ATP1A3

ATP1A3
Identifikatori
Aliasi	ATP1A3
Vanjski ID-jevi	OMIM: 182350 MGI: 88107 HomoloGene: 113729 GeneCards: ATP1A3
Lokacija gena (čovjek)
Hrom.	Hromosom 19 (čovjek)
Kraj	41,997,497 bp
Lokacija gena (miš)
Hrom.	Hromosom 7 (miš)
Kraj	24,705,383 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• steroid hormone binding; • nucleotide binding; • chaperone binding; • P-type sodium:potassium-exchanging transporter activity; • vezivanje iona metala; • P-type sodium:potassium-exchanging transporter activity involved in regulation of cardiac muscle cell membrane potential; • heparan sulfate proteoglycan binding; • D1 dopamine receptor binding; • hydrolase activity; • ATP binding; • amyloid-beta binding; • P-type potassium transmembrane transporter activity; • ion antiporter activity involved in regulation of presynaptic membrane potential;
Ćelijska komponenta	• citoplazma; • integral component of membrane; • dendritic spine neck; • extracellular vesicle; • Golđijev aparat; • membrana; • myelin sheath; • ćelijska membrana; • sinapsa; • sodium:potassium-exchanging ATPase complex; • Akson; • dendritic spine head; • Endoplazmatski retikulum; • Sarkolema; • jedro; • neuronal cell body membrane; • soma;
Biološki proces	• visual learning; • cellular response to steroid hormone stimulus; • regulation of cardiac conduction; • cardiac muscle contraction; • sodium ion transport; • cellular sodium ion homeostasis; • adult locomotory behavior; • sodium ion export across plasma membrane; • cell communication by electrical coupling involved in cardiac conduction; • response to glycoside; • ion transport; • Memorija; • GO:0097301 cellular potassium ion homeostasis; • potassium ion transport; • ion transmembrane transport; • ionotropic glutamate receptor signaling pathway; • GO:0015915 transport; • regulation of cardiac muscle cell membrane potential; • establishment or maintenance of transmembrane electrochemical gradient; • cerebral cortex development; • cellular response to retinoic acid; • cellular response to thyroid hormone stimulus; • regulation of resting membrane potential; • regulation of presynaptic membrane potential; • cellular response to amyloid-beta; • neuron projection maintenance; • potassium ion import across plasma membrane;
	Izvori:Amigo / QuickGO
Ortolozi
	478
	232975
	ENSG00000105409
	ENSMUSG00000040907
	P13637
	Q6PIC6
	NM_001256213; NM_001256214; NM_152296
	NM_001290469; NM_144921; NM_001374627
	NP_001243142; NP_001243143; NP_689509
	NP_001277398; NP_001361556
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Podjedinica alfa-3 natrij/kalij-transportirajuče ATPaze je enzim koji je kod ljudi kodiran gen ATP1A3.^[5]^[6]

Aminokisekinska sekvenca

Simboli

C: Cistein
D: Asparaginska kiselina
E: Glutaminska kiselina
F: Fenilalanin
G: Glicin
H: Histidin
I: Izoleucin
K: Lizin
L: Leucin
M: Metionin
N: Asparagin
P: Prolin
Q: Glutamin
R: Arginin
S: Serin
T: Treonin
V: Valin
W: Triptofan
Y: Tirozin

10	20	30	40	50
MGDKKDDKDS	PKKNKGKERR	DLDDLKKEVA	MTEHKMSVEE	VCRKYNTDCV
QGLTHSKAQE	ILARDGPNAL	TPPPTTPEWV	KFCRQLFGGF	SILLWIGAIL
CFLAYGIQAG	TEDDPSGDNL	YLGIVLAAVV	IITGCFSYYQ	EAKSSKIMES
FKNMVPQQAL	VIREGEKMQV	NAEEVVVGDL	VEIKGGDRVP	ADLRIISAHG
CKVDNSSLTG	ESEPQTRSPD	CTHDNPLETR	NITFFSTNCV	EGTARGVVVA
TGDRTVMGRI	ATLASGLEVG	KTPIAIEIEH	FIQLITGVAV	FLGVSFFILS
LILGYTWLEA	VIFLIGIIVA	NVPEGLLATV	TVCLTLTAKR	MARKNCLVKN
LEAVETLGST	STICSDKTGT	LTQNRMTVAH	MWFDNQIHEA	DTTEDQSGTS
FDKSSHTWVA	LSHIAGLCNR	AVFKGGQDNI	PVLKRDVAGD	ASESALLKCI
ELSSGSVKLM	RERNKKVAEI	PFNSTNKYQL	SIHETEDPND	NRYLLVMKGA
PERILDRCST	ILLQGKEQPL	DEEMKEAFQN	AYLELGGLGE	RVLGFCHYYL
PEEQFPKGFA	FDCDDVNFTT	DNLCFVGLMS	MIDPPRAAVP	DAVGKCRSAG
IKVIMVTGDH	PITAKAIAKG	VGIISEGNET	VEDIAARLNI	PVSQVNPRDA
KACVIHGTDL	KDFTSEQIDE	ILQNHTEIVF	ARTSPQQKLI	IVEGCQRQGA
IVAVTGDGVN	DSPALKKADI	GVAMGIAGSD	VSKQAADMIL	LDDNFASIVT
GVEEGRLIFD	NLKKSIAYTL	TSNIPEITPF	LLFIMANIPL	PLGTITILCI
DLGTDMVPAI	SLAYEAAESD	IMKRQPRNPR	TDKLVNERLI	SMAYGQIGMI
QALGGFFSYF	VILAENGFLP	GNLVGIRLNW	DDRTVNDLED	SYGQQWTYEQ
RKVVEFTCHT	AFFVSIVVVQ	WADLIICKTR	RNSVFQQGMK	NKILIFGLFE
ETALAAFLSY	CPGMDVALRM	YPLKPSWWFC	AFPYSFLIFV	YDEIRKLILR
RNPGGWVEKE	TYY

