AT2B3_HUMAN
ID AT2B3_HUMAN Reviewed; 1220 AA.
AC Q16720; B7WNR8; B7WNY5; Q12995; Q16858;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 3.
DT 03-AUG-2022, entry version 208.
DE RecName: Full=Plasma membrane calcium-transporting ATPase 3;
DE Short=PMCA3 {ECO:0000303|PubMed:18029012};
DE EC=7.2.2.10 {ECO:0000305|PubMed:22912398, ECO:0000305|PubMed:25953895};
DE AltName: Full=Plasma membrane calcium ATPase isoform 3;
DE AltName: Full=Plasma membrane calcium pump isoform 3;
GN Name=ATP2B3 {ECO:0000303|PubMed:8187550, ECO:0000312|HGNC:HGNC:816};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS XA AND XB).
RC TISSUE=Brain;
RX PubMed=8765088; DOI=10.1016/0005-2736(96)00108-3;
RA Brown B., Hilfiker H., Demarco S.J., Zacharias D.A., Greenwood T.M.,
RA Carafoli E., Strehler E.E.;
RT "Primary structure of human plasma membrane Ca(2+)-ATPase isoform 3.";
RL Biochim. Biophys. Acta 1283:10-13(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-319, ALTERNATIVE SPLICING (ISOFORMS
RP XB/XA/XE/XG), TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=8187550; DOI=10.1159/000133794;
RA Wang M.G., Yi H., Hilfiker H., Carafoli E., Strehler E.E., McBride O.W.;
RT "Localization of two genes encoding plasma membrane Ca2+ ATPases isoforms 2
RT (ATP2B2) and 3 (ATP2B3) to human chromosomes 3p26-->p25 and Xq28,
RT respectively.";
RL Cytogenet. Cell Genet. 67:41-45(1994).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-1053, AND ALTERNATIVE SPLICING
RP (ISOFORMS XB/XA/XE/XG).
RX PubMed=10854409; DOI=10.1101/gr.10.6.758;
RA Mallon A.-M., Platzer M., Bate R., Gloeckner G., Botcherby M.R.M.,
RA Nordsiek G., Strivens M.A., Kioschis P., Dangel A., Cunningham D.,
RA Straw R.N.A., Weston P., Gilbert M., Fernando S., Goodall K., Hunter G.,
RA Greystrong J.S., Clarke D., Kimberley C., Goerdes M., Blechschmidt K.,
RA Rump A., Hinzmann B., Mundy C.R., Miller W., Poustka A., Herman G.E.,
RA Rhodes M., Denny P., Rosenthal A., Brown S.D.M.;
RT "Comparative genome sequence analysis of the Bpa/Str region in mouse and
RT man.";
RL Genome Res. 10:758-775(2000).
RN [6]
RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS XG/ZG AND XA/ZA), AND
RP ALTERNATIVE SPLICING.
RC TISSUE=Brain cortex;
RX PubMed=8245032; DOI=10.1016/s0021-9258(19)74484-6;
RA Stauffer T.P., Hilfiker H., Carafoli E., Strehler E.E.;
RT "Quantitative analysis of alternative splicing options of human plasma
RT membrane calcium pump genes.";
RL J. Biol. Chem. 268:25993-26003(1993).
RN [7]
RP ERRATUM OF PUBMED:8245032.
RX PubMed=7989379; DOI=10.1016/s0021-9258(18)31797-6;
RA Stauffer T.P., Hilfiker H., Carafoli E., Strehler E.E.;
RL J. Biol. Chem. 269:32022-32022(1994).
RN [8]
RP INTERACTION WITH PDZD11.
RX PubMed=12763866; DOI=10.1111/j.1749-6632.2003.tb07230.x;
RA Goellner G.M., DeMarco S.J., Strehler E.E.;
RT "Characterization of PISP, a novel single-PDZ protein that binds to all
RT plasma membrane Ca2+-ATPase b-splice variants.";
RL Ann. N. Y. Acad. Sci. 986:461-471(2003).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH YWHAE, AND ACTIVITY
RP REGULATION.
