LIG4 - DNA ligase 4 Gene

Also Known as LIG4S

Species: Homo sapiens

Gene Type: protein coding

Gene ID: 3981

About LIG4

Cytogenetic location: 13q33.3 Genomic coordinates (GRCh38): 13:108,207,442-108,218,349 (from NCBI)

This gene has 19 transcripts (splice variants), 198 orthologues, 2 paralogues and is associated with 6 phenotypes. Ubiquitous expression in brain (RPKM 5.8), testis (RPKM 4.8) and 25 other tissues.

Summary

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]

LIG4 Products (12)

mRNA	Protein	Name
NM_001098268.2	NP_001091738.1	DNA ligase 4 isoform 1
NM_001330595.2	NP_001317524.1	DNA ligase 4 isoform 2
NM_001352598.2	NP_001339527.1	DNA ligase 4 isoform 1
NM_001352599.2	NP_001339528.1	DNA ligase 4 isoform 1
NM_001352600.2	NP_001339529.1	DNA ligase 4 isoform 1
NM_001352601.2	NP_001339530.1	DNA ligase 4 isoform 1
NM_001352602.2	NP_001339531.1	DNA ligase 4 isoform 1
NM_001352603.1	NP_001339532.1	DNA ligase 4 isoform 1
NM_001352604.2	NP_001339533.1	DNA ligase 4 isoform 3
NM_001379095.1	NP_001366024.1	DNA ligase 4 isoform 1
NM_002312.3	NP_002303.2	DNA ligase 4 isoform 1
NM_206937.2	NP_996820.1	DNA ligase 4 isoform 1

Gene Ontology

Molecular Function
Biological Process
Cellular Component

Molecular Function GO Annotation	Evidence	References	Source
enables DNA binding	IDA IDA: Inferred from direct assay	8798671	GOA
enables DNA ligase (ATP) activity	IDA IDA: Inferred from direct assay	8798671	GOA
enables DNA ligase (ATP) activity	IMP IMP: Inferred from mutant phenotype	29980672	GOA
enables DNA ligase activity	IDA IDA: Inferred from direct assay	12517771	GOA
enables ligase activity	IDA IDA: Inferred from direct assay	9242410	GOA
enables magnesium ion binding	IDA IDA: Inferred from direct assay	29980672	GOA
enables protein binding	IPI IPI: Inferred from physical interaction	9242410	GOA

Biological Process GO Annotation	Evidence	References	Source
involved in DNA ligation	IDA IDA: Inferred from direct assay	12517771	GOA
involved in DNA ligation involved in DNA repair	IDA IDA: Inferred from direct assay	12517771	GOA
involved in V(D)J recombination	IDA IDA: Inferred from direct assay	9809069	GOA
involved in cellular response to ionizing radiation	IGI IGI: Inferred from genetic interaction	29463814	GOA
involved in double-strand break repair	IDA IDA: Inferred from direct assay	9242410	GOA
involved in double-strand break repair via classical nonhomologous end joining	IMP IMP: Inferred from mutant phenotype	24837021	GOA
involved in double-strand break repair via nonhomologous end joining	IDA IDA: Inferred from direct assay	12517771	GOA
involved in double-strand break repair via nonhomologous end joining	IGI IGI: Inferred from genetic interaction	23275564	GOA
involved in double-strand break repair via nonhomologous end joining	IMP IMP: Inferred from mutant phenotype	9809069	GOA
involved in nucleotide-excision repair, DNA gap filling	IDA IDA: Inferred from direct assay	12517771	GOA
involved in positive regulation of chromosome organization	IMP IMP: Inferred from mutant phenotype	23275564	GOA
involved in response to X-ray	IMP IMP: Inferred from mutant phenotype	9809069	GOA
involved in single strand break repair	IDA IDA: Inferred from direct assay	8798671	GOA

Cellular Component GO Annotation	Evidence	References	Source
part of DNA ligase IV complex	IMP IMP: Inferred from mutant phenotype	9809069	GOA
part of DNA-dependent protein kinase-DNA ligase 4 complex	IDA IDA: Inferred from direct assay	15194694	GOA
located in condensed chromosome	IDA IDA: Inferred from direct assay	12589063	GOA
part of nonhomologous end joining complex	IDA IDA: Inferred from direct assay	20383123	GOA
is active in nucleus	IDA IDA: Inferred from direct assay	25934149	GOA
located in nucleus	IDA IDA: Inferred from direct assay	8798671	GOA

