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Protein

Phospholipid-transporting ATPase IB

Gene

Atp8a2

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. Reconstituted to liposomes, the ATP8A2:TMEM30A flippase complex predomiminantly transports phosphatidylserine (PS) and to a lesser extent phosphatidylethanolamine (PE). ATP8A2:TMEM30A may be involved in regulation of neurite outgrowth. Proposed to function in the generation and maintenance of phospholipid asymmetry in photoreceptor disk membranes and neuronal axon membranes. May be involved in vesicle trafficking in neuronal cells. Required for normal visual and auditory function; involved in photoreceptor and inner ear spiral ganglion cell survival.3 Publications

Catalytic activityi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei388 – 38814-aspartylphosphate intermediateBy similarity
Metal bindingi781 – 7811MagnesiumBy similarity
Metal bindingi785 – 7851MagnesiumBy similarity

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • magnesium ion binding Source: InterPro
  • phospholipid-translocating ATPase activity Source: UniProtKB

GO - Biological processi

  • aging Source: MGI
  • axonogenesis Source: MGI
  • detection of light stimulus involved in visual perception Source: UniProtKB
  • eating behavior Source: MGI
  • Golgi vesicle budding Source: GO_Central
  • inner ear morphogenesis Source: UniProtKB
  • involuntary skeletal muscle contraction Source: MGI
  • neurofilament cytoskeleton organization Source: UniProtKB
  • neuromuscular process controlling posture Source: MGI
  • neuron development Source: MGI
  • neuron projection development Source: MGI
  • positive regulation of multicellular organism growth Source: MGI
  • positive regulation of neuron projection development Source: UniProtKB
  • positive regulation of phospholipid translocation Source: UniProtKB
  • response to auditory stimulus Source: UniProtKB
  • retina layer formation Source: UniProtKB
  • skin development Source: MGI
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

BRENDAi3.6.3.1. 3474.

Protein family/group databases

TCDBi3.A.3.8.8. the p-type atpase (p-atpase) superfamily.

Names & Taxonomyi

Protein namesi
Recommended name:
Phospholipid-transporting ATPase IB (EC:3.6.3.1)
Alternative name(s):
ATPase class I type 8A member 2
P4-ATPase flippase complex alpha subunit ATP8A2
Gene namesi
Name:Atp8a2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 14

Organism-specific databases

MGIiMGI:1354710. Atp8a2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 4444CytoplasmicSequence analysisAdd
BLAST
Transmembranei45 – 6622HelicalSequence analysisAdd
BLAST
Topological domaini67 – 715Exoplasmic loopSequence analysis
Transmembranei72 – 9423HelicalSequence analysisAdd
BLAST
Topological domaini95 – 276182CytoplasmicSequence analysisAdd
BLAST
Transmembranei277 – 29822HelicalSequence analysisAdd
BLAST
Topological domaini299 – 32325Exoplasmic loopSequence analysisAdd
BLAST
Transmembranei324 – 34522HelicalSequence analysisAdd
BLAST
Topological domaini346 – 837492CytoplasmicSequence analysisAdd
BLAST
Transmembranei838 – 85821HelicalSequence analysisAdd
BLAST
Topological domaini859 – 87012Exoplasmic loopSequence analysisAdd
BLAST
Transmembranei871 – 89020HelicalSequence analysisAdd
BLAST
Topological domaini891 – 92030CytoplasmicSequence analysisAdd
BLAST
Transmembranei921 – 94222HelicalSequence analysisAdd
BLAST
Topological domaini943 – 95614Exoplasmic loopSequence analysisAdd
BLAST
Transmembranei957 – 97923HelicalSequence analysisAdd
BLAST
Topological domaini980 – 9856CytoplasmicSequence analysis
Transmembranei986 – 100621HelicalSequence analysisAdd
BLAST
Topological domaini1007 – 102418Exoplasmic loopSequence analysisAdd
BLAST
Transmembranei1025 – 104925HelicalSequence analysisAdd
BLAST
Topological domaini1050 – 114899CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • endosome Source: UniProtKB
  • Golgi apparatus Source: UniProtKB
  • Golgi membrane Source: GOC
  • integral component of membrane Source: UniProtKB-KW
  • membrane Source: UniProtKB
  • photoreceptor outer segment Source: UniProtKB-SubCell
  • plasma membrane Source: MGI
  • trans-Golgi network Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Endosome, Golgi apparatus, Membrane

Pathology & Biotechi

Involvement in diseasei

Defects in Atp8a2 are the cause of Wabbler-lethal (wl) phenotype. Homozygotes show severe neurological annormalities that include ataxia and body tremors linked to progressive axonal degeneration in several areas of the nervous system.