RX PubMed=18029012; DOI=10.1016/j.ceca.2007.09.003;
RA Linde C.I., Di Leva F., Domi T., Tosatto S.C., Brini M., Carafoli E.;
RT "Inhibitory interaction of the 14-3-3 proteins with ubiquitous (PMCA1) and
RT tissue-specific (PMCA3) isoforms of the plasma membrane Ca2+ pump.";
RL Cell Calcium 43:550-561(2008).
RN [10]
RP FUNCTION, TISSUE SPECIFICITY, AND CHARACTERIZATION OF VARIANT
RP 425-LEU-VAL-426 DEL.
RX PubMed=27035656; DOI=10.1210/en.2015-2029;
RA Tauber P., Aichinger B., Christ C., Stindl J., Rhayem Y., Beuschlein F.,
RA Warth R., Bandulik S.;
RT "Cellular Pathophysiology of an Adrenal Adenoma-Associated Mutant of the
RT Plasma Membrane Ca(2+)-ATPase ATP2B3.";
RL Endocrinology 157:2489-2499(2016).
RN [11]
RP INVOLVEMENT IN SCAX1, VARIANT SCAX1 ASP-1107, CHARACTERIZATION OF VARIANT
RP SCAX1 ASP-1107, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=22912398; DOI=10.1073/pnas.1207488109;
RA Zanni G., Cali T., Kalscheuer V.M., Ottolini D., Barresi S., Lebrun N.,
RA Montecchi-Palazzi L., Hu H., Chelly J., Bertini E., Brini M., Carafoli E.;
RT "Mutation of plasma membrane Ca2+ ATPase isoform 3 in a family with X-
RT linked congenital cerebellar ataxia impairs Ca2+ homeostasis.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:14514-14519(2012).
RN [12]
RP INVOLVEMENT IN SCAX1, CHARACTERIZATION OF VARIANT SCAX1 HIS-482, FUNCTION,
RP CATALYTIC ACTIVITY, MUTAGENESIS OF ASP-473, AND SUBCELLULAR LOCATION.
RX PubMed=25953895; DOI=10.1074/jbc.m115.656496;
RA Cali T., Lopreiato R., Shimony J., Vineyard M., Frizzarin M., Zanni G.,
RA Zanotti G., Brini M., Shinawi M., Carafoli E.;
RT "A Novel Mutation in Isoform 3 of the Plasma Membrane Ca2+ Pump Impairs
RT Cellular Ca2+ Homeostasis in a Patient with Cerebellar Ataxia and Laminin
RT Subunit 1alpha Mutations.";
RL J. Biol. Chem. 290:16132-16141(2015).
CC -!- FUNCTION: ATP-driven Ca(2+) ion pump involved in the maintenance of
CC basal intracellular Ca(2+) levels at the presynaptic terminals
CC (PubMed:25953895, PubMed:27035656, PubMed:22912398, PubMed:18029012).
CC Uses ATP as an energy source to transport cytosolic Ca(2+) ions across
CC the plasma membrane to the extracellular compartment (PubMed:25953895,
CC PubMed:27035656). May counter-transport protons, but the mechanism and
CC the stoichiometry of this Ca(2+)/H(+) exchange remains to be
CC established (By similarity). {ECO:0000250|UniProtKB:Q64568,
CC ECO:0000269|PubMed:18029012, ECO:0000269|PubMed:22912398,
CC ECO:0000269|PubMed:25953895, ECO:0000269|PubMed:27035656}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + Ca(2+)(in) + H2O = ADP + Ca(2+)(out) + H(+) + phosphate;
CC Xref=Rhea:RHEA:18105, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29108, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:456216; EC=7.2.2.10;
CC Evidence={ECO:0000305|PubMed:22912398, ECO:0000305|PubMed:25953895};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18106;
CC Evidence={ECO:0000305|PubMed:22912398, ECO:0000305|PubMed:25953895};
CC -!- ACTIVITY REGULATION: Down-regulated by YWHAE.
