AT2B1_HUMAN
ID AT2B1_HUMAN Reviewed; 1220 AA.
AC P20020; Q12992; Q12993; Q13819; Q13820; Q13821; Q16504; Q93082;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 12-SEP-2018, sequence version 4.
DT 03-AUG-2022, entry version 231.
DE RecName: Full=Plasma membrane calcium-transporting ATPase 1 {ECO:0000305};
DE EC=7.2.2.10 {ECO:0000305|PubMed:30190470};
DE AltName: Full=Plasma membrane calcium ATPase isoform 1 {ECO:0000303|PubMed:8396145};
DE Short=PMCA1 {ECO:0000303|PubMed:8396145};
DE AltName: Full=Plasma membrane calcium pump isoform 1;
GN Name=ATP2B1 {ECO:0000312|HGNC:HGNC:814};
GN Synonyms=PMCA1 {ECO:0000303|PubMed:8396145};
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 B).
RC TISSUE=Erythrocyte;
RX PubMed=2844759; DOI=10.1016/s0021-9258(18)68198-0;
RA Verma A.K., Filoteo A.G., Stanford D.R., Wieben E.D., Penniston J.T.,
RA Strehler E.E., Fischer R., Heim R., Vogel G., Mathews S.,
RA Strehler-Page M.-A., James P., Vorherr T.E., Krebs J., Carafoli E.;
RT "Complete primary structure of a human plasma membrane Ca2+ pump.";
RL J. Biol. Chem. 263:14152-14159(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B).
RC TISSUE=Osteoblast;
RX PubMed=8386431; DOI=10.1002/jbmr.5650080415;
RA Kumar R., Haugen J.D., Penniston J.T.;
RT "Molecular cloning of a plasma membrane calcium pump from human
RT osteoblasts.";
RL J. Bone Miner. Res. 8:505-513(1993).
RN [3]
RP PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS A AND B).
RC TISSUE=Leukocyte;
RX PubMed=8396145; DOI=10.1016/s0021-9258(19)36574-3;
RA Hilfiker H., Strehler-Page M.-A., Stauffer T.P., Carafoli E.,
RA Strehler E.E.;
RT "Structure of the gene encoding the human plasma membrane calcium pump
RT isoform 1.";
RL J. Biol. Chem. 268:19717-19725(1993).
RN [4]
RP SEQUENCE REVISION.
RA Strehler E.E., Strehler-Page M.-A.;
RL Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS A; C AND D).
RC TISSUE=Fetal skeletal muscle;
RX PubMed=2528729; DOI=10.1073/pnas.86.18.6908;
RA Strehler E.E., Strehler-Page M.-A., Vogel G., Carafoli E.;
RT "mRNAs for plasma membrane calcium pump isoforms differing in their
RT regulatory domain are generated by alternative splicing that involves two
RT internal donor sites in a single exon.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:6908-6912(1989).
RN [6]
RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), REGION, ALTERNATIVE
RP SPLICING, AND SUBUNIT.
RC TISSUE=Fetal brain;
RX PubMed=1332771; DOI=10.1021/bi00162a016;
RA Kessler F., Falchetto R., Heim R., Meili R., Vorherr T.E., Strehler E.E.,
RA Carafoli E.;
RT "Study of calmodulin binding to the alternatively spliced C-terminal domain
RT of the plasma membrane Ca2+ pump.";
RL Biochemistry 31:11785-11792(1992).
RN [7]
RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND E).
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 [8]
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 [9]
RP ALTERNATIVE SPLICING (ISOFORM K).
RC TISSUE=Small intestine mucosa;
RX PubMed=7694502; DOI=10.1152/ajpgi.1993.265.5.g917;
RA Howard A., Legon S., Walters J.R.;
RT "Human and rat intestinal plasma membrane calcium pump isoforms.";
RL Am. J. Physiol. 265:G917-G925(1993).
RN [10]
RP PHOSPHORYLATION BY CAMP KINASE.
