AT2B2_HUMAN
ID AT2B2_HUMAN Reviewed; 1243 AA.
AC Q01814; O00766; Q12994; Q16818;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 2.
DT 03-AUG-2022, entry version 223.
DE RecName: Full=Plasma membrane calcium-transporting ATPase 2;
DE Short=PMCA2 {ECO:0000303|PubMed:15829536};
DE EC=7.2.2.10 {ECO:0000269|PubMed:15829536, ECO:0000269|PubMed:17234811};
DE AltName: Full=Plasma membrane calcium ATPase isoform 2;
DE AltName: Full=Plasma membrane calcium pump isoform 2;
GN Name=ATP2B2 {ECO:0000303|PubMed:15829536, ECO:0000312|HGNC:HGNC:815};
GN Synonyms=PMCA2 {ECO:0000303|PubMed:15829536};
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] (ISOFORM ZB).
RC TISSUE=Brain;
RX PubMed=1427863; DOI=10.1016/s0888-7543(05)80246-0;
RA Brandt P., Ibrahim E., Bruns G.A.P., Neve R.L.;
RT "Determination of the nucleotide sequence and chromosomal localization of
RT the ATP2B2 gene encoding human Ca(2+)-pumping ATPase isoform PMCA2.";
RL Genomics 14:484-487(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ZB), AND ALTERNATIVE SPLICING.
RX PubMed=8428366;
RA Latif F., Duh F.-M., Gnarra J., Tory K., Kuzmin I., Yao M., Stackhouse T.,
RA Modi W., Geil L., Schmidt L., Li H., Orcutt M.L., Maher E., Richards F.,
RA Phipps M., Ferguson-Smith M., le Paslier D., Linehan W.M., Zbar B.,
RA Lerman M.I.;
RT "von Hippel-Lindau syndrome: cloning and identification of the plasma
RT membrane Ca(++)-transporting ATPase isoform 2 gene that resides in the von
RT Hippel-Lindau gene region.";
RL Cancer Res. 53:861-867(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM WB), AND ALTERNATIVE SPLICING.
RC TISSUE=Brain, and Skeletal muscle;
RX PubMed=1313367; DOI=10.1111/j.1432-1033.1992.tb16784.x;
RA Heim R., Hug M., Iwata T., Strehler E.E., Carafoli E.;
RT "Microdiversity of human-plasma-membrane calcium-pump isoform 2 generated
RT by alternative RNA splicing in the N-terminal coding region.";
RL Eur. J. Biochem. 205:333-340(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [5]
RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS WA; YA AND ZA), AND TISSUE
RP SPECIFICITY.
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 [6]
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 [7]
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 [8]
RP SUBCELLULAR LOCATION (ISOFORMS WA; WB; XB; ZA AND ZB).
RX PubMed=12624087; DOI=10.1074/jbc.m301482200;
RA Chicka M.C., Strehler E.E.;
RT "Alternative splicing of the first intracellular loop of plasma membrane
RT Ca2+-ATPase isoform 2 alters its membrane targeting.";
RL J. Biol. Chem. 278:18464-18470(2003).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1177 (ISOFORM WA),
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1146 (ISOFORM XA),
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1163 (ISOFORM YA),
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1132 (ISOFORM ZA), AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1211, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-1165 (ISOFORM WA), PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-1134 (ISOFORM XA), PHOSPHORYLATION [LARGE SCALE ANALYSIS]
RP AT SER-1151 (ISOFORM YA), PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT
RP SER-1120 (ISOFORM ZA), AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [11]
RP FUNCTION.
RX PubMed=25690014; DOI=10.1126/scisignal.2005672;
RA Paszty K., Caride A.J., Bajzer Z., Offord C.P., Padanyi R., Hegedus L.,
RA Varga K., Strehler E.E., Enyedi A.;
RT "Plasma membrane Ca2+-ATPases can shape the pattern of Ca2+ transients
RT induced by store-operated C2+ entry.";
RL Sci. Signal. 8:ra19-ra19(2015).
