ID DNLI4_PONAB Reviewed; 911 AA.
AC Q5R6L3;
DT 07-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 27-MAR-2024, entry version 85.
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:0000250|UniProtKB:P49917};
DE AltName: Full=Polydeoxyribonucleotide synthase [ATP] 4;
GN Name=LIG4 {ECO:0000250|UniProtKB:P49917};
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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:P49917};
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
CC DCLRE1C; the interaction is direct. Interacts with APLF.
CC {ECO:0000250|UniProtKB:P49917}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P49917}.
CC -!- SIMILARITY: Belongs to the ATP-dependent DNA ligase family.
CC {ECO:0000305}.
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DR EMBL; CR860475; CAH92597.1; -; mRNA.
DR RefSeq; NP_001126522.1; NM_001133050.1.
DR AlphaFoldDB; Q5R6L3; -.
DR SMR; Q5R6L3; -.
DR STRING; 9601.ENSPPYP00000006314; -.
DR GeneID; 100173511; -.
DR KEGG; pon:100173511; -.
DR CTD; 3981; -.
DR eggNOG; KOG0966; Eukaryota.
DR InParanoid; Q5R6L3; -.
DR OrthoDB; 8251at2759; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0005958; C:DNA-dependent protein kinase-DNA ligase 4 complex; ISS:UniProtKB.
DR GO; GO:0070419; C:nonhomologous end joining complex; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003677; F:DNA binding; IEA:InterPro.
DR GO; GO:0003910; F:DNA ligase (ATP) activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0071897; P:DNA biosynthetic process; IEA:InterPro.
DR GO; GO:0051103; P:DNA ligation involved in DNA repair; IEA:InterPro.
DR GO; GO:0006310; P:DNA recombination; IEA:UniProtKB-KW.
DR GO; GO:0097680; P:double-strand break repair via classical nonhomologous end joining; ISS:UniProtKB.
DR CDD; cd07903; Adenylation_DNA_ligase_IV; 1.
DR CDD; cd17722; BRCT_DNA_ligase_IV_rpt1; 1.
DR CDD; cd17717; BRCT_DNA_ligase_IV_rpt2; 1.
DR CDD; cd07968; OBF_DNA_ligase_IV; 1.
DR Gene3D; 6.10.250.520; -; 1.
DR Gene3D; 3.40.50.10190; BRCT domain; 2.
DR Gene3D; 1.10.3260.10; DNA ligase, ATP-dependent, N-terminal domain; 1.
DR Gene3D; 3.30.470.30; DNA ligase/mRNA capping enzyme; 1.
DR Gene3D; 2.40.50.140; Nucleic acid-binding proteins; 1.
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 NCBIfam; TIGR00574; dnl1; 1.
DR PANTHER; PTHR45997; DNA LIGASE 4; 1.
DR PANTHER; PTHR45997:SF1; DNA LIGASE 4; 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; ATP-dependent DNA ligase DNA-binding domain; 1.
DR SUPFAM; SSF52113; BRCT domain; 2.
DR SUPFAM; SSF56091; DNA ligase/mRNA capping enzyme, catalytic domain; 1.
DR SUPFAM; SSF50249; Nucleic acid-binding proteins; 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; Ligase; Magnesium; Metal-binding; Nucleotide-binding; Nucleus;
KW Reference proteome; Repeat.
FT CHAIN 1..911
FT /note="DNA ligase 4"
FT /id="PRO_0000059578"
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 REGION 610..620
FT /note="Required for catalytic activity"
FT /evidence="ECO:0000250|UniProtKB:P49917"
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:P49917"
FT BINDING 272
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P49917"
FT BINDING 273
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P49917"
FT BINDING 274
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P49917"
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 345
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P49917"
FT BINDING 367
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P49917"
FT BINDING 427
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P49917"
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 BINDING 451
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P49917"
SQ SEQUENCE 911 AA; 104053 MW; C6AD9817E9EC2B59 CRC64;
MAASQTSQTV ASHVPFADLC STLERIQKSK GRAEKIRHFR EFLDSWRKFH DAFHKNQKDV
TDSFYPAMRL ILPQLERERM AYGIKETMLA KLYIELLNLP RDGKDALKLL NYRTPTGTHG
DAGDFAMIAY FVLKPRCLQK GSLTIQQVND LLDSIASNNS AKRKDLIKKS LLQLITQSSA
LEQKWLIRMI IKDLKLGVSQ QTIFSVFHSD AVELHNVTTD LEKVCRQLHD PSVGLSDISI
TLFSAFKPML AAIADIEHIE KDMKHQSFYI ETKLDGERMQ MHKDGDVYKY FSRNGYNYTD
QFGASPTEGS LTPFIHNAFK TDIQICILDG EMMAYNPNTQ TFMQKGTKFD IKRMVEDSDL
QTCYCVFDVL MVNNKKLGHE TLRKRYEILS SIFTPIPGRI EIVQKTQAHT KNEVIDALNE
AIDKREEGIM IKQPLSIYKP DKRGEGWLKI KPEYVSGLMD ELDILIVGGY WGKGSRGGMM
SHFLCAVAEK PPPGEKPSVF HTLSRVGSGC TMKELYDLGL KLAKYWKPFH KKAPPSSILC
GTEKPEVYIE PCNSVIVQIK AAEIVPSDMY KTGCTLRFPR IEKIRDDKEW HECMTLDDLE
QLRGKASGKL ASKHFYVGGD DEPQEKKRKA APKMKKVIGI IEHLKAPNLT NVNKISNIFE
DVEFCVMSGT DSQPKPDLEN RIAEFGGYIV QNPGPDTYCV IAGSKNIRVK NIILSNKHDV
VKPAWLLECF KTKSFVPWQP HFMIHMCPST KEHFAREYDC YGDSYFVDTD LNQLKEVFSG
IKNSNEQTPE EMASLIADLE YRYSWDCSPL SMFRRHTVYL DLYAVINDLS TKNEGTRLAI
KALELRFHGA KVVSCLAEGV SHVIIGEDHS RIADFKAFRR TFKRKFKILK ESWITDSIDK
CELQEENQYL I
//
