PNKP_MOUSE
ID PNKP_MOUSE Reviewed; 522 AA.
AC Q9JLV6; Q6PFA3;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2004, sequence version 2.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Bifunctional polynucleotide phosphatase/kinase;
DE AltName: Full=DNA 5'-kinase/3'-phosphatase;
DE AltName: Full=Polynucleotide kinase-3'-phosphatase;
DE Includes:
DE RecName: Full=Polynucleotide 3'-phosphatase;
DE EC=3.1.3.32;
DE AltName: Full=2'(3')-polynucleotidase;
DE Includes:
DE RecName: Full=Polynucleotide 5'-hydroxyl-kinase;
DE EC=2.7.1.78;
GN Name=Pnkp;
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 [MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Spleen;
RA Beaulieu N., Lasko D.D.;
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Mammary tumor;
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 THR-122, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Lung, 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).
RN [5]
RP STRUCTURE BY NMR OF 1-106.
RG RIKEN structural genomics initiative (RSGI);
RT "The forkhead-associated (FHA) domain-like structure from mouse
RT polynucleotide kinase 3'-phosphatase.";
RL Submitted (FEB-2004) to the PDB data bank.
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS), DOMAIN ARCHITECTURE, MUTAGENESIS OF
RP ARG-44; LYS-45 AND ARG-48, FHA DOMAIN, AND SUBUNIT.
RX PubMed=15749016; DOI=10.1016/j.molcel.2005.02.012;
RA Bernstein N.K., Williams R.S., Rakovszky M.L., Cui D., Green R.,
RA Karimi-Busheri F., Mani R.S., Galicia S., Koch C.A., Cass C.E.,
RA Durocher D., Weinfeld M., Glover J.N.;
RT "The molecular architecture of the mammalian DNA repair enzyme,
RT polynucleotide kinase.";
RL Mol. Cell 17:657-670(2005).
CC -!- FUNCTION: Plays a key role in the repair of DNA damage, functioning as
CC part of both the non-homologous end-joining (NHEJ) and base excision
CC repair (BER) pathways. Through its two catalytic activities, PNK
CC ensures that DNA termini are compatible with extension and ligation by
CC either removing 3'-phosphates from, or by phosphorylating 5'-hydroxyl
CC groups on, the ribose sugar of the DNA backbone.
CC {ECO:0000250|UniProtKB:Q96T60}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 3'end (2'-deoxyribonucleotide 3'-phosphate)-DNA + H2O = a
CC 3'-end 2'-deoxyribonucleotide-DNA + phosphate; Xref=Rhea:RHEA:14113,
CC Rhea:RHEA-COMP:13863, Rhea:RHEA-COMP:13864, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:138147, ChEBI:CHEBI:138148;
CC EC=3.1.3.32; Evidence={ECO:0000250|UniProtKB:Q96T60};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 5'-end dephospho-2'-deoxyribonucleoside-DNA + ATP = a 5'-end
CC 5'-monophospho-2'-deoxyribonucleoside-DNA + ADP + H(+);
CC Xref=Rhea:RHEA:15669, Rhea:RHEA-COMP:13180, Rhea:RHEA-COMP:13184,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:136412,
CC ChEBI:CHEBI:136416, ChEBI:CHEBI:456216; EC=2.7.1.78;
CC Evidence={ECO:0000250|UniProtKB:Q96T60};
CC -!- SUBUNIT: Monomer (PubMed:15749016). Interacts (via FHA domain) with
CC XRCC4; mainly interacts with XRCC4 phosphorylated by CK2 but is also
CC able to interact at much lower level with unphosphorylated PNKP (By
CC similarity). {ECO:0000250|UniProtKB:Q96T60,
CC ECO:0000269|PubMed:15749016}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q96T60}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9JLV6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9JLV6-2; Sequence=VSP_010771;
CC -!- DOMAIN: The FHA domain binds threonine-phosphorylated peptides from
CC XRCC1/4, and is responsible for the recruitment of PNKP to the sites of
CC DNA repair. The affinity is ten times greater if peptides are also
CC phosphorylated on the serine preceeding the phosphothreonine.
CC {ECO:0000269|PubMed:15749016}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the DNA 3'
CC phosphatase family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF129451; AAF36487.1; -; mRNA.