CC {ECO:0000269|PubMed:18029012}.
CC -!- SUBUNIT: Interacts with PDZD11 (PubMed:12763866). Interacts (via N-
CC terminus) with YWHAE (PubMed:18029012). {ECO:0000269|PubMed:12763866,
CC ECO:0000269|PubMed:18029012}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:18029012,
CC ECO:0000269|PubMed:25953895}; Multi-pass membrane protein
CC {ECO:0000255}. Presynaptic cell membrane
CC {ECO:0000250|UniProtKB:Q64568}; Multi-pass membrane protein
CC {ECO:0000255}. Note=Localized at parallel fiber terminals.
CC {ECO:0000250|UniProtKB:Q64568}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=8;
CC Comment=There is a combination of two alternatively spliced domains
CC at N-terminal site A (X and Z) and at C-terminal site C (A, B, E and
CC G). The splice sites have mostly been studied independently. Full
CC isoforms so far detected are isoform XA and isoform XB. Experimental
CC confirmation may be lacking for some isoforms.;
CC Name=XB; Synonyms=AIICI;
CC IsoId=Q16720-1; Sequence=Displayed;
CC Name=XA; Synonyms=AIICII;
CC IsoId=Q16720-2; Sequence=VSP_000393;
CC Name=ZA; Synonyms=AICII;
CC IsoId=Q16720-3; Sequence=VSP_000392, VSP_000393;
CC Name=ZB; Synonyms=AICI;
CC IsoId=Q16720-4; Sequence=VSP_000392;
CC Name=XE; Synonyms=AIICV;
CC IsoId=Q16720-5; Sequence=VSP_000394;
CC Name=ZE; Synonyms=AICV;
CC IsoId=Q16720-6; Sequence=VSP_000392, VSP_000394;
CC Name=XG; Synonyms=AIICVII;
CC IsoId=Q16720-7; Sequence=VSP_000395;
CC Name=ZG; Synonyms=AICVII;
CC IsoId=Q16720-8; Sequence=VSP_000392, VSP_000395;
CC -!- TISSUE SPECIFICITY: Highly expressed in the cerebellum
CC (PubMed:8187550). Expressed in adrenal glands (PubMed:27035656).
CC {ECO:0000269|PubMed:27035656, ECO:0000269|PubMed:8187550}.
CC -!- DEVELOPMENTAL STAGE: Expressed in fetal skeletal muscle.
CC {ECO:0000269|PubMed:8187550}.
CC -!- DISEASE: Spinocerebellar ataxia, X-linked 1 (SCAX1) [MIM:302500]:
CC Spinocerebellar ataxia is a clinically and genetically heterogeneous
CC group of cerebellar disorders. Patients show progressive incoordination
CC of gait and often poor coordination of hands, speech and eye movements,
CC due to degeneration of the cerebellum with variable involvement of the
CC brainstem and spinal cord. SCAX1 is characterized by hypotonia at
CC birth, delayed motor development, gait ataxia, difficulty standing,
CC dysarthria, and slow eye movements. Brain MRI shows cerebellar ataxia.
CC {ECO:0000269|PubMed:22912398, ECO:0000269|PubMed:25953895}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the cation transport ATPase (P-type) (TC 3.A.3)
CC family. Type IIB subfamily. {ECO:0000305}.
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DR EMBL; U57971; AAB09762.1; -; mRNA.
DR EMBL; U60414; AAB38530.1; -; mRNA.
DR EMBL; AH006061; AAC15078.1; -; Genomic_DNA.
DR EMBL; CH471172; EAW72859.1; -; Genomic_DNA.
DR EMBL; U82695; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; U15689; AAA60986.1; -; mRNA.
DR EMBL; U15690; AAA60987.1; -; mRNA.