EXP: Inferred from Experiment IDA: Inferred from direct assay IPI: Inferred from physical interaction IMP: Inferred from mutant phenotype IGI: Inferred from genetic interaction IEP: Inferred from expression pattern

LIG4 Protein Structure

DNA_ligase_A_N

DNA_ligase_A_M

DNA_ligase_A_C

BRCT

DNA_ligase_IV

BRCT

0
200
400
600
800
911 a.a.

Protein Preferred Names	Protein Names
DNA ligase 4	DNA joinase

LIG4 Protein-protein interaction Information

Type	Protein Name	Protein ID	Interactor	Interactor Species	Interactor ID	Detection Method	References
Intra	LIG4	P49917	DCLRE1C	Homo sapiens	Q96SD1	ITC	23219551
Intra	LIG4	P49917	DCLRE1C	Homo sapiens	Q96SD1	Anti Tag CoIP	22529269
Intra	LIG4	P49917	DCLRE1C	Homo sapiens	Q96SD1	Anti Bait CoIP	22529269
Intra	LIG4	P49917	DCLRE1C	Homo sapiens	Q96SD1	Anti Tag CoIP	23219551
Intra	LIG4	P49917	DCLRE1C	Homo sapiens	Q96SD1	X-Ray Diffraction	23219551
Intra	LIG4	P49917	DCLRE1C	Homo sapiens	Q96SD1	FPS	23219551
Intra	LIG4	P49917	XRCC4	Homo sapiens	Q13426-2	Pull Down	22658747
Intra	LIG4	P49917	XRCC4	Homo sapiens	Q13426-2	GMS	22658747
Intra	LIG4	P49917	XRCC4	Homo sapiens	Q13426-2	SAXS	21070942
Intra	LIG4	P49917	XRCC4	Homo sapiens	Q13426-2	Light Scattering	21070942
Intra	LIG4	P49917	XRCC4	Homo sapiens	Q13426-2	GMS	21070942
Intra	LIG4	P49917	XRCC4	Homo sapiens	Q13426-2	SAXS	22658747
Intra	LIG4	P49917	XRCC4	Homo sapiens	Q13426	GMS	31548606
Intra	LIG4	P49917	XRCC4	Homo sapiens	Q13426	Anti Tag CoIP	31548606
Intra	LIG4	P49917	XRCC4	Homo sapiens	Q13426	Validated Y2H	25910212
Intra	LIG4	P49917	XRCC4	Homo sapiens	Q13426	Y2H Prey Pooling	25416956
Intra	LIG4	P49917	XRCC4	Homo sapiens	Q13426	Anti Tag CoIP	22529269
Intra	LIG4	P49917	XRCC4	Homo sapiens	Q13426	Validated Y2H	32296183
Intra	LIG4	P49917	XRCC4	Homo sapiens	Q13426	Y2H Array	25910212
Intra	LIG4	P49917	XRCC4	Homo sapiens	Q13426	Y2H Prey Pooling	32296183
Intra	LIG4	P49917	XRCC4	Homo sapiens	Q13426	Y2H Array	32296183
Intra	LIG4	P49917	XRCC4	Homo sapiens	Q13426	Anti Tag CoIP	23219551
Intra	LIG4	P49917	XRCC4	Homo sapiens	Q13426	Y2H Bait-Prey Pool	25910212
Intra	LIG4	P49917	XRCC4	Homo sapiens	Q13426	Anti Tag CoIP	33961781
Intra	LIG4	P49917	NHEJ1	Homo sapiens	Q9H9Q4	Anti Bait CoIP	16439205

Cross: Cross-species interaction Intra: Intraspecies interaction

LIG4 Antibodies

Cat. No.	Product Name	Application	Reactivity
HY-P82954	DNA Ligase IV Antibody (YA2699)	WB	Human
HY-P82954A	DNA Ligase IV Antibody (YA2699)(PBS only)	WB	Human