RN [12]
RP CHARACTERIZATION OF VARIANT MET-631, FUNCTION, CATALYTIC ACTIVITY, AND
RP ACTIVITY REGULATION.
RX PubMed=15829536; DOI=10.1056/nejmoa043899;
RA Schultz J.M., Yang Y., Caride A.J., Filoteo A.G., Penheiter A.R.,
RA Lagziel A., Morell R.J., Mohiddin S.A., Fananapazir L., Madeo A.C.,
RA Penniston J.T., Griffith A.J.;
RT "Modification of human hearing loss by plasma-membrane calcium pump
RT PMCA2.";
RL N. Engl. J. Med. 352:1557-1564(2005).
RN [13]
RP CHARACTERIZATION OF VARIANT SER-293, FUNCTION, CATALYTIC ACTIVITY, AND
RP SUBCELLULAR LOCATION.
RX PubMed=17234811; DOI=10.1073/pnas.0609775104;
RA Ficarella R., Di Leva F., Bortolozzi M., Ortolano S., Donaudy F.,
RA Petrillo M., Melchionda S., Lelli A., Domi T., Fedrizzi L., Lim D.,
RA Shull G.E., Gasparini P., Brini M., Mammano F., Carafoli E.;
RT "A functional study of plasma-membrane calcium-pump isoform 2 mutants
RT causing digenic deafness.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1516-1521(2007).
CC -!- FUNCTION: ATP-driven Ca(2+) ion pump involved in the maintenance of
CC basal intracellular Ca(2+) levels in specialized cells of cerebellar
CC circuit and vestibular and cochlear systems (PubMed:17234811,
CC PubMed:15829536). Uses ATP as an energy source to transport cytosolic
CC Ca(2+) ions across the plasma membrane to the extracellular compartment
CC (PubMed:17234811, PubMed:15829536). Has fast activation and Ca(2+)
CC clearance rate suited to control fast neuronal Ca(2+) dynamics. At
CC parallel fiber to Purkinje neuron synapse, mediates presynaptic Ca(2+)
CC efflux in response to climbing fiber-induced Ca(2+) rise. Provides for
CC fast return of Ca(2+) concentrations back to their resting levels,
CC ultimately contributing to long-term depression induction and motor
CC learning (By similarity). Plays an essential role in hearing and
CC balance (PubMed:17234811, PubMed:15829536). In cochlear hair cells,
CC shuttles Ca(2+) ions from stereocilia to the endolymph and dissipates
CC Ca(2+) transients generated by the opening of the mechanoelectrical
CC transduction channels. Regulates Ca(2+) levels in the vestibular
CC system, where it contributes to the formation of otoconia
CC (PubMed:17234811, PubMed:15829536). In non-excitable cells, regulates
CC Ca(2+) signaling through spatial control of Ca(2+) ions extrusion and
CC dissipation of Ca(2+) transients generated by store-operated channels
CC (PubMed:25690014). In lactating mammary gland, allows for the high
CC content of Ca(2+) ions in the milk (By similarity).
CC {ECO:0000250|UniProtKB:Q9R0K7, ECO:0000269|PubMed:15829536,
CC ECO:0000269|PubMed:17234811, ECO:0000269|PubMed:25690014}.
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:0000269|PubMed:15829536, ECO:0000269|PubMed:17234811};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18106;
CC Evidence={ECO:0000305|PubMed:15829536, ECO:0000305|PubMed:17234811};
CC -!- ACTIVITY REGULATION: Up-regulated by calmodulin which increases the
CC affinity of the pump for Ca(2+) ions. {ECO:0000269|PubMed:15829536}.
CC -!- SUBUNIT: Interacts with PDZD11. {ECO:0000269|PubMed:12763866}.
