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FLASH GENE
Symbol ATP7A contributors: mct - updated : 01-10-2014
HGNC name ATPase, Cu++ transporting, alpha polypeptide (Menkes syndrome)
HGNC id 869
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
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    23 - 8488 163.3 1500 - 2010 20333435
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrain     Homo sapiens
    Reproductivefemale systemplacenta    Homo sapiens
     male systemtestis    Homo sapiens
    Respiratorylung     Homo sapiens
    Urinarykidney     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
  • 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)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein 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
    SystemTypeDisorderPubmed
    diabetemetabolic syndrom 
    restoring copper transporter function is an essential therapeutic approach for oxidant stress-dependent vascular and metabolic diseases
    ANIMAL & CELL MODELS