ID AT2B4_HUMAN Reviewed; 1241 AA. AC P23634; B1APW5; B1APW6; Q13450; Q13452; Q13455; Q16817; Q7Z3S1; DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2001, sequence version 2. DT 27-MAR-2024, entry version 231. DE RecName: Full=Plasma membrane calcium-transporting ATPase 4 {ECO:0000305}; DE Short=PMCA4 {ECO:0000303|PubMed:1531651, ECO:0000312|EMBL:AAA50819.1}; DE EC=7.2.2.10 {ECO:0000269|PubMed:8530416}; DE AltName: Full=Matrix-remodeling-associated protein 1; DE AltName: Full=Plasma membrane calcium ATPase isoform 4; DE AltName: Full=Plasma membrane calcium pump isoform 4; GN Name=ATP2B4 {ECO:0000312|HGNC:HGNC:817}; Synonyms=ATP2B2, MXRA1; 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 XB), PARTIAL PROTEIN SEQUENCE, AND RP SUBCELLULAR LOCATION. RC TISSUE=Erythrocyte; RX PubMed=2137451; DOI=10.1016/s0021-9258(19)39877-1; RA Strehler E.E., James P., Fischer R., Heim R., Vorherr T.E., Filoteo A.G., RA Penniston J.T., Carafoli E.; RT "Peptide sequence analysis and molecular cloning reveal two calcium pump RT isoforms in the human erythrocyte membrane."; RL J. Biol. Chem. 265:2835-2842(1990). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM XA), AND TISSUE SPECIFICITY. RC TISSUE=Fetal brain; RX PubMed=1531651; DOI=10.1016/s0021-9258(18)42846-3; RA Brandt P., Neve R.L., Kammesheidt A., Rhoads R.E., Vanaman T.C.; RT "Analysis of the tissue-specific distribution of mRNAs encoding the plasma RT membrane calcium-pumping ATPases and characterization of an alternately RT spliced form of PMCA4 at the cDNA and genomic levels."; RL J. Biol. Chem. 267:4376-4385(1992). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM XB). RC TISSUE=Fetal kidney; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [5] 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM XA). RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS XA; XB; XK; ZA; ZB AND ZK). RC TISSUE=Heart muscle; RX PubMed=8700162; DOI=10.1007/bf00229314; RA Santiago-Garcia J., Mas-Oliva J., Saavedra D., Zarain-Herzberg A.; RT "Analysis of mRNA expression and cloning of a novel plasma membrane Ca(2+)- RT ATPase splice variant in human heart."; RL Mol. Cell. Biochem. 155:173-182(1996). RN [8] RP PROTEIN SEQUENCE OF 1085-1153 (ISOFORMS XB/ZB), AND CALMODULIN-BINDING RP SUBDOMAIN A. RX PubMed=2963820; DOI=10.1016/s0021-9258(18)69154-9; RA James P., Maeda M., Fischer R., Verma A.K., Krebs J., Penniston J.T., RA Carafoli E.; RT "Identification and primary structure of a calmodulin binding domain of the RT Ca2+ pump of human erythrocytes."; RL J. Biol. Chem. 263:2905-2910(1988). RN [9] RP PROTEIN SEQUENCE OF 1177-1190. RX PubMed=2966397; DOI=10.1073/pnas.85.9.2914; RA Brandt P., Zurini M., Neve R.L., Rhoads R.E., Vanaman T.C.; RT "A C-terminal, calmodulin-like regulatory domain from the plasma membrane RT Ca2+-pumping ATPase."; RL Proc. Natl. Acad. Sci. U.S.A. 85:2914-2918(1988). RN [10] RP ALTERNATIVE SPLICING (ISOFORMS X AND Z). RC TISSUE=Heart; 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 [11] 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 [12] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND MUTAGENESIS OF RP ASP-672; VAL-674; ARG-675; LYS-686 AND ARG-693. RX PubMed=8530416; DOI=10.1074/jbc.270.50.30111; RA Adamo H.P., Filoteo A.G., Enyedi A., Penniston J.T.; RT "Mutants in the putative nucleotide-binding region of the plasma membrane RT Ca(2+)-pump. A reduction in activity due to slow dephosphorylation."; RL J. Biol. Chem. 270:30111-30114(1995). RN [13] 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 [14] 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 [15] 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 [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13 AND SER-328, AND RP 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 [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13, 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 [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [19] RP STRUCTURE BY NMR OF 1086-1104 IN COMPLEX WITH CALMODULIN. RX PubMed=10493800; DOI=10.1021/bi9908235; RA Elshorst B., Hennig M., Foersterling H., Diener A., Maurer M., Schulte P., RA Schwalbe H., Griesinger C., Krebs J., Schmid H., Vorherr T.E., Carafoli E.; RT "NMR solution structure of a complex of calmodulin with a binding peptide RT of the Ca(2+) pump."; RL Biochemistry 38:12320-12332(1999). CC -!- FUNCTION: Calcium/calmodulin-regulated and magnesium-dependent enzyme CC that catalyzes the hydrolysis of ATP coupled with the transport of CC calcium out of the cell (PubMed:8530416). By regulating sperm cell CC calcium homeostasis, may play a role in sperm motility (By similarity). CC {ECO:0000250|UniProtKB:Q6Q477, ECO:0000269|PubMed:8530416}. 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:8530416}; CC -!- ACTIVITY REGULATION: Activated by calcium/calmodulin. CC {ECO:0000269|PubMed:8530416}. CC -!- SUBUNIT: Interacts with PDZD11 (PubMed:12763866). Interacts with CC SLC35G1 and STIM1 (PubMed:22084111). Interacts with calmodulin CC (PubMed:2963820, PubMed:10493800). {ECO:0000269|PubMed:10493800, CC ECO:0000269|PubMed:12763866, ECO:0000269|PubMed:22084111, CC ECO:0000269|PubMed:2963820}. CC -!- INTERACTION: CC P23634; P01258: CALCA; NbExp=2; IntAct=EBI-1174388, EBI-1018474; CC P23634; Q5VYX0: RNLS; NbExp=3; IntAct=EBI-1174388, EBI-3386081; CC P23634-6; Q63622: Dlg2; Xeno; NbExp=2; IntAct=EBI-1174437, EBI-396947; CC P23634-6; Q62936: Dlg3; Xeno; NbExp=2; IntAct=EBI-1174437, EBI-349596; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:2137451}; CC Multi-pass membrane protein {ECO:0000255}. Cell projection, cilium, CC flagellum membrane {ECO:0000250|UniProtKB:Q6Q477}; Multi-pass membrane CC protein {ECO:0000255}. 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 B/C (A, B, D CC and K). 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=XD; Synonyms=AIICIV; CC IsoId=P23634-1; Sequence=Displayed; CC Name=XA; Synonyms=AIICII; CC IsoId=P23634-2; Sequence=VSP_000405; CC Name=ZA; Synonyms=AICII; CC IsoId=P23634-3; Sequence=VSP_000402, VSP_000405; CC Name=XK; Synonyms=XG; CC IsoId=P23634-4; Sequence=VSP_000403, VSP_000405; CC Name=ZK; Synonyms=ZG; CC IsoId=P23634-5; Sequence=VSP_000402, VSP_000403, VSP_000405; CC Name=XB; Synonyms=AIICI, hPMCA4b; CC IsoId=P23634-6; Sequence=VSP_000404; CC Name=ZB; Synonyms=AICI; CC IsoId=P23634-7; Sequence=VSP_000402, VSP_000404; CC Name=ZD; Synonyms=AICIV; CC IsoId=P23634-8; Sequence=VSP_000402; CC -!- TISSUE SPECIFICITY: Isoform XB is the most abundant isoform and is CC expressed ubiquitously. Isoforms containing segment Z have only been CC detected in heart, while isoforms containing segment a have been found CC in heart, stomach and brain cortex. {ECO:0000269|PubMed:1531651}. CC -!- SIMILARITY: Belongs to the cation transport ATPase (P-type) (TC 3.A.3) CC family. Type IIB subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M25874; AAA50819.1; -; mRNA. DR EMBL; M83363; AAA36455.1; -; mRNA. DR EMBL; BX537444; CAD97686.1; -; mRNA. DR EMBL; U42026; AAB17577.1; -; mRNA. DR EMBL; U42061; AAB17578.1; -; mRNA. DR EMBL; U42062; AAB17579.1; -; mRNA. DR EMBL; U42378; AAB17580.1; -; mRNA. DR EMBL; AC114402; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL513343; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471067; EAW91483.1; -; Genomic_DNA. DR EMBL; CH471067; EAW91486.1; -; Genomic_DNA. DR EMBL; BC140774; AAI40775.1; -; mRNA. DR CCDS; CCDS1440.1; -. [P23634-6] DR CCDS; CCDS30977.1; -. [P23634-2] DR PIR; A35547; A35547. DR RefSeq; NP_001001396.1; NM_001001396.2. [P23634-2] DR RefSeq; NP_001675.3; NM_001684.4. [P23634-6] DR PDB; 1CFF; NMR; -; B=1086-1104. DR PDB; 2KNE; NMR; -; B=1086-1149. DR PDBsum; 1CFF; -. DR PDBsum; 2KNE; -. DR AlphaFoldDB; P23634; -. DR SMR; P23634; -. DR BioGRID; 106983; 180. DR DIP; DIP-6128N; -. DR ELM; P23634; -. DR IntAct; P23634; 84. DR MINT; P23634; -. DR STRING; 9606.ENSP00000350310; -. DR DrugBank; DB01189; Desflurane. DR DrugBank; DB01159; Halothane. DR DrugBank; DB00867; Ritodrine. DR DrugBank; DB01236; Sevoflurane. DR TCDB; 3.A.3.2.1; the p-type atpase (p-atpase) superfamily. DR GlyCosmos; P23634; 1 site, 1 glycan. DR GlyGen; P23634; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; P23634; -. DR MetOSite; P23634; -. DR PhosphoSitePlus; P23634; -. DR SwissPalm; P23634; -. DR BioMuta; ATP2B4; -. DR DMDM; 14286105; -. DR EPD; P23634; -. DR jPOST; P23634; -. DR MassIVE; P23634; -. DR MaxQB; P23634; -. DR PaxDb; 9606-ENSP00000350310; -. DR PeptideAtlas; P23634; -. DR ProteomicsDB; 54137; -. [P23634-1] DR ProteomicsDB; 54138; -. [P23634-2] DR ProteomicsDB; 54139; -. [P23634-3] DR ProteomicsDB; 54140; -. [P23634-4] DR ProteomicsDB; 54141; -. [P23634-5] DR ProteomicsDB; 54142; -. [P23634-6] DR ProteomicsDB; 54143; -. [P23634-7] DR ProteomicsDB; 54144; -. [P23634-8] DR Pumba; P23634; -. DR Antibodypedia; 4241; 168 antibodies from 23 providers. DR DNASU; 493; -. DR Ensembl; ENST00000341360.7; ENSP00000340930.2; ENSG00000058668.16. [P23634-2] DR Ensembl; ENST00000357681.10; ENSP00000350310.5; ENSG00000058668.16. [P23634-6] DR Ensembl; ENST00000705901.1; ENSP00000516177.1; ENSG00000058668.16. [P23634-3] DR GeneID; 493; -. DR KEGG; hsa:493; -. DR MANE-Select; ENST00000357681.10; ENSP00000350310.5; NM_001684.5; NP_001675.3. [P23634-6] DR UCSC; uc001gzv.4; human. [P23634-1] DR AGR; HGNC:817; -. DR CTD; 493; -. DR DisGeNET; 493; -. DR GeneCards; ATP2B4; -. DR HGNC; HGNC:817; ATP2B4. DR HPA; ENSG00000058668; Tissue enhanced (smooth). DR MIM; 108732; gene. DR neXtProt; NX_P23634; -. DR OpenTargets; ENSG00000058668; -. DR PharmGKB; PA25110; -. DR VEuPathDB; HostDB:ENSG00000058668; -. DR eggNOG; KOG0204; Eukaryota. DR GeneTree; ENSGT00940000154527; -. DR HOGENOM; CLU_002360_9_0_1; -. DR InParanoid; P23634; -. DR OMA; MINVHDI; -. DR OrthoDB; 847at2759; -. DR PhylomeDB; P23634; -. DR TreeFam; TF300330; -. DR PathwayCommons; P23634; -. 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; P23634; -. DR SIGNOR; P23634; -. DR BioGRID-ORCS; 493; 16 hits in 1155 CRISPR screens. DR ChiTaRS; ATP2B4; human. DR EvolutionaryTrace; P23634; -. DR GeneWiki; ATP2B4; -. DR GenomeRNAi; 493; -. DR Pharos; P23634; Tbio. DR PRO; PR:P23634; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; P23634; Protein. DR Bgee; ENSG00000058668; Expressed in saphenous vein and 213 other cell types or tissues. DR ExpressionAtlas; P23634; baseline and differential. DR GO; GO:0016323; C:basolateral plasma membrane; IEA:Ensembl. DR GO; GO:0005901; C:caveola; TAS:BHF-UCL. DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central. DR GO; GO:0016020; C:membrane; IDA:ARUK-UCL. DR GO; GO:0045121; C:membrane raft; IDA:ARUK-UCL. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0048787; C:presynaptic active zone membrane; IEA:Ensembl. DR GO; GO:0032991; C:protein-containing complex; ISS:BHF-UCL. DR GO; GO:0036126; C:sperm flagellum; ISS:UniProtKB. DR GO; GO:0097228; C:sperm principal piece; IEA:Ensembl. DR GO; GO:0030315; C:T-tubule; IDA:BHF-UCL. DR GO; GO:0030018; C:Z disc; IDA:BHF-UCL. 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:ARUK-UCL. DR GO; GO:0005516; F:calmodulin binding; IDA:BHF-UCL. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0050998; F:nitric-oxide synthase binding; IPI:BHF-UCL. DR GO; GO:0036487; F:nitric-oxide synthase inhibitor activity; IDA:BHF-UCL. DR GO; GO:0005388; F:P-type calcium transporter activity; IMP:BHF-UCL. DR GO; GO:0030165; F:PDZ domain binding; IBA:GO_Central. DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl. DR GO; GO:0030346; F:protein phosphatase 2B binding; IDA:BHF-UCL. DR GO; GO:0097110; F:scaffold protein binding; ISS:BHF-UCL. DR GO; GO:0017080; F:sodium channel regulator activity; ISS:BHF-UCL. DR GO; GO:1901660; P:calcium ion export; IDA:ARUK-UCL. DR GO; GO:0098703; P:calcium ion import across plasma membrane; IC:BHF-UCL. DR GO; GO:0097553; P:calcium ion transmembrane import into cytosol; IC:BHF-UCL. DR GO; GO:0070588; P:calcium ion transmembrane transport; IMP:BHF-UCL. DR GO; GO:1905145; P:cellular response to acetylcholine; ISS:UniProtKB. DR GO; GO:0071872; P:cellular response to epinephrine stimulus; IDA:BHF-UCL. DR GO; GO:0030317; P:flagellated sperm motility; ISS:UniProtKB. DR GO; GO:0021766; P:hippocampus development; IEA:Ensembl. DR GO; GO:0006874; P:intracellular calcium ion homeostasis; IDA:BHF-UCL. DR GO; GO:0034220; P:monoatomic ion transmembrane transport; TAS:Reactome. DR GO; GO:0071878; P:negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0016525; P:negative regulation of angiogenesis; IDA:ARUK-UCL. DR GO; GO:1900082; P:negative regulation of arginine catabolic process; IDA:BHF-UCL. DR GO; GO:0043537; P:negative regulation of blood vessel endothelial cell migration; IDA:ARUK-UCL. DR GO; GO:0070885; P:negative regulation of calcineurin-NFAT signaling cascade; IDA:BHF-UCL. DR GO; GO:1903243; P:negative regulation of cardiac muscle hypertrophy in response to stress; IMP:BHF-UCL. DR GO; GO:1902548; P:negative regulation of cellular response to vascular endothelial growth factor stimulus; IDA:ARUK-UCL. DR GO; GO:1903249; P:negative regulation of citrulline biosynthetic process; IDA:BHF-UCL. DR GO; GO:0010629; P:negative regulation of gene expression; IDA:ARUK-UCL. DR GO; GO:0045019; P:negative regulation of nitric oxide biosynthetic process; IDA:BHF-UCL. DR GO; GO:0010751; P:negative regulation of nitric oxide mediated signal transduction; IDA:BHF-UCL. DR GO; GO:0051001; P:negative regulation of nitric-oxide synthase activity; IDA:BHF-UCL. DR GO; GO:1902083; P:negative regulation of peptidyl-cysteine S-nitrosylation; NAS:BHF-UCL. DR GO; GO:0098736; P:negative regulation of the force of heart contraction; IDA:BHF-UCL. DR GO; GO:0003407; P:neural retina development; IEA:Ensembl. DR GO; GO:2000481; P:positive regulation of cAMP-dependent protein kinase activity; IDA:BHF-UCL. DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:BHF-UCL. DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; IDA:ARUK-UCL. DR GO; GO:1903779; P:regulation of cardiac conduction; TAS:Reactome. DR GO; GO:1902806; P:regulation of cell cycle G1/S phase transition; IMP:CACAO. DR GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; IBA:GO_Central. DR GO; GO:1902305; P:regulation of sodium ion transmembrane transport; IC:BHF-UCL. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IMP:BHF-UCL. DR GO; GO:0051599; P:response to hydrostatic pressure; IMP:BHF-UCL. DR GO; GO:0007283; P:spermatogenesis; IEA:Ensembl. DR GO; GO:0150104; P:transport across blood-brain barrier; NAS:ARUK-UCL. DR GO; GO:0014832; P:urinary bladder smooth muscle contraction; ISS:UniProtKB. 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; 3. DR Gene3D; 3.40.50.1000; HAD superfamily/HAD-like; 1. DR IDEAL; IID00510; -. 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:SF435; PLASMA MEMBRANE CALCIUM-TRANSPORTING ATPASE 4; 1. DR Pfam; PF12424; ATP_Ca_trans_C; 2. 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; SFLDG00002; C1.7:_P-type_atpase_like; 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; P23634; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Calcium; KW Calcium transport; Calmodulin-binding; Cell membrane; Cell projection; KW Cilium; Direct protein sequencing; Flagellum; Ion transport; Magnesium; KW Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein; KW Reference proteome; Translocase; Transmembrane; Transmembrane helix; KW Transport. FT CHAIN 1..1241 FT /note="Plasma membrane calcium-transporting ATPase 4" FT /id="PRO_0000046220" FT TOPO_DOM 1..92 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 93..113 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 114..150 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 151..171 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 172..356 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 357..376 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 377..409 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 410..427 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 428..840 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 841..860 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 861..870 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 871..891 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 892..911 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 912..934 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 935..952 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 953..974 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 975..993 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 994..1015 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1016..1025 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 1026..1047 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1048..1241 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REGION 294..318 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1086..1103 FT /note="Calmodulin-binding subdomain A" FT /evidence="ECO:0000269|PubMed:2963820" FT REGION 1104..1113 FT /note="Calmodulin-binding subdomain B" FT /evidence="ECO:0000250|UniProtKB:P20020" FT COMPBIAS 294..310 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 465 FT /note="4-aspartylphosphate intermediate" FT /evidence="ECO:0000250|UniProtKB:P19156" FT BINDING 785 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250" FT BINDING 789 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250" FT MOD_RES 13 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 328 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1102 FT /note="Phosphothreonine; by PKC" FT /evidence="ECO:0000250" FT VAR_SEQ 301..312 FT /note="Missing (in isoform ZA, isoform