Q64568

SS
Gene name
Atp2b3 (Pmca3)
Protein name
Plasma membrane calcium-transporting ATPase 3
Names
PMCA3 , EC 7.2.2.10 , Plasma membrane calcium ATPase isoform 3 , Plasma membrane calcium pump isoform 3
Species
Rattus norvegicus (Rat)
KEGG Pathway
rno:29599
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. <br>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+. <br>Mutation D170N activates the PMCA by increasing the affinity for Ca2+. In the absence of calmodulin, the affinity for Ca2+ of the D170N mutant shows as high as in the presence of calmodulin. The D170N mutation does not affect the inhibition by the portion of the C-terminal regulatory domain downstream from the calmodulin-binding site. Thus, the activation of the D170N PMCA takes place without fully disengaging the C-terminal domain from the catalytic core. <br> The C-terminal segment of the loop between transmembrane helices 2 and 3 (AL region) of the PMCA acts as an acidic lipid-binding inhibitory domain capable of adjusting the Ca2+ affinity of the PMCA to the lipid composition of the membrane. Mutants with deletions in the segment (296-349) have full Ca2+ transport activity by enhancing its response to Ca2+. The function of the segment is independent of the autoinhibition by the C-terminal calmodulin-binding region.

Autoinhibitory domains (AIDs)

1060-1193 (C-terminal segment/Calmodulin binding domain) SS

Target domain

453-1055 (P-type ATPase domain)

Relief mechanism

Partner binding, Ligand binding

Assay

175-176 (Asp170 in the putative A domain) SS

Target domain

453-1055 (P-type ATPase domain)

Relief mechanism

Partner binding

Assay

301-357 (the C-terminal segment of the loop between helices 2 and 3, AL region) SS

Target domain

453-1055 (P-type ATPase domain)

Relief mechanism

Partner binding, Ligand binding

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

1 structures for Q64568

Entry ID Method Resolution Chain Position Source
AF-Q64568-F1 Predicted AlphaFoldDB

No variants for Q64568

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for Q64568

No associated diseases with Q64568

6 regional properties for Q64568

Type Name Position InterPro Accession
domain Cation-transporting P-type ATPase, N-terminal 50 - 126 IPR004014
domain Cation-transporting P-type ATPase, C-terminal 877 - 1055 IPR006068
ptm P-type ATPase, phosphorylation site 473 - 479 IPR018303
domain Plasma membrane calcium transporting P-type ATPase, C-terminal 1100 - 1130 IPR022141-1
domain Plasma membrane calcium transporting P-type ATPase, C-terminal 1151 - 1184 IPR022141-2
domain P-type ATPase, haloacid dehalogenase domain 453 - 844 IPR044492

Functions

Description
EC Number 7.2.2.10 Linked to the hydrolysis of a nucleoside triphosphate
Subcellular Localization
  • Cell membrane ; Multi-pass membrane protein
  • Presynaptic cell membrane ; Multi-pass membrane protein
  • Localized at parallel fiber terminals
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

7 GO annotations of cellular component

Name Definition
GABA-ergic synapse A synapse that uses GABA as a neurotransmitter. These synapses are typically inhibitory.
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.
parallel fiber A parallel fiber results from the bifurcation of a cerebellar granule cell axon in the molecular layer into two diametrically opposed branches, that are oriented parallel to the long axis of the folium.
parallel fiber to Purkinje cell synapse An excitatory synapse formed by the parallel fibers of granule cells synapsing onto the dendrites of Purkinje cells.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
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.

8 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.
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
P-type calcium transporter activity involved in regulation of presynaptic cytosolic calcium ion concentration A calcium-transporting P-type ATPase activity involved in regulation of presynaptic cytosolic calcium ion concentration.
PDZ domain binding Binding to a PDZ domain of a protein, a domain found in diverse signaling proteins.

3 GO annotations of biological process

Name Definition
calcium ion export across plasma membrane The directed movement of calcium ions from inside of a cell, across the plasma membrane and into the extracellular region.
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.
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.