Disruption phenotypei

Atp8a2 and Atp8a1 double mutant mice die soon after birth.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi388 – 3881D → A: Abolishes phosphatidylserine translocase activity, abolishes effect on neurite outgrowth. 2 Publications

Keywords - Diseasei

Disease mutation

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 11481148Phospholipid-transporting ATPase IBPRO_0000046363Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei5 – 51PhosphothreonineCombined sources

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiP98200.
PaxDbiP98200.
PeptideAtlasiP98200.
PRIDEiP98200.

PTM databases

iPTMnetiP98200.

Expressioni

Tissue specificityi

Found in testis, heart and brain. Most abundant in testis. Also detected in fetal tissues. Expressed in retinal photoreceptor cells; detected in retina outer nuclear layer and inner segment (at protein level).2 Publications

Gene expression databases

BgeeiENSMUSG00000021983.
ExpressionAtlasiP98200. baseline and differential.
GenevisibleiP98200. 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 (By similarity).By similarity

Protein-protein interaction databases

IntActiP98200. 1 interaction.
MINTiMINT-4088697.
STRINGi10090.ENSMUSP00000079238.

Structurei

3D structure databases

ProteinModelPortaliP98200.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410ITKD. Eukaryota.
ENOG410XPYK. LUCA.
GeneTreeiENSGT00770000120474.
HOGENOMiHOG000202528.
HOVERGENiHBG050601.
InParanoidiP98200.
KOiK14802.
OMAiHNGANSE.
OrthoDBiEOG091G0139.
PhylomeDBiP98200.
TreeFamiTF300654.

Family and domain databases

Gene3Di2.70.150.10. 2 hits.
3.40.1110.10. 1 hit.
3.40.50.1000. 2 hits.
InterProiIPR030344. ATP8A2.
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:SF66. PTHR24092:SF66. 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. 2 hits.
TIGRFAMsiTIGR01652. ATPase-Plipid. 1 hit.
TIGR01494. ATPase_P-type. 2 hits.
PROSITEiPS00154. ATPASE_E1_E2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P98200-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSRATSVGDQ LEAPARIIYL NQSHLNKFCD NRISTAKYSV LTFLPRFLYE
60 70 80 90 100
QIRRAANAFF LFIALLQQIP DVSPTGRYTT LVPLVIILTI AGIKEIIEDF
110 120 130 140 150
KRHKADNAVN KKKTIVLRNG MWHTIMWKEV AVGDIVKVLN GQYLPADMVL
160 170 180 190 200
FSSSEPQGMC YVETANLDGE TNLKIRQGLS HTTDMQTRDV LMKLSGRIEC
210 220 230 240 250
EGPNRHLYDF TGNLHLDGKS SVALGPDQIL LRGTQLRNTQ WVFGVVVYTG
260 270 280 290 300
HDSKLMQNST KAPLKRSNVE KVTNVQILVL FGILLVMALV SSVGALFWNG
310 320 330 340 350
SHGGKSWYIK KMDTNSDNFG YNLLTFIILY NNLIPISLLV TLEVVKYTQA
360 370 380 390 400
LFINWDMDMY YIENDTPAMA RTSNLNEELG QVKYLFSDKT GTLTCNIMNF
410 420 430 440 450
KKCSIAGVTY GHFPELAREQ SSDDFCRMTS CTNDSCDFND PRLLKNIEDQ
460 470 480 490 500
HPTAPCIQEF LTLLAVCHTV VPEKDGDEII YQASSPDEAA LVKGAKKLGF
510 520 530 540 550
VFTGRTPYSV IIEAMGQEQT FGILNVLEFS SDRKRMSVIV RLPSGQLRLY
560 570 580 590 600
CKGADNVIFE RLSKDSKYME ETLCHLEYFA TEGLRTLCVA YADLSENEYE
610 620 630 640 650
EWLKVYQEAS IILKDRAQRL EECYEIIEKN LLLLGATAIE DRLQAGVPET
660 670 680 690 700
IATLLKAEIK IWVLTGDKQE TAINIGYSCR LVSQNMALIL LKEDSLDATR
710 720 730 740 750
AAITQHCTDL GNLLGKENDV ALIIDGHTLK YALSFEVRRS FLDLALSCKA
760 770 780 790 800
VICCRVSPLQ KSEIVDVVKK RVKAITLAIG DGANDVGMIQ TAHVGVGISG
810 820 830 840 850
NEGMQATNNS DYAIAQFSYL EKLLLVHGAW SYNRVTKCIL YCFYKNVVLY
860 870 880 890 900
IIELWFAFVN GFSGQILFER WCIGLYNVIF TALPPFTLGI FERSCTQESM
910 920 930 940 950
LRFPQLYRIT QNAEGFNTKV FWGHCINALV HSLILFWVPM KALEHDTPVT
960 970 980 990 1000
SGHATDYLFV GNIVYTYVVV TVCLKAGLET TAWTKFSHLA VWGSMLIWLV
1010 1020 1030 1040 1050
FFGVYSTIWP TIPIAPDMKG QATMVLSSAY FWLGLFLVPT ACLIEDVAWR
1060 1070 1080 1090 1100
AAKHTCKKTL LEEVQELETK SRVMGKAMLR DSNGKRMNER DRLIKRLSRK
1110 1120 1130 1140
TPPTLFRTGS IQQCVSHGYA FSQEEHGAVT QEEIVRAYDT TKENSRKK
Length:1,148
Mass (Da):129,417
Last modified:May 30, 2000 - v1
Checksum:iA668D6F343CAAAB8
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti637 – 6437Missing in wl; abolishes phosphatidylserine translocase activity. 1 Publication

