Q6Q477

SS
Gene name
Atp2b4
Protein name
Plasma membrane calcium-transporting ATPase 4
Names
PMCA4 , EC 7.2.2.10
Species
Mus musculus (Mouse)
KEGG Pathway
mmu:381290
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)

1083-1113 (C-terminal segment/Calmodulin binding domain) SS

Target domain

347-1052 (P-type ATPase domain)

Relief mechanism

Partner binding, Ligand binding

Assay

170-171 (Asp170 in the putative A domain) SS

Target domain

446-1047 (P-type ATPase domain)

Relief mechanism

Partner binding

Assay

297-350 (the C-terminal segment of the loop between helices 2 and 3, AL region) SS

Target domain

446-1047 (P-type ATPase domain)

Relief mechanism

Partner binding, Ligand binding

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

1 structures for Q6Q477

Entry ID Method Resolution Chain Position Source
AF-Q6Q477-F1 Predicted AlphaFoldDB

70 variants for Q6Q477

Variant ID(s) Position Change Description Diseaes Association Provenance
rs3388501191 7 Q>E No EVA
rs37014571 9 V>M No EVA
rs234154731 13 T>A No EVA
rs3388500456 73 L>F No EVA
rs3388497662 109 L>V No EVA
rs36930281 138 S>N No EVA
rs3390627898 153 A>E No EVA
rs3390652950 156 L>I No EVA
rs240503492 188 Q>H No EVA
rs3388497622 207 V>M No EVA
rs3388501582 216 Y>N No EVA
rs3388498021 247 K>* No EVA
rs3388497309 250 L>M No EVA
rs3388501553 256 L>* No EVA
rs3388501618 282 I>F No EVA
rs251480263 296 D>E No EVA
rs3388500414 324 I>T No EVA
rs233239978 343 A>G No EVA
rs37503625 343 A>T No EVA
rs3388501659 359 R>C No EVA
rs3388500262 374 L>I No EVA
rs3388500764 383 F>I No EVA
rs1132644203 388 F>L No EVA
rs260829568 394 E>A No EVA
rs3388500712 431 T>N No EVA
rs3412959015 481 A>V No EVA
rs3388500455 489 R>L No EVA
rs254228330 491 I>V No EVA
rs3388500674 510 S>P No EVA
rs3539741003 542 G>D No EVA
rs3388500733 543 F>I No EVA
rs3388500500 591 S>G No EVA
rs37338876 614 S>A No EVA
rs3388501022 615 F>L No EVA
rs252379854 648 G>D No EVA
rs3388496214 676 R>L No EVA
rs224823808 681 D>N No EVA
rs1133115426 728 F>L No EVA
rs245663096 730 S>R No EVA
rs3388500689 743 K>N No EVA
rs3388500736 771 D>A No EVA
rs3388497653 792 P>H No EVA
rs3388500669 850 T>I No EVA
rs3388500608 876 M>* No EVA
rs3388500276 916 T>S No EVA
rs3388500788 922 L>M No EVA
rs3388501560 928 Q>R No EVA
rs107887141 941 T>R No EVA
rs3388500791 988 V>E No EVA
rs3388501241 990 A>T No EVA
rs3388496194 992 V>I No EVA
rs3388499213 998 F>L No EVA
rs257726505 1003 L>F No EVA
rs3388499687 1005 T>I No EVA
rs3388501192 1030 W>R No EVA
rs3388501586 1034 L>F No EVA
rs3388498031 1047 I>V No EVA
rs254548827 1068 E>D No EVA
rs223419740 1089 R>Q No EVA
rs3388501267 1090 G>D No EVA
rs3390647238 1093 L>* No EVA
rs234809039 1110 L>M No EVA
rs225767173 1112 H>Y No EVA
rs255996255 1114 N>I No EVA
rs3388497323 1123 N>H No EVA
rs3388499174 1133 Q>H No EVA
rs3539733503 1140 D>N No EVA
rs3388501209 1156 L>M No EVA
rs3388501264 1159 K>N No EVA
rs3388498057 1176 N>I No EVA

No associated diseases with Q6Q477

5 regional properties for Q6Q477

Type Name Position InterPro Accession
domain Cation-transporting P-type ATPase, N-terminal 45 - 121 IPR004014
domain Cation-transporting P-type ATPase, C-terminal 869 - 1048 IPR006068
ptm P-type ATPase, phosphorylation site 466 - 472 IPR018303
domain Plasma membrane calcium transporting P-type ATPase, C-terminal 1090 - 1135 IPR022141
domain P-type ATPase, haloacid dehalogenase domain 446 - 836 IPR044492

Functions

Description
EC Number 7.2.2.10 Linked to the hydrolysis of a nucleoside triphosphate
Subcellular Localization
  • Membrane ; Multi-pass membrane protein
  • Cell projection, cilium, flagellum membrane ; Multi-pass membrane protein
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

11 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 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.
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 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.
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.