RX PubMed=2548572; DOI=10.1021/bi00436a020;
RA James P.H., Pruschy M., Vorherr T.E., Penniston J.T., Carafoli E.;
RT "Primary structure of the cAMP-dependent phosphorylation site of the plasma
RT membrane calcium pump.";
RL Biochemistry 28:4253-4258(1989).
RN [11]
RP PHOSPHORYLATION AT THR-1116 BY PROTEIN KINASE C.
RX PubMed=1827443; DOI=10.1016/s0021-9258(18)31554-0;
RA Wang K.K.W., Wright L.C., Machan C.L., Allen B.G., Conigrave A.D.,
RA Roufogalis B.D.;
RT "Protein kinase C phosphorylates the carboxyl terminus of the plasma
RT membrane Ca(2+)-ATPase from human erythrocytes.";
RL J. Biol. Chem. 266:9078-9085(1991).
RN [12]
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 [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1155 AND SER-1182, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [14]
RP INTERACTION WITH YWHAE, AND SUBCELLULAR LOCATION.
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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-17; SER-1155; THR-1165;
RP SER-1178 AND SER-1182, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT GLY-2, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-1155 AND THR-1165, CLEAVAGE OF INITIATOR METHIONINE [LARGE
RP SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=21400627; DOI=10.1002/mrd.21303;
RA Yang H., Choi K.C., Hyun S.H., Jeung E.B.;
RT "Coexpression and estrogen-mediated regulation of TRPV6 and PMCA1 in the
RT human endometrium during the menstrual cycle.";
RL Mol. Reprod. Dev. 78:274-282(2011).
RN [19]
RP INTERACTION WITH SLC35G1 AND STIM1.
RX PubMed=22084111; DOI=10.1073/pnas.1117231108;
RA Krapivinsky G., Krapivinsky L., Stotz S.C., Manasian Y., Clapham D.E.;
RT "POST, partner of stromal interaction molecule 1 (STIM1), targets STIM1 to
RT multiple transporters.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:19234-19239(2011).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1155; SER-1178 AND SER-1182,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-8; SER-17; SER-1155 AND
RP THR-1165, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1155, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE 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 [23]
RP FUNCTION.
RX PubMed=29104511; DOI=10.7150/ijbs.19666;
RA Long Y., Xia J.Y., Chen S.W., Gao C.L., Liang G.N., He X.M., Wu J.,
RA Jiang C.X., Liu X., Huang W., Wan Q., Xu Y.;
RT "ATP2B1 gene Silencing Increases Insulin Sensitivity through Facilitating
RT Akt Activation via the Ca2+/calmodulin Signaling Pathway and Ca2+-
RT associated eNOS Activation in Endothelial Cells.";
RL Int. J. Biol. Sci. 13:1203-1212(2017).
RN [24] {ECO:0007744|PDB:6A69}
RP STRUCTURE BY ELECTRON MICROSCOPY (4.11 ANGSTROMS) IN COMPLEX WITH NPTN,
RP BIOPHYSICOCHEMICAL PROPERTIES, CATALYTIC ACTIVITY, AND TOPOLOGY.
RX PubMed=30190470; DOI=10.1038/s41467-018-06075-7;
RA Gong D., Chi X., Ren K., Huang G., Zhou G., Yan N., Lei J., Zhou Q.;
RT "Structure of the human plasma membrane Ca2+-ATPase 1 in complex with its
RT obligatory subunit neuroplastin.";
RL Nat. Commun. 9:3623-3623(2018).
RN [25]
RP VARIANT ARG-267.
RX PubMed=9020386; DOI=10.1007/s001090050088;
RA Benkwitz C., Kubsisch C., Kraft K., Neyses L.;
RT "Investigation of the Met-267 Arg exchange in isoform 1 of the human plasma
RT membrane calcium pump in patients with essential hypertension by the
RT amplification-created restriction site technique.";
RL J. Mol. Med. 75:62-66(1997).