DR EMBL; BC057659; AAH57659.1; -; mRNA.
DR CCDS; CCDS39945.1; -. [Q9JLV6-1]
DR PDB; 1UJX; NMR; -; A=1-106.
DR PDB; 1YJ5; X-ray; 2.80 A; A/B=140-522, C=1-143.
DR PDB; 1YJM; X-ray; 2.20 A; A/B/C=1-110.
DR PDB; 3U7E; X-ray; 1.70 A; B=142-522.
DR PDB; 3U7F; X-ray; 1.80 A; B=142-522.
DR PDB; 3U7G; X-ray; 2.10 A; A=144-522.
DR PDB; 3U7H; X-ray; 2.00 A; B=142-522.
DR PDB; 3ZVL; X-ray; 1.65 A; A=111-522.
DR PDB; 3ZVM; X-ray; 2.00 A; A/B=111-522.
DR PDB; 3ZVN; X-ray; 2.15 A; A=111-522.
DR PDBsum; 1UJX; -.
DR PDBsum; 1YJ5; -.
DR PDBsum; 1YJM; -.
DR PDBsum; 3U7E; -.
DR PDBsum; 3U7F; -.
DR PDBsum; 3U7G; -.
DR PDBsum; 3U7H; -.
DR PDBsum; 3ZVL; -.
DR PDBsum; 3ZVM; -.
DR PDBsum; 3ZVN; -.
DR AlphaFoldDB; Q9JLV6; -.
DR BMRB; Q9JLV6; -.
DR SMR; Q9JLV6; -.
DR IntAct; Q9JLV6; 1.
DR STRING; 10090.ENSMUSP00000003044; -.
DR ChEMBL; CHEMBL4523466; -.
DR iPTMnet; Q9JLV6; -.
DR PhosphoSitePlus; Q9JLV6; -.
DR EPD; Q9JLV6; -.
DR jPOST; Q9JLV6; -.
DR MaxQB; Q9JLV6; -.
DR PaxDb; Q9JLV6; -.
DR PeptideAtlas; Q9JLV6; -.
DR PRIDE; Q9JLV6; -.
DR ProteomicsDB; 289709; -. [Q9JLV6-1]
DR ProteomicsDB; 289710; -. [Q9JLV6-2]
DR UCSC; uc012fjx.1; mouse. [Q9JLV6-1]
DR MGI; MGI:1891698; Pnkp.
DR eggNOG; KOG2134; Eukaryota.
DR InParanoid; Q9JLV6; -.
DR PhylomeDB; Q9JLV6; -.
DR BRENDA; 2.7.1.78; 3474.
DR BRENDA; 3.1.3.32; 3474.
DR Reactome; R-MMU-5649702; APEX1-Independent Resolution of AP Sites via the Single Nucleotide Replacement Pathway.
DR EvolutionaryTrace; Q9JLV6; -.
DR PRO; PR:Q9JLV6; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q9JLV6; protein.
DR GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0019005; C:SCF ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0035861; C:site of double-strand break; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003690; F:double-stranded DNA binding; IBA:GO_Central.
DR GO; GO:0046404; F:polydeoxyribonucleotide 5'-hydroxyl-kinase activity; ISO:MGI.
DR GO; GO:0046403; F:polynucleotide 3'-phosphatase activity; ISO:MGI.
DR GO; GO:1990756; F:ubiquitin ligase-substrate adaptor activity; IDA:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0051103; P:DNA ligation involved in DNA repair; ISS:UniProtKB.
DR GO; GO:0006281; P:DNA repair; ISO:MGI.
DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; ISS:UniProtKB.
DR GO; GO:0010836; P:negative regulation of protein ADP-ribosylation; ISO:MGI.
DR GO; GO:0046939; P:nucleotide phosphorylation; ISO:MGI.
DR GO; GO:2001034; P:positive regulation of double-strand break repair via nonhomologous end joining; ISO:MGI.
DR GO; GO:0051973; P:positive regulation of telomerase activity; ISO:MGI.
DR GO; GO:1904355; P:positive regulation of telomere capping; ISO:MGI.
DR GO; GO:0032212; P:positive regulation of telomere maintenance via telomerase; ISO:MGI.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0006979; P:response to oxidative stress; ISO:MGI.
