APLF_HUMAN
ID APLF_HUMAN Reviewed; 511 AA.
AC Q8IW19; A8K476; Q53P47; Q53PB9; Q53QU0;
DT 16-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Aprataxin and PNK-like factor {ECO:0000303|PubMed:17353262};
DE EC=3.1.-.- {ECO:0000269|PubMed:17396150};
DE AltName: Full=Apurinic-apyrimidinic endonuclease APLF {ECO:0000305};
DE AltName: Full=PNK and APTX-like FHA domain-containing protein {ECO:0000303|PubMed:17396150};
DE AltName: Full=XRCC1-interacting protein 1 {ECO:0000303|PubMed:17507382};
GN Name=APLF {ECO:0000303|PubMed:17353262, ECO:0000312|HGNC:HGNC:28724};
GN Synonyms=C2orf13 {ECO:0000312|HGNC:HGNC:28724},
GN PALF {ECO:0000303|PubMed:17396150}, XIP1 {ECO:0000303|PubMed:17507382};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, POLY-ADP-RIBOSYLATION,
RP AND INTERACTION WITH LIG4; PARP1; XRCC4 AND XRCC5.
RX PubMed=17396150; DOI=10.1038/sj.emboj.7601663;
RA Kanno S., Kuzuoka H., Sasao S., Hong Z., Lan L., Nakajima S., Yasui A.;
RT "A novel human AP endonuclease with conserved zinc-finger-like motifs
RT involved in DNA strand break responses.";
RL EMBO J. 26:2094-2103(2007).
RN [5]
RP SUBCELLULAR LOCATION, INTERACTION WITH XRCC1, PHOSPHORYLATION AT SER-116,
RP AND MUTAGENESIS OF SER-116.
RX PubMed=17507382; DOI=10.1074/jbc.c700060200;
RA Bekker-Jensen S., Fugger K., Danielsen J.R., Gromova I., Sehested M.,
RA Celis J., Bartek J., Lukas J., Mailand N.;
RT "Human Xip1 (C2orf13) is a novel regulator of cellular responses to DNA
RT strand breaks.";
RL J. Biol. Chem. 282:19638-19643(2007).
RN [6]
RP FUNCTION, INTERACTION WITH PARP1; XRCC1; XRCC4 AND XRCC5, SUBCELLULAR
RP LOCATION, AND PHOSPHORYLATION.
RX PubMed=17353262; DOI=10.1128/mcb.02269-06;
RA Iles N., Rulten S., El-Khamisy S.F., Caldecott K.W.;
RT "APLF (C2orf13) is a novel human protein involved in the cellular response
RT to chromosomal DNA strand breaks.";
RL Mol. Cell. Biol. 27:3793-3803(2007).
RN [7]
RP INTERACTION WITH XRCC4, AND PHOSPHORYLATION.
RX PubMed=18077224; DOI=10.1016/j.dnarep.2007.10.008;
RA Macrae C.J., McCulloch R.D., Ylanko J., Durocher D., Koch C.A.;
RT "APLF (C2orf13) facilitates nonhomologous end-joining and undergoes ATM-
RT dependent hyperphosphorylation following ionizing radiation.";
RL DNA Repair 7:292-302(2008).
RN [8]
RP SUBCELLULAR LOCATION, AND ADP-RIBOSE-BINDING.
RX PubMed=18474613; DOI=10.1128/mcb.02243-07;
RA Rulten S.L., Cortes-Ledesma F., Guo L., Iles N.J., Caldecott K.W.;
RT "APLF (C2orf13) is a novel component of poly(ADP-ribose) signaling in
RT mammalian cells.";
RL Mol. Cell. Biol. 28:4620-4628(2008).
RN [9]
RP SUBCELLULAR LOCATION, DOMAIN PBZ-TYPE, POLY-ADP-RIBOSYLATION,
RP ADP-RIBOSE-BINDING, AND MUTAGENESIS OF ARG-376; CYS-379; CYS-385; CYS-421
RP AND CYS-427.
