AT8A2_HUMAN
ID AT8A2_HUMAN Reviewed; 1188 AA.
AC Q9NTI2; Q6ZSP3; Q9H527; Q9NPU6; Q9NTL2; Q9NYM3;
DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT 12-SEP-2018, sequence version 3.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Phospholipid-transporting ATPase IB {ECO:0000305|PubMed:31397519};
DE EC=7.6.2.1 {ECO:0000305|PubMed:31397519};
DE AltName: Full=ATPase class I type 8A member 2;
DE AltName: Full=ML-1;
DE AltName: Full=P4-ATPase flippase complex alpha subunit ATP8A2;
GN Name=ATP8A2 {ECO:0000312|HGNC:HGNC:13533}; Synonyms=ATPIB;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Sun X.L., Milo G.E., Li D.;
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 359-1188 (ISOFORM 1).
RC TISSUE=Amygdala, and Hippocampus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [4]
RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10551800;
RA Sun X.L., Li D., Fang J., Noyes I., Casto B., Theil K., Shuler C.,
RA Milo G.E.;
RT "Changes in levels of normal ML-1 gene transcripts associated with the
RT conversion of human nontumorigenic to tumorigenic phenotypes.";
RL Gene Expr. 8:129-139(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 195-1188 (ISOFORM 1).
RC TISSUE=Amygdala, and Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP TISSUE SPECIFICITY, AND CHROMOSOMAL TRANSLOCATION.
RX PubMed=20683487; DOI=10.1038/ejhg.2010.126;
RA Cacciagli P., Haddad M.R., Mignon-Ravix C., El-Waly B., Moncla A.,
RA Missirian C., Chabrol B., Villard L.;
RT "Disruption of the ATP8A2 gene in a patient with a t(10;13) de novo
RT balanced translocation and a severe neurological phenotype.";
RL Eur. J. Hum. Genet. 18:1360-1363(2010).
RN [7]
RP INTERACTION WITH TMEM30A, AND SUBCELLULAR LOCATION.
RX PubMed=20947505; DOI=10.1074/jbc.m110.139006;
RA van der Velden L.M., Wichers C.G., van Breevoort A.E., Coleman J.A.,
RA Molday R.S., Berger R., Klomp L.W., van de Graaf S.F.;
RT "Heteromeric interactions required for abundance and subcellular
RT localization of human CDC50 proteins and class 1 P4-ATPases.";
RL J. Biol. Chem. 285:40088-40096(2010).
RN [8]
RP INTERACTION WITH TMEM30A.
RX PubMed=21454556; DOI=10.1074/jbc.m111.229419;
RA Coleman J.A., Molday R.S.;
RT "Critical role of the beta-subunit CDC50A in the stable expression,
RT assembly, subcellular localization, and lipid transport activity of the P4-
RT ATPase ATP8A2.";
RL J. Biol. Chem. 286:17205-17216(2011).
RN [9]
RP TISSUE SPECIFICITY, AND VARIANT CAMRQ4 MET-376.
RX PubMed=22892528; DOI=10.1038/ejhg.2012.170;
RA Onat O.E., Gulsuner S., Bilguvar K., Nazli Basak A., Topaloglu H., Tan M.,
RA Tan U., Gunel M., Ozcelik T.;
RT "Missense mutation in the ATPase, aminophospholipid transporter protein
RT ATP8A2 is associated with cerebellar atrophy and quadrupedal locomotion.";
RL Eur. J. Hum. Genet. 21:281-285(2013).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH TMEM30A, CHARACTERIZATION OF
RP VARIANTS CAMRQ4 MET-376; MET-429; ASN-429; PRO-544; TRP-625 AND ARG-702,
RP AND MUTAGENESIS OF LYS-429.
RX PubMed=31397519; DOI=10.1002/humu.23889;
RA Choi H., Andersen J.P., Molday R.S.;
RT "Expression and functional characterization of missense mutations in ATP8A2
RT linked to severe neurological disorders.";
RL Hum. Mutat. 40:2353-2364(2019).
RN [11]
RP VARIANTS CAMRQ4 ASN-429; PRO-544 AND TRP-625.