10 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.
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.

28 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 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 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
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
P23634 ATP2B4 Plasma membrane calcium-transporting ATPase 4 Homo sapiens (Human) EV
Q9R0K7 Atp2b2 Plasma membrane calcium-transporting ATPase 2 Mus musculus (Mouse) SS
G5E829 Atp2b1 Plasma membrane calcium-transporting ATPase 1 Mus musculus (Mouse) SS
P23220 ATP2B1 Plasma membrane calcium-transporting ATPase 1 Sus scrofa (Pig) 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
P11506 Atp2b2 Plasma membrane calcium-transporting ATPase 2 Rattus norvegicus (Rat) SS
Q64542 Atp2b4 Plasma membrane calcium-transporting ATPase 4 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
MTNPPGQSVS ANTVAESHEG EFGCTLMDLR KLMELRGADA VAQISAHYGG VQEICTRLKT
70 80 90 100 110 120
SPIEGLSGNP ADLEKRRLVF GKNVIPPKRP KTFLELVWEA LQDVTLIILE IAAIISLVLS
130 140 150 160 170 180
FYRPPGGDNE ICGHIASSPE EEEEGETGWI EGAAILASVI IVVLVTAFND WSKEKQFRGL
190 200 210 220 230 240
QSRIELEQKF SIIRNGQLIQ LPVAEIVVGD IAQIKYGDLL PADGILIQGN DLKIDESSLT
250 260 270 280 290 300
GESDHVKKTL DKDPMLLSGT HVMEGSGRMV VTAVGVNSQT GIIFTLLGAS EEEDDDDKKK
310 320 330 340 350 360
KGKKQGAPEN RNKAKTQDGV ALEIQPLNSQ EGLDSEDKEK KIARIPKKEK SVLQGKLTRL
370 380 390 400 410 420
AVQIGKAGLI MSVLTVVILI LYFVVDNFVI QRREWLPECT PVYIQYFVKF FIIGVTVLVV
430 440 450 460 470 480
AVPEGLPLAV TISLAYSVKK MMKDNNLVRH LDACETMGNA TAICSDKTGT LTMNRMTVVQ
490 500 510 520 530 540
AYIGGTHYRQ IPQPDVFPPK VLELIVNGIS INCAYTSKIQ PPEKEGGLPR QVGNKTECGL
550 560 570 580 590 600
LGFVTDLKQD YQAVRNEVPE EKLFKVYTFN SVRKSMSTVI RKPEGGFRMF SKGASEIMLR
610 620 630 640 650 660
RCDRILNKEG EIKSFRSKDR DNMVRNVIEP MASEGLRTIC LAYRDFDGTE PSWDIEGEIL
670 680 690 700 710 720
TSLICIAVVG IEDPVRPEVP DAIAKCKRAG ITVRMVTGDN VNTARAIATK CGILTPKDDF
730 740 750 760 770 780
LCLEGKEFNS LIRNEKGEVE QEKLDKIWPK LRVLARSSPT DKHTLVKGII DSTAGEQRQV
790 800 810 820 830 840
VAVTGDGTND GPALKKADVG FAMGIAGTDV AKEASDIILT DDNFTSIVKA VMWGRNVYDS
850 860 870 880 890 900
ISKFLQFQLT VNVVAVIVAF TGACITQDSP LKAVQMLWVN LIMDTFASLA LATEPPTESL
910 920 930 940 950 960
LRRRPYGRNK PLISRTMMKN ILGHAVYQLL IVFLLVFAGD TLFDIDSGRK APLNSPPSQH
970 980 990 1000 1010 1020
YTIVFNTFVL MQLFNEINAR KIHGEKNVFA GVYRNIIFCT VVLGTFFCQI MIVELGGKPF
1030 1040 1050 1060 1070 1080
SCTSLTMEQW MWCLFIGIGE LLWGQVISAI PTKSLKFLKE AGHGSDKEDI SRDTEGMDEI
1090 1100 1110 1120 1130 1140
DLAEMELRRG QILWVRGLNR IQTQIRVVKL FHNNHEVAHK PKNRSSIHTF MTQPEYPADD
1150 1160 1170 1180 1190 1200
ELSQSFLDIQ EGNPELVSKA GTSVLLLDGE AASHDNINNN AVDCHQVQIV ASHSDSPLPS
LETPV