RX PubMed=18172500; DOI=10.1038/nature06420;
RA Ahel I., Ahel D., Matsusaka T., Clark A.J., Pines J., Boulton S.J.,
RA West S.C.;
RT "Poly(ADP-ribose)-binding zinc finger motifs in DNA repair/checkpoint
RT proteins.";
RL Nature 451:81-85(2008).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND ADP-RIBOSE-BINDING.
RX PubMed=21211721; DOI=10.1016/j.molcel.2010.12.006;
RA Rulten S.L., Fisher A.E., Robert I., Zuma M.C., Rouleau M., Ju L.,
RA Poirier G., Reina-San-Martin B., Caldecott K.W.;
RT "PARP-3 and APLF function together to accelerate nonhomologous end-
RT joining.";
RL Mol. Cell 41:33-45(2011).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH XRCC5 AND XRCC6, DOMAIN,
RP AND MUTAGENESIS OF ARG-27; 182-ARG--ARG-184; ARG-182; ARG-184;
RP 189-TRP--LEU-191; TRP-189; MET-190 AND LEU-191.
RX PubMed=23689425; DOI=10.1074/jbc.m112.440388;
RA Shirodkar P., Fenton A.L., Meng L., Koch C.A.;
RT "Identification and functional characterization of a Ku-binding motif in
RT aprataxin polynucleotide kinase/phosphatase-like factor (APLF).";
RL J. Biol. Chem. 288:19604-19613(2013).
RN [12]
RP DOMAIN, AND SUBCELLULAR LOCATION.
RX PubMed=27063109; DOI=10.1038/ncomms11242;
RA Grundy G.J., Rulten S.L., Arribas-Bosacoma R., Davidson K., Kozik Z.,
RA Oliver A.W., Pearl L.H., Caldecott K.W.;
RT "The Ku-binding motif is a conserved module for recruitment and stimulation
RT of non-homologous end-joining proteins.";
RL Nat. Commun. 7:11242-11242(2016).
RN [13]
RP STRUCTURE BY NMR OF 368-451 ALONE AND IN COMPLEX WITH ADP-RIBOSE ANALOG,
RP AND POLY-ADP-RIBOSE BINDING SITES.
RX PubMed=20098424; DOI=10.1038/nsmb.1747;
RA Eustermann S., Brockmann C., Mehrotra P.V., Yang J.C., Loakes D.,
RA West S.C., Ahel I., Neuhaus D.;
RT "Solution structures of the two PBZ domains from human APLF and their
RT interaction with poly(ADP-ribose).";
RL Nat. Struct. Mol. Biol. 17:241-243(2010).
RN [14]
RP STRUCTURE BY NMR OF 360-448, LINKER REGION, AND POLY-ADP-RIBOSE BINDING
RP SITES.
RX PubMed=20439749; DOI=10.1073/pnas.1000556107;
RA Li G.Y., McCulloch R.D., Fenton A.L., Cheung M., Meng L., Ikura M.,
RA Koch C.A.;
RT "Structure and identification of ADP-ribose recognition motifs of APLF and
RT role in the DNA damage response.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:9129-9134(2010).
CC -!- FUNCTION: Nuclease involved in single-strand and double-strand DNA
CC break repair (PubMed:17353262, PubMed:17396150). Recruited to sites of
CC DNA damage through interaction with poly(ADP-ribose), a polymeric post-
CC translational modification synthesized transiently at sites of
CC chromosomal damage to accelerate DNA strand break repair reactions
CC (PubMed:17353262, PubMed:17396150, PubMed:21211721). Displays apurinic-
CC apyrimidinic (AP) endonuclease and 3'-5' exonuclease activities in
CC vitro. Also able to introduce nicks at hydroxyuracil and other types of
CC pyrimidine base damage (PubMed:17353262, PubMed:17396150). Together
CC with PARP3, promotes the retention of the LIG4-XRCC4 complex on
CC chromatin and accelerate DNA ligation during non-homologous end-joining
CC (NHEJ) (PubMed:21211721, PubMed:23689425).
CC {ECO:0000269|PubMed:17353262, ECO:0000269|PubMed:17396150,
CC ECO:0000269|PubMed:21211721, ECO:0000269|PubMed:23689425}.
