ATP7A ATPase copper transporting alpha [Homo sapiens (human)] - Gene

Summary

Official Symbol: ATP7Aprovided by HGNC
Official Full Name: ATPase copper transporting alphaprovided by HGNC
Primary source: HGNC:HGNC:869
See related: Ensembl:ENSG00000165240 MIM:300011; Vega:OTTHUMG00000021885
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: MK; MNK; DSMAX; SMAX3
Summary: This gene encodes a transmembrane protein that functions in copper transport across membranes. This protein is localized to the trans Golgi network, where it is predicted to supply copper to copper-dependent enzymes in the secretory pathway. It relocalizes to the plasma membrane under conditions of elevated extracellular copper, and functions in the efflux of copper from cells. Mutations in this gene are associated with Menkes disease, X-linked distal spinal muscular atrophy, and occipital horn syndrome. Alternatively-spliced transcript variants have been observed. [provided by RefSeq, Aug 2013]
Expression: Ubiquitous expression in skin (RPKM 5.4), thyroid (RPKM 2.9) and 25 other tissues See more
Orthologs: mouse all

Genomic context

Location:: Xq21.1

Exon count:: 23

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	X	NC_000023.11 (77910656..78050395)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	X	NC_000023.10 (77166194..77305892)

Chromosome X - NC_000023.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Jun 15 11:32:44 2016

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

the severity of MD correlate with cellular localization of ATP7A and support previous studies indicating that phosphorylation is crucial for the exit of ATP7A from TGN, while dephosphorylation is crucial for recycling back to TGN.
Title: Characterization of ATP7A missense mutants suggests a correlation between intracellular trafficking and severity of Menkes disease.
We determined in silico that all the mutations leading to the classical Menkes disease leave no residual activity of ATP7A including the apparently less severe in-frame deletions. Whereas milder forms of the disease are characterized by mutations that allow a limited residual activity of ATP7A, including the nonsense mutation observed.
Title: 13 novel putative mutations in ATP7A found in a cohort of 25 Italian families.
Candidate RNAi screen revealed copper-transporting ATPase (ATP7A) as a target for inducing cisplatin sensitivity.
Title: Ammonium tetrathiomolybdate treatment targets the copper transporter ATP7A and enhances sensitivity of breast cancer to cisplatin.
Mnk inhibition enhances apoptotic activity of cytarabine in acute myeloid leukemia cells
Title: Inhibition of Mnk enhances apoptotic activity of cytarabine in acute myeloid leukemia cells.
The authors conclude that the ATP7A interactome encompasses a novel Golgi-localized conserved oligomeric Golgi (COG) complex-dependent mechanism to specify neuronal development and survival.
Title: The interactome of the copper transporter ATP7A belongs to a network of neurodevelopmental and neurodegeneration factors.
Mutation in ATP7A gene is associated with X-linked distal hereditary motor neuropathy.
Title: Characterizing the molecular phenotype of an Atp7a(T985I) conditional knock in mouse model for X-linked distal hereditary motor neuropathy (dHMNX).
MNK orchestrates counterbalancing forces that regulate mTORC1 enzymatic activity.
Title: MNK Controls mTORC1:Substrate Association through Regulation of TELO2 Binding with mTORC1.
11 single-nucleotide polymorphisms (SNPs) in CTR1, CTR2, ATP7A, and ATP7B were genotyped in these patients.
Title: Association between polymorphisms in CTR1, CTR2, ATP7A, and ATP7B and platinum resistance in epithelial ovarian cancer.
The P-type copper ATPases ATP7A and ATP7B provide an important system for acquisition, active transport, distribution and elimination of copper. Relevance of copper metabolism to human diseases and therapy is already known. It is quite certain that further studies will reveal detailed and useful information on biochemical mechanisms and relevance to diseases
Title: Molecular features of copper binding proteins involved in copper homeostasis.
the mechanism of copper-dependent regulation of ATP7B and ATP7A, the roles of individual MBDs, and the relationship between the regulatory and catalytic copper binding are still unknown. We describe the structure and dynamics of the MBDs, review the current knowledge about their functional roles and propose a mechanism of regulation of ATP7B by copper-dependent changes in the dynamics and conformation of the MBD chain.
Title: Dynamics of the metal binding domains and regulation of the human copper transporters ATP7B and ATP7A.

