NHEJ1
entrez
79840
canonical
uniprot
Q9H9Q4
canonical
ensembl
ENSG00000187736
resolver
ensp
ENSP00000349313
resolver
ensp
ENSP00000394896
resolver
ensp
ENSP00000407201
resolver
ensp
ENSP00000599494
resolver
ensp
ENSP00000599495
resolver
enst
ENST00000426304
resolver
enst
ENST00000929435
resolver
enst
ENST00000929436
resolver
genesymbol
NHEJ1
resolver
genesymbol_syn
XLF
resolver
hgnc
HGNC:25737
resolver
uniprot
B8ZZA4
resolver
uniprot
H7C0G7
resolver
uniprot
Q4ZFW7
resolver
uniprot
Q6IA64
resolver
uniprot
Q96JS9
resolver
uniprot_entry
H7C0G7_HUMAN
resolver
uniprot_entry
NHEJ1_HUMAN
resolver
uniprot_sec
B8ZZA4
resolver
uniprot_sec
Q4ZFW7
resolver
uniprot_sec
Q6IA64
resolver
uniprot_sec
Q96JS9
resolver
amino_acid_sequence
MEELEQGLLMQPWAWLQLAENSLLAKVFITKQGYALLVSDLQQVWHEQVDTSVVSQRAKELNKRLTAPPAAFLCHLDNLLRPLLKDAAHPSEATFSCDCVADALILRVRSELSGLPFYWNFHCMLASPSLVSQHLIRPLMGMSLALQCQVRELATLLHMKDLEIQDYQESGATLIRDRLKTEPFEENSFLEQFMIEKLPEACSIGDGKPFVMNLQDLYMAVTTQEVQVGQKHQGAGDPHTSNSASLQGIDSQCVNQPEQLVSSAPTLSAPEKESTGTSGPLQRPQLSKVKRKKPRGLFS
uniprot
proteins
disease_involvement
DISEASE: Immunodeficiency 124, severe combined (IMD124) [MIM:611291]: A form of severe combined immunodeficiency (SCID), a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia and low or absent antibody levels. Patients with SCID present in infancy with recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T- cell development. IMD124 is characterized by a profound T- and B- lymphocytopenia associated with increased cellular sensitivity to ionizing radiation, shortened telomeres and premature senescence of hematopoietic stem cells, microcephaly and growth retardation. Some patients may manifest SCID with sensitivity to ionizing radiation without microcephaly and mild growth retardation, probably due to hypomorphic NHEJ1 variants. {ECO:0000269|PubMed:16439204, ECO:0000269|PubMed:16439205, ECO:0000269|PubMed:17317666, ECO:0000269|PubMed:20558749, ECO:0000269|PubMed:20597108, ECO:0000269|PubMed:24511403, ECO:0000269|PubMed:28369633, ECO:0000269|PubMed:35812385, ECO:0000269|PubMed:37703920}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Microphthalmia/coloboma 13 (MCOPCB13) [MIM:620968]: A form of colobomatous microphthalmia, a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like coloboma, opacities of the cornea and lens, scaring of the retina and choroid, and other abnormalities may also be present. Ocular colobomas are a set of malformations resulting from abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). MCOPCB13 is an autosomal recessive form characterized by variable ocular anomalies, even between eyes within the same patient. Patients may also exhibit high myopia, strabismus, nystagmus, and/or retinal pigmentary changes and atrophy. {ECO:0000269|PubMed:37580330}. Note=The disease is caused by variants affecting the gene represented in this entry. The disease is caused by a homozygous NHEJ1 intronic variant that disrupts a conserved enhancer of IHH expression (i8), a gene known to be involved in eye development in mice. {ECO:0000269|PubMed:37580330}.; DISEASE: Note=A chromosomal aberration involving NHEJ1 is found in a patient with polymicrogyria. Translocation t(2;7)(q35;p22). {ECO:0000269|PubMed:12604777}.