RX PubMed=27679995; DOI=10.1007/s10048-016-0496-y;
RA Martin-Hernandez E., Rodriguez-Garcia M.E., Camacho A., Matilla-Duenas A.,
RA Garcia-Silva M.T., Quijada-Fraile P., Corral-Juan M., Tejada-Palacios P.,
RA de Las Heras R.S., Arenas J., Martin M.A., Martinez-Azorin F.;
RT "New ATP8A2 gene mutations associated with a novel syndrome:
RT encephalopathy, intellectual disability, severe hypotonia, chorea and optic
RT atrophy.";
RL Neurogenetics 17:259-263(2016).
RN [12]
RP VARIANTS CAMRQ4 581-ARG--LYS-1188 DEL AND ASP-917.
RX PubMed=29531481; DOI=10.1177/1179573518759682;
RA Alsahli S., Alrifai M.T., Al Tala S., Mutairi F.A., Alfadhel M.;
RT "Further Delineation of the Clinical Phenotype of Cerebellar Ataxia, Mental
RT Retardation, and Disequilibrium Syndrome Type 4.";
RL J. Cent. Nerv. Syst. Dis. 10:1179573518759682-1179573518759682(2018).
RN [13]
RP VARIANTS CAMRQ4 MET-429; 586-ARG--LYS-1188 DEL AND ARG-702.
RX PubMed=30012219; DOI=10.1186/s13023-018-0825-3;
RA McMillan H.J., Telegrafi A., Singleton A., Cho M.T., Lelli D., Lynn F.C.,
RA Griffin J., Asamoah A., Rinne T., Erasmus C.E., Koolen D.A., Haaxma C.A.,
RA Keren B., Doummar D., Mignot C., Thompson I., Velsher L., Dehghani M.,
RA Vahidi Mehrjardi M.Y., Maroofian R., Tchan M., Simons C., Christodoulou J.,
RA Martin-Hernandez E., Guillen Sacoto M.J., Henderson L.B., McLaughlin H.,
RA Molday L.L., Molday R.S., Yoon G.;
RT "Recessive mutations in ATP8A2 cause severe hypotonia, cognitive
RT impairment, hyperkinetic movement disorders and progressive optic
RT atrophy.";
RL Orphanet J. Rare Dis. 13:86-86(2018).
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 (Probable). Phospholipid translocation seems also to be
CC implicated in vesicle formation and in uptake of lipid signaling
CC molecules (By similarity). Reconstituted to liposomes, the
CC ATP8A2:TMEM30A flippase complex predominantly transports
CC phosphatidylserine (PS) and to a lesser extent phosphatidylethanolamine
CC (PE) (By similarity). Phospholipid translocation is not associated with
CC a countertransport of an inorganic ion or other charged substrate from
CC the cytoplasmic side toward the exoplasm in connection with the
CC phosphorylation from ATP (By similarity). ATP8A2:TMEM30A may be
CC involved in regulation of neurite outgrowth (By similarity). Proposed
CC to function in the generation and maintenance of phospholipid asymmetry
CC in photoreceptor disk membranes and neuronal axon membranes (By
CC similarity). May be involved in vesicle trafficking in neuronal cells
CC (By similarity). Required for normal visual and auditory function;
CC involved in photoreceptor and inner ear spiral ganglion cell survival
CC (By similarity). {ECO:0000250|UniProtKB:C7EXK4,
CC ECO:0000305|PubMed:31397519}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + phospholipidSide 1 = ADP + phosphate +
CC phospholipidSide 2.; EC=7.6.2.1;
CC Evidence={ECO:0000305|PubMed:31397519};
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:0000305|PubMed:31397519};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38568;
CC Evidence={ECO:0000305|PubMed:31397519};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(in) + ATP + H2O
CC = a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(out) + ADP + H(+) +
CC phosphate; Xref=Rhea:RHEA:36439, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:64612, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000305|PubMed:31397519};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36440;
CC Evidence={ECO:0000305|PubMed:31397519};
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. {ECO:0000269|PubMed:20947505,
CC ECO:0000269|PubMed:21454556, ECO:0000269|PubMed:31397519}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305|PubMed:20947505}; Multi-
CC pass membrane protein {ECO:0000255}. Golgi apparatus membrane
CC {ECO:0000269|PubMed:20947505}. Endosome membrane
CC {ECO:0000250|UniProtKB:P98200}. Cell membrane
CC {ECO:0000269|PubMed:20947505}. Photoreceptor outer segment membrane
CC {ECO:0000250|UniProtKB:P98200}. Photoreceptor inner segment membrane
CC {ECO:0000250|UniProtKB:C7EXK4}. Note=Localizes to the Golgi and
CC endosomes in photoreceptor cells (By similarity). Localizes to disk
CC membranes of rod photoreceptor outer segments (ROS) (By similarity).
