AT8A2_BOVIN
ID AT8A2_BOVIN Reviewed; 1148 AA.
AC C7EXK4;
DT 09-JUL-2014, integrated into UniProtKB/Swiss-Prot.
DT 09-JUL-2014, sequence version 4.
DT 03-AUG-2022, entry version 83.
DE RecName: Full=Phospholipid-transporting ATPase IB {ECO:0000250|UniProtKB:Q9NTI2};
DE EC=7.6.2.1 {ECO:0000269|PubMed:19778899, ECO:0000269|PubMed:22307598, ECO:0000269|PubMed:24706822, ECO:0000269|PubMed:26592152, ECO:0000269|PubMed:31371510};
DE AltName: Full=ATPase class I type 8A member 2;
DE AltName: Full=P4-ATPase flippase complex alpha subunit ATP8A2;
GN Name=ATP8A2 {ECO:0000250|UniProtKB:Q9NTI2};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Retina;
RX PubMed=19778899; DOI=10.1074/jbc.m109.047415;
RA Coleman J.A., Kwok M.C., Molday R.S.;
RT "Localization, purification, and functional reconstitution of the P4-ATPase
RT Atp8a2, a phosphatidylserine flippase in photoreceptor disc membranes.";
RL J. Biol. Chem. 284:32670-32679(2009).
RN [2]
RP FUNCTION OF THE ATP8A2:TMEM30A FLIPPASE COMPLEX, IDENTIFICATION IN
RP ATP8A2:TMEM30A FLIPPASE COMPLEX, AND SUBCELLULAR LOCATION.
RX PubMed=21454556; DOI=10.1074/jbc.m111.229419;
RA Coleman J.A., Molday R.S.;
RT "Critical role of the beta-subunit CDC50A in the stable expression,
RT assembly, subcellular localization, and lipid transport activity of the P4-
RT ATPase ATP8A2.";
RL J. Biol. Chem. 286:17205-17216(2011).
RN [3]
RP CATALYTIC ACTIVITY, REACTION MECHANISM, AND MUTAGENESIS OF ASP-168;
RP GLU-170; ASP-388; LYS-837; LYS-845 AND ASN-846.
RX PubMed=22307598; DOI=10.1073/pnas.1108862109;
RA Coleman J.A., Vestergaard A.L., Molday R.S., Vilsen B., Andersen J.P.;
RT "Critical role of a transmembrane lysine in aminophospholipid transport by
RT mammalian photoreceptor P4-ATPase ATP8A2.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:1449-1454(2012).
RN [4]
RP MUTAGENESIS OF PHE-60; LEU-84; ILE-87; PHE-326; TYR-330; ASN-331; ASN-332;
RP LEU-333; ILE-334; ILE-336; SER-337; LEU-339; THR-341; GLU-343 AND LYS-346,
RP SITE, CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=24706822; DOI=10.1073/pnas.1321165111;
RA Vestergaard A.L., Coleman J.A., Lemmin T., Mikkelsen S.A., Molday L.L.,
RA Vilsen B., Molday R.S., Dal Peraro M., Andersen J.P.;
RT "Critical roles of isoleucine-364 and adjacent residues in a hydrophobic
RT gate control of phospholipid transport by the mammalian P4-ATPase ATP8A2.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:E1334-E1343(2014).
RN [5]
RP COMPONENT OF A P4-ATPASE FLIPPASE COMPLEX, MUTAGENESIS OF GLU-98; ILE-277;
RP LEU-333; LEU-338; LEU-339 AND TYR-850, CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=26592152; DOI=10.1016/j.febslet.2015.11.031;
RA Vestergaard A.L., Mikkelsen S.A., Coleman J.A., Molday R.S., Vilsen B.,
RA Andersen J.P.;
RT "Specific mutations in mammalian P4-ATPase ATP8A2 catalytic subunit entail
RT differential glycosylation of the accessory CDC50A subunit.";
RL FEBS Lett. 589:3908-3914(2015).
RN [6]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=31371510; DOI=10.1073/pnas.1910211116;
RA Tadini-Buoninsegni F., Mikkelsen S.A., Mogensen L.S., Molday R.S.,
RA Andersen J.P.;
RT "Phosphatidylserine flipping by the P4-ATPase ATP8A2 is electrogenic.";
RL Proc. Natl. Acad. Sci. U.S.A. 116:16332-16337(2019).
