Human Gene LIG3 (uc002hik.2) Description and Page Index
  Description: Homo sapiens ligase III, DNA, ATP-dependent (LIG3), nuclear gene encoding mitochondrial protein, transcript variant alpha, mRNA.
RefSeq Summary (NM_013975): 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].
Transcript (Including UTRs)
   Position: hg19 chr17:33,307,517-33,332,088 Size: 24,572 Total Exon Count: 20 Strand: +
Coding Region
   Position: hg19 chr17:33,310,025-33,331,525 Size: 21,501 Coding Exon Count: 19 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr17:33,307,517-33,332,088)mRNA (may differ from genome)Protein (1009 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDLynxMGI
neXtProtOMIMPubMedReactomeStanford SOURCETreefam
UniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: DNLI3_HUMAN
DESCRIPTION: RecName: Full=DNA ligase 3; EC=6.5.1.1; AltName: Full=DNA ligase III; AltName: Full=Polydeoxyribonucleotide synthase [ATP] 3;
FUNCTION: Interacts with DNA-repair protein XRCC1 and can correct defective DNA strand-break repair and sister chromatid exchange following treatment with ionizing radiation and alkylating agents.
CATALYTIC ACTIVITY: ATP + (deoxyribonucleotide)(n) + (deoxyribonucleotide)(m) = AMP + diphosphate + (deoxyribonucleotide)(n+m).
COFACTOR: Magnesium (By similarity).
SUBCELLULAR LOCATION: Nucleus.
TISSUE SPECIFICITY: Testis, thymus, prostate and heart.
SIMILARITY: Belongs to the ATP-dependent DNA ligase family.
SIMILARITY: Contains 1 BRCT domain.
SIMILARITY: Contains 1 PARP-type zinc finger.
SEQUENCE CAUTION: Sequence=AAA85022.1; Type=Erroneous initiation; Sequence=AAL91592.1; Type=Erroneous initiation; Sequence=CAA59230.1; Type=Erroneous initiation;
WEB RESOURCE: Name=Wikipedia; Note=DNA ligase entry; URL="http://en.wikipedia.org/wiki/DNA_ligase";
WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/mpg/";

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): LIG3
CDC HuGE Published Literature: LIG3
Positive Disease Associations: Electrocardiography , QT interval
Related Studies:
  1. Electrocardiography
    Christopher Newton-Cheh et al. Nature genetics 2009, Common variants at ten loci influence QT interval duration in the QTGEN Study., Nature genetics. [PubMed 19305408]
  2. QT interval
    Newton-Cheh ,et al. 2009, Common variants at ten loci influence QT interval duation in the QTGEN Study, Nature genetics 2009 41- 4 : 399-406. [PubMed 19305408]

-  MalaCards Disease Associations
  MalaCards Gene Search: LIG3
Diseases sorted by gene-association score: cloacal exstrophy (11), bloom syndrome (11), intracranial abscess (11), hyperornithinemia-hyperammonemia-homocitrullinemia syndrome (6), meninges hemangiopericytoma (6), cutaneous anthrax (6), hypertrichotic osteochondrodysplasia cantu type (5), deafness, autosomal recessive 16 (4), coproporphyria (4)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 18.25 RPKM in Testis
Total median expression: 296.50 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -59.30129-0.460 Picture PostScript Text
3' UTR -149.20563-0.265 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR001357 - BRCT_dom
IPR000977 - DNA_ligase_ATP-dep
IPR012309 - DNA_ligase_ATP-dep_C
IPR012310 - DNA_ligase_ATP-dep_cent
IPR016059 - DNA_ligase_ATP-dep_CS
IPR012308 - DNA_ligase_ATP-dep_N
IPR012340 - NA-bd_OB-fold
IPR016027 - NA-bd_OB-fold-like
IPR001510 - Znf_PARP

Pfam Domains:
PF00645 - Poly(ADP-ribose) polymerase and DNA-Ligase Zn-finger region
PF01068 - ATP dependent DNA ligase domain
PF04675 - DNA ligase N terminus
PF04679 - ATP dependent DNA ligase C terminal region
PF16589 - BRCT domain, a BRCA1 C-terminus domain
PF16759 - DNA ligase 3 BRCT domain

SCOP Domains:
52113 - BRCT domain
56091 - DNA ligase/mRNA capping enzyme, catalytic domain
57716 - Glucocorticoid receptor-like (DNA-binding domain)

Protein Data Bank (PDB) 3-D Structure
MuPIT help

1IMO
- NMR MuPIT

1IN1
- NMR MuPIT

1UW0
- NMR MuPIT
To conserve bandwidth, only the images from the first 3 structures are shown.
3L2P - X-ray MuPIT 3PC7 - X-ray MuPIT 3PC8 - X-ray MuPIT
3QVG - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P49916
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologGenome BrowserNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
  Ensembl   
  Protein Sequence   
  Alignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0003677 DNA binding
GO:0003909 DNA ligase activity
GO:0003910 DNA ligase (ATP) activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0008270 zinc ion binding
GO:0016874 ligase activity
GO:0046872 metal ion binding