Related Diseases

Diseases	Alias
Lig4 Syndrome	Dna Ligase Iv Deficiency Ligase 4 Syndrome LIG4S
Myeloma, Multiple	Multiple Myeloma Plasma Cell Myeloma Kahler Disease Myelomatosis Medullary Plasmacytoma Multiple Myeloma, Resistance To Myeloma Plasma Cell Dyscrasia Kahler'S Disease Multiple Myeloma, Susceptibility To Myeloma - Multiple Kahler-Bozzolo Disease Plasma Cell Myelomas MM Plasma Cell Neoplasm Primary Systemic Amyloidosis Primary Amyloidosis Immunoglobulin Deposition Disease Plasmacytic Myeloma Multiple Myelomata Multiple Myeloma Nos Multiple Myeloma Without Mention Of Remission Monostotic Plasma Cell Myeloma Mm - [Multiple Myeloma]
Dubowitz Syndrome	Dubowitz'S Syndrome Dwarfism-Eczema-Peculiar Facies Syndrome Intrauterine Growth Restriction, Short Stature, Microcephaly, Mild Intellectual Disability With Behavior Problems, Eczema, And Unusual And Distinctive Faci
Plasma Cell Neoplasm	Plasma Cell Dyscrasia Paraproteinemias Plasma Cell Tumour Plasmacytic Tumor Multiple Myeloma Plasmacytoma Plasma Cell Tumours Plasma Cells Dyscrasia
Severe Combined Immunodeficiency	Scid Severe Combined Immunodeficiency Disease Combined T And B Cell Inborn Immunodeficiency Immunodeficiency, Severe Combined Scid - [Severe Combined Immunodeficiencies]
Omenn Syndrome	Histiocytic Medullary Reticulosis Severe Combined Immunodeficiency With Hypereosinophilia Combined Immunodeficiency With Hypereosinophilia Reticuloendotheliosis, Familial, With Eosinophilia Reticuloendotheliosis Familial With Eosinophilia Familial Reticuloendotheliosis Omenn'S Syndrome OS Malignant Histiocytosis
Nijmegen Breakage Syndrome	Berlin Breakage Syndrome NBS Microcephaly, Normal Intelligence And Immunodeficiency Ataxia-Telangiectasia Variant Ataxia-Telangiectasia Variant V1 Seemanova Syndrome Ii Immunodeficiency-Microcephaly-Chromosomal Instability Syndrome Seemanova Syndrome Type 2 At-V1 Microcephaly With Normal Intelligence, Immunodeficiency, And Lymphoreticular Malignancies Nonsyndromal Microcephaly, Autosomal Recessive, With Normal Intelligence Immunodeficiency, Microcephaly, And Chromosomal Instability Microcephaly-Immunodeficiency-Lymphoreticuloma Syndrome Microcephaly Immunodeficiency Lymphoreticuloma Microcephaly With Normal Intelligence Immunodeficiency And Lymphoreticular Malignancies Nonsyndromal Microcephaly Autosomal Recessive With Normal Intelligence Seemanova Syndrome 2 Ataxia-Telangiectasia Variant 1 Seemanova Syndrome At V1 Ataxia-Telangiectasia, Variant 1 Microcephaly-Immunodeficiency-Lymphoid Malignancy Syndrome V-At Ataxia Telangiectasia Variant V1
Combined Immunodeficiency	Combined T Cell And B Cell Immunodeficiency Congenital Combined Immunodeficiency Syndrome With Combined Immunodeficiency Combined T And B Cell Immunodeficiency Combined Immunity Deficiency Combined Immunodeficiency Syndrome Combined T-Cell And B-Cell Immunodeficiency Lymphopenic Agammaglobulinaemia
Seckel Syndrome	Microcephalic Primordial Dwarfism Bird-Headed Dwarfism Harper'S Syndrome Virchow-Seckel Dwarfism Nanocephalic Dwarfism Sckl Seckel-Type Dwarfism
Microcephaly	Microencephaly Microcephalus Microcephalic Nanocephaly Congenital Microcephaly Brain Hypoplasia Brain Nondevelopment Cephalic Hypoplasia Undeveloped Cerebrum Undeveloped Brain Micrencephalon Micrencephaly
Fanconi Anemia, Complementation Group A	Fanconi Anemia Fanconi Pancytopenia Fanconi Anemia Complementation Group A FANCA Fa Fanconi Panmyelopathy Fanconi'S Anemia Fanconi Anaemia Fanconi'S Anaemia Fanconi Hypoplastic Anemia Estren-Dameshek Variant Of Fanconi Anemia Estren-Dameshek Variant Of Fanconi Pancytopenia Fanconi Anemia Estren-Dameshek Variant Fanconis Anemia
