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FLASH GENE

Symbol

DOCK1

contributors: mct - updated : 31-12-2018

HGNC name	dedicator of cytokinesis 1
HGNC id	2987

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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 Digestive mouth tongue     highly Endocrine pancreas       highly   parathyroid       highly Reproductive female system placenta     highly   female system ovary     highly   male system testis       Homo sapiens Respiratory lung       highly   respiratory tract larynx     highly Urinary kidney       highly Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Reproductive Sertoli cell Homo sapiens Urinary podocyte Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

pregnancy

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a SH3 domain (signal transduction)
	two conserved domains, called DOCK homology region (DHR)-1 and -2 , DHR1 is required for binding to phosphoinositides
	and DHR2 (CZH-2) is necessary and sufficient for the GEF activity

conjugated

PhosphoP

HOMOLOGY

interspecies

homolog to murine Dock1 (96.5pc)

Homologene

FAMILY	DOCK180-family proteins
	CZH proteins family

CATEGORY

adaptor

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,endosome
text	associating with cell membrane when farnesylated
	colocalizing with CRK-II and ELMO1 in membrane ruffles
	colocalized with DOCK1 at endosomes

basic FUNCTION	engulfment and removal of cells undergoing apoptosis
	involved in cytoskeletal rearrangements required for phagocytosis of apoptotic cells and cell motility
	implicated in cell migration, phagocytosis of apoptotic cells, T-cell activation and neurite outgrowth, and probably arose relatively early in eukaryotic evolution
	functionning as a GRF, which activates Rac Rho small GTPases
	essential role in mediating attractive resposnes by neurons to netrin 1
	plays an essential role in a wide variety of biological functions including cell migration, phagocytosis of apoptotic cells, and myoblast fusion
	regulates cation-independent mannose 6-phosphate receptor (CI-MPR) trafficking via SNX5 and this function is independent of its guanine nucleotide exchange factor activity toward RAC1
	has an essential role in embryonic development
	DOCK1 and DOCK5 are critical regulators of the fusion step during primary myogenesis
	ELMO1 and DOCK1 function through the RAC1 GTPase in hippocampal neurons
	DOCK1 and DOCK5 are not the important exchange factors regulating RAC1 activity during the establishment and maintenance of the glomerular barrier

CELLULAR PROCESS	cell life, cell death/apoptosis
	cell organization/biogenesis

PHYSIOLOGICAL PROCESS

text	cytoskeletal rearrangements during phagocytosis and cell motility, in the late steps of apoptotic process (complementation group 2 in C elegans)

PATHWAY

metabolism

signaling

a component	RHOG-ELMO-DOCK1 pathway is required for activation of RAC1 and cell spreading mediated by integrin, as well as for neurite outgrowth induced by nerve growth factor
	forms a trimeric complex with ELMO1 and BAI1
	ELMO1/DOCK1 complex functions through Rac1 in various cellular contexts including migration and phagocytosis

INTERACTION

DNA

RNA

small molecule

protein	binding to CRK and ELMO1
	activating RAC1
	DOCK1-ELMO1 interaction is necessary to modulate actin cytoskeleton for phagocytosis and cell migration
	GRASP and IPCEF1 promote ARF-to-RAC1 signaling and cell migration by coordinating the association of CYTH2 with DOCK1
	ELMO1 is necessary for functions of DOCK1, functioning in a complex with DOCK1 in spine morphogenesis through activating the RAC1 GTPase
	DOCK1 is required for signaling by ELMO1-MACF1
	GRASP binds directly both CYTH2 and DOCK1 to coordinate their activities, and by doing so promotes crosstalk between ARF and RAC1
	unlike DOCK5, DOCK1 bound to phosphatidic acid (PA) through the C-terminal polybasic amino acid cluster and was localized to dorsal ruffles

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in acute myeloid leukemia with increased mortality

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

T-lymphoid progenitor cells in fetal mice express two closely related CDM family molecules, Dock2 and Dock1, 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