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Protein

Phospholipid-transporting ATPase IB

Gene

ATP8A2

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. Reconstituted to liposomes, the ATP8A2:TMEM30A flippase complex predomiminantly transports phosphatidylserine (PS) and to a lesser extent phosphatidylethanolamine (PE). 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. Involved in regulation of neurite outgrowth; acting in synergy with TMEM30A. Required for normal visual and auditory function; involved in photoreceptor and inner ear spiral ganglion cell survival.

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). ATPase activity is inhibited by N-ethylmaleimide (NEM) and vanadate. Flippase activity is inhibited by NEM and 1,2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPS) (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei3884-aspartylphosphate intermediateBy similarity1
Metal bindingi781MagnesiumBy similarity1
Metal bindingi785MagnesiumBy similarity1

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-936837 Ion transport by P-type ATPases

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
ML-1
P4-ATPase flippase complex alpha subunit ATP8A2
Gene namesi
Name:ATP8A2
Synonyms:ATPIB
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 13

Organism-specific databases

EuPathDBiHostDB:ENSG00000132932.16
HGNCiHGNC:13533 ATP8A2
MIMi605870 gene
neXtProtiNX_Q9NTI2

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 – 44CytoplasmicSequence analysisAdd BLAST44
Transmembranei45 – 66HelicalSequence analysisAdd BLAST22
Topological domaini67 – 71Exoplasmic loopSequence analysis5
Transmembranei72 – 94HelicalSequence analysisAdd BLAST23
Topological domaini95 – 276CytoplasmicSequence analysisAdd BLAST182
Transmembranei277 – 298HelicalSequence analysisAdd BLAST22
Topological domaini299 – 323Exoplasmic loopSequence analysisAdd BLAST25
Transmembranei324 – 345HelicalSequence analysisAdd BLAST22
Topological domaini346 – 837CytoplasmicSequence analysisAdd BLAST492
Transmembranei838 – 858HelicalSequence analysisAdd BLAST21
Topological domaini859 – 870Exoplasmic loopSequence analysisAdd BLAST12
Transmembranei871 – 890HelicalSequence analysisAdd BLAST20
Topological domaini891 – 920CytoplasmicSequence analysisAdd BLAST30
Transmembranei921 – 942HelicalSequence analysisAdd BLAST22
Topological domaini943 – 956Exoplasmic loopSequence analysisAdd BLAST14
Transmembranei957 – 979HelicalSequence analysisAdd BLAST23
Topological domaini980 – 985CytoplasmicSequence analysis6
Transmembranei986 – 1006HelicalSequence analysisAdd BLAST21
Topological domaini1007 – 1024Exoplasmic loopSequence analysisAdd BLAST18
Transmembranei1025 – 1049HelicalSequence analysisAdd BLAST25
Topological domaini1050 – 1148CytoplasmicSequence analysisAdd BLAST99

Keywords - Cellular componenti

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

Pathology & Biotechi

Involvement in diseasei

Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 4 (CMARQ4)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA congenital cerebellar ataxia associated with dysarthia, quadrupedal gait and mental retardation.
See also OMIM:615268
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_069928336I → M in CMARQ4. 1 Publication1
A chromosomal aberration disrupting ATP8A2 has been found in a patient with severe mental retardation and major hypotonia. Translocation t(10;13)(p12.1;q12.13) (PubMed:20683487).1 Publication

Keywords - Diseasei

Disease mutation, Mental retardation

Organism-specific databases

DisGeNETi51761
MalaCardsiATP8A2
MIMi615268 phenotype
Orphaneti1766 Dysequilibrium syndrome
PharmGKBiPA25166

Polymorphism and mutation databases

BioMutaiATP8A2
DMDMi30316390

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000463621 – 1148Phospholipid-transporting ATPase IBAdd BLAST1148

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei5PhosphothreonineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9NTI2
PeptideAtlasiQ9NTI2
PRIDEiQ9NTI2
ProteomicsDBi82608
82609 [Q9NTI2-3]
TopDownProteomicsiQ9NTI2-1 [Q9NTI2-1]

Expressioni

Tissue specificityi

Strongly expressed in the brain, cerebellum, retina and testis.2 Publications

Gene expression databases

BgeeiENSG00000132932
CleanExiHS_ATP8A2
ExpressionAtlasiQ9NTI2 baseline and differential
GenevisibleiQ9NTI2 HS

Organism-specific databases

HPAiHPA040033

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.2 Publications

Protein-protein interaction databases

BioGridi119718, 2 interactors
IntActiQ9NTI2, 1 interactor
STRINGi9606.ENSP00000371070

Structurei

3D structure databases

ProteinModelPortaliQ9NTI2
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410ITKD Eukaryota
ENOG410XPYK LUCA
HOVERGENiHBG050601
InParanoidiQ9NTI2
KOiK14802
OrthoDBiEOG091G0139
PhylomeDBiQ9NTI2
TreeFamiTF300654