Severe Combined Immunodeficiency With Sensitivity To Ionizing Radiation	Severe Combined Immunodeficiency, Athabascan Type Severe Combined Immunodeficiency Due To Dclre1c Deficiency Rs-Scid Scid, Autosomal Recessive, T Cell-Negative, B Cell-Negative, Nk Cell-Positive, With Sensitivity To Ionizing Radiation Scid Due To Artemis Deficiency Scid Due To Dclre1c Deficiency Scid, Athabascan Type Scid, Athabaskan Type Severe Combined Immunodeficiency Due To Artemis Deficiency Severe Combined Immunodeficiency, Athabaskan Type SCIDA Severe Combined Immunodeficiency, Athabascan-Type Artemis Deficiency Severe Combined Immunodeficiency Athabaskan Type Severe Combined Immunodeficiency Autosomal Recessive T-Cell-Negative/B-Cell-Negative/Nk-Cell-Positive With Sensitivity To Ionizing Radiation RSSCID Athabascan Scid Immunodeficiency, Severe Combined, Athabascan Type Severe Combined Immunodeficiency, Athabaskan-Type
Xeroderma Pigmentosum, Variant Type	Xeroderma Pigmentosum XPV Xeroderma Pigmentosum Variant Type Xeroderma Pigmentosum With Normal Dna Repair Rates Photosensitivity With Defective Dna Synthesis Xp De Sanctis-Cacchione Syndrome Desanctis-Cacchione Syndrome Xeroderma Pigmentosa Xerodermic Idiocy Xeroderma Pigmentosum Variant Xp - [Xeroderma Pigmentosum] Atrophoderma Pigmentosum
Dyskeratosis Congenita	Dyskeratosis Congenita Autosomal Dominant Dc Dkc Zinsser-Engman-Cole Syndrome Dyskeratosis Congenita, Autosomal Dominant Autosomal Dominant Dyskeratosis Congenita Dkca Dyskeratosis Congenita Scoggins Type Zinsser-Cole-Engman Syndrome X-Linked Dyskeratosis Congenita Hoyeraal-Hreidarsson Syndrome
Pancytopenia
Ataxia-Telangiectasia	Ataxia Telangiectasia Louis-Bar Syndrome AT At1 Ataxia-Telangiectasia Syndrome Ataxia - Telangiectasia Variant Boder-Sedgwick Syndrome Louis Bar Syndrome Cerebello-Oculocutaneous Telangiectasia Immunodeficiency With Ataxia Telangiectasia A-T Ataxia Telangiectasia Syndrome Atm Telangiectasia, Cerebello-Oculocutaneous Ataxia-Telangiectasia Variant
Janus Kinase-3 Deficiency
Bare Lymphocyte Syndrome, Type Ii	Mhc Class Ii Deficiency Bare Lymphocyte Syndrome Major Histocompatibility Complex Class Ii Deficiency Bare Lymphocyte Syndrome 2 Bare Lymphocyte Syndrome Type 2 Severe Combined Immunodeficiency, Hla Class Ii-Negative Bare Lymphocyte Syndrome, Type Ii, Complementation Group C Bare Lymphocyte Syndrome, Type Ii, Complementation Group D Bare Lymphocyte Syndrome Type Ii Scid, Hla Class Ii-Negative Bare Lymphocyte Syndrome, Type Ii, Complementation Group A Bare Lymphocyte Syndrome, Type Ii, Complementation Group B Scid Due To Absent Class Ii Hla Antigens Hla Class 1 Deficiency Scid, Hla Class 2-Negative Bls Type Ii Bare Lymphocyte Syndrome Type 2, Complementation Group A Bare Lymphocyte Syndrome Type 2, Complementation Group E Severe Combined Immunodeficiency Bls, Type Ii Bls Bare Lymphocyte Syndrome, Type Ii, Complementation Group E Blsii Bls Type 1 Bls 2 Scid Due To Absence Of Class Ii Hla Antigens Severe Combined Immunodeficiency Due To Absent Class Ii Human Leukocyte Antigens Immunodeficiency By Defective Expression Of Mhc Class Ii BLS2 Bare Lymphocyte Syndrome Type Ii Complementation Group A Bare Lymphocyte Syndrome Type Ii Complementation Group B Bare Lymphocyte Syndrome Type Ii Complementation Group C Bare Lymphocyte Syndrome Type Ii Complementation Group D Bare Lymphocyte Syndrome Type Ii Complementation Group E Bls Ii Hereditary Mhc Class Ii Deficiency Hla Class Ii Deficient Combined Immunodeficiency Mhc-Ii Deficiency Scid Hla Class Ii-Negative Severe Combined Immunodeficiency Hla Class Ii-Negative Bl-2 Immunodeficiency By Defective Expression Of Hla Class 2 Hla Class 2-Negative Severe Combined Immunodeficiency
Autosomal Recessive Cerebellar Ataxia	Arca
