ATP1A3

Last updated
ATP1A3
Identifiers
Aliases ATP1A3 , AHC2, DYT12, RDP, CAPOS, ATPase Na+/K+ transporting subunit alpha 3, ATP1A1, DEE99
External IDs OMIM: 182350; MGI: 88107; HomoloGene: 113729; GeneCards: ATP1A3; OMA:ATP1A3 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001256213
NM_001256214
NM_152296

NM_001290469
NM_144921
NM_001374627

RefSeq (protein)

NP_001243142
NP_001243143
NP_689509

NP_001277398
NP_001361556

Location (UCSC) Chr 19: 41.97 – 42 Mb Chr 7: 24.68 – 24.71 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Sodium/potassium-transporting ATPase subunit alpha-3 is an enzyme that in humans is encoded by the ATP1A3 gene. [5] [6]

Contents

Function

The protein encoded by this gene belongs to the family of P-type cation transport ATPases, and to the subfamily of Na+/K+-ATPases. Na+/K+-ATPase is an integral membrane protein responsible for establishing and maintaining the electrochemical gradients of Na and K ions across the plasma membrane. These gradients are essential for osmoregulation, for sodium-coupled transport of a variety of organic and inorganic molecules, and for electrical excitability of nerve and muscle. This enzyme is composed of two subunits, a large catalytic subunit (alpha) and a smaller glycoprotein subunit (beta). The catalytic subunit of Na+/K+-ATPase is encoded by multiple genes. This gene encodes an alpha 3 subunit. [6] ATP1A3 is expressed early in human development, likely underlying pathophysiology related to several ATP1A3 related diseases. [7]

Clinical significance

Disease causing variants of the ATP1A3 gene are known to cause a variety of movement disorders and epilepsies. [8] The known associations include a variety of syndromes, in approximate order of presentation:

  1. Malformation of Cortex Development, including polymicrogyria; [7]
  2. Developmental and epileptic encephalopathy 99 (DEE99); [9]
  3. Alternating hemiplegia of childhood 2 (AHC2); [10]
  4. Cerebellar ataxia, Areflexia, Pes cavus, Optic atrophy and Sensorineural hearing loss (CAPOS/CAOS syndrome);
  5. Very early-onset schizophrenia; [11]
  6. Rapid-onset dystonia parkinsonism (RDP, also known as DYT12);
  7. Fever-induced paroxysmal weakness and encephalopathy (FIPWE);
  8. Recurrent episodes of cerebellar ataxia (RECA).

In mice, mutations in this gene are associated with epilepsy. By manipulating this gene in the offspring of such mice, epilepsy can be avoided. [12]

Related Research Articles

<span class="mw-page-title-main">Sodium–potassium pump</span> Enzyme found in the membrane of all animal cells

The sodium–potassium pump is an enzyme found in the membrane of all animal cells. It performs several functions in cell physiology.

<span class="mw-page-title-main">Dystonia</span> Neurological movement disorder

Dystonia is a neurological hyperkinetic movement disorder in which sustained or repetitive muscle contractions occur involuntarily, resulting in twisting and repetitive movements or abnormal fixed postures. The movements may resemble a tremor. Dystonia is often intensified or exacerbated by physical activity, and symptoms may progress into adjacent muscles.

<span class="mw-page-title-main">Ubiquitin carboxy-terminal hydrolase L1</span> Protein-coding gene in the species Homo sapiens

Ubiquitin carboxy-terminal hydrolase L1 is a deubiquitinating enzyme.

Torsion dystonia, also known as dystonia musculorum deformans, is a disease characterized by painful muscle contractions resulting in uncontrollable distortions. This specific type of dystonia is frequently found in children, with symptoms starting around the ages of 11 or 12. It commonly begins with contractions in one general area such as an arm or a leg that continue to progress throughout the rest of the body. It takes roughly 5 years for the symptoms to completely progress to a debilitating state.