Submit: New GeneRIF Correction See all GeneRIFs (100)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Cutis laxa, X-linked MedGen: C0268353 OMIM: 304150 GeneReviews: ATP7A-Related Copper Transport Disorders	Compare labs
Distal spinal muscular atrophy, X-linked 3 MedGen: C1845359 OMIM: 300489 GeneReviews: ATP7A-Related Copper Transport Disorders	Compare labs
Menkes kinky-hair syndrome MedGen: C0022716 OMIM: 309400 GeneReviews: ATP7A-Related Copper Transport Disorders	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated (2012-05-17) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated (2012-05-17) ClinGen Genome Curation Page

Variation

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See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from BioSystems

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Antimicrobial peptides, organism-specific biosystem (from REACTOME)
Antimicrobial peptides, organism-specific biosystemAntimicrobial peptides (AMPs) are small molecular weight proteins with broad spectrum of antimicrobial activity against bacteria, viruses, and fungi (Zasloff M 2002; Radek K & Gallo R 2007). The majo...
Cellular responses to stress, organism-specific biosystem (from REACTOME)
Cellular responses to stress, organism-specific biosystemCells are subject to external molecular and physical stresses such as foreign molecules that perturb metabolic or signaling processes, and changes in temperature or pH. The ability of cells and tissu...
Copper homeostasis, organism-specific biosystem (from WikiPathways)
Copper homeostasis, organism-specific biosystemCopper is a redox-active transition metal and an essential trace element for life. It is a catalytic cofactor for numerous enzymes involved in critical biological processes (eg. detoxyfication by oxy...
Detoxification of Reactive Oxygen Species, organism-specific biosystem (from REACTOME)
Detoxification of Reactive Oxygen Species, organism-specific biosystemReactive oxygen species such as superoxide (O2.-), peroxides (ROOR), singlet oxygen, peroxynitrite (ONOO-), and hydroxyl radical (OH.) are generated by cellular processes such as respiration (reviewe...
Immune System, organism-specific biosystem (from REACTOME)
Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
Innate Immune System, organism-specific biosystem (from REACTOME)
Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
Ion channel transport, organism-specific biosystem (from REACTOME)
Ion channel transport, organism-specific biosystemIon channels mediate the flow of ions across the plasma membrane of cells. They are integral membrane proteins, typically a multimer of proteins, which, when arranged in the membrane, create a pore f...
Ion influx/efflux at host-pathogen interface, organism-specific biosystem (from REACTOME)
Ion influx/efflux at host-pathogen interface, organism-specific biosystemEssential metal ions act as co-factors that enable enzymes to catalyse a wider range of chemical transformations than would be achievable using solely organic catalysts. The precise metal requirement...
Ion transport by P-type ATPases, organism-specific biosystem (from REACTOME)
Ion transport by P-type ATPases, organism-specific biosystemThe P-type ATPases (E1-E2 ATPases) are a large group of evolutionarily related ion pumps that are found in bacteria, archaea and eukaryotes. They are referred to as P-type ATPases because they catal...
Mineral absorption, organism-specific biosystem (from KEGG)
Mineral absorption, organism-specific biosystemMinerals are one of the five fundamental groups of nutrients needed to sustain life. Of the minerals, calcium plays innumerable roles in our bodies, serving as a main component of bone as well as an ...
Mineral absorption, conserved biosystem (from KEGG)
Mineral absorption, conserved biosystemMinerals are one of the five fundamental groups of nutrients needed to sustain life. Of the minerals, calcium plays innumerable roles in our bodies, serving as a main component of bone as well as an ...
Platinum drug resistance, organism-specific biosystem (from KEGG)
Platinum drug resistance, organism-specific biosystemPlatinum-based drugs cisplatin, carboplatin and oxaliplatin are widely used in the therapy of solid malignancies, including testicular, ovarian, head and neck, colorectal, bladder and lung cancers. T...
Platinum drug resistance, conserved biosystem (from KEGG)
Platinum drug resistance, conserved biosystemPlatinum-based drugs cisplatin, carboplatin and oxaliplatin are widely used in the therapy of solid malignancies, including testicular, ovarian, head and neck, colorectal, bladder and lung cancers. T...
Transmembrane transport of small molecules, organism-specific biosystem (from REACTOME)
Transmembrane transport of small molecules, organism-specific biosystem
Transmembrane transport of small molecules

