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Protein

Aprataxin and PNK-like factor

Gene

APLF

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Nuclease involved in single-strand and double-strand DNA break repair. Recruited to sites of DNA damage through interaction with poly(ADP-ribose), a polymeric post-translational modification synthesized transiently at sites of chromosomal damage to accelerate DNA strand break repair reactions. Displays apurinic-apyrimidinic (AP) endonuclease and 3'-5' exonuclease activities in vitro. Also able to introduce nicks at hydroxyuracil and other types of pyrimidine base damage.2 Publications

Catalytic activityi

The C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei376Poly-ADP-ribose1
Binding sitei381Poly-ADP-ribose1
Binding sitei386Poly-ADP-ribose1
Binding sitei387Poly-ADP-ribose1
Binding sitei423Poly-ADP-ribose1
Binding sitei428Poly-ADP-ribose1
Binding sitei429Poly-ADP-ribose1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri377 – 398PBZ-type 1Add BLAST22
Zinc fingeri419 – 440PBZ-type 2Add BLAST22

GO - Molecular functioni

GO - Biological processi

  • cellular response to DNA damage stimulus Source: UniProtKB
  • double-strand break repair Source: UniProtKB
  • positive regulation of DNA ligation Source: MGI
  • regulation of isotype switching Source: Ensembl
  • single strand break repair Source: UniProtKB

Keywordsi

Molecular functionLyase
Biological processDNA damage, DNA repair
LigandMetal-binding, Nucleotide-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Aprataxin and PNK-like factor (EC:4.2.99.18)
Alternative name(s):
Apurinic-apyrimidinic endonuclease APLF
PNK and APTX-like FHA domain-containing protein
XRCC1-interacting protein 1
Gene namesi
Name:APLF
Synonyms:C2orf13, PALF, XIP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000169621.9
HGNCiHGNC:28724 APLF
MIMi611035 gene
neXtProtiNX_Q8IW19

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi116S → A: Decreases phosphorylation by ATM. 1 Publication1
Mutagenesisi376R → A: Abolishes poly(ADP-ribose)-binding and poly-ADP-ribosylation by PARP1; when associated with A-421 and A-427. 1 Publication1
Mutagenesisi379C → A: Abolishes poly(ADP-ribose)-binding and poly-ADP-ribosylation by PARP1; when associated with A-385; A-421 and A-427. 1 Publication1
Mutagenesisi385C → A: Abolishes poly(ADP-ribose)-binding and poly-ADP-ribosylation by PARP1; when associated with A-379; A-421 and A-427. 1 Publication1
Mutagenesisi421C → A: Abolishes poly(ADP-ribose)-binding and poly-ADP-ribosylation by PARP1; when associated with A-379; A-385 and A-427. Abolishes poly(ADP-ribose)-binding and poly-ADP-ribosylation by PARP1; when associated with A-376 and A-427. 1 Publication1
Mutagenesisi427C → A: Abolishes poly(ADP-ribose)-binding and poly-ADP-ribosylation by PARP1; when associated with A-379; A-385 and A-421. Abolishes poly(ADP-ribose)-binding and poly-ADP-ribosylation by PARP1; when associated with A-376 and A-421. 1 Publication1

Organism-specific databases

DisGeNETi200558
OpenTargetsiENSG00000169621
PharmGKBiPA164715842

Polymorphism and mutation databases

BioMutaiAPLF
DMDMi73619699

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000893421 – 511Aprataxin and PNK-like factorAdd BLAST511

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei116Phosphoserine; by ATM1 Publication1
Modified residuei149PhosphoserineBy similarity1

Post-translational modificationi

Poly-ADP-ribosylated. In addition to binding non covalently poly(ADP-ribose) via its PBZ-type zinc fingers, the protein is also covalently poly-ADP-ribosylated by PARP1.
Phosphorylated in an ATM-dependent manner upon double-strand DNA break.3 Publications

Keywords - PTMi

ADP-ribosylation, Phosphoprotein

Proteomic databases

EPDiQ8IW19
MaxQBiQ8IW19
PaxDbiQ8IW19
PeptideAtlasiQ8IW19
PRIDEiQ8IW19
ProteomicsDBi70796

PTM databases

iPTMnetiQ8IW19
PhosphoSitePlusiQ8IW19

Expressioni

Gene expression databases

BgeeiENSG00000169621 Expressed in 116 organ(s), highest expression level in corpus callosum
CleanExiHS_APLF
ExpressionAtlasiQ8IW19 baseline and differential
GenevisibleiQ8IW19 HS

Organism-specific databases

HPAiHPA034642
HPA034643

Interactioni

Subunit structurei

Interacts with LIG4, PARP1, XRCC1, XRCC4 and XRCC5.5 Publications

Binary interactionsi

Protein-protein interaction databases

BioGridi128334, 33 interactors
DIPiDIP-39136N
IntActiQ8IW19, 15 interactors
MINTiQ8IW19
STRINGi9606.ENSP00000307004

