Atp7a ATPase, Cu++ transporting, alpha polypeptide [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Atp7aprovided by MGI
Official Full Name: ATPase, Cu++ transporting, alpha polypeptideprovided by MGI
Primary source: MGI:MGI:99400
See related: Ensembl:ENSMUSG00000033792 AllianceGenome:MGI:99400
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: MNK
Summary: Enables P-type divalent copper transporter activity and superoxide dismutase copper chaperone activity. Acts upstream of or within several processes, including animal organ development; cellular biogenic amine metabolic process; and copper ion transport. Located in several cellular components, including cytoplasmic vesicle membrane; neuronal cell body; and trans-Golgi network membrane. Is expressed in several structures, including genitourinary system; gut mucosa; liver; spleen; and thoracic ganglion. Used to study Menkes disease; X-linked distal spinal muscular atrophy 3; aortic aneurysm; and osteoarthritis. Human ortholog(s) of this gene implicated in Menkes disease; X-linked distal spinal muscular atrophy 3; cutis laxa; and occipital horn syndrome. Orthologous to human ATP7A (ATPase copper transporting alpha). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Broad expression in placenta adult (RPKM 10.0), liver E18 (RPKM 4.8) and 24 other tissues See more
Orthologs: human all
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Genomic context

Location:: X D; X 47.36 cM

Exon count:: 23

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	X	NC_000086.8 (105070830..105171766)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	X	NC_000086.7 (106027224..106128161)

Chromosome X - NC_000086.8 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Decreased Expression of the Slc31a1 Gene and Cytoplasmic Relocalization of Membrane CTR1 Protein in Renal Epithelial Cells: A Potent Protective Mechanism against Copper Nephrotoxicity in a Mouse Model of Menkes Disease.
Title: Decreased Expression of the Slc31a1 Gene and Cytoplasmic Relocalization of Membrane CTR1 Protein in Renal Epithelial Cells: A Potent Protective Mechanism against Copper Nephrotoxicity in a Mouse Model of Menkes Disease.
The P-type ATPase transporter ATP7A promotes angiogenesis by limiting autophagic degradation of VEGFR2.
Title: The P-type ATPase transporter ATP7A promotes angiogenesis by limiting autophagic degradation of VEGFR2.
Caveolin-1 stabilizes ATP7A, a copper transporter for extracellular SOD, in vascular tissue to maintain endothelial function.
Title: Caveolin-1 stabilizes ATP7A, a copper transporter for extracellular SOD, in vascular tissue to maintain endothelial function.
Metallothioneins regulate ATP7A trafficking and control cell viability during copper deficiency and excess.
Title: Metallothioneins regulate ATP7A trafficking and control cell viability during copper deficiency and excess.
Our results show a previously unappreciated role of adipocyte Atp7a in the regulation of ageing-related metabolic disease and identify new metallophysiologies in whole-body fat metabolism.
Title: Adipocyte-specific disruption of ATPase copper transporting α in mice accelerates lipoatrophy.
Data show that steady-state levels of ATPase copper (Cu)transporting alpha (ATP7A) are lower in peripheral tissues (including the heart, spleen, and liver) under Cu deficiency.
Title: Organ-specific regulation of ATP7A abundance is coordinated with systemic copper homeostasis.
DBH-containing neurons express both ATP7A and ATP7B. The two transporters are located in distinct cellular compartments and oppositely regulate the export of soluble DBH from cultured neuronal cells under resting conditions.
Title: ATP7A and ATP7B copper transporters have distinct functions in the regulation of neuronal dopamine-β-hydroxylase.
A key copper homeostasis gene, Atp7a, undergoes dynamic changes in expression during myogenic differentiation.
Title: Dynamic changes in copper homeostasis and post-transcriptional regulation of Atp7a during myogenic differentiation.
Akt2 plays a critical role in ATP7A protein stabilization and translocation to plasma membrane in vascular smooth muscle cells, which contributes to full activation of vascular SOD3 that protects against endothelial dysfunction in T2DM.
Title: Akt2 (Protein Kinase B Beta) Stabilizes ATP7A, a Copper Transporter for Extracellular Superoxide Dismutase, in Vascular Smooth Muscle: Novel Mechanism to Limit Endothelial Dysfunction in Type 2 Diabetes Mellitus.
Copper therapy reduces intravascular hemolysis and derepresses ferroportin in mice with mosaic mutation (Atp7a(mo-ms)): An implication for copper-mediated regulation of the Slc40a1 gene expression.
Title: Copper therapy reduces intravascular hemolysis and derepresses ferroportin in mice with mosaic mutation (Atp7a(mo-ms)): An implication for copper-mediated regulation of the Slc40a1 gene expression.

Submit: New GeneRIF Correction See all GeneRIFs (51)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Targeted (3) 1 citation
Spontaneous (40) 1 citation
Chemically induced (other) (3) 1 citation
Chemically and radiation induced (2)
Radiation induced (6) 1 citation
Chemically induced (ENU) (4) 1 citation
Endonuclease-mediated (1)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

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

Atp7a (e-PCR), detects polymorphism
- UniSTS:141141

px-61g11 (e-PCR)
- UniSTS:258441

Atp7a (e-PCR), detects polymorphism
- UniSTS:527263

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

NoName (e-PCR)
- UniSTS:238066

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables ATP binding	ISO Inferred from Sequence Orthology more info
enables ATP hydrolysis activity	IEA Inferred from Electronic Annotation more info
enables ATPase-coupled monoatomic cation transmembrane transporter activity	IEA Inferred from Electronic Annotation more info
enables P-type divalent copper transporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables P-type divalent copper transporter activity	IDA Inferred from Direct Assay more info	PubMed
enables P-type monovalent copper transporter activity	ISO Inferred from Sequence Orthology more info
enables copper ion binding	IBA Inferred from Biological aspect of Ancestor more info
enables copper ion binding	ISO Inferred from Sequence Orthology more info
enables copper ion transmembrane transporter activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables copper-dependent protein binding	ISO Inferred from Sequence Orthology more info
enables cuprous ion binding	ISO Inferred from Sequence Orthology more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables nucleotide binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-folding chaperone binding	ISO Inferred from Sequence Orthology more info
enables small GTPase binding	ISO Inferred from Sequence Orthology more info
enables superoxide dismutase copper chaperone activity	IDA Inferred from Direct Assay more info	PubMed
enables transporter activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within ATP metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within T-helper cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within blood vessel development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within blood vessel remodeling	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cartilage development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of catecholamine metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within catecholamine metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to amino acid stimulus	ISO Inferred from Sequence Orthology more info
involved_in cellular response to copper ion	ISO Inferred from Sequence Orthology more info
involved_in cellular response to platelet-derived growth factor stimulus	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within central nervous system neuron development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cerebellar Purkinje cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within collagen fibril organization	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within copper ion export	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in copper ion export	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in copper ion export	ISO Inferred from Sequence Orthology more info
involved_in copper ion homeostasis	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within copper ion import	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within copper ion transport	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within copper ion transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in copper ion transport	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within dendrite morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within detoxification of copper ion	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within dopamine metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within elastic fiber assembly	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within elastin biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within epinephrine metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within establishment of localization in cell	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within extracellular matrix organization	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within hair follicle morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within hindlimb morphogenesis	IMP Inferred from Mutant Phenotype more info
acts_upstream_of_or_within intracellular copper ion homeostasis	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within intracellular copper ion homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intracellular copper ion homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intracellular copper ion homeostasis	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within locomotory behavior	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within lung alveolus development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within mitochondrion organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in monoatomic cation transport	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within monoatomic ion transport	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within negative regulation of catecholamine metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of iron ion transmembrane transport	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of neuron apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of neuron apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within neuron cellular homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within neuron projection morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within norepinephrine biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within norepinephrine metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within peptidyl-lysine modification	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within pigmentation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of catalytic activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cell size	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of cytochrome-c oxidase activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of epithelial cell proliferation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of lamellipodium assembly	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of melanin biosynthetic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of response to wounding	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of superoxide dismutase activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of tyrosinase activity	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of vascular associated smooth muscle cell migration	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within pyramidal neuron development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of oxidative phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within release of cytochrome c from mitochondria	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within removal of superoxide radicals	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to copper ion	ISO Inferred from Sequence Orthology more info
involved_in response to manganese ion	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within serotonin metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within skin development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within tryptophan metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within tyrosine metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
located_in Golgi apparatus	ISO Inferred from Sequence Orthology more info
located_in apical plasma membrane	ISO Inferred from Sequence Orthology more info
located_in axon	ISO Inferred from Sequence Orthology more info
located_in basolateral plasma membrane	ISO Inferred from Sequence Orthology more info
located_in brush border membrane	ISO Inferred from Sequence Orthology more info
located_in cell leading edge	ISO Inferred from Sequence Orthology more info
located_in cell projection	IEA Inferred from Electronic Annotation more info
located_in cytoplasmic vesicle	IDA Inferred from Direct Assay more info	PubMed
located_in dendrite	ISO Inferred from Sequence Orthology more info
located_in early endosome membrane	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum	ISO Inferred from Sequence Orthology more info
located_in endosome	IEA Inferred from Electronic Annotation more info
located_in late endosome	ISO Inferred from Sequence Orthology more info
located_in melanosome membrane	IDA Inferred from Direct Assay more info	PubMed
is_active_in membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	ISO Inferred from Sequence Orthology more info
located_in microvillus	ISO Inferred from Sequence Orthology more info
located_in neuron projection	IDA Inferred from Direct Assay more info	PubMed
located_in neuronal cell body	IDA Inferred from Direct Assay more info	PubMed
located_in perikaryon	ISO Inferred from Sequence Orthology more info
located_in perinuclear region of cytoplasm	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
located_in secretory granule	ISO Inferred from Sequence Orthology more info
located_in synapse	IEA Inferred from Electronic Annotation more info
located_in trans-Golgi network	IDA Inferred from Direct Assay more info	PubMed
located_in trans-Golgi network	ISO Inferred from Sequence Orthology more info
located_in trans-Golgi network membrane	IDA Inferred from Direct Assay more info	PubMed
located_in trans-Golgi network membrane	ISO Inferred from Sequence Orthology more info
located_in trans-Golgi network transport vesicle	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: copper-transporting ATPase 1

Names: Menkes protein; copper pump 1; menkes disease-associated protein homolog

NP_001103227.1

EC 7.2.2.8

NP_033856.3

EC 7.2.2.8

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.

mRNA and Protein(s)

NM_001109757.2 → NP_001103227.1 copper-transporting ATPase 1 isoform 1

Status: VALIDATED

Description

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

Source sequence(s)

AL672288

Consensus CDS

CCDS53169.1

UniProtKB/TrEMBL

A2AG68, B9EJ97

Related

ENSMUSP00000058840.7, ENSMUST00000055941.7

Conserved Domains (2) summary

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 ...

cd02094
Location:646 → 1380

P-type_ATPase_Cu-like; P-type heavy metal-transporting ATPase, similar to human copper-transporting ATPases, ATP7A and ATP7B
NM_009726.5 → NP_033856.3 copper-transporting ATPase 1 isoform 2

See identical proteins and their annotated locations for NP_033856.3

Status: VALIDATED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 5' coding region compared to variant 1. This results in a shorter protein (isoform 2) compared to isoform 1.

Source sequence(s)

AL672288

Consensus CDS

CCDS41097.1

UniProtKB/Swiss-Prot

A2AG69, O35101, P97422, Q64430, Q64431

UniProtKB/TrEMBL

B9EJ97

Related

ENSMUSP00000109186.2, ENSMUST00000113557.8

Conserved Domains (2) summary

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 ...

cd02094
Location:645 → 1379

P-type_ATPase_Cu-like; P-type heavy metal-transporting ATPase, similar to human copper-transporting ATPases, ATP7A and ATP7B