APLF_MOUSE
ID APLF_MOUSE Reviewed; 499 AA.
AC Q9D842; Q8BZL5; Q99LX6;
DT 16-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2005, sequence version 2.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Aprataxin and PNK-like factor;
DE EC=3.1.-.- {ECO:0000250|UniProtKB:Q8IW19};
DE AltName: Full=Apurinic-apyrimidinic endonuclease APLF;
GN Name=Aplf;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC STRAIN=C57BL/6J; TISSUE=Diencephalon, and Small intestine;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=FVB/N; TISSUE=Mammary gland;
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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-149, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Nuclease involved in single-strand and double-strand DNA
CC break repair. Recruited to sites of DNA damage through interaction with
CC poly(ADP-ribose), a polymeric post-translational modification
CC synthesized transiently at sites of chromosomal damage to accelerate
CC DNA strand break repair reactions. Displays apurinic-apyrimidinic (AP)
CC endonuclease and 3'-5' exonuclease activities in vitro. Also able to
CC introduce nicks at hydroxyuracil and other types of pyrimidine base
CC damage. Together with PARP3, promotes the retention of the LIG4-XRCC4
CC complex on chromatin and accelerate DNA ligation during non-homologous
CC end-joining (NHEJ). {ECO:0000250|UniProtKB:Q8IW19}.
CC -!- SUBUNIT: Interacts with LIG4. Interacts with PARP1. Interacts with
CC XRCC4. Interacts (via KBM motif) with XRCC5 and XRCC6; promoting
CC recruitment to DNA damage sites. Interacts with XRCC1.
CC {ECO:0000250|UniProtKB:Q8IW19}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q8IW19}.
CC Chromosome {ECO:0000250|UniProtKB:Q8IW19}. Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q8IW19}. Note=Localizes to DNA damage sites.
CC Accumulates at single-strand breaks and double-strand breaks via the
CC PBZ-type zinc fingers. {ECO:0000250|UniProtKB:Q8IW19}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9D842-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9D842-2; Sequence=VSP_014983, VSP_014984;
CC Name=3;
CC IsoId=Q9D842-3; Sequence=VSP_014982, VSP_014984;
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:0000250|UniProtKB:Q8IW19}.
CC -!- DOMAIN: The KBM (Ku-binding motif) mediates interaction with XRCC5/Ku80
CC and XRCC6/Ku70 and recruitment to DNA damage sites.
CC {ECO:0000250|UniProtKB:Q8IW19}.
CC -!- DOMAIN: The FHA-like domain mediates interaction with XRCC1 and XRCC4.
CC {ECO:0000250|UniProtKB:Q8IW19}.
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.
CC {ECO:0000250|UniProtKB:Q8IW19}.
CC -!- PTM: Phosphorylated in an ATM-dependent manner upon double-strand DNA
CC break. {ECO:0000250|UniProtKB:Q8IW19}.
CC -!- SIMILARITY: Belongs to the APLF family. {ECO:0000305}.
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DR EMBL; AK008513; BAB25711.1; -; mRNA.
DR EMBL; AK034191; BAC28625.1; -; mRNA.
DR EMBL; BC002179; AAH02179.1; -; mRNA.
DR CCDS; CCDS20324.1; -. [Q9D842-3]
DR CCDS; CCDS51839.1; -. [Q9D842-1]
DR RefSeq; NP_001163960.1; NM_001170489.1. [Q9D842-1]
DR RefSeq; NP_077213.2; NM_024251.4. [Q9D842-3]
DR AlphaFoldDB; Q9D842; -.
DR SMR; Q9D842; -.
DR BioGRID; 215153; 5.
DR STRING; 10090.ENSMUSP00000032130; -.
DR iPTMnet; Q9D842; -.
DR PhosphoSitePlus; Q9D842; -.
DR EPD; Q9D842; -.
DR jPOST; Q9D842; -.
DR MaxQB; Q9D842; -.
DR PaxDb; Q9D842; -.
DR PeptideAtlas; Q9D842; -.
DR PRIDE; Q9D842; -.
DR ProteomicsDB; 296375; -. [Q9D842-1]
DR ProteomicsDB; 296376; -. [Q9D842-2]
DR ProteomicsDB; 296377; -. [Q9D842-3]
DR Antibodypedia; 30942; 270 antibodies from 27 providers.
DR Ensembl; ENSMUST00000032130; ENSMUSP00000032130; ENSMUSG00000030051. [Q9D842-1]
DR Ensembl; ENSMUST00000065997; ENSMUSP00000066232; ENSMUSG00000030051. [Q9D842-3]
DR GeneID; 72103; -.
DR KEGG; mmu:72103; -.
DR UCSC; uc009ctq.2; mouse. [Q9D842-3]
DR UCSC; uc009ctr.2; mouse. [Q9D842-1]
DR UCSC; uc012eon.1; mouse. [Q9D842-2]
DR CTD; 200558; -.
DR MGI; MGI:1919353; Aplf.
DR VEuPathDB; HostDB:ENSMUSG00000030051; -.
DR eggNOG; ENOG502R7QZ; Eukaryota.
DR GeneTree; ENSGT00390000010591; -.
DR HOGENOM; CLU_043152_0_0_1; -.
DR InParanoid; Q9D842; -.
DR OMA; PMKTNLW; -.
DR OrthoDB; 1606181at2759; -.
DR PhylomeDB; Q9D842; -.
DR TreeFam; TF326160; -.
DR BioGRID-ORCS; 72103; 1 hit in 109 CRISPR screens.
DR ChiTaRS; Aplf; mouse.
DR PRO; PR:Q9D842; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q9D842; protein.
DR Bgee; ENSMUSG00000030051; Expressed in otic placode and 163 other tissues.
DR ExpressionAtlas; Q9D842; baseline and differential.
DR Genevisible; Q9D842; MM.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0035861; C:site of double-strand break; ISS:UniProtKB.
DR GO; GO:0008408; F:3'-5' exonuclease activity; ISS:UniProtKB.
DR GO; GO:0003906; F:DNA-(apurinic or apyrimidinic site) endonuclease activity; ISS:UniProtKB.
DR GO; GO:0004520; F:endodeoxyribonuclease activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000166; F:nucleotide binding; ISS:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0006302; P:double-strand break repair; IMP:MGI.
DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; ISS:UniProtKB.
DR GO; GO:0051106; P:positive regulation of DNA ligation; ISO:MGI.
DR GO; GO:0045191; P:regulation of isotype switching; IMP:MGI.
DR GO; GO:0000012; P:single strand break repair; ISS:UniProtKB.
DR CDD; cd00060; FHA; 1.
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 ADP-ribosylation; Alternative splicing; 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..499
FT /note="Aprataxin and PNK-like factor"
FT /id="PRO_0000089343"
FT DOMAIN 1..108
FT /note="FHA-like"
FT ZN_FING 372..393
FT /note="PBZ-type 1"
FT ZN_FING 414..435
FT /note="PBZ-type 2"
FT REGION 134..183
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 197..292
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 305..358
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 401..411
FT /note="Flexible linker"
FT /evidence="ECO:0000250, ECO:0000250|UniProtKB:Q8IW19"
FT REGION 440..499
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 182..191
FT /note="KBM"
FT /evidence="ECO:0000250|UniProtKB:Q8IW19"
FT COMPBIAS 134..162
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 222..249
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 267..281
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 316..351
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 449..485
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 371
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:0000250|UniProtKB:Q8IW19"
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:0000250|UniProtKB:Q8IW19"
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:0000250|UniProtKB:Q8IW19"
FT BINDING 382
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:0000250|UniProtKB:Q8IW19"
FT BINDING 418
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:0000250|UniProtKB:Q8IW19"
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:0000250|UniProtKB:Q8IW19"
FT BINDING 424
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:0000250|UniProtKB:Q8IW19"
FT MOD_RES 116
FT /note="Phosphoserine; by ATM"
FT /evidence="ECO:0000250|UniProtKB:Q8IW19"
FT MOD_RES 149
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 1..108
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_014983"
FT VAR_SEQ 1..32
FT /note="MPSDFFLQPLDGGPRVPVGPGQTVIGRGPLLG -> MPSVPEGGGYE (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_014982"
FT VAR_SEQ 493..499
FT /note="SSLHLKH -> RFMRRKK (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_014984"
FT CONFLICT 178
FT /note="R -> H (in Ref. 2; AAH02179)"
FT /evidence="ECO:0000305"
FT CONFLICT 470
FT /note="S -> F (in Ref. 1; BAB25711)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 499 AA; 54968 MW; 4B41A9C0C8937963 CRC64;
MPSDFFLQPL DGGPRVPVGP GQTVIGRGPL LGITDKRVSR RHAILEVVDS QLRIKPIHRN
PCFYQSSEKS QHSPMETQVW SQLHPGDSFS LLLDKYAFRV FSAESEVEME CTLRNSQMLD
EDDILSEMQK SPVVNLPDKT TGASQLQGSP EITKTKCPTI DPMSSSGECR AFSEHQPRPT
QRKRILPAWM LAESLSDQSL STPAEGGDKD VIQRSGKAGT CEDRTPGNTS WHGKKRLSPS
GNSKSVSAEQ DPGKKCRKAD QEGPGVSSEN VPESSSSNIV KDPDVDIVKT NKQKDGILIE
ELGEVSKHKA ATKPTTNEEG ESCARVQSKS PPEKSQGCHP ESSSAPSSPD ALHTDTADPV
LGCSEESKVR RTACMYGANC YRRNPLHFQH FSHPGDSDYG EVHGTDEGVI GDRPECPYGA
SCYRKNPQHK MEYRHSALPA RVALDEDDDD VGQPSDDEDE EDYEPTDEDS DWHPGKDDEE
QEDVDELLKE AKSSLHLKH
