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FLASH GENE

Symbol

ATP7B

contributors: mct - updated : 26-03-2015

HGNC name	ATPase, Cu++ transporting, beta polypeptide
HGNC id	870

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	WND Wilson disease
Location	13q14.3      Physical location : 52.506.805 - 52.585.630
Synonym name	ATPase, Cu++ transporting, beta polypeptide (Wilson disease)
	Wilson disease
	Copper pump 2
	Wilson disease-associated protein
	copper-transporting ATPase 2
Synonym symbol(s)	ATPP2, WNDP, WD, WC1, PWD
EC.number	3.6.3.4

DNA

TYPE	functioning gene
STRUCTURE	78.83 kb     21 Exon(s)

10 Kb 5' upstream gene genomic sequence study

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_000053 21 splicing 6644 NP_000044 157.3 1465 - 2008 18637198 NM_001005918 17 splicing 6023 NP_001005918 133.5 1258 trans Golgi network 2008 18637198 lacking exons 6, 7, 8 & 12 variant 3 - - - isoform 3 140 ? mitochondria - also called ATP7B mt post translational cleavage at the N terminus of ATP7R

EXPRESSION

Type	restricted

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 liver       predominantly Nervous brain       highly

cells

System Cell Pubmed Species Stage Rna symbol Nervous Purkinje cell

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

pregnancy

Text

placenta

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	extended N-terminus protruding into the cytosol with six N-terminal cytosolic copper-binding domains (CXXC) contained within an approximately 72 amino acid consensus motif and the first four of these domains, denoted WLN1-4, are implicated in copper acquisition from the metallochaperone HAH1
	metal-binding site 2 (MBS2) in the N-terminal domain, retaining copper much better than ATOX1, and this may facilitate the metal transfer process
	eight transmembrane spanning segments (6TM)
	a phosphorylation domain (DKTGTIT) and a phosphatase domain [TGE]

conjugated

MetalloP

HOMOLOGY

interspecies	homolog to rattus Atp7b (83.12 pc)
	homolog to murine Atp7b (83.52 pc)

intraspecies

homolog to MNK

Homologene

FAMILY	cation transport ATPase (P-type) family
	type IB subfamily

CATEGORY

enzyme , protooncogene , transport carrier

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endosome
	intracellular,cytoplasm,cytosolic
text	late endosome-associated membrane protein
	translocate copper from the cytosol to the late endosomal lumen, thus participating in biliary copper excretion via lysosomes

basic FUNCTION	central to hepatic and systemic copper homeostasis
	involved in subcellular transport and copper efflux
	copper-transporting ATPase regulating distribution of copper in the liver, mediating the excretion of excess copper from hepatocytes into bile
	might play an important role in physiological sweat production
	role for renal ATP7B in intracellular copper storage
	play a central role in distribution of copper in the central nervous system
	P 1B-type ATPase involved in copper homeostasis
	transport Cu across cellular membranes for biosynthetic and protective functions, enabling Cu to fulfill its role as a catalytic and structural cofactor for many essential enzymes, and to prevent a toxic build-up of Cu inside cells
	one of the major determinants responsible for copper homeostasis

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

cellular trafficking transport

PATHWAY

metabolism

signaling

a component	ATP7B interaction with DCTN4 is a key component of the copper-induced trafficking pathway that delivers ATP7B to subapical vesicles of hepatocytes for the removal of excess copper into bile
	ability of ATOX1 to form a complex only with some domains of ATP7B is an interesting property of this class of proteins and may have a signaling role in the function of the ATPases

INTERACTION

DNA

RNA

small molecule	metal binding,
	copper Cu2+
	ATP

protein	linking copper-translocation activity with copper-induced intracellular trafficking of ATP7B
	interacting with ATOX1, a cytosolic metallochaperone that delivers copper
	COMMD1 maintains the amount of ATP7b and facilitates recruitment of ATP7B from cytoplasmic vesicles to the trans-Golgi network membrane
	interacting with GLRX, having important new roles in redox regulation of the Cu-ATPases, through modulation of Cu binding by the Cu-ATPase cysteine motifs
	interacting with CLU (chaperone-like role for clusterin in facilitating the degradation of ATP7A, ATP7B)
	DBH-containing neurons express both ATP7A and ATP7B

cell & other

REGULATION

Other	formed after proleolytic cleavage at the N terminus of ATP7B
	ATP7B trafficking is regulated with its copper-translocation cycle, with cytosolic vesicular localization associated with the acyl-phosphate intermediate

ASSOCIATED DISORDERS

corresponding disease(s)

WND

related resource

Wilson disease Mutation Database Wilson's Disease at GeneDis

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in breast carcinoma poorly differentiated and with chemoresistance to cisplatin

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed metabolism copper   ATP7B overexpression provides an important selection advantage to mesenchymal stem cells in high copper microenvironments, and may represent novel cell transplants for therapy of Wilson disease

ANIMAL & CELL MODELS