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

GDB:435280 (e-PCR)
- UniSTS:157219

GDB:435283 (e-PCR)
- UniSTS:157220

GDB:435290 (e-PCR)
- UniSTS:157222

GDB:435294 (e-PCR)
- UniSTS:157223

DXS6743 (e-PCR)
- UniSTS:51241

G18202 (e-PCR)
- UniSTS:50490

ATP7A__4401 (e-PCR)
- UniSTS:471355

L77252 (e-PCR)
- UniSTS:20550

L47618 (e-PCR)
- UniSTS:20551

L18426 (e-PCR)
- UniSTS:34648

D1S1425 (e-PCR)
- UniSTS:149621

GDB:437238 (e-PCR)
- UniSTS:99447

G10612 (e-PCR)
- UniSTS:33412

DXS986 (e-PCR), detects polymorphism
- UniSTS:32649

D11S3114 (e-PCR)
- UniSTS:152207

L17877 (e-PCR)
- UniSTS:61334

Atp7a (e-PCR), detects polymorphism
- UniSTS:516512

SHGC-8964 (e-PCR)
- UniSTS:69287

DXS990 (e-PCR), detects polymorphism
- UniSTS:13738

L17971 (e-PCR)
- UniSTS:43966

AL023617 (e-PCR)
- UniSTS:47558

DXS1494 (e-PCR)
- UniSTS:99810

SHGC-31483 (e-PCR)
- UniSTS:42981

GDB:392043 (e-PCR)
- UniSTS:157183

Homology

Homologs of the ATP7A gene: The ATP7A gene is conserved in chimpanzee, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, C.elegans, S.cerevisiae, K.lactis, S.pombe, M.oryzae, N.crassa, A.thaliana, and rice.
Orthologs from Annotation Pipeline: 223 organisms have orthologs with human gene ATP7A
The Hierarchical Catalog of Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
ATP binding	TAS Traceable Author Statement more info	PubMed
Rac GTPase binding	IEA Inferred from Electronic Annotation more info
chaperone binding	IEA Inferred from Electronic Annotation more info
copper ion binding	IDA Inferred from Direct Assay more info	PubMed
copper ion transmembrane transporter activity	ISS Inferred from Sequence or Structural Similarity more info
copper-dependent protein binding	IPI Inferred from Physical Interaction more info	PubMed
copper-exporting ATPase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
copper-exporting ATPase activity	ISS Inferred from Sequence or Structural Similarity more info
copper-transporting ATPase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cuprous ion binding	IMP Inferred from Mutant Phenotype more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
superoxide dismutase copper chaperone activity	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
ATP hydrolysis coupled cation transmembrane transport	IEA Inferred from Electronic Annotation more info
T-helper cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
blood vessel development	ISS Inferred from Sequence or Structural Similarity more info
blood vessel remodeling	ISS Inferred from Sequence or Structural Similarity more info
cartilage development	ISS Inferred from Sequence or Structural Similarity more info
catecholamine metabolic process	ISS Inferred from Sequence or Structural Similarity more info
cellular copper ion homeostasis	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cellular copper ion homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
cellular response to amino acid stimulus	IEA Inferred from Electronic Annotation more info
cellular response to antibiotic	IEA Inferred from Electronic Annotation more info
cellular response to cadmium ion	IEA Inferred from Electronic Annotation more info
cellular response to cobalt ion	IEA Inferred from Electronic Annotation more info
cellular response to copper ion	IEA Inferred from Electronic Annotation more info
cellular response to hypoxia	IEA Inferred from Electronic Annotation more info
cellular response to iron ion	IEA Inferred from Electronic Annotation more info
cellular response to lead ion	IEA Inferred from Electronic Annotation more info
cellular response to platelet-derived growth factor stimulus	IEA Inferred from Electronic Annotation more info
central nervous system neuron development	ISS Inferred from Sequence or Structural Similarity more info
cerebellar Purkinje cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
collagen fibril organization	ISS Inferred from Sequence or Structural Similarity more info
copper ion export	IBA Inferred from Biological aspect of Ancestor more info	PubMed
copper ion export	ISS Inferred from Sequence or Structural Similarity more info
copper ion import	ISS Inferred from Sequence or Structural Similarity more info
copper ion transport	IMP Inferred from Mutant Phenotype more info	PubMed
detoxification of copper ion	ISS Inferred from Sequence or Structural Similarity more info
dopamine metabolic process	ISS Inferred from Sequence or Structural Similarity more info
elastic fiber assembly	ISS Inferred from Sequence or Structural Similarity more info
