3II6

Structure of human Xrcc4 in complex with the tandem BRCT domains of DNA LigaseIV.

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Domain Annotation: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A	d3ii6a1	All beta proteins	XRCC4, N-terminal domain	XRCC4, N-terminal domain	XRCC4, N-terminal domain	XRCC4, N-terminal domain	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d3ii6a2	Coiled coil proteins	Parallel coiled-coil	XRCC4, C-terminal oligomerization domain	XRCC4, C-terminal oligomerization domain	XRCC4, C-terminal oligomerization domain	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d3ii6b1	All beta proteins	XRCC4, N-terminal domain	XRCC4, N-terminal domain	XRCC4, N-terminal domain	XRCC4, N-terminal domain	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d3ii6b2	Coiled coil proteins	Parallel coiled-coil	XRCC4, C-terminal oligomerization domain	XRCC4, C-terminal oligomerization domain	XRCC4, C-terminal oligomerization domain	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C	d3ii6c1	All beta proteins	XRCC4, N-terminal domain	XRCC4, N-terminal domain	XRCC4, N-terminal domain	XRCC4, N-terminal domain	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C	d3ii6c2	Coiled coil proteins	Parallel coiled-coil	XRCC4, C-terminal oligomerization domain	XRCC4, C-terminal oligomerization domain	XRCC4, C-terminal oligomerization domain	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D	d3ii6d1	All beta proteins	XRCC4, N-terminal domain	XRCC4, N-terminal domain	XRCC4, N-terminal domain	XRCC4, N-terminal domain	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D	d3ii6d2	Coiled coil proteins	Parallel coiled-coil	XRCC4, C-terminal oligomerization domain	XRCC4, C-terminal oligomerization domain	XRCC4, C-terminal oligomerization domain	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2B Superfamily	XRCC4 C-terminal oligomerization domain-like	8036636	3001502	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	XRCC4 N-terminal domain-like	8036633	3001319	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	XRCC4 C-terminal oligomerization domain-like	8036636	3001502	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	XRCC4 N-terminal domain-like	8036633	3001319	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	XRCC4 C-terminal oligomerization domain-like	8036636	3001502	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	XRCC4 N-terminal domain-like	8036633	3001319	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	XRCC4 C-terminal oligomerization domain-like	8036636	3001502	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	XRCC4 N-terminal domain-like	8036633	3001319	SCOP2B (2022-06-29)
E [auth X]	SCOP2B Superfamily	DNA ligase IV Xrcc4-binding domain-like	8095958	3002713	SCOP2B (2022-06-29)
F [auth Y]	SCOP2B Superfamily	DNA ligase IV Xrcc4-binding domain-like	8095958	3002713	SCOP2B (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	XRCC4_1st	e3ii6A1	A: beta barrels	X: XRCC4, N-terminal domain-like	H: XRCC4, N-terminal domain (From Topology)	T: XRCC4, N-terminal domain	F: XRCC4_1st	ECOD (1.6)
A	XRCC4_2nd	e3ii6A2	A: alpha arrays	X: HTH	H: HTH	T: HTH motif inserted in other structures	F: XRCC4_2nd	ECOD (1.6)
A	XRCC4_3rd	e3ii6A3	A: alpha duplicates or obligate multimers	X: XRCC4 C-terminal oligomerization domain (From Topology)	H: XRCC4 C-terminal oligomerization domain (From Topology)	T: XRCC4 C-terminal oligomerization domain	F: XRCC4_3rd	ECOD (1.6)
B	XRCC4_1st	e3ii6B1	A: beta barrels	X: XRCC4, N-terminal domain-like	H: XRCC4, N-terminal domain (From Topology)	T: XRCC4, N-terminal domain	F: XRCC4_1st	ECOD (1.6)
B	XRCC4_2nd	e3ii6B2	A: alpha arrays	X: HTH	H: HTH	T: HTH motif inserted in other structures	F: XRCC4_2nd	ECOD (1.6)
B	XRCC4_3rd	e3ii6B3	A: alpha duplicates or obligate multimers	X: XRCC4 C-terminal oligomerization domain (From Topology)	H: XRCC4 C-terminal oligomerization domain (From Topology)	T: XRCC4 C-terminal oligomerization domain	F: XRCC4_3rd	ECOD (1.6)
C	XRCC4_1st	e3ii6C1	A: beta barrels	X: XRCC4, N-terminal domain-like	H: XRCC4, N-terminal domain (From Topology)	T: XRCC4, N-terminal domain	F: XRCC4_1st	ECOD (1.6)
C	XRCC4_2nd	e3ii6C2	A: alpha arrays	X: HTH	H: HTH	T: HTH motif inserted in other structures	F: XRCC4_2nd	ECOD (1.6)
C	XRCC4_3rd	e3ii6C3	A: alpha duplicates or obligate multimers	X: XRCC4 C-terminal oligomerization domain (From Topology)	H: XRCC4 C-terminal oligomerization domain (From Topology)	T: XRCC4 C-terminal oligomerization domain	F: XRCC4_3rd	ECOD (1.6)