CC -!- INTERACTION:
CC Q01814; P01258: CALCA; NbExp=2; IntAct=EBI-1174243, EBI-1018474;
CC Q01814; Q14160: SCRIB; NbExp=2; IntAct=EBI-1174243, EBI-357345;
CC Q01814-1; Q63622: Dlg2; Xeno; NbExp=2; IntAct=EBI-1174262, EBI-396947;
CC Q01814-1; Q8SQG9: SLC9A3R2; Xeno; NbExp=3; IntAct=EBI-1174262, EBI-1174758;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17234811};
CC Multi-pass membrane protein {ECO:0000255}. Synapse
CC {ECO:0000250|UniProtKB:Q9R0K7}.
CC -!- SUBCELLULAR LOCATION: [Isoform WA]: Apical cell membrane
CC {ECO:0000269|PubMed:12624087}; Multi-pass membrane protein
CC {ECO:0000255}. Basolateral cell membrane {ECO:0000269|PubMed:12624087};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- SUBCELLULAR LOCATION: [Isoform WB]: Apical cell membrane
CC {ECO:0000269|PubMed:12624087}; Multi-pass membrane protein
CC {ECO:0000255}. Basolateral cell membrane {ECO:0000269|PubMed:12624087};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- SUBCELLULAR LOCATION: [Isoform XB]: Basolateral cell membrane
CC {ECO:0000269|PubMed:12624087}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- SUBCELLULAR LOCATION: [Isoform ZA]: Basolateral cell membrane
CC {ECO:0000269|PubMed:12624087}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- SUBCELLULAR LOCATION: [Isoform ZB]: Basolateral cell membrane
CC {ECO:0000269|PubMed:12624087}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=8;
CC Comment=There is a combination of two alternative spliced domains at
CC N-terminal site A (Z, X, Y and W) and at C-terminal site C (A and B).
CC So far the splice sites have only been studied independently.
CC Experimental confirmation may be lacking for some isoforms.;
CC Name=WB; Synonyms=AIIICI;
CC IsoId=Q01814-1; Sequence=Displayed;
CC Name=WA; Synonyms=AIIICII;
CC IsoId=Q01814-2; Sequence=VSP_000386;
CC Name=YA; Synonyms=AIICII;
CC IsoId=Q01814-3; Sequence=VSP_000385, VSP_000386;
CC Name=ZA; Synonyms=AICII;
CC IsoId=Q01814-4; Sequence=VSP_000384, VSP_000386;
CC Name=YB; Synonyms=AIICI;
CC IsoId=Q01814-5; Sequence=VSP_000385;
CC Name=ZB; Synonyms=AICI;
CC IsoId=Q01814-6; Sequence=VSP_000384;
CC Name=XA;
CC IsoId=Q01814-7; Sequence=VSP_040837, VSP_000386;
CC Name=XB;
CC IsoId=Q01814-8; Sequence=VSP_040837;
CC -!- TISSUE SPECIFICITY: Mainly expressed in brain cortex. Found in low
CC levels in skeletal muscle, heart muscle, stomach, liver, kidney and
CC lung. Isoforms containing segment B are found in brain cortex and at
CC low levels in other tissues. Isoforms containing segments X and W are
CC found at low levels in all tissues. Isoforms containing segment A and
CC segment Z are found at low levels in skeletal muscle and heart muscle.
CC {ECO:0000269|PubMed:8245032}.
CC -!- DISEASE: Note=May act as a disease modifier. ATP2B2 variants may
CC exacerbate the severity of non-syndromic sensorineural hearing loss in
CC patients carrying causative variants in the CDH23 gene. Sensorineural
CC deafness results from damage to the neural receptors of the inner ear,
CC the nerve pathways to the brain, or the area of the brain that receives
CC sound information. {ECO:0000269|PubMed:15829536,
CC ECO:0000269|PubMed:17234811}.
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; M97260; AAA36456.1; -; mRNA.
DR EMBL; L20977; AAA50877.1; -; mRNA.