CC {ECO:0000250|UniProtKB:C7EXK4, ECO:0000250|UniProtKB:P98200}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=3;
CC IsoId=Q9NTI2-4; Sequence=Displayed;
CC Name=1;
CC IsoId=Q9NTI2-1; Sequence=VSP_059718;
CC Name=2;
CC IsoId=Q9NTI2-3; Sequence=VSP_059718, VSP_059719, VSP_059720;
CC -!- TISSUE SPECIFICITY: Strongly expressed in the brain, cerebellum, retina
CC and testis. {ECO:0000269|PubMed:20683487, ECO:0000269|PubMed:22892528}.
CC -!- DISEASE: Cerebellar ataxia, intellectual disability, and dysequilibrium
CC syndrome 4 (CAMRQ4) [MIM:615268]: An autosomal recessive, congenital
CC cerebellar ataxia associated with dysarthia, quadrupedal gait and
CC intellectual disability. {ECO:0000269|PubMed:22892528,
CC ECO:0000269|PubMed:27679995, ECO:0000269|PubMed:29531481,
CC ECO:0000269|PubMed:30012219, ECO:0000269|PubMed:31397519}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Note=A chromosomal aberration disrupting ATP8A2 has been found
CC in a patient with severe intellectual disability and major hypotonia.
CC Translocation t(10;13)(p12.1;q12.13) (PubMed:20683487).
CC {ECO:0000269|PubMed:20683487}.
CC -!- SIMILARITY: Belongs to the cation transport ATPase (P-type) (TC 3.A.3)
CC family. Type IV subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC04396.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC -!- SEQUENCE CAUTION: [Isoform 2]:
CC Sequence=AAF40215.2; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF236871; AAF40215.2; ALT_FRAME; mRNA.
DR EMBL; AK094653; BAC04396.1; ALT_INIT; mRNA.
DR EMBL; AK127263; BAC86905.1; -; mRNA.
DR EMBL; AL136438; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL138815; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL138958; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL157366; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL356316; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL669971; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL137256; CAB70658.1; -; mRNA.
DR EMBL; AL390129; CAB99084.1; -; mRNA.
DR EMBL; BX537836; CAD97848.1; -; mRNA.
DR CCDS; CCDS41873.1; -. [Q9NTI2-4]
DR PIR; T46328; T46328.
DR PIR; T51867; T51867.
DR RefSeq; NP_001300670.1; NM_001313741.1.
DR RefSeq; NP_057613.4; NM_016529.5. [Q9NTI2-4]
DR RefSeq; XP_005266476.1; XM_005266419.1. [Q9NTI2-1]
DR AlphaFoldDB; Q9NTI2; -.
DR SMR; Q9NTI2; -.
DR BioGRID; 119718; 4.
DR ComplexPortal; CPX-6301; ATP8A2-CDC50A P4-ATPase complex.
DR IntAct; Q9NTI2; 1.
DR STRING; 9606.ENSP00000371070; -.
DR iPTMnet; Q9NTI2; -.
DR PhosphoSitePlus; Q9NTI2; -.
DR BioMuta; ATP8A2; -.
DR DMDM; 30316390; -.
DR jPOST; Q9NTI2; -.
DR MassIVE; Q9NTI2; -.
DR MaxQB; Q9NTI2; -.
DR PaxDb; Q9NTI2; -.
DR PeptideAtlas; Q9NTI2; -.
DR PRIDE; Q9NTI2; -.
DR ProteomicsDB; 82608; -. [Q9NTI2-1]
DR ProteomicsDB; 82609; -. [Q9NTI2-3]
DR TopDownProteomics; Q9NTI2-1; -. [Q9NTI2-1]
DR Antibodypedia; 50027; 97 antibodies from 16 providers.
DR DNASU; 51761; -.
DR Ensembl; ENST00000381655.7; ENSP00000371070.2; ENSG00000132932.19. [Q9NTI2-4]
DR Ensembl; ENST00000684424.1; ENSP00000507489.1; ENSG00000132932.19. [Q9NTI2-1]
DR GeneID; 51761; -.
DR KEGG; hsa:51761; -.
DR MANE-Select; ENST00000381655.7; ENSP00000371070.2; NM_016529.6; NP_057613.4.
DR UCSC; uc001uqk.4; human. [Q9NTI2-4]
DR CTD; 51761; -.
DR DisGeNET; 51761; -.
DR GeneCards; ATP8A2; -.
DR HGNC; HGNC:13533; ATP8A2.
DR HPA; ENSG00000132932; Group enriched (brain, pituitary gland, retina).
DR MalaCards; ATP8A2; -.
DR MIM; 605870; gene.
DR MIM; 615268; phenotype.
DR neXtProt; NX_Q9NTI2; -.
DR OpenTargets; ENSG00000132932; -.
DR Orphanet; 1766; Dysequilibrium syndrome.
DR PharmGKB; PA25166; -.
DR VEuPathDB; HostDB:ENSG00000132932; -.
DR eggNOG; KOG0206; Eukaryota.
DR GeneTree; ENSGT00940000157332; -.
DR HOGENOM; CLU_000846_3_2_1; -.
DR InParanoid; Q9NTI2; -.
DR OMA; YWEIGVQ; -.
DR OrthoDB; 587717at2759; -.
DR PhylomeDB; Q9NTI2; -.
DR TreeFam; TF300654; -.
DR BRENDA; 7.6.2.1; 2681.
DR PathwayCommons; Q9NTI2; -.
DR Reactome; R-HSA-936837; Ion transport by P-type ATPases.
DR SignaLink; Q9NTI2; -.
DR BioGRID-ORCS; 51761; 10 hits in 1071 CRISPR screens.
DR ChiTaRS; ATP8A2; human.
DR GenomeRNAi; 51761; -.
DR Pharos; Q9NTI2; Tbio.
DR PRO; PR:Q9NTI2; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; Q9NTI2; protein.
DR Bgee; ENSG00000132932; Expressed in middle temporal gyrus and 135 other tissues.
DR ExpressionAtlas; Q9NTI2; baseline and differential.
DR Genevisible; Q9NTI2; HS.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-KW.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:1990531; C:phospholipid-translocating ATPase complex; IPI:ComplexPortal.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
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:0090555; F:phosphatidylethanolamine flippase activity; ISS:UniProtKB.
DR GO; GO:0140346; F:phosphatidylserine flippase activity; ISS:UniProtKB.
DR GO; GO:0090556; F:phosphatidylserine floppase activity; IEA:RHEA.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0140331; P:aminophospholipid translocation; ISS:UniProtKB.
DR GO; GO:0007409; P:axonogenesis; IEA:Ensembl.
DR GO; GO:0050908; P:detection of light stimulus involved in visual perception; IEA:Ensembl.
DR GO; GO:0042755; P:eating behavior; IEA:Ensembl.
DR GO; GO:0042472; P:inner ear morphogenesis; IEA:Ensembl.
DR GO; GO:0003011; P:involuntary skeletal muscle contraction; IEA:Ensembl.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; TAS:ProtInc.
DR GO; GO:0060052; P:neurofilament cytoskeleton organization; IEA:Ensembl.
DR GO; GO:0050884; P:neuromuscular process controlling posture; IEA:Ensembl.
DR GO; GO:0048666; P:neuron development; IBA:GO_Central.
DR GO; GO:0045332; P:phospholipid translocation; IBA:GO_Central.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; IEA:Ensembl.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IEA:Ensembl.
DR GO; GO:0061092; P:positive regulation of phospholipid translocation; IEA:Ensembl.