D	XRCC4_1st	e3ii6D1	A: beta barrels	X: XRCC4, N-terminal domain-like	H: XRCC4, N-terminal domain (From Topology)	T: XRCC4, N-terminal domain	F: XRCC4_1st	ECOD (1.6)
D	XRCC4_2nd	e3ii6D2	A: alpha arrays	X: HTH	H: HTH	T: HTH motif inserted in other structures	F: XRCC4_2nd	ECOD (1.6)
D	XRCC4_3rd	e3ii6D3	A: alpha duplicates or obligate multimers	X: XRCC4 C-terminal oligomerization domain (From Topology)	H: XRCC4 C-terminal oligomerization domain (From Topology)	T: XRCC4 C-terminal oligomerization domain	F: XRCC4_3rd	ECOD (1.6)
E [auth X]	PTCB-BRCT	e3ii6X2	A: a/b three-layered sandwiches	X: BRCT domain (From Topology)	H: BRCT domain (From Topology)	T: BRCT domain	F: PTCB-BRCT	ECOD (1.6)
E [auth X]	BRCT_2_1	e3ii6X3	A: a/b three-layered sandwiches	X: BRCT domain (From Topology)	H: BRCT domain (From Topology)	T: BRCT domain	F: BRCT_2_1	ECOD (1.6)
F [auth Y]	PTCB-BRCT	e3ii6Y6	A: a/b three-layered sandwiches	X: BRCT domain (From Topology)	H: BRCT domain (From Topology)	T: BRCT domain	F: PTCB-BRCT	ECOD (1.6)
F [auth Y]	BRCT_2_1	e3ii6Y2	A: a/b three-layered sandwiches	X: BRCT domain (From Topology)	H: BRCT domain (From Topology)	T: BRCT domain	F: BRCT_2_1	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	2.170.210.10	Mainly Beta	Beta Complex	Dna Repair Protein Xrcc4	Chain: A, domain 1	CATH (4.3.0)
A	1.20.5.370	Mainly Alpha	Up-down Bundle	Single alpha-helices involved in coiled-coils or other helix-helix interfaces		CATH (4.3.0)
B	2.170.210.10	Mainly Beta	Beta Complex	Dna Repair Protein Xrcc4	Chain: A, domain 1	CATH (4.3.0)
B	1.20.5.370	Mainly Alpha	Up-down Bundle	Single alpha-helices involved in coiled-coils or other helix-helix interfaces		CATH (4.3.0)
C	2.170.210.10	Mainly Beta	Beta Complex	Dna Repair Protein Xrcc4	Chain: A, domain 1	CATH (4.3.0)
C	1.20.5.370	Mainly Alpha	Up-down Bundle	Single alpha-helices involved in coiled-coils or other helix-helix interfaces		CATH (4.3.0)
D	2.170.210.10	Mainly Beta	Beta Complex	Dna Repair Protein Xrcc4	Chain: A, domain 1	CATH (4.3.0)
D	1.20.5.370	Mainly Alpha	Up-down Bundle	Single alpha-helices involved in coiled-coils or other helix-helix interfaces		CATH (4.3.0)
E [auth X]	3.40.50.10190	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	BRCT domain	CATH (4.3.0)
E [auth X]	6.10.250.520	Special	Helix non-globular	Single alpha-helices involved in coiled-coils or other helix-helix interfaces		CATH (4.3.0)
F [auth Y]	3.40.50.10190	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	BRCT domain	CATH (4.3.0)
F [auth Y]	6.10.250.520	Special	Helix non-globular	Single alpha-helices involved in coiled-coils or other helix-helix interfaces		CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B, C, D	PF06632	DNA double-strand break repair and V(D)J recombination protein XRCC4 (XRCC4)	DNA double-strand break repair and V(D)J recombination protein XRCC4	-	Family
E [auth X], F [auth Y]	PF11411	DNA ligase IV (DNA_ligase_IV)	DNA ligase IV	-	Family
E [auth X], F [auth Y]	PF00533	BRCA1 C Terminus (BRCT) domain (BRCT)	BRCA1 C Terminus (BRCT) domain	-	Family

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B, C, D	DNA repair protein XRCC4	protein binding binding FHA domain binding protein domain specific binding identical protein binding	cellular response to stimulus cellular response to inorganic substance cellular response to metal ion cellular response to lithium ion response to stimulus response to inorganic substance cellular response to chemical stimulus response to lithium ion response to metal ion response to chemical cellular process positive regulation of molecular function regulation of molecular function regulation of ligase activity cellular response to stimulus cellular response to inorganic substance cellular response to metal ion cellular response to lithium ion response to stimulus response to inorganic substance cellular response to chemical stimulus response to lithium ion response to metal ion response to chemical cellular process positive regulation of molecular function regulation of molecular function regulation of ligase activity regulation of catalytic activity biological regulation positive regulation of catalytic activity positive regulation of ligase activity response to X-ray response to ionizing radiation response to radiation response to abiotic stimulus DNA ligation involved in DNA repair primary metabolic process DNA metabolic process nucleic acid metabolic process DNA ligation nucleobase-containing compound metabolic process organic cyclic compound metabolic process organic substance metabolic process cellular response to stress DNA damage response response to stress