Plasma membrane calcium-transporting ATPase 1

Details

Name
Plasma membrane calcium-transporting ATPase 1
Synonyms
  • 7.2.2.10
  • Plasma membrane calcium ATPase isoform 1
  • Plasma membrane calcium pump isoform 1
  • PMCA1
Gene Name
ATP2B1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0052473|Plasma membrane calcium-transporting ATPase 1
MGDMANNSVAYSGVKNSLKEANHDGDFGITLAELRALMELRSTDALRKIQESYGDVYGIC
TKLKTSPNEGLSGNPADLERREAVFGKNFIPPKKPKTFLQLVWEALQDVTLIILEIAAIV
SLGLSFYQPPEGDNALCGEVSVGEEEGEGETGWIEGAAILLSVVCVVLVTAFNDWSKEKQ
FRGLQSRIEQEQKFTVIRGGQVIQIPVADITVGDIAQVKYGDLLPADGILIQGNDLKIDE
SSLTGESDHVKKSLDKDPLLLSGTHVMEGSGRMVVTAVGVNSQTGIIFTLLGAGGEEEEK
KDEKKKEKKNKKQDGAIENRNKAKAQDGAAMEMQPLKSEEGGDGDEKDKKKANLPKKEKS
VLQGKLTKLAVQIGKAGLLMSAITVIILVLYFVIDTFWVQKRPWLAECTPIYIQYFVKFF
IIGVTVLVVAVPEGLPLAVTISLAYSVKKMMKDNNLVRHLDACETMGNATAICSDKTGTL
TMNRMTVVQAYINEKHYKKVPEPEAIPPNILSYLVTGISVNCAYTSKILPPEKEGGLPRH
VGNKTECALLGLLLDLKRDYQDVRNEIPEEALYKVYTFNSVRKSMSTVLKNSDGSYRIFS
KGASEIILKKCFKILSANGEAKVFRPRDRDDIVKTVIEPMASEGLRTICLAFRDFPAGEP
EPEWDNENDIVTGLTCIAVVGIEDPVRPEVPDAIKKCQRAGITVRMVTGDNINTARAIAT
KCGILHPGEDFLCLEGKDFNRRIRNEKGEIEQERIDKIWPKLRVLARSSPTDKHTLVKGI
IDSTVSDQRQVVAVTGDGTNDGPALKKADVGFAMGIAGTDVAKEASDIILTDDNFTSIVK
AVMWGRNVYDSISKFLQFQLTVNVVAVIVAFTGACITQDSPLKAVQMLWVNLIMDTLASL
ALATEPPTESLLLRKPYGRNKPLISRTMMKNILGHAFYQLVVVFTLLFAGEKFFDIDSGR
NAPLHAPPSEHYTIVFNTFVLMQLFNEINARKIHGERNVFEGIFNNAIFCTIVLGTFVVQ
IIIVQFGGKPFSCSELSIEQWLWSIFLGMGTLLWGQLISTIPTSRLKFLKEAGHGTQKEE
IPEEELAEDVEEIDHAERELRRGQILWFRGLNRIQTQIRVVNAFRSSLYEGLEKPESRSS
IHNFMTHPEFRIEDSEPHIPLIDDTDAEDDAPTKRNSSPPPSPNKNNNAVDSGIHLTIEM
NKSATSSSPGSPLHSLETSL
Number of residues
1220
Molecular Weight
134683.595
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / ATPase activity / ATPase-coupled cation transmembrane transporter activity / calcium ion transmembrane transporter activity / calcium transmembrane transporter activity, phosphorylative mechanism / calcium-transporting ATPase activity involved in regulation of presynaptic cytosolic calcium ion concentration / calmodulin binding / metal ion binding / PDZ domain binding
Processes
aging / brain development / calcium ion export across plasma membrane / cellular calcium ion homeostasis / cellular response to corticosterone stimulus / cellular response to vitamin D / ion transmembrane transport / negative regulation of cytokine production / negative regulation of cytosolic calcium ion concentration / neural retina development / positive regulation of bone mineralization / positive regulation of calcium ion transport / regulation of blood pressure / regulation of cardiac conduction / regulation of cellular response to insulin stimulus / regulation of cytosolic calcium ion concentration / regulation of vascular smooth muscle contraction / response to cold
Components
apical plasma membrane / basolateral plasma membrane / cell / cell junction / cytoplasmic side of plasma membrane / dendritic spine membrane / extracellular exosome / GABA-ergic synapse / glutamatergic synapse / immunological synapse / integral component of plasma membrane / integral component of presynaptic active zone membrane / intracellular membrane-bounded organelle / membrane / membrane raft / neuronal cell body membrane / nucleoplasm / plasma membrane
General Function
Catalyzes the hydrolysis of ATP coupled with the transport of calcium from the cytoplasm to the extracellular space thereby maintaining intracellular calcium homeostasis. Plays a role in blood pressure regulation through regulation of intracellular calcium concentration and nitric oxide production leading to regulation of vascular smooth muscle cells vasoconstriction. Positively regulates bone mineralization through absorption of calcium from the intestine. Plays dual roles in osteoclast differentiation and survival by regulating RANKL-induced calcium oscillations in preosteoclasts and mediating calcium extrusion in mature osteoclasts (By similarity). Regulates insulin sensitivity through calcium/calmodulin signaling pathway by regulating AKT1 activation and NOS3 activation in endothelial cells (PubMed:29104511).
Specific Function
Atp binding
Pfam Domain Function
Transmembrane Regions
106-126 155-175 367-386 419-439 856-876 883-903 928-948 972-991 1006-1027 1040-1060
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0052474|Plasma membrane calcium-transporting ATPase 1 (ATP2B1)
ATGGGCGACATGGCAAACAACTCAGTTGCTTACAGTGGTGTGAAAAACTCTTTGAAGGAA
GCTAATCATGATGGAGACTTTGGAATTACGCTCGCAGAGCTGCGGGCTCTCATGGAGCTC
AGGTCCACAGATGCATTACGAAAAATACAGGAAAGCTATGGAGATGTCTATGGAATTTGC
ACCAAATTGAAAACATCTCCCAATGAAGGTTTAAGTGGAAACCCTGCAGATTTAGAAAGA
AGAGAAGCAGTGTTTGGAAAGAATTTTATACCTCCTAAAAAGCCAAAAACCTTTCTTCAA
TTAGTATGGGAAGCATTACAAGATGTCACTTTAATTATATTAGAAATTGCAGCCATAGTA
TCATTGGGCCTTTCTTTTTATCAGCCTCCAGAAGGGGATAATGCACTTTGTGGAGAAGTT
TCTGTTGGGGAGGAAGAAGGTGAAGGTGAAACTGGTTGGATTGAAGGAGCTGCAATCCTC
TTGTCTGTAGTGTGTGTGGTGTTAGTAACAGCTTTCAATGACTGGAGTAAGGAAAAACAG
TTTAGAGGTTTGCAGAGCCGAATTGAACAAGAACAGAAGTTCACTGTCATCAGGGGTGGT
CAGGTCATTCAGATACCTGTAGCTGACATTACTGTTGGAGATATTGCTCAAGTGAAATAT
GGTGATCTTCTTCCAGCTGACGGCATACTTATTCAAGGCAACGATCTTAAAATTGATGAA
AGCTCATTGACTGGTGAATCAGATCATGTTAAAAAGTCTTTAGATAAGGATCCCTTACTT
CTATCAGGTACTCATGTAATGGAAGGCTCTGGAAGAATGGTAGTTACAGCTGTAGGTGTA
AATTCTCAAACTGGAATTATCTTTACCTTACTTGGAGCTGGAGGTGAAGAGGAAGAGAAG
AAAGATGAGAAGAAAAAGGAAAAGAAAAATAAGAAACAAGATGGAGCTATTGAGAATCGC
AACAAAGCAAAAGCCCAGGATGGTGCAGCCATGGAAATGCAGCCATTGAAGAGTGAAGAA
GGTGGAGATGGTGATGAAAAAGATAAAAAGAAAGCAAATTTGCCAAAAAAGGAAAAATCT
GTTTTACAAGGGAAACTTACAAAACTGGCTGTTCAGATTGGCAAAGCAGGTCTGTTGATG
TCTGCCATCACAGTTATCATTCTAGTATTATATTTTGTCATTGACACCTTCTGGGTTCAG
AAAAGACCATGGCTTGCTGAGTGCACACCAATTTATATACAATACTTTGTGAAGTTCTTC
ATTATTGGAGTTACAGTTTTAGTGGTCGCAGTGCCAGAAGGTCTTCCACTTGCAGTCACG
ATCTCACTGGCTTATTCAGTCAAAAAAATGATGAAAGATAATAACTTAGTAAGGCATCTG
GATGCTTGTGAAACCATGGGAAATGCTACAGCTATTTGTTCAGATAAAACAGGAACTTTG
ACAATGAACAGAATGACAGTCGTTCAAGCTTACATAAATGAAAAACATTATAAAAAGGTT
CCTGAACCAGAAGCTATTCCACCAAATATTTTGTCCTATCTTGTAACAGGAATTTCTGTG
AATTGTGCTTATACATCAAAAATATTGCCACCAGAGAAAGAGGGTGGATTACCTCGTCAC
GTTGGTAATAAAACTGAATGTGCCTTGTTGGGACTTCTTTTGGATTTAAAACGGGATTAT
CAGGATGTTAGAAATGAAATACCAGAAGAAGCACTGTACAAAGTCTACACCTTCAATTCT
GTTAGGAAGTCCATGAGTACTGTCCTGAAAAATTCAGATGGAAGTTATCGAATATTCAGC
AAGGGTGCATCTGAGATAATTCTGAAAAAGTGTTTCAAAATCTTGAGTGCTAATGGTGAG
GCAAAAGTATTCAGACCAAGGGACCGTGATGATATTGTAAAAACTGTGATTGAACCGATG
GCATCAGAAGGCTTGAGAACCATATGTCTTGCATTCAGAGATTTTCCAGCAGGAGAACCA
GAACCAGAGTGGGATAATGAAAATGATATTGTCACCGGCCTTACATGCATTGCTGTTGTG
GGGATTGAAGATCCTGTGAGACCTGAGGTGCCAGATGCAATTAAAAAGTGTCAGAGGGCT
GGAATTACTGTGCGGATGGTCACTGGTGATAATATTAATACTGCTCGGGCCATTGCTACC
AAATGTGGTATTTTACATCCTGGGGAAGATTTTCTGTGCCTAGAAGGTAAAGATTTTAAC
AGAAGAATACGAAATGAAAAAGGAGAGATTGAGCAAGAGAGGATAGACAAGATTTGGCCA
AAACTTCGAGTACTTGCAAGATCATCTCCTACTGATAAGCATACACTGGTTAAAGGTATA
ATTGACAGCACTGTCTCAGACCAACGCCAGGTTGTAGCTGTAACTGGTGATGGTACAAAT
GATGGCCCAGCACTAAAGAAAGCAGATGTTGGATTTGCAATGGGTATTGCTGGAACTGAT
GTAGCTAAAGAAGCATCCGATATTATTCTCACAGATGACAACTTTACAAGCATTGTTAAA
GCAGTTATGTGGGGACGAAATGTCTATGACAGCATCTCAAAATTCCTTCAGTTCCAACTT
ACTGTTAATGTAGTAGCAGTGATTGTTGCTTTTACGGGCGCCTGCATTACTCAAGACTCA
CCGCTTAAGGCTGTGCAGATGCTGTGGGTAAACCTCATAATGGATACACTCGCTTCCCTG
GCTCTGGCAACGGAACCACCCACTGAGTCTCTCTTGCTTCGGAAACCTTATGGTAGAAAT
AAGCCTCTCATCTCACGTACAATGATGAAGAATATTTTGGGTCATGCATTCTATCAACTT
GTAGTAGTCTTTACACTCTTATTTGCTGGAGAAAAGTTTTTTGACATTGATAGTGGAAGA
AATGCTCCTTTGCATGCTCCTCCTTCAGAACATTATACTATTGTTTTTAATACCTTTGTG
CTGATGCAACTTTTCAACGAAATAAATGCCCGGAAAATTCATGGTGAAAGAAATGTATTC
GAAGGAATCTTTAACAATGCCATCTTCTGCACAATTGTTTTAGGCACTTTTGTGGTACAG
ATAATAATTGTGCAGTTTGGTGGAAAACCTTTCAGTTGTTCAGAACTTTCAATAGAACAG
TGGCTATGGTCAATATTCCTAGGAATGGGAACATTACTCTGGGGCCAGCTTATTTCAACA
ATTCCAACTAGCCGTTTAAAATTCCTCAAAGAAGCTGGTCATGGAACACAAAAGGAAGAA
ATACCTGAGGAGGAATTAGCAGAGGATGTTGAAGAGATTGATCACGCTGAAAGGGAGTTG
CGGCGTGGCCAAATCTTGTGGTTTAGAGGTCTGAACAGAATCCAAACACAGATTCGAGTG
GTGAATGCATTTCGTAGTTCTTTATATGAAGGGTTAGAAAAACCGGAATCAAGAAGTTCG
ATTCACAACTTTATGACACATCCTGAGTTTAGGATAGAAGATTCAGAGCCTCATATCCCC
CTTATTGATGACACTGATGCCGAAGATGATGCTCCTACAAAACGTAACTCCAGTCCTCCA
