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Protein

Phospholipid-transporting ATPase IA

Gene

Atp8a1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and ensures the maintenance of asymmetric distribution of phospholipids. Phospholipid translocation seems also to be implicated in vesicle formation and in uptake of lipid signaling molecules. In vitro, its ATPase activity is selectively and stereospecifically stimulated by phosphatidylserine (PS). The flippase complex ATP8A1:TMEM30A seems to play a role in regulation of cell migration probably involving flippase-mediated translocation of phosphatidylethanolamine (PE) at the plasma membrane. Acts as aminophospholipid translocase at the plasma membrane in neuronal cells; the activity is associated with hippocampus-dependent learning.4 Publications

Catalytic activityi

ATP + H2O + phospholipid(Side 1) = ADP + phosphate + phospholipid(Side 2).

Enzyme regulationi

ATPase activity is stimulated by phosphatidylserine (PS) and minimally by phosphatidylethanolamine (PE).1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei4094-aspartylphosphate intermediateBy similarity1
Metal bindingi801MagnesiumBy similarity1
Metal bindingi805MagnesiumBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi741 – 748ATPSequence analysis8
Nucleotide bindingi1095 – 1102ATPSequence analysis8

GO - Molecular functioni

GO - Biological processi

  • Golgi vesicle budding Source: GO_Central
  • learning Source: UniProtKB
  • positive regulation of cell migration Source: UniProtKB
  • positive regulation of phospholipid translocation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Lipid transport, Transport

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-6798695. Neutrophil degranulation.
R-MMU-936837. Ion transport by P-type ATPases.

Chemistry databases

SwissLipidsiSLP:000000333.

Names & Taxonomyi

Protein namesi
Recommended name:
Phospholipid-transporting ATPase IA (EC:3.6.3.1)
Alternative name(s):
ATPase class I type 8A member 1
Chromaffin granule ATPase II
P4-ATPase flippase complex alpha subunit ATP8A1
Gene namesi
Name:Atp8a1
Synonyms:Atpc1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:1330848. Atp8a1.

Subcellular locationi

  • Cytoplasmic vesiclesecretory vesiclechromaffin granule membrane 1 Publication; Multi-pass membrane protein Sequence analysis
  • Cytoplasmic granule 1 Publication
  • Cell membrane By similarity
  • Endoplasmic reticulum By similarity
  • Golgi apparatus By similarity

  • Note: Exit from the endoplasmic reticulum requires the presence of TMEM30A, but not TMEM30B. In the presence of TMEM30A, predominantly located in cytoplasmic punctate structures (By similarity). Localizes to plasma membranes of red blood cells (PubMed:16643453).By similarity1 Publication

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 75CytoplasmicSequence analysisAdd BLAST75
Transmembranei76 – 96HelicalSequence analysisAdd BLAST21
Topological domaini97 – 100Exoplasmic loopSequence analysis4
Transmembranei101 – 121HelicalSequence analysisAdd BLAST21
Topological domaini122 – 297CytoplasmicSequence analysisAdd BLAST176
Transmembranei298 – 318HelicalSequence analysisAdd BLAST21
Topological domaini319 – 339Exoplasmic loopSequence analysisAdd BLAST21
Transmembranei340 – 360HelicalSequence analysisAdd BLAST21
Topological domaini361 – 866CytoplasmicSequence analysisAdd BLAST506
Transmembranei867 – 887HelicalSequence analysisAdd BLAST21
Topological domaini888 – 890Exoplasmic loopSequence analysis3
Transmembranei891 – 911HelicalSequence analysisAdd BLAST21
Topological domaini912 – 939CytoplasmicSequence analysisAdd BLAST28
Transmembranei940 – 960HelicalSequence analysisAdd BLAST21
Topological domaini961 – 977Exoplasmic loopSequence analysisAdd BLAST17
Transmembranei978 – 998HelicalSequence analysisAdd BLAST21
Topological domaini999 – 1008CytoplasmicSequence analysis10
Transmembranei1009 – 1029HelicalSequence analysisAdd BLAST21
Topological domaini1030 – 1044Exoplasmic loopSequence analysisAdd BLAST15
Transmembranei1045 – 1065HelicalSequence analysisAdd BLAST21
Topological domaini1066 – 1164CytoplasmicSequence analysisAdd BLAST99

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasmic vesicle, Endoplasmic reticulum, Golgi apparatus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi409D → K: Decreases plasma membrane aminophospholipid translocation in neuronal cells. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000463611 – 1164Phospholipid-transporting ATPase IAAdd BLAST1164

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei25PhosphoserineCombined sources1
Modified residuei28PhosphothreonineCombined sources1
Modified residuei29PhosphoserineCombined sources1
Modified residuei443PhosphoserineCombined sources1
Modified residuei1126PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP70704.
PeptideAtlasiP70704.
PRIDEiP70704.

PTM databases

iPTMnetiP70704.
PhosphoSitePlusiP70704.

Expressioni

Tissue specificityi

Found in most tissues except liver and testis. Most abundant in brain and lung. Also detected in fetal tissues. Isoform 1 is expressed in brain. Isoform 2 and isoform 3 are expressed in reticulocytes.1 Publication

Gene expression databases

BgeeiENSMUSG00000037685.
ExpressionAtlasiP70704. baseline and differential.
GenevisibleiP70704. MM.

Interactioni

Subunit structurei

Component of a P4-ATPase flippase complex which consists of a catalytic alpha subunit and an accessory beta subunit. Interacts with TMEM30A to form a flippase complex.1 Publication

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000042215.

Structurei

3D structure databases

ProteinModelPortaliP70704.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410ITKD. Eukaryota.
ENOG410XPYK. LUCA.
GeneTreeiENSGT00860000133712.
HOGENOMiHOG000202528.
HOVERGENiHBG050601.
InParanoidiP70704.
KOiK14802.
OMAiKDLDMHY.
OrthoDBiEOG091G0139.