metabolic process macromolecule metabolic process DNA repair protein localization localization cellular localization protein localization to chromosome protein localization to organelle cellular macromolecule localization macromolecule localization protein localization to site of double-strand break double-strand break repair immune system development multicellular organismal process immunoglobulin production cellular biosynthetic process somatic cell DNA recombination multicellular organism development V(D)J recombination somatic recombination of immunoglobulin gene segments anatomical structure development organic substance biosynthetic process somatic diversification of immune receptors system development developmental process production of molecular mediator of immune response DNA recombination cellular metabolic process gene expression macromolecule biosynthetic process somatic diversification of immunoglobulins immunoglobulin V(D)J recombination biosynthetic process immune system process somatic diversification of immune receptors via germline recombination within a single locus double-strand break repair via nonhomologous end joining	protein-containing complex nonhomologous end joining complex catalytic complex intracellular protein-containing complex DNA repair complex membrane-bounded organelle intracellular anatomical structure nucleus nuclear protein-containing complex intracellular membrane-bounded organelle cellular anatomical entity intracellular organelle organelle DNA-dependent protein kinase-DNA ligase 4 complex protein-containing complex nonhomologous end joining complex catalytic complex intracellular protein-containing complex DNA repair complex membrane-bounded organelle intracellular anatomical structure nucleus nuclear protein-containing complex intracellular membrane-bounded organelle cellular anatomical entity intracellular organelle organelle DNA-dependent protein kinase-DNA ligase 4 complex cytoplasm cytosol DNA ligase IV complex site of double-strand break intracellular non-membrane-bounded organelle site of DNA damage chromosome non-membrane-bounded organelle membrane-enclosed lumen intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen
E [auth X], F [auth Y]	DNA ligase 4	ligase activity, forming phosphoric ester bonds DNA ligase (ATP) activity catalytic activity, acting on DNA catalytic activity, acting on a nucleic acid catalytic activity DNA ligase activity ligase activity binding adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding ligase activity, forming phosphoric ester bonds DNA ligase (ATP) activity catalytic activity, acting on DNA catalytic activity, acting on a nucleic acid catalytic activity DNA ligase activity ligase activity binding adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding anion binding adenyl nucleotide binding ATP binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding small molecule binding DNA binding nucleic acid binding cation binding magnesium ion binding metal ion binding	cellular response to stimulus cellular response to inorganic substance cellular response to metal ion cellular response to lithium ion response to stimulus response to inorganic substance cellular response to chemical stimulus response to lithium ion response to metal ion response to chemical cellular process developmental process multicellular organism development multicellular organismal process cellular response to stimulus cellular response to inorganic substance cellular response to metal ion cellular response to lithium ion response to stimulus response to inorganic substance cellular response to chemical stimulus response to lithium ion response to metal ion response to chemical cellular process developmental process multicellular organism development multicellular organismal process central nervous system development anatomical structure development nervous system development system development cell division response to X-ray response to ionizing radiation response to radiation response to abiotic stimulus cell population proliferation cellular response to ionizing radiation cellular response to radiation cellular response to abiotic stimulus cellular response to environmental stimulus embryo development ending in birth or egg hatching chordate embryonic development embryo development in utero embryonic development DNA recombination primary metabolic process DNA metabolic process nucleic acid metabolic process DNA ligation nucleobase-containing compound metabolic process organic cyclic compound metabolic process organic