DR GO; GO:0010996; P:response to auditory stimulus; IEA:Ensembl.
DR GO; GO:0010842; P:retina layer formation; IEA:Ensembl.
DR GO; GO:0043588; P:skin development; IEA:Ensembl.
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 Alternative splicing; ATP-binding; Cell membrane; Cell projection;
KW Chromosomal rearrangement; Disease variant; Endosome; Golgi apparatus;
KW Intellectual disability; Lipid transport; Magnesium; Membrane;
KW Metal-binding; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Translocase; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..1188
FT /note="Phospholipid-transporting ATPase IB"
FT /id="PRO_0000046362"
FT TOPO_DOM 1..94
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 95..115
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 116..119
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 120..140
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 141..316
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 317..337
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 338..364
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 365..385
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 386..887
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 888..908
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 909..910
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 911..931
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 932..959
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 960..980
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 981..997
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 998..1018
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1019..1028
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1029..1049
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1050..1063
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1064..1084
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1085..1188
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 1162..1188
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 428
FT /note="4-aspartylphosphate intermediate"
FT /evidence="ECO:0000250"
FT BINDING 821
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 825
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT SITE 371
FT /note="Involved in the recognition of the lipid substrate
FT on the exoplasmic side"
FT /evidence="ECO:0000250|UniProtKB:C7EXK4"
FT SITE 376
FT /note="Involved in the release of the transported lipid
FT into the cytosolic leaflet"
FT /evidence="ECO:0000250|UniProtKB:C7EXK4"
FT MOD_RES 45
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P98200"
FT VAR_SEQ 1..40
FT /note="Missing (in isoform 1 and isoform 2)"
FT /id="VSP_059718"
FT VAR_SEQ 555..568
FT /note="MGQEQTFGILNVLE -> VSNMRVHISDHLLL (in isoform 2)"
FT /id="VSP_059719"
FT VAR_SEQ 569..1188
FT /note="Missing (in isoform 2)"
FT /id="VSP_059720"
FT VARIANT 376
FT /note="I -> M (in CAMRQ4; abolishes ATPase activity. No
FT effect on interaction with TMEM30A; dbSNP:rs546968533)"
FT /evidence="ECO:0000269|PubMed:22892528,
FT ECO:0000269|PubMed:31397519"
FT /id="VAR_069928"
FT VARIANT 429
FT /note="K -> M (in CAMRQ4; unknown pathological
FT significance; abolishes ATPase activity. No effect on
FT interaction with TMEM30A; dbSNP:rs1057522489)"
FT /evidence="ECO:0000269|PubMed:30012219,
FT ECO:0000269|PubMed:31397519"
FT /id="VAR_084371"
FT VARIANT 429
FT /note="K -> N (in CAMRQ4; unknown pathological
FT significance; abolishes ATPase activity and results in
FT protein misfolding and proteasomal degradation. No effect
FT on interaction with TMEM30A)"
FT /evidence="ECO:0000269|PubMed:27679995,
FT ECO:0000269|PubMed:31397519"
FT /id="VAR_084370"
FT VARIANT 544
FT /note="A -> P (in CAMRQ4; unknown pathological
FT significance; results in protein misfolding and proteasomal
FT degradation)"
FT /evidence="ECO:0000269|PubMed:27679995,
FT ECO:0000269|PubMed:31397519"
FT /id="VAR_084372"
FT VARIANT 581..1188
FT /note="Missing (in CAMRQ4; unknown pathological
FT significance; dbSNP:rs755133567)"
FT /evidence="ECO:0000269|PubMed:29531481"
FT /id="VAR_084373"
FT VARIANT 586..1188
FT /note="Missing (in CAMRQ4; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:30012219"
FT /id="VAR_084374"
FT VARIANT 625
FT /note="R -> W (in CAMRQ4; unknown pathological
FT significance; results in protein misfolding and proteasomal
FT degradation; dbSNP:rs764911379)"
FT /evidence="ECO:0000269|PubMed:27679995,
FT ECO:0000269|PubMed:31397519"
FT /id="VAR_084375"
FT VARIANT 702
FT /note="W -> R (in CAMRQ4; unknown pathological
FT significance; results in protein misfolding and proteasomal
FT degradation)"
FT /evidence="ECO:0000269|PubMed:30012219,
FT ECO:0000269|PubMed:31397519"
FT /id="VAR_084376"
FT VARIANT 917
FT /note="N -> D (in CAMRQ4; unknown pathological
FT significance; dbSNP:rs1593410369)"
FT /evidence="ECO:0000269|PubMed:29531481"
FT /id="VAR_084377"
FT VARIANT 1069
FT /note="A -> T (in dbSNP:rs2296242)"
FT /id="VAR_055543"
FT MUTAGEN 429
FT /note="K->A: Abolishes ATPase activity."