CC -!- FUNCTION: Catalyzes the hydrolysis of ATP coupled with the transport of
CC calcium from the cytoplasm to the extracellular space thereby
CC maintaining intracellular calcium homeostasis. Plays a role in blood
CC pressure regulation through regulation of intracellular calcium
CC concentration and nitric oxide production leading to regulation of
CC vascular smooth muscle cells vasoconstriction. Positively regulates
CC bone mineralization through absorption of calcium from the intestine.
CC Plays dual roles in osteoclast differentiation and survival by
CC regulating RANKL-induced calcium oscillations in preosteoclasts and
CC mediating calcium extrusion in mature osteoclasts (By similarity).
CC Regulates insulin sensitivity through calcium/calmodulin signaling
CC pathway by regulating AKT1 activation and NOS3 activation in
CC endothelial cells (PubMed:29104511). May play a role in synaptic
CC transmission by modulating calcium and proton dynamics at the synaptic
CC vesicles. {ECO:0000250|UniProtKB:G5E829, ECO:0000269|PubMed:29104511}.
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:30190470};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18106;
CC Evidence={ECO:0000305|PubMed:30190470};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=519.5 uM for ATP (in complex with NPTN)
CC {ECO:0000269|PubMed:30190470};
CC Vmax=325.5 nmol/min/mg enzyme {ECO:0000269|PubMed:30190470};
CC -!- SUBUNIT: Monomer (PubMed:1332771). Dimer (PubMed:1332771). Oligomer
CC (PubMed:1332771). Calmodulin binding (PubMed:1332771). Interacts with
CC PDZD11 (PubMed:12763866). Interacts with SLC35G1 and STIM1; inhibits
CC calcium-transporting ATPase activity after store depletion
CC (PubMed:22084111). Interacts with YWHAE; interacts with the monomeric
CC and dimeric forms of the YWHAE but prefer the monomer form; this
CC interaction inhibits calcium-transporting ATPase activity
CC (PubMed:18029012). Interacts with NPTN; this interaction stabilizes
CC ATP2B1 and increases ATPase activity; this interaction controls T cell
CC calcium homeostasis following T cell activation (PubMed:30190470).
CC Interacts with EPB41; regulates small intestinal calcium absorption
CC through regulation of membrane expression of ATP2B1 (By similarity).
CC {ECO:0000250|UniProtKB:G5E829, ECO:0000269|PubMed:12763866,
CC ECO:0000269|PubMed:1332771, ECO:0000269|PubMed:18029012,
CC ECO:0000269|PubMed:22084111, ECO:0000269|PubMed:30190470}.
CC -!- INTERACTION:
CC P20020; Q14160: SCRIB; NbExp=2; IntAct=EBI-5279998, EBI-357345;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:18029012};
CC Multi-pass membrane protein {ECO:0000255}. Basolateral cell membrane
CC {ECO:0000250|UniProtKB:G5E829}. Synapse {ECO:0000250|UniProtKB:G5E829}.
CC Presynaptic cell membrane {ECO:0000250|UniProtKB:G5E829}; Multi-pass
CC membrane protein {ECO:0000255}. Cytoplasmic vesicle, secretory vesicle,
CC synaptic vesicle membrane {ECO:0000250|UniProtKB:G5E829}; Multi-pass
CC membrane protein {ECO:0000255}. Note=Colocalizes with SV2A in
CC photoreceptor synaptic terminals. Colocalizes with NPTN to the
CC immunological synapse. Colocalizes with EPB41 to the basolateral
CC membrane in enterocyte. Preferentially sorted to recycling synaptic
CC vesicles. {ECO:0000250|UniProtKB:G5E829}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=B; Synonyms=CI, hPMCA1b {ECO:0000303|PubMed:1332771};
CC IsoId=P20020-3; Sequence=Displayed;
CC Name=D; Synonyms=CIV, hPMCA1d {ECO:0000303|PubMed:1332771};
CC IsoId=P20020-1; Sequence=VSP_059773;
CC Name=A; Synonyms=CII, hPMCA1a {ECO:0000303|PubMed:1332771};
CC IsoId=P20020-2; Sequence=VSP_059774, VSP_059775;
CC Name=C; Synonyms=CIII, hPMCA1c {ECO:0000303|PubMed:1332771};
CC IsoId=P20020-4; Sequence=VSP_059772;
CC Name=E; Synonyms=CV;
CC IsoId=P20020-5; Sequence=VSP_059774, VSP_059776;
CC Name=K;
CC IsoId=P20020-6; Sequence=VSP_059771;
CC -!- TISSUE SPECIFICITY: Isoform B: Ubiquitously expressed. Isoform C: Found
CC in brain cortex, skeletal muscle and heart muscle. Isoform D: Has only
CC been found in fetal skeletal muscle. Isoform K: Found in small
CC intestine and liver. Abundantly expressed in the endometrial epithelial
CC cells and glandular epithelial cells in early-proliferative phase and
CC early-secretory phases (PubMed:21400627).