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
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
Q16720 ATP2B3 Plasma membrane calcium-transporting ATPase 3 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
Q64542 Atp2b4 Plasma membrane calcium-transporting ATPase 4 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
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
MGDMANSSIE FHPKPQQQRE VPHVGGFGCT LAELRSLMEL RGAEALQKIQ EAYGDVSGLC
70 80 90 100 110 120
RRLKTSPTEG LADNTNDLEK RRQIYGQNFI PPKQPKTFLQ LVWEALQDVT LIILEVAAIV
130 140 150 160 170 180
SLGLSFYAPP GEESEACGNV SGGAEDEGEA EAGWIEGAAI LLSVICVVLV TAFNDWSKEK
190 200 210 220 230 240
QFRGLQSRIE QEQKFTVIRN GQLLQVPVAA LVVGDIAQVK YGDLLPADGV LIQGNDLKID
250 260 270 280 290 300
ESSLTGESDH VRKSADKDPM LLSGTHVMEG SGRMVVTAVG VNSQTGIIFT LLGAGGEEEE
310 320 330 340 350 360
KKDKKGKQQD GAMESSQTKA KKQDGAVAME MQPLKSAEGG EMEEREKKKA NVPKKEKSVL
370 380 390 400 410 420
QGKLTKLAVQ IGKAGLVMSA ITVIILVLYF VIETFVVDGR VWLAECTPVY VQYFVKFFII
430 440 450 460 470 480
GVTVLVVAVP EGLPLAVTIS LAYSVKKMMK DNNLVRHLDA CETMGNATAI CSDKTGTLTT
490 500 510 520 530 540
NRMTVVQSYL GDTHYKEIPA PSALTPKILD LLVHAISINS AYTTKILPPE KEGALPRQVG
550 560 570 580 590 600
NKTECALLGF ILDLKRDFQP VREQIPEDQL YKVYTFNSVR KSMSTVIRMP DGGFRLFSKG
610 620 630 640 650 660
ASEILLKKCT NILNSNGELR GFRPRDRDDM VKKIIEPMAC DGLRTICIAY RDFSAIQEPD
670 680 690 700 710 720
WDNENEVVGD LTCIAVVGIE DPVRPEVPEA IRKCQRAGIT VRMVTGDNIN TARAIAAKCG
730 740 750 760 770 780
IIQPGEDFLC LEGKEFNRRI RNEKGEIEQE RLDKVWPKLR VLARSSPTDK HTLVKGIIDS
790 800 810 820 830 840
TTGEQRQVVA VTGDGTNDGP ALKKADVGFA MGIAGTDVAK EASDIILTDD NFTSIVKAVM
850 860 870 880 890 900
WGRNVYDSIS KFLQFQLTVN VVAVIVAFTG ACITQDSPLK AVQMLWVNLI MDTFASLALA
910 920 930 940 950 960
TEPPTESLLL RKPYGRDKPL ISRTMMKNIL GHAVYQLTII FTLLFVGELF FDIDSGRNAP
970 980 990 1000 1010 1020
LHSPPSEHYT IIFNTFVMMQ LFNEINARKI HGERNVFDGI FSNPIFCTIV LGTFGIQIVI
1030 1040 1050 1060 1070 1080
VQFGGKPFSC SPLSTEQWLW CLFVGVGELV WGQVIATIPT SQLKCLKEAG HGPGKDEMTD
1090 1100 1110 1120 1130 1140
EELAEGEEEI DHAERELRRG QILWFRGLNR IQTQMEVVST FKRSGSFQGA VRRRSSVLSQ
1150 1160 1170 1180 1190 1200
LHDVTNLSTP THIRVVKAFR SSLYEGLEKP ESKSCIHNFM ATPEFLINDY THNIPLIDDT
1210 1220 1230 1240 1250
DVDENEERLR APPPPPPNQN NNAIDSGIYL TTHATKSATS SAFSSRPGSP LHSMETSL