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FLASH GENE

Symbol

APTX

contributors: mct/pgu - updated : 26-11-2010

HGNC name	aprataxin
HGNC id	15984

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	AOA1 ataxia-ocular apraxia 1
Location	9p21.1      Physical location : 32.972.604 - 33.001.639
Synonym name	forkhead-associated domain histidine triad-like protein
Synonym symbol(s)	AOA, EAOH, FLJ20157, AXA1, EOAHA, FHA-HIT, EOAHA, MGC1072
EC.number	3.-.-.-

DNA

TYPE	functioning gene
STRUCTURE	29.02 kb     9 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Binding site
text structure	putative DNA binding site

MAPPING

cloned

Y

linked

Y

status

confirmed

RNA

TRANSCRIPTS	type	messenger

text	three transcripts are not completely described

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_175073 9 - 2116 NP_778243 38.9 342 highly expressed in cerebral cortex and cerebellum, and is largely nuclear 2011 21502511 starting from exon 1 full exon 3 a nuclear localization signal located near the amino terminus isoform a, which lacks this N-terminal extension interacting with ERCC1 NM_001195248 - - 2010 NP_001182177 - 356 - 2006 16439205 also called isoform e NM_175071 8 initiation site 1836 NP_778241 19.6 168 lower expression 2006 16439205 eight exons using a downstream codon initiation, resulting in a protein (isoform d) with a shorter N-terminus compared to isoform a NM_175069 8 - 2046 NP_778239 34.8 306 - 2011 21502511 isoform b using an upstream codon initiation resulting in a protein (isoform b) with distinct N- and C-termini compared to isoform a one of the isoforms that has the putative mitochondrial localization N-terminal signal NM_001195249 - - 2179 NP_001182178 - 342 - 2006 16439205 also called isoform a NM_001195250 - - 1848 NP_001182179 - 302 - 2006 16439205 also called isoform f NM_001195251 - - 2152 NP_001182180 - 292 - 2006 16439205 also called isoform g NM_001195252 - - 1794 NP_001182181 - 284 - 2006 16439205 also called isoform i NM_001195254 - - 1870 NP_001182183 - 288 - 2006 16439205 also called isoform h

EXPRESSION

Type	ubiquitous

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 Cardiovascular heart         Digestive esophagus       highly   liver           salivary gland       highly Endocrine parathyroid       highly Nervous brain hindbrain cerebellum   predominantly Homo sapiens   brain limbic system hippocampus   highly Homo sapiens Reproductive female system uterus cervix   highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal

cells

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

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a N-terminal domain homolog to polynucleotide kinase 3'-phosphatase (PKNT) domain and FHA domain, mediating complex formation with XRCC1-DNA ligase III by interaction with phosphorylated residues in XRCC1 , targeting certain isoforms of the protein to the mitochondrial intracellular compartment
	a nuclear localization signal (NLS)
	a middle region including the histidine triad motif HIT, having enzymatic activity that is negatively regulated by the intramolecular interaction of the N-terminal domain
	one C2H2 type zinc finger
	C-terminal domain implicated in possessing general DNA binding capacity

HOMOLOGY

interspecies	homolog to murine Aptx (87.1pc)
	homolog to rattus Aptx (84.4pc)

Homologene

FAMILY

histidine triad superfamily of nucleotide hydrolases and transferases

CATEGORY

DNA associated

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,mitochondria
	intracellular,nucleus,chromatin/chromosome
	intracellular,nucleus,nucleolus
text	cross-dependence between aprataxin and nucleolin in the nucleolus and its nucleolar localization is dependent on rRNA synthesis
	localizes to mitochondria in human cells
	Purkinje cells had both nuclear and cytoplasmic aprataxin

basic FUNCTION	involved in DNA repair in the nucleolus, through its interactions with deadenylating XRCC1 and/or other components of DNA repair
	influencing the cellular response to genotoxic stress very likely by its capacity to interact with a number of proteins involved in DNA repair
	may have a general proofreading function in DNA repair, removing DNA adenylates as they arise during single-strand break repair, double-strand break repair, and in base excision repair
	having an important and direct role in single-strand break repair, that is, it removes blocking molecules from DNA 3'-ends
	first protein to adopt canonical histidine triad-type reaction chemistry for the repair of DNA
	possesses nick sensor activity, which is ideally suited to locate and repair 5'-DNA adenylates
	direct and indirect modulating functions on base excision repair
	catalyzes removal of adenosine monophosphate (AMP) from the 5 prime end of a DNA strand, which results from an aborted attempt to ligate a strand break containing a damaged end
	having potentially a direct role in mtDNA processing
	plays an important role in the repair of mtDNA and that defects in aprataxin expression and/or function lead to mitochondrial dysfunction and oxidative stress
	role of TDP1 and APTX in mitochondrial DNA repair

CELLULAR PROCESS	cell life, cell death/apoptosis
	nucleotide, repair, base excision repair
	nucleotide, repair, nucleotide excision repair

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

sensory transduction/vision

a component

constitute with XRCC1 a multiprotein complex involved in single-strand DNA break repair

INTERACTION

DNA

binding

RNA

binding

small molecule

protein	interacting with XRCC1, ADPRT, TP53, XRCC4
	interacting with several nucleolar proteins, including nucleolin, nucleophosmin and upstream binding factor-1 (UBF-1), involved in ribosomal RNA (rRNA) synthesis and cellular stress signaling
	interaction with PARP1, APEX1 (synergistic functions of aprataxin, PARP1 and APEX1 in the cellular response to DNA damage and the modulating function of aprataxin on base excision and long patch repair)
	XRCC1 phosphorylation affects APTX recruitment and DNA deadenylation activity

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

AOA1

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --low   result in mitochondrial dysfunction and an accumulation of mtDNA damage

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

aprataxin resolves abortive DNA ligation intermediates in Aptrx-/- mouse primary neural cells