elastin biosynthetic process	ISS Inferred from Sequence or Structural Similarity more info
epinephrine metabolic process	ISS Inferred from Sequence or Structural Similarity more info
extracellular matrix organization	ISS Inferred from Sequence or Structural Similarity more info
hair follicle morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
in utero embryonic development	IEA Inferred from Electronic Annotation more info
lactation	IEA Inferred from Electronic Annotation more info
liver development	IEA Inferred from Electronic Annotation more info
locomotory behavior	ISS Inferred from Sequence or Structural Similarity more info
lung alveolus development	ISS Inferred from Sequence or Structural Similarity more info
mitochondrion organization	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of catalytic activity	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of iron ion transmembrane transport	IEA Inferred from Electronic Annotation more info
neuron projection morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
norepinephrine metabolic process	ISS Inferred from Sequence or Structural Similarity more info
peptidyl-lysine modification	ISS Inferred from Sequence or Structural Similarity more info
pigmentation	ISS Inferred from Sequence or Structural Similarity more info
plasma membrane copper ion transport	IEA Inferred from Electronic Annotation more info
positive regulation of catalytic activity	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of cell size	IEA Inferred from Electronic Annotation more info
positive regulation of epithelial cell proliferation	IEA Inferred from Electronic Annotation more info
positive regulation of lamellipodium assembly	IEA Inferred from Electronic Annotation more info
positive regulation of oxidoreductase activity	IDA Inferred from Direct Assay more info	PubMed
positive regulation of response to wounding	IEA Inferred from Electronic Annotation more info
positive regulation of vascular associated smooth muscle cell migration	IEA Inferred from Electronic Annotation more info
pyramidal neuron development	ISS Inferred from Sequence or Structural Similarity more info
regulation of cytochrome-c oxidase activity	IEA Inferred from Electronic Annotation more info
regulation of gene expression	IEA Inferred from Electronic Annotation more info
regulation of oxidative phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
removal of superoxide radicals	ISS Inferred from Sequence or Structural Similarity more info
response to iron(III) ion	IEA Inferred from Electronic Annotation more info
response to manganese ion	IEA Inferred from Electronic Annotation more info
response to zinc ion	IEA Inferred from Electronic Annotation more info
serotonin metabolic process	ISS Inferred from Sequence or Structural Similarity more info
skin development	ISS Inferred from Sequence or Structural Similarity more info
tryptophan metabolic process	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
apical plasma membrane	IEA Inferred from Electronic Annotation more info
basolateral plasma membrane	IDA Inferred from Direct Assay more info	PubMed
brush border membrane	IEA Inferred from Electronic Annotation more info
cell leading edge	IEA Inferred from Electronic Annotation more info
cytosol	IEA Inferred from Electronic Annotation more info
endoplasmic reticulum	IEA Inferred from Electronic Annotation more info
integral component of membrane	IEA Inferred from Electronic Annotation more info
late endosome	IDA Inferred from Direct Assay more info	PubMed
membrane	HDA more info	PubMed
membrane raft	IEA Inferred from Electronic Annotation more info
microvillus	IEA Inferred from Electronic Annotation more info
neuron projection	ISS Inferred from Sequence or Structural Similarity more info
neuronal cell body	ISS Inferred from Sequence or Structural Similarity more info
nucleus	IEA Inferred from Electronic Annotation more info
perikaryon	IEA Inferred from Electronic Annotation more info
perinuclear region of cytoplasm	IBA Inferred from Biological aspect of Ancestor more info	PubMed
perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed
phagocytic vesicle membrane	TAS Traceable Author Statement more info
plasma membrane	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	TAS Traceable Author Statement more info
secretory granule	IEA Inferred from Electronic Annotation more info
trans-Golgi network	IBA Inferred from Biological aspect of Ancestor more info	PubMed
trans-Golgi network	IDA Inferred from Direct Assay more info	PubMed
trans-Golgi network transport vesicle	IMP Inferred from Mutant Phenotype more info	PubMed