CC -!- SUBUNIT: Interacts with LIG4 (PubMed:17396150). Interacts with PARP1
CC (PubMed:17396150, PubMed:17353262). Interacts with XRCC4
CC (PubMed:17396150, PubMed:17353262, PubMed:18077224). Interacts (via KBM
CC motif) with XRCC5 and XRCC6; promoting recruitment to DNA damage sites
CC (PubMed:17396150, PubMed:17353262, PubMed:23689425). Interacts with
CC XRCC1 (PubMed:17353262, PubMed:17507382). {ECO:0000269|PubMed:17353262,
CC ECO:0000269|PubMed:17396150, ECO:0000269|PubMed:17507382,
CC ECO:0000269|PubMed:18077224, ECO:0000269|PubMed:23689425}.
CC -!- INTERACTION:
CC Q8IW19; Q53SE7: FLJ13057; NbExp=3; IntAct=EBI-1256044, EBI-10172181;
CC Q8IW19; P49917: LIG4; NbExp=3; IntAct=EBI-1256044, EBI-847896;
CC Q8IW19; P09874: PARP1; NbExp=8; IntAct=EBI-1256044, EBI-355676;
CC Q8IW19; P18887: XRCC1; NbExp=11; IntAct=EBI-1256044, EBI-947466;
CC Q8IW19; Q13426: XRCC4; NbExp=5; IntAct=EBI-1256044, EBI-717592;
CC Q8IW19; P13010: XRCC5; NbExp=14; IntAct=EBI-1256044, EBI-357997;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17353262,
CC ECO:0000269|PubMed:17396150, ECO:0000269|PubMed:17507382,
CC ECO:0000269|PubMed:23689425}. Chromosome {ECO:0000269|PubMed:18172500,
CC ECO:0000269|PubMed:18474613, ECO:0000269|PubMed:21211721,
CC ECO:0000269|PubMed:23689425, ECO:0000269|PubMed:27063109}. Cytoplasm,
CC cytosol {ECO:0000269|PubMed:17353262}. Note=Localizes to DNA damage
CC sites (PubMed:18474613, PubMed:18172500, PubMed:21211721,
CC PubMed:23689425). Accumulates at single-strand breaks and double-strand
CC breaks via the PBZ-type zinc fingers (PubMed:18172500).
CC {ECO:0000269|PubMed:18172500, ECO:0000269|PubMed:18474613,
CC ECO:0000269|PubMed:21211721, ECO:0000269|PubMed:23689425}.
CC -!- DOMAIN: The PBZ-type zinc fingers (also named CYR) mediate non-covalent
CC poly(ADP-ribose)-binding. Poly(ADP-ribose)-binding is dependent on the
CC presence of zinc and promotes its recruitment to DNA damage sites.
CC {ECO:0000269|PubMed:18172500}.
CC -!- DOMAIN: The KBM (Ku-binding motif) mediates interaction with XRCC5/Ku80
CC and XRCC6/Ku70 and recruitment to DNA damage sites.
CC {ECO:0000269|PubMed:23689425, ECO:0000269|PubMed:27063109}.
CC -!- DOMAIN: The FHA-like domain mediates interaction with XRCC1 and XRCC4.
CC {ECO:0000269|PubMed:18172500}.
CC -!- PTM: Poly-ADP-ribosylated. In addition to binding non covalently
CC poly(ADP-ribose) via its PBZ-type zinc fingers, the protein is also
CC covalently poly-ADP-ribosylated by PARP1. {ECO:0000269|PubMed:17396150,
CC ECO:0000269|PubMed:18172500}.
CC -!- PTM: Phosphorylated in an ATM-dependent manner upon double-strand DNA
CC break. {ECO:0000269|PubMed:17353262, ECO:0000269|PubMed:17507382,
CC ECO:0000269|PubMed:18077224}.
CC -!- SIMILARITY: Belongs to the APLF family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAY14945.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK290841; BAF83530.1; -; mRNA.
DR EMBL; AC105054; AAY24113.1; -; Genomic_DNA.
DR EMBL; AC127383; AAY24008.1; -; Genomic_DNA.
DR EMBL; AC130709; AAY14945.1; ALT_INIT; Genomic_DNA.
DR EMBL; BC041144; AAH41144.1; -; mRNA.
