P23220
SS
Gene name |
ATP2B1 |
Protein name |
Plasma membrane calcium-transporting ATPase 1 |
Names |
EC 7.2.2.10 , Plasma membrane calcium ATPase isoform 1 , PMCA1 , Plasma membrane calcium pump isoform 1 |
Species |
Sus scrofa (Pig) |
KEGG Pathway |
ssc:397636 |
EC number |
7.2.2.10: Linked to the hydrolysis of a nucleoside triphosphate |
Protein Class |
|
Descriptions
The plasmid membrane Ca2+ pump (PMCA) extrudes Ca2+ from the cytosol to the extracellular space playing an important role in the maintenance of the resting level of intracellular Ca2+ and in the control of the Ca2+ transients. The PMCAs are of major physiological importance, with different isoforms being essential for presynaptic and postsynaptic Ca2+ regulation in neurons and for feedback signaling in the heart and sperm motility. The PMCAs belong to the subtype 2B of P-type ATPases. The C-terminal segment of the PMCA functions as an autoinhibitory domain by interacting with the catalytic core. Ca2+-calmodulin binds to the C-terminal segment and stops inhibition by switching the PMCA to an activated state of higher maximum activity and affinity for Ca2+. In the PMCA3, the G1107D replacement impairs the autoinhibition mechanism by introducing a negative charge perturbing the contacts between the calmodulin binding domain and the pump core.
Autoinhibitory domains (AIDs)
Target domain |
455-1058 (P-type ATPase domain) |
Relief mechanism |
Partner binding |
Assay |
|
Target domain |
455-1058 (P-type ATPase domain) |
Relief mechanism |
Partner binding, Ligand binding |
Assay |
|
Accessory elements
No accessory elements
References
- Yeon JH et al. (2016) "Systems-wide Identification of cis-Regulatory Elements in Proteins", Cell systems, 2, 89-100
- Calì T et al. (2017) "The ataxia related G1107D mutation of the plasma membrane Ca(2+) ATPase isoform 3 affects its interplay with calmodulin and the autoinhibition process", Biochimica et biophysica acta. Molecular basis of disease, 1863, 165-173
- Carafoli E (1994) "Biogenesis: plasma membrane calcium ATPase: 15 years of work on the purified enzyme", FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 8, 993-1002
- Tidow H et al. (2010) "Expression, purification, crystallization and preliminary X-ray analysis of calmodulin in complex with the regulatory domain of the plasma-membrane Ca2+-ATPase ACA8", Acta crystallographica. Section F, Structural biology and crystallization communications, 66, 361-3
- Saffioti NA et al. (2021) "Conformational changes during the reaction cycle of plasma membrane Ca2+-ATPase in the autoinhibited and activated states", The Biochemical journal, 478, 2019-2034
- Calì T et al. (2018) "The PMCA pumps in genetically determined neuronal pathologies", Neuroscience letters, 663, 2-11
- Corradi GR et al. (2007) "Intramolecular fluorescence resonance energy transfer between fused autofluorescent proteins reveals rearrangements of the N- and C-terminal segments of the plasma membrane Ca2+ pump involved in the activation", The Journal of biological chemistry, 282, 35440-8
- Osborn KD et al. (2005) "Single-molecule characterization of the dynamics of calmodulin bound to oxidatively modified plasma-membrane Ca2+-ATPase", Biochemistry, 44, 11074-81
- Lopreiato R et al. (2014) "The plasma membrane calcium pump: new ways to look at an old enzyme", The Journal of biological chemistry, 289, 10261-10268
- Bredeston LM et al. (2004) "Loss of autoinhibition of the plasma membrane Ca(2+) pump by substitution of aspartic 170 by asparagin. A ctivation of plasma membrane calcium ATPase 4 without disruption of the interaction between the catalytic core and the C-terminal regulatory domain", The Journal of biological chemistry, 279, 41619-25