CC -!- FUNCTION: Catalytic component of a P4-ATPase flippase complex which
CC catalyzes the hydrolysis of ATP coupled to the transport of
CC aminophospholipids from the outer to the inner leaflet of various
CC membranes and ensures the maintenance of asymmetric distribution of
CC phospholipids (PubMed:19778899, PubMed:24706822, PubMed:31371510,
CC PubMed:26592152). Phospholipid translocation seems also to be
CC implicated in vesicle formation and in uptake of lipid signaling
CC molecules. Reconstituted to liposomes, the ATP8A2:TMEM30A flippase
CC complex predominantly transports phosphatidylserine (PS) and to a
CC lesser extent phosphatidylethanolamine (PE) (PubMed:19778899,
CC PubMed:24706822, PubMed:31371510, PubMed:26592152). Phospholipid
CC translocation is not associated with a countertransport of an inorganic
CC ion or other charged substrate from the cytoplasmic side toward the
CC exoplasm in connection with the phosphorylation from ATP
CC (PubMed:31371510). ATP8A2:TMEM30A may be involved in regulation of
CC neurite outgrowth. Proposed to function in the generation and
CC maintenance of phospholipid asymmetry in photoreceptor disk membranes
CC and neuronal axon membranes. May be involved in vesicle trafficking in
CC neuronal cells. Required for normal visual and auditory function;
CC involved in photoreceptor and inner ear spiral ganglion cell survival.
CC {ECO:0000269|PubMed:19778899, ECO:0000269|PubMed:21454556,
CC ECO:0000269|PubMed:24706822, ECO:0000269|PubMed:26592152,
CC ECO:0000269|PubMed:31371510}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + phospholipidSide 1 = ADP + phosphate +
CC phospholipidSide 2.; EC=7.6.2.1;
CC Evidence={ECO:0000269|PubMed:19778899, ECO:0000269|PubMed:22307598,
CC ECO:0000269|PubMed:24706822, ECO:0000269|PubMed:26592152,
CC ECO:0000269|PubMed:31371510};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-L-serine(out) + ATP + H2O =
CC a 1,2-diacyl-sn-glycero-3-phospho-L-serine(in) + ADP + H(+) +
CC phosphate; Xref=Rhea:RHEA:38567, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57262, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:19778899, ECO:0000269|PubMed:24706822,
CC ECO:0000269|PubMed:26592152, ECO:0000269|PubMed:31371510};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38568;
CC Evidence={ECO:0000269|PubMed:19778899, ECO:0000269|PubMed:24706822,
CC ECO:0000269|PubMed:26592152, ECO:0000269|PubMed:31371510};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(in) + ATP + H2O
CC = a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(out) + ADP + H(+) +
CC phosphate; Xref=Rhea:RHEA:36439, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:64612, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:24706822};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36440;
CC Evidence={ECO:0000305|PubMed:24706822};
CC -!- ACTIVITY REGULATION: ATPase activity is stimulated by
CC phosphatidylserine (PS) and minimally by phosphatidylethanolamine (PE).
CC ATPase activity is inhibited by N-ethylmaleimide (NEM) and vanadate.
CC Flippase activity is inhibited by NEM and 1,2-dioleoyl-sn-glycero-3-
CC phospho-L-serine (DOPS). {ECO:0000269|PubMed:19778899}.
CC -!- SUBUNIT: Component of a P4-ATPase flippase complex which consists of a
CC catalytic alpha subunit and an accessory beta subunit (PubMed:21454556,
CC PubMed:26592152). Interacts with TMEM30A to form a flippase complex
CC (PubMed:21454556). {ECO:0000269|PubMed:21454556,
CC ECO:0000269|PubMed:26592152}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305|PubMed:19778899,
CC ECO:0000305|PubMed:21454556}; Multi-pass membrane protein
CC {ECO:0000255}. Golgi apparatus membrane {ECO:0000250|UniProtKB:P98200}.