uniprot
proteins
function
FUNCTION: DNA repair protein involved in DNA non-homologous end joining (NHEJ); it is required for double-strand break (DSB) repair and V(D)J recombination and is also involved in telomere maintenance (PubMed:16439204, PubMed:16439205, PubMed:17317666, PubMed:17470781, PubMed:17717001, PubMed:18158905, PubMed:18644470, PubMed:20558749, PubMed:26100018, PubMed:28369633). Plays a key role in NHEJ by promoting the ligation of various mismatched and non-cohesive ends (PubMed:17470781, PubMed:17717001, PubMed:19056826). Together with PAXX, collaborates with DNA polymerase lambda (POLL) to promote joining of non-cohesive DNA ends (PubMed:25670504, PubMed:30250067). May act in concert with XRCC5-XRCC6 (Ku) to stimulate XRCC4-mediated joining of blunt ends and several types of mismatched ends that are non-complementary or partially complementary (PubMed:16439204, PubMed:16439205, PubMed:17317666, PubMed:17470781). In some studies, has been shown to associate with XRCC4 to form alternating helical filaments that bridge DNA and act like a bandage, holding together the broken DNA until it is repaired (PubMed:21768349, PubMed:21775435, PubMed:22228831, PubMed:22287571, PubMed:26100018, PubMed:27437582, PubMed:28500754). Alternatively, it has also been shown that rather than forming filaments, a single NHEJ1 dimer interacts through both head domains with XRCC4 to promote the close alignment of DNA ends (By similarity). The XRCC4-NHEJ1/XLF subcomplex binds to the DNA fragments of a DSB in a highly diffusive manner and robustly bridges two independent DNA molecules, holding the broken DNA fragments in close proximity to one other (PubMed:27437582, PubMed:28500754). The mobility of the bridges ensures that the ends remain accessible for further processing by other repair factors (PubMed:27437582). Binds DNA in a length-dependent manner (PubMed:17317666, PubMed:18158905). {ECO:0000250|UniProtKB:A0A1L8ENT6, ECO:0000269|PubMed:16439204, ECO:0000269|PubMed:16439205, ECO:0000269|PubMed:17317666, ECO:0000269|PubMed:17470781, ECO:0000269|PubMed:17717001, ECO:0000269|PubMed:18158905, ECO:0000269|PubMed:18644470, ECO:0000269|PubMed:19056826, ECO:0000269|PubMed:20558749, ECO:0000269|PubMed:21768349, ECO:0000269|PubMed:21775435, ECO:0000269|PubMed:22228831, ECO:0000269|PubMed:22287571, ECO:0000269|PubMed:25670504, ECO:0000269|PubMed:26100018, ECO:0000269|PubMed:27437582, ECO:0000269|PubMed:28369633, ECO:0000269|PubMed:28500754, ECO:0000269|PubMed:30250067}.
uniprot
proteins
mass_dalton
33337
uniprot
proteins
mutagenesis
MUTAGEN 11; /note="Q->A: Does not affect ability to participate in V(D)J recombination."; /evidence="ECO:0000269|PubMed:20558749"; MUTAGEN 13; /note="W->A: Does not affect ability to participate in V(D)J recombination."; /evidence="ECO:0000269|PubMed:20558749"; MUTAGEN 15; /note="W->A: Does not affect ability to participate in V(D)J recombination."; /evidence="ECO:0000269|PubMed:20558749"; MUTAGEN 24; /note="L->A: Does not affect ability to participate in V(D)J recombination."; /evidence="ECO:0000269|PubMed:20558749"; MUTAGEN 26; /note="K->A: Abolished ability to participate in V(D)J recombination."; /evidence="ECO:0000269|PubMed:20558749"; MUTAGEN 37; /note="L->A: Does not affect ability to participate in V(D)J recombination."; /evidence="ECO:0000269|PubMed:20558749"; MUTAGEN 40; /note="D->A,P: Does not affect ability to participate in V(D)J recombination."; /evidence="ECO:0000269|PubMed:20558749"; MUTAGEN 41; /note="L->A: Does not affect ability to participate in V(D)J recombination."; /evidence="ECO:0000269|PubMed:20558749"; MUTAGEN 43; /note="Q->A: Does not affect ability to participate in V(D)J recombination."; /evidence="ECO:0000269|PubMed:20558749"; MUTAGEN 61; /note="L->E: Does not affect ability to participate in V(D)J recombination."; /evidence="ECO:0000269|PubMed:20558749"; MUTAGEN 64..65; /note="RL->ED: Abolished interaction with