DNLI4_CRIGR
ID DNLI4_CRIGR Reviewed; 912 AA.
AC G3GTP0;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2011, sequence version 1.
DT 03-AUG-2022, entry version 55.
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:10047779};
DE AltName: Full=Polydeoxyribonucleotide synthase [ATP] 4;
GN Name=LIG4 {ECO:0000303|PubMed:10047779};
GN ORFNames=I79_001027 {ECO:0000303|PubMed:21804562};
OS Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Cricetulus.
OX NCBI_TaxID=10029;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=21804562; DOI=10.1038/nbt.1932;
RA Xu X., Nagarajan H., Lewis N.E., Pan S., Cai Z., Liu X., Chen W., Xie M.,
RA Wang W., Hammond S., Andersen M.R., Neff N., Passarelli B., Koh W.,
RA Fan H.C., Wang J., Gui Y., Lee K.H., Betenbaugh M.J., Quake S.R.,
RA Famili I., Palsson B.O., Wang J.;
RT "The genomic sequence of the Chinese hamster ovary (CHO)-K1 cell line.";
RL Nat. Biotechnol. 29:735-741(2011).
RN [2]
RP INTERACTION WITH XRCC4.
RX PubMed=10047779; DOI=10.1016/s0921-8777(98)00063-9;
RA Bryans M., Valenzano M.C., Stamato T.D.;
RT "Absence of DNA ligase IV protein in XR-1 cells: evidence for stabilization
RT by XRCC4.";
RL Mutat. Res. 433:53-58(1999).
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
CC (PubMed:10047779). Component of the core long-range non-homologous end
CC joining (NHEJ) complex (also named DNA-PK complex) composed of PRKDC,
CC LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF (By similarity).
CC Additional component of the NHEJ complex includes PAXX (By similarity).
CC Following autophosphorylation, PRKDC dissociates from DNA, leading to
CC formation of the short-range NHEJ complex, composed of LIG4, XRCC4,
CC XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF (By similarity). Interacts with
CC APLF (By similarity). {ECO:0000250|UniProtKB:P49917,
CC ECO:0000269|PubMed:10047779}.
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; JH000021; EGW00081.1; -; Genomic_DNA.
DR RefSeq; XP_003495812.1; XM_003495764.3.
DR SMR; G3GTP0; -.
DR STRING; 10029.XP_007634008.1; -.
DR Ensembl; ENSCGRT00001014315; ENSCGRP00001010095; ENSCGRG00001012072.
DR GeneID; 100754640; -.
DR KEGG; cge:100754640; -.
DR CTD; 3981; -.
DR eggNOG; KOG0966; Eukaryota.
DR GeneTree; ENSGT00860000133881; -.
DR InParanoid; G3GTP0; -.
DR OMA; EGIMIKH; -.
DR OrthoDB; 274264at2759; -.
DR Proteomes; UP000001075; Unassembled WGS sequence.
DR GO; GO:0000793; C:condensed chromosome; IEA:Ensembl.
DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; IEA:Ensembl.
DR GO; GO:0032807; C:DNA ligase IV complex; IEA:Ensembl.
DR GO; GO:0005958; C:DNA-dependent protein kinase-DNA ligase 4 complex; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003677; F:DNA binding; IEA:Ensembl.
DR GO; GO:0003910; F:DNA ligase (ATP) activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008022; F:protein C-terminus binding; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0007417; P:central nervous system development; IEA:Ensembl.
DR GO; GO:0051276; P:chromosome organization; IEA:Ensembl.
DR GO; GO:1904155; P:DN2 thymocyte differentiation; IEA:Ensembl.
DR GO; GO:0071897; P:DNA biosynthetic process; IEA:InterPro.
DR GO; GO:0051102; P:DNA ligation involved in DNA recombination; IEA:Ensembl.
DR GO; GO:0051103; P:DNA ligation involved in DNA repair; IEA:Ensembl.
DR GO; GO:0006260; P:DNA replication; IEA:UniProtKB-KW.