Family and domain databases

Gene3Di2.70.150.10. 2 hits.
3.40.1110.10. 1 hit.
3.40.50.1000. 2 hits.
InterProiIPR030342. ATP8A1.
IPR023299. ATPase_P-typ_cyto_domN.
IPR018303. ATPase_P-typ_P_site.
IPR008250. ATPase_P-typ_transduc_dom_A.
IPR023214. HAD-like_dom.
IPR006539. P-type_ATPase_IV.
IPR032631. P-type_ATPase_N.
IPR001757. P_typ_ATPase.
IPR032630. P_typ_ATPase_c.
[Graphical view]
PANTHERiPTHR24092. PTHR24092. 1 hit.
PTHR24092:SF56. PTHR24092:SF56. 1 hit.
PfamiPF00122. E1-E2_ATPase. 1 hit.
PF16212. PhoLip_ATPase_C. 1 hit.
PF16209. PhoLip_ATPase_N. 1 hit.
[Graphical view]
SUPFAMiSSF56784. SSF56784. 3 hits.
SSF81660. SSF81660. 1 hit.
TIGRFAMsiTIGR01652. ATPase-Plipid. 1 hit.
TIGR01494. ATPase_P-type. 3 hits.
PROSITEiPS00154. ATPASE_E1_E2. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P70704-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MPTMRRTVSE IRSRAEGYEK TDDVSEKTSL ADQEEVRTIF INQPQLTKFC
60 70 80 90 100
NNHVSTAKYN VITFLPRFLY SQFRRAANSF FLFIALLQQI PDVSPTGRYT
110 120 130 140 150
TLVPLLFILA VAAIKEIIED IKRHKADNAV NKKQTQVLRN GAWEIVHWEK
160 170 180 190 200
VAVGEIVKVT NGEHLPADLL SLSSSEPQAM CYIETSNLDG ETNLKIRQGL
210 220 230 240 250
PATSDIKDID SLMRISGRIE CESPNRHLYD FVGNIRLDGH GTVPLGADQI
260 270 280 290 300
LLRGAQLRNT QWVHGIVVYT GHDTKLMQNS TSPPLKLSNV ERITNVQILI
310 320 330 340 350
LFCILIAMSL VCSVGSAIWN RRHSGKDWYL HLHYGGASNF GLNFLTFIIL
360 370 380 390 400
FNNLIPISLL VTLEVVKFTQ AYFINWDLDM HYEPTDTAAM ARTSNLNEEL
410 420 430 440 450
GQVKYIFSDK TGTLTCNVMQ FKKCTIAGVA YGHVPEPEDY GCSPDEWQSS
460 470 480 490 500
QFGDEKTFND PSLLDNLQNN HPTAPIICEF LTMMAVCHTA VPEREGDKII
510 520 530 540 550
YQAASPDEGA LVRAAKQLNF VFTGRTPDSV IIDSLGQEER YELLNVLEFT
560 570 580 590 600
SARKRMSVVV RTPSGKLRLY CKGADTVIYE RLAETSKYKE ITLKHLEQFA
610 620 630 640 650
TEGLRTLCFA VAEISESDFE EWRAVYHRAS TSVQNRLLKL EESYELIEKN
660 670 680 690 700
LQLLGATAIE DKLQDQVPET IETLMKADIK IWILTGDKQE TAINIGHSCR
710 720 730 740 750
LLKRNMGMIV INEGSLDGTR ETLSRHCTTL GDALRKENDF ALIIDGKTLK
760 770 780 790 800
YALTFGVRQY FLDLALSCKA VICCRVSPLQ KSEVVEMVKK QVKVITLAIG
810 820 830 840 850
DGANDVSMIQ TAHVGVGISG NEGLQAANSS DYSIAQFKYL KNLLMVHGAW
860 870 880 890 900
NYNRVSKCIL YCFYKNIVLY IIEIWFAFVN GFSGQILFER WCIGLYNVMF
910 920 930 940 950
TAMPPLTLGI FERSCRKENM LKYPELYKTS QNALDFNTKV FWVHCLNGLF
960 970 980 990 1000
HSVILFWFPL KALQYGTVFG NGKTSDYLLL GNFVYTFVVI TVCLKAGLET
1010 1020 1030 1040 1050
SYWTWFSHIA IWGSIALWVV FFGIYSSLWP AVPMAPDMSG EAAMLFSSGV
1060 1070 1080 1090 1100
FWVGLLSIPV ASLLLDVLYK VIKRTAFKTL VDEVQELEAK SQDPGAVVLG
1110 1120 1130 1140 1150
KSLTERAQLL KNVFKKNHVN LYRSESLQQN LLHGYAFSQD ENGIVSQSEV
1160
IRAYDTTKQR PDEW
Length:1,164
Mass (Da):131,413
Last modified:July 9, 2014 - v2
Checksum:i2639DDDA00B15754
GO
Isoform 2 (identifier: P70704-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     152-171: AVGEIVKVTNGEHLPADLLS → NVGDIVIIKGKEYIPADTVL
     433-447: Missing.

Show »
Length:1,149
Mass (Da):129,767
Checksum:i95F70B2B091FD31E
GO
Isoform 3 (identifier: P70704-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     433-447: Missing.

Show »
Length:1,149
Mass (Da):129,672
Checksum:iD9FF0CBBC68521C3
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_055306152 – 171AVGEI…ADLLS → NVGDIVIIKGKEYIPADTVL in isoform 2. 1 PublicationAdd BLAST20
Alternative sequenceiVSP_055307433 – 447Missing in isoform 2 and isoform 3. 1 PublicationAdd BLAST15

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U75321 mRNA. Translation: AAB18627.1.
AK045367 mRNA. Translation: BAC32330.1.
AK141559 mRNA. Translation: BAE24734.1.
AC102916 Genomic DNA. No translation available.
AC123662 Genomic DNA. No translation available.
AC161516 Genomic DNA. No translation available.
CCDSiCCDS39104.1. [P70704-1]
CCDS39105.1. [P70704-2]
PIRiT30869.
RefSeqiNP_001034088.1. NM_001038999.2. [P70704-1]
NP_001271274.1. NM_001284345.1.
NP_033857.1. NM_009727.3. [P70704-2]
UniGeneiMm.153230.