CC Endosome membrane {ECO:0000250|UniProtKB:P98200}. Cell membrane
CC {ECO:0000250|UniProtKB:P98200}. Photoreceptor outer segment membrane
CC {ECO:0000269|PubMed:19778899, ECO:0000269|PubMed:21454556}.
CC Photoreceptor inner segment membrane {ECO:0000269|PubMed:21454556}.
CC Note=Localizes to the Golgi and endosomes in photoreceptor cells (By
CC similarity). Localizes to disk membranes of rod photoreceptor outer
CC segments (ROS) (PubMed:21454556). {ECO:0000250|UniProtKB:P98200,
CC ECO:0000269|PubMed:21454556}.
CC -!- TISSUE SPECIFICITY: Expressed in retinal photoreceptor cells and
CC testis. {ECO:0000269|PubMed:19778899}.
CC -!- SIMILARITY: Belongs to the cation transport ATPase (P-type) (TC 3.A.3)
CC family. Type IV subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=ACT46164.3; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; GQ303567; ACT46164.3; ALT_INIT; mRNA.
DR RefSeq; NP_001157274.3; NM_001163802.3.
DR AlphaFoldDB; C7EXK4; -.
DR SMR; C7EXK4; -.
DR STRING; 9913.ENSBTAP00000053709; -.
DR SwissLipids; SLP:000000379; -.
DR SwissPalm; C7EXK4; -.
DR GeneID; 508723; -.
DR KEGG; bta:508723; -.
DR CTD; 51761; -.
DR OrthoDB; 587717at2759; -.
DR BRENDA; 7.6.2.1; 908.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0097381; C:photoreceptor disc membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0090555; F:phosphatidylethanolamine flippase activity; IDA:UniProtKB.
DR GO; GO:0140346; F:phosphatidylserine flippase activity; IDA:UniProtKB.
DR GO; GO:0090556; F:phosphatidylserine floppase activity; IDA:GO_Central.
DR GO; GO:0140331; P:aminophospholipid translocation; IDA:UniProtKB.
DR Gene3D; 3.40.1110.10; -; 1.
DR Gene3D; 3.40.50.1000; -; 1.
DR InterPro; IPR023299; ATPase_P-typ_cyto_dom_N.
DR InterPro; IPR018303; ATPase_P-typ_P_site.
DR InterPro; IPR023298; ATPase_P-typ_TM_dom_sf.
DR InterPro; IPR008250; ATPase_P-typ_transduc_dom_A_sf.
DR InterPro; IPR036412; HAD-like_sf.
DR InterPro; IPR023214; HAD_sf.
DR InterPro; IPR006539; P-type_ATPase_IV.
DR InterPro; IPR032631; P-type_ATPase_N.
DR InterPro; IPR001757; P_typ_ATPase.
DR InterPro; IPR032630; P_typ_ATPase_c.
DR InterPro; IPR044492; P_typ_ATPase_HD_dom.
DR Pfam; PF16212; PhoLip_ATPase_C; 1.
DR Pfam; PF16209; PhoLip_ATPase_N; 1.
DR SFLD; SFLDF00027; p-type_atpase; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
DR SUPFAM; SSF81653; SSF81653; 1.
DR SUPFAM; SSF81660; SSF81660; 1.
DR SUPFAM; SSF81665; SSF81665; 1.
DR TIGRFAMs; TIGR01652; ATPase-Plipid; 1.
DR TIGRFAMs; TIGR01494; ATPase_P-type; 2.
