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 01-MAY-2013, entry version 87.
DE RecName: Full=Aprataxin and PNK-like factor;
DE EC=4.2.99.18;
DE AltName: Full=Apurinic-apyrimidinic endonuclease APLF;
DE AltName: Full=PNK and APTX-like FHA domain-containing protein;
DE AltName: Full=XRCC1-interacting protein 1;
GN Name=APLF; Synonyms=C2orf13, PALF, XIP1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA 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.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA 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.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION,
RP POLY-ADP-RIBOSYLATION, AND INTERACTION WITH LIG4; PARP1; XRCC4 AND
RP XRCC5.
RX PubMed=17396150; DOI=10.1038/sj.emboj.7601663;
RA Kanno S., Kuzuoka H., Sasao S., Hong Z., Lan L., Nakajima S.,
RA 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
RP SER-116, 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
RT DNA 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
RT response 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
RT ATM-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;
RP CYS-421 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 STRUCTURE BY NMR OF 368-451 ALONE AND IN COMPLEX WITH ADP-RIBOSE
RP ANALOG, 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 [11]
RP STRUCTURE BY NMR OF 360-448, LINKER REGION, AND POLY-ADP-RIBOSE
RP BINDING 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
RT and 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. Recruited to sites of DNA damage through interaction
CC with poly(ADP-ribose), a polymeric post-translational modification
CC synthesized transiently at sites of chromosomal damage to
CC accelerate DNA strand break repair reactions. Displays apurinic-
CC apyrimidinic (AP) endonuclease and 3'-5' exonuclease activities in
CC vitro. Also able to introduce nicks at hydroxyuracil and other
CC types of pyrimidine base damage.
CC -!- CATALYTIC ACTIVITY: The C-O-P bond 3' to the apurinic or
CC apyrimidinic site in DNA is broken by a beta-elimination reaction,
CC leaving a 3'-terminal unsaturated sugar and a product with a
CC terminal 5'-phosphate.
CC -!- SUBUNIT: Interacts with LIG4, PARP1, XRCC1, XRCC4 and XRCC5.
CC -!- INTERACTION:
CC P18887:XRCC1; NbExp=7; IntAct=EBI-1256044, EBI-947466;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm, cytosol. Note=Localizes
CC to DNA damage sites. Accumulates at single-strand breaks and
CC double-strand breaks via the PBZ-type zinc fingers.
CC -!- DOMAIN: The PBZ-type zinc fingers (also named CYR) mediate non-
CC covalent poly(ADP-ribose)-binding. Poly(ADP-ribose)-binding is
CC dependent on the presence of zinc and promotes its recruitment to
CC DNA damage sites.
CC -!- DOMAIN: The FHA-like domain mediates interaction with XRCC1 and
CC XRCC4.
CC -!- PTM: Poly-ADP-ribosylated. In addition to binding non covalently
CC poly(ADP-ribose) via its PBZ-type zinc fingers, the protein is
CC also covalently poly-ADP-ribosylated by PARP1.
CC -!- PTM: Phosphorylated in an ATM-dependent manner upon double-strand
CC DNA break.
CC -!- SIMILARITY: Belongs to the APLF family.
CC -!- SIMILARITY: Contains 1 FHA-like domain.
CC -!- SIMILARITY: Contains 2 PBZ-type zinc fingers.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAY14945.1; Type=Erroneous initiation;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
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 IPI; IPI00217108; -.
DR RefSeq; NP_775816.1; NM_173545.2.
DR UniGene; Hs.720369; -.
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 PDBsum; 2KQB; -.
DR PDBsum; 2KQC; -.
DR PDBsum; 2KQD; -.
DR PDBsum; 2KQE; -.
DR PDBsum; 2KUO; -.
DR ProteinModelPortal; Q8IW19; -.
DR DIP; DIP-39136N; -.
DR IntAct; Q8IW19; 3.
DR MINT; MINT-3037419; -.
DR STRING; 9606.ENSP00000307004; -.
DR PhosphoSite; Q8IW19; -.
DR DMDM; 73619699; -.
DR PaxDb; Q8IW19; -.
DR PRIDE; Q8IW19; -.
DR Ensembl; ENST00000303795; ENSP00000307004; ENSG00000169621.
DR GeneID; 200558; -.
DR KEGG; hsa:200558; -.
DR UCSC; uc002sep.3; human.
DR CTD; 200558; -.
DR GeneCards; GC02P068694; -.
DR HGNC; HGNC:28724; APLF.
DR HPA; HPA034643; -.
DR MIM; 611035; gene.
DR neXtProt; NX_Q8IW19; -.
DR PharmGKB; PA164715842; -.
DR eggNOG; NOG85452; -.
DR HOGENOM; HOG000033995; -.
DR HOVERGEN; HBG095728; -.
DR InParanoid; Q8IW19; -.
DR KO; K13295; -.
DR OMA; ECTLRNS; -.
DR OrthoDB; EOG4Q8501; -.
DR PhylomeDB; Q8IW19; -.
DR ChiTaRS; APLF; human.
DR EvolutionaryTrace; Q8IW19; -.
DR GenomeRNAi; 200558; -.
DR NextBio; 89940; -.
DR ArrayExpress; Q8IW19; -.
DR Bgee; Q8IW19; -.
DR CleanEx; HS_APLF; -.
DR Genevestigator; Q8IW19; -.
DR GermOnline; ENSG00000169621; Homo sapiens.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0008408; F:3'-5' exonuclease activity; IDA:UniProtKB.
DR GO; GO:0003906; F:DNA-(apurinic or apyrimidinic site) lyase 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:0006302; P:double-strand break repair; IMP:UniProtKB.
DR GO; GO:0000012; P:single strand break repair; IMP:UniProtKB.
DR Gene3D; 2.60.200.20; -; 1.
DR InterPro; IPR000253; FHA_dom.
DR InterPro; IPR008984; SMAD_FHA_domain.
DR InterPro; IPR019406; Znf_C2H2_APLF-like.
DR Pfam; PF10283; zf-CCHH; 2.
DR SUPFAM; SSF49879; SMAD_FHA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ADP-ribosylation; Coiled coil; Complete proteome;
KW Cytoplasm; DNA damage; DNA repair; Lyase; Metal-binding;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism;
KW Reference proteome; Repeat; Zinc; Zinc-finger.
FT CHAIN 1 511 Aprataxin and PNK-like factor.
FT /FTId=PRO_0000089342.
FT DOMAIN 1 108 FHA-like.
FT ZN_FING 377 398 PBZ-type 1.
FT ZN_FING 419 440 PBZ-type 2.
FT REGION 406 416 Flexible linker.
FT COILED 487 511 Potential.
FT BINDING 376 376 Poly-ADP-ribose.
FT BINDING 381 381 Poly-ADP-ribose.
FT BINDING 386 386 Poly-ADP-ribose.
FT BINDING 387 387 Poly-ADP-ribose.
FT BINDING 423 423 Poly-ADP-ribose.
FT BINDING 428 428 Poly-ADP-ribose.
FT BINDING 429 429 Poly-ADP-ribose.
FT MOD_RES 116 116 Phosphoserine; by ATM.
FT VARIANT 100 100 I -> V (in dbSNP:rs11902811).
FT /FTId=VAR_032299.
FT VARIANT 224 224 S -> T (in dbSNP:rs35002937).
FT /FTId=VAR_061557.
FT VARIANT 336 336 L -> F (in dbSNP:rs13404469).
FT /FTId=VAR_032300.
FT MUTAGEN 116 116 S->A: Decreases phosphorylation by ATM.
FT MUTAGEN 376 376 R->A: Abolishes poly(ADP-ribose)-binding
FT and poly-ADP-ribosylation by PARP1; when
FT associated with A-421 and A-427.
FT MUTAGEN 379 379 C->A: Abolishes poly(ADP-ribose)-binding
FT and poly-ADP-ribosylation by PARP1; when
FT associated with A-385; A-421 and A-427.
FT MUTAGEN 385 385 C->A: Abolishes poly(ADP-ribose)-binding
FT and poly-ADP-ribosylation by PARP1; when
FT associated with A-379; A-421 and A-427.
FT MUTAGEN 421 421 C->A: Abolishes poly(ADP-ribose)-binding
FT and poly-ADP-ribosylation by PARP1; when
FT associated with A-379; A-385 and A-427.
FT Abolishes poly(ADP-ribose)-binding and
FT poly-ADP-ribosylation by PARP1; when
FT associated with A-376 and A-427.
FT MUTAGEN 427 427 C->A: Abolishes poly(ADP-ribose)-binding
FT and poly-ADP-ribosylation by PARP1; when
FT associated with A-379; A-385 and A-421.
FT Abolishes poly(ADP-ribose)-binding and
FT poly-ADP-ribosylation by PARP1; when
FT associated with A-376 and A-421.
FT CONFLICT 313 313 Missing (in Ref. 1; BAF83530).
FT STRAND 371 374
FT TURN 380 383
FT HELIX 392 395
FT TURN 412 414
FT HELIX 424 426
FT HELIX 432 437
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
//
