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Q8IW19 (APLF_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 93. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:APLF
Synonyms:C2orf13, PALF, XIP1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length511 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.4 Ref.6

Catalytic activity

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. Ref.4

Subunit structure

Interacts with LIG4, PARP1, XRCC1, XRCC4 and XRCC5. Ref.4 Ref.5 Ref.6 Ref.7

Subcellular location

Nucleus. Cytoplasmcytosol. Note: Localizes to DNA damage sites. Accumulates at single-strand breaks and double-strand breaks via the PBZ-type zinc fingers. Ref.4 Ref.5 Ref.6 Ref.8 Ref.9

Domain

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. Ref.9

The FHA-like domain mediates interaction with XRCC1 and XRCC4. Ref.9

Post-translational modification

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. Ref.4 Ref.9

Phosphorylated in an ATM-dependent manner upon double-strand DNA break. Ref.5 Ref.6 Ref.7

Sequence similarities

Belongs to the APLF family.

Contains 1 FHA-like domain.

Contains 2 PBZ-type zinc fingers.

Sequence caution

The sequence AAY14945.1 differs from that shown. Reason: Erroneous initiation.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 511511Aprataxin and PNK-like factor
PRO_0000089342

Regions

Domain1 – 108108FHA-like
Zinc finger377 – 39822PBZ-type 1
Zinc finger419 – 44022PBZ-type 2
Region406 – 41611Flexible linker
Coiled coil487 – 51125 Potential

Sites

Binding site3761Poly-ADP-ribose
Binding site3811Poly-ADP-ribose
Binding site3861Poly-ADP-ribose
Binding site3871Poly-ADP-ribose
Binding site4231Poly-ADP-ribose
Binding site4281Poly-ADP-ribose
Binding site4291Poly-ADP-ribose

Amino acid modifications

Modified residue1161Phosphoserine; by ATM Ref.5

Natural variations

Natural variant1001I → V.
Corresponds to variant rs11902811 [ dbSNP | Ensembl ].
VAR_032299
Natural variant2241S → T.
Corresponds to variant rs35002937 [ dbSNP | Ensembl ].
VAR_061557
Natural variant3361L → F.
Corresponds to variant rs13404469 [ dbSNP | Ensembl ].
VAR_032300

Experimental info

Mutagenesis1161S → A: Decreases phosphorylation by ATM. Ref.5
Mutagenesis3761R → A: Abolishes poly(ADP-ribose)-binding and poly-ADP-ribosylation by PARP1; when associated with A-421 and A-427. Ref.9
Mutagenesis3791C → A: Abolishes poly(ADP-ribose)-binding and poly-ADP-ribosylation by PARP1; when associated with A-385; A-421 and A-427. Ref.9
Mutagenesis3851C → A: Abolishes poly(ADP-ribose)-binding and poly-ADP-ribosylation by PARP1; when associated with A-379; A-421 and A-427. Ref.9
Mutagenesis4211C → 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. Ref.9
Mutagenesis4271C → 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. Ref.9
Sequence conflict3131Missing in BAF83530. Ref.1

Secondary structure

............. 511
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q8IW19 [UniParc].

Last modified March 1, 2003. Version 1.
Checksum: CBBF0096843298DA

FASTA51156,956
        10         20         30         40         50         60 
MSGGFELQPR DGGPRVALAP GETVIGRGPL LGITDKRVSR RHAILEVAGG QLRIKPIHTN 

        70         80         90        100        110        120 
PCFYQSSEKS QLLPLKPNLW CYLNPGDSFS LLVDKYIFRI LSIPSEVEMQ CTLRNSQVLD 

       130        140        150        160        170        180 
EDNILNETPK SPVINLPHET TGASQLEGST EIAKTQMTPT NSVSFLGENR DCNKQQPILA 

       190        200        210        220        230        240 
ERKRILPTWM LAEHLSDQNL SVPAISGGNV IQGSGKEEIC KDKSQLNTTQ QGRRQLISSG 

       250        260        270        280        290        300 
SSENTSAEQD TGEECKNTDQ EESTISSKEM PQSFSAITLS NTEMNNIKTN AQRNKLPIEE 

       310        320        330        340        350        360 
LGKVSKHKIA TKRTPHKEDE AMSCSENCSS AQGDSLQDES QGSHSESSSN PSNPETLHAK 

       370        380        390        400        410        420 
ATDSVLQGSE GNKVKRTSCM YGANCYRKNP VHFQHFSHPG DSDYGGVQIV GQDETDDRPE 

       430        440        450        460        470        480 
CPYGPSCYRK NPQHKIEYRH NTLPVRNVLD EDNDNVGQPN EYDLNDSFLD DEEEDYEPTD 