DR PROSITE; PS00154; ATPASE_E1_E2; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell membrane; Cell projection; Endosome; Golgi apparatus;
KW Lipid transport; Magnesium; Membrane; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Translocase; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..1148
FT /note="Phospholipid-transporting ATPase IB"
FT /id="PRO_0000429838"
FT TOPO_DOM 1..54
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 55..75
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 76..79
FT /note="Exoplasmic loop"
FT /evidence="ECO:0000255"
FT TRANSMEM 80..100
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 101..276
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 277..297
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 298..324
FT /note="Exoplasmic loop"
FT /evidence="ECO:0000255"
FT TRANSMEM 325..345
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 346..847
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 848..868
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 869..870
FT /note="Exoplasmic loop"
FT /evidence="ECO:0000255"
FT TRANSMEM 871..891
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 892..919
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 920..940
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 941..957
FT /note="Exoplasmic loop"
FT /evidence="ECO:0000255"
FT TRANSMEM 958..978
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 979..988
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 989..1009
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1010..1023
FT /note="Exoplasmic loop"
FT /evidence="ECO:0000255"
FT TRANSMEM 1024..1044
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1045..1148
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1102..1126
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1103..1119
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 388
FT /note="4-aspartylphosphate intermediate"
FT /evidence="ECO:0000305"
FT BINDING 781
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 785
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT SITE 331
FT /note="Involved in the recognition of the lipid substrate
FT on the exoplasmic side"
FT /evidence="ECO:0000269|PubMed:24706822"
FT SITE 336
FT /note="Involved in the release of the transported lipid
FT into the cytosolic leaflet"
FT /evidence="ECO:0000269|PubMed:24706822"
FT MOD_RES 5
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P98200"
FT MUTAGEN 60
FT /note="F->A: Enhances substrate affinities. Reduces
FT considerably the Vmax."
FT /evidence="ECO:0000269|PubMed:24706822"
FT MUTAGEN 84
FT /note="L->A: Does not affect Vmax. Does not affect the
FT apparent affinities for the substrates. Does not affect the
FT phosphorylation rate."
FT /evidence="ECO:0000269|PubMed:24706822"
FT MUTAGEN 87
FT /note="I->A: Reduces approximately twofold the apparent
FT affinity for PS. Does not affect the apparent affinity for
FT PE."
FT /evidence="ECO:0000269|PubMed:24706822"
FT MUTAGEN 98
FT /note="E->A: Decreases TMEM30A glycosylation. Does not
FT affect velocity of ATP hydrolyze of P4-ATPase flippase
FT complex. Reduces markedly the flipping activity."
FT /evidence="ECO:0000269|PubMed:26592152"
FT MUTAGEN 168
FT /note="D->T: Reduces flipping of PS; reduces ATPAse
FT activity by 3-fold."
FT /evidence="ECO:0000269|PubMed:22307598"
FT MUTAGEN 170
FT /note="E->Q: Slightly reverses flipping of PS, no ATPase
FT activity. Abolishes the transient current establishes in
FT the presence of ATP and the negatively charged lipid
FT substrate phosphatidylserine."
FT /evidence="ECO:0000269|PubMed:22307598,
FT ECO:0000269|PubMed:31371510"
FT MUTAGEN 277
FT /note="I->A: Decreases TMEM30A glycosylation. Does not
FT affect velocity of ATP hydrolyze of P4-ATPase flippase
FT complex."
FT /evidence="ECO:0000269|PubMed:26592152"
FT MUTAGEN 326
FT /note="F->A: Does not affect affinity for PS."
FT /evidence="ECO:0000269|PubMed:24706822"
FT MUTAGEN 330
FT /note="Y->A: Does not affect affinity for PS."
FT /evidence="ECO:0000269|PubMed:24706822"
FT MUTAGEN 331
FT /note="N->A: Reduces dramaticaly the maximal velocity
FT (Vmax) to 11% that of the wild type (WT) for PS and 9% for
FT PE. Reduces approximately sixfold the apparent affinity for
FT PS and PE. Reduces strongly ATPase activity. Loss of the PS
FT flipping. Enhances approximately threefold the
FT phosphorylation rate. Reduces highly the apparent affinity
FT for vanadate."
FT /evidence="ECO:0000269|PubMed:24706822"
FT MUTAGEN 332
FT /note="N->A: Increases the apparent affinity for PS.
FT Reduces approximately twofold the PS flipping rate relative
FT to the WT. Does not affect the phosphorylation rate."
FT /evidence="ECO:0000269|PubMed:24706822"
FT MUTAGEN 333
FT /note="L->A: Does not affect affinity for PS. Decreases
FT TMEM30A glycosylation. Does not affect velocity of ATP
FT hydrolyze of P4-ATPase flippase complex. Reduces markedly
FT the flipping activity."
FT /evidence="ECO:0000269|PubMed:24706822,
FT ECO:0000269|PubMed:26592152"
FT MUTAGEN 334
FT /note="I->A: Increases the apparent affinity for PS."
