AT8A1_BOVIN
ID AT8A1_BOVIN Reviewed; 1149 AA.
AC Q29449;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1999, sequence version 2.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Probable phospholipid-transporting ATPase IA {ECO:0000305};
DE EC=7.6.2.1 {ECO:0000250|UniProtKB:P70704};
DE AltName: Full=ATPase class I type 8A member 1;
DE AltName: Full=Chromaffin granule ATPase II;
GN Name=ATP8A1 {ECO:0000250|UniProtKB:Q9Y2Q0};
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], AND PROTEIN SEQUENCE OF 502-678 AND 1144-1149.
RC TISSUE=Adrenal medulla;
RX PubMed=8633245; DOI=10.1126/science.272.5267.1495;
RA Tang X., Halleck M.S., Schlegel R.A., Williamson P.L.;
RT "A subfamily of P-type ATPases with aminophospholipid transporting
RT activity.";
RL Science 272:1495-1497(1996).
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 (By similarity). Phospholipid translocation seems also to
CC be implicated in vesicle formation and in uptake of lipid signaling
CC molecules. In vitro, its ATPase activity is selectively and
CC stereospecifically stimulated by phosphatidylserine (PS) (By
CC similarity). The flippase complex ATP8A1:TMEM30A seems to play a role
CC in regulation of cell migration probably involving flippase-mediated
CC translocation of phosphatidylethanolamine (PE) at the plasma membrane
CC (By similarity). Acts as aminophospholipid translocase at the plasma
CC membrane in neuronal cells (By similarity).
CC {ECO:0000250|UniProtKB:P70704, ECO:0000250|UniProtKB:Q9Y2Q0}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + phospholipidSide 1 = ADP + phosphate +
CC phospholipidSide 2.; EC=7.6.2.1;
CC Evidence={ECO:0000250|UniProtKB:Q9Y2Q0};
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:0000250|UniProtKB:Q9Y2Q0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38568;
CC Evidence={ECO:0000250|UniProtKB:Q9Y2Q0};
CC -!- SUBUNIT: Component of a P4-ATPase flippase complex which consists of a
CC catalytic alpha subunit and an accessory beta subunit. Interacts with
CC TMEM30A to form a flippase complex; this complex forms an intermediate
CC phosphoenzyme. Interacts with TMEM30B; this interaction is reported
CC conflictingly. {ECO:0000250|UniProtKB:Q9Y2Q0}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle,
CC chromaffin granule membrane {ECO:0000250|UniProtKB:P70704}; Multi-pass
CC membrane protein {ECO:0000250|UniProtKB:P70704}. Cytoplasmic granule
CC {ECO:0000250|UniProtKB:Q9Y2Q0}. Cell membrane
CC {ECO:0000250|UniProtKB:Q9Y2Q0}. Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:Q9Y2Q0}. Golgi apparatus
CC {ECO:0000250|UniProtKB:Q9Y2Q0}. Note=Exit from the endoplasmic
CC reticulum requires the presence of TMEM30A, but not TMEM30B. In the
CC presence of TMEM30A, predominantly located in cytoplasmic punctate
CC structures and localizes to the plasma membrane (By similarity).
CC Localizes to plasma membranes of red blood cells (By similarity).
CC {ECO:0000250|UniProtKB:P70704, ECO:0000250|UniProtKB:Q9Y2Q0}.
CC -!- TISSUE SPECIFICITY: Kidney.
CC -!- PTM: Cleaved by calpain in a caspase- and calcium influx-dependent
CC manner during platelet apoptosis leading to a 100 kDa polypeptide.
CC {ECO:0000250|UniProtKB:Q9Y2Q0}.
CC -!- SIMILARITY: Belongs to the cation transport ATPase (P-type) (TC 3.A.3)
CC family. Type IV subfamily. {ECO:0000305}.
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DR EMBL; U51100; AAD03352.1; -; mRNA.
DR PIR; T18515; T18515.
DR RefSeq; NP_777263.1; NM_174838.2.
DR AlphaFoldDB; Q29449; -.
DR SMR; Q29449; -.
DR STRING; 9913.ENSBTAP00000014818; -.
DR TCDB; 3.A.3.8.1; the p-type atpase (p-atpase) superfamily.
DR PRIDE; Q29449; -.
DR GeneID; 317692; -.
DR KEGG; bta:317692; -.
DR CTD; 10396; -.
DR eggNOG; KOG0206; Eukaryota.
DR InParanoid; Q29449; -.
DR OrthoDB; 587717at2759; -.
DR BRENDA; 7.6.2.1; 908.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0042584; C:chromaffin granule membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031090; C:organelle membrane; ISS:UniProtKB.