Immune Deficiency Disease	Immunodeficiency Primary Immunodeficiency Primary Immunodeficiency Disease Immunologic Deficiency Syndromes Hypoimmunity Immune Deficiency Disorder Immunodeficiency Syndrome Immune Disorder Primary Immune Deficiency Disorder Immune System Diseases Human Immunodeficiency Virus Infection Hiv - [Human Immunodeficiency Virus Infection] Hiv Positive Nos Hiv Disease Acquired Immune Deficiency Syndrome-Related Complex Aids-Like Syndrome Aids-Related Complex Nos Arc - [Aids-Related Complex] Immunodeficiency Due To Human Immunodeficiency Virus Infection Unspecified Human Immunodeficiency Virus Disease Hiv Disease Nos Human Immunodeficiency Virus Positive Nos Hiv Nos Deficiency Of Complement Initial Pathway Deficiency Of Complement Terminal Pathway Cfdd - [Complement Factor D Deficiency] Immunodeficiency With Nk-Cell - [Natural-Killer Cell] Deficiency Nonfamilial Hypogammaglobulinaemia Common Variable Immune Deficiency Nonfamilial Agammaglobulinaemia Common Variable Agammaglobulinaemia Agammaglobulinaemia Nos Agammaglobulinaemia Antibody Deficiency Syndrome Hypogammaglobulinaemia Antibody Deficiency Syndrome Acquired Agammaglobulinaemia Nos Hypogammaglobulinaemia Nos Hyper Igm
Medulloblastoma	MDB Cpnet Localized Primitive Neuroectodermal Tumor Classic Medulloblastoma Medulloblastoma Predisposition Syndrome Medulloblastoma, Somatic Brain Medulloblastoma Cns Pnet Infratentorial Primitive Neuroectodermal Tumor Neuroectodermal Tumors, Primitive Medulloblastomas Desmoplastic Medulloblastoma Medulloblastoma, With Extensive Nodularity Medulloblastoma Of Unspecified Site Medullomyoblastoma Of Unspecified Site
Breast Cancer	Breast Carcinoma Male Breast Cancer Breast Cancer, Familial Malignant Neoplasm Of Breast Breast Cancer, Susceptibility To Breast Cancer, Early-Onset Malignant Tumor Of Breast Carcinoma Of Male Breast Breast Cancer, Invasive Ductal Breast Cancer, Protection Against Breast Cancer, Somatic Breast Cancer, Male Breast Cancer, Lobular, Somatic Breast Tumor Mammary Cancer Mammary Tumor Malignant Neoplasm Of Male Breast Mammary Carcinoma Male Breast Carcinoma Familial Cancer Of Breast Invasive Ductal Breast Carcinoma Breast Cancer Susceptibility Breast Cancer, Male, Susceptibility To Breast Cancer, Early-Onset, Susceptibility To Malignant Tumor Of The Breast Mammary Neoplasm Primary Breast Cancer Neoplasm Of Male Breast Carcinoma Of Breast Breast Cancer In Men Familial Breast Cancer Cancer Of Breast BC Breast Cancer Familial Breast Cancer Familial Male Breast Cancer, Familial Male Breast Male Carcinoma Breast Neoplasms Breast Neoplasms, Male Mammary Tumors Mammary Carcinomas Cancer, Breast Cancer, Breast, Susceptibility Invasive Breast Ductal Carcinoma Breast Neoplasm Susceptibility To Breast Cancer Mammary Neoplasms Animal Mammary Neoplasms Primary Malignant Neoplasm Of Breast Infiltrating Ductal Carcinoma Of Breast Infiltrating Duct Carcinoma Of Unspecified Site Infiltrating Ductular Carcinoma Of Unspecified Site Invasive Breast Carcinoma Of No Special Type Microinvasive Carcinoma Of Breast Carcinoma With Apocrine Differentiation
Congenital Nervous System Abnormality	Congenital Neurologic Anomaly Congenital Nervous System Disorder
Aplastic Anemia	Aplastic Anemia, Susceptibility To Anemia Aplastic Idiopathic Aplastic Anemia Secondary Aplastic Anemia Idiopathic Bone Marrow Failure Aplastic Anemia Idiopathic AA Anemia, Aplastic Aplastic Anemia, Idiopathic Erythroid Aplasia Aa - [Aplastic Anaemia] Haematopoietic Aplasia Aleukia Haemorrhagica Anaemia Due To Decreased Red Cell Production Aplasia Bone Marrow Aplastic Bone Marrow Hypoplastic Anaemia Nos Myeloid Bone Marrow Aplasia Pancytopenia Panhaematopenia Hypoproliferative Anaemia Medullary Hypoplasia Red Blood Cells Hypoplastic Anaemia Panmyelophthisis Panhemocytopenia Refractive Hypoproliferative Anaemia Toxic Anaemia Toxic Aplastic Anaemia Aplastic Anaemia Due To Toxic Cause Idiopathic Aplastic Anaemia Nos
Hereditary Breast Ovarian Cancer Syndrome	Hereditary Breast And Ovarian Cancer Syndrome Brca1- And Brca2-Associated Hereditary Breast And Ovarian Cancer Breast And/Or Ovarian Cancer Breast And Ovarian Cancer Syndrome Hboc Syndrome Hereditary Breast And Ovarian Cancer Brca1- Brca2-Associated Hboc

