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FLASH GENE

Symbol

FZD8

contributors: npt/mct - updated : 04-09-2013

HGNC name	frizzled homolog 8 (Drosophila)
HGNC id	4046

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	10p11.21      Physical location : 35.927.176 - 35.930.362
Synonym symbol(s)	FZD4S, FZ-8, hFZ8

DNA

TYPE	functioning gene
STRUCTURE	3.19 kb     1 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	Binding site
text structure	ELK1- and PAX4-binding sites in the promoter

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_031866 1 - 3186 NP_114072 73.2 694 - 2001 11295046

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 Cardiovascular heart       moderately Endocrine pancreas       highly   parathyroid       highly Lymphoid/Immune thymus       highly Reproductive female system uterus cervix   highly Urinary kidney       highly Visual eye       predominantly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial secretory glandular endocrine   Epithelial secretory glandular exocrine   Lymphoid         Muscular striatum cardiac     Muscular striatum skeletal

cell lineage
cell lines	cervical uterus and lung cancers cell lines
fluid/secretion

at STAGE

physiological period

fetal

Text	kidney, brain and lung, highly

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	an N-terminal signal peptide
	two Asn-linked glycosylation sites within the N-terminal extracellular region
	lys-thr-X-X-X-thr motif involved in the activation of the WNT/beta-catenin signaling pathway
	a fz domain involved in binding with WNT ligands
	a CRD
	seven transmenbrane domains
	three N-linked glycosylation sites
	a C-terminal ser/thr-X-val motif which is a binding site for scaffold proteins with multiple PDZ domains

conjugated

GlycoP

HOMOLOGY

interspecies	homolog to rattus Fzd8 (97.2 pc)
	homolog to murine Fzd8 (96.9 pc)

intraspecies

homolog to FZD5

Homologene

FAMILY

FZ/SMO family of G-protein coupled receptor

CATEGORY

receptor membrane G

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,Golgi
text	multi-pass membrane protein

basic FUNCTION	acting as a receptor for WNT proteins
	coupled to the beta-catenin canonical signaling pathway, leading to the activation of dishvelled proteins, inhibition of GSK3 kinase, nuclear accumulation of beta-catenin and activation of WNT target genes
	playing a role in several types of human cancer through activation of the beta-catenin-TCF pathway
	may be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues
	may be functionally important for aberrant activation of the canonical Wnt signaling pathway in human lung cancer cells
	may play an important role in aberrant activation of the canonical Wnt pathway which is critical for the proliferation and survival of lung cancer cells
	FZD5 and FZD8 are involved in dose-dependent regulation of signaling in optic fissure/disc formation and progenitor expansion

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

development

PATHWAY

metabolism

signaling

signal transduction

Wnt signaling pathway

a component

INTERACTION

DNA

RNA

small molecule

protein	WNT receptor
	scaffold proteins with multiple PDZ domains
	interacting with GOPC
	interacting with RSPO1 and RSPO3
	binding to IGFBP4
	IGFBP4 physically interacted with FZD8, and a Wnt co-receptor, LRP6, and inhibited the binding of WNT3A to FZD8 and LRP6
	interacting with INVS (INVS is essential for the morphogenesis of the proximal and intermediate pronephric system and relays Frizzled-8–dependent signals to recruit Dishevelled to the plasma membrane)

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in cervical uterus and lung cancers tumoral     --over   in acute lymphoblastic leukaemia (ALL)

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer lung   putative therapeutic target for human lung cancer

ANIMAL & CELL MODELS