FT /evidence="ECO:0000269|PubMed:31397519"
FT MUTAGEN 429
FT /note="K->L: Abolishes ATPase activity."
FT /evidence="ECO:0000269|PubMed:31397519"
FT MUTAGEN 429
FT /note="K->R: Abolishes ATPase activity."
FT /evidence="ECO:0000269|PubMed:31397519"
FT CONFLICT 573
FT /note="R -> K (in Ref. 2; BAC86905)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1188 AA; 133599 MW; 93DF0640FB189CD9 CRC64;
MLNGAGLDKA LKMSLPRRSR IRSSVGPVRS SLGYKKAEDE MSRATSVGDQ LEAPARTIYL
NQPHLNKFRD NQISTAKYSV LTFLPRFLYE QIRRAANAFF LFIALLQQIP DVSPTGRYTT
LVPLIIILTI AGIKEIVEDF KRHKADNAVN KKKTIVLRNG MWHTIMWKEV AVGDIVKVVN
GQYLPADVVL LSSSEPQAMC YVETANLDGE TNLKIRQGLS HTADMQTREV LMKLSGTIEC
EGPNRHLYDF TGNLNLDGKS LVALGPDQIL LRGTQLRNTQ WVFGIVVYTG HDTKLMQNST
KAPLKRSNVE KVTNVQILVL FGILLVMALV SSAGALYWNR SHGEKNWYIK KMDTTSDNFG
YNLLTFIILY NNLIPISLLV TLEVVKYTQA LFINWDTDMY YIGNDTPAMA RTSNLNEELG
QVKYLFSDKT GTLTCNIMNF KKCSIAGVTY GHFPELAREP SSDDFCRMPP PCSDSCDFDD
PRLLKNIEDR HPTAPCIQEF LTLLAVCHTV VPEKDGDNII YQASSPDEAA LVKGAKKLGF
VFTARTPFSV IIEAMGQEQT FGILNVLEFS SDRKRMSVIV RTPSGRLRLY CKGADNVIFE
RLSKDSKYME ETLCHLEYFA TEGLRTLCVA YADLSENEYE EWLKVYQEAS TILKDRAQRL
EECYEIIEKN LLLLGATAIE DRLQAGVPET IATLLKAEIK IWVLTGDKQE TAINIGYSCR
LVSQNMALIL LKEDSLDATR AAITQHCTDL GNLLGKENDV ALIIDGHTLK YALSFEVRRS
FLDLALSCKA VICCRVSPLQ KSEIVDVVKK RVKAITLAIG DGANDVGMIQ TAHVGVGISG
NEGMQATNNS DYAIAQFSYL EKLLLVHGAW SYNRVTKCIL YCFYKNVVLY IIELWFAFVN
GFSGQILFER WCIGLYNVIF TALPPFTLGI FERSCTQESM LRFPQLYKIT QNGEGFNTKV
FWGHCINALV HSLILFWFPM KALEHDTVLT SGHATDYLFV GNIVYTYVVV TVCLKAGLET
TAWTKFSHLA VWGSMLTWLV FFGIYSTIWP TIPIAPDMRG QATMVLSSAH FWLGLFLVPT
ACLIEDVAWR AAKHTCKKTL LEEVQELETK SRVLGKAVLR DSNGKRLNER DRLIKRLGRK
TPPTLFRGSS LQQGVPHGYA FSQEEHGAVS QEEVIRAYDT TKKKSRKK