CCCTCTCCCAACAAAAATAACAATGCTGTTGACAGTGGAATTCACCTTACAATAGAAATG
AACAAGTCTGCTACCTCTTCATCCCCAGGAAGCCCACTACATAGTTTGGAAACATCACTC
TGA
Chromosome Location
12
Locus
12q21.33
External Identifiers
ResourceLink
UniProtKB IDP20020
UniProtKB Entry NameAT2B1_HUMAN
HGNC IDHGNC:814
General References
  1. Verma AK, Filoteo AG, Stanford DR, Wieben ED, Penniston JT, Strehler EE, Fischer R, Heim R, Vogel G, Mathews S, et al.: Complete primary structure of a human plasma membrane Ca2+ pump. J Biol Chem. 1988 Oct 5;263(28):14152-9. [Article]
  2. Kumar R, Haugen JD, Penniston JT: Molecular cloning of a plasma membrane calcium pump from human osteoblasts. J Bone Miner Res. 1993 Apr;8(4):505-13. [Article]
  3. Hilfiker H, Strehler-Page MA, Stauffer TP, Carafoli E, Strehler EE: Structure of the gene encoding the human plasma membrane calcium pump isoform 1. J Biol Chem. 1993 Sep 15;268(26):19717-25. [Article]
  4. Strehler EE, Strehler-Page MA, Vogel G, Carafoli E: mRNAs for plasma membrane calcium pump isoforms differing in their regulatory domain are generated by alternative splicing that involves two internal donor sites in a single exon. Proc Natl Acad Sci U S A. 1989 Sep;86(18):6908-12. [Article]
  5. Kessler F, Falchetto R, Heim R, Meili R, Vorherr T, Strehler EE, Carafoli E: Study of calmodulin binding to the alternatively spliced C-terminal domain of the plasma membrane Ca2+ pump. Biochemistry. 1992 Dec 1;31(47):11785-92. [Article]
  6. Stauffer TP, Hilfiker H, Carafoli E, Strehler EE: Quantitative analysis of alternative splicing options of human plasma membrane calcium pump genes. J Biol Chem. 1993 Dec 5;268(34):25993-6003. [Article]
  7. Stauffer TP, Hilfiker H, Carafoli E, Strehler EE: Quantitative analysis of alternative splicing options of human plasma membrane calcium pump genes. J Biol Chem. 1994 Dec 16;269(50):32022. [Article]
  8. Howard A, Legon S, Walters JR: Human and rat intestinal plasma membrane calcium pump isoforms. Am J Physiol. 1993 Nov;265(5 Pt 1):G917-25. [Article]
  9. James PH, Pruschy M, Vorherr TE, Penniston JT, Carafoli E: Primary structure of the cAMP-dependent phosphorylation site of the plasma membrane calcium pump. Biochemistry. 1989 May 16;28(10):4253-8. [Article]
  10. Wang KK, Wright LC, Machan CL, Allen BG, Conigrave AD, Roufogalis BD: Protein kinase C phosphorylates the carboxyl terminus of the plasma membrane Ca(2+)-ATPase from human erythrocytes. J Biol Chem. 1991 May 15;266(14):9078-85. [Article]
  11. Goellner GM, DeMarco SJ, Strehler EE: Characterization of PISP, a novel single-PDZ protein that binds to all plasma membrane Ca2+-ATPase b-splice variants. Ann N Y Acad Sci. 2003 Apr;986:461-71. [Article]
