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Protein

Phospholipid-transporting ATPase IA

Gene

ATP8A1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.

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).By similarity

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

Keywordsi

Molecular functionHydrolase
Biological processLipid transport, Transport
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi3.6.3.1 2681
ReactomeiR-HSA-6798695 Neutrophil degranulation
R-HSA-936837 Ion transport by P-type ATPases

Protein family/group databases

TCDBi3.A.3.8.13 the p-type atpase (p-atpase) superfamily

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:ATPIA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000124406.16
HGNCiHGNC:13531 ATP8A1
MIMi609542 gene
neXtProtiNX_Q9Y2Q0

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 65CytoplasmicSequence analysisAdd BLAST65
Transmembranei66 – 86HelicalSequence analysisAdd BLAST21
Topological domaini87 – 92Exoplasmic loopSequence analysis6
Transmembranei93 – 115HelicalSequence analysisAdd BLAST23
Topological domaini116 – 297CytoplasmicSequence analysisAdd BLAST182
Transmembranei298 – 319HelicalSequence analysisAdd BLAST22
Topological domaini320 – 344Exoplasmic loopSequence analysisAdd BLAST25
Transmembranei345 – 366HelicalSequence analysisAdd BLAST22
Topological domaini367 – 857CytoplasmicSequence analysisAdd BLAST491
Transmembranei858 – 878HelicalSequence analysisAdd BLAST21
Topological domaini879 – 890Exoplasmic loopSequence analysisAdd BLAST12
Transmembranei891 – 910HelicalSequence analysisAdd BLAST20
Topological domaini911 – 940CytoplasmicSequence analysisAdd BLAST30
Transmembranei941 – 962HelicalSequence analysisAdd BLAST22
Topological domaini963 – 976Exoplasmic loopSequence analysisAdd BLAST14
Transmembranei977 – 999HelicalSequence analysisAdd BLAST23
Topological domaini1000 – 1005CytoplasmicSequence analysis6
Transmembranei1006 – 1026HelicalSequence analysisAdd BLAST21
Topological domaini1027 – 1044Exoplasmic loopSequence analysisAdd BLAST18
Transmembranei1045 – 1070HelicalSequence analysisAdd BLAST26
Topological domaini1071 – 1164CytoplasmicSequence analysisAdd BLAST94

Keywords - Cellular componenti

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

Pathology & Biotechi

Organism-specific databases

DisGeNETi10396
OpenTargetsiENSG00000124406
PharmGKBiPA25165

Chemistry databases

DrugBankiDB00144 Phosphatidyl serine

Polymorphism and mutation databases

BioMutaiATP8A1
DMDMi8134331

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000463601 – 1164Phospholipid-transporting ATPase IAAdd BLAST1164

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei25PhosphoserineCombined sources1
Modified residuei28PhosphothreonineBy similarity1
Modified residuei29PhosphoserineBy similarity1
Modified residuei443PhosphoserineBy similarity1
Modified residuei1126PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ9Y2Q0
PaxDbiQ9Y2Q0
PeptideAtlasiQ9Y2Q0
PRIDEiQ9Y2Q0

PTM databases

iPTMnetiQ9Y2Q0
PhosphoSitePlusiQ9Y2Q0

Expressioni

Tissue specificityi

Found in most adult tissues except liver, testis and placenta. Most abundant in heart, brain and skeletal muscle. Also detected in fetal tissues. Isoform 1 is only detected in brain, skeletal muscle and heart and is the most abundant form in skeletal muscle.

Gene expression databases

BgeeiENSG00000124406
CleanExiHS_ATP8A1
ExpressionAtlasiQ9Y2Q0 baseline and differential
GenevisibleiQ9Y2Q0 HS

Organism-specific databases

HPAiHPA049948
HPA052935

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; the interaction with TMEM30B is reported conflictingly.3 Publications

Protein-protein interaction databases

BioGridi1156683 interactors.
IntActiQ9Y2Q0 1 interactor.
STRINGi9606.ENSP00000371084

Structurei

3D structure databases

ProteinModelPortaliQ9Y2Q0
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410ITKD Eukaryota
ENOG410XPYK LUCA
GeneTreeiENSGT00910000144008
HOGENOMiHOG000202528
HOVERGENiHBG050601
InParanoidiQ9Y2Q0
KOiK14802
OMAiRMRKQRG
OrthoDBiEOG091G0139
PhylomeDBiQ9Y2Q0
TreeFamiTF300654

Family and domain databases

Gene3Di3.40.1110.101 hit
3.40.50.10001 hit
InterProiView protein in InterPro
IPR023299 ATPase_P-typ_cyto_dom_N
IPR018303 ATPase_P-typ_P_site
IPR023298 ATPase_P-typ_TM_dom_sf
IPR008250 ATPase_P-typ_transduc_dom_A_sf
IPR036412 HAD-like_sf
IPR023214 HAD_sf
IPR006539 P-type_ATPase_IV
IPR032631 P-type_ATPase_N
IPR001757 P_typ_ATPase
IPR032630 P_typ_ATPase_c
PANTHERiPTHR24092 PTHR24092, 1 hit
PfamiView protein in Pfam
PF16212 PhoLip_ATPase_C, 1 hit
PF16209 PhoLip_ATPase_N, 1 hit
SUPFAMiSSF56784 SSF56784, 3 hits
SSF81653 SSF81653, 2 hits
SSF81660 SSF81660, 1 hit
SSF81665 SSF81665, 3 hits
TIGRFAMsiTIGR01652 ATPase-Plipid, 1 hit
TIGR01494 ATPase_P-type, 3 hits
PROSITEiView protein in PROSITE
PS00154 ATPASE_E1_E2, 1 hit

Sequences (3)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q9Y2Q0-1) [UniParc]FASTAAdd to basket
Also known as: Long

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 IITFLPRFLY SQFRRAANSF FLFIALLQQI PDVSPTGRYT
110 120 130 140 150
TLVPLLFILA VAAIKEIIED IKRHKADNAV NKKQTQVLRN GAWEIVHWEK
160 170 180 190 200
VAVGEIVKVT NGEHLPADLI SLSSSEPQAM CYIETSNLDG ETNLKIRQGL
210 220 230 240 250
PATSDIKDVD SLMRISGRIE CESPNRHLYD FVGNIRLDGH GTVPLGADQI
260 270 280 290 300
LLRGAQLRNT QWVHGIVVYT GHDTKLMQNS TSPPLKLSNV ERITNVQILI
310 320 330 340 350
LFCILIAMSL VCSVGSAIWN RRHSGKDWYL NLNYGGASNF GLNFLTFIIL
360 370 380 390 400
FNNLIPISLL VTLEVVKFTQ AYFINWDLDM HYEPTDTAAM ARTSNLNEEL
410 420 430 440 450
GQVKYIFSDK TGTLTCNVMQ FKKCTIAGVA YGHVPEPEDY GCSPDEWQNS
460 470 480 490 500
QFGDEKTFSD SSLLENLQNN HPTAPIICEF LTMMAVCHTA VPEREGDKII
510 520 530 540 550
YQAASPDEGA LVRAAKQLNF VFTGRTPDSV IIDSLGQEER YELLNVLEFT
560 570 580 590 600
SARKRMSVIV RTPSGKLRLY CKGADTVIYD RLAETSKYKE ITLKHLEQFA
610 620 630 640 650
TEGLRTLCFA VAEISESDFQ EWRAVYQRAS TSVQNRLLKL EESYELIEKN
660 670 680 690 700
LQLLGATAIE DKLQDQVPET IETLMKADIK IWILTGDKQE TAINIGHSCK
710 720 730 740 750
LLKKNMGMIV INEGSLDGTR ETLSRHCTTL GDALRKENDF ALIIDGKTLK
760 770 780 790 800
YALTFGVRQY FLDLALSCKA VICCRVSPLQ KSEVVEMVKK QVKVVTLAIG
810 820 830 840 850
DGANDVSMIQ TAHVGVGISG NEGLQAANSS DYSIAQFKYL KNLLMIHGAW
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 KALQYGTAFG NGKTSDYLLL GNFVYTFVVI TVCLKAGLET
1010 1020 1030 1040 1050
SYWTWFSHIA IWGSIALWVV FFGIYSSLWP AIPMAPDMSG EAAMLFSSGV
1060 1070 1080 1090 1100
FWMGLLFIPV ASLLLDVVYK VIKRTAFKTL VDEVQELEAK SQDPGAVVLG
1110 1120 1130 1140 1150
KSLTERAQLL KNVFKKNHVN LYRSESLQQN LLHGYAFSQD ENGIVSQSEV
1160
IRAYDTTKQR PDEW
Length:1,164
Mass (Da):131,369
Last modified:November 1, 1999 - v1
Checksum:iCE1EAF0206CD36F7
GO
Isoform 2 (identifier: Q9Y2Q0-2) [UniParc]FASTAAdd to basket
Also known as: Short

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

Show »
Length:1,149
Mass (Da):129,628
Checksum:iDC609CEA87E9F9B1
GO
Isoform 3 (identifier: Q9Y2Q0-3) [UniParc]FASTAAdd to basket

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

Show »
Length:1,149
Mass (Da):129,723
Checksum:i83D2F58984DDF966
GO

Sequence cautioni

The sequence AAI09318 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAA77248 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti364E → K in BAA77248 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_022003673T → M. Corresponds to variant dbSNP:rs3792687Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_040977152 – 171AVGEI…ADLIS → NVGDIVIIKGKEYIPADTVL in isoform 3. 1 PublicationAdd BLAST20
Alternative sequenceiVSP_000431433 – 447Missing in isoform 2 and isoform 3. 2 PublicationsAdd BLAST15

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF067820 mRNA Translation: AAD34706.1
AC084010 Genomic DNA Translation: AAY40980.1
AC096734 Genomic DNA Translation: AAY40924.1
AC110788 Genomic DNA No translation available.
AC139717 Genomic DNA No translation available.
CH471069 Genomic DNA Translation: EAW93003.1
BC109317 mRNA Translation: AAI09318.1 Different initiation.
BC109318 mRNA Translation: AAI09319.1
AB013452 mRNA Translation: BAA77248.1 Different initiation.
CCDSiCCDS3466.1 [Q9Y2Q0-1]
CCDS47049.1 [Q9Y2Q0-3]
RefSeqiNP_001098999.1, NM_001105529.1 [Q9Y2Q0-3]
NP_006086.1, NM_006095.2 [Q9Y2Q0-1]
XP_016863134.1, XM_017007645.1 [Q9Y2Q0-2]
UniGeneiHs.435052

Genome annotation databases

EnsembliENST00000264449; ENSP00000264449; ENSG00000124406 [Q9Y2Q0-3]
ENST00000381668; ENSP00000371084; ENSG00000124406 [Q9Y2Q0-1]
GeneIDi10396
KEGGihsa:10396
UCSCiuc003gwr.3 human [Q9Y2Q0-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiAT8A1_HUMAN
AccessioniPrimary (citable) accession number: Q9Y2Q0
Secondary accession number(s): Q32M35
, Q32M36, Q4W5J7, Q4W5P2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: November 1, 1999
Last modified: February 28, 2018
This is version 167 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome