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Literature summary extracted from

  • Vestergaard, A.L.; Coleman, J.A.; Lemmin, T.; Mikkelsen, S.A.; Molday, L.L.; Vilsen, B.; Molday, R.S.; Dal Peraro, M.; Andersen, J.P.
    Critical roles of isoleucine-364 and adjacent residues in a hydrophobic gate control of phospholipid transport by the mammalian P4-ATPase ATP8A2 (2014), Proc. Natl. Acad. Sci. USA, 111, E1334-E1343.
    View publication on PubMedView publication on EuropePMC

Activating Compound

EC Number Activating Compound Comment Organism Structure
7.6.2.1 phosphatidylserine stimulates the ATPase activity about 20fold Bos taurus

Protein Variants

EC Number Protein Variants Comment Organism
7.6.2.1 E371Q affinity to phosphatidylserine similar to wild-type Bos taurus
7.6.2.1 F354A affinity to phosphatidylserine similar to wild-type Bos taurus
7.6.2.1 F88A tendency for inhibition at high substrate concentration Bos taurus
7.6.2.1 I115A biphasic phosphatidylserine concentration dependence with inhibition at the highest concentration Bos taurus
7.6.2.1 I362A increase in the apparent affinity for phosphatidylserine Bos taurus
7.6.2.1 I364A 80% of wild-type activity Bos taurus
7.6.2.1 I364E 3-5fold reduction in affinity for phosphatidylserine Bos taurus
7.6.2.1 I364F 3-5fold reduction in affinity for phosphatidylserine Bos taurus
7.6.2.1 I364M 3-5fold reduction in affinity for phosphatidylserine Bos taurus
7.6.2.1 I364Q activation phase is followed by an inhibition phase at high phosphatidylserine concentration Bos taurus
7.6.2.1 I364S 30% of wild-type activity Bos taurus
7.6.2.1 K374A affinity to phosphatidylserine similar to wild-type Bos taurus
7.6.2.1 L112A mutation does not appreciably affect Vmax, the apparent affinities for the substrates, or the phosphorylation rate Bos taurus
7.6.2.1 L361A affinity to phosphatidylserine similar to wild-type Bos taurus
7.6.2.1 L367A significant reduction in affinity to phosphatidylserine Bos taurus
7.6.2.1 N359A dramatic reduction of Vmax to 9-11% of wild-type Bos taurus
7.6.2.1 N360A increase in the apparent affinity for phosphatidylserine Bos taurus
7.6.2.1 P363A complete loss of activity Bos taurus
7.6.2.1 S365A significant reduction in affinity to phosphatidylserine Bos taurus
7.6.2.1 T369A increase in the apparent affinity for phosphatidylserine Bos taurus
7.6.2.1 V906A pronounced inhibition at high phosphatidylethanol concentration with only a slight inhibition at high phosphatidylserine concentration Bos taurus
7.6.2.1 Y358A affinity to phosphatidylserine similar to wild-type Bos taurus