FT /evidence="ECO:0000269|PubMed:24706822"
FT MUTAGEN 336
FT /note="I->A: Decreases flipping activity of 20%.
FT Phosphatidylserine stimulates the ATPase activity to
FT maximum levels of 59% of the wild type level.
FT Phosphatityletanolamine (PE)-stimulated maximum activity is
FT only 16% of wild type. The phosphorylation rates is
FT fourfold reduced. Enhances approximately twofold the
FT apparent affinity for PS. Increases significantly apparent
FT vanadate affinity. Strongly interfers with the electrogenic
FT lipid translocation."
FT /evidence="ECO:0000269|PubMed:31371510"
FT MUTAGEN 336
FT /note="I->E: Loss of flipping activity. PS- and PE-
FT stimulated activity is very low. Does not affect the
FT phosphorylation rates. Reduces substantialy the apparent
FT affinity for PS. Reduces only slightly vanadate affinuity."
FT /evidence="ECO:0000269|PubMed:24706822"
FT MUTAGEN 336
FT /note="I->F: Loss of flipping activity. PS- and PE-
FT stimulated activity is very low. The phosphorylation rates
FT is fourfold reduced. Reduces substantialy the apparent
FT affinity for PS. Does not affect vanadate affinity."
FT /evidence="ECO:0000269|PubMed:24706822"
FT MUTAGEN 336
FT /note="I->M: Loss of flipping activity. PS- and PE-
FT stimulated activity is very low. The phosphorylation rates
FT is twofold reduced. Reduces substantialy the apparent
FT affinity for PS. Reduces markedly reduced vanadate
FT affinity."
FT /evidence="ECO:0000269|PubMed:24706822"
FT MUTAGEN 336
FT /note="I->Q: Decreases flipping activity of about 90%.
FT PS- and PE-stimulated activity is very low. The
FT phosphorylation rates is twofold reduced. Reduces markedly
FT reduced vanadate affinity."
FT /evidence="ECO:0000269|PubMed:24706822"
FT MUTAGEN 336
FT /note="I->S: Decreases flipping activity of 70%.
FT Phosphatidylserine (PS) stimulates the ATPase activity to
FT maximum levels of 43% of the wild type level.
FT Phosphatityletanolamine (PE)-stimulated maximum activity is
FT only 22% of wild type. The phosphorylation rates is
FT fourfold reduced. Enhances approximately twofold the
FT apparent affinity for PS. Increases significantly apparent
FT vanadate affinity."
FT /evidence="ECO:0000269|PubMed:24706822"
FT MUTAGEN 337
FT /note="S->A: Reduces significantly affinity for PS. Reduces
FT apparent affinity for PE."
FT /evidence="ECO:0000269|PubMed:24706822"
FT MUTAGEN 338
FT /note="L->A: Decreases TMEM30A glycosylation. Does not
FT affect velocity of ATP hydrolyze of P4-ATPase flippase
FT complex."
FT /evidence="ECO:0000269|PubMed:26592152"
FT MUTAGEN 339
FT /note="L->A: Reduces significantly affinity for PS. Does
FT not affect apparent affinity for PE."
FT /evidence="ECO:0000269|PubMed:24706822"
FT MUTAGEN 339
FT /note="L->F: Does not affect velocity of ATP hydrolyze of
FT P4-ATPase flippase complex. Reduces markedly the flipping
FT activity."
FT /evidence="ECO:0000269|PubMed:26592152"
FT MUTAGEN 341
FT /note="T->A: Increases the apparent affinity for PS."
FT /evidence="ECO:0000269|PubMed:24706822"
FT MUTAGEN 343
FT /note="E->Q: Does not affect affinity for PS."
FT /evidence="ECO:0000269|PubMed:24706822"
FT MUTAGEN 346
FT /note="K->A: Does not affect affinity for PS."
FT /evidence="ECO:0000269|PubMed:24706822"
FT MUTAGEN 388
FT /note="D->N: Abolishes ATPAse activity."
FT /evidence="ECO:0000269|PubMed:22307598"
FT MUTAGEN 837
FT /note="K->A: No effect on flipping of PS and ATPase
FT activity."