Biological Process:
GO:0000724 double-strand break repair via homologous recombination
GO:0006260 DNA replication
GO:0006266 DNA ligation
GO:0006281 DNA repair
GO:0006283 transcription-coupled nucleotide-excision repair
GO:0006288 base-excision repair, DNA ligation
GO:0006297 nucleotide-excision repair, DNA gap filling
GO:0006302 double-strand break repair
GO:0006310 DNA recombination
GO:0006974 cellular response to DNA damage stimulus
GO:0007005 mitochondrion organization
GO:0007049 cell cycle
GO:0043504 mitochondrial DNA repair
GO:0051103 DNA ligation involved in DNA repair
GO:0051301 cell division
GO:0071897 DNA biosynthetic process
GO:0090298 negative regulation of mitochondrial DNA replication
GO:0097681 double-strand break repair via alternative nonhomologous end joining
GO:0006273 lagging strand elongation
GO:0033151 V(D)J recombination

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005739 mitochondrion
GO:0070421 DNA ligase III-XRCC1 complex


-  Descriptions from all associated GenBank mRNAs
  BC068005 - Homo sapiens ligase III, DNA, ATP-dependent, mRNA (cDNA clone MGC:75006 IMAGE:6092747), complete cds.
AK308407 - Homo sapiens cDNA, FLJ98355.
AK300363 - Homo sapiens cDNA FLJ61710 complete cds, highly similar to DNA ligase 3 (EC 6.5.1.1).
U40671 - Human DNA ligase III mRNA, complete cds.
X84740 - H.sapiens mRNA for DNA ligase III.
BC009026 - Homo sapiens ligase III, DNA, ATP-dependent, mRNA (cDNA clone IMAGE:4184595), complete cds.
KJ901552 - Synthetic construct Homo sapiens clone ccsbBroadEn_10946 LIG3 gene, encodes complete protein.
CU686601 - Synthetic construct Homo sapiens gateway clone IMAGE:100022853 5' read LIG3 mRNA.
KJ891547 - Synthetic construct Homo sapiens clone ccsbBroadEn_00941 LIG3 gene, encodes complete protein.
JD052265 - Sequence 33289 from Patent EP1572962.
JD492374 - Sequence 473398 from Patent EP1572962.
AK125853 - Homo sapiens cDNA FLJ43865 fis, clone TESTI4007810.
JD060815 - Sequence 41839 from Patent EP1572962.
JD565283 - Sequence 546307 from Patent EP1572962.
JD131824 - Sequence 112848 from Patent EP1572962.
JD560047 - Sequence 541071 from Patent EP1572962.
JD465898 - Sequence 446922 from Patent EP1572962.
JD385426 - Sequence 366450 from Patent EP1572962.
JD109553 - Sequence 90577 from Patent EP1572962.
JD228875 - Sequence 209899 from Patent EP1572962.
JD545341 - Sequence 526365 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa03410 - Base excision repair

Reactome (by CSHL, EBI, and GO)

Protein P49916 (Reactome details) participates in the following event(s):

R-HSA-110376 Recruitment of LIG3:XRCC1 complex to the site of repair by POLB
R-HSA-5649726 LIG3:XRCC1 and PNKP bind NEIL1,NEIL2:POLB:SSB(3'Pi)-gap-dsDNA
R-HSA-5687673 MRN recruits LIG3:XRCC1 to MMEJ sites
R-HSA-110380 Dissociation of LIG3:XRCC1 complex from the BER site
R-HSA-5649724 LIG3:XRCC1, POLB, NEIL1,NEIL2 and PNKP dissociate from the BER site
R-HSA-5687675 LIG3 ligates remaining SSBs in MMEJ
R-HSA-73932 Resynthesis of excised residue by POLB
R-HSA-73931 LIG3-mediated DNA ligation via the single-nucleotide replacement pathway
R-HSA-5649734 LIG3 ligates NEIL1,NEIL2-generated single strand break
R-HSA-5649705 PNKP hydrolyzes the terminal 3'Pi at the NEIL1,NEIL2-generated single strand break (SSB)
R-HSA-5649723 POLB incorporates a single nucleotide in place of excised AP residue in NEIL1,NEIL2-mediated AP site resolution
R-HSA-5690997 Ligation of newly synthesized repair patch to incised DNA in GG-NER
R-HSA-6782227 Ligation of newly synthesized repair patch to incised DNA in TC-NER
R-HSA-110381 Resolution of AP sites via the single-nucleotide replacement pathway
R-HSA-5649702 APEX1-Independent Resolution of AP Sites via the Single Nucleotide Replacement Pathway
R-HSA-5685939 HDR through MMEJ (alt-NHEJ)
R-HSA-73933 Resolution of Abasic Sites (AP sites)
R-HSA-5693538 Homology Directed Repair
R-HSA-5696397 Gap-filling DNA repair synthesis and ligation in GG-NER
R-HSA-6782210 Gap-filling DNA repair synthesis and ligation in TC-NER
R-HSA-73884 Base Excision Repair
R-HSA-5693532 DNA Double-Strand Break Repair
R-HSA-5696399 Global Genome Nucleotide Excision Repair (GG-NER)
R-HSA-6781827 Transcription-Coupled Nucleotide Excision Repair (TC-NER)
R-HSA-73894 DNA Repair
R-HSA-5696398 Nucleotide Excision Repair

-  Other Names for This Gene
  Alternate Gene Symbols: DNLI3_HUMAN, NM_013975, NP_039269, P49916, Q16714, Q6NVK3
UCSC ID: uc002hik.2
RefSeq Accession: NM_013975
Protein: P49916 (aka DNLI3_HUMAN)
CCDS: CCDS11284.2

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_013975.3
exon count: 20CDS single in 3' UTR: no RNA size: 3722
ORF size: 3030CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 6133.00frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.