DR GO; GO:0097680; P:double-strand break repair via classical nonhomologous end joining; IEA:Ensembl.
DR GO; GO:0048144; P:fibroblast proliferation; IEA:Ensembl.
DR GO; GO:0033152; P:immunoglobulin V(D)J recombination; IEA:Ensembl.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0045190; P:isotype switching; IEA:Ensembl.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0022008; P:neurogenesis; IEA:Ensembl.
DR GO; GO:0051402; P:neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0006297; P:nucleotide-excision repair, DNA gap filling; IEA:Ensembl.
DR GO; GO:2001252; P:positive regulation of chromosome organization; IEA:Ensembl.
DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IEA:Ensembl.
DR GO; GO:0050769; P:positive regulation of neurogenesis; IEA:Ensembl.
DR GO; GO:0002328; P:pro-B cell differentiation; IEA:Ensembl.
DR GO; GO:0010332; P:response to gamma radiation; IEA:Ensembl.
DR GO; GO:0010165; P:response to X-ray; IEA:Ensembl.
DR GO; GO:0000012; P:single strand break repair; IEA:Ensembl.
DR GO; GO:0035019; P:somatic stem cell population maintenance; IEA:Ensembl.
DR GO; GO:0072089; P:stem cell proliferation; IEA:Ensembl.
DR GO; GO:0033153; P:T cell receptor V(D)J recombination; IEA:Ensembl.
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 1: Evidence at protein 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..912
FT /note="DNA ligase 4"
FT /id="PRO_0000453300"
FT DOMAIN 654..743
FT /note="BRCT 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT DOMAIN 846..912
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"
SQ SEQUENCE 912 AA; 104363 MW; D26A37DA48E6775A CRC64;
MATSQTSQTV AAHVPFADLC STLERIQKSK ERAEKIRHFK EFLDSWRKFH DALHKNKKDV
TDSFYPAMRL ILPQLERERM AYGIKETMLA KLYIELLNLP REGKDALKLL NYRTPSGART
DAGDFAVIAY FVLKPRCLQK GSLTIQQVNE LLDLVASNNS GKRKDLVKKS LLQLITQSSA
LEQKWLIRMI IKDLKLGVSQ QTILNIFHND AVELHNVTTD LEKVCRQLHD PAVGLSDISI
TLFSAFKPML AAVADVERVE KDMKQQSFYI ETKLDGERMQ MHKDGSVYQY FSRNGYNYTD
QFGASPQEGT LTPFIHDAFR TDVQVCILDG EMMAYNPTTQ TFMQKGVKFD IKRMVEDSDL
QTCYCVFDVL MVNNKKLGRE TLRKRYDILN STFTPIQGRI EIVQKKLAQT KNEVVDALNE
AIDKREEGIM IKHPLSIYKP DKRGEGWLKI KPEYVSGLMD ELDLLIVGGY WGKGSRGGMM
SHFLCAVAEK PPHGEKPSVF HTLCRVGSGY TMKELYDLGL KLAKYWKPFH KKSPPSSILC
GTEKPEVYIE PCNSVIVQIK AAEIVPSDMY KTGTTLRFPR IEKIRDDKEW HECMTLGDLE
ELRGKASGKL ATKHLHVGDD DEPREKRRKP VSKMKKTIGI IEHLKAPNLS NISKVSNVFE
DVEFCVMSGL DGYPKSDLEN RIAEFGGYIV QNPGPDTYCV IAGCENIRVK NIISSDQHDV
VKPEWLLECF KTKTCVPWQP RFMIHMCPST KQHFAREYDC YGDSYFVDTD LDQLKEVFLG
IKKAGEHQTP EEMAPVIADL EYRYSWDHSP LCMFRHCTVY LDLYAVINDS SSKIKATRLD
VTALELRFHG AKVVSHLSEG VSHVIIGENQ SRVSDFKVFR RTLKKKFKIL QERWVTDSVD
KGELQEENQY LL