Funkcija

Protein koji je kodiran ovim genom pripada porodici P-tipa kationskog transporta ATPaza i potporodice Na⁺/K⁺-ATPaza. Na⁺/K⁺ -ATPaza je integralni membranski protein, odgovoran za uspostavljanje i održavanje elektrohemijskog gradijenta Na i K iona preko plazmatske membrane. Ovi gradijenti su neophodni za osmoregulaciju, za natrijev – pregnuti transport različitih organskih i neorganskih molekula, te za električnu ekscitabilnost živaca i mišića. Ovaj enzim sastoji se od dvije podjedinice, velike katalitske podjedinice (alfa) i manje glikoproteinske podjedinice (beta). Katalitska podjedinica Na⁺ /K⁺ -ATPaza kodirana je sa više gena. Ovaj gen kodira podjedinicu alfa-3.^[6]

Klinički značaj

Poznato je da varijante gena ATP1A3 koje uzrokuju bolest izazivaju razne poremećaje pokreta i epilepsije.^[7] Poznata pridružena stanja uključuju razne sindrome:

1) Naizmjenična hemiplegija djetinjstva (AHC)

2) Brzonastaljuća distonija-parkinsonizam (RDP, poznat i kao DYT12)

3) Cerebelarne ataksija, arefleksija, pes cavus, optička atrofija i senzorineuralni gubitak sluha (CAPOS /CAOS sindrom)

4) Razvojna i epilepsijska encefalopatija

5) Paroksizamska slabost i encefalopatija izazvana vrućicom (FIPWE)

6) Ponavljajuće epizode cerebralne ataksije (RECA)

7) Vrlo rana shizofrenija.^[8]

Kod miševa su mutacije ovog gena povezane sa epilepsijom. Manipuliranjem ovog gena u potomstvu takvih miševa epilepsija se može izbjeći.^[9]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000105409 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000040907 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 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.
^ ^a ^b "Entrez Gene: ATP1A3 ATPase, Na⁺/K⁺ transporting, alpha 3 polypeptide".
^ Papandreou A, Danti FR, Spaull R, Leuzzi V, Mctague A, Kurian MA (februar 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.
^ 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 (septembar 2016). "A novel de novo mutation in ATP1A3 and childhood-onset schizophrenia". Cold Spring Harb Mol Case Stud. 2 (5): a001008. doi:10.1101/mcs.a001008. PMC 5002930. PMID 27626066.
^ 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.