DR EMBL; L00620; AAA51893.1; -; mRNA.
DR EMBL; X63575; CAA45131.1; -; mRNA.
DR EMBL; AC018839; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC090841; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; U15688; AAA60985.1; -; mRNA.
DR CCDS; CCDS2601.1; -. [Q01814-6]
DR CCDS; CCDS33701.1; -. [Q01814-1]
DR CCDS; CCDS82733.1; -. [Q01814-4]
DR PIR; S22393; S22393.
DR RefSeq; NP_001001331.1; NM_001001331.2. [Q01814-1]
DR RefSeq; NP_001317540.1; NM_001330611.1. [Q01814-4]
DR RefSeq; XP_005265236.1; XM_005265179.4. [Q01814-1]
DR RefSeq; XP_006713238.1; XM_006713175.3. [Q01814-1]
DR RefSeq; XP_011532054.1; XM_011533752.2. [Q01814-1]
DR RefSeq; XP_016861970.1; XM_017006481.1. [Q01814-1]
DR RefSeq; XP_016861971.1; XM_017006482.1. [Q01814-1]
DR RefSeq; XP_016861972.1; XM_017006483.1. [Q01814-8]
DR RefSeq; XP_016861973.1; XM_017006484.1. [Q01814-8]
DR RefSeq; XP_016861975.1; XM_017006486.1. [Q01814-2]
DR RefSeq; XP_016861978.1; XM_017006489.1. [Q01814-7]
DR AlphaFoldDB; Q01814; -.
DR SMR; Q01814; -.
DR BioGRID; 106981; 208.
DR ELM; Q01814; -.
DR IntAct; Q01814; 113.
DR MINT; Q01814; -.
DR STRING; 9606.ENSP00000353414; -.
DR DrugBank; DB01189; Desflurane.
DR DrugBank; DB01159; Halothane.
DR TCDB; 3.A.3.2.40; the p-type atpase (p-atpase) superfamily.
DR iPTMnet; Q01814; -.
DR PhosphoSitePlus; Q01814; -.
DR SwissPalm; Q01814; -.
DR BioMuta; ATP2B2; -.
DR DMDM; 14286115; -.
DR EPD; Q01814; -.
DR jPOST; Q01814; -.
DR MassIVE; Q01814; -.
DR MaxQB; Q01814; -.
DR PaxDb; Q01814; -.
DR PeptideAtlas; Q01814; -.
DR PRIDE; Q01814; -.
DR ProteomicsDB; 57993; -. [Q01814-1]
DR ProteomicsDB; 57994; -. [Q01814-2]
DR ProteomicsDB; 57995; -. [Q01814-3]
DR ProteomicsDB; 57996; -. [Q01814-4]
DR ProteomicsDB; 57997; -. [Q01814-5]
DR ProteomicsDB; 57998; -. [Q01814-6]
DR ProteomicsDB; 57999; -. [Q01814-7]
DR ProteomicsDB; 58000; -. [Q01814-8]
DR Antibodypedia; 26012; 129 antibodies from 24 providers.
DR DNASU; 491; -.
DR Ensembl; ENST00000360273.7; ENSP00000353414.2; ENSG00000157087.20. [Q01814-1]
DR Ensembl; ENST00000397077.6; ENSP00000380267.1; ENSG00000157087.20. [Q01814-6]
DR Ensembl; ENST00000452124.2; ENSP00000414854.2; ENSG00000157087.20. [Q01814-8]
DR Ensembl; ENST00000460129.5; ENSP00000424494.1; ENSG00000157087.20. [Q01814-4]
DR Ensembl; ENST00000643662.1; ENSP00000495924.1; ENSG00000157087.20. [Q01814-7]
DR Ensembl; ENST00000644807.1; ENSP00000495228.1; ENSG00000157087.20. [Q01814-4]
DR Ensembl; ENST00000645850.1; ENSP00000494716.1; ENSG00000157087.20. [Q01814-1]
DR Ensembl; ENST00000646379.1; ENSP00000494381.1; ENSG00000157087.20. [Q01814-6]
DR GeneID; 491; -.