substance metabolic process DNA ligation involved in DNA recombination metabolic process macromolecule metabolic process cellular developmental process hemopoiesis cell activation cell development mononuclear cell differentiation lymphocyte activation lymphocyte differentiation leukocyte activation T cell differentiation in thymus T cell activation immune system process cell differentiation T cell differentiation leukocyte differentiation cellular biosynthetic process cellular metabolic process nucleobase-containing compound biosynthetic process macromolecule biosynthetic process nucleic acid biosynthetic process biosynthetic process organic cyclic compound biosynthetic process organic substance biosynthetic process DNA biosynthetic process stem cell proliferation fibroblast proliferation somatic stem cell population maintenance maintenance of cell number stem cell population maintenance positive regulation of nervous system development regulation of cellular process regulation of developmental process positive regulation of biological process regulation of cell differentiation regulation of neurogenesis regulation of cell development regulation of nervous system development positive regulation of developmental process neurogenesis positive regulation of cell differentiation positive regulation of neurogenesis regulation of multicellular organismal process positive regulation of cellular process regulation of multicellular organismal development regulation of biological process biological regulation positive regulation of cell development positive regulation of multicellular organismal process adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains lymphocyte mediated immunity B cell activation involved in immune response cell activation involved in immune response leukocyte mediated immunity somatic diversification of immune receptors somatic recombination of immunoglobulin genes involved in immune response immune response immune effector process somatic diversification of immunoglobulins B cell mediated immunity isotype switching immune system development immunoglobulin production immunoglobulin production involved in immunoglobulin-mediated immune response somatic cell DNA recombination somatic diversification of immunoglobulins involved in immune response somatic recombination of immunoglobulin gene segments leukocyte activation involved in immune response lymphocyte activation involved in immune response production of molecular mediator of immune response B cell activation gene expression immunoglobulin mediated immune response adaptive immune response somatic diversification of immune receptors via germline recombination within a single locus V(D)J recombination T cell receptor V(D)J recombination somatic diversification of T cell receptor genes somatic recombination of T cell receptor gene segments pro-B cell differentiation lymphoid progenitor cell differentiation hematopoietic progenitor cell differentiation double-strand break repair via classical nonhomologous end joining double-strand break repair double-strand break repair via nonhomologous end joining cellular response to stress DNA damage response response to stress DNA repair cellular component organization organelle organization chromosome organization cellular component organization or biogenesis positive regulation of cell population proliferation regulation of fibroblast proliferation regulation of cell population proliferation positive regulation of fibroblast proliferation establishment of integrated proviral latency viral latency viral process establishment of viral latency DNA ligation involved in DNA repair neuron apoptotic process negative regulation of neuron apoptotic process negative regulation of programmed cell death regulation of apoptotic process negative regulation of biological process regulation of programmed cell death cell death negative regulation of apoptotic process negative regulation of cellular process apoptotic process programmed cell death regulation of neuron apoptotic process cell cycle single strand break repair DN2 thymocyte differentiation nucleotide-excision repair, DNA gap filling nucleotide-excision repair response to gamma radiation immunoglobulin V(D)J recombination positive regulation of organelle organization regulation of cellular component organization positive regulation of cellular component organization regulation of chromosome organization regulation of organelle organization positive regulation of chromosome organization	membrane-bounded organelle protein-containing