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    LIG3 DNA ligase 3 [ Homo sapiens (human) ]

    Gene ID: 3980, updated on 28-Oct-2024

    Summary

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    Official Symbol
    LIG3provided by HGNC
    Official Full Name
    DNA ligase 3provided by HGNC
    Primary source
    HGNC:HGNC:6600
    See related
    Ensembl:ENSG00000005156 MIM:600940; AllianceGenome:HGNC:6600
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    LIG2; MTDPS20; LIG3alpha
    Summary
    This gene is a member of the DNA ligase family. Each member of this family encodes a protein that catalyzes the joining of DNA ends but they each have a distinct role in DNA metabolism. The protein encoded by this gene is involved in excision repair and is located in both the mitochondria and nucleus, with translation initiation from the upstream start codon allowing for transport to the mitochondria and translation initiation from a downstream start codon allowing for transport to the nucleus. Additionally, alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in testis (RPKM 7.0), thyroid (RPKM 4.6) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See LIG3 in Genome Data Viewer
    Location:
    17q12
    Exon count:
    23
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 17 NC_000017.11 (34980512..35010872)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 17 NC_060941.1 (35928368..35957659)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (33307531..33336762)

    Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene chaperonin containing TCP1 subunit 6B Neighboring gene Sharpr-MPRA regulatory region 18 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12049 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12050 Neighboring gene zinc finger protein 830 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8432 Neighboring gene RAD51L3-RFFL readthrough Neighboring gene oligosaccharyltransferase complex subunit pseudogene 7 Neighboring gene ring finger and FYVE like domain containing E3 ubiquitin protein ligase Neighboring gene ReSE screen-validated silencer GRCh37_chr17:33354498-33354674 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12051 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12052 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12053 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12054 Neighboring gene small nucleolar RNA U13 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr17:33390277-33391476 Neighboring gene ribosomal protein L37 pseudogene 22

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Escape from telomere-driven crisis is DNA ligase III dependent. Jones RE, et al. Cell Rep, 2014 Aug 21. PMID 25127141
    2. Structure and function of the DNA ligases encoded by the mammalian LIG3 gene. Tomkinson AE, et al. Gene, 2013 Dec 1. PMID 24013086, Free PMC Article
    3. Polymorphism of the LIG3 gene in keratoconus and Fuchs endothelial corneal dystrophy. Synowiec E, et al. Cell Mol Biol (Noisy-le-grand), 2015 Mar 28. PMID 25817347
    4. LIG3 gene polymorphisms and risk of gastric cancer in a Southern Chinese population. Hua RX, et al. Gene, 2019 Jul 15. PMID 31034940
    5. Association between single nucleotide polymorphisms in the DNA repair gene LIG3 and acute adverse skin reactions following radiotherapy. Murray RJ, et al. Radiother Oncol, 2011 May. PMID 21620500

    See all (207) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Direct interaction of DNA repair protein tyrosyl DNA phosphodiesterase 1 and the DNA ligase III catalytic domain is regulated by phosphorylation of its flexible N-terminus.
      Title: Direct interaction of DNA repair protein tyrosyl DNA phosphodiesterase 1 and the DNA ligase III catalytic domain is regulated by phosphorylation of its flexible N-terminus.
    2. Toxicity and therapy outcome associations in LIG3, SLCO1B3, ABCB1, OPRM1 and GSTP1 in high-grade serous ovarian cancer.
      Title: Toxicity and therapy outcome associations in LIG3, SLCO1B3, ABCB1, OPRM1 and GSTP1 in high-grade serous ovarian cancer.
    3. Human DNA ligases I and III have stand-alone end-joining capability, but differ in ligation efficiency and specificity.
      Title: Human DNA ligases I and III have stand-alone end-joining capability, but differ in ligation efficiency and specificity.
    4. Rac GTPase activating protein 1 promotes gallbladder cancer via binding DNA ligase 3 to reduce apoptosis.
      Title: Rac GTPase activating protein 1 promotes gallbladder cancer via binding DNA ligase 3 to reduce apoptosis.
    5. Biallelic variants in LIG3 cause a novel mitochondrial neurogastrointestinal encephalomyopathy.
      Title: Biallelic variants in LIG3 cause a novel mitochondrial neurogastrointestinal encephalomyopathy.
    6. Human DNA ligases in replication and repair.
      Title: Human DNA ligases in replication and repair.
    7. Altered DNA ligase activity in human disease.
      Title: Altered DNA ligase activity in human disease.
    8. An atypical BRCT-BRCT interaction with the XRCC1 scaffold protein compacts human DNA Ligase IIIalpha within a flexible DNA repair complex.
      Title: An atypical BRCT-BRCT interaction with the XRCC1 scaffold protein compacts human DNA Ligase IIIα within a flexible DNA repair complex.
    9. MM express elevated MALAT1 and involve in alternative non-homozygous end joining (A-NHEJ) pathway by binding to PARP1 and LIG3, two key components of the A-NHEJ protein complex.
      Title: Targeting the MALAT1/PARP1/LIG3 complex induces DNA damage and apoptosis in multiple myeloma.
    10. Data report that polymorphisms in LIG3 gene are not associated with the susceptibility to gastric cancer. The study helps to provide novel insight into the role of LIG3 polymorphisms in gastric cancer risk.
      Title: LIG3 gene polymorphisms and risk of gastric cancer in a Southern Chinese population.
    Submit: New GeneRIF Correction See all GeneRIFs (45)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Mitochondrial DNA depletion syndrome 20 (mngie type)
    MedGen: C5676934 OMIM: 619780 GeneReviews: Not available
    		not available