DR KEGG; hsa:491; -.
DR MANE-Select; ENST00000360273.7; ENSP00000353414.2; NM_001001331.4; NP_001001331.1.
DR UCSC; uc003bvt.3; human. [Q01814-1]
DR CTD; 491; -.
DR DisGeNET; 491; -.
DR GeneCards; ATP2B2; -.
DR HGNC; HGNC:815; ATP2B2.
DR HPA; ENSG00000157087; Tissue enhanced (brain, choroid plexus, salivary gland, skeletal muscle).
DR MalaCards; ATP2B2; -.
DR MIM; 108733; gene.
DR neXtProt; NX_Q01814; -.
DR OpenTargets; ENSG00000157087; -.
DR Orphanet; 90636; Autosomal recessive non-syndromic sensorineural deafness type DFNB.
DR PharmGKB; PA25108; -.
DR VEuPathDB; HostDB:ENSG00000157087; -.
DR eggNOG; KOG0204; Eukaryota.
DR GeneTree; ENSGT00940000161461; -.
DR HOGENOM; CLU_002360_9_0_1; -.
DR InParanoid; Q01814; -.
DR OMA; GMVYKDF; -.
DR OrthoDB; 115892at2759; -.
DR PhylomeDB; Q01814; -.
DR TreeFam; TF300330; -.
DR BRENDA; 7.2.2.10; 2681.
DR PathwayCommons; Q01814; -.
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 Reactome; R-HSA-9662360; Sensory processing of sound by inner hair cells of the cochlea. [Q01814-2]
DR Reactome; R-HSA-9662361; Sensory processing of sound by outer hair cells of the cochlea. [Q01814-2]
DR SignaLink; Q01814; -.
DR SIGNOR; Q01814; -.
DR BioGRID-ORCS; 491; 8 hits in 1062 CRISPR screens.
DR ChiTaRS; ATP2B2; human.
DR GeneWiki; ATP2B2; -.
DR GenomeRNAi; 491; -.
DR Pharos; Q01814; Tbio.
DR PRO; PR:Q01814; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q01814; protein.
DR Bgee; ENSG00000157087; Expressed in lateral nuclear group of thalamus and 149 other tissues.
DR ExpressionAtlas; Q01814; baseline and differential.
DR Genevisible; Q01814; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0032591; C:dendritic spine membrane; ISS:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; 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:0099061; C:integral component of postsynaptic density membrane; IEA:Ensembl.
DR GO; GO:0099059; C:integral component of presynaptic active zone membrane; IEA:Ensembl.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0045121; C:membrane raft; IEA:Ensembl.
DR GO; GO:0032809; C:neuronal cell body membrane; IEA:Ensembl.
DR GO; GO:0098688; C:parallel fiber to Purkinje cell synapse; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0098839; C:postsynaptic density membrane; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
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:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; IDA:UniProtKB.
DR GO; GO:0035254; F:glutamate receptor binding; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005388; F:P-type calcium transporter activity; IDA:UniProtKB.
DR GO; GO:1905059; F:P-type calcium transporter activity involved in regulation of postsynaptic cytosolic calcium ion concentration; IDA:SynGO.
DR GO; GO:1905056; F:P-type calcium transporter activity involved in regulation of presynaptic cytosolic calcium ion concentration; IMP:SynGO.
DR GO; GO:0030165; F:PDZ domain binding; IDA:UniProtKB.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB.
DR GO; GO:0007420; P:brain development; IEA:Ensembl.
DR GO; GO:0006816; P:calcium ion transport; IMP:DFLAT.
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:0003407; P:neural retina development; IEA:Ensembl.
DR GO; GO:0030182; P:neuron differentiation; IDA:UniProtKB.