DR Gene3D; 3.40.50.1000; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR041388; FHA_2.
DR InterPro; IPR036412; HAD-like_sf.
DR InterPro; IPR006549; HAD-SF_hydro_IIIA.
DR InterPro; IPR023214; HAD_sf.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR013954; PNK3P.
DR InterPro; IPR006550; PNKP.
DR InterPro; IPR006551; Polynucleotide_phosphatase.
DR InterPro; IPR008984; SMAD_FHA_dom_sf.
DR Pfam; PF17913; FHA_2; 1.
DR Pfam; PF08645; PNK3P; 1.
DR SUPFAM; SSF49879; SSF49879; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
DR TIGRFAMs; TIGR01664; DNA-3'-Pase; 1.
DR TIGRFAMs; TIGR01662; HAD-SF-IIIA; 1.
DR TIGRFAMs; TIGR01663; PNK-3'Pase; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; DNA damage;
KW DNA repair; Hydrolase; Kinase; Multifunctional enzyme; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..522
FT /note="Bifunctional polynucleotide phosphatase/kinase"
FT /id="PRO_0000058479"
FT DOMAIN 6..110
FT /note="FHA"
FT REGION 110..142
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 145..336
FT /note="Phosphatase"
FT /evidence="ECO:0000303|PubMed:15749016"
FT REGION 340..517
FT /note="Kinase"
FT /evidence="ECO:0000303|PubMed:15749016"
FT BINDING 371..378
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q96T60"
FT MOD_RES 114
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96T60"
FT MOD_RES 122
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17525332"
FT VAR_SEQ 163..191
FT /note="QGKVAAFDLDGTLITTRSGKVFPTSPSDW -> RA (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_010771"
FT MUTAGEN 44
FT /note="R->A: Abrogates phosphopeptide recognition."
FT /evidence="ECO:0000269|PubMed:15749016"
FT MUTAGEN 45
FT /note="K->N: No effect on phosphopeptide recognition."
FT /evidence="ECO:0000269|PubMed:15749016"
FT MUTAGEN 48
FT /note="R->A: Abrogates phosphopeptide recognition."
FT /evidence="ECO:0000269|PubMed:15749016"
FT CONFLICT 77
FT /note="H -> Q (in Ref. 1; AAF36487)"
FT /evidence="ECO:0000305"
FT CONFLICT 216
FT /note="Missing (in Ref. 1; AAF36487)"
FT /evidence="ECO:0000305"
FT STRAND 6..13
FT /evidence="ECO:0007829|PDB:1YJM"
FT STRAND 16..18
FT /evidence="ECO:0007829|PDB:1UJX"
FT TURN 26..28
FT /evidence="ECO:0007829|PDB:1YJ5"
FT STRAND 31..36
FT /evidence="ECO:0007829|PDB:1YJM"
FT TURN 37..40
FT /evidence="ECO:0007829|PDB:1YJM"
FT STRAND 44..46
FT /evidence="ECO:0007829|PDB:1YJ5"
FT STRAND 51..56
FT /evidence="ECO:0007829|PDB:1YJM"
FT TURN 57..60
FT /evidence="ECO:0007829|PDB:1YJM"
FT STRAND 61..66
FT /evidence="ECO:0007829|PDB:1YJM"
FT STRAND 68..70
FT /evidence="ECO:0007829|PDB:1YJM"
FT STRAND 73..78
FT /evidence="ECO:0007829|PDB:1UJX"
FT STRAND 84..88
FT /evidence="ECO:0007829|PDB:1YJM"
FT STRAND 92..96
FT /evidence="ECO:0007829|PDB:1YJM"