- Pinto Fde T et al. (2002) "Deletions in the acidic lipid-binding region of the plasma membrane Ca2+ pump. A mutant with high affinity for Ca2+ resembling the acidic lipid-activated enzyme", The Journal of biological chemistry, 277, 12784-9
Autoinhibited structure
Activated structure
1 structures for P23220
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-P23220-F1 | Predicted | AlphaFoldDB |
No variants for P23220
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| No variants for P23220 | |||||
No associated diseases with P23220
7 regional properties for P23220
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | C2 domain | 1203 - 1329 | IPR000008-1 |
| domain | C2 domain | 2044 - 2171 | IPR000008-2 |
| domain | Protein kinase C-like, phorbol ester/diacylglycerol-binding domain | 1097 - 1147 | IPR002219 |
| domain | MUN domain | 1539 - 2028 | IPR010439 |
| domain | Munc13 homology 1 | 1637 - 1780 | IPR014770 |
| domain | Mammalian uncoordinated homology 13, domain 2 | 1886 - 2028 | IPR014772 |
| domain | Protein Unc-13, C2B domain | 1220 - 1346 | IPR037302 |
Functions
| Description | ||
|---|---|---|
| EC Number | 7.2.2.10 | Linked to the hydrolysis of a nucleoside triphosphate |
| Subcellular Localization |
|
|
| PANTHER Family | ||
| PANTHER Subfamily | ||
| PANTHER Protein Class | ||
| PANTHER Pathway Category | No pathway information available | |
6 GO annotations of cellular component
| Name | Definition |
|---|---|
| basolateral plasma membrane | The region of the plasma membrane that includes the basal end and sides of the cell. Often used in reference to animal polarized epithelial membranes, where the basal membrane is the part attached to the extracellular matrix, or in plant cells, where the basal membrane is defined with respect to the zygotic axis. |
| cell projection | A prolongation or process extending from a cell, e.g. a flagellum or axon. |
| immunological synapse | An area of close contact between a lymphocyte (T-, B-, or natural killer cell) and a target cell formed through the clustering of particular signaling and adhesion molecules and their associated membrane rafts on both the lymphocyte and the target cell and facilitating activation of the lymphocyte, transfer of membrane from the target cell to the lymphocyte, and in some situations killing of the target cell through release of secretory granules and/or death-pathway ligand-receptor interaction. |
| intracellular membrane-bounded organelle | Organized structure of distinctive morphology and function, bounded by a single or double lipid bilayer membrane and occurring within the cell. Includes the nucleus, mitochondria, plastids, vacuoles, and vesicles. Excludes the plasma membrane. |
| presynaptic membrane | A specialized area of membrane of the axon terminal that faces the plasma membrane of the neuron or muscle fiber with which the axon terminal establishes a synaptic junction; many synaptic junctions exhibit structural presynaptic characteristics, such as conical, electron-dense internal protrusions, that distinguish it from the remainder of the axon plasma membrane. |
| synaptic vesicle membrane | The lipid bilayer surrounding a synaptic vesicle. |
6 GO annotations of molecular function
| Name | Definition |
|---|---|
| ATP binding | Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator. |
| ATP hydrolysis activity | Catalysis of the reaction |
| calmodulin binding | Binding to calmodulin, a calcium-binding protein with many roles, both in the calcium-bound and calcium-free states. |
| metal ion binding | Binding to a metal ion. |
| P-type calcium transporter activity | Enables the transfer of a solute or solutes from one side of a membrane to the other according to the reaction |
| PDZ domain binding | Binding to a PDZ domain of a protein, a domain found in diverse signaling proteins. |
9 GO annotations of biological process
| Name | Definition |
|---|---|
| intracellular calcium ion homeostasis | A homeostatic process involved in the maintenance of a steady state level of calcium ions within a cell. |
| negative regulation of cytokine production | Any process that stops, prevents, or reduces the rate of production of a cytokine. |
| negative regulation of cytosolic calcium ion concentration | Any process that decreases the concentration of calcium ions in the cytosol. |
| positive regulation of bone mineralization | Any process that activates or increases the frequency, rate or extent of bone mineralization. |
| positive regulation of calcium ion transport | Any process that activates or increases the frequency, rate or extent of the directed movement of calcium ions into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. |
| regulation of blood pressure | Any process that modulates the force with which blood travels through the circulatory system. The process is controlled by a balance of processes that increase pressure and decrease pressure. |
| regulation of cellular response to insulin stimulus | Any process that modulates the frequency, rate or extent of cellular response to insulin stimulus. |
| regulation of cytosolic calcium ion concentration | Any process involved in the maintenance of an internal steady state of calcium ions within the cytosol of a cell or between the cytosol and its surroundings. |
| regulation of vascular associated smooth muscle contraction | Any process that increases the frequency, rate or extent of vascular smooth muscle contraction. |
31 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| P38929 | PMC1 | Calcium-transporting ATPase 2 | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) | PR |
| D3K0R6 | ATP2B4 | Plasma membrane calcium-transporting ATPase 4 | Bos taurus (Bovine) | SS |
| Q16720 | ATP2B3 | Plasma membrane calcium-transporting ATPase 3 | Homo sapiens (Human) | EV |
| P23634 | ATP2B4 | Plasma membrane calcium-transporting ATPase 4 | Homo sapiens (Human) | EV |
| Q01814 | ATP2B2 | Plasma membrane calcium-transporting ATPase 2 | Homo sapiens (Human) | SS |
| P20020 | ATP2B1 | Plasma membrane calcium-transporting ATPase 1 | Homo sapiens (Human) | SS |
| Q9R0K7 | Atp2b2 | Plasma membrane calcium-transporting ATPase 2 | Mus musculus (Mouse) | SS |
| Q6Q477 | Atp2b4 | Plasma membrane calcium-transporting ATPase 4 | Mus musculus (Mouse) | SS |
| G5E829 | Atp2b1 | Plasma membrane calcium-transporting ATPase 1 | Mus musculus (Mouse) | SS |
| Q64542 | Atp2b4 | Plasma membrane calcium-transporting ATPase 4 | Rattus norvegicus (Rat) | SS |
| Q64568 | Atp2b3 | Plasma membrane calcium-transporting ATPase 3 | Rattus norvegicus (Rat) | SS |
| P11506 | Atp2b2 | Plasma membrane calcium-transporting ATPase 2 | Rattus norvegicus (Rat) | SS |
| P11505 | Atp2b1 | Plasma membrane calcium-transporting ATPase 1 | Rattus norvegicus (Rat) | SS |
| Q2QMX9 | ACA10 | Calcium-transporting ATPase 10, plasma membrane-type | Oryza sativa subsp japonica (Rice) | SS |
| Q2QY12 | ACA9 | Probable calcium-transporting ATPase 9, plasma membrane-type | Oryza sativa subsp japonica (Rice) | SS |
| Q6ATV4 | ACA3 | Calcium-transporting ATPase 3, plasma membrane-type | Oryza sativa subsp japonica (Rice) | SS |
| Q7X8B5 | ACA5 | Calcium-transporting ATPase 5, plasma membrane-type | Oryza sativa subsp japonica (Rice) | SS |
| Q7XEK4 | ACA7 | Calcium-transporting ATPase 7, plasma membrane-type | Oryza sativa subsp japonica (Rice) | EV |
| Q8RUN1 | ACA1 | Calcium-transporting ATPase 1, plasma membrane-type | Oryza sativa subsp japonica (Rice) | SS |
| Q65X71 | ACA6 | Probable calcium-transporting ATPase 6, plasma membrane-type | Oryza sativa subsp japonica (Rice) | SS |
| Q2RAS0 | ACA8 | Probable calcium-transporting ATPase 8, plasma membrane-type | Oryza sativa subsp japonica (Rice) | SS |
| O22218 | ACA4 | Calcium-transporting ATPase 4, plasma membrane-type | Arabidopsis thaliana (Mouse-ear cress) | SS |
| O64806 | ACA7 | Putative calcium-transporting ATPase 7, plasma membrane-type | Arabidopsis thaliana (Mouse-ear cress) | SS |
| O81108 | ACA2 | Calcium-transporting ATPase 2, plasma membrane-type | Arabidopsis thaliana (Mouse-ear cress) | EV |
| Q9LF79 | ACA8 | Calcium-transporting ATPase 8, plasma membrane-type | Arabidopsis thaliana (Mouse-ear cress) | EV |
| Q9LIK7 | ACA13 | Putative calcium-transporting ATPase 13, plasma membrane-type | Arabidopsis thaliana (Mouse-ear cress) | SS |
| Q9LU41 | ACA9 | Calcium-transporting ATPase 9, plasma membrane-type | Arabidopsis thaliana (Mouse-ear cress) | SS |
| Q9LY77 | ACA12 | Calcium-transporting ATPase 12, plasma membrane-type | Arabidopsis thaliana (Mouse-ear cress) | SS |
| Q9M2L4 | ACA11 | Putative calcium-transporting ATPase 11, plasma membrane-type | Arabidopsis thaliana (Mouse-ear cress) | SS |
| Q9SZR1 | ACA10 | Calcium-transporting ATPase 10, plasma membrane-type | Arabidopsis thaliana (Mouse-ear cress) | SS |
| Q37145 | ACA1 | Calcium-transporting ATPase 1 | Arabidopsis thaliana (Mouse-ear cress) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MGDMANNSVA | YGGVKNSLKE | ANHDGDFGIT | LADVRALMEL | RSTDALRKIQ | ESYGDVYGIC |
| 70 | 80 | 90 | 100 | 110 | 120 |
| TRLKTSPVEG | LSGNPADIER | REAVFGKNFI | PPKKPKTFLQ | LVWEALQDVT | LIILEIAAIV |
| 130 | 140 | 150 | 160 | 170 | 180 |
| SLGLSFYQPP | EGDNALCGEV | SVGEEEGEGE | TGWIEGAAIL | LSVVCVVLVT | AFNDWSKEKQ |
| 190 | 200 | 210 | 220 | 230 | 240 |
| FRGLQSRIEQ | EQKFTVIRGG | QVIQIPVADI | TVGDIAQVKY | GDLLPADGIL | IQGNDLKIDE |
| 250 | 260 | 270 | 280 | 290 | 300 |
| SSLTGESDHV | KKSLDKDPLL | LSGTHVMEGS | GRMVVTAVGI | NSQTGIIFTL | LGAGGEEEEK |
| 310 | 320 | 330 | 340 | 350 | 360 |
| KDEKKKEKKN | KKQDGAIENR | NKAKAQDGAA | MEMQPLKSEE | GGDGDEKDKK | KANLPKKEKS |
| 370 | 380 | 390 | 400 | 410 | 420 |
| VLQGKLTKLA | VQIGKAGLLM | SAITVIILVL | YFVIDTFWVQ | KRPWLAECTP | IYIQYFVKFF |
| 430 | 440 | 450 | 460 | 470 | 480 |
| IIGVTVLVVA | VPEGLPLAVT | ISLAYSVKKM | MKDNNLVRHL | DACETMGNAT | AICSDKTGTL |
| 490 | 500 | 510 | 520 | 530 | 540 |
| TMNRMTVVQA | YINEKHYKKI | PEPEAIPPNI | LSYLVTGISV | NCAYTSKILP | PEKEGGLPRH |
| 550 | 560 | 570 | 580 | 590 | 600 |
| VGNKTECALL | GLLLDLKRDY | QDVRNEIPEE | ALYKVYTFNS | VRKSMSTVLK | NSDGSYRIFS |
| 610 | 620 | 630 | 640 | 650 | 660 |
| KGASEIILKK | CFKILSANGE | AKVFRPRDRD | DIVKTVIEPM | ASEGLRTICL | AFRDFPAGEP |
| 670 | 680 | 690 | 700 | 710 | 720 |
| EPEWDNENDI | VTGLTCIAVV | GIEDPVRPEV | PDAIKKCQRA | GITVRMVTGD | NINTARAIAT |
| 730 | 740 | 750 | 760 | 770 | 780 |
| KCGILHPGED | FLCLEGKDFN | RRIRNEKGEI | EQERIDKIWP | KLRVLARSSP | TDKHTLVKGI |
| 790 | 800 | 810 | 820 | 830 | 840 |
| IDSTVSDQRQ | VVAVTGDGTN | DGPALKKADV | GFAMGIAGTD | VAKEASDIIL | TDDNFTSIVK |
| 850 | 860 | 870 | 880 | 890 | 900 |
| AVMWGRNVYD | SISKFLQFQL | TVNVVAVIVA | FTGACITQDS | PLKAVQMLWV | NLIMDTLASL |
| 910 | 920 | 930 | 940 | 950 | 960 |
| ALATEPPTES | LLLRKPYGRN | KPLISRTMMK | NILGHAFYQL | VVVFTLLFAG | EKFFDIDSGR |
| 970 | 980 | 990 | 1000 | 1010 | 1020 |
| NAPLHAPPSE | HYTIVFNTFV | LMQLFNEINA | RKIHGERNVF | EGIFNNAIFC | TIVLGTFVVQ |
| 1030 | 1040 | 1050 | 1060 | 1070 | 1080 |
| IIIVQFGGKP | FSCSELSIEQ | WLWSIFLGMG | TLLWGQLIST | IPTSRLKFLK | EAGHGTQKEE |
| 1090 | 1100 | 1110 | 1120 | 1130 | 1140 |
| IPEEELAEDV | EEIDHAEREL | RRGQILWFRG | LNRIQTQIRV | VNAFRSSLYE | GLEKPESRSS |
| 1150 | 1160 | 1170 | 1180 | 1190 | 1200 |
| IHNFMTHPEF | RIEDSEPHIP | LIDDTDAEDD | APTKRNCSPP | PSPNKNNNAV | DSGIYLTIEM |
| 1210 | |||||
| NKSATSSSPG | SPLHSLETSL |