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF156550 mRNA. Translation: AAF09448.1.
BC137896 mRNA. Translation: AAI37897.1.
CCDSiCCDS27174.1.
RefSeqiNP_056618.1. NM_015803.2.
XP_006519297.1. XM_006519234.2.
XP_006519298.1. XM_006519235.2.
UniGeneiMm.319599.

Genome annotation databases

EnsembliENSMUST00000080368; ENSMUSP00000079238; ENSMUSG00000021983.
GeneIDi50769.
KEGGimmu:50769.
UCSCiuc007uet.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF156550 mRNA. Translation: AAF09448.1.
BC137896 mRNA. Translation: AAI37897.1.
CCDSiCCDS27174.1.
RefSeqiNP_056618.1. NM_015803.2.
XP_006519297.1. XM_006519234.2.
XP_006519298.1. XM_006519235.2.
UniGeneiMm.319599.

3D structure databases

ProteinModelPortaliP98200.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP98200. 1 interaction.
MINTiMINT-4088697.
STRINGi10090.ENSMUSP00000079238.

Protein family/group databases

TCDBi3.A.3.8.8. the p-type atpase (p-atpase) superfamily.

PTM databases

iPTMnetiP98200.

Proteomic databases

MaxQBiP98200.
PaxDbiP98200.
PeptideAtlasiP98200.
PRIDEiP98200.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000080368; ENSMUSP00000079238; ENSMUSG00000021983.
GeneIDi50769.
KEGGimmu:50769.
UCSCiuc007uet.1. mouse.

Organism-specific databases

CTDi51761.
MGIiMGI:1354710. Atp8a2.

Phylogenomic databases

eggNOGiENOG410ITKD. Eukaryota.
ENOG410XPYK. LUCA.
GeneTreeiENSGT00770000120474.
HOGENOMiHOG000202528.
HOVERGENiHBG050601.
InParanoidiP98200.
KOiK14802.
OMAiHNGANSE.
OrthoDBiEOG091G0139.
PhylomeDBiP98200.
TreeFamiTF300654.

Enzyme and pathway databases

BRENDAi3.6.3.1. 3474.

Miscellaneous databases

ChiTaRSiAtp8a2. mouse.
PROiP98200.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000021983.
ExpressionAtlasiP98200. baseline and differential.
GenevisibleiP98200. MM.

Family and domain databases

Gene3Di2.70.150.10. 2 hits.
3.40.1110.10. 1 hit.
3.40.50.1000. 2 hits.
InterProiIPR030344. ATP8A2.
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:SF66. PTHR24092:SF66. 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. 2 hits.
TIGRFAMsiTIGR01652. ATPase-Plipid. 1 hit.
TIGR01494. ATPase_P-type. 2 hits.
PROSITEiPS00154. ATPASE_E1_E2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiAT8A2_MOUSE
AccessioniPrimary (citable) accession number: P98200
Secondary accession number(s): B2RQF2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 30, 2000
Last modified: September 7, 2016
This is version 135 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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.