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FLASH GENE

Symbol

DDX6

contributors: mct - updated : 08-10-2019

HGNC name	DEAD (Asp-Glu-Ala-Asp) box polypeptide 6
HGNC id	2747

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_004397 14 - 6246 NP_004388 54.4 483 - 1992 1579499 NM_001257191 14 - 6173 NP_001244120 - 483 - 1992 1579499

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 Nervous brain       lowly Homo sapiens   brain hindbrain cerebellum     Homo sapiens Reproductive female system breast mammary gland   highly   male system testis     highly Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Nervous neuron Homo sapiens Reproductive spermatid Homo sapiens Reproductive spermatocyte Homo sapiens

cell lineage
cell lines	neuroblastoma cell lines
fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	DEAD/H box (Asp-Glu-Ala-Asp/His)
	an helicase ATP-binding domain, an ATPase/helicase motif essential for viral replication
	a C terminal RNA helicase domain, and C-terminal RecA-like domain

HOMOLOGY

interspecies	homolog to Drosophila oocyte specific helicase ME31
	homolog to murine Ddx6 (97,7pc)

Homologene

FAMILY	DEAD box helicase family
	DDX6/DHH1 subfamily

CATEGORY

enzyme , RNA associated

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleolus
text	in spermatogenic cells, localizes to both the nucleus and cytoplasm

basic FUNCTION	shuttling protein involved in nuclear assembly of stored mRNP particles
	in the process of mRNA degradation, may play a role in mRNA decapping
	possibly involved in the replication of hepatitis C virus genomes in hepatocytes and in tumourigenesis of hepatocellular carcinomas
	DEAD-box RNA helicase with ATP-dependent RNA-unwinding activity
	it is possible that DDX6 may be an important driver of the aggregation process within P bodies (was shown to be essential for P-body formation in human cells)
	is required for efficient genome packaging of foamy virus, a spumaretrovirus
	located at the 5prime extremity of mRNA can then recruit the decapping complex, thus coupling translational repression and mRNA degradation
	reduction of DDX6 under prolonged hypoxia activates expression of proangiogenic VEGFA that is critical in fast growing tissues during normal development and in pathologic processes
	is present in nuage and non-nuage structures as well as nuclei, suggesting that DDX6 has diverse functions in spermatogenic cells
	having versatile functions in mRNA metabolism, which characterize them as important post-transcriptional regulators of gene expression
	DDX6 is necessary and sufficient for neuronal differentiation and that it functions in cooperation with TRIM32
	conserved DEAD-box protein (DBP) that plays central roles in cytoplasmic RNA regulation, including processing body (P-body) assembly, mRNA decapping, and translational repression
	has a variety of functions such as translation initiation, pre-mRNA splicing, and ribosome assembly
	parental mRNA clearance is a prerequisite for cellular reprogramming and that DDX6 plays a central role in this process
	is an essential component of membrane-less organelles called processing bodies (PBs)
	plays a key role in adult progenitors where it controls the balance between self-renewal and differentiation in a context-dependent manner

CELLULAR PROCESS	cell life, proliferation/growth

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	component of P-bodies and stress granules, representing cellular structures of mRNA triage
	EIF4E/EIF4ENIF1 complex is present in granules with the processing body proteins LSM1 and DDX6, and disruption of this complex causes premature and enhanced neurogenesis and neural precursor depletion

INTERACTION

DNA

RNA

small molecule

protein	interacting with ATXN2
	interacts with argonaute proteins, EIF2C1, EIF2C2
	interacting with EDC3 (DDX6 C-terminal RecA-like domain bound to a highly conserved FDF sequence motif in the decapping activator EDC3)
	general translational repressor DDX6 may cooperate with ZFP36 to regulate AU-rich elements (AREs)-mRNA translation
	ATXN2L associates with known interaction partners of ATXN2, the RNA helicase DDX6 and the poly(A)-binding protein, and with ATXN2 itself
	hypoxia-induced DDX6 reduction positively affects proangiogenic VEGFA expression
	CNOT1 modulates the conformation of DDX6 and stimulates ATPase activity
	can remodel and release nuclear DMPK messenger ribonucleoprotein foci, leading to normalization of pathogenic alternative splicing events
	DDX6 binds to a conserved CNOT1 subdomain in a manner resembling the interaction of the translation initiation factor EIF4A with EIF4G
	CNOT1 facilitates recruitment of DDX6 to miRNA-targeted mRNAs, placing DDX6 as a downstream effector in the miRNA silencing pathway
	TRIM32 associates with proteins involved in neurogenesis and RNA-related processes, such as the RNA helicase DDX6, which has been implicated in microRNA regulation
	interacts with the CNOT complex and functions in concert with several post-transcriptional regulators, including EDC3, and EIF4ENIF1
	EIF4ENIF1 through conserved CUP-homology domain (CHD) interacts directly with DDX6 in both the presence and absence of the central MIF4G domain of CNOT1
	DDX6-EIF4ENIF1 interaction mediates translational repression and P-body assembly
	DDX6 protein acted as an RNA-binding protein for ERBB2 and FGFR2 mRNAs and positively regulated their post-transcriptional processes

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

IDDF

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in intestine, colon, rectum adenocarcinomas tumoral   translocation     translocated in B-cell lymphoma, RCK gene (RC-K8 cell line) target of the translocation t(11;14)(q23;q32) constitutional     --over   in hepatitis C virus-related chronic hepatitis constitutional     --low   under hypoxia contributes to the activation of VEGFA expression and promotes its proangiogenic function

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS