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
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
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Genomic context

Location:: Xq21.1

Exon count:: 23

Annotation release	Status	Assembly	Chr	Location
109.20211119	current	GRCh38.p13 (GCF_000001405.39)	X	NC_000023.11 (77910693..78050395)
105.20201022	previous assembly	GRCh37.p13 (GCF_000001405.25)	X	NC_000023.10 (77166190..77305892)

Chromosome X - NC_000023.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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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 Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The M1311V variant of ATP7A is associated with impaired trafficking and copper homeostasis in models of motor neuron disease.
Title: The M1311V variant of ATP7A is associated with impaired trafficking and copper homeostasis in models of motor neuron disease.
At sixes and sevens: cryptic domain in the metal binding chain of the human copper transporter ATP7A.
Title: At sixes and sevens: cryptic domain in the metal binding chain of the human copper transporter ATP7A.
CRISPR-mediated gene correction links the ATP7A M1311V mutations with amyotrophic lateral sclerosis pathogenesis in one individual.
Title: CRISPR-mediated gene correction links the ATP7A M1311V mutations with amyotrophic lateral sclerosis pathogenesis in one individual.
[Pedigree study and analysis of ATP7A gene variants in three children with Menkes disease].
Title: [Pedigree study and analysis of ATP7A gene variants in three children with Menkes disease].
Neck masses due to internal jugular vein phlebectasia: Frequency in Menkes disease and literature review of 85 pediatric subjects.
Title: Neck masses due to internal jugular vein phlebectasia: Frequency in Menkes disease and literature review of 85 pediatric subjects.
Impaired copper transport in schizophrenia results in a copper-deficient brain state: A new side to the dysbindin story.
Title: Impaired copper transport in schizophrenia results in a copper-deficient brain state: A new side to the dysbindin story.
High ATP7A expression is associated with breast cancer cell migration.
Title: Single-cell tracking demonstrates copper chaperone Atox1 to be required for breast cancer cell migration.
Involving MNK targeting to sensitize medulloblastoma CSCs to PI3Kalpha inhibition.
Title: Potent Antineoplastic Effects of Combined PI3Kα-MNK Inhibition in Medulloblastoma.
Binding of TAp73 to the ATP7A promoter occurs in non-small cell lung carcinoma cells.
Title: TAp73 regulates ATP7A: possible implications for ageing-related diseases.
An early definite diagnosis is necessary for the early treatment of Menkes disease, and gene analysis serves as an effective method for detecting mutations in ATP7A.
Title: ATP7A mutations in 66 Japanese patients with Menkes disease and carrier detection: A gene analysis.

Submit: New GeneRIF Correction See all GeneRIFs (112)

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 2021-03-24) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2021-03-24) ClinGen Genome Curation PagePubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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: 403 organisms have orthologs with human gene ATP7A
Orthologs

Gene Ontology Provided by GOA

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

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

Component	Evidence Code	Pubs
located_in Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
located_in apical plasma membrane	IEA Inferred from Electronic Annotation more info
located_in axon	ISS Inferred from Sequence or Structural Similarity more info
located_in basolateral plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in brush border membrane	IEA Inferred from Electronic Annotation more info
located_in cell leading edge	IEA Inferred from Electronic Annotation more info
located_in cytosol	IEA Inferred from Electronic Annotation more info
located_in dendrite	ISS Inferred from Sequence or Structural Similarity more info
located_in early endosome membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in endoplasmic reticulum	IEA Inferred from Electronic Annotation more info
located_in integral component of membrane	IEA Inferred from Electronic Annotation more info
located_in late endosome	IDA Inferred from Direct Assay more info	PubMed
located_in melanosome membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in membrane	HDA more info	PubMed
is_active_in membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in membrane raft	IEA Inferred from Electronic Annotation more info
located_in microvillus	IEA Inferred from Electronic Annotation more info
located_in neuron projection	ISS Inferred from Sequence or Structural Similarity more info
located_in neuronal cell body	ISS Inferred from Sequence or Structural Similarity more info
located_in nucleus	IEA Inferred from Electronic Annotation more info
located_in perikaryon	IEA Inferred from Electronic Annotation more info
is_active_in perinuclear region of cytoplasm	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in phagocytic vesicle membrane	TAS Traceable Author Statement more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
located_in postsynaptic density	IEA Inferred from Electronic Annotation more info
located_in secretory granule	IEA Inferred from Electronic Annotation more info
is_active_in trans-Golgi network	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in trans-Golgi network	IDA Inferred from Direct Assay more info	PubMed
located_in trans-Golgi network membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in 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 7.2.2.8

NP_001269153.1

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.

Genomic

NG_013224.2 RefSeqGene

Range

4997..144699

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000052.7 → 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, ENST00000341514.11

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:652 → 1388

P-type_ATPase_Cu-like; P-type heavy metal-transporting ATPase, similar to human copper-transporting ATPases, ATP7A and ATP7B
NM_001282224.2 → 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

ENSP00000509477.1, ENST00000686543.1

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_104109.2 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

Related

ENST00000685033.1