<span class="mw-page-title-main">Glucagon receptor</span> Protein-coding gene in the species Homo sapiens

The glucagon receptor is a 62 kDa protein that is activated by glucagon and is a member of the class B G-protein coupled family of receptors, coupled to G alpha i, Gs and to a lesser extent G alpha q. Stimulation of the receptor results in the activation of adenylate cyclase and phospholipase C and in increased levels of the secondary messengers intracellular cAMP and calcium. In humans, the glucagon receptor is encoded by the GCGR gene.

<span class="mw-page-title-main">Aspartylglucosaminidase</span> Protein-coding gene in the species Homo sapiens

N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase is an enzyme that in humans is encoded by the AGA gene.

<span class="mw-page-title-main">PSMC3</span> Enzyme found in humans

26S protease regulatory subunit 6A, also known as 26S proteasome AAA-ATPase subunit Rpt5, is an enzyme that in humans is encoded by the PSMC3 gene. This protein is one of the 19 essential subunits of a complete assembled 19S proteasome complex Six 26S proteasome AAA-ATPase subunits together with four non-ATPase subunits form the base sub complex of 19S regulatory particle for proteasome complex.

<span class="mw-page-title-main">Gamma-aminobutyric acid receptor subunit alpha-1</span> Protein-coding gene in humans

Gamma-aminobutyric acid receptor subunit alpha-1 is a protein that in humans is encoded by the GABRA1 gene.

<span class="mw-page-title-main">Torsin A</span> Protein-coding gene in the species Homo sapiens

Torsin-1A (TorA) also known as dystonia 1 protein (DYT1) is a protein that in humans is encoded by the TOR1A gene. TorA localizes to the endoplasmic reticulum and contiguous perinuclear space, where its ATPase activity is activated by either LULL1 or LAP1, respectively.

<span class="mw-page-title-main">PSMC5</span> Enzyme found in humans

26S protease regulatory subunit 8, also known as 26S proteasome AAA-ATPase subunit Rpt6, is an enzyme that in humans is encoded by the PSMC5 gene. This protein is one of the 19 essential subunits of a complete assembled 19S proteasome complex Six 26S proteasome AAA-ATPase subunits together with four non-ATPase subunits form the base sub complex of 19S regulatory particle for proteasome complex.

ATPase, Na<sup>+</sup>/K<sup>+</sup> transporting, alpha 1 Protein-coding gene in the species Homo sapiens

Sodium/potassium-transporting ATPase subunit alpha-1 is an enzyme that in humans is encoded by the ATP1A1 gene.

<span class="mw-page-title-main">ATP1A2</span> Protein-coding gene in the species Homo sapiens

Sodium/potassium-transporting ATPase subunit alpha-2 is a protein which in humans is encoded by the ATP1A2 gene.

<span class="mw-page-title-main">KCNA5</span> Protein-coding gene in humans

Potassium voltage-gated channel, shaker-related subfamily, member 5, also known as KCNA5 or Kv1.5, is a protein that in humans is encoded by the KCNA5 gene.

<span class="mw-page-title-main">ATP6V1B1</span> Protein-coding gene in the species Homo sapiens

V-type proton ATPase subunit B, kidney isoform is an enzyme that in humans is encoded by the ATP6V1B1 gene.

SCN2A Protein-coding gene in the species Homo sapiens

Sodium channel protein type 2 subunit alpha, is a protein that in humans is encoded by the SCN2A gene. Functional sodium channels contain an ion conductive alpha subunit and one or more regulatory beta subunits. Sodium channels which contain sodium channel protein type 2 subunit alpha are sometimes called Nav1.2 channels.

<span class="mw-page-title-main">ATP5F1A</span> Protein-coding gene in the species Homo sapiens

ATP synthase F1 subunit alpha, mitochondrial is an enzyme that in humans is encoded by the ATP5F1A gene.

