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3.A.3.2.25
Plasma membrane Ca2+-ATPase, isoform 1a (PMCA1) (78% identical to PMCA4 (TC# 3.A.3.2.1)). Maitotoxin converts it into a Ca2+-permeable nonselective cation channel (Sinkins et al., 2009). The C-terminal tail contains most of the regulatory sites including that for calmodulin. The pump is also regulated by acidic phospholipids, kinases, a dimerization process, and numerous protein interactors. In mammals, four genes code for the four basic isoforms. Isoform complexity is increased by alternative splicing of primary transcripts. Pumps 2 and 3 are expressed preferentially in the nervous system (Calì et al. 2017). This enzyme has two essential auxillary subunits, basigin and neuroplastin (NPTN), and the 3-d structure of the complex of PMCA1 with NPTN has been solved at 3.9 Å resolution (Gong et al. 2018). Methylene blue activates PMCA activity and cross-interacts with amyloid beta-peptide, blocking Abeta-mediated PMCA inhibition (Berrocal et al. 2018). Mutations leading to pathological neurooplastin (Np) variants, as exemplified by deafness causing Np mutants, can affect Np-dependent Ca2+ regulatory mechanisms and may potentially cause intellectual and cognitive deficits in humans (Liang et al. 2024).

Accession Number:P20020
Protein Name:Plasma membrane calcium-transporting ATPase 1
Length:1258
Molecular Weight:138755.00
Species: [9606]
Number of TMSs:10
Location1 / Topology2 / Orientation3: Cell membrane1 / Multi-pass membrane protein2
Substrate calcium(2+)

Cross database links:

RefSeq: NP_001001323.1    NP_001673.2   
Entrez Gene ID: 490   
Pfam: PF12424    PF00689    PF00690    PF00122    PF00702   
OMIM: 108731  gene
KEGG: hsa:490   

Gene Ontology

GO:0005887 C:integral to plasma membrane
GO:0005524 F:ATP binding
GO:0005388 F:calcium-transporting ATPase activity
GO:0005516 F:calmodulin binding
GO:0046872 F:metal ion binding
GO:0005515 F:protein binding
GO:0006754 P:ATP biosynthetic process
GO:0006816 P:calcium ion transport

References (13)

[1] “Complete primary structure of a human plasma membrane Ca2+ pump.”  Verma A.K.et.al.   2844759
[2] “Molecular cloning of a plasma membrane calcium pump from human osteoblasts.”  Kumar R.et.al.   8386431
[3] “Structure of the gene encoding the human plasma membrane calcium pump isoform 1.”  Hilfiker H.et.al.   8396145
[4] “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.”  Strehler E.E.et.al.   2528729
[5] “Study of calmodulin binding to the alternatively spliced C-terminal domain of the plasma membrane Ca2+ pump.”  Kessler F.et.al.   1332771
[6] “Quantitative analysis of alternative splicing options of human plasma membrane calcium pump genes.”  Stauffer T.P.et.al.   8245032
[7] “”  Stauffer T.P.et.al.   7989379
[8] “Human and rat intestinal plasma membrane calcium pump isoforms.”  Howard A.et.al.   7694502
[9] “Primary structure of the cAMP-dependent phosphorylation site of the plasma membrane calcium pump.”  James P.H.et.al.   2548572
[10] “Protein kinase C phosphorylates the carboxyl terminus of the plasma membrane Ca(2+)-ATPase from human erythrocytes.”  Wang K.K.W.et.al.   1827443
[11] “Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.”  Olsen J.V.et.al.   17081983
[12] “A quantitative atlas of mitotic phosphorylation.”  Dephoure N.et.al.   18669648
[13] “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.”  Benkwitz C.et.al.   9020386
Structure:
6A69     

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence 
1:	MGDMANNSVA YSGVKNSLKE ANHDGDFGIT LAELRALMEL RSTDALRKIQ ESYGDVYGIC 
61:	TKLKTSPNEG LSGNPADLER REAVFGKNFI PPKKPKTFLQ LVWEALQDVT LIILEIAAIV 
121:	SLGLSFYQPP EGDNALCGEV SVGEEEGEGE TGWIEGAAIL LSVVCVVLVT AFNDWSKEKQ 
181:	FRGLQSRIEQ EQKFTVIRGG QVIQIPVADI TVGDIAQVKY GDLLPADGIL IQGNDLKIDE 
241:	SSLTGESDHV KKSLDKDPLL LSGTHVMEGS GRMVVTAVGV NSQTGIIFTL LGAGGEEEEK 
301:	KDEKKKEKKN KKQDGAIENR NKAKAQDGAA MEMQPLKSEE GGDGDEKDKK KANLPKKEKS 
361:	VLQGKLTKLA VQIGKAGLLM SAITVIILVL YFVIDTFWVQ KRPWLAECTP IYIQYFVKFF 
421:	IIGVTVLVVA VPEGLPLAVT ISLAYSVKKM MKDNNLVRHL DACETMGNAT AICSDKTGTL 
481:	TMNRMTVVQA YINEKHYKKV PEPEAIPPNI LSYLVTGISV NCAYTSKILP PEKEGGLPRH 
541:	VGNKTECALL GLLLDLKRDY QDVRNEIPEE ALYKVYTFNS VRKSMSTVLK NSDGSYRIFS 
601:	KGASEIILKK CFKILSANGE AKVFRPRDRD DIVKTVIEPM ASEGLRTICL AFRDFPAGEP 
661:	EPEWDNENDI VTGLTCIAVV GIEDPVRPEV PDAIKKCQRA GITVRMVTGD NINTARAIAT 
721:	KCGILHPGED FLCLEGKDFN RRIRNEKGEI EQERIDKIWP KLRVLARSSP TDKHTLVKGI 
781:	IDSTVSDQRQ VVAVTGDGTN DGPALKKADV GFAMGIAGTD VAKEASDIIL TDDNFTSIVK 
841:	AVMWGRNVYD SISKFLQFQL TVNVVAVIVA FTGACITQDS PLKAVQMLWV NLIMDTLASL 
901:	ALATEPPTES LLLRKPYGRN KPLISRTMMK NILGHAFYQL VVVFTLLFAG EKFFDIDSGR 
961:	NAPLHAPPSE HYTIVFNTFV LMQLFNEINA RKIHGERNVF EGIFNNAIFC TIVLGTFVVQ 
1021:	IIIVQFGGKP FSCSELSIEQ WLWSIFLGMG TLLWGQLIST IPTSRLKFLK EAGHGTQKEE 
1081:	IPEEELAEDV EEIDHAEREL RRGQILWFRG LNRIQTQMDV VNAFQSGSSI QGALRRQPSI 
1141:	ASQHHDVTNI STPTHIRVVN AFRSSLYEGL EKPESRSSIH NFMTHPEFRI EDSEPHIPLI 
1201:	DDTDAEDDAP TKRNSSPPPS PNKNNNAVDS GIHLTIEMNK SATSSSPGSP LHSLETSL