DR CCDS; CCDS1888.1; -.
DR RefSeq; NP_775816.1; NM_173545.2.
DR PDB; 2KQB; NMR; -; A=368-451.
DR PDB; 2KQC; NMR; -; A=368-451.
DR PDB; 2KQD; NMR; -; A=368-451.
DR PDB; 2KQE; NMR; -; A=368-451.
DR PDB; 2KUO; NMR; -; A=360-448.
DR PDB; 5E50; X-ray; 1.38 A; A/B=1-105.
DR PDB; 5W7W; X-ray; 1.35 A; A/T=1-105.
DR PDB; 5W7X; X-ray; 2.00 A; A/B/C/D=1-105.
DR PDB; 5W7Y; X-ray; 2.10 A; A/B=1-105.
DR PDB; 6ERF; X-ray; 3.01 A; Q/R/S/T=174-191.
DR PDB; 6TYT; X-ray; 2.40 A; C=179-194.
DR PDB; 6TYW; X-ray; 1.70 A; B=179-194.
DR PDB; 6TYZ; X-ray; 1.51 A; B=179-194.
DR PDB; 6YN1; X-ray; 2.35 A; E/J/O/T/Y/d/i/n=449-490.
DR PDBsum; 2KQB; -.
DR PDBsum; 2KQC; -.
DR PDBsum; 2KQD; -.
DR PDBsum; 2KQE; -.
DR PDBsum; 2KUO; -.
DR PDBsum; 5E50; -.
DR PDBsum; 5W7W; -.
DR PDBsum; 5W7X; -.
DR PDBsum; 5W7Y; -.
DR PDBsum; 6ERF; -.
DR PDBsum; 6TYT; -.
DR PDBsum; 6TYW; -.
DR PDBsum; 6TYZ; -.
DR PDBsum; 6YN1; -.
DR AlphaFoldDB; Q8IW19; -.
DR BMRB; Q8IW19; -.
DR SMR; Q8IW19; -.
DR BioGRID; 128334; 41.
DR DIP; DIP-39136N; -.
DR IntAct; Q8IW19; 33.
DR MINT; Q8IW19; -.
DR STRING; 9606.ENSP00000307004; -.
DR GlyGen; Q8IW19; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8IW19; -.
DR PhosphoSitePlus; Q8IW19; -.
DR BioMuta; APLF; -.
DR DMDM; 73619699; -.
DR EPD; Q8IW19; -.
DR jPOST; Q8IW19; -.
DR MassIVE; Q8IW19; -.
DR MaxQB; Q8IW19; -.
DR PaxDb; Q8IW19; -.
DR PeptideAtlas; Q8IW19; -.
DR PRIDE; Q8IW19; -.
DR ProteomicsDB; 70796; -.
DR Antibodypedia; 30942; 270 antibodies from 27 providers.
DR DNASU; 200558; -.
DR Ensembl; ENST00000303795.9; ENSP00000307004.4; ENSG00000169621.10.
DR GeneID; 200558; -.
DR KEGG; hsa:200558; -.
DR MANE-Select; ENST00000303795.9; ENSP00000307004.4; NM_173545.3; NP_775816.1.
DR UCSC; uc002sep.4; human.
DR CTD; 200558; -.
DR DisGeNET; 200558; -.
DR GeneCards; APLF; -.
DR HGNC; HGNC:28724; APLF.
DR HPA; ENSG00000169621; Low tissue specificity.
DR MIM; 611035; gene.
DR neXtProt; NX_Q8IW19; -.
DR OpenTargets; ENSG00000169621; -.
DR PharmGKB; PA164715842; -.
DR VEuPathDB; HostDB:ENSG00000169621; -.
DR eggNOG; ENOG502R7QZ; Eukaryota.
DR GeneTree; ENSGT00390000010591; -.
DR HOGENOM; CLU_043152_0_0_1; -.
DR InParanoid; Q8IW19; -.
DR OrthoDB; 1606181at2759; -.
DR PhylomeDB; Q8IW19; -.
DR TreeFam; TF326160; -.
DR PathwayCommons; Q8IW19; -.
DR SignaLink; Q8IW19; -.
