Q64542
SS
Gene name |
Atp2b4 |
Protein name |
Plasma membrane calcium-transporting ATPase 4 |
Names |
PMCA4 , EC 7.2.2.10 , Plasma membrane calcium ATPase isoform 4 , Plasma membrane calcium pump isoform 4 |
Species |
Rattus norvegicus (Rat) |
KEGG Pathway |
rno:29600 |
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 |
346-1051 (P-type ATPase domain) |
Relief mechanism |
Partner binding, Ligand binding |
Assay |
|
Target domain |
445-1046 (P-type ATPase domain) |
Relief mechanism |
Partner binding |
Assay |
|
Target domain |
445-1046 (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 Q64542
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-Q64542-F1 | Predicted | AlphaFoldDB |
1 variants for Q64542
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs3322233992 | 294 | D>E | No | EVA |
No associated diseases with Q64542
5 regional properties for Q64542
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | Cation-transporting P-type ATPase, N-terminal | 45 - 121 | IPR004014 |
| domain | Cation-transporting P-type ATPase, C-terminal | 868 - 1047 | IPR006068 |
| ptm | P-type ATPase, phosphorylation site | 465 - 471 | IPR018303 |
| domain | Plasma membrane calcium transporting P-type ATPase, C-terminal | 1089 - 1134 | IPR022141 |
| domain | P-type ATPase, haloacid dehalogenase domain | 445 - 835 | IPR044492 |
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 | |
12 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. |
| glutamatergic synapse | A synapse that uses glutamate as a neurotransmitter. |
| 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. |
| membrane | A lipid bilayer along with all the proteins and protein complexes embedded in it and attached to it. |
| membrane raft | Any of the small (10-200 nm), heterogeneous, highly dynamic, sterol- and sphingolipid-enriched membrane domains that compartmentalize cellular processes. Small rafts can sometimes be stabilized to form larger platforms through protein-protein and protein-lipid interactions. |
| presynaptic active zone membrane | The membrane portion of the presynaptic active zone; it is the site where docking and fusion of synaptic vesicles occurs for the release of neurotransmitters. |
| protein-containing complex | A stable assembly of two or more macromolecules, i.e. proteins, nucleic acids, carbohydrates or lipids, in which at least one component is a protein and the constituent parts function together. |
| sarcolemma | The outer membrane of a muscle cell, consisting of the plasma membrane, a covering basement membrane (about 100 nm thick and sometimes common to more than one fiber), and the associated loose network of collagen fibers. |
| sperm flagellum | A microtubule-based flagellum (or cilium) that is part of a sperm, a mature male germ cell that develops from a spermatid. |
| sperm principal piece | The segment of the sperm flagellum where the mitochondrial sheath ends, and the outer dense fibers (ODFs) associated with outer axonemal doublets 3 and 8 are replaced by the 2 longitudinal columns of the fibrous sheath (FS) which run the length of the principal piece and are stabilized by circumferential ribs. The principal piece makes up ~2/3 of the length of the sperm flagellum and is defined by the presence of the FS and of only 7 (rather than 9) ODFs which taper and then terminate near the distal end of the principal piece. |
| T-tubule | Invagination of the plasma membrane of a muscle cell that extends inward from the cell surface around each myofibril. The ends of T-tubules make contact with the sarcoplasmic reticulum membrane. |
| Z disc | Platelike region of a muscle sarcomere to which the plus ends of actin filaments are attached. |
