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Protein

Aprataxin and PNK-like factor

Gene

APLF

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

  • 3'-5' exonuclease activity Source: UniProtKB
  • DNA-(apurinic or apyrimidinic site) lyase activity Source: UniProtKB
  • endodeoxyribonuclease activity Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • nucleotide binding Source: UniProtKB

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
Complete GO annotation...

Keywords - Molecular functioni

Lyase

Keywords - Biological processi

DNA damage, DNA repair

Keywords - Ligandi

Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:HS15795-MONOMER.

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

HGNCiHGNC:28724. APLF.

Subcellular locationi

  • Nucleus
  • Cytoplasmcytosol

  • Note: Localizes to DNA damage sites. Accumulates at single-strand breaks and double-strand breaks via the PBZ-type zinc fingers.

GO - Cellular componenti

  • cytosol Source: UniProtKB-SubCell
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
  • site of double-strand break Source: MGI
Complete GO annotation...

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

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.

PTM databases

iPTMnetiQ8IW19.
PhosphoSitePlusiQ8IW19.

Expressioni

Gene expression databases

BgeeiENSG00000169621.
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

WithEntry#Exp.IntActNotes
FLJ13057Q53SE73EBI-1256044,EBI-10172181
LIG4P499172EBI-1256044,EBI-847896
PARP1P098743EBI-1256044,EBI-355676
XRCC1P1888710EBI-1256044,EBI-947466
XRCC4Q134264EBI-1256044,EBI-717592
XRCC5P1301012EBI-1256044,EBI-357997

Protein-protein interaction databases

BioGridi128334. 32 interactors.
DIPiDIP-39136N.
IntActiQ8IW19. 15 interactors.
MINTiMINT-3037419.
STRINGi9606.ENSP00000307004.

Structurei

Secondary structure

1511
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi4 – 9Combined sources6
Beta strandi20 – 28Combined sources9
Turni29 – 32Combined sources4
Beta strandi43 – 48Combined sources6
Beta strandi51 – 56Combined sources6
Beta strandi58 – 60Combined sources3
Beta strandi63 – 65Combined sources3
Beta strandi81 – 83Combined sources3
Beta strandi88 – 92Combined sources5
Beta strandi95 – 103Combined sources9
Beta strandi371 – 374Combined sources4
Turni380 – 383Combined sources4
Helixi392 – 395Combined sources4
Turni412 – 414Combined sources3
Helixi424 – 426Combined sources3
Helixi432 – 437Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2KQBNMR-A368-451[»]
2KQCNMR-A368-451[»]
2KQDNMR-A368-451[»]
2KQENMR-A368-451[»]
2KUONMR-A360-448[»]
5E50X-ray1.38A/B1-105[»]
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
Contains 1 FHA-like domain.Curated
Contains 2 PBZ-type zinc fingers.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

Gene3Di2.60.200.20. 1 hit.
InterProiIPR000253. FHA_dom.
IPR008984. SMAD_FHA_domain.
IPR019406. Znf_C2H2_APLF-like.
[Graphical view]
PfamiPF10283. zf-CCHH. 2 hits.
[Graphical view]
SUPFAMiSSF49879. SSF49879. 1 hit.

Sequencei

Sequence statusi: Complete.

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

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 rs11902811dbSNPEnsembl.1
Natural variantiVAR_061557224S → T.Corresponds to variant rs35002937dbSNPEnsembl.1
Natural variantiVAR_032300336L → F.Corresponds to variant rs13404469dbSNPEnsembl.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

Cross-referencesi

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2KQBNMR-A368-451[»]
2KQCNMR-A368-451[»]
2KQDNMR-A368-451[»]
2KQENMR-A368-451[»]
2KUONMR-A360-448[»]
5E50X-ray1.38A/B1-105[»]
ProteinModelPortaliQ8IW19.
SMRiQ8IW19.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi128334. 32 interactors.
DIPiDIP-39136N.
IntActiQ8IW19. 15 interactors.
MINTiMINT-3037419.
STRINGi9606.ENSP00000307004.

PTM databases

iPTMnetiQ8IW19.
PhosphoSitePlusiQ8IW19.

Polymorphism and mutation databases

BioMutaiAPLF.
DMDMi73619699.

Proteomic databases

EPDiQ8IW19.
MaxQBiQ8IW19.
PaxDbiQ8IW19.
PeptideAtlasiQ8IW19.
PRIDEiQ8IW19.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi200558.
GeneCardsiAPLF.
HGNCiHGNC:28724. APLF.
HPAiHPA034642.
HPA034643.
MIMi611035. gene.
neXtProtiNX_Q8IW19.
OpenTargetsiENSG00000169621.
PharmGKBiPA164715842.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:HS15795-MONOMER.

Miscellaneous databases

ChiTaRSiAPLF. human.
EvolutionaryTraceiQ8IW19.
GenomeRNAii200558.
PROiQ8IW19.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000169621.
CleanExiHS_APLF.
ExpressionAtlasiQ8IW19. baseline and differential.
GenevisibleiQ8IW19. HS.

Family and domain databases

Gene3Di2.60.200.20. 1 hit.
InterProiIPR000253. FHA_dom.
IPR008984. SMAD_FHA_domain.
IPR019406. Znf_C2H2_APLF-like.
[Graphical view]
PfamiPF10283. zf-CCHH. 2 hits.
[Graphical view]
SUPFAMiSSF49879. SSF49879. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiAPLF_HUMAN
AccessioniPrimary (citable) accession number: Q8IW19
Secondary accession number(s): A8K476
, Q53P47, Q53PB9, Q53QU0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 16, 2005
Last sequence update: March 1, 2003
Last modified: November 2, 2016
This is version 116 of the entry and version 1 of the sequence. [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

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.