CC {ECO:0000269|PubMed:21400627}.
CC -!- INDUCTION: Up-regulated at the proliferative phase of the mentrual
CC cycle. Up-regulated by estrogen. {ECO:0000269|PubMed:21400627}.
CC -!- DOMAIN: Isoforms A, C, D and E contain an additional calmodulin-binding
CC subdomain B which is different in the different splice variants and
CC shows pH dependent calmodulin binding properties.
CC {ECO:0000269|PubMed:1332771}.
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; J04027; AAA74511.1; -; mRNA.
DR EMBL; M95541; AAA35999.1; -; mRNA.
DR EMBL; M95542; AAA36000.1; -; mRNA.
DR EMBL; L14561; AAD09924.1; -; Genomic_DNA.
DR EMBL; L14561; AAD09925.1; -; Genomic_DNA.
DR EMBL; M25824; AAA58383.1; -; Genomic_DNA.
DR EMBL; M25824; AAA58382.1; -; Genomic_DNA.
DR EMBL; M25824; AAA58381.1; -; Genomic_DNA.
DR EMBL; S49852; AAB24324.1; -; mRNA.
DR EMBL; U15686; AAA60983.1; -; mRNA.
DR EMBL; U15687; AAA60984.1; -; mRNA.
DR CCDS; CCDS41817.1; -. [P20020-2]
DR CCDS; CCDS9035.1; -. [P20020-3]
DR PIR; A30802; A30802.
DR PIR; E49570; E49570.
DR PIR; I55491; I55491.
DR PIR; I70165; I70165.
DR RefSeq; NP_001001323.1; NM_001001323.1. [P20020-2]
DR RefSeq; NP_001673.2; NM_001682.2. [P20020-3]
DR RefSeq; XP_011536709.1; XM_011538407.2.
DR RefSeq; XP_016874847.1; XM_017019358.1.
DR PDB; 6A69; EM; 4.11 A; A=1-1220.
DR PDBsum; 6A69; -.
DR AlphaFoldDB; P20020; -.
DR SMR; P20020; -.
DR BioGRID; 106980; 236.
DR IntAct; P20020; 62.
DR MINT; P20020; -.
DR STRING; 9606.ENSP00000392043; -.
DR DrugBank; DB01189; Desflurane.
DR DrugBank; DB01159; Halothane.
DR TCDB; 3.A.3.2.25; the p-type atpase (p-atpase) superfamily.
DR iPTMnet; P20020; -.
DR PhosphoSitePlus; P20020; -.
DR SwissPalm; P20020; -.
DR BioMuta; ATP2B1; -.
DR DMDM; 14286104; -.
DR EPD; P20020; -.
DR jPOST; P20020; -.
DR MassIVE; P20020; -.
DR MaxQB; P20020; -.
DR PaxDb; P20020; -.
DR PeptideAtlas; P20020; -.
DR PRIDE; P20020; -.