DR GO; GO:1990531; C:phospholipid-translocating ATPase complex; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005802; C:trans-Golgi network; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR GO; GO:0140326; F:ATPase-coupled intramembrane lipid transporter activity; IBA:GO_Central.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0140346; F:phosphatidylserine flippase activity; ISS:UniProtKB.
DR GO; GO:0090556; F:phosphatidylserine floppase activity; IEA:RHEA.
DR GO; GO:0140331; P:aminophospholipid translocation; ISS:UniProtKB.
DR GO; GO:0045332; P:phospholipid translocation; IBA:GO_Central.
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; Cytoplasmic vesicle; Direct protein sequencing;
KW Endoplasmic reticulum; Golgi apparatus; Magnesium; Membrane; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Translocase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..1149
FT /note="Probable phospholipid-transporting ATPase IA"
FT /id="PRO_0000046359"
FT TOPO_DOM 1..65
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 66..86
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 87..92
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 93..115
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 116..297
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 298..319
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 320..344
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 345..366
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 367..842
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 843..863
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 864..875
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 876..895
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 896..925
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 926..947
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 948..961
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 962..984
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 985..990
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 991..1011
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1012..1029
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1030..1055
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1056..1149
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT ACT_SITE 409
FT /note="4-aspartylphosphate intermediate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2Q0"
FT BINDING 409..411
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2Q0"
FT BINDING 409
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2Q0"
FT BINDING 411
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2Q0"
FT BINDING 534
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2Q0"
FT BINDING 726..733
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT BINDING 786
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2Q0"
FT BINDING 789..790
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2Q0"
FT BINDING 790
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 1080..1087
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT MOD_RES 25
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2Q0"
FT MOD_RES 28
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P70704"
FT MOD_RES 29
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70704"
FT MOD_RES 1111
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70704"
SQ SEQUENCE 1149 AA; 130026 MW; 0EE71C958E8C5BE1 CRC64;
MPTMRRTVSE IRSRAEGYEK TDDVSEKTSL ADQEEIRTIF INQPQLTKFC NNHVSTAKYN
IITFLPRFLY SQFRRAANSF FLFIALLQQI PDVSPTGRYT TLVPLLFILA VAAIKEIIED
IKRHKADNAV NKKQTQVLRN GAWEIVHWEK VNVGDIVIIK GKEYIPADTV LLSSSEPQAM
CYIETSNLDG ETNLKIRQGL PATSDIKDID SLMRLSGRIE CESPNRHLYD FVGNIRLDGR
STVPLGADQI LLRGAQLRNT QWVHGIVVYT GHDTKLMQNS TSPPLKLSNV ERITNVQILI
LFCILIAMSL VCSVGSAIWN RRHSGRDWYL NLNYGGANNF GLNFLTFIIL FNNLIPISLL
VTLEVVKFTQ AYFINWDLDM HYEPTDTAAM ARTSNLNVEL GQVKYIFSDK TGTLTCNVMQ
FKKCTIAGVA YGQNSQFGDE KTFSDSSLLE NLQNNHPTAP IICEFLTMMA VCHTAVPERE
GDKIIYQAAS PDEGALVRAA KQLNFVFTGR TPDSVIIDSL GQEERYELLN VLEFTSARKR
MSVIVRTPSG KLRLYCKGAD TVIYDRLAET SKYKEITLKH LEQFATEGLR TLCFAVAEIS
ESDFQEWRAV YHRASTSVQN RLLKLEESYE LIEKNLQLLG ATAIEDKLQD QVPETIETLM
KADIKIWILT GDKQETAINI GHSCKLRRKN MGMIVINEGS LDGTRETLSR HCTTLGDALR
KENDFALIID GKTLKYALTF GVRQYFLDLA LSCKAVICCR VSPLQKSEVV EMVKKQVKVI
TLAIGDGAND VSMIQTAHVG VGISGNEGLQ AANSSDYSIA QFKYLKNLLM VHGAWNYNRG
SKCILYCFYK NIVLYIIEIW FAFVNGFSGQ ILFERWCIGL YNVMFTAMPP LTLGIFERSC
RKEYMLKYPE LYKTSQNALD FNTKVFWVHC LNGLFHSVIL FWFPLKALQY GTVFENGRTS
DYLLLGNFVY TFVVITVCLK AGLETSYWTW FSHIAIWGSI ALWVVFFGIY SSLWPAVPMA
PDMSGEAAML FSSGVFWMGL LFIPVASLLL DVVYKVIKRT AFKTLVDEVQ ELEAKSQDPG
AVVLGKSLTE RAQLLKNVFK KNHVNLYRSE SLQQNLLHGY AFSQDENGIV SQSEVIRAYD
TTKQRPDEW