    EBI GWAS Catalog

    Description
    Common variants at ten loci influence QT interval duration in the QTGEN Study.
    EBI GWAS Catalog
    Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Rev rev HIV-1 Rev interacting protein, ligase III, DNA, ATP-dependent (LIG3), is identified by the in-vitro binding experiments involving cytosolic or nuclear extracts from HeLa cells. The interaction of Rev with LIG3 is increased by RRE PubMed
    Tat tat Both HIV-1 Tat 47-59 and FITC-labeled Tat 47-59 peptides downregulate gene expression of ligase III, DNA, ATP-dependent (LIG3) in U-937 macrophages PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables DNA binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables DNA ligase (ATP) activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables DNA ligase (ATP) activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables DNA ligase (ATP) activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables DNA ligase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables DNA ligase activity TAS
    Traceable Author Statement
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables zinc ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in DNA biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in DNA ligation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    NOT involved_in V(D)J recombination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in base-excision repair, DNA ligation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in base-excision repair, DNA ligation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in base-excision repair, DNA ligation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in base-excision repair, DNA ligation TAS
    Traceable Author Statement
    more info
    		  
    involved_in base-excision repair, gap-filling TAS
    Traceable Author Statement
    more info
    		  
    involved_in cell division IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in double-strand break repair IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in double-strand break repair IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in double-strand break repair via alternative nonhomologous end joining IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    involved_in double-strand break repair via homologous recombination TAS
    Traceable Author Statement
    more info
    		  
    involved_in lagging strand elongation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in mitochondrial DNA repair IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in mitochondrion organization IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of mitochondrial DNA replication IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    part_of DNA ligase III-XRCC1 complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrion HTP PubMed 
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    DNA ligase 3
    Names
    ligase II, DNA, ATP-dependent
    ligase III, DNA, ATP-dependent
    polydeoxyribonucleotide synthase [ATP] 3
    NP_002302.2
    NP_039269.2
    XP_005258027.1
    XP_006721959.1
    XP_016880113.1
    XP_047291924.1
    XP_047291925.1
    XP_047291926.1
    XP_047291927.1
    XP_047291928.1
    XP_054172026.1
    XP_054172027.1
    XP_054172028.1
    XP_054172029.1
    XP_054172030.1
    XP_054172031.1
    XP_054172032.1
    XP_054172033.1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_029221.2 RefSeqGene

      Range
      5002..34233
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_002311.5 → NP_002302.2  DNA ligase 3 isoform beta precursor

      See identical proteins and their annotated locations for NP_002302.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (beta) contains an alternate in-frame exon in the coding region which includes an in-frame stop codon, compared to variant alpha. This isoform (beta) is shorter and has a distinct C-terminus, compared to isoform alpha.
      Source sequence(s)
      BG470103, DB100562, U40671
      Consensus CDS
      CCDS11285.2
      UniProtKB/Swiss-Prot
      P49916
      Related
      ENSP00000262327.4, ENST00000262327.9
      Conserved Domains (5) summary
      cd07967
      Location:686 → 824
      OBF_DNA_ligase_III; The Oligonucleotide/oligosaccharide binding (OB)-fold domain of ATP-dependent DNA ligase III is a DNA-binding module that is part of the catalytic core unit
      cd07902
      Location:468 → 680
      Adenylation_DNA_ligase_III; Adenylation domain of DNA Ligase III
      TIGR00574
      Location:318 → 830
      dnl1; DNA ligase I, ATP-dependent (dnl1)
      pfam00645
      Location:97 → 179
      zf-PARP; Poly(ADP-ribose) polymerase and DNA-Ligase Zn-finger region
      pfam04675
      Location:264 → 429
      DNA_ligase_A_N; DNA ligase N terminus