Family and domain databases

Gene3Di3.40.1110.10, 1 hit
3.40.50.1000, 1 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, 2 hits
SSF81665 SSF81665, 3 hits
TIGRFAMsiTIGR01652 ATPase-Plipid, 1 hit
TIGR01494 ATPase_P-type, 2 hits
PROSITEiView protein in PROSITE
PS00154 ATPASE_E1_E2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9NTI2-1) [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
MSRATSVGDQ LEAPARTIYL NQPHLNKFRD NQISTAKYSV LTFLPRFLYE
60 70 80 90 100
QIRRAANAFF LFIALLQQIP DVSPTGRYTT LVPLIIILTI AGIKEIVEDF
110 120 130 140 150
KRHKADNAVN KKKTIVLRNG MWHTIMWKEV AVGDIVKVVN GQYLPADVVL
160 170 180 190 200
LSSSEPQAMC YVETANLDGE TNLKIRQGLS HTADMQTREV LMKLSGTIEC
210 220 230 240 250
EGPNRHLYDF TGNLNLDGKS LVALGPDQIL LRGTQLRNTQ WVFGIVVYTG
260 270 280 290 300
HDTKLMQNST KAPLKRSNVE KVTNVQILVL FGILLVMALV SSAGALYWNR
310 320 330 340 350
SHGEKNWYIK KMDTTSDNFG YNLLTFIILY NNLIPISLLV TLEVVKYTQA
360 370 380 390 400
LFINWDTDMY YIGNDTPAMA RTSNLNEELG QVKYLFSDKT GTLTCNIMNF
410 420 430 440 450
KKCSIAGVTY GHFPELAREP SSDDFCRMPP PCSDSCDFDD PRLLKNIEDR
460 470 480 490 500
HPTAPCIQEF LTLLAVCHTV VPEKDGDNII YQASSPDEAA LVKGAKKLGF
510 520 530 540 550
VFTARTPFSV IIEAMGQEQT FGILNVLEFS SDRKRMSVIV RTPSGRLRLY
560 570 580 590 600
CKGADNVIFE RLSKDSKYME ETLCHLEYFA TEGLRTLCVA YADLSENEYE
610 620 630 640 650
EWLKVYQEAS TILKDRAQRL 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
LRFPQLYKIT QNGEGFNTKV FWGHCINALV HSLILFWFPM KALEHDTVLT
960 970 980 990 1000
SGHATDYLFV GNIVYTYVVV TVCLKAGLET TAWTKFSHLA VWGSMLTWLV
1010 1020 1030 1040 1050
FFGIYSTIWP TIPIAPDMRG QATMVLSSAH FWLGLFLVPT ACLIEDVAWR
1060 1070 1080 1090 1100
AAKHTCKKTL LEEVQELETK SRVLGKAVLR DSNGKRLNER DRLIKRLGRK
1110 1120 1130 1140
TPPTLFRGSS LQQGVPHGYA FSQEEHGAVS QEEVIRAYDT TKKKSRKK
Note: No experimental confirmation available.
Length:1,148
Mass (Da):129,242
Last modified:April 30, 2003 - v2
Checksum:iE9F363B568C7EE82
GO
Isoform 2 (identifier: Q9NTI2-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     515-528: MGQEQTFGILNVLE → VSNMRVHISDHLLL
     529-1148: Missing.

Note: No experimental confirmation available.Curated
Show »
Length:528
Mass (Da):59,296
Checksum:i1CAD4BDC7B38F391
GO

Sequence cautioni

Isoform 2 : The sequence AAF40215 differs from that shown. Reason: Frameshift at position 522.Curated
The sequence BAC04396 differs from that shown. Reason: Erroneous initiation.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_069928336I → M in CMARQ4. 1 Publication1
Natural variantiVAR_0555431029A → T. Corresponds to variant dbSNP:rs2296242Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_037646515 – 528MGQEQ…LNVLE → VSNMRVHISDHLLL in isoform 2. 1 PublicationAdd BLAST14
Alternative sequenceiVSP_037647529 – 1148Missing in isoform 2. 1 PublicationAdd BLAST620

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF236871 mRNA Translation: AAF40215.2 Frameshift.
AL136438 Genomic DNA No translation available.
AL138815 Genomic DNA No translation available.
AL138958 Genomic DNA No translation available.
AL157366 Genomic DNA No translation available.
AL356316 Genomic DNA No translation available.
AL669971 Genomic DNA No translation available.
AL137256 mRNA Translation: CAB70658.1
AL390129 mRNA Translation: CAB99084.1
BX537836 mRNA Translation: CAD97848.1
AK094653 mRNA Translation: BAC04396.1 Different initiation.
PIRiT46328
T51867
RefSeqiNP_001300670.1, NM_001313741.1
NP_057613.4, NM_016529.5
XP_005266476.1, XM_005266419.1 [Q9NTI2-1]
UniGeneiHs.444957
Hs.599723

Genome annotation databases

EnsembliENST00000381655; ENSP00000371070; ENSG00000132932
GeneIDi51761
KEGGihsa:51761
UCSCiuc001uqk.4 human [Q9NTI2-1]

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiAT8A2_HUMAN
AccessioniPrimary (citable) accession number: Q9NTI2
Secondary accession number(s): Q9H527
, Q9NPU6, Q9NTL2, Q9NYM3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 18, 2001
Last sequence update: April 30, 2003
Last modified: June 20, 2018
This is version 154 of the entry and version 2 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

Documents

  1. Human chromosome 13
    Human chromosome 13: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

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