ZK, isoform ZB and FT isoform ZD)" FT /evidence="ECO:0000305" FT /id="VSP_000402" FT VAR_SEQ 1009..1044 FT /note="Missing (in isoform XK and isoform ZK)" FT /evidence="ECO:0000305" FT /id="VSP_000403" FT VAR_SEQ 1104..1139 FT /note="Missing (in isoform XB and isoform ZB)" FT /evidence="ECO:0000303|PubMed:17974005, FT ECO:0000303|PubMed:2137451" FT /id="VSP_000404" FT VAR_SEQ 1140..1241 FT /note="IKVVKAFHSSLHESIQKPYNQKSIHSFMTHPEFAIEEELPRTPLLDEEEEEN FT PDKASKFGTRVLLLDGEVTPYANTNNNAVDCNQVQLPQSDSSLQSLETSV -> VAVAP FT VKSSPTTSVPAVSSPPMGNQSGQSVP (in isoform XA, isoform XK, FT isoform ZA and isoform ZK)" FT /evidence="ECO:0000303|PubMed:1531651, FT ECO:0000303|PubMed:15489334" FT /id="VSP_000405" FT MUTAGEN 672 FT /note="D->Q: Strongly decreased calcium transport activity. FT Slowed decomposition of the phosphorylated intermediate." FT /evidence="ECO:0000269|PubMed:8530416" FT MUTAGEN 674 FT /note="V->P: Decreased calcium transport activity." FT /evidence="ECO:0000269|PubMed:8530416" FT MUTAGEN 675 FT /note="R->K,D,L: Decreased calcium transport activity." FT /evidence="ECO:0000269|PubMed:8530416" FT MUTAGEN 686 FT /note="K->L: Decreased calcium transport activity." FT /evidence="ECO:0000269|PubMed:8530416" FT MUTAGEN 693 FT /note="R->I: Mildly decreased calcium transport activity." FT /evidence="ECO:0000269|PubMed:8530416" FT CONFLICT 492 FT /note="S -> C (in Ref. 3; CAD97686)" FT /evidence="ECO:0000305" FT CONFLICT 1144 FT /note="K -> N (in Ref. 8; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 1147 FT /note="H -> S (in Ref. 8; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 1153 FT /note="S -> F (in Ref. 8; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 1178 FT /note="L -> Q (in Ref. 9; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 1187 FT /note="E -> Q (in Ref. 9; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 1190 FT /note="E -> G (in Ref. 3; CAD97686)" FT /evidence="ECO:0000305" FT TURN 1087..1089 FT /evidence="ECO:0007829|PDB:2KNE" FT TURN 1090..1092 FT /evidence="ECO:0007829|PDB:1CFF" FT HELIX 1093..1102 FT /evidence="ECO:0007829|PDB:1CFF" SQ SEQUENCE 1241 AA; 137920 MW; 568544103CD5F494 CRC64; MTNPSDRVLP ANSMAESREG DFGCTVMELR KLMELRSRDA LTQINVHYGG VQNLCSRLKT SPVEGLSGNP ADLEKRRQVF GHNVIPPKKP KTFLELVWEA LQDVTLIILE IAAIISLVLS FYRPAGEENE LCGQVATTPE DENEAQAGWI EGAAILFSVI IVVLVTAFND WSKEKQFRGL QCRIEQEQKF SIIRNGQLIQ LPVAEIVVGD IAQVKYGDLL PADGILIQGN DLKIDESSLT GESDHVKKSL DKDPMLLSGT HVMEGSGRMV VTAVGVNSQT GIILTLLGVN EDDEGEKKKK GKKQGVPENR NKAKTQDGVA LEIQPLNSQE GIDNEEKDKK AVKVPKKEKS VLQGKLTRLA VQIGKAGLLM SALTVFILIL YFVIDNFVIN RRPWLPECTP IYIQYFVKFF IIGITVLVVA VPEGLPLAVT ISLAYSVKKM MKDNNLVRHL DACETMGNAT AICSDKTGTL TMNRMTVVQA YIGGIHYRQI PSPDVFLPKV LDLIVNGISI NSAYTSKILP PEKEGGLPRQ VGNKTECALL GFVTDLKQDY QAVRNEVPEE KLYKVYTFNS VRKSMSTVIR NPNGGFRMYS KGASEIILRK CNRILDRKGE AVPFKNKDRD DMVRTVIEPM ACDGLRTICI AYRDFDDTEP SWDNENEILT ELTCIAVVGI EDPVRPEVPD AIAKCKQAGI TVRMVTGDNI NTARAIATKC GILTPGDDFL CLEGKEFNRL IRNEKGEVEQ EKLDKIWPKL RVLARSSPTD KHTLVKGIID STVGEHRQVV AVTGDGTNDG PALKKADVGF AMGIAGTDVA KEASDIILTD DNFTSIVKAV MWGRNVYDSI SKFLQFQLTV NVVAVIVAFT GACITQDSPL KAVQMLWVNL IMDTFASLAL ATEPPTESLL KRRPYGRNKP LISRTMMKNI LGHAFYQLIV IFILVFAGEK FFDIDSGRKA PLHSPPSQHY TIVFNTFVLM QLFNEINSRK IHGEKNVFSG IYRNIIFCSV VLGTFICQIF IVEFGGKPFS CTSLSLSQWL WCLFIGIGEL LWGQFISAIP TRSLKFLKEA GHGTTKEEIT KDAEGLDEID HAEMELRRGQ ILWFRGLNRI QTQIDVINTF QTGASFKGVL RRQNMGQHLD VKLVPSSSYI KVVKAFHSSL HESIQKPYNQ KSIHSFMTHP EFAIEEELPR TPLLDEEEEE NPDKASKFGT RVLLLDGEVT PYANTNNNAV DCNQVQLPQS DSSLQSLETS V //