ATP8A1 ATPase phospholipid transporting 8A1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ATP8A1provided by HGNC
Official Full Name: ATPase phospholipid transporting 8A1provided by HGNC
Primary source: HGNC:HGNC:13531
See related: Ensembl:ENSG00000124406 MIM:609542; AllianceGenome:HGNC:13531
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ATPIA; ATPP2; ATPASEII
Summary: The P-type adenosinetriphosphatases (P-type ATPases) are a family of proteins which use the free energy of ATP hydrolysis to drive uphill transport of ions across membranes. Several subfamilies of P-type ATPases have been identified. One subfamily catalyzes transport of heavy metal ions. Another subfamily transports non-heavy metal ions (NMHI). The protein encoded by this gene is a member of the third subfamily of P-type ATPases and acts to transport amphipaths, such as phosphatidylserine. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Expression: Broad expression in brain (RPKM 28.9), thyroid (RPKM 28.5) and 20 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 4p13

Exon count:: 39

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (42408373..42657105, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (42382233..42630975, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (42410390..42659122, complement)

Chromosome 4 - NC_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Exosome circATP8A1 induces macrophage M2 polarization by regulating the miR-1-3p/STAT6 axis to promote gastric cancer progression.
Title: Exosome circATP8A1 induces macrophage M2 polarization by regulating the miR-1-3p/STAT6 axis to promote gastric cancer progression.
AP-3-dependent targeting of flippase ATP8A1 to lamellar bodies suppresses activation of YAP in alveolar epithelial type 2 cells.
Title: AP-3-dependent targeting of flippase ATP8A1 to lamellar bodies suppresses activation of YAP in alveolar epithelial type 2 cells.
cryo-electron microscopy structure of six intermediates of the human flippase ATP8A1 bound to the partner protein CDC50a; ATP binding and autophosphorylation of ATP8A1 drive a cycle of conformations in which lipids bind differently, powering translocation.
Title: Cryo-EM structures capture the transport cycle of the P4-ATPase flippase.
ATP8A1 is cleaved by the cysteine protease calpain during apoptosis, and the cleavage is prevented indirectly by caspase inhibition, involving blockage of calcium influx into platelets and subsequent calpain activation.
Title: Calpain cleaves phospholipid flippase ATP8A1 during apoptosis in platelets.
Single-nucleotide polymorphism, rs17448506, located in ATP8A1 intron, reached the significance threshold for interaction with tobacco smoke expose and bronchial hyperresponsiveness (p=10-5).
Title: Interactive effect between ATPase-related genes and early-life tobacco smoke exposure on bronchial hyper-responsiveness detected in asthma-ascertained families.
Over-expression of ATP8A1 alleviated ethanol-induced hepatocyte injury. Moreover, the PI3K/Akt signaling pathway appears to participate in inhibition of ethanol-induced hepatocyte apoptosis.
Title: Over-Expression of ATPase II Alleviates Ethanol-Induced Hepatocyte Injury in HL-7702 Cells.
A pronounced induction of the flippase Atp8a1 was observed in post-mortem tissue homogenates from the hippocampus and temporal lobe of juvenile autistic subjects compared to age-matched controls.
Title: Aberrant hippocampal Atp8a1 levels are associated with altered synaptic strength, electrical activity, and autistic-like behavior.
Knockdown of ATP8A1 (a recycling endosome phosphatidlyserine-flippase) suppresses nuclear localization of YAP and YAP-dependent transcription. ATP8A1 knockdown increases the phosphorylated (activated) form of Lats1 that phosphorylates and inactivates YAP.
Title: Endosomal phosphatidylserine is critical for the YAP signalling pathway in proliferating cells.
The increased level of intracellular ATP8A1 protein attenuated the inhibitor role of miR-140-3p in the growth and mobility of NSCLC cell.
Title: MiR-140-3p suppressed cell growth and invasion by downregulating the expression of ATP8A1 in non-small cell lung cancer.
Depletion of ATP8A1 impaired the asymmetric transbilayer distribution of phosphatidylserine in recycling endosomes, dissociated EHD1 from recycling endosomes, and generated aberrant endosomal tubules that appear resistant to fission.
Title: Transport through recycling endosomes requires EHD1 recruitment by a phosphatidylserine translocase.

