DNLI4_MOUSE
ID DNLI4_MOUSE Reviewed; 911 AA.
AC Q8BTF7; G3UWC4; Q3UG76;
DT 07-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 2.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=DNA ligase 4 {ECO:0000305};
DE EC=6.5.1.1 {ECO:0000255|PROSITE-ProRule:PRU10135};
DE AltName: Full=DNA ligase IV {ECO:0000303|PubMed:9889105};
DE AltName: Full=Polydeoxyribonucleotide synthase [ATP] 4;
GN Name=Lig4 {ECO:0000312|MGI:MGI:1335098};
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].
RC STRAIN=C57BL/6J; TISSUE=Testis;
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 GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=9889105; DOI=10.1016/s0960-9822(98)00021-9;
RA Barnes D.E., Stamp G., Rosewell I., Denzel A., Lindahl T.;
RT "Targeted disruption of the gene encoding DNA ligase IV leads to lethality
RT in embryonic mice.";
RL Curr. Biol. 8:1395-1398(1998).
CC -!- FUNCTION: DNA ligase involved in DNA non-homologous end joining (NHEJ);
CC required for double-strand break (DSB) repair and V(D)J recombination.
CC Catalyzes the NHEJ ligation step of the broken DNA during DSB repair by
CC resealing the DNA breaks after the gap filling is completed. Joins
CC single-strand breaks in a double-stranded polydeoxynucleotide in an
CC ATP-dependent reaction. LIG4 is mechanistically flexible: it can ligate
CC nicks as well as compatible DNA overhangs alone, while in the presence
CC of XRCC4, it can ligate ends with 2-nucleotides (nt) microhomology and
CC 1-nt gaps. Forms a subcomplex with XRCC4; the LIG4-XRCC4 subcomplex is
CC responsible for the NHEJ ligation step and XRCC4 enhances the joining
CC activity of LIG4. Binding of the LIG4-XRCC4 complex to DNA ends is
CC dependent on the assembly of the DNA-dependent protein kinase complex
CC DNA-PK to these DNA ends. LIG4 regulates nuclear localization of XRCC4.
CC {ECO:0000250|UniProtKB:P49917}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + (deoxyribonucleotide)n-3'-hydroxyl + 5'-phospho-
CC (deoxyribonucleotide)m = (deoxyribonucleotide)n+m + AMP +
CC diphosphate.; EC=6.5.1.1; Evidence={ECO:0000255|PROSITE-
CC ProRule:PRU10135};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P18858};
CC -!- SUBUNIT: Interacts with XRCC4; the LIG4-XRCC4 subcomplex has a 1:2
CC stoichiometry and XRCC4 is required for LIG4 stability. Component of
CC the core long-range non-homologous end joining (NHEJ) complex (also
CC named DNA-PK complex) composed of PRKDC, LIG4, XRCC4, XRCC6/Ku70,
CC XRCC5/Ku86 and NHEJ1/XLF. Additional component of the NHEJ complex
CC includes PAXX. Following autophosphorylation, PRKDC dissociates from
CC DNA, leading to formation of the short-range NHEJ complex, composed of
CC LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF. Interacts with APLF.
CC {ECO:0000250|UniProtKB:P49917}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P49917}.
CC -!- DISRUPTION PHENOTYPE: Embryonic lethality associated with extensive
CC apoptotic cell death in the embryonic central nervous system.
CC {ECO:0000269|PubMed:9889105}.
CC -!- SIMILARITY: Belongs to the ATP-dependent DNA ligase family.
CC {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; AK030029; BAC26747.1; -; mRNA.
DR EMBL; AK148081; BAE28333.1; -; mRNA.
DR EMBL; AC138397; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466566; EDL22038.1; -; Genomic_DNA.
DR EMBL; CH466566; EDL22040.1; -; Genomic_DNA.
DR CCDS; CCDS22092.1; -.
DR RefSeq; NP_795927.2; NM_176953.3.
DR RefSeq; XP_017168343.1; XM_017312854.1.
DR AlphaFoldDB; Q8BTF7; -.
DR SMR; Q8BTF7; -.
DR BioGRID; 235376; 2.
DR CORUM; Q8BTF7; -.
DR STRING; 10090.ENSMUSP00000093130; -.
DR iPTMnet; Q8BTF7; -.
DR PhosphoSitePlus; Q8BTF7; -.
DR MaxQB; Q8BTF7; -.
DR PaxDb; Q8BTF7; -.
DR PRIDE; Q8BTF7; -.
DR ProteomicsDB; 279793; -.
DR Antibodypedia; 705; 316 antibodies from 32 providers.
DR DNASU; 319583; -.
DR Ensembl; ENSMUST00000095476; ENSMUSP00000093130; ENSMUSG00000049717.
DR Ensembl; ENSMUST00000170033; ENSMUSP00000130807; ENSMUSG00000049717.
DR GeneID; 319583; -.
DR KEGG; mmu:319583; -.
DR UCSC; uc009kul.1; mouse.
DR CTD; 3981; -.
DR MGI; MGI:1335098; Lig4.
DR VEuPathDB; HostDB:ENSMUSG00000049717; -.
DR eggNOG; KOG0966; Eukaryota.
DR GeneTree; ENSGT00860000133881; -.
DR HOGENOM; CLU_004844_2_0_1; -.
DR InParanoid; Q8BTF7; -.
DR OMA; EGIMIKH; -.
DR OrthoDB; 274264at2759; -.
DR PhylomeDB; Q8BTF7; -.
DR TreeFam; TF312980; -.
DR Reactome; R-MMU-5693571; Nonhomologous End-Joining (NHEJ).
DR BioGRID-ORCS; 319583; 39 hits in 109 CRISPR screens.
DR PRO; PR:Q8BTF7; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q8BTF7; protein.
DR Bgee; ENSMUSG00000049717; Expressed in primary oocyte and 221 other tissues.
DR Genevisible; Q8BTF7; MM.
DR GO; GO:0000793; C:condensed chromosome; ISO:MGI.
DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; ISO:MGI.
DR GO; GO:0032807; C:DNA ligase IV complex; ISO:MGI.
DR GO; GO:0005958; C:DNA-dependent protein kinase-DNA ligase 4 complex; IDA:MGI.
DR GO; GO:0070419; C:nonhomologous end joining complex; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IDA:MGI.
DR GO; GO:0003677; F:DNA binding; ISO:MGI.
DR GO; GO:0003910; F:DNA ligase (ATP) activity; IDA:MGI.
DR GO; GO:0003909; F:DNA ligase activity; ISO:MGI.
DR GO; GO:0016874; F:ligase activity; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:MGI.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0071479; P:cellular response to ionizing radiation; ISO:MGI.
DR GO; GO:0071285; P:cellular response to lithium ion; IEA:Ensembl.
DR GO; GO:0007417; P:central nervous system development; IMP:MGI.
DR GO; GO:0051276; P:chromosome organization; IGI:MGI.
DR GO; GO:1904155; P:DN2 thymocyte differentiation; IMP:MGI.
DR GO; GO:0071897; P:DNA biosynthetic process; IEA:InterPro.
DR GO; GO:0006266; P:DNA ligation; IDA:MGI.
DR GO; GO:0051102; P:DNA ligation involved in DNA recombination; IMP:MGI.
DR GO; GO:0051103; P:DNA ligation involved in DNA repair; IMP:MGI.
DR GO; GO:0006281; P:DNA repair; IMP:MGI.
DR GO; GO:0006260; P:DNA replication; IEA:UniProtKB-KW.
DR GO; GO:0006302; P:double-strand break repair; IMP:MGI.
DR GO; GO:0097680; P:double-strand break repair via classical nonhomologous end joining; ISO:MGI.
DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; IMP:BHF-UCL.
DR GO; GO:0048144; P:fibroblast proliferation; IMP:MGI.
DR GO; GO:0033152; P:immunoglobulin V(D)J recombination; IMP:MGI.
DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
DR GO; GO:0045190; P:isotype switching; IMP:MGI.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:MGI.
DR GO; GO:0022008; P:neurogenesis; IMP:MGI.
DR GO; GO:0051402; P:neuron apoptotic process; IMP:MGI.
DR GO; GO:0006297; P:nucleotide-excision repair, DNA gap filling; ISO:MGI.
DR GO; GO:2001252; P:positive regulation of chromosome organization; ISO:MGI.
DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IMP:MGI.
DR GO; GO:0050769; P:positive regulation of neurogenesis; IMP:MGI.
DR GO; GO:0002328; P:pro-B cell differentiation; IMP:MGI.
DR GO; GO:0010332; P:response to gamma radiation; IMP:MGI.
DR GO; GO:0010212; P:response to ionizing radiation; IMP:MGI.
DR GO; GO:0010165; P:response to X-ray; ISO:MGI.
DR GO; GO:0000012; P:single strand break repair; ISO:MGI.
DR GO; GO:0035019; P:somatic stem cell population maintenance; IMP:MGI.
DR GO; GO:0072089; P:stem cell proliferation; IMP:MGI.
DR GO; GO:0033153; P:T cell receptor V(D)J recombination; IMP:MGI.
DR GO; GO:0033151; P:V(D)J recombination; IDA:MGI.
DR CDD; cd07903; Adenylation_DNA_ligase_IV; 1.
DR Gene3D; 1.10.3260.10; -; 1.
DR Gene3D; 2.40.50.140; -; 1.
DR Gene3D; 3.40.50.10190; -; 2.
DR InterPro; IPR044125; Adenylation_DNA_ligase_IV.
DR InterPro; IPR001357; BRCT_dom.
DR InterPro; IPR036420; BRCT_dom_sf.
DR InterPro; IPR000977; DNA_ligase_ATP-dep.
DR InterPro; IPR012309; DNA_ligase_ATP-dep_C.
DR InterPro; IPR012310; DNA_ligase_ATP-dep_cent.
DR InterPro; IPR016059; DNA_ligase_ATP-dep_CS.
DR InterPro; IPR012308; DNA_ligase_ATP-dep_N.
DR InterPro; IPR021536; DNA_ligase_IV_dom.
DR InterPro; IPR036599; DNA_ligase_N_sf.
DR InterPro; IPR029710; LIG4.
DR InterPro; IPR012340; NA-bd_OB-fold.
DR PANTHER; PTHR45997; PTHR45997; 1.
DR Pfam; PF00533; BRCT; 2.
DR Pfam; PF04679; DNA_ligase_A_C; 1.
DR Pfam; PF01068; DNA_ligase_A_M; 1.
DR Pfam; PF04675; DNA_ligase_A_N; 1.
DR Pfam; PF11411; DNA_ligase_IV; 1.
DR SMART; SM00292; BRCT; 2.
DR SUPFAM; SSF117018; SSF117018; 1.
DR SUPFAM; SSF50249; SSF50249; 1.
DR SUPFAM; SSF52113; SSF52113; 2.
DR TIGRFAMs; TIGR00574; dnl1; 1.
DR PROSITE; PS50172; BRCT; 2.
DR PROSITE; PS00697; DNA_LIGASE_A1; 1.
DR PROSITE; PS00333; DNA_LIGASE_A2; 1.
DR PROSITE; PS50160; DNA_LIGASE_A3; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Cell cycle; Cell division; DNA damage; DNA recombination;
KW DNA repair; DNA replication; Ligase; Magnesium; Metal-binding;
KW Nucleotide-binding; Nucleus; Reference proteome; Repeat.
FT CHAIN 1..911
FT /note="DNA ligase 4"
FT /id="PRO_0000059577"
FT DOMAIN 654..743
FT /note="BRCT 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT DOMAIN 808..911
FT /note="BRCT 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT ACT_SITE 273
FT /note="N6-AMP-lysine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10135"
FT BINDING 271
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P18858"
FT BINDING 278
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P18858"
FT BINDING 331
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P18858"
FT BINDING 331
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255"
FT BINDING 427
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255"
FT BINDING 432
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P18858"
FT BINDING 449
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P18858"
FT CONFLICT 268
FT /note="F -> L (in Ref. 1; BAC26747)"
FT /evidence="ECO:0000305"
FT CONFLICT 758
FT /note="Y -> C (in Ref. 1; BAE28333)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 911 AA; 104120 MW; 20CDD0F6465355A2 CRC64;
MASSQTSQTV AAHVPFADLC STLERIQKGK DRAEKIRHFK EFLDSWRKFH DALHKNRKDV
TDSFYPAMRL ILPQLERERM AYGIKETMLA KLYIELLNLP REGKDAQKLL NYRTPSGART
DAGDFAMIAY FVLKPRCLQK GSLTIQQVNE LLDLVASNNS GKKKDLVKKS LLQLITQSSA
LEQKWLIRMI IKDLKLGISQ QTIFSIFHND AVELHNVTTD LEKVCRQLHD PSVGLSDISI
TLFSAFKPML AAVADVERVE KDMKQQSFYI ETKLDGERMQ MHKDGALYRY FSRNGYNYTD
QFGESPQEGS LTPFIHNAFG TDVQACILDG EMMAYNPTTQ TFMQKGVKFD IKRMVEDSGL
QTCYSVFDVL MVNKKKLGRE TLRKRYEILS STFTPIQGRI EIVQKTQAHT KKEVVDALND
AIDKREEGIM VKHPLSIYKP DKRGEGWLKI KPEYVSGLMD ELDVLIVGGY WGKGSRGGMM
SHFLCAVAET PPPGDRPSVF HTLCRVGSGY TMKELYDLGL KLAKYWKPFH KKSPPSSILC
GTEKPEVYIE PQNSVIVQIK AAEIVPSDMY KTGSTLRFPR IEKIRDDKEW HECMTLGDLE
QLRGKASGKL ATKHLHVGDD DEPREKRRKP ISKTKKAIRI IEHLKAPNLS NVNKVSNVFE
DVEFCVMSGL DGYPKADLEN RIAEFGGYIV QNPGPDTYCV IAGSENVRVK NIISSDKNDV
VKPEWLLECF KTKTCVPWQP RFMIHMCPST KQHFAREYDC YGDSYFVDTD LDQLKEVFLG
IKPSEQQTPE EMAPVIADLE CRYSWDHSPL SMFRHYTIYL DLYAVINDLS SRIEATRLGI
TALELRFHGA KVVSCLSEGV SHVIIGEDQR RVTDFKIFRR MLKKKFKILQ ESWVSDSVDK
GELQEENQYL L