DR ProteomicsDB; 53706; -. [P20020-1]
DR ProteomicsDB; 53707; -. [P20020-2]
DR ProteomicsDB; 53708; -. [P20020-3]
DR ProteomicsDB; 53709; -. [P20020-4]
DR ProteomicsDB; 53710; -. [P20020-5]
DR ProteomicsDB; 53711; -. [P20020-6]
DR Antibodypedia; 2168; 135 antibodies from 29 providers.
DR DNASU; 490; -.
DR Ensembl; ENST00000261173.6; ENSP00000261173.2; ENSG00000070961.16. [P20020-3]
DR Ensembl; ENST00000359142.7; ENSP00000352054.3; ENSG00000070961.16. [P20020-2]
DR Ensembl; ENST00000428670.8; ENSP00000392043.3; ENSG00000070961.16. [P20020-3]
DR GeneID; 490; -.
DR KEGG; hsa:490; -.
DR MANE-Select; ENST00000428670.8; ENSP00000392043.3; NM_001366521.1; NP_001353450.1.
DR UCSC; uc001tbg.4; human. [P20020-3]
DR CTD; 490; -.
DR DisGeNET; 490; -.
DR GeneCards; ATP2B1; -.
DR HGNC; HGNC:814; ATP2B1.
DR HPA; ENSG00000070961; Tissue enhanced (bone).
DR MIM; 108731; gene.
DR neXtProt; NX_P20020; -.
DR OpenTargets; ENSG00000070961; -.
DR PharmGKB; PA25107; -.
DR VEuPathDB; HostDB:ENSG00000070961; -.
DR eggNOG; KOG0204; Eukaryota.
DR GeneTree; ENSGT00940000158686; -.
DR InParanoid; P20020; -.
DR OMA; KTAHVGF; -.
DR OrthoDB; 115892at2759; -.
DR PhylomeDB; P20020; -.
DR TreeFam; TF300330; -.
DR BRENDA; 7.2.2.10; 2681.
DR PathwayCommons; P20020; -.
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.
DR SignaLink; P20020; -.
DR SIGNOR; P20020; -.
DR BioGRID-ORCS; 490; 84 hits in 1078 CRISPR screens.
DR ChiTaRS; ATP2B1; human.
DR GeneWiki; ATP2B1; -.
DR GenomeRNAi; 490; -.
DR Pharos; P20020; Tbio.
DR PRO; PR:P20020; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P20020; protein.
DR Bgee; ENSG00000070961; Expressed in frontal pole and 203 other tissues.
DR ExpressionAtlas; P20020; baseline and differential.
DR Genevisible; P20020; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
DR GO; GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB.
DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; IEA:Ensembl.
DR GO; GO:0032591; C:dendritic spine membrane; IEA:Ensembl.
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:0001772; C:immunological synapse; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0099059; C:integral component of presynaptic active zone membrane; IEA:Ensembl.
DR GO; GO:0099056; C:integral component of presynaptic membrane; ISS:UniProtKB.
DR GO; GO:0030285; C:integral component of synaptic vesicle membrane; ISS:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IEA:Ensembl.
DR GO; GO:0032809; C:neuronal cell body membrane; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
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; IDA:UniProtKB.
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:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0007420; P:brain development; IEA:Ensembl.
DR GO; GO:1901660; P:calcium ion export; IEA:Ensembl.
DR GO; GO:1990034; P:calcium ion export across plasma membrane; IDA:SynGO-UCL.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IBA:GO_Central.
DR GO; GO:0071386; P:cellular response to corticosterone stimulus; IEA:Ensembl.
DR GO; GO:0071305; P:cellular response to vitamin D; IEA:Ensembl.
DR GO; GO:0034220; P:ion transmembrane transport; TAS:Reactome.
DR GO; GO:0001818; P:negative regulation of cytokine production; ISS:UniProtKB.
DR GO; GO:0051481; P:negative regulation of cytosolic calcium ion concentration; IMP:UniProtKB.
DR GO; GO:0003407; P:neural retina development; IEA:Ensembl.
DR GO; GO:0030501; P:positive regulation of bone mineralization; ISS:UniProtKB.