  12. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. [Article]
  13. Linde CI, Di Leva F, Domi T, Tosatto SC, Brini M, Carafoli E: Inhibitory interaction of the 14-3-3 proteins with ubiquitous (PMCA1) and tissue-specific (PMCA3) isoforms of the plasma membrane Ca2+ pump. Cell Calcium. 2008 Jun;43(6):550-61. doi: 10.1016/j.ceca.2007.09.003. Epub 2007 Oct 29. [Article]
  14. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [Article]
  15. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [Article]
  16. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  17. Yang H, Choi KC, Hyun SH, Jeung EB: Coexpression and estrogen-mediated regulation of TRPV6 and PMCA1 in the human endometrium during the menstrual cycle. Mol Reprod Dev. 2011 Apr;78(4):274-82. doi: 10.1002/mrd.21303. Epub 2011 Mar 11. [Article]
  18. Krapivinsky G, Krapivinsky L, Stotz SC, Manasian Y, Clapham DE: POST, partner of stromal interaction molecule 1 (STIM1), targets STIM1 to multiple transporters. Proc Natl Acad Sci U S A. 2011 Nov 29;108(48):19234-9. doi: 10.1073/pnas.1117231108. Epub 2011 Nov 14. [Article]
  19. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570. [Article]
  20. Zhou H, Di Palma S, Preisinger C, Peng M, Polat AN, Heck AJ, Mohammed S: Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res. 2013 Jan 4;12(1):260-71. doi: 10.1021/pr300630k. Epub 2012 Dec 18. [Article]
  21. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
  22. Long Y, Xia JY, Chen SW, Gao CL, Liang GN, He XM, Wu J, Jiang CX, Liu X, Huang W, Wan Q, Xu Y: ATP2B1 gene Silencing Increases Insulin Sensitivity through Facilitating Akt Activation via the Ca(2+)/calmodulin Signaling Pathway and Ca(2+)-associated eNOS Activation in Endothelial Cells. Int J Biol Sci. 2017 Sep 5;13(9):1203-1212. doi: 10.7150/ijbs.19666. eCollection 2017. [Article]
  23. Gong D, Chi X, Ren K, Huang G, Zhou G, Yan N, Lei J, Zhou Q: Structure of the human plasma membrane Ca(2+)-ATPase 1 in complex with its obligatory subunit neuroplastin. Nat Commun. 2018 Sep 6;9(1):3623. doi: 10.1038/s41467-018-06075-7. [Article]
  24. Benkwitz C, Kubisch C, Kraft K, Neyses L: Investigation of the Met-267 Arg exchange in isoform 1 of the human plasma membrane calcium pump in patients with essential hypertension by the amplification-created restriction site technique. J Mol Med (Berl). 1997 Jan;75(1):62-6. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01159Halothaneapproved, vet_approvedyesinhibitorDetails
DB01189DesfluraneapprovedyesinhibitorDetails
DB00867Ritodrineapproved, investigationalunknowninhibitorDetails
DB01236Sevofluraneapproved, vet_approvedyesinhibitorDetails