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
7.6.2.1 0.016
-
ATP mutant I364A, presence of phosphatidylserine, K0.5 value, pH 7.5, 37°C Bos taurus
7.6.2.1 0.016
-
ATP mutant I364S, presence of phosphatidylserine, K0.5 value, pH 7.5, 37°C Bos taurus
7.6.2.1 0.019
-
ATP mutant I364Q, presence of phosphatidylserine, K0.5 value, pH 7.5, 37°C Bos taurus
7.6.2.1 0.02
-
ATP mutant T369A, presence of phosphatidylserine, K0.5 value, pH 7.5, 37°C Bos taurus
7.6.2.1 0.02
-
ATP mutant V906A, presence of phosphatidylserine, K0.5 value, pH 7.5, 37°C Bos taurus
7.6.2.1 0.023
-
ATP mutant N360A, presence of phosphatidylserine, K0.5 value, pH 7.5, 37°C Bos taurus
7.6.2.1 0.024
-
ATP mutant I362A, presence of phosphatidylserine, K0.5 value, pH 7.5, 37°C Bos taurus
7.6.2.1 0.027
-
ATP mutant F88A, presence of phosphatidylserine, K0.5 value, pH 7.5, 37°C Bos taurus
7.6.2.1 0.036
-
ATP mutant Y358A, presence of phosphatidylserine, K0.5 value, pH 7.5, 37°C Bos taurus
7.6.2.1 0.038
-
ATP wild-type, presence of phosphatidylserine, K0.5 value, pH 7.5, 37°C Bos taurus
7.6.2.1 0.042
-
ATP mutant F354A, presence of phosphatidylserine, K0.5 value, pH 7.5, 37°C Bos taurus
7.6.2.1 0.045
-
ATP mutant L112A, presence of phosphatidylserine, K0.5 value, pH 7.5, 37°C Bos taurus
7.6.2.1 0.049
-
ATP mutant E371Q, presence of phosphatidylserine, K0.5 value, pH 7.5, 37°C Bos taurus
7.6.2.1 0.049
-
ATP mutant K374A, presence of phosphatidylserine, K0.5 value, pH 7.5, 37°C Bos taurus
7.6.2.1 0.058
-
ATP mutant L361A, presence of phosphatidylserine, K0.5 value, pH 7.5, 37°C Bos taurus
7.6.2.1 0.068
-
ATP mutant L367A, presence of phosphatidylserine, K0.5 value, pH 7.5, 37°C Bos taurus
7.6.2.1 0.073
-
ATP mutant I115A, presence of phosphatidylserine, K0.5 value, pH 7.5, 37°C Bos taurus
7.6.2.1 0.103
-
ATP mutant V906A, presence of phosphatidylethanolamine, K0.5 value, pH 7.5, 37°C Bos taurus
7.6.2.1 0.104
-
ATP mutant S365A, presence of phosphatidylserine, K0.5 value, pH 7.5, 37°C Bos taurus
7.6.2.1 0.105
-
ATP mutant I364S, presence of phosphatidylethanolamine, K0.5 value, pH 7.5, 37°C Bos taurus
7.6.2.1 0.111
-
ATP mutant I364E, presence of phosphatidylserine, K0.5 value, pH 7.5, 37°C Bos taurus
7.6.2.1 0.131
-
ATP mutant I364A, presence of phosphatidylethanolamine, K0.5 value, pH 7.5, 37°C Bos taurus
7.6.2.1 0.148
-
ATP mutant I364M, presence of phosphatidylserine, K0.5 value, pH 7.5, 37°C Bos taurus
7.6.2.1 0.149
-
ATP mutant I362A, presence of phosphatidylethanolamine, K0.5 value, pH 7.5, 37°C Bos taurus
7.6.2.1 0.178
-
ATP mutant I364F, presence of phosphatidylserine, K0.5 value, pH 7.5, 37°C Bos taurus
7.6.2.1 0.22
-
ATP mutant N359A, presence of phosphatidylserine, K0.5 value, pH 7.5, 37°C Bos taurus
7.6.2.1 0.25
-
ATP mutant F88A, presence of phosphatidylethanolamine, K0.5 value, pH 7.5, 37°C Bos taurus
7.6.2.1 0.288
-
ATP mutant I364Q, presence of phosphatidylethanolamine, K0.5 value, pH 7.5, 37°C Bos taurus
7.6.2.1 0.292
-
ATP mutant I364E, presence of phosphatidylethanolamine, K0.5 value, pH 7.5, 37°C Bos taurus
7.6.2.1 0.369
-
ATP mutant I364M, presence of phosphatidylethanolamine, K0.5 value, pH 7.5, 37°C Bos taurus
7.6.2.1 0.371
-
ATP wild-type, presence of phosphatidylethanolamine, K0.5 value, pH 7.5, 37°C Bos taurus
7.6.2.1 0.376
-
ATP mutant I115A, presence of phosphatidylethanolamine, K0.5 value, pH 7.5, 37°C Bos taurus
7.6.2.1 0.379
-
ATP mutant L367A, presence of phosphatidylethanolamine, K0.5 value, pH 7.5, 37°C Bos taurus
7.6.2.1 0.394
-
ATP mutant L112A, presence of phosphatidylethanolamine, K0.5 value, pH 7.5, 37°C Bos taurus
7.6.2.1 0.862
-
ATP mutant S365A, presence of phosphatidylethanolamine, K0.5 value, pH 7.5, 37°C Bos taurus
7.6.2.1 1.12
-
ATP mutant I364F, presence of phosphatidylethanolamine, K0.5 value, pH 7.5, 37°C Bos taurus
7.6.2.1 2.215
-
ATP mutant N359A, presence of phosphatidylethanolamine, K0.5 value, pH 7.5, 37°C Bos taurus

Organism

EC Number Organism UniProt Comment Textmining
7.6.2.1 Bos taurus C7EXK4
-
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
7.6.2.1 ATP + H2O
-
Bos taurus ADP + phosphate
-
?
7.6.2.1 ATP + H2O + phosphatidylethanolamine/in
-
Bos taurus ADP + phosphate + phosphatidylethanolamine/out
-
?
7.6.2.1 ATP + H2O + phosphatidylserine/in
-
Bos taurus ADP + phosphate + phosphatidylserine/out
-
?
7.6.2.1 additional information during the transport across the membrane, the phosphatidylserine head group passes near residue I364. I364 is critical to the release of the transported lipid into the cytosolic leaflet. Transmembrane segment M4 residue N359 is involved in recognition of the lipid substrate on the exoplasmic side. Residue I364 and adjacent hydrophobic residues function as a hydrophobic gate that separates the entry and exit sites of the lipid and directs sequential formation and annihilation of water-filled cavities, thereby enabling transport of the hydrophilic phospholipid head group in a groove outlined by the transmembrane segments M1, M2, M4, and M6, with the hydrocarbon chains following passively, still in the membrane lipid phase Bos taurus ?
-
?

Synonyms

EC Number Synonyms Comment Organism
7.6.2.1 Atp8a2
-
Bos taurus
7.6.2.1 phospholipid-transporting ATPase IB
-
Bos taurus