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FLASH GENE

Symbol

ZNRF3

contributors: mct - updated : 03-01-2019

HGNC name	zinc and ring finger 3
HGNC id	18126

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	22q12.1      Physical location : 29.279.889 - 29.453.475
Synonym name	RING finger protein 203
	novel C3HC4 type Zinc finger (ring finger)
Synonym symbol(s)	KIAA1133, BK747E2.3, FLJ22057, RNF203
EC.number	6.3.2.-

DNA

TYPE	functioning gene
STRUCTURE	173.72 kb     9 Exon(s)

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_001206998 9 - 6696 NP_001193927 - 936 - 2001 11318611 NM_032173 9 - 6489 NP_115549 90 836 - 2001 11318611

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 intestine large intestine colon   highly   liver       moderately   mouth tongue     predominantly   stomach       moderately Nervous brain       moderately Reproductive female system placenta     moderately   male system testis     moderately   male system prostate     highly Respiratory lung       moderately   respiratory tract larynx     highly Urinary bladder       moderately   kidney       moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

pregnancy

Text

placenta

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

a RING-type zinc finger

HOMOLOGY

interspecies

homolog to RNF43

Homologene

FAMILY

CATEGORY

unknown/unspecified

SUBCELLULAR LOCALIZATION

plasma membrane

basic FUNCTION	RNF43 and ZNRF3 reduce Wnt signals by selectively ubiquitinating frizzled receptors, thereby targeting these Wnt receptors for degradation
	membrane-located tumourigenesis inhibitors RNF43 and ZNRF3 mediating the degradation of the Wnt receptor components FZDS and LRP5/6
	RNF43 (RING finger protein 43) and ZNRF3 (zinc/RING finger protein 3) (RZ) are two closely related transmembrane E3 ligases, encoded by WNT target genes, that remove surface WNT (wingless-int) receptors
	important but distinct functions of RNF43/ZNRF3 in regulating taste versus lingual epithelial tissue homeostasis

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule	metal binding,
	Zn2+

protein	associated with the Wnt receptor complex, and inhibits Wnt signalling by promoting the turnover of frizzled and LRP6
	RSPO1 mimics ZNRF3 inhibition by increasing the membrane level of Wnt receptors
	RSPO1 interacts with the extracellular domain of ZNRF3 and induces the association between ZNRF3 and LGR4, which results in membrane clearance of ZNRF3
	RSPO1 interacts with ZNRF3/RNF43 and LGR4 through distinct motifs
	ZNRF3 binds RSPO1 and LGR5-RSPO1 with micromolar affinity via RSPO1 furin-like 1 (Fu1) domain
	RSPO2 interacts with LGR5 to stabilize the membrane-associated zinc and ring finger 3 (ZNRF3)
	DVL1 is a dual function adaptor to recruit negative regulators ZNRF3/RNF43 to Wnt receptors to ensure proper control of pathway activity
	ZNRF3/RNF43--a direct linkage of extracellular recognition and E3 ligase activity to modulate cell surface signalling
	RSPO2, serves as a direct antagonistic ligand to RNF43 and ZNRF3, which together constitute a master switch that governs limb specification
	ZNRF3 and RNF43 cooperate to safeguard liver homeostasis by spatially and temporally restricting WNT/CTNNB activity, balancing metabolic function and hepatocyte proliferation
	LGR6 expression appeared to be downregulated by the ubiquitin-proteasome system involving ZNRF3

cell & other

REGULATION

ASSOCIATED DISORDERS

ANIMAL & CELL MODELS