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FLASH GENE

Symbol

ATP13A2

contributors: mct/npt - updated : 23-05-2017

HGNC name	ATPase type 13A2
HGNC id	30213

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	CLN12 ceroid-lipofuscinosis, neuronal, 12 PARK9 Parkinson disease 9 SPG78 spastic paraplegia 78, autosomal recessive
Location	1p36.13      Physical location : 17.312.452 - 17.338.423
Synonym name	putative ATPase
Synonym symbol(s)	HSA9947, RP1-37C10.4, FLJ26510, KRPPD, PARK9, SPG78
EC.number	3.6.3.8

DNA

TYPE	functioning gene
STRUCTURE	25.97 kb     29 Exon(s)

regulatory sequence	Promoter
	Binding site   HRE
text structure	contains hypoxia response elements which can bind to transcription factor hypoxia-inducible factor 1alpha (HIF1A)

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_022089 29 - 3996 NP_071372 130 1180 . localized to lysosomes 2011 21665991 Isoform 1 10 transmembrane domains NM_001141973 29 - 3981 NP_001135445 128 1175 - 2011 21665991 Isoform 2 containing a small five amino acid in-frame deletion near the N-terminus NM_001141974 27 - 3694 NP_001135446 126 1158 . localized to the ER and rapidly degraded 2011 21665991 Isoform 3 contains an additional downstream in-frame deletion of 117 bases and an out-of-frame deletion of 170 bases removing 39 amino acids and generating a highly diverged C-terminus

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive intestine small intestine       Endocrine pancreas       highly Nervous brain midbrain substantia nigra     Homo sapiens   brain       predominantly Homo sapiens   brain forebrain cerebral cortex     Homo sapiens   nerve cranial nerve     highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow     highly

cells

System Cell Pubmed Species Stage Rna symbol Nervous neuron Homo sapiens Nervous pyramidal cell Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

Text

brain

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N-terminal domain of ATP13A2 may hold key regulatory functions , a unique N-terminal hydrophobic extension that lies on the cytosolic membrane surface of the lysosome, where it interacts with the lysosomal signaling lipids phosphatidic acid (PA) and phosphatidylinositol(3,5)bisphosphate [PI(3,5)P2]
	10 transmembrane domains

HOMOLOGY

interspecies

homolog to murine Atp13a2

Homologene

FAMILY	cation transport ATPase (P-type) family
	type V subfamily

CATEGORY

enzyme , transport

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,lumen
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endosome
	intracellular,cytoplasm,organelle,lysosome
	intracellular,cytoplasm,cytosolic,vesicle
text	localized, at least in part, to lysosomes where it may participate in the ATP-dependent transport of cations across vesicular membranes
	localized to a number of acidic vesicular compartments within cortical neurons, particularly lysosomes and endosomes
	normal ATP13A2 localizes in the lysosome, whereas disease-associated variants remain in the endoplasmic reticulum

basic FUNCTION	having a ATPase activity, coupled to transmembrane movement of ions, phosphorylative mechanism
	protein with similarity to P-type ATPases
	regulates mitochondrial bioenergetics through macroautophagy
	is predicted to mediate the transport of heavy metal cations, including cadmium, nickel, manganese and selenium
	role for ATP13A2 in regulating intracellular cation transport
	may play a role in regulating calcium homeostasis
	ATP13A2 is the first Parkinson disease (PD)-associated gene involved in exosome biogenesis
	regulates exosome biogenesis through functional interaction with the endosomal sorting complex required for transport machinery
	implicated in vesicular trafficking
	ATP13A2 expression caused an enlargement of lysosomes and late endosomes
	its overexpression improves the lysosome membrane integrity and protects against the iron-induced cell damage
	ATP13A2 and SYT11 form a new functional network in the regulation of the autophagy-lysosome pathway
	transmembrane endo-/lysosomal-associated P5 type transport ATPase
	activity-independent scaffolding role of ATP13A2 in trafficking/export of intracellular cargo in response to proteotoxic stress

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

text	cation transport

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule	metal binding, nucleotide,
	ATP
	ion Mg2+

protein	regulation of ATP13A2 via EGLN1-HIF1A signaling is critical for cellular iron homeostasis
	endolysosomal protein ATP13A2 can determine the fate of alpha-synuclein (SNCA)

cell & other

REGULATION

Other

hypoxia signaling plays a very important role in the regulation of human ATP13A2 gene expression

ASSOCIATED DISORDERS

corresponding disease(s)

PARK9 , CLN12 , SPG78

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --low   plays a role in SNCA misfolding and toxicity constitutional         silencing of ATP13A2 expression in cortical and dopaminergic neurons promotes basal mitochondrial fragmentation and sensitizes to the effects of cadmium exposure constitutional       loss of function results in zinc dyshomeostasis and mitochondrial dysfunction

Susceptibility

to Parkinson disease

Variant & Polymorphism other	rare variant of the ATP13A2 associated with an increased risk of Parkinson disease among ethnic Chinese in Asia Lin 2008)

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed neurology neurodegenerative Parkinson/dementia Parkinsonism increasing ATP13A2 levels may offer potential therapeutic benefits to patients with Lewy body diseases

ANIMAL & CELL MODELS

Atp13a2(-/-) mice displayed late-onset sensorimotor deficits