DR BioGRID-ORCS; 200558; 9 hits in 1073 CRISPR screens.
DR ChiTaRS; APLF; human.
DR EvolutionaryTrace; Q8IW19; -.
DR GenomeRNAi; 200558; -.
DR Pharos; Q8IW19; Tbio.
DR PRO; PR:Q8IW19; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q8IW19; protein.
DR Bgee; ENSG00000169621; Expressed in calcaneal tendon and 108 other tissues.
DR ExpressionAtlas; Q8IW19; baseline and differential.
DR Genevisible; Q8IW19; HS.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0035861; C:site of double-strand break; IDA:UniProtKB.
DR GO; GO:0008408; F:3'-5' exonuclease activity; IDA:UniProtKB.
DR GO; GO:0003906; F:DNA-(apurinic or apyrimidinic site) endonuclease activity; IDA:UniProtKB.
DR GO; GO:0004520; F:endodeoxyribonuclease activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000166; F:nucleotide binding; IDA:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0006302; P:double-strand break repair; IMP:UniProtKB.
DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; IMP:UniProtKB.
DR GO; GO:0051106; P:positive regulation of DNA ligation; IGI:MGI.
DR GO; GO:0045191; P:regulation of isotype switching; IEA:Ensembl.
DR GO; GO:0000012; P:single strand break repair; IMP:UniProtKB.
DR CDD; cd00060; FHA; 1.
DR DisProt; DP01465; -.
DR InterPro; IPR039253; APLF.
DR InterPro; IPR019406; APLF_PBZ.
DR InterPro; IPR041388; FHA_2.
DR InterPro; IPR000253; FHA_dom.
DR InterPro; IPR008984; SMAD_FHA_dom_sf.
DR PANTHER; PTHR21315; PTHR21315; 1.
DR Pfam; PF17913; FHA_2; 1.
DR Pfam; PF10283; zf-CCHH; 2.
DR SUPFAM; SSF49879; SSF49879; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ADP-ribosylation; Chromosome; Coiled coil; Cytoplasm;
KW DNA damage; DNA repair; Hydrolase; Metal-binding; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat; Zinc; Zinc-finger.
FT CHAIN 1..511
FT /note="Aprataxin and PNK-like factor"
FT /id="PRO_0000089342"
FT DOMAIN 1..108
FT /note="FHA-like"
FT ZN_FING 377..398
FT /note="PBZ-type 1"
FT ZN_FING 419..440
FT /note="PBZ-type 2"
FT REGION 223..370
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 406..416
FT /note="Flexible linker"
FT /evidence="ECO:0000305|PubMed:20439749"
FT REGION 449..497
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 487..511
FT /evidence="ECO:0000255"
FT MOTIF 182..191
FT /note="KBM"
FT /evidence="ECO:0000269|PubMed:23689425,
FT ECO:0000269|PubMed:27063109"
FT COMPBIAS 224..248
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 249..263
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 264..293
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 299..323
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 324..370
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 465..497
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 376
FT /ligand="a glycoprotein"
FT /ligand_id="ChEBI:CHEBI:17089"
FT /ligand_part="poly[(1''->2')-ADP-alpha-D-ribose] group"
FT /ligand_part_id="ChEBI:CHEBI:157741"
FT /evidence="ECO:0000269|PubMed:18172500"
FT BINDING 381
FT /ligand="a glycoprotein"
FT /ligand_id="ChEBI:CHEBI:17089"
FT /ligand_part="poly[(1''->2')-ADP-alpha-D-ribose] group"
FT /ligand_part_id="ChEBI:CHEBI:157741"
FT /evidence="ECO:0000269|PubMed:18172500"
FT BINDING 386
FT /ligand="a glycoprotein"
FT /ligand_id="ChEBI:CHEBI:17089"
FT /ligand_part="poly[(1''->2')-ADP-alpha-D-ribose] group"
FT /ligand_part_id="ChEBI:CHEBI:157741"
FT /evidence="ECO:0000269|PubMed:18172500"
FT BINDING 387
FT /ligand="a glycoprotein"
FT /ligand_id="ChEBI:CHEBI:17089"
FT /ligand_part="poly[(1''->2')-ADP-alpha-D-ribose] group"
FT /ligand_part_id="ChEBI:CHEBI:157741"
FT /evidence="ECO:0000269|PubMed:18172500"
FT BINDING 423
FT /ligand="a glycoprotein"
FT /ligand_id="ChEBI:CHEBI:17089"
FT /ligand_part="poly[(1''->2')-ADP-alpha-D-ribose] group"
FT /ligand_part_id="ChEBI:CHEBI:157741"
FT /evidence="ECO:0000269|PubMed:18172500"
FT BINDING 428
FT /ligand="a glycoprotein"
FT /ligand_id="ChEBI:CHEBI:17089"
FT /ligand_part="poly[(1''->2')-ADP-alpha-D-ribose] group"
FT /ligand_part_id="ChEBI:CHEBI:157741"
FT /evidence="ECO:0000269|PubMed:18172500"
FT BINDING 429
FT /ligand="a glycoprotein"
FT /ligand_id="ChEBI:CHEBI:17089"
FT /ligand_part="poly[(1''->2')-ADP-alpha-D-ribose] group"
FT /ligand_part_id="ChEBI:CHEBI:157741"
FT /evidence="ECO:0000269|PubMed:18172500"
FT MOD_RES 116
FT /note="Phosphoserine; by ATM"
FT /evidence="ECO:0000269|PubMed:17507382"
FT MOD_RES 149
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9D842"
FT VARIANT 100
FT /note="I -> V (in dbSNP:rs11902811)"
FT /id="VAR_032299"
FT VARIANT 224
FT /note="S -> T (in dbSNP:rs35002937)"
FT /id="VAR_061557"
FT VARIANT 336
FT /note="L -> F (in dbSNP:rs13404469)"
FT /id="VAR_032300"
FT MUTAGEN 27
FT /note="R->A: Does not affect interaction with XRCC5 and
FT XRCC6; decreased ability to promote non-homologous end-
FT joining (NHEJ)."
FT /evidence="ECO:0000269|PubMed:23689425"
FT MUTAGEN 116
FT /note="S->A: Decreases phosphorylation by ATM."
FT /evidence="ECO:0000269|PubMed:17507382"
FT MUTAGEN 182..184
FT /note="RKR->AKA: Abolished interaction with XRCC5 and
FT XRCC6."
FT /evidence="ECO:0000269|PubMed:23689425"
FT MUTAGEN 182
FT /note="R->A: Reduced interaction with XRCC5 and XRCC6;
FT impaired localization to the nucleus."
FT /evidence="ECO:0000269|PubMed:23689425"
FT MUTAGEN 184
FT /note="R->A: Abolished interaction with XRCC5 and XRCC6;
FT impaired localization to the nucleus."
FT /evidence="ECO:0000269|PubMed:23689425"
FT MUTAGEN 189..191
FT /note="WML->AAA: Abolished interaction with XRCC5 and
FT XRCC6."
FT /evidence="ECO:0000269|PubMed:23689425"
FT MUTAGEN 189
FT /note="W->A: Abolished interaction with XRCC5 and XRCC6;
FT impaired localization to the nucleus; decreased ability to
FT promote non-homologous end-joining (NHEJ)."
FT /evidence="ECO:0000269|PubMed:23689425"
FT MUTAGEN 190
FT /note="M->A: Reduced interaction with XRCC5 and XRCC6."
FT /evidence="ECO:0000269|PubMed:23689425"
FT MUTAGEN 191
FT /note="L->A: Does not affect interaction with XRCC5 and
FT XRCC6."
FT /evidence="ECO:0000269|PubMed:23689425"
FT MUTAGEN 376
FT /note="R->A: Abolishes poly(ADP-ribose)-binding and poly-
FT ADP-ribosylation by PARP1; when associated with A-421 and
FT A-427."
FT /evidence="ECO:0000269|PubMed:18172500"
FT MUTAGEN 379
FT /note="C->A: Abolishes poly(ADP-ribose)-binding and poly-
FT ADP-ribosylation by PARP1; when associated with A-385; A-
FT 421 and A-427."