DR CCDS; CCDS14722.1; -. [Q16720-2]
DR CCDS; CCDS35440.1; -. [Q16720-1]
DR RefSeq; NP_001001344.1; NM_001001344.2. [Q16720-1]
DR RefSeq; NP_068768.2; NM_021949.3. [Q16720-2]
DR RefSeq; XP_005274747.1; XM_005274690.3. [Q16720-1]
DR RefSeq; XP_005274748.1; XM_005274691.3. [Q16720-4]
DR RefSeq; XP_005274749.1; XM_005274692.3. [Q16720-2]
DR AlphaFoldDB; Q16720; -.
DR SMR; Q16720; -.
DR BioGRID; 106982; 85.
DR IntAct; Q16720; 30.
DR MINT; Q16720; -.
DR STRING; 9606.ENSP00000263519; -.
DR DrugBank; DB01189; Desflurane.
DR DrugBank; DB01159; Halothane.
DR iPTMnet; Q16720; -.
DR PhosphoSitePlus; Q16720; -.
DR SwissPalm; Q16720; -.
DR BioMuta; ATP2B3; -.
DR DMDM; 116241261; -.
DR EPD; Q16720; -.
DR jPOST; Q16720; -.
DR MassIVE; Q16720; -.
DR MaxQB; Q16720; -.
DR PaxDb; Q16720; -.
DR PeptideAtlas; Q16720; -.
DR PRIDE; Q16720; -.
DR ProteomicsDB; 61042; -. [Q16720-1]
DR ProteomicsDB; 61043; -. [Q16720-2]
DR ProteomicsDB; 61044; -. [Q16720-3]
DR ProteomicsDB; 61045; -. [Q16720-4]
DR ProteomicsDB; 61046; -. [Q16720-5]
DR ProteomicsDB; 61047; -. [Q16720-6]
DR ProteomicsDB; 61048; -. [Q16720-7]
DR ProteomicsDB; 61049; -. [Q16720-8]
DR Antibodypedia; 443; 71 antibodies from 21 providers.
DR DNASU; 492; -.
DR Ensembl; ENST00000263519.5; ENSP00000263519.4; ENSG00000067842.18. [Q16720-1]
DR Ensembl; ENST00000349466.6; ENSP00000343886.2; ENSG00000067842.18. [Q16720-1]
DR Ensembl; ENST00000359149.8; ENSP00000352062.3; ENSG00000067842.18. [Q16720-2]
DR Ensembl; ENST00000370186.5; ENSP00000359205.1; ENSG00000067842.18. [Q16720-3]
DR Ensembl; ENST00000393842.5; ENSP00000377425.1; ENSG00000067842.18. [Q16720-6]
DR GeneID; 492; -.
DR KEGG; hsa:492; -.
DR MANE-Select; ENST00000263519.5; ENSP00000263519.4; NM_001001344.3; NP_001001344.1.
DR UCSC; uc004fhs.2; human. [Q16720-1]
DR CTD; 492; -.
DR DisGeNET; 492; -.
DR GeneCards; ATP2B3; -.
DR HGNC; HGNC:816; ATP2B3.
DR HPA; ENSG00000067842; Tissue enriched (choroid).
DR MalaCards; ATP2B3; -.
DR MIM; 300014; gene.
DR MIM; 302500; phenotype.
DR neXtProt; NX_Q16720; -.
DR OpenTargets; ENSG00000067842; -.
DR Orphanet; 85142; NON RARE IN EUROPE: Aldosterone-producing adenoma.
DR Orphanet; 314978; X-linked non progressive cerebellar ataxia.
DR PharmGKB; PA25109; -.
DR VEuPathDB; HostDB:ENSG00000067842; -.
DR eggNOG; KOG0204; Eukaryota.
DR GeneTree; ENSGT00940000160765; -.
DR HOGENOM; CLU_002360_9_0_1; -.
DR InParanoid; Q16720; -.
DR OMA; NRSPDFG; -.