Submit: New GeneRIF Correction See all GeneRIFs (14)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genetic analysis of the pathogenic molecular sub-phenotype interferon-alpha identifies multiple novel loci involved in systemic lupus erythematosus. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide analysis of polymorphisms associated with cytokine responses in smallpox vaccine recipients. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-36481 (e-PCR)
- UniSTS:60166

SHGC-148448 (e-PCR)
- UniSTS:176400

ATP8A1_9102 (e-PCR)
- UniSTS:468024

SHGC-59604 (e-PCR)
- UniSTS:23622

WI-19830 (e-PCR)
- UniSTS:51549

D4S3277 (e-PCR)
- UniSTS:77724

D4S1207 (e-PCR)
- UniSTS:69860

SHGC-146639 (e-PCR)
- UniSTS:175343

G09524 (e-PCR)
- UniSTS:10999

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables ATP hydrolysis activity	IEA Inferred from Electronic Annotation more info
enables ATPase-coupled intramembrane lipid transporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables ATPase-coupled intramembrane lipid transporter activity	TAS Traceable Author Statement more info
enables ATPase-coupled monoatomic cation transmembrane transporter activity	NAS Non-traceable Author Statement more info	PubMed
enables magnesium ion binding	IEA Inferred from Electronic Annotation more info
enables phosphatidylserine flippase activity	IDA Inferred from Direct Assay more info	PubMed
enables phosphatidylserine flippase activity	ISS Inferred from Sequence or Structural Similarity more info
enables phosphatidylserine floppase activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in aminophospholipid translocation	IDA Inferred from Direct Assay more info	PubMed
involved_in aminophospholipid translocation	ISS Inferred from Sequence or Structural Similarity more info
involved_in learning	IEA Inferred from Electronic Annotation more info
involved_in monoatomic cation transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in monoatomic ion transmembrane transport	TAS Traceable Author Statement more info
involved_in phospholipid translocation	IBA Inferred from Biological aspect of Ancestor more info
involved_in phospholipid translocation	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of cell migration	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of phospholipid translocation	IEA Inferred from Electronic Annotation more info
involved_in transport across blood-brain barrier	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
located_in azurophil granule membrane	TAS Traceable Author Statement more info
located_in chromaffin granule membrane	IEA Inferred from Electronic Annotation more info
located_in cytoplasmic vesicle	ISS Inferred from Sequence or Structural Similarity more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular exosome	HDA more info	PubMed
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
located_in membrane	HDA more info	PubMed
located_in organelle membrane	ISS Inferred from Sequence or Structural Similarity more info
part_of phospholipid-translocating ATPase complex	IDA Inferred from Direct Assay more info	PubMed
part_of phospholipid-translocating ATPase complex	IPI Inferred from Physical Interaction more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
located_in specific granule membrane	TAS Traceable Author Statement more info
located_in synaptic vesicle membrane	IEA Inferred from Electronic Annotation more info
is_active_in trans-Golgi network	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: phospholipid-transporting ATPase IA

Names: ATPase II; ATPase class I type 8A member 1; ATPase, aminophospholipid transporter (APLT), class I, type 8A, member 1; P4-ATPase flippase complex alpha subunit ATP8A1; aminophospholipid translocase; chromaffin granule ATPase II; probable phospholipid-transporting ATPase IA

NP_001098999.1

EC 7.6.2.1

NP_001386953.1

EC 7.6.2.1

NP_001386954.1

EC 7.6.2.1

NP_001386955.1

EC 7.6.2.1

NP_001386956.1

EC 7.6.2.1

NP_006086.1

EC 7.6.2.1

XP_011511917.1

EC 7.6.2.1

XP_011511918.1

EC 7.6.2.1

XP_047305464.1

EC 7.6.2.1

XP_047305465.1

EC 7.6.2.1

XP_047305466.1

EC 7.6.2.1

XP_047305467.1

EC 7.6.2.1

XP_054204713.1

EC 7.6.2.1

XP_054204714.1

EC 7.6.2.1

XP_054204715.1

EC 7.6.2.1

XP_054204716.1

EC 7.6.2.1

XP_054204717.1

EC 7.6.2.1

XP_054204718.1

EC 7.6.2.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001105529.1 → NP_001098999.1 phospholipid-transporting ATPase IA isoform b

See identical proteins and their annotated locations for NP_001098999.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) has multiple changes in the coding region compared to variant 1. The resulting isoform (b) has the same N- and C-termini but is shorter compared to isoform a.