FT /evidence="ECO:0000269|PubMed:18172500"
FT MUTAGEN 385
FT /note="C->A: Abolishes poly(ADP-ribose)-binding and poly-
FT ADP-ribosylation by PARP1; when associated with A-379; A-
FT 421 and A-427."
FT /evidence="ECO:0000269|PubMed:18172500"
FT MUTAGEN 421
FT /note="C->A: Abolishes poly(ADP-ribose)-binding and poly-
FT ADP-ribosylation by PARP1; when associated with A-379; A-
FT 385 and A-427. Abolishes poly(ADP-ribose)-binding and poly-
FT ADP-ribosylation by PARP1; when associated with A-376 and
FT A-427."
FT /evidence="ECO:0000269|PubMed:18172500"
FT MUTAGEN 427
FT /note="C->A: Abolishes poly(ADP-ribose)-binding and poly-
FT ADP-ribosylation by PARP1; when associated with A-379; A-
FT 385 and A-421. Abolishes poly(ADP-ribose)-binding and poly-
FT ADP-ribosylation by PARP1; when associated with A-376 and
FT A-421."
FT /evidence="ECO:0000269|PubMed:18172500"
FT CONFLICT 313
FT /note="Missing (in Ref. 1; BAF83530)"
FT /evidence="ECO:0000305"
FT STRAND 4..9
FT /evidence="ECO:0007829|PDB:5W7W"
FT STRAND 16..18
FT /evidence="ECO:0007829|PDB:5W7W"
FT STRAND 20..28
FT /evidence="ECO:0007829|PDB:5W7W"
FT TURN 29..32
FT /evidence="ECO:0007829|PDB:5W7W"
FT STRAND 43..48
FT /evidence="ECO:0007829|PDB:5W7W"
FT STRAND 51..56
FT /evidence="ECO:0007829|PDB:5W7W"
FT STRAND 58..60
FT /evidence="ECO:0007829|PDB:5W7W"
FT STRAND 63..65
FT /evidence="ECO:0007829|PDB:5W7W"
FT STRAND 81..83
FT /evidence="ECO:0007829|PDB:5E50"
FT STRAND 88..92
FT /evidence="ECO:0007829|PDB:5W7W"
FT STRAND 95..102
FT /evidence="ECO:0007829|PDB:5W7W"
FT HELIX 188..191
FT /evidence="ECO:0007829|PDB:6TYZ"
FT STRAND 371..374
FT /evidence="ECO:0007829|PDB:2KQB"
FT TURN 380..383
FT /evidence="ECO:0007829|PDB:2KQB"
FT HELIX 392..395
FT /evidence="ECO:0007829|PDB:2KQB"
FT TURN 412..414
FT /evidence="ECO:0007829|PDB:2KQB"
FT HELIX 424..426
FT /evidence="ECO:0007829|PDB:2KQC"
FT HELIX 432..437
FT /evidence="ECO:0007829|PDB:2KQC"
SQ SEQUENCE 511 AA; 56956 MW; CBBF0096843298DA CRC64;
MSGGFELQPR DGGPRVALAP GETVIGRGPL LGITDKRVSR RHAILEVAGG QLRIKPIHTN
PCFYQSSEKS QLLPLKPNLW CYLNPGDSFS LLVDKYIFRI LSIPSEVEMQ CTLRNSQVLD
EDNILNETPK SPVINLPHET TGASQLEGST EIAKTQMTPT NSVSFLGENR DCNKQQPILA
ERKRILPTWM LAEHLSDQNL SVPAISGGNV IQGSGKEEIC KDKSQLNTTQ QGRRQLISSG
SSENTSAEQD TGEECKNTDQ EESTISSKEM PQSFSAITLS NTEMNNIKTN AQRNKLPIEE
LGKVSKHKIA TKRTPHKEDE AMSCSENCSS AQGDSLQDES QGSHSESSSN PSNPETLHAK
ATDSVLQGSE GNKVKRTSCM YGANCYRKNP VHFQHFSHPG DSDYGGVQIV GQDETDDRPE
CPYGPSCYRK NPQHKIEYRH NTLPVRNVLD EDNDNVGQPN EYDLNDSFLD DEEEDYEPTD
EDSDWEPGKE DEEKEDVEEL LKEAKRFMKR K