DR GO; GO:0051928; P:positive regulation of calcium ion transport; ISS:UniProtKB.
DR GO; GO:0008217; P:regulation of blood pressure; ISS:UniProtKB.
DR GO; GO:1903779; P:regulation of cardiac conduction; TAS:Reactome.
DR GO; GO:1900076; P:regulation of cellular response to insulin stimulus; IMP:UniProtKB.
DR GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; IDA:SynGO-UCL.
DR GO; GO:0003056; P:regulation of vascular associated smooth muscle contraction; ISS:UniProtKB.
DR GO; GO:0009409; P:response to cold; IEA:Ensembl.
DR Gene3D; 3.40.1110.10; -; 1.
DR Gene3D; 3.40.50.1000; -; 1.
DR InterPro; IPR030320; ATP2B1.
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:SF245; PTHR24093:SF245; 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 3D-structure; Acetylation; Alternative splicing; ATP-binding; Calcium;
KW Calcium transport; Calmodulin-binding; Cell membrane; Cell projection;
KW Cytoplasmic vesicle; Ion transport; Magnesium; Membrane; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Synapse;
KW Translocase; Transmembrane; Transmembrane helix; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:20068231"
FT CHAIN 2..1220
FT /note="Plasma membrane calcium-transporting ATPase 1"
FT /id="PRO_0000046209"
FT TOPO_DOM 2..105
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 106..126
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30190470"
FT TOPO_DOM 127..154
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 155..175
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30190470"
FT TOPO_DOM 176..366
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 367..386
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30190470"
FT TOPO_DOM 387..418
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 419..439
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 440..855
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 856..876
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 877..882
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 883..903
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 904..927
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 928..948
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30190470"
FT TOPO_DOM 949..971
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 972..991
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30190470"
FT TOPO_DOM 992..1005
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1006..1027
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30190470"
FT TOPO_DOM 1028..1039
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1040..1060
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30190470"
FT TOPO_DOM 1061..1220
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 297..356
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1100..1117
FT /note="Calmodulin-binding subdomain A"
FT /evidence="ECO:0000305|PubMed:1332771"
FT REGION 1118..1220
FT /note="Required for basolateral membrane targeting"
FT /evidence="ECO:0000250|UniProtKB:P11505"
FT REGION 1160..1220
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 297..321
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 338..356
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1180..1220
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 475
FT /note="4-aspartylphosphate intermediate"
FT /evidence="ECO:0000250|UniProtKB:Q5ZWR1"
