenitor cell Homo sapiens Lymphoid/Immune macrophage Homo sapiens Nervous glia Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	SH3 domain at the N terminus
	a DHR-1 domain for binding to PIP3 and mediating the GTP-GDP exchange reaction for Rac
	a DOCK homology region (DHR)-2 (CZH2 or Docker domain)

mono polymer

dimer

HOMOLOGY

interspecies	homolog to murine Dock2 (95.2pc)
	homolog to rattus Dock2 (93.8pc)

intraspecies

homolog to DOCK180, CED5

Homologene

FAMILY	CDM protein family
	DOCK family

CATEGORY

regulatory

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm
	intracellular,nucleus
text	upon stimulation, translocates to the plasma membrane in a phosphatidylinositol 3,4,5 triphosphate-dependent manner

basic FUNCTION	being indispensable for lymphocyte chemotaxis
	activating RAC1 in non-adherent cells
	playing a critical role in lymphocyte migration by regulating actin cytoskeleton through Rac activation
	playing a significant role in bone marrow lymphopoiesis, but is dispensable for hematopoietic stem/progenitor cell engraftment
	major Rac GEF that controls motility and polarity during neutrophil chemotaxis
	regulates microglial innate immunity independent of PTGS2 induction and DOCK2+ microglia are associated with human AD pathology
	regulating the cell proliferation in B cell lymphoma through RAC1 and MAPK activation thus having a prominent role in hematopoietic malignancy regulates cell motility and cytokine production through the activation of RAC1 in hematopoietic cells and plays a pivotal role in the modulation of the immune system
	role for DOCK2 in proliferation of hormone-refractory CXCR5-positive psostate carcinoma cells
	activate the Rho-family GTPases RAC1 and CDC42 to control cell migration, morphogenesis, and phagocytosis
	hematopoietic cell-specific, atypical guanine nucleotide exchange factor, controls lymphocyte migration through ras-related C3 botulinum toxin substrate (Rac) activation
	mediates the GTP-GDP exchange reaction for RAC1 via its DOCK homology region (DHR)-2
	modulates microglia cytokine secretion, phagocytosis, and paracrine neurotoxicity
	DOCK2 contributes to APP plaque burden via regulation of microglial innate immune function
	DOCK5 acts with DOCK2 in neutrophils to regulate multiple cellular functions
	DOCK2 and DOCK5 act additively in neutrophils to regulate chemotaxis, superoxide production, and extracellular trap formation
	is a novel regulator for vascular smooth muscle cell (SMC) phenotypic modulation and vascular lesion formation after vascular injury
	is involved in cell motility, polarity, adhesion, proliferation, and apoptosis, and is essential for lymphocyte migration and activation as well as neutrophil chemotaxis
	key molecule for lymphocyte activation and migration

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

DOCK2 dimerization is functionally important under the physiological condition where only limited amounts of DOCK2 and RAC1 are localized to the plasma membrane

INTERACTION

DNA

RNA

small molecule

protein	binding to RAC1 in non adherent cells
	associating with engulfment and cell motility (ELMO1) through its Src-homology 3 (SH3) domain (critical for DOCK2-mediated Rac activation)
	links T cell receptor signals to downregulation of IL4R to control the lineage commitment of CD4+ T cells
	interacting with Rac2 and Cdc42 (specifically recognize Rac2 and Cdc42 through its switch 1 as well as 2-3regions)
	the entire regions of both DOCK2 and ELMO1 assemble to create a rigid structure, which is required for the DOCK2/ELMO1 binding, that is structural basis by which DOCK2 and ELMO1 mutually relieve their autoinhibition for the activation of RAC1 for lymphocyte chemotaxis
	PREX1, acting as a GEF for RHOG, regulates RAC1-dependent functions indirectly through RHOG-dependent recruitment of DOCK2
	role for ELMO1 in controlling DOCK2 levels and DOCK2-dependent T cell migration in primary lymphocytes

cell & other

REGULATION

Other

DOCK2 dynamics are sequentially regulated by distinct phospholipids to localize to Rac activation during neutrophils chemotaxis

ASSOCIATED DISORDERS

corresponding disease(s)

IMD40

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed neurology neurodegenerative alzheimer DOCK2 is a COX2 expression-independent therapeutic target for neurodegenerative diseases such as AD immunology     therapeutic target for immunologic disorders caused by lymphocyte infiltration cancer hemopathy   is a potential therapeutic target for novel AML treatments, as this protein regulates the survival of leukemia cells with elevated FLT3 activity and sensitizes FLT3/ITD leukemic cells to conventional antileukemic agents

ANIMAL & CELL MODELS

T-lymphoid progenitor cells in fetal mice express two closely related CDM family molecules, Dock2 and Dock1, and and the impaired fetal thymus colonization in mice deficient for Dock2 and Dock1 was not as severe as that in mice doubly deficient for Ccr7 and Ccr9