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FLASH GENE

Symbol

ATP7A

contributors: mct - updated : 01-10-2017

HGNC name	ATPase, Cu++ transporting, alpha polypeptide (Menkes syndrome)
HGNC id	869

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	DSMAX distal, spinal muscular atrophy, recessive MNK Menkes syndrome OHS occipital horn syndrome, cutis laxa
Location	Xq21.1      Physical location : 77.166.193 - 77.305.891
Synonym name	Copper pump 1
	Copper-transporting ATPase 1
	Menkes disease-associated protein
	Cu++-transporting P-type ATPase
Synonym symbol(s)	ATPP1, MK, MC1, SMAX3, FLJ17790
EC.number	3.6.3.4, 3.6.3.10

DNA

TYPE	functioning gene
SPECIAL FEATURE
text	PGAM1P embedded in large (60kb) intron 1, see symbol
STRUCTURE	139.70 kb     23 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_000052 23 - 8488 NP_000043 163.3 1500 - 2010 20333435

EXPRESSION

Type	ubiquitous

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         Homo sapiens Reproductive female system placenta       Homo sapiens   male system testis       Homo sapiens Respiratory lung         Homo sapiens Urinary kidney         Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo

Text	essential for notochord development

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	six repeats of the heavy metal-associated sequence GMTCXXC in the N terminus
	eight transmembrane spanning segments, with a Golgi localization signal in the third transmembrane domain, missing in the alternatively spliced form
	a di-leucine motif at the C terminus (essential for the basal perinuclear localization of ATP7A)

conjugated

MetalloP

HOMOLOGY

interspecies	homolog to rattus Atp7a (89.27 pc)
	homolog to murine Atp7a (89.54 pc)
	homolog to drosophila ATP7A (51.07 pc)

Homologene

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

CATEGORY

enzyme , transport carrier

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,organelle,Golgi
	intracellular,cytoplasm,organelle,endosome
	intracellular,cytoplasm,cytosolic
text	the trans-Golgi network of all tissues except liver for the full length protein and in the endoplasmic reticulum for the spliced form
	localization between the trans-Golgi network and the plasma membrane that may be regulated by the accumulation of the adducts with ATOX1
	resides in the trans-Golgi network (TGN) and transports cytoplasmic copper to that compartment for incorporation into copper enzymes, and relocates to the plasma membrane (PM) of cells in response to increased intracellular concentration of this metal

basic FUNCTION	copper binding P-type ATPase 7A, involved in subcellular transport and copper efflux
	rapidly relocalized to the plasma membrane using a C teminal di-leucine endocytic signal in case of elevated copper levels
	incorporating the copper in cuproenzyme like cytochrome oxidase, dopamine B-hydroxylase, lysyl oxydase
	play a central role in distribution of copper in the central nervous system
	may be having an important role of transporter in motor-neuron maintenance and function
	play a previously unrecognized role in the pathogenesis of atherosclerosis
	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
	P-type ATPase that regulates cellular copper homeostasis by activity at the trans-Golgi network (TGN) and plasma membrane (PM)
	ATP7A normally traffics down axons and mediates copper release from the axonal membrane of motor neurons
	trans-Golgi, copper-transporting ATPase that traffics to the plasma membrane during copper overload to promote efflux

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

development

text	Cu2+ transport
	notochord development

PATHWAY

metabolism

metal

signaling

a component

INTERACTION

DNA

RNA

small molecule	metal binding,
	Cu2+

protein	tyrosinase, copper dependent enzyme (activation of tyrosinase)
	interaction between ATOX1 and a metal-binding domain in ATP7A
	interacting with CLU (chaperone-like role for clusterin in facilitating the degradation of ATP7A, ATP7B)
	ATP7A-mediated copper homeostasis is important for the formation of pathogenic proteinase-resistant prion protein
	COX19 is necessary for the transduction of a SCO1-dependent mitochondrial redox signal that regulates ATP7A-mediated cellular copper efflux
	important role for both COMMD1 and CCDC22 in copper homeostasis and ATP7A trafficking
	DBH-containing neurons express both ATP7A and ATP7B

cell & other

REGULATION

Other

mechanism of ATP7A regulation in which copper stabilizes the protein, possibly complementing HIF2A-mediated transcriptional induction during iron deficiency

ASSOCIATED DISORDERS

corresponding disease(s)

MNK , OHS , DSMAX

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --low   contributes to impaired SOD3 activity, resulting in O2(•-) overproduction and endothelial dysfunction in blood vessels of T1 diabetes mellitus constitutional germinal mutation       mutation can delay the onset of prion disease

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed diabete metabolic syndrom   restoring copper transporter function is an essential therapeutic approach for oxidant stress-dependent vascular and metabolic diseases

ANIMAL & CELL MODELS