APLF aprataxin and PNKP like factor [Homo sapiens (human)] - Gene

Summary

Official Symbol: APLFprovided by HGNC
Official Full Name: aprataxin and PNKP like factorprovided by HGNC
Primary source: HGNC:HGNC:28724
See related: Ensembl:ENSG00000169621 MIM:611035; AllianceGenome:HGNC:28724
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: APFL; PALF; Xip1; ZCCHH1; C2orf13
Summary: Enables DNA-(apurinic or apyrimidinic site) endonuclease activity; nuclease activity; and nucleotide binding activity. Involved in double-strand break repair via nonhomologous end joining and single strand break repair. Acts upstream of or within positive regulation of DNA ligation. Located in nucleoplasm. Is active in site of double-strand break. [provided by Alliance of Genome Resources, Apr 2022]
Expression: Ubiquitous expression in testis (RPKM 1.6), skin (RPKM 1.2) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2p13.3

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (68467585..68580162)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (68479947..68592502)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (68694717..68807294)

Chromosome 2 - NC_000002.12 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?

MIR888-dependent inhibition of APLF by E2F1 was demonstrated using overexpression and knockdown experiments, in combination with luciferase assays.
Title: Rewiring E2F1 with classical NHEJ via APLF suppression promotes bladder cancer invasiveness.
The crystal structures of the Ku-binding motifs (KBM) of the non-homologous end joining (NHEJ) proteins APLF (A-KBM) and XLF (X-KBM) bound to a Ku-DNA complex are discussed.
Title: XLF and APLF bind Ku80 at two remote sites to ensure DNA repair by non-homologous end joining.
The acidic domain of APLF is a histone chaperone that can bind both the histone H2A-H2B dimer and H3-H4 tetramer.
Title: DNA repair factor APLF acts as a H2A-H2B histone chaperone through binding its DNA interaction surface.
Data provided novel evidence for enrichment of APLF in breast tumors, which could regulate metastasis-associated epithelial-to-mesenchymal transition in invasive breast cancer.
Title: Enhanced expression of histone chaperone APLF associate with breast cancer.
characterization of the interaction of the APLF FHA domain with phosphorylated XRCC1 peptides
Title: Characterization of the APLF FHA-XRCC1 phosphopeptide interaction and its structural and functional implications.
These data suggest functional requirements for Ku and XRCC4 in APLF-dependent NHEJ and a unique role for Ku as a factor required to facilitate the nuclear retention of APLF.
Title: Identification and functional characterization of a Ku-binding motif in aprataxin polynucleotide kinase/phosphatase-like factor (APLF).
APLF promotes the assembly and activity of multi-protein Ku-DNA complexes containing all of the Non-homologous end joining (NHEJ) factors required for DNA ligation.
Title: APLF promotes the assembly and activity of non-homologous end joining protein complexes.
Polynucleotide kinase and aprataxin-like forkhead-associated protein (PALF) acts as both a single-stranded DNA endonuclease and a single-stranded DNA 3' exonuclease and can participate in DNA end joining in a biochemical system.
Title: Polynucleotide kinase and aprataxin-like forkhead-associated protein (PALF) acts as both a single-stranded DNA endonuclease and a single-stranded DNA 3' exonuclease and can participate in DNA end joining in a biochemical system.
only a positive association (OR=1.58, 95% CI 1.05-2.46, P=0.027) was obtained for XRCC1 (Arg280His
Title: Association studies of OGG1, XRCC1, XRCC2 and XRCC3 polymorphisms with differentiated thyroid cancer.
The poly(ADP-ribose)-regulated protein APLF as a DNA-damage-specific histone chaperone.
Title: DNA repair factor APLF is a histone chaperone.

Submit: New GeneRIF Correction See all GeneRIFs (17)

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
Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci. 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

D2S2874 (e-PCR)
- UniSTS:68124

RH17523 (e-PCR)
- UniSTS:79443

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables 3'-5' exonuclease activity	IDA Inferred from Direct Assay more info	PubMed
enables ADP-D-ribose modification-dependent protein binding	IDA Inferred from Direct Assay more info	PubMed
enables DNA endonuclease activity	IDA Inferred from Direct Assay more info	PubMed
enables DNA-(apurinic or apyrimidinic site) endonuclease activity	IBA Inferred from Biological aspect of Ancestor more info
enables DNA-(apurinic or apyrimidinic site) endonuclease activity	IDA Inferred from Direct Assay more info	PubMed
enables histone binding	IDA Inferred from Direct Assay more info	PubMed
enables histone chaperone activity	IDA Inferred from Direct Assay more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables nucleotide binding	IDA Inferred from Direct Assay more info	PubMed
enables poly-ADP-D-ribose binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein folding chaperone	EXP Inferred from Experiment more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA damage response	IDA Inferred from Direct Assay more info	PubMed
involved_in DNA repair	IDA Inferred from Direct Assay more info	PubMed
involved_in DNA repair-dependent chromatin remodeling	IDA Inferred from Direct Assay more info	PubMed
involved_in double-strand break repair	IBA Inferred from Biological aspect of Ancestor more info
involved_in double-strand break repair	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in double-strand break repair via nonhomologous end joining	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in embryo implantation	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within positive regulation of DNA ligation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in protein folding	IEA Inferred from Electronic Annotation more info
involved_in protein localization to chromatin	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of epithelial to mesenchymal transition	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of isotype switching	IEA Inferred from Electronic Annotation more info
involved_in single strand break repair	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in cytosol	IEA Inferred from Electronic Annotation more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
is_active_in site of DNA damage	IDA Inferred from Direct Assay more info	PubMed
located_in site of DNA damage	IDA Inferred from Direct Assay more info	PubMed
is_active_in site of double-strand break	IBA Inferred from Biological aspect of Ancestor more info
is_active_in site of double-strand break	IDA Inferred from Direct Assay more info	PubMed
located_in site of double-strand break	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: aprataxin and PNK-like factor

Names: PNK and APTX-like FHA domain-containing protein; PNK and APTX-like FHA protein; XRCC1-interacting protein 1; aprataxin- and PNK-like factor; apurinic-apyrimidinic endonuclease APLF; zinc finger, CX5CX6HX5H motif containing 1

NP_775816.1

EC 4.2.99.18

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_173545.3 → NP_775816.1 aprataxin and PNK-like factor

See identical proteins and their annotated locations for NP_775816.1

Status: VALIDATED

Source sequence(s)

BC041144, DA641644

Consensus CDS

CCDS1888.1

UniProtKB/Swiss-Prot

A8K476, Q53P47, Q53PB9, Q53QU0, Q8IW19

Related

ENSP00000307004.4, ENST00000303795.9

Conserved Domains (2) summary

cd00060
Location:21 → 102

FHA; Forkhead associated domain (FHA); found in eukaryotic and prokaryotic proteins. Putative nuclear signalling domain. FHA domains may bind phosphothreonine, phosphoserine and sometimes phosphotyrosine. In eukaryotes, many FHA domain-containing proteins ...

pfam10283
Location:378 → 401

zf-CCHH; Zinc-finger (CX5CX6HX5H) motif