Genome annotation databases

EnsembliENSMUST00000037380; ENSMUSP00000042215; ENSMUSG00000037685. [P70704-1]
ENSMUST00000135930; ENSMUSP00000118379; ENSMUSG00000037685. [P70704-2]
GeneIDi11980.
KEGGimmu:11980.
UCSCiuc008xqa.2. mouse. [P70704-1]
uc008xqb.2. mouse. [P70704-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U75321 mRNA. Translation: AAB18627.1.
AK045367 mRNA. Translation: BAC32330.1.
AK141559 mRNA. Translation: BAE24734.1.
AC102916 Genomic DNA. No translation available.
AC123662 Genomic DNA. No translation available.
AC161516 Genomic DNA. No translation available.
CCDSiCCDS39104.1. [P70704-1]
CCDS39105.1. [P70704-2]
PIRiT30869.
RefSeqiNP_001034088.1. NM_001038999.2. [P70704-1]
NP_001271274.1. NM_001284345.1.
NP_033857.1. NM_009727.3. [P70704-2]
UniGeneiMm.153230.

3D structure databases

ProteinModelPortaliP70704.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000042215.

Chemistry databases

SwissLipidsiSLP:000000333.

PTM databases

iPTMnetiP70704.
PhosphoSitePlusiP70704.

Proteomic databases

PaxDbiP70704.
PeptideAtlasiP70704.
PRIDEiP70704.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000037380; ENSMUSP00000042215; ENSMUSG00000037685. [P70704-1]
ENSMUST00000135930; ENSMUSP00000118379; ENSMUSG00000037685. [P70704-2]
GeneIDi11980.
KEGGimmu:11980.
UCSCiuc008xqa.2. mouse. [P70704-1]
uc008xqb.2. mouse. [P70704-2]

Organism-specific databases

CTDi10396.
MGIiMGI:1330848. Atp8a1.

Phylogenomic databases

eggNOGiENOG410ITKD. Eukaryota.
ENOG410XPYK. LUCA.
GeneTreeiENSGT00860000133712.
HOGENOMiHOG000202528.
HOVERGENiHBG050601.
InParanoidiP70704.
KOiK14802.
OMAiKDLDMHY.
OrthoDBiEOG091G0139.

Enzyme and pathway databases

ReactomeiR-MMU-6798695. Neutrophil degranulation.
R-MMU-936837. Ion transport by P-type ATPases.

Miscellaneous databases

ChiTaRSiAtp8a1. mouse.
PROiP70704.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000037685.
ExpressionAtlasiP70704. baseline and differential.
GenevisibleiP70704. MM.

Family and domain databases

Gene3Di2.70.150.10. 2 hits.
3.40.1110.10. 1 hit.
3.40.50.1000. 2 hits.
InterProiIPR030342. ATP8A1.
IPR023299. ATPase_P-typ_cyto_domN.
IPR018303. ATPase_P-typ_P_site.
IPR008250. ATPase_P-typ_transduc_dom_A.
IPR023214. HAD-like_dom.
IPR006539. P-type_ATPase_IV.
IPR032631. P-type_ATPase_N.
IPR001757. P_typ_ATPase.
IPR032630. P_typ_ATPase_c.
[Graphical view]
PANTHERiPTHR24092. PTHR24092. 1 hit.
PTHR24092:SF56. PTHR24092:SF56. 1 hit.
PfamiPF00122. E1-E2_ATPase. 1 hit.
PF16212. PhoLip_ATPase_C. 1 hit.
PF16209. PhoLip_ATPase_N. 1 hit.
[Graphical view]
SUPFAMiSSF56784. SSF56784. 3 hits.
SSF81660. SSF81660. 1 hit.
TIGRFAMsiTIGR01652. ATPase-Plipid. 1 hit.
TIGR01494. ATPase_P-type. 3 hits.
PROSITEiPS00154. ATPASE_E1_E2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiAT8A1_MOUSE
AccessioniPrimary (citable) accession number: P70704
Secondary accession number(s): Q8BR88
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: July 9, 2014
Last modified: November 30, 2016
This is version 153 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

Initial characterization studies with purified Atp8a1 enzyme demonstrated similar but distinct properties compared to the plasma membrane aminophospholipid flippase; however, the flippase complex accessory beta subunit was not included in the assays.1 Publication

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.