DR GO; GO:1903779; P:regulation of cardiac conduction; TAS:Reactome.
DR GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; IMP:DFLAT.
DR GO; GO:0007605; P:sensory perception of sound; IMP:UniProtKB.
DR Gene3D; 3.40.1110.10; -; 1.
DR Gene3D; 3.40.50.1000; -; 1.
DR InterPro; IPR030322; ATP2B2.
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 PANTHER; PTHR24093:SF377; PTHR24093:SF377; 1.
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; Ion transport; Magnesium; Membrane;
KW Metal-binding; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Synapse; Translocase; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..1243
FT /note="Plasma membrane calcium-transporting ATPase 2"
FT /id="PRO_0000046214"
FT TOPO_DOM 1..94
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 95..115
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 116..152
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 153..173
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 174..390
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 391..410
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 411..443
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 444..461
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 462..875
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 876..895
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 896..905
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 906..926
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 927..946
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 947..969
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 970..987
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 988..1009
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1010..1028
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1029..1050
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1051..1060
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1061..1082
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1083..1243
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 334..381
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1123..1140
FT /note="Calmodulin-binding subdomain A"
FT /evidence="ECO:0000250"
FT REGION 1141..1150
FT /note="Calmodulin-binding subdomain B"
FT /evidence="ECO:0000250"
FT REGION 1194..1243
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..21
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 334..351
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 365..381
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1195..1243
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 499
FT /note="4-aspartylphosphate intermediate"
FT BINDING 820
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 824
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT MOD_RES 18
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9R0K7"
FT MOD_RES 1139
FT /note="Phosphothreonine; by PKC"
FT /evidence="ECO:0000250|UniProtKB:P20020"
FT MOD_RES 1178
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9R0K7"
FT MOD_RES 1188
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9R0K7"
FT MOD_RES 1201
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:Q9R0K7"
FT MOD_RES 1211
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VAR_SEQ 303..347
FT /note="Missing (in isoform ZA and isoform ZB)"
FT /evidence="ECO:0000303|PubMed:1427863,
FT ECO:0000303|PubMed:8428366"
FT /id="VSP_000384"
