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   27-MAR-2024, entry version 217.
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   CCDS; CCDS94697.1; -. [Q16720-6]
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.
DR   RefSeq; XP_005274748.1; XM_005274691.3. [Q16720-4]
DR   RefSeq; XP_005274749.1; XM_005274692.3.
DR   AlphaFoldDB; Q16720; -.
DR   SMR; Q16720; -.
DR   BioGRID; 106982; 88.
DR   IntAct; Q16720; 30.
DR   MINT; Q16720; -.
DR   STRING; 9606.ENSP00000263519; -.
DR   DrugBank; DB01189; Desflurane.
DR   DrugBank; DB01159; Halothane.
DR   DrugBank; DB00867; Ritodrine.
DR   DrugBank; DB01236; Sevoflurane.
DR   TCDB; 3.A.3.2.50; the p-type atpase (p-atpase) superfamily.
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; 9606-ENSP00000263519; -.
DR   PeptideAtlas; 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   Pumba; Q16720; -.
DR   Antibodypedia; 443; 88 antibodies from 21 providers.
DR   DNASU; 492; -.
DR   Ensembl; ENST00000263519.5; ENSP00000263519.4; ENSG00000067842.19. [Q16720-1]
DR   Ensembl; ENST00000349466.6; ENSP00000343886.2; ENSG00000067842.19. [Q16720-1]
DR   Ensembl; ENST00000359149.9; ENSP00000352062.3; ENSG00000067842.19. [Q16720-2]
DR   Ensembl; ENST00000370186.5; ENSP00000359205.1; ENSG00000067842.19. [Q16720-3]
DR   Ensembl; ENST00000393842.5; ENSP00000377425.1; ENSG00000067842.19. [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   AGR; HGNC:816; -.
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; QLAVTFM; -.
DR   OrthoDB; 847at2759; -.
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 770 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 110 other cell types or tissues.
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: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:0042734; C:presynaptic membrane; ISS:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
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:0034220; P:monoatomic 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   CDD; cd02081; P-type_ATPase_Ca_PMCA-like; 1.
DR   Gene3D; 3.40.1110.10; Calcium-transporting ATPase, cytoplasmic domain N; 1.
DR   Gene3D; 2.70.150.10; Calcium-transporting ATPase, cytoplasmic transduction domain A; 1.
DR   Gene3D; 1.20.1110.10; Calcium-transporting ATPase, transmembrane domain; 2.
DR   Gene3D; 3.40.50.1000; HAD superfamily/HAD-like; 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   NCBIfam; TIGR01517; ATPase-IIB_Ca; 1.
DR   NCBIfam; TIGR01494; ATPase_P-type; 3.
DR   PANTHER; PTHR24093; CATION TRANSPORTING ATPASE; 1.
DR   PANTHER; PTHR24093:SF284; PLASMA MEMBRANE CALCIUM-TRANSPORTING ATPASE 3; 1.
DR   Pfam; PF12424; ATP_Ca_trans_C; 1.
DR   Pfam; PF13246; Cation_ATPase; 1.
DR   Pfam; PF00689; Cation_ATPase_C; 1.
DR   Pfam; PF00690; Cation_ATPase_N; 1.
DR   Pfam; PF00122; E1-E2_ATPase; 2.
DR   Pfam; PF00702; Hydrolase; 1.
DR   PRINTS; PR00119; CATATPASE.
DR   SFLD; SFLDS00003; Haloacid_Dehalogenase; 1.
DR   SFLD; SFLDF00027; p-type_atpase; 1.
DR   SMART; SM00831; Cation_ATPase_N; 1.
DR   SUPFAM; SSF81653; Calcium ATPase, transduction domain A; 1.
DR   SUPFAM; SSF81665; Calcium ATPase, transmembrane domain M; 1.
DR   SUPFAM; SSF56784; HAD-like; 1.
DR   SUPFAM; SSF81660; Metal cation-transporting ATPase, ATP-binding domain N; 1.
DR   PROSITE; PS00154; ATPASE_E1_E2; 1.
DR   Genevisible; Q16720; HS.
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
//