       490        500        510 
EDSDWEPGKE DEEKEDVEEL LKEAKRFMKR K 

« Hide

References

« Hide 'large scale' references
[1]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Liver.
[2]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Testis.
[4]"A novel human AP endonuclease with conserved zinc-finger-like motifs involved in DNA strand break responses."
Kanno S., Kuzuoka H., Sasao S., Hong Z., Lan L., Nakajima S., Yasui A.
EMBO J. 26:2094-2103(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, POLY-ADP-RIBOSYLATION, INTERACTION WITH LIG4; PARP1; XRCC4 AND XRCC5.
[5]"Human Xip1 (C2orf13) is a novel regulator of cellular responses to DNA strand breaks."
Bekker-Jensen S., Fugger K., Danielsen J.R., Gromova I., Sehested M., Celis J., Bartek J., Lukas J., Mailand N.
J. Biol. Chem. 282:19638-19643(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH XRCC1, PHOSPHORYLATION AT SER-116, MUTAGENESIS OF SER-116.
[6]"APLF (C2orf13) is a novel human protein involved in the cellular response to chromosomal DNA strand breaks."
Iles N., Rulten S., El-Khamisy S.F., Caldecott K.W.
Mol. Cell. Biol. 27:3793-3803(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH PARP1; XRCC1; XRCC4 AND XRCC5, SUBCELLULAR LOCATION, PHOSPHORYLATION.
[7]"APLF (C2orf13) facilitates nonhomologous end-joining and undergoes ATM-dependent hyperphosphorylation following ionizing radiation."
Macrae C.J., McCulloch R.D., Ylanko J., Durocher D., Koch C.A.
DNA Repair 7:292-302(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH XRCC4, PHOSPHORYLATION.
[8]"APLF (C2orf13) is a novel component of poly(ADP-ribose) signaling in mammalian cells."
Rulten S.L., Cortes-Ledesma F., Guo L., Iles N.J., Caldecott K.W.
Mol. Cell. Biol. 28:4620-4628(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, ADP-RIBOSE-BINDING.
[9]"Poly(ADP-ribose)-binding zinc finger motifs in DNA repair/checkpoint proteins."
Ahel I., Ahel D., Matsusaka T., Clark A.J., Pines J., Boulton S.J., West S.C.
Nature 451:81-85(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, DOMAIN PBZ-TYPE, POLY-ADP-RIBOSYLATION, ADP-RIBOSE-BINDING, MUTAGENESIS OF ARG-376; CYS-379; CYS-385; CYS-421 AND CYS-427.
[10]"Solution structures of the two PBZ domains from human APLF and their interaction with poly(ADP-ribose)."
Eustermann S., Brockmann C., Mehrotra P.V., Yang J.C., Loakes D., West S.C., Ahel I., Neuhaus D.
Nat. Struct. Mol. Biol. 17:241-243(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 368-451 ALONE AND IN COMPLEX WITH ADP-RIBOSE ANALOG, POLY-ADP-RIBOSE BINDING SITES.
[11]"Structure and identification of ADP-ribose recognition motifs of APLF and role in the DNA damage response."
Li G.Y., McCulloch R.D., Fenton A.L., Cheung M., Meng L., Ikura M., Koch C.A.
Proc. Natl. Acad. Sci. U.S.A. 107:9129-9134(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 360-448, LINKER REGION, POLY-ADP-RIBOSE BINDING SITES.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_775816.1. NM_173545.2.
UniGeneHs.720369.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2KQBNMR-A368-451[»]
2KQCNMR-A368-451[»]
2KQDNMR-A368-451[»]
2KQENMR-A368-451[»]
2KUONMR-A360-448[»]
ProteinModelPortalQ8IW19.
SMRQ8IW19. Positions 3-101, 359-451.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid128334. 7 interactions.
DIPDIP-39136N.
IntActQ8IW19. 14 interactions.
MINTMINT-3037419.
STRING9606.ENSP00000307004.

PTM databases

PhosphoSiteQ8IW19.

Polymorphism databases

DMDM73619699.

Proteomic databases

PaxDbQ8IW19.
PRIDEQ8IW19.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000303795; ENSP00000307004; ENSG00000169621.
GeneID200558.
KEGGhsa:200558.
UCSCuc002sep.3. human.

Organism-specific databases

CTD200558.
GeneCardsGC02P068694.
HGNCHGNC:28724. APLF.
HPAHPA034642.
HPA034643.
MIM611035. gene.
neXtProtNX_Q8IW19.
PharmGKBPA164715842.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG85452.
HOGENOMHOG000033995.
HOVERGENHBG095728.
InParanoidQ8IW19.
KOK13295.
OMAKRILPAW.
OrthoDBEOG73805W.
PhylomeDBQ8IW19.
TreeFamTF326160.

Gene expression databases

ArrayExpressQ8IW19.
BgeeQ8IW19.
CleanExHS_APLF.
GenevestigatorQ8IW19.

Family and domain databases

Gene3D2.60.200.20. 1 hit.
InterProIPR000253. FHA_dom.
IPR008984. SMAD_FHA_domain.
IPR019406. Znf_C2H2_APLF-like.
[Graphical view]
PfamPF10283. zf-CCHH. 2 hits.
[Graphical view]
SUPFAMSSF49879. SSF49879. 1 hit.
ProtoNetSearch...

Other

ChiTaRSAPLF. human.
EvolutionaryTraceQ8IW19.
GenomeRNAi200558.
NextBio89940.
PROQ8IW19.
SOURCESearch...

Entry information

Entry nameAPLF_HUMAN
AccessionPrimary (citable) accession number: Q8IW19
Secondary accession number(s): A8K476 expand/collapse secondary AC list , Q53P47, Q53PB9, Q53QU0
Entry history
Integrated into UniProtKB/Swiss-Prot: August 16, 2005
Last sequence update: March 1, 2003
Last modified: March 19, 2014
This is version 93 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM