AT2B4_HUMAN
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 03-AUG-2022, entry version 222.
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}.
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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; 164.
DR DIP; DIP-6128N; -.
DR ELM; P23634; -.
DR IntAct; P23634; 77.
DR MINT; P23634; -.
DR STRING; 9606.ENSP00000350310; -.
DR DrugBank; DB01189; Desflurane.
DR DrugBank; DB01159; Halothane.
DR TCDB; 3.A.3.2.1; the p-type atpase (p-atpase) superfamily.
DR GlyGen; P23634; 1 site, 1 O-linked glycan (1 site).
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; P23634; -.
DR PeptideAtlas; P23634; -.
DR PRIDE; 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 Antibodypedia; 4241; 158 antibodies from 23 providers.
DR DNASU; 493; -.
DR Ensembl; ENST00000341360.6; ENSP00000340930.2; ENSG00000058668.15. [P23634-2]
DR Ensembl; ENST00000357681.10; ENSP00000350310.5; ENSG00000058668.15. [P23634-6]
DR Ensembl; ENST00000367218.7; ENSP00000356187.3; ENSG00000058668.15. [P23634-2]
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 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; IMGQNIY; -.
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 1077 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 211 other tissues.
DR ExpressionAtlas; P23634; baseline and differential.
DR Genevisible; P23634; HS.
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: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: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:0043005; C:neuron projection; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
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:0019829; F:ATPase-coupled cation transmembrane transporter activity; IBA:GO_Central.
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:0006874; P:cellular calcium ion homeostasis; IDA: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:0034220; P:ion transmembrane transport; TAS:Reactome.
DR GO; GO:0140199; P:negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process; 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 Gene3D; 3.40.1110.10; -; 1.
DR Gene3D; 3.40.50.1000; -; 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 Pfam; PF12424; ATP_Ca_trans_C; 2.
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; 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