FT STRAND 99..108
FT /evidence="ECO:0007829|PDB:1YJM"
FT STRAND 145..149
FT /evidence="ECO:0007829|PDB:3ZVL"
FT STRAND 152..156
FT /evidence="ECO:0007829|PDB:3ZVL"
FT STRAND 164..169
FT /evidence="ECO:0007829|PDB:3ZVL"
FT TURN 172..174
FT /evidence="ECO:0007829|PDB:3ZVL"
FT STRAND 175..177
FT /evidence="ECO:0007829|PDB:3ZVL"
FT STRAND 179..181
FT /evidence="ECO:0007829|PDB:1YJ5"
FT STRAND 182..184
FT /evidence="ECO:0007829|PDB:3ZVL"
FT STRAND 192..194
FT /evidence="ECO:0007829|PDB:3ZVL"
FT HELIX 198..207
FT /evidence="ECO:0007829|PDB:3ZVL"
FT STRAND 211..217
FT /evidence="ECO:0007829|PDB:3ZVL"
FT HELIX 219..222
FT /evidence="ECO:0007829|PDB:3ZVL"
FT HELIX 228..242
FT /evidence="ECO:0007829|PDB:3ZVL"
FT STRAND 247..251
FT /evidence="ECO:0007829|PDB:3ZVL"
FT STRAND 253..255
FT /evidence="ECO:0007829|PDB:3ZVL"
FT HELIX 263..271
FT /evidence="ECO:0007829|PDB:3ZVL"
FT STRAND 273..275
FT /evidence="ECO:0007829|PDB:3ZVN"
FT HELIX 280..282
FT /evidence="ECO:0007829|PDB:3ZVL"
FT STRAND 284..286
FT /evidence="ECO:0007829|PDB:3ZVL"
FT STRAND 297..299
FT /evidence="ECO:0007829|PDB:3ZVN"
FT HELIX 308..316
FT /evidence="ECO:0007829|PDB:3ZVL"
FT HELIX 323..327
FT /evidence="ECO:0007829|PDB:3ZVL"
FT HELIX 342..344
FT /evidence="ECO:0007829|PDB:3ZVL"
FT STRAND 351..354
FT /evidence="ECO:0007829|PDB:3ZVL"
FT STRAND 366..371
FT /evidence="ECO:0007829|PDB:3ZVL"
FT HELIX 377..384
FT /evidence="ECO:0007829|PDB:3ZVL"
FT HELIX 386..388
FT /evidence="ECO:0007829|PDB:3ZVL"
FT STRAND 391..393
FT /evidence="ECO:0007829|PDB:3U7E"
FT HELIX 395..397
FT /evidence="ECO:0007829|PDB:3ZVL"
FT HELIX 401..413
FT /evidence="ECO:0007829|PDB:3ZVL"
FT STRAND 418..422
FT /evidence="ECO:0007829|PDB:3ZVL"
FT HELIX 427..440
FT /evidence="ECO:0007829|PDB:3ZVL"
FT STRAND 444..449
FT /evidence="ECO:0007829|PDB:3ZVL"
FT HELIX 453..466
FT /evidence="ECO:0007829|PDB:3ZVL"
FT HELIX 475..484
FT /evidence="ECO:0007829|PDB:3ZVL"
FT HELIX 490..492
FT /evidence="ECO:0007829|PDB:3ZVL"
FT STRAND 495..500
FT /evidence="ECO:0007829|PDB:3ZVL"
FT HELIX 510..516
FT /evidence="ECO:0007829|PDB:3ZVL"
SQ SEQUENCE 522 AA; 57223 MW; C691C0A6DA9F47FE CRC64;
MSQLGSRGRL WLQSPTGGPP PIFLPSDGQA LVLGRGPLTQ VTDRKCSRNQ VELIADPESR
TVAVKQLGVN PSTVGVHELK PGLSGSLSLG DVLYLVNGLY PLTLRWEELS TSGSQPDAPP
DTPGDPEEGE DTEPQKKRVR KSSLGWESLK KLLVFTASGV KPQGKVAAFD LDGTLITTRS
GKVFPTSPSD WRILYPEIPK KLQELAAEGY KLVIFTNQMG IGRGKLPAEV FKGKVEAVLE
KLGVPFQVLV ATHAGLNRKP VSGMWDHLQE QANEGIPISV EDSVFVGDAA GRLANWAPGR
KKKDFSCADR LFALNVGLPF ATPEEFFLKW PAARFELPAF DPRTISSAGP LYLPESSSLL
SPNPEVVVAV GFPGAGKSTF IQEHLVSAGY VHVNRDTLGS WQRCVSSCQA ALRQGKRVVI
DNTNPDVPSR ARYIQCAKDA GVPCRCFNFC ATIEQARHNN RFREMTDPSH APVSDMVMFS
YRKQFEPPTL AEGFLEILEI PFRLQEHLDP ALQRLYRQFS EG