    2. NM_013975.4 → NP_039269.2  DNA ligase 3 isoform alpha precursor

      See identical proteins and their annotated locations for NP_039269.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (alpha) represents the longer transcript and encodes the longer isoform (alpha).
      Source sequence(s)
      AA872458, AC004223, AW166526, BC068005, BM726768, DB100562
      Consensus CDS
      CCDS11284.2
      UniProtKB/Swiss-Prot
      E5KLB5, E5KLB6, P49916, Q16714, Q6NVK3
      Related
      ENSP00000367787.3, ENST00000378526.9
      Conserved Domains (3) summary
      TIGR00574
      Location:318 → 830
      dnl1; DNA ligase I, ATP-dependent (dnl1)
      pfam00645
      Location:96 → 181
      zf-PARP; Poly(ADP-ribose) polymerase and DNA-Ligase Zn-finger region
      pfam16759
      Location:933 → 1004
      LIG3_BRCT; DNA ligase 3 BRCT domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000017.11 Reference GRCh38.p14 Primary Assembly

      Range
      34980512..35010872
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047435969.1 → XP_047291925.1  DNA ligase 3 isoform X2

    2. XM_047435968.1 → XP_047291924.1  DNA ligase 3 isoform X1

    3. XM_047435971.1 → XP_047291927.1  DNA ligase 3 isoform X5

    4. XM_047435972.1 → XP_047291928.1  DNA ligase 3 isoform X7

      UniProtKB/TrEMBL
      B7Z6I3

    5. XM_005257970.5 → XP_005258027.1  DNA ligase 3 isoform X3

      Conserved Domains (6) summary
      cd07967
      Location:695 → 833
      OBF_DNA_ligase_III; The Oligonucleotide/oligosaccharide binding (OB)-fold domain of ATP-dependent DNA ligase III is a DNA-binding module that is part of the catalytic core unit
      cd07902
      Location:477 → 689
      Adenylation_DNA_ligase_III; Adenylation domain of DNA Ligase III
      TIGR00574
      Location:327 → 839
      dnl1; DNA ligase I, ATP-dependent (dnl1)
      pfam00645
      Location:106 → 188
      zf-PARP; Poly(ADP-ribose) polymerase and DNA-Ligase Zn-finger region
      pfam04675
      Location:273 → 438
      DNA_ligase_A_N; DNA ligase N terminus
      pfam16759
      Location:942 → 1013
      LIG3_BRCT; DNA ligase 3 BRCT domain

    6. XM_006721896.4 → XP_006721959.1  DNA ligase 3 isoform X6

      Conserved Domains (5) summary
      cd07967
      Location:695 → 833
      OBF_DNA_ligase_III; The Oligonucleotide/oligosaccharide binding (OB)-fold domain of ATP-dependent DNA ligase III is a DNA-binding module that is part of the catalytic core unit
      cd07902
      Location:477 → 689
      Adenylation_DNA_ligase_III; Adenylation domain of DNA Ligase III
      TIGR00574
      Location:327 → 839
      dnl1; DNA ligase I, ATP-dependent (dnl1)
      pfam00645
      Location:106 → 188
      zf-PARP; Poly(ADP-ribose) polymerase and DNA-Ligase Zn-finger region
      pfam04675
      Location:273 → 438
      DNA_ligase_A_N; DNA ligase N terminus

    7. XM_017024624.2 → XP_016880113.1  DNA ligase 3 isoform X4

      UniProtKB/Swiss-Prot
      E5KLB5, E5KLB6, P49916, Q16714, Q6NVK3
      Conserved Domains (3) summary
      TIGR00574
      Location:318 → 830
      dnl1; DNA ligase I, ATP-dependent (dnl1)
      pfam00645
      Location:96 → 181
      zf-PARP; Poly(ADP-ribose) polymerase and DNA-Ligase Zn-finger region
      pfam16759
      Location:933 → 1004
      LIG3_BRCT; DNA ligase 3 BRCT domain

    8. XM_047435970.1 → XP_047291926.1  DNA ligase 3 isoform X2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060941.1 Alternate T2T-CHM13v2.0

      Range
      35928368..35957659
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054316054.1 → XP_054172029.1  DNA ligase 3 isoform X3

    2. XM_054316057.1 → XP_054172032.1  DNA ligase 3 isoform X6

    3. XM_054316051.1 → XP_054172026.1  DNA ligase 3 isoform X1

    4. XM_054316056.1 → XP_054172031.1  DNA ligase 3 isoform X5

    5. XM_054316058.1 → XP_054172033.1  DNA ligase 3 isoform X7

      UniProtKB/TrEMBL
      B7Z6I3

    6. XM_054316052.1 → XP_054172027.1  DNA ligase 3 isoform X2

    7. XM_054316055.1 → XP_054172030.1  DNA ligase 3 isoform X4

      UniProtKB/Swiss-Prot
      E5KLB5, E5KLB6, P49916, Q16714, Q6NVK3

    8. XM_054316053.1 → XP_054172028.1  DNA ligase 3 isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P49916.2 GenPept UniProtKB/Swiss-Prot:P49916

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