complex nonhomologous end joining complex intracellular anatomical structure catalytic complex nucleus nuclear protein-containing complex intracellular membrane-bounded organelle cellular anatomical entity intracellular organelle organelle intracellular protein-containing complex DNA ligase IV complex DNA repair complex membrane-bounded organelle protein-containing complex nonhomologous end joining complex intracellular anatomical structure catalytic complex nucleus nuclear protein-containing complex intracellular membrane-bounded organelle cellular anatomical entity intracellular organelle organelle intracellular protein-containing complex DNA ligase IV complex DNA repair complex intracellular non-membrane-bounded organelle chromosome chromosome, telomeric region chromosomal region non-membrane-bounded organelle condensed chromosome membrane-enclosed lumen intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen DNA-dependent protein kinase-DNA ligase 4 complex

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B, C, D	IPR014751	DNA repair protein XRCC4-like, C-terminal	Homologous Superfamily
A, B, C, D	IPR010585	DNA repair protein XRCC4	Family
A, B, C, D	IPR038051	XRCC4-like, N-terminal domain superfamily	Homologous Superfamily
A, B, C, D	IPR009089	XRCC4, N-terminal domain superfamily	Homologous Superfamily
E [auth X], F [auth Y]	IPR029710	DNA ligase 4	Family
E [auth X], F [auth Y]	IPR012310	DNA ligase, ATP-dependent, central	Domain
E [auth X], F [auth Y]	IPR012308	DNA ligase, ATP-dependent, N-terminal	Domain
E [auth X], F [auth Y]	IPR044125	DNA Ligase 4, adenylation domain	Domain
E [auth X], F [auth Y]	IPR012340	Nucleic acid-binding, OB-fold	Homologous Superfamily
E [auth X], F [auth Y]	IPR021536	DNA ligase IV domain	Domain
E [auth X], F [auth Y]	IPR036599	DNA ligase, ATP-dependent, N-terminal domain superfamily	Homologous Superfamily
E [auth X], F [auth Y]	IPR001357	BRCT domain	Domain
E [auth X], F [auth Y]	IPR036420	BRCT domain superfamily	Homologous Superfamily
E [auth X], F [auth Y]	IPR016059	DNA ligase, ATP-dependent, conserved site	Conserved Site
E [auth X], F [auth Y]	IPR000977	DNA ligase, ATP-dependent	Family
E [auth X], F [auth Y]	IPR012309	DNA ligase, ATP-dependent, C-terminal	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B, C, D	Pharos: Q13426	short stature, microcephaly, and endocrine dysfunction DNA ligase IV deficiency Chromosome Aberrations pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia schizophrenia astrocytic tumor congestive heart failure isolated growth hormone deficiency type IA malignant mesothelioma microcephalic primordial dwarfism-insulin resistance syndrome pancreatic intraductal papillary-mucinous carcinoma pilocytic astrocytoma primitive neuroectodermal tumor malignant colon neoplasm malignant pancreatic neoplasm short stature, microcephaly, and endocrine dysfunction DNA ligase IV deficiency Chromosome Aberrations pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia schizophrenia astrocytic tumor congestive heart failure isolated growth hormone deficiency type IA malignant mesothelioma microcephalic primordial dwarfism-insulin resistance syndrome pancreatic intraductal papillary-mucinous carcinoma pilocytic astrocytoma primitive neuroectodermal tumor malignant colon neoplasm malignant pancreatic neoplasm oligodendroglioma pancreatic intraductal papillary-mucinous neoplasm pituitary cancer psoriasis tuberculosis intellectual disability malignant ependymoma medulloblastoma osteosarcoma
E [auth X], F [auth Y]	Pharos: P49917	DNA ligase IV deficiency plasma cell myeloma Omenn syndrome Dubowitz syndrome progressive supranuclear palsy Alzheimer disease hematopoietic and lymphoid system neoplasm leukemia pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia plasma cell neoplasm severe combined immunodeficiency due to DCLRE1C deficiency atypical teratoid rhabdoid tumor Gaucher disease intellectual disability microcephaly DNA ligase IV deficiency plasma cell myeloma Omenn syndrome Dubowitz syndrome progressive supranuclear palsy Alzheimer disease hematopoietic and lymphoid system neoplasm leukemia pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia plasma cell neoplasm severe combined immunodeficiency due to DCLRE1C deficiency atypical teratoid rhabdoid tumor Gaucher disease intellectual disability microcephaly osteosarcoma Pick disease Primary microcephaly glioblastoma large cell medulloblastoma myeloid neoplasm pancreatic intraductal papillary-mucinous neoplasm

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM133198.