FT /evidence="ECO:0000269|PubMed:22307598"
FT MUTAGEN 845
FT /note="K->A: Greatly reduces flipping of PS; reduces
FT affinity PS by 7- and 8-fold; for reduces ATPase activity
FT by 30- and 70-fold; reduces PS-activated dephosphorylation
FT of intermediate; reduces affinity to vanadate."
FT /evidence="ECO:0000269|PubMed:22307598"
FT MUTAGEN 845
FT /note="K->E: Greatly reduces flipping of PS; reduces
FT affinity PS by 7- and 8-fold; for reduces ATPase activity
FT by 30- and 70-fold."
FT /evidence="ECO:0000269|PubMed:22307598"
FT MUTAGEN 845
FT /note="K->R: Reduces flipping of PS; reduces affinity PS by
FT 4-fold; reduces ATPase activity by 10-fold."
FT /evidence="ECO:0000269|PubMed:22307598"
FT MUTAGEN 846
FT /note="N->A: Reduces flipping of PS; reduces affinity PS by
FT 3-fold; reduces ATPase activity by 10-fold."
FT /evidence="ECO:0000269|PubMed:22307598"
FT MUTAGEN 850
FT /note="Y->A: Decreases TMEM30A glycosylation. Does not
FT affect velocity of ATP hydrolyze of P4-ATPase flippase
FT complex."
FT /evidence="ECO:0000269|PubMed:26592152"
SQ SEQUENCE 1148 AA; 129037 MW; 9D0DC179F8BF62EF CRC64;
MSRATSVGDQ LDVPARTIYL NQPHLNKFCD NQISTAKYSV VTFLPRFLYE QIRRAANAFF
LFIALLQQIP DVSPTGRYTT LVPLIIILTI AGIKEIVEDF KRHKADNAVN KKKTIVLRNG
MWQTIVWKEV AVGDIVKVVN GQYLPADVVL LSSSEPQAMC YVETANLDGE TNLKIRQGLS
HTADMQTREV LMKLSGTIEC EGPNRHLYDF TGNLNLDGKS PVALGPDQIL LRGTQLRNTQ
WGFGIVVYTG HDTKLMQNST KAPLKRSNVE KVTNVQILVL FGILLVMALV SSVGALYWNG
SQGGKNWYIK KMDATSDNFG YNLLTFIILY NNLIPISLLV TLEVVKYTQA LFINWDTDMY
YLGNDTPAMA RTSNLNEELG QVKYLFSDKT GTLTCNIMNF KKCSIAGVTY GHFPELTREP
SSDDFSRIPP PPSDSCDFDD PRLLKNIEDH HPTAPCIQEF LTLLAVCHTV VPERDGDSIV
YQASSPDEAA LVKGARKLGF VFTARTPYSV IIEAMGQEQT FGILNVLEFS SDRKRMSVIV
RTPSGQLRLY CKGADNVIFE RLSKDSKYME ETLCHLEYFA TEGLRTLCVA YADLSERDYE
EWLKVYQEAS TILKDRAQRL EECYEIIEKN LLLLGATAIE DRLQAGVPET IATLLKAEIK
IWVLTGDKQE TAINIGYSCR LVSQNMALIL LKEDSLDATR AAITQHCADL GSLLGKENDA
ALIIDGHTLK YALSFEVRRS FLDLALSCKA VICCRVSPLQ KSEIVDVVKK RVKAITLAIG
DGANDVGMIQ TAHVGVGISG NEGMQATNNS DYAIAQFSYL EKLLLVHGAW SYNRVTKCIL
YCFYKNVVLY IIELWFAFVN GFSGQILFER WCIGLYNVIF TALPPFTLGI FERSCSQESM
LRFPQLYKIT QNAEGFNTKV FWGHCINALV HSLILFWFPM KALEHDTVLA NGHATDYLFV
GNIVYTYVVV TVCLKAGLET TAWTKFSHLA VWGSMLIWLV FFGIYSTIWP TIPIAPDMKG
QATMVLSSAH FWLGLFLVPT ACLIEDVAWR AAKHTCKKTL LEEVQELEMK SRVMGRAMLR
DSNGKRMNER DRLLKRLSRK TPPTLFRGSS LQQSMPHGYA FSQEEHGAVT QEEIVRAYDT
TKQKSRKK