FT BINDING 475
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q5ZWR1"
FT BINDING 477
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q5ZWR1"
FT BINDING 797
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q5ZWR1"
FT MOD_RES 2
FT /note="N-acetylglycine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 8
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 17
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 338
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:G5E829"
FT MOD_RES 1116
FT /note="Phosphothreonine; by PKC"
FT /evidence="ECO:0000269|PubMed:1827443"
FT MOD_RES 1140
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11505"
FT MOD_RES 1155
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 1165
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 1178
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 1182
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:21406692"
FT VAR_SEQ 1021..1056
FT /note="Missing (in isoform K)"
FT /id="VSP_059771"
FT VAR_SEQ 1117
FT /note="Q -> QMDVVNAFQSGSSIQGALRRQPSIASQHHD (in isoform C)"
FT /id="VSP_059772"
FT VAR_SEQ 1117
FT /note="Q -> QMDVVNAFQSGSSIQGALRRQPSIASQHHDVTNISTPTH (in
FT isoform D)"
FT /id="VSP_059773"
FT VAR_SEQ 1118..1119
FT /note="IR -> MD (in isoform A and isoform E)"
FT /id="VSP_059774"
FT VAR_SEQ 1125..1220
FT /note="RSSLYEGLEKPESRSSIHNFMTHPEFRIEDSEPHIPLIDDTDAEDDAPTKRN
FT SSPPPSPNKNNNAVDSGIHLTIEMNKSATSSSPGSPLHSLETSL -> QSGSSIQGALR
FT RQPSIASQHHDVTNISTPTHVVFSSSTASTTVGYSSGECIS (in isoform A)"
FT /id="VSP_059775"
FT VAR_SEQ 1125..1220
FT /note="RSSLYEGLEKPESRSSIHNFMTHPEFRIEDSEPHIPLIDDTDAEDDAPTKRN
FT SSPPPSPNKNNNAVDSGIHLTIEMNKSATSSSPGSPLHSLETSL -> QSGSSIQGALR
FT RQPSIASQHHDVTNISTPTHVVFSSSTASTTVGFEW (in isoform E)"
FT /id="VSP_059776"
FT VARIANT 267
FT /note="M -> R"
FT /evidence="ECO:0000269|PubMed:9020386"
FT /id="VAR_000698"
FT CONFLICT 259..262
FT /note="LLLS -> MSAT (in Ref. 2; AAA36000)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1220 AA; 134685 MW; 7E75C19B1A501423 CRC64;
MGDMANNSVA YSGVKNSLKE ANHDGDFGIT LAELRALMEL RSTDALRKIQ ESYGDVYGIC
TKLKTSPNEG LSGNPADLER REAVFGKNFI PPKKPKTFLQ LVWEALQDVT LIILEIAAIV
SLGLSFYQPP EGDNALCGEV SVGEEEGEGE TGWIEGAAIL LSVVCVVLVT AFNDWSKEKQ
FRGLQSRIEQ EQKFTVIRGG QVIQIPVADI TVGDIAQVKY GDLLPADGIL IQGNDLKIDE
SSLTGESDHV KKSLDKDPLL LSGTHVMEGS GRMVVTAVGV NSQTGIIFTL LGAGGEEEEK
KDEKKKEKKN KKQDGAIENR NKAKAQDGAA MEMQPLKSEE GGDGDEKDKK KANLPKKEKS
VLQGKLTKLA VQIGKAGLLM SAITVIILVL YFVIDTFWVQ KRPWLAECTP IYIQYFVKFF
IIGVTVLVVA VPEGLPLAVT ISLAYSVKKM MKDNNLVRHL DACETMGNAT AICSDKTGTL
TMNRMTVVQA YINEKHYKKV PEPEAIPPNI LSYLVTGISV NCAYTSKILP PEKEGGLPRH
VGNKTECALL GLLLDLKRDY QDVRNEIPEE ALYKVYTFNS VRKSMSTVLK NSDGSYRIFS
KGASEIILKK CFKILSANGE AKVFRPRDRD DIVKTVIEPM ASEGLRTICL AFRDFPAGEP
EPEWDNENDI VTGLTCIAVV GIEDPVRPEV PDAIKKCQRA GITVRMVTGD NINTARAIAT
KCGILHPGED FLCLEGKDFN RRIRNEKGEI EQERIDKIWP KLRVLARSSP TDKHTLVKGI
IDSTVSDQRQ VVAVTGDGTN DGPALKKADV GFAMGIAGTD VAKEASDIIL TDDNFTSIVK
AVMWGRNVYD SISKFLQFQL TVNVVAVIVA FTGACITQDS PLKAVQMLWV NLIMDTLASL
ALATEPPTES LLLRKPYGRN KPLISRTMMK NILGHAFYQL VVVFTLLFAG EKFFDIDSGR
NAPLHAPPSE HYTIVFNTFV LMQLFNEINA RKIHGERNVF EGIFNNAIFC TIVLGTFVVQ
IIIVQFGGKP FSCSELSIEQ WLWSIFLGMG TLLWGQLIST IPTSRLKFLK EAGHGTQKEE
IPEEELAEDV EEIDHAEREL RRGQILWFRG LNRIQTQIRV VNAFRSSLYE GLEKPESRSS
IHNFMTHPEF RIEDSEPHIP LIDDTDAEDD APTKRNSSPP PSPNKNNNAV DSGIHLTIEM
NKSATSSSPG SPLHSLETSL
