Seroatlas · Human Serome Atlas

LIG4

DNA ligase 4

Also known as: DNLI4_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
P49917
Gene
LIG4
Ensembl
ENSG00000174405
Chromosome
13
Canonical length
911 aa
Protein class
Cancer-related genes, Disease related genes, Enzymes, Human disease related genes, Potential drug targets, Predicted intracellular proteins
Subcellular location
Nucleoplasm,Vesicles

OverviewNCBI Gene

The protein encoded by this gene is a DNA ligase that joins single-strand breaks in a double-stranded polydeoxynucleotide in an ATP-dependent reaction. This protein is essential for V(D)J recombination and DNA double-strand break (DSB) repair through nonhomologous end joining (NHEJ). This protein forms a complex with the X-ray repair cross complementing protein 4 (XRCC4), and further interacts with the DNA-dependent protein kinase (DNA-PK). Both XRCC4 and DNA-PK are known to be required for NHEJ. The crystal structure of the complex formed by this protein and XRCC4 has been resolved. Defects in this gene are the cause of LIG4 syndrome. Alternatively spliced transcript variants encoding the same protein have been observed. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

911 residues, UniProt reviewed canonical sequence.

>P49917|LIG4
     1  MAASQTSQTV ASHVPFADLC STLERIQKSK GRAEKIRHFR EFLDSWRKFH DALHKNHKDV
    61  TDSFYPAMRL ILPQLERERM AYGIKETMLA KLYIELLNLP RDGKDALKLL NYRTPTGTHG
   121  DAGDFAMIAY FVLKPRCLQK GSLTIQQVND LLDSIASNNS AKRKDLIKKS LLQLITQSSA
   181  LEQKWLIRMI IKDLKLGVSQ QTIFSVFHND AAELHNVTTD LEKVCRQLHD PSVGLSDISI
   241  TLFSAFKPML AAIADIEHIE KDMKHQSFYI ETKLDGERMQ MHKDGDVYKY FSRNGYNYTD
   301  QFGASPTEGS LTPFIHNAFK ADIQICILDG EMMAYNPNTQ TFMQKGTKFD IKRMVEDSDL
   361  QTCYCVFDVL MVNNKKLGHE TLRKRYEILS SIFTPIPGRI EIVQKTQAHT KNEVIDALNE
   421  AIDKREEGIM VKQPLSIYKP DKRGEGWLKI KPEYVSGLMD ELDILIVGGY WGKGSRGGMM
   481  SHFLCAVAEK PPPGEKPSVF HTLSRVGSGC TMKELYDLGL KLAKYWKPFH RKAPPSSILC
   541  GTEKPEVYIE PCNSVIVQIK AAEIVPSDMY KTGCTLRFPR IEKIRDDKEW HECMTLDDLE
   601  QLRGKASGKL ASKHLYIGGD DEPQEKKRKA APKMKKVIGI IEHLKAPNLT NVNKISNIFE
   661  DVEFCVMSGT DSQPKPDLEN RIAEFGGYIV QNPGPDTYCV IAGSENIRVK NIILSNKHDV
   721  VKPAWLLECF KTKSFVPWQP RFMIHMCPST KEHFAREYDC YGDSYFIDTD LNQLKEVFSG
   781  IKNSNEQTPE EMASLIADLE YRYSWDCSPL SMFRRHTVYL DSYAVINDLS TKNEGTRLAI
   841  KALELRFHGA KVVSCLAEGV SHVIIGEDHS RVADFKAFRR TFKRKFKILK ESWVTDSIDK
   901  CELQEENQYL I

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against LIG4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability
Intracellular
Secreted
No
Transmembrane segments
0
Mean surface accessibility (rSASA)
0.28
Highest tissue expression
24 nTPM

Expression across tissuesHPA

Tissue

  • retina: 24 nTPM
  • thymus: 21 nTPM
  • liver: 12 nTPM
  • cerebral cortex: 11 nTPM
  • parathyroid gland: 11 nTPM
  • lymph node: 11 nTPM

Single-cell type

  • neutrophils: 30 nCPM
  • choroid plexus epithelial cells: 27 nCPM
  • ependymal cells: 27 nCPM
  • astrocytes: 25 nCPM
  • late primary spermatocytes: 23 nCPM
  • oligodendrocytes: 23 nCPM

Immune cell

  • non-classical monocyte: 10 nTPM
  • eosinophil: 5.6 nTPM
  • intermediate monocyte: 2.9 nTPM
  • neutrophil: 2.6 nTPM
  • naive B-cell: 2.5 nTPM
  • NK-cell: 2.2 nTPM

Brain region

  • hypothalamus: 25 nTPM
  • choroid plexus: 23 nTPM
  • white matter: 19 nTPM
  • hippocampal formation: 18 nTPM
  • thalamus: 18 nTPM
  • cerebral cortex: 18 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about LIG4.

Disease | AllUniProt

Conditions LIG4 is implicated in, by any mechanism.

  • LIG4 syndrome (LIG4S) MIM:606593
  • Severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-negative/NK-cell-positive with sensitivity to ionizing radiation (RSSCID) MIM:602450

Disease | GeneticClinVar

112 pathogenic / likely-pathogenic of 806 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)
0.8
gnomAD pLI
0
gnomAD missense Z
0.2
DepMap mean gene effect
-0.07
DepMap dependency class
selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of LIG4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads LIG4 as an antibody target. Whether an autoantibody or antibody against LIG4 could matter depends on whether native LIG4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

LIG4 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label LIG4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/LIG4. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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