Diseases	Alias
Waldenstroem'S Macroglobulinemia	Waldenstroem'S Macroglobulinemia Waldenstroem'S Macroglobulinemia Macroglobulinemia Of Waldenstrom Lymphoplasmacytic Lymphoma With Igm Gammopathy Lymphoplasmacytic Lymphoma Waldenstroem'S Macroglobulinemia Waldenstroem'S Macroglobulinemia Macroglobulinemia Of Waldenstrom Lymphoplasmacytic Lymphoma With Igm Gammopathy Lymphoplasmacytic Lymphoma

Related Agents

Pre-clinical Phase

Pre-clinical Phase

Bioactive Molecules (3)

Cat. No.	Product Name	Effect	Purity	Rare Diseases
HY-RS07644	LIG4 Human Pre-designed siRNA Set A	Pre-designed Set	/	Unkown
HY-RS19909	Lig4 Mouse Pre-designed siRNA Set A	Pre-designed Set	/	Unkown
HY-RS26410	Lig4 Rat Pre-designed siRNA Set A	Pre-designed Set	/	Unkown

Orthologs Information

Species	Symbol	Source	ID
Macaca mulatta	LIG4	VGNC	VGNC:74267
Rattus norvegicus	LIG4	RGD	RGD:1304639
Bos taurus	LIG4	VGNC	VGNC:30884
Felis catus	LIG4	VGNC	VGNC:68049
Canis familiaris	LIG4	VGNC	VGNC:42675
Mus musculus	LIG4	MGD	MGI:1335098
Others	LIG4	NCBI