DR OrthoDB; 115892at2759; -.
DR PhylomeDB; Q16720; -.
DR TreeFam; TF300330; -.
DR BRENDA; 7.2.2.10; 2681.
DR PathwayCommons; Q16720; -.
DR Reactome; R-HSA-418359; Reduction of cytosolic Ca++ levels.
DR Reactome; R-HSA-5578775; Ion homeostasis.
DR Reactome; R-HSA-936837; Ion transport by P-type ATPases.
DR SignaLink; Q16720; -.
DR BioGRID-ORCS; 492; 13 hits in 696 CRISPR screens.
DR ChiTaRS; ATP2B3; human.
DR GeneWiki; ATP2B3; -.
DR GenomeRNAi; 492; -.
DR Pharos; Q16720; Tbio.
DR PRO; PR:Q16720; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q16720; protein.
DR Bgee; ENSG00000067842; Expressed in endothelial cell and 109 other tissues.
DR Genevisible; Q16720; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:1903561; C:extracellular vesicle; HDA:UniProtKB.
DR GO; GO:0098982; C:GABA-ergic synapse; IDA:SynGO.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0099056; C:integral component of presynaptic membrane; ISS:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:1990032; C:parallel fiber; ISS:UniProtKB.
DR GO; GO:0098688; C:parallel fiber to Purkinje cell synapse; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:SynGO-UCL.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR GO; GO:0019829; F:ATPase-coupled cation transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0015085; F:calcium ion transmembrane transporter activity; IDA:SynGO-UCL.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005388; F:P-type calcium transporter activity; IBA:GO_Central.
DR GO; GO:1905056; F:P-type calcium transporter activity involved in regulation of presynaptic cytosolic calcium ion concentration; IDA:SynGO.
DR GO; GO:0030165; F:PDZ domain binding; IBA:GO_Central.
DR GO; GO:1990034; P:calcium ion export across plasma membrane; IDA:UniProtKB.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IBA:GO_Central.
DR GO; GO:0034220; P:ion transmembrane transport; TAS:Reactome.
DR GO; GO:1903779; P:regulation of cardiac conduction; TAS:Reactome.
DR GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; IDA:SynGO-UCL.
DR Gene3D; 3.40.1110.10; -; 1.
DR Gene3D; 3.40.50.1000; -; 1.
DR InterPro; IPR022141; ATP_Ca_trans_C.
DR InterPro; IPR006068; ATPase_P-typ_cation-transptr_C.
DR InterPro; IPR004014; ATPase_P-typ_cation-transptr_N.
DR InterPro; IPR023299; ATPase_P-typ_cyto_dom_N.
DR InterPro; IPR018303; ATPase_P-typ_P_site.
DR InterPro; IPR023298; ATPase_P-typ_TM_dom_sf.
DR InterPro; IPR008250; ATPase_P-typ_transduc_dom_A_sf.
DR InterPro; IPR036412; HAD-like_sf.
DR InterPro; IPR023214; HAD_sf.
DR InterPro; IPR006408; P-type_ATPase_IIB.
DR InterPro; IPR001757; P_typ_ATPase.
DR InterPro; IPR044492; P_typ_ATPase_HD_dom.
DR Pfam; PF12424; ATP_Ca_trans_C; 1.
DR Pfam; PF00689; Cation_ATPase_C; 1.
DR Pfam; PF00690; Cation_ATPase_N; 1.
DR SFLD; SFLDF00027; p-type_atpase; 1.
DR SMART; SM00831; Cation_ATPase_N; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
DR SUPFAM; SSF81653; SSF81653; 1.
DR SUPFAM; SSF81660; SSF81660; 1.
DR SUPFAM; SSF81665; SSF81665; 1.
DR TIGRFAMs; TIGR01517; ATPase-IIB_Ca; 1.
DR TIGRFAMs; TIGR01494; ATPase_P-type; 3.
DR PROSITE; PS00154; ATPASE_E1_E2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Calcium; Calcium transport;
KW Calmodulin-binding; Cell membrane; Cell projection; Disease variant;
KW Ion transport; Magnesium; Membrane; Metal-binding; Neurodegeneration;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Synapse;
KW Translocase; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..1220
FT /note="Plasma membrane calcium-transporting ATPase 3"
FT /id="PRO_0000046218"
FT TOPO_DOM 1..97
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 98..118
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 119..155
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 156..176
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 177..364
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 365..384
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 385..417
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 418..435
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 436..849
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 850..869
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 870..879
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 880..900
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 901..920
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 921..943
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 944..961
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 962..983
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 984..1002
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1003..1024
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1025..1034
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1035..1056
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1057..1220
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 298..355
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1097..1114
FT /note="Calmodulin-binding subdomain A"
FT /evidence="ECO:0000250"
FT REGION 1115..1124
FT /note="Calmodulin-binding subdomain B"
FT /evidence="ECO:0000250"
FT REGION 1166..1186
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 337..355
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 473
FT /note="4-aspartylphosphate intermediate"
FT /evidence="ECO:0000250"
FT BINDING 794
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 798
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT MOD_RES 8
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64568"
FT MOD_RES 1079
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q64568"
FT MOD_RES 1113
FT /note="Phosphothreonine; by PKC"
FT /evidence="ECO:0000250"
FT VAR_SEQ 306..319
FT /note="Missing (in isoform ZA, isoform ZB, isoform ZE and
FT isoform ZG)"
FT /evidence="ECO:0000305"
FT /id="VSP_000392"
FT VAR_SEQ 1115..1220
FT /note="IRVVKAFRSSLYEGLEKPESKTSIHNFMATPEFLINDYTHNIPLIDDTDVDE
FT NEERLRAPPPPSPNQNNNAIDSGIYLTTHVTKSATSSVFSSSPGSPLHSVETSL -> M
FT EVVSTFKRSGSVQGAVRRRSSVLSQLHDVTNLSTPTHAILSAANPTSAAGNPGGESVP
FT (in isoform XA and isoform ZA)"
FT /evidence="ECO:0000303|PubMed:8765088"
FT /id="VSP_000393"
FT VAR_SEQ 1115..1220
FT /note="IRVVKAFRSSLYEGLEKPESKTSIHNFMATPEFLINDYTHNIPLIDDTDVDE
FT NEERLRAPPPPSPNQNNNAIDSGIYLTTHVTKSATSSVFSSSPGSPLHSVETSL -> M
FT EVVSTFKRSGSVQGAVRRRSSVLSQLHDVTNLSTPTHAILSAANPTSAAGSES (in
FT isoform XE and isoform ZE)"
FT /evidence="ECO:0000305"
FT /id="VSP_000394"
FT VAR_SEQ 1115..1220
FT /note="IRVVKAFRSSLYEGLEKPESKTSIHNFMATPEFLINDYTHNIPLIDDTDVDE
FT NEERLRAPPPPSPNQNNNAIDSGIYLTTHVTKSATSSVFSSSPGSPLHSVETSL -> V
FT CWDGKKMLRTTEVG (in isoform XG and isoform ZG)"
FT /evidence="ECO:0000305"
FT /id="VSP_000395"
FT VARIANT 198
FT /note="I -> M (in dbSNP:rs2269409)"
FT /id="VAR_027928"
FT VARIANT 425..426
FT /note="Missing (in an aldosterone-producing adenoma sample;
FT somatic mutation; increases intracellular calcium
FT concentration that leads to autonomous aldosterone
FT secretion)"
FT /evidence="ECO:0000269|PubMed:27035656"
FT /id="VAR_084697"
FT VARIANT 482
FT /note="R -> H (in SCAX1; the mutant protein is expressed at
FT the plasma membrane, but shows impaired extrusion of
FT intracellular calcium)"
FT /evidence="ECO:0000269|PubMed:25953895"
FT /id="VAR_084698"
FT VARIANT 1107
FT /note="G -> D (in SCAX1; the mutant protein is expressed at
FT the plasma membrane but shows impaired extrusion of
FT intracellular calcium with prolonged retention of
FT cytoplasmic calcium compared to wild-type under physiologic
FT conditions; dbSNP:rs397514619)"
FT /evidence="ECO:0000269|PubMed:22912398"
FT /id="VAR_069308"
FT MUTAGEN 473
FT /note="D->A: Impaired ATPase activity."