Structurei

Secondary structure

1511
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ8IW19
SMRiQ8IW19
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ8IW19

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 108FHA-likeAdd BLAST108

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni406 – 416Flexible linkerAdd BLAST11

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili487 – 511Sequence analysisAdd BLAST25

Domaini

The PBZ-type zinc fingers (also named CYR) mediate non-covalent poly(ADP-ribose)-binding. Poly(ADP-ribose)-binding is dependent on the presence of zinc and promotes its recruitment to DNA damage sites.1 Publication
The FHA-like domain mediates interaction with XRCC1 and XRCC4.1 Publication

Sequence similaritiesi

Belongs to the APLF family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri377 – 398PBZ-type 1Add BLAST22
Zinc fingeri419 – 440PBZ-type 2Add BLAST22

Keywords - Domaini

Coiled coil, Repeat, Zinc-finger

Phylogenomic databases

eggNOGiENOG410IGNB Eukaryota
ENOG41126IA LUCA
GeneTreeiENSGT00390000010591
HOGENOMiHOG000033995
HOVERGENiHBG095728
InParanoidiQ8IW19
KOiK13295
OrthoDBiEOG091G0QER
PhylomeDBiQ8IW19
TreeFamiTF326160

Family and domain databases

CDDicd00060 FHA, 1 hit
InterProiView protein in InterPro
IPR039253 APLF
IPR000253 FHA_dom
IPR008984 SMAD_FHA_dom_sf
IPR019406 Znf_C2H2_APLF-like
PANTHERiPTHR21315 PTHR21315, 1 hit
PfamiView protein in Pfam
PF10283 zf-CCHH, 2 hits
SUPFAMiSSF49879 SSF49879, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.iShow all

Q8IW19-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MSGGFELQPR DGGPRVALAP GETVIGRGPL LGITDKRVSR RHAILEVAGG
60 70 80 90 100
QLRIKPIHTN PCFYQSSEKS QLLPLKPNLW CYLNPGDSFS LLVDKYIFRI
110 120 130 140 150
LSIPSEVEMQ CTLRNSQVLD EDNILNETPK SPVINLPHET TGASQLEGST
160 170 180 190 200
EIAKTQMTPT NSVSFLGENR DCNKQQPILA ERKRILPTWM LAEHLSDQNL
210 220 230 240 250
SVPAISGGNV IQGSGKEEIC KDKSQLNTTQ QGRRQLISSG SSENTSAEQD
260 270 280 290 300
TGEECKNTDQ EESTISSKEM PQSFSAITLS NTEMNNIKTN AQRNKLPIEE
310 320 330 340 350
LGKVSKHKIA TKRTPHKEDE AMSCSENCSS AQGDSLQDES QGSHSESSSN
360 370 380 390 400
PSNPETLHAK ATDSVLQGSE GNKVKRTSCM YGANCYRKNP VHFQHFSHPG
410 420 430 440 450
DSDYGGVQIV GQDETDDRPE CPYGPSCYRK NPQHKIEYRH NTLPVRNVLD
460 470 480 490 500
EDNDNVGQPN EYDLNDSFLD DEEEDYEPTD EDSDWEPGKE DEEKEDVEEL
510
LKEAKRFMKR K
Length:511
Mass (Da):56,956
Last modified:March 1, 2003 - v1
Checksum:iCBBF0096843298DA
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F8WET0F8WET0_HUMAN
Aprataxin and PNK-like factor
APLF
280Annotation score:
E9PRH6E9PRH6_HUMAN
Aprataxin and PNK-like factor
APLF
185Annotation score:

Sequence cautioni

The sequence AAY14945 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti313Missing in BAF83530 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_032299100I → V. Corresponds to variant dbSNP:rs11902811Ensembl.1
Natural variantiVAR_061557224S → T. Corresponds to variant dbSNP:rs35002937Ensembl.1
Natural variantiVAR_032300336L → F. Corresponds to variant dbSNP:rs13404469Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK290841 mRNA Translation: BAF83530.1
AC105054 Genomic DNA Translation: AAY24113.1
AC127383 Genomic DNA Translation: AAY24008.1
AC130709 Genomic DNA Translation: AAY14945.1 Different initiation.
BC041144 mRNA Translation: AAH41144.1
CCDSiCCDS1888.1
RefSeqiNP_775816.1, NM_173545.2
UniGeneiHs.720369

Genome annotation databases

EnsembliENST00000303795; ENSP00000307004; ENSG00000169621
GeneIDi200558
KEGGihsa:200558
UCSCiuc002sep.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiAPLF_HUMAN
AccessioniPrimary (citable) accession number: Q8IW19
Secondary accession number(s): A8K476
, Q53P47, Q53PB9, Q53QU0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 16, 2005
Last sequence update: March 1, 2003
Last modified: September 12, 2018
This is version 128 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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