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 27-MAR-2024, entry version 187. 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 MUTAGENESIS OF GLN-107, AND FUNCTION. RX PubMed=34403372; DOI=10.1172/jci148005; RA Segawa K., Kikuchi A., Noji T., Sugiura Y., Hiraga K., Suzuki C., RA Haginoya K., Kobayashi Y., Matsunaga M., Ochiai Y., Yamada K., RA Nishimura T., Iwasawa S., Shoji W., Sugihara F., Nishino K., Kosako H., RA Ikawa M., Uchiyama Y., Suematsu M., Ishikita H., Kure S., Nagata S.; RT "A sublethal ATP11A mutation associated with neurological deterioration RT causes aberrant phosphatidylcholine flipping in plasma membranes."; RL J. Clin. Invest. 131:0-0(2021). RN [12] 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 [13] 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 [14] 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 (By similarity). Able to translocate phosphatidylserine, CC but not phosphatidylcholine (PubMed:34403372). Phospholipid CC translocation seems also to be implicated in vesicle formation and in CC uptake of lipid signaling molecules (By similarity). Reconstituted to CC liposomes, the 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:0000269|PubMed:34403372, 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 -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000250|UniProtKB:Q9Y2Q0}; 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, impaired intellectual development, and CC dysequilibrium syndrome 4 (CAMRQ4) [MIM:615268]: An autosomal CC recessive, congenital cerebellar ataxia associated with dysarthia, CC quadrupedal gait and intellectual disability. CC {ECO:0000269|PubMed:22892528, ECO:0000269|PubMed:27679995, CC ECO:0000269|PubMed:29531481, ECO:0000269|PubMed:30012219, CC ECO:0000269|PubMed:31397519}. Note=The disease is caused by variants CC affecting the gene represented in this 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=AAF40215.2; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 6. DR ComplexPortal; CPX-6301; ATP8A2-CDC50A P4-ATPase complex. DR IntAct; Q9NTI2; 1. DR STRING; 9606.ENSP00000371070; -. DR GlyGen; Q9NTI2; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9NTI2; -. DR PhosphoSitePlus; Q9NTI2; -. DR BioMuta; ATP8A2; -. DR DMDM; 30316390; -. DR jPOST; Q9NTI2; -. DR MassIVE; Q9NTI2; -. DR MaxQB; Q9NTI2; -. DR PaxDb; 9606-ENSP00000371070; -. DR PeptideAtlas; Q9NTI2; -. DR ProteomicsDB; 82608; -. [Q9NTI2-1] DR ProteomicsDB; 82609; -. [Q9NTI2-3] DR TopDownProteomics; Q9NTI2-1; -. [Q9NTI2-1] DR Antibodypedia; 50027; 99 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 AGR; HGNC:13533; -. 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; DMMIYQR; -. DR OrthoDB; 275833at2759; -. 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; 12 hits in 1151 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 136 other cell types or tissues. DR ExpressionAtlas; Q9NTI2; baseline and differential. 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:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:1990531; C:phospholipid-translocating ATPase complex; IPI:ComplexPortal. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. 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: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:0008340; P:determination of adult lifespan; 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 CDD; cd02073; P-type_ATPase_APLT_Dnf-like; 1. DR Gene3D; 3.40.1110.10; Calcium-transporting ATPase, cytoplasmic domain N; 1. DR Gene3D; 2.70.150.10; Calcium-transporting ATPase, cytoplasmic transduction domain A; 1. DR Gene3D; 3.40.50.1000; HAD superfamily/HAD-like; 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 NCBIfam; TIGR01652; ATPase-Plipid; 1. DR NCBIfam; TIGR01494; ATPase_P-type; 2. DR PANTHER; PTHR24092:SF98; PHOSPHOLIPID-TRANSPORTING ATPASE IB; 1. DR PANTHER; PTHR24092; PROBABLE PHOSPHOLIPID-TRANSPORTING ATPASE; 1. DR Pfam; PF13246; Cation_ATPase; 1. DR Pfam; PF00122; E1-E2_ATPase; 1. DR Pfam; PF16212; PhoLip_ATPase_C; 1. DR Pfam; PF16209; PhoLip_ATPase_N; 1. DR PRINTS; PR00119; CATATPASE. DR SFLD; SFLDG00002; C1.7:_P-type_atpase_like; 1. DR SFLD; SFLDF00027; p-type_atpase; 1. DR SUPFAM; SSF81653; Calcium ATPase, transduction domain A; 1. DR SUPFAM; SSF81665; Calcium ATPase, transmembrane domain M; 1. DR SUPFAM; SSF56784; HAD-like; 1. DR SUPFAM; SSF81660; Metal cation-transporting ATPase, ATP-binding domain N; 1. DR PROSITE; PS00154; ATPASE_E1_E2; 1. DR Genevisible; Q9NTI2; HS. 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|UniProtKB:Q9Y2Q0" FT BINDING 428 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:Q9Y2Q0" FT BINDING 428 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:Q9Y2Q0" FT BINDING 429 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:Q9Y2Q0" FT BINDING 430 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 430 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:Q9Y2Q0" FT BINDING 528 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 569 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:Q9Y2Q0" FT BINDING 592 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 625 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 705 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 706 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 707 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 795 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 801 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P04191" FT BINDING 821 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:Q9Y2Q0" FT BINDING 824 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:Q9Y2Q0" FT BINDING 825 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:Q9Y2Q0" FT BINDING 825 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:Q8NB49" 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; uncertain significance; abolishes FT ATPase activity. No effect on interaction with TMEM30A; FT 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; uncertain significance; abolishes FT ATPase activity and results in protein misfolding and FT proteasomal degradation. No effect on interaction with FT 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; uncertain significance; results FT in protein misfolding and proteasomal 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; uncertain significance; FT dbSNP:rs755133567)" FT /evidence="ECO:0000269|PubMed:29531481" FT /id="VAR_084373" FT VARIANT 586..1188 FT /note="Missing (in CAMRQ4; uncertain significance)" FT /evidence="ECO:0000269|PubMed:30012219" FT /id="VAR_084374" FT VARIANT 625 FT /note="R -> W (in CAMRQ4; uncertain significance; results FT in protein misfolding and proteasomal degradation; FT 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; uncertain significance; results FT in protein misfolding and proteasomal 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; uncertain significance; FT 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 107 FT /note="Q->A: No effect on flippase activity toward FT phosphatidylserine. Like the wild type, it is unable to FT translocate phosphatidylcholine." FT /evidence="ECO:0000269|PubMed:34403372" FT MUTAGEN 107 FT /note="Q->E: Reduced flippase activity toward FT phosphatidylserine. Like the wild type, it is unable to FT translocate phosphatidylcholine." FT /evidence="ECO:0000269|PubMed:34403372" 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 //