FT VAR_SEQ 304..334
FT /note="Missing (in isoform XA and isoform XB)"
FT /evidence="ECO:0000305"
FT /id="VSP_040837"
FT VAR_SEQ 334..347
FT /note="Missing (in isoform YA and isoform YB)"
FT /evidence="ECO:0000305"
FT /id="VSP_000385"
FT VAR_SEQ 1141..1243
FT /note="IRVVKAFRSSLYEGLEKPESRTSIHNFMAHPEFRIEDSQPHIPLIDDTDLEE
FT DAALKQNSSPPSSLNKNNSAIDSGINLTTDTSKSATSSSPGSPIHSLETSL -> IEVV
FT NTFKSGASFQGALRRQSSVTSQSQDVANLSSPSRVSLSNALSSPTSLPPAAAGQG (in
FT isoform WA, isoform XA, isoform YA and isoform ZA)"
FT /evidence="ECO:0000305"
FT /id="VSP_000386"
FT VARIANT 293
FT /note="G -> S (may exacerbate the severity of non-syndromic
FT sensorineural hearing loss; delayed calcium export)"
FT /evidence="ECO:0000269|PubMed:17234811"
FT /id="VAR_084464"
FT VARIANT 631
FT /note="V -> M (may exacerbate the severity of non-syndromic
FT sensorineural hearing loss; resulted in 50% decrease of the
FT calcium ATPase activity)"
FT /evidence="ECO:0000269|PubMed:15829536"
FT /id="VAR_084465"
FT CONFLICT 92..94
FT /note="PKT -> AKP (in Ref. 1; AAA36456)"
FT /evidence="ECO:0000305"
FT CONFLICT 126
FT /note="P -> R (in Ref. 2; AAA50877/AAA51893)"
FT /evidence="ECO:0000305"
FT CONFLICT 517
FT /note="G -> D (in Ref. 2; AAA50877/AAA51893)"
FT /evidence="ECO:0000305"
FT CONFLICT 667..668
FT /note="DG -> EW (in Ref. 1; AAA36456)"
FT /evidence="ECO:0000305"
FT CONFLICT 1212
FT /note="A -> S (in Ref. 1; AAA36456)"
FT /evidence="ECO:0000305"
FT MOD_RES Q01814-2:1165
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES Q01814-2:1177
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES Q01814-3:1151
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES Q01814-3:1163
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES Q01814-4:1120
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES Q01814-4:1132
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES Q01814-7:1134
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES Q01814-7:1146
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
SQ SEQUENCE 1243 AA; 136876 MW; 7F10221B7B9AC3A2 CRC64;
MGDMTNSDFY SKNQRNESSH GGEFGCTMEE LRSLMELRGT EAVVKIKETY GDTEAICRRL
KTSPVEGLPG TAPDLEKRKQ IFGQNFIPPK KPKTFLQLVW EALQDVTLII LEIAAIISLG
LSFYHPPGEG NEGCATAQGG AEDEGEAEAG WIEGAAILLS VICVVLVTAF NDWSKEKQFR
GLQSRIEQEQ KFTVVRAGQV VQIPVAEIVV GDIAQVKYGD LLPADGLFIQ GNDLKIDESS
LTGESDQVRK SVDKDPMLLS GTHVMEGSGR MLVTAVGVNS QTGIIFTLLG AGGEEEEKKD
KKGVKKGDGL QLPAADGAAA SNAADSANAS LVNGKMQDGN VDASQSKAKQ QDGAAAMEMQ
PLKSAEGGDA DDRKKASMHK KEKSVLQGKL TKLAVQIGKA GLVMSAITVI ILVLYFTVDT
FVVNKKPWLP ECTPVYVQYF VKFFIIGVTV LVVAVPEGLP LAVTISLAYS VKKMMKDNNL
VRHLDACETM GNATAICSDK TGTLTTNRMT VVQAYVGDVH YKEIPDPSSI NTKTMELLIN
AIAINSAYTT KILPPEKEGA LPRQVGNKTE CGLLGFVLDL KQDYEPVRSQ MPEEKLYKVY
TFNSVRKSMS TVIKLPDESF RMYSKGASEI VLKKCCKILN GAGEPRVFRP RDRDEMVKKV
IEPMACDGLR TICVAYRDFP SSPEPDWDNE NDILNELTCI CVVGIEDPVR PEVPEAIRKC
QRAGITVRMV TGDNINTARA IAIKCGIIHP GEDFLCLEGK EFNRRIRNEK GEIEQERIDK
IWPKLRVLAR SSPTDKHTLV KGIIDSTHTE QRQVVAVTGD GTNDGPALKK ADVGFAMGIA
GTDVAKEASD IILTDDNFSS IVKAVMWGRN VYDSISKFLQ FQLTVNVVAV IVAFTGACIT
QDSPLKAVQM LWVNLIMDTF ASLALATEPP TETLLLRKPY GRNKPLISRT MMKNILGHAV
YQLALIFTLL FVGEKMFQID SGRNAPLHSP PSEHYTIIFN TFVMMQLFNE INARKIHGER
NVFDGIFRNP IFCTIVLGTF AIQIVIVQFG GKPFSCSPLQ LDQWMWCIFI GLGELVWGQV
IATIPTSRLK FLKEAGRLTQ KEEIPEEELN EDVEEIDHAE RELRRGQILW FRGLNRIQTQ
IRVVKAFRSS LYEGLEKPES RTSIHNFMAH PEFRIEDSQP HIPLIDDTDL EEDAALKQNS
SPPSSLNKNN SAIDSGINLT TDTSKSATSS SPGSPIHSLE TSL