<span class="mw-page-title-main">ATP1B1</span> Protein-coding gene in the species Homo sapiens

Sodium/potassium-transporting ATPase subunit beta-1 is an enzyme that in humans is encoded by the ATP1B1 gene.

<span class="mw-page-title-main">ATP1A4</span> Protein-coding gene in the species Homo sapiens

Sodium/potassium-transporting ATPase subunit alpha-4 is an enzyme that in humans is encoded by the ATP1A4 gene.

<span class="mw-page-title-main">ATP12A</span> Protein-coding gene in the species Homo sapiens

Potassium-transporting ATPase alpha chain 2 is a protein that in humans is encoded by the ATP12A gene.

<span class="mw-page-title-main">ATP1B3</span> Protein-coding gene in the species Homo sapiens

Sodium/potassium-transporting ATPase subunit beta-3 is an enzyme that in humans is encoded by the ATP1B3 gene. ATP1B3 has also been designated as CD298.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000105409 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000040907 Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Brashear A, Dobyns WB, de Carvalho Aguiar P, Borg M, Frijns CJ, Gollamudi S, Green A, Guimaraes J, Haake BC, Klein C, Linazasoro G, Münchau A, Raymond D, Riley D, Saunders-Pullman R, Tijssen MA, Webb D, Zaremba J, Bressman SB, Ozelius LJ (Mar 2007). "The phenotypic spectrum of rapid-onset dystonia-parkinsonism (RDP) and mutations in the ATP1A3 gene". Brain. 130 (Pt 3): 828–35. doi: 10.1093/brain/awl340 . PMID   17282997.
  6. 1 2 "Entrez Gene: ATP1A3 ATPase, Na+/K+ transporting, alpha 3 polypeptide".
  7. 1 2 Smith RS, Florio M, Akula SK, Neil JE, Wang Y, Hill RS, et al. (2021-06-22). "Early role for a Na + ,K + -ATPase ( ATP1A3 ) in brain development". Proceedings of the National Academy of Sciences. 118 (25): e2023333118. Bibcode:2021PNAS..11823333S. doi: 10.1073/pnas.2023333118 . PMC   8237684 . PMID   34161264.
  8. Papandreou A, Danti FR, Spaull R, Leuzzi V, Mctague A, Kurian MA (February 2020). "The expanding spectrum of movement disorders in genetic epilepsies". Developmental Medicine and Child Neurology. 62 (2): 178–191. doi:10.1111/dmcn.14407. PMID   31784983. S2CID   208498567.
  9. "UniProt". www.uniprot.org. Retrieved 2023-10-31.
  10. "UniProt".
  11. Smedemark-Margulies N, Brownstein CA, Vargas S, Tembulkar SK, Towne MC, Shi J, Gonzalez-Cuevas E, Liu KX, Bilguvar K, Kleiman RJ, Han MJ, Torres A, Berry GT, Yu TW, Beggs AH, Agrawal PB, Gonzalez-Heydrich J (September 2016). "A novel de novo mutation in ATP1A3 and childhood-onset schizophrenia". Cold Spring Harbor Molecular Case Studies. 2 (5): a001008. doi:10.1101/mcs.a001008. PMC   5002930 . PMID   27626066.
  12. Clapcote SJ, Duffy S, Xie G, Kirshenbaum G, Bechard AR, Rodacker Schack V, Petersen J, Sinai L, Saab BJ, Lerch JP, Minassian BA, Ackerley CA, Sled JG, Cortez MA, Henderson JT, Vilsen B, Roder JC (August 2009). "Mutation I810N in the alpha3 isoform of Na+,K+-ATPase causes impairments in the sodium pump and hyperexcitability in the CNS". Proc. Natl. Acad. Sci. U.S.A. 106 (33): 14085–90. Bibcode:2009PNAS..10614085C. doi: 10.1073/pnas.0904817106 . PMC   2729024 . PMID   19666602.

Further reading