General protein information

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Preferred Names: copper-transporting ATPase 1

Names: ATPase, Cu++ transporting, alpha polypeptide; Cu++-transporting P-type ATPase; Menkes disease-associated protein; copper pump 1

NP_000043.4

EC 3.6.3.54

NP_001269153.1

EC 3.6.3.54

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_013224.2 RefSeqGene

Range

4960..144699

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000052.6 → NP_000043.4 copper-transporting ATPase 1 isoform 1

See identical proteins and their annotated locations for NP_000043.4

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (1).

Source sequence(s)

AB117973, AK299449, AL356235, AL645821, BU753163, DB164588, L06476

Consensus CDS

CCDS35339.1

UniProtKB/Swiss-Prot

Q04656

UniProtKB/TrEMBL

B4DRW0, Q762B6

Related

ENSP00000345728.6, OTTHUMP00000023593, ENST00000341514.10, OTTHUMT00000057306

Conserved Domains (4) summary

COG2217
Location:566 → 1389

ZntA; Cation transport ATPase [Inorganic ion transport and metabolism]

cd00371
Location:380 → 443

HMA; Heavy-metal-associated domain (HMA) is a conserved domain of approximately 30 amino acid residues found in a number of proteins that transport or detoxify heavy metals, for example, the CPx-type heavy metal ATPases and copper chaperones. HMA domain ...

pfam00122
Location:786 → 1033

E1-E2_ATPase; E1-E2 ATPase

cl21460
Location:1198 → 1341

HAD_like; Haloacid Dehalogenase-like Hydrolases
NM_001282224.1 → NP_001269153.1 copper-transporting ATPase 1 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon, compared to variant 1. The encoded isoform (2) is shorter than isoform 1. This variant is supported by data in PMIDs 7490081 and 10970802.

Source sequence(s)

AB117973, AK299449, AL356235, AL645821, BU753163, DB164588, L06476

Consensus CDS

CCDS75997.1

UniProtKB/Swiss-Prot

Q04656

UniProtKB/TrEMBL

B4DRW0, Q762B6

Related

ENSP00000343026.5, ENST00000343533.9

Conserved Domains (4) summary

COG2217
Location:566 → 1311

ZntA; Cation transport ATPase [Inorganic ion transport and metabolism]

cd00371
Location:380 → 443

HMA; Heavy-metal-associated domain (HMA) is a conserved domain of approximately 30 amino acid residues found in a number of proteins that transport or detoxify heavy metals, for example, the CPx-type heavy metal ATPases and copper chaperones. HMA domain ...

pfam00122
Location:711 → 955

E1-E2_ATPase; E1-E2 ATPase

cl21460
Location:1120 → 1263

HAD_like; Haloacid Dehalogenase-like Hydrolases

RNA

NR_104109.1 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks multiple consecutive internal exons, compared to variant 1. This variant is represented as non-coding because it lacks a large portion of the coding region found in variant 1. This variant is supported by data in PMID 9693104.

Source sequence(s)

AB117973, AK299449, AL356235, AL645821, BU753163, DB164588