Source sequence(s)

AC084010, BC109317, BP232466

Consensus CDS

CCDS47049.1

UniProtKB/TrEMBL

Q59EX4

Related

ENSP00000264449.10, ENST00000264449.14

Conserved Domains (6) summary

TIGR01652
Location:49 → 1071

ATPase-Plipid; phospholipid-translocating P-type ATPase, flippase

pfam00122
Location:106 → 191

E1-E2_ATPase; E1-E2 ATPase

pfam13246
Location:471 → 566

Cation_ATPase; Cation transport ATPase (P-type)

pfam16209
Location:38 → 100

PhoLip_ATPase_N; Phospholipid-translocating ATPase N-terminal

pfam16212
Location:812 → 1064

PhoLip_ATPase_C; Phospholipid-translocating P-type ATPase C-terminal

cl21460
Location:781 → 831

HAD_like; Haloacid Dehalogenase-like Hydrolases
NM_001400024.1 → NP_001386953.1 phospholipid-transporting ATPase IA isoform c

Status: REVIEWED

Source sequence(s)

AC084010, AC096734, AC110788, AC139717
NM_001400025.1 → NP_001386954.1 phospholipid-transporting ATPase IA isoform d

Status: REVIEWED

Source sequence(s)

AC084010, AC096734, AC110788, AC139717
NM_001400026.1 → NP_001386955.1 phospholipid-transporting ATPase IA isoform e

Status: REVIEWED

Source sequence(s)

AC084010, AC096734, AC110788, AC139717

Consensus CDS

CCDS93493.1

Related

ENSP00000515003.1, ENST00000700470.1
NM_001400027.1 → NP_001386956.1 phospholipid-transporting ATPase IA isoform f

Status: REVIEWED

Source sequence(s)

AC084010, AC096734, AC110788, AC139717
NM_006095.2 → NP_006086.1 phospholipid-transporting ATPase IA isoform a

See identical proteins and their annotated locations for NP_006086.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (a).

Source sequence(s)

AC084010, AF067820, BP232466

Consensus CDS

CCDS3466.1

UniProtKB/Swiss-Prot

Q32M35, Q32M36, Q4W5J7, Q4W5P2, Q9Y2Q0

UniProtKB/TrEMBL

Q59EX4

Related

ENSP00000371084.5, ENST00000381668.9

Conserved Domains (6) summary

TIGR01652
Location:49 → 1086

ATPase-Plipid; phospholipid-translocating P-type ATPase, flippase

pfam00122
Location:106 → 191

E1-E2_ATPase; E1-E2 ATPase

pfam13246
Location:486 → 581

Cation_ATPase; Cation transport ATPase (P-type)

pfam16209
Location:38 → 100

PhoLip_ATPase_N; Phospholipid-translocating ATPase N-terminal

pfam16212
Location:827 → 1079

PhoLip_ATPase_C; Phospholipid-translocating P-type ATPase C-terminal

cl21460
Location:796 → 846

HAD_like; Haloacid Dehalogenase-like Hydrolases

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000004.12 Reference GRCh38.p14 Primary Assembly

Range

42408373..42657105 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047449508.1 → XP_047305464.1 phospholipid-transporting ATPase IA isoform X3
XM_011513616.3 → XP_011511918.1 phospholipid-transporting ATPase IA isoform X2

UniProtKB/TrEMBL

Q59EX4

Conserved Domains (6) summary

TIGR01652
Location:49 → 1093

ATPase-Plipid; phospholipid-translocating P-type ATPase, flippase

pfam00122
Location:106 → 191

E1-E2_ATPase; E1-E2 ATPase

pfam13246
Location:486 → 581

Cation_ATPase; Cation transport ATPase (P-type)

pfam16209
Location:38 → 100

PhoLip_ATPase_N; Phospholipid-translocating ATPase N-terminal

pfam16212
Location:834 → 1086

PhoLip_ATPase_C; Phospholipid-translocating P-type ATPase C-terminal

cl21460
Location:803 → 853

HAD_like; Haloacid Dehalogenase-like Hydrolases
XM_011513615.2 → XP_011511917.1 phospholipid-transporting ATPase IA isoform X1

UniProtKB/TrEMBL

Q59EX4

Conserved Domains (6) summary

TIGR01652
Location:49 → 1093

ATPase-Plipid; phospholipid-translocating P-type ATPase, flippase

pfam00122
Location:106 → 191

E1-E2_ATPase; E1-E2 ATPase

pfam13246
Location:486 → 581

Cation_ATPase; Cation transport ATPase (P-type)

pfam16209
Location:38 → 100

PhoLip_ATPase_N; Phospholipid-translocating ATPase N-terminal

pfam16212
Location:834 → 1086

PhoLip_ATPase_C; Phospholipid-translocating P-type ATPase C-terminal

cl21460
Location:803 → 853

HAD_like; Haloacid Dehalogenase-like Hydrolases
XM_047449509.1 → XP_047305465.1 phospholipid-transporting ATPase IA isoform X4
XM_047449510.1 → XP_047305466.1 phospholipid-transporting ATPase IA isoform X5
XM_047449511.1 → XP_047305467.1 phospholipid-transporting ATPase IA isoform X6