FT /evidence="ECO:0000269|PubMed:25953895"
FT CONFLICT 587
FT /note="I -> V (in Ref. 1; AAB09762/AAB38530)"
FT /evidence="ECO:0000305"
FT CONFLICT 654
FT /note="S -> Y (in Ref. 1; AAB09762/AAB38530)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1220 AA; 134197 MW; 03B2BA8A0A33B193 CRC64;
MGDMANSSIE FHPKPQQQRD VPQAGGFGCT LAELRTLMEL RGAEALQKIE EAYGDVSGLC
RRLKTSPTEG LADNTNDLEK RRQIYGQNFI PPKQPKTFLQ LVWEALQDVT LIILEVAAIV
SLGLSFYAPP GEESEACGNV SGGAEDEGEA EAGWIEGAAI LLSVICVVLV TAFNDWSKEK
QFRGLQSRIE QEQKFTVIRN GQLLQVPVAA LVVGDIAQVK YGDLLPADGV LIQANDLKID
ESSLTGESDH VRKSADKDPM LLSGTHVMEG SGRMVVTAVG VNSQTGIIFT LLGAGGEEEE
KKDKKGKQQD GAMESSQTKA KKQDGAVAME MQPLKSAEGG EMEEREKKKA NAPKKEKSVL
QGKLTKLAVQ IGKAGLVMSA ITVIILVLYF VIETFVVEGR TWLAECTPVY VQYFVKFFII
GVTVLVVAVP EGLPLAVTIS LAYSVKKMMK DNNLVRHLDA CETMGNATAI CSDKTGTLTT
NRMTVVQSYL GDTHYKEIPA PSALTPKILD LLVHAISINS AYTTKILPPE KEGALPRQVG
NKTECALLGF VLDLKRDFQP VREQIPEDKL YKVYTFNSVR KSMSTVIRMP DGGFRLFSKG
ASEILLKKCT NILNSNGELR GFRPRDRDDM VRKIIEPMAC DGLRTICIAY RDFSAGQEPD
WDNENEVVGD LTCIAVVGIE DPVRPEVPEA IRKCQRAGIT VRMVTGDNIN TARAIAAKCG
IIQPGEDFLC LEGKEFNRRI RNEKGEIEQE RLDKVWPKLR VLARSSPTDK HTLVKGIIDS
TTGEQRQVVA VTGDGTNDGP ALKKADVGFA MGIAGTDVAK EASDIILTDD NFTSIVKAVM
WGRNVYDSIS KFLQFQLTVN VVAVIVAFTG ACITQDSPLK AVQMLWVNLI MDTFASLALA
TEPPTESLLL RKPYGRDKPL ISRTMMKNIL GHAVYQLAII FTLLFVGELF FDIDSGRNAP
LHSPPSEHYT IIFNTFVMMQ LFNEINARKI HGERNVFDGI FSNPIFCTIV LGTFGIQIVI
VQFGGKPFSC SPLSTEQWLW CLFVGVGELV WGQVIATIPT SQLKCLKEAG HGPGKDEMTD
EELAEGEEEI DHAERELRRG QILWFRGLNR IQTQIRVVKA FRSSLYEGLE KPESKTSIHN
FMATPEFLIN DYTHNIPLID DTDVDENEER LRAPPPPSPN QNNNAIDSGI YLTTHVTKSA
TSSVFSSSPG SPLHSVETSL