12 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 |
| calcium ion transmembrane transporter activity | Enables the transfer of calcium (Ca) ions from one side of a membrane to the other. |
| 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. |
| nitric-oxide synthase binding | Binding to nitric-oxide synthase. |
| nitric-oxide synthase inhibitor activity | Binds to and stops, prevents or reduces the activity of nitric oxide synthase. |
| 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. |
| protein kinase binding | Binding to a protein kinase, any enzyme that catalyzes the transfer of a phosphate group, usually from ATP, to a protein substrate. |
| protein phosphatase 2B binding | Binding to a protein phosphatase 2B. |
| scaffold protein binding | Binding to a scaffold protein. Scaffold proteins are crucial regulators of many key signaling pathways. Although not strictly defined in function, they are known to interact and/or bind with multiple members of a signaling pathway, tethering them into complexes. |
30 GO annotations of biological process
| Name | Definition |
|---|---|
| calcium ion export | The directed movement of calcium ion out of a cell or organelle. |
| calcium ion transmembrane transport | A process in which a calcium ion is transported from one side of a membrane to the other by means of some agent such as a transporter or pore. |
| calcium ion transport | The directed movement of calcium (Ca) ions into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. |
| cellular response to acetylcholine | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an acetylcholine stimulus. |
| cellular response to epinephrine stimulus | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an epinephrine stimulus. Epinephrine is a catecholamine that has the formula C9H13NO3; it is secreted by the adrenal medulla to act as a hormone, and released by certain neurons to act as a neurotransmitter active in the central nervous system. |
| flagellated sperm motility | The directed, self-propelled movement of a cilium (aka flagellum) that contributes to the movement of a flagellated sperm. |
| hippocampus development | The progression of the hippocampus over time from its initial formation until its mature state. |
| 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 adenylate cyclase-activating adrenergic receptor signaling pathway | Any process that stops, prevents, or reduces the frequency, rate or extent of an adenylate cyclase-activating adrenergic receptor protein signaling pathway activity. An adrenergic receptor signaling pathway is the series of molecular signals generated as a consequence of an adrenergic receptor binding to one of its physiological ligands. |
| negative regulation of angiogenesis | Any process that stops, prevents, or reduces the frequency, rate or extent of angiogenesis. |
| negative regulation of arginine catabolic process | Any process that stops, prevents or reduces the frequency, rate or extent of arginine catabolic process. |
| negative regulation of blood vessel endothelial cell migration | Any process that stops, prevents, or reduces the frequency, rate or extent of the migration of the endothelial cells of blood vessels. |
| negative regulation of calcineurin-NFAT signaling cascade | Any process that stops, prevents, or reduces the frequency, rate or extent of the calcineurin-NFAT signaling cascade. |
| negative regulation of cardiac muscle hypertrophy in response to stress | Any process that stops, prevents or reduces the frequency, rate or extent of cardiac muscle hypertrophy in response to stress. |
| negative regulation of cellular response to vascular endothelial growth factor stimulus | Any process that stops, prevents or reduces the frequency, rate or extent of cellular response to vascular endothelial growth factor stimulus. |
| negative regulation of citrulline biosynthetic process | Any process that stops, prevents or reduces the frequency, rate or extent of citrulline biosynthetic process. |
| negative regulation of gene expression | Any process that decreases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA). |
| negative regulation of nitric oxide biosynthetic process | Any process that stops, prevents, or reduces the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of nitric oxide. |
| negative regulation of nitric oxide mediated signal transduction | Any process that decreases the rate, frequency or extent of nitric oxide mediated signal transduction. Nitric oxide mediated signal transduction is The series of molecular signals mediated by the detection of nitric oxide (NO). |
| negative regulation of the force of heart contraction | Any process that decreases the force of heart muscle contraction. |
| neural retina development | The progression of the neural retina over time from its initial formation to the mature structure. The neural retina is the part of the retina that contains neurons and photoreceptor cells. |
| nitric oxide-cGMP-mediated signaling pathway | Any intracellular signal transduction in which the signal is passed on within the cell by nitric oxide (NO) activating soluble guanylyl cyclase (sGC). Includes synthesis of nitric oxide, guanylyl cyclase activity, and downstream effectors that further transmit the signal within the cell following activation by cGMP. |
| positive regulation of peptidyl-serine phosphorylation | Any process that activates or increases the frequency, rate or extent of the phosphorylation of peptidyl-serine. |
| positive regulation of protein localization to plasma membrane | Any process that activates or increases the frequency, rate or extent of protein localization to plasma membrane. |
| regulation of cell cycle G1/S phase transition | Any signalling pathway that modulates the activity of a cell cycle cyclin-dependent protein kinase to modulate the switch from G1 phase to S phase of the cell cycle. |
| 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 transcription by RNA polymerase II | Any process that modulates the frequency, rate or extent of transcription mediated by RNA polymerase II. |
| response to hydrostatic pressure | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a hydrostatic pressure stimulus. Hydrostatic pressure is the force acting on an object in a system where the fluid is at rest (as opposed to moving). The weight of the fluid above the object creates pressure on it. |
| spermatogenesis | The developmental process by which male germ line stem cells self renew or give rise to successive cell types resulting in the development of a spermatozoa. |
| urinary bladder smooth muscle contraction | A process in which force is generated within smooth muscle tissue, resulting in a change in muscle geometry. This process occurs in the urinary bladder. Force generation involves a chemo-mechanical energy conversion step that is carried out by the actin/myosin complex activity, which generates force through ATP hydrolysis. The urinary bladder is a musculomembranous sac along the urinary tract. |
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 |
| Q01814 | ATP2B2 | Plasma membrane calcium-transporting ATPase 2 | Homo sapiens (Human) | SS |
| P20020 | ATP2B1 | Plasma membrane calcium-transporting ATPase 1 | Homo sapiens (Human) | SS |
| P23634 | ATP2B4 | Plasma membrane calcium-transporting ATPase 4 | Homo sapiens (Human) | EV |
| G5E829 | Atp2b1 | Plasma membrane calcium-transporting ATPase 1 | Mus musculus (Mouse) | 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 |
| P23220 | ATP2B1 | Plasma membrane calcium-transporting ATPase 1 | Sus scrofa (Pig) | 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 |
| Q64568 | Atp2b3 | Plasma membrane calcium-transporting ATPase 3 | Rattus norvegicus (Rat) | SS |
| Q8RUN1 | ACA1 | Calcium-transporting ATPase 1, 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 |
| Q2QMX9 | ACA10 | Calcium-transporting ATPase 10, plasma membrane-type | Oryza sativa subsp japonica (Rice) | SS |
| Q7XEK4 | ACA7 | Calcium-transporting ATPase 7, plasma membrane-type | Oryza sativa subsp japonica (Rice) | EV |
| Q7X8B5 | ACA5 | Calcium-transporting ATPase 5, 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 |
| Q65X71 | ACA6 | Probable calcium-transporting ATPase 6, plasma membrane-type | Oryza sativa subsp japonica (Rice) | SS |
| O22218 | ACA4 | Calcium-transporting ATPase 4, 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 |
| 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 |
| Q9LY77 | ACA12 | Calcium-transporting ATPase 12, plasma membrane-type | Arabidopsis thaliana (Mouse-ear cress) | SS |
| 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 |
| Q9LF79 | ACA8 | Calcium-transporting ATPase 8, plasma membrane-type | Arabidopsis thaliana (Mouse-ear cress) | EV |
| 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 |
| MTNPSGHNLP | ANSVAESYEG | EFGCTLMDLR | KLMELRAADA | VTQISAHYGS | VQEICARLKT |
| 70 | 80 | 90 | 100 | 110 | 120 |
| SPVEGLSGNP | ADLEKRRLVF | GKNMIPPKKP | KTFLELVWEA | LQDVTLIILE | IAAIISLVLS |
| 130 | 140 | 150 | 160 | 170 | 180 |
| FYRPPGGENE | ICGHIVSNPE | EDEEGETGWI | EGAAILASVI | IVVFVTAFND | WSKEKQFRGL |
| 190 | 200 | 210 | 220 | 230 | 240 |
| QSRIELEQKF | SIIRNGQLIQ | LPVAEIVVGD | IAQVKYGDLL | PADGILIQGN | DLKIDESSLT |
| 250 | 260 | 270 | 280 | 290 | 300 |
| GESDHVKKTL | DKDPMLLSGT | HVMEGSGRMV | VTAVGINSQT | GIIFTLLGAN | EEEDDEKKKK |
| 310 | 320 | 330 | 340 | 350 | 360 |
| GKKQGVSENR | NKAKTQDGVA | LEIQPLNSQE | GLDSEEKEKK | ASKGPKKEKS | VLQGKLTRLA |
| 370 | 380 | 390 | 400 | 410 | 420 |
| VQIGKAGLIM | SILTVLILIL | YFVVDNFVIQ | RRAWLPECTP | VYIQYFVKFF | IIGVTVLVVA |
| 430 | 440 | 450 | 460 | 470 | 480 |
| VPEGLPLAVT | ISLAYSVKKM | MKDNNLVRHL | DACETMGNAT | AICSDKTGTL | TMNRMTVVQA |
| 490 | 500 | 510 | 520 | 530 | 540 |
| YIGGTHYRQI | PKPDDLPPNV | LDLIVNSICI | NSAYTSKILP | PEKEGGLPRQ | VGNKTECGLL |
| 550 | 560 | 570 | 580 | 590 | 600 |
| GFVTDLKQDY | QAVRSEMPEE | KLFKVYTFNS | VRKSMSTVIR | KPEGGFRVFS | KGASEIMLRK |
| 610 | 620 | 630 | 640 | 650 | 660 |
| CDRILNKEGG | IVPFKTKDRD | NMVRNVIEPM | ASEGLRTIGI | AYRDFDGEEP | SWENENEIFT |
| 670 | 680 | 690 | 700 | 710 | 720 |
| GLVCIAVVGI | EDPVRPEVPD | AINKCKRAGI | TVRMVTGDNV | NTARAIATKC | GILTPGDDFL |
| 730 | 740 | 750 | 760 | 770 | 780 |
| CLEGKEFNRL | IRNEKGEVEQ | EKLDKVWPRL | RVLARSSPTD | KHTLVKGIID | SNIGEQRQVV |
| 790 | 800 | 810 | 820 | 830 | 840 |
| AVTGDGTNDG | PALKKADVGF | AMGIAGTDVA | KEASDIILTD | DNFTSIVKAV | MWGRNVYDSI |
| 850 | 860 | 870 | 880 | 890 | 900 |
| SKFLQFQLTV | NVVAVIVAFS | GACITQDSPL | KAVQMLWVNL | IMDTFASLAL | ATEPPTDSLL |
| 910 | 920 | 930 | 940 | 950 | 960 |
| RRRPYGRNKP | LISRTMMKNI | LGHAVYQLGI | VFLLVFAGDK | LFDIDSGRKA | PLNSPPSQHY |
| 970 | 980 | 990 | 1000 | 1010 | 1020 |
| TIVFNTFVLM | QLFNEINSRK | IHGEKNVFAG | VYRNIIFCSV | VLGTFFCQIL | IVEVGGKPFS |
| 1030 | 1040 | 1050 | 1060 | 1070 | 1080 |
| CTNLTMEQWM | WCLFIGIGEL | LWGQVISAIP | TKSLKFLKEA | GHGSDKEEIS | KDAEGLEEID |
| 1090 | 1100 | 1110 | 1120 | 1130 | 1140 |
| HAEMELRRGQ | ILWVRGLNRI | QTQIRVVKVF | HSFRDVIHKS | KNQVSIHSFM | TQPEYAADDE |
| 1150 | 1160 | 1170 | 1180 | 1190 | 1200 |
| MSQSFLNQEE | SPSLASKSRI | TKRLSDAETV | SQNNTNNNAV | DCHQVQIVAS | HPNSPLQSQE |
| TPV |