Dopunska literatura

Lingrel JB, Orlowski J, Shull MM, Price EM (1990). "Molecular genetics of Na,K-ATPase". Prog. Nucleic Acid Res. Mol. Biol. Progress in Nucleic Acid Research and Molecular Biology. 38: 37–89. doi:10.1016/S0079-6603(08)60708-4. ISBN 978-0-12-540038-1. PMID 2158121.
Sverdlov ED, Monastyrskaia GS, Broude NE, Ushkarev IuA, Melkov AM (1988). "The family of human Na⁺,K⁺-ATPase genes. Structure of the gene for isozyme alphaII" [The family of human Na⁺,⁺-ATPase genes. Structure of the gene for isozyme alphaII]. Doklady Akademii Nauk SSSR. 297 (6): 1488–94. PMID 2834163.
Monastyrskaya GS, Broude NE, Melkov AM, Malyshev IV, Allikmets RL, Kostina MB, Dulubova IE (1988). "Family of human Na⁺, K⁺-ATPase genes. Structure of the gene for the catalytic subunit (alpha III-form) and its relationship with structural features of the protein". FEBS Lett. 233 (1): 87–94. doi:10.1016/0014-5793(88)81361-9. PMID 2838329. S2CID 1378625.
Yang-Feng TL, Schneider JW, Lindgren V, Shull MM, Benz EJ, Lingrel JB, Francke U (1988). "Chromosomal localization of human Na⁺, K⁺-ATPase alpha- and beta-subunit genes". Genomics. 2 (2): 128–38. doi:10.1016/0888-7543(88)90094-8. PMID 2842249.
Sverdlov ED, Broude NE, Sverdlov VE, Monastyrskaya GS, Grishin AV, Petrukhin KE, Akopyanz NS, Modyanov NN (1987). "Family of Na⁺,K⁺-ATPase genes. Intra-individual tissue-specific restriction fragment length polymorphism". FEBS Lett. 221 (1): 129–33. doi:10.1016/0014-5793(87)80366-6. PMID 2887455. S2CID 32756405.
Harley HG, Brook JD, Jackson CL, Glaser T, Walsh KV, Sarfarazi M, Kent R, Lager M, Koch M, Harper PS (1989). "Localization of a human Na⁺,K⁺-ATPase alpha subunit gene to chromosome 19q12----q13.2 and linkage to the myotonic dystrophy locus". Genomics. 3 (4): 380–4. doi:10.1016/0888-7543(88)90131-0. PMID 2907504.
Monastyrskaya GS, Broude NE, Allikmets RL, Melkov AM, Malyshev IV, Dulubova IE, Petrukhin KE (1987). "The family of human Na⁺,K⁺-ATPase genes. A partial nucleotide sequence related to the alpha-subunit". FEBS Lett. 213 (1): 73–80. doi:10.1016/0014-5793(87)81467-9. PMID 3030810. S2CID 35674738.
Shull MM, Lingrel JB (1987). "Multiple genes encode the human Na⁺,K⁺-ATPase catalytic subunit". Proc. Natl. Acad. Sci. U.S.A. 84 (12): 4039–43. Bibcode:1987PNAS...84.4039S. doi:10.1073/pnas.84.12.4039. PMC 305017. PMID 3035563.
Sverdlov ED, Monastyrskaya GS, Broude NE, Allikmets RL, Melkov AM, Malyshev IV, Dulobova IE, Petrukhin KE (1987). "The family of human Na⁺,K⁺-ATPase genes. No less than five genes and/or pseudogenes related to the alpha-subunit". FEBS Lett. 217 (2): 275–8. doi:10.1016/0014-5793(87)80677-4. PMID 3036582. S2CID 44449386.
Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
Kramer PL, Mineta M, Klein C, Schilling K, de Leon D, Farlow MR, Breakefield XO, Bressman SB, Dobyns WB, Ozelius LJ, Brashear A (1999). "Rapid-onset dystonia-parkinsonism: linkage to chromosome 19q13". Ann. Neurol. 46 (2): 176–82. doi:10.1002/1531-8249(199908)46:2<176::AID-ANA6>3.0.CO;2-2. PMID 10443882.
Esplin MS, Fausett MB, Faux DS, Graves SW (2003). "Changes in the isoforms of the sodium pump in the placenta and myometrium of women in labor". Am. J. Obstet. Gynecol. 188 (3): 759–64. doi:10.1067/mob.2003.166. PMID 12634653.
de Carvalho Aguiar P, Sweadner KJ, Penniston JT, Zaremba J, Liu L, Caton M, Linazasoro G, Borg M, Tijssen MA, Bressman SB, Dobyns WB, Brashear A, Ozelius LJ (2004). "Mutations in the Na⁺/⁺-ATPase alpha3 gene ATP1A3 are associated with rapid-onset dystonia parkinsonism". Neuron. 43 (2): 169–75. doi:10.1016/j.neuron.2004.06.028. PMID 15260953. S2CID 15874616.
Benfante R, Antonini RA, Vaccari M, Flora A, Chen F, Clementi F, Fornasari D (2005). "The expression of the human neuronal α3 Na⁺,K⁺-ATPase subunit gene is regulated by the activity of the Sp1 and NF-Y transcription factors". Biochem. J. 386 (Pt 1): 63–72. doi:10.1042/BJ20041294. PMC 1134767. PMID 15462673.
Lim J, Hao T, Shaw C, Patel AJ, Szabó G, Rual JF, Fisk CJ, Li N, Smolyar A, Hill DE, Barabási AL, Vidal M, Zoghbi HY (2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell. 125 (4): 801–14. doi:10.1016/j.cell.2006.03.032. PMID 16713569. S2CID 13709685.

Vanjski linkovi

GeneReview/NCBI/NIH/UW entry on Rapid-Onset Dystonia Parkinsonism
Lokacija ljudskog genoma ATP1A3 i stranica sa detaljima o genu ATP1A3 u UCSC Genome Browseru.

Šablon:ATPaze

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000105409 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000040907 - Ensembl, maj 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.

[pmid17282997-5] 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.

[entrez-6] "Entrez Gene: ATP1A3 ATPase, Na⁺/K⁺ transporting, alpha 3 polypeptide".

[7] Papandreou A, Danti FR, Spaull R, Leuzzi V, Mctague A, Kurian MA (februar 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.

[pmid27626066-8] 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 (septembar 2016). "A novel de novo mutation in ATP1A3 and childhood-onset schizophrenia". Cold Spring Harb Mol Case Stud. 2 (5): a001008. doi:10.1101/mcs.a001008. PMC 5002930. PMID 27626066.

[pmid19666602-9] 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.

[5]

[6]

[1]

[2]

[3]

[4]

[7]

[8]

[9]