XRCC4."; /evidence="ECO:0000269|PubMed:21775435"; MUTAGEN 64; /note="R->E: Abolished ability to repair double-strand breaks (DSBs). Abolished interaction with XRCC4. Abolished ability to participate in V(D)J recombination."; /evidence="ECO:0000269|PubMed:20558749, ECO:0000269|PubMed:21768349"; MUTAGEN 64; /note="R->G: Does not affect ability to participate in V(D)J recombination."; /evidence="ECO:0000269|PubMed:20558749"; MUTAGEN 65; /note="L->D: Abolished ability to repair double-strand breaks (DSBs). Abolished ability to participate in V(D)J recombination. Decreased interaction with XRCC4."; /evidence="ECO:0000269|PubMed:20558749"; MUTAGEN 105; /note="I->S: Does not affect ability to repair double-strand breaks (DSBs). Does not affect interaction with XRCC4."; /evidence="ECO:0000269|PubMed:18158905"; MUTAGEN 111; /note="E->A: Does not affect ability to repair double-strand breaks (DSBs). Does not affect interaction with XRCC4."; /evidence="ECO:0000269|PubMed:18158905"; MUTAGEN 111; /note="E->K: Does not affect interaction with XRCC4."; /evidence="ECO:0000269|PubMed:21768349"; MUTAGEN 115; /note="L->A: Impaired ability to repair double-strand breaks (DSBs). Abolished ability to bridge DNA. Some studies show lack of interaction with XRCC4 while another shows that this mutant retains the ability to interact with XRCC4."; /evidence="ECO:0000269|PubMed:18158905, ECO:0000269|PubMed:21775435, ECO:0000269|PubMed:22287571, ECO:0000269|PubMed:26100018, ECO:0000269|PubMed:30177755"; MUTAGEN 115; /note="L->D: Impaired ability to repair double-strand breaks (DSBs). Abolished ability to bridge DNA. Abolished ability to participate in V(D)J recombination. Abolished interaction with XRCC4."; /evidence="ECO:0000269|PubMed:18158905, ECO:0000269|PubMed:20558749, ECO:0000269|PubMed:21775435, ECO:0000269|PubMed:22287571, ECO:0000269|PubMed:26100018"; MUTAGEN 116; /note="P->D: Does not affect ability to participate in V(D)J recombination."; /evidence="ECO:0000269|PubMed:20558749"; MUTAGEN 117; /note="F->A: Does not affect ability to participate in V(D)J recombination."; /evidence="ECO:0000269|PubMed:20558749"; MUTAGEN 117; /note="F->D: Abolished ability to participate in V(D)J recombination."; /evidence="ECO:0000269|PubMed:20558749"; MUTAGEN 118; /note="Y->A,D: Does not affect ability to participate in V(D)J recombination."; /evidence="ECO:0000269|PubMed:20558749"; MUTAGEN 119; /note="W->A: Abolished ability to participate in V(D)J recombination."; /evidence="ECO:0000269|PubMed:20558749"; MUTAGEN 132; /note="S->A: In 6A mutant; abolished phosphorylation; does not affect ability to repair double-strand breaks (DSBs), possibly because of redundancy with XRCC4 phosphorylation sites; when associated with A-203, A-245, A-251, A-263 and A-266. In XLF-Ala mutant; abolished phosphorylation by PRKDC; does not affect ability to bridge DNA when associated with XRCC4 phosphorylation-defective mutant; when associated with A-203, A-245 and A-251."; /evidence="ECO:0000269|PubMed:18644470, ECO:0000269|PubMed:28500754"; MUTAGEN 132; /note="S->D: In XLF-Asp mutant; phospho-mimetic mutant; abolished ability to bridge DNA when associated with XRCC4 phospho-mimetic mutant; when associated with D-203, D-245 and D-251."; /evidence="ECO:0000269|PubMed:28500754"; MUTAGEN 135; /note="L->A: Does not affect ability to participate in V(D)J recombination."; /evidence="ECO:0000269|PubMed:20558749"; MUTAGEN 137; /note="R->A,N: Does not affect ability to participate in V(D)J recombination."; /evidence="ECO:0000269|PubMed:20558749"; MUTAGEN 138; /note="P->A: Does not affect ability to participate in V(D)J recombination."; /evidence="ECO:0000269|PubMed:20558749"; MUTAGEN 139; /note="L->A: Does not affect ability to participate in V(D)J recombination."; /evidence="ECO:0000269|PubMed:20558749"; MUTAGEN 169; /note="E->A: Does not affect ability to repair double-strand breaks (DSBs). Does not affect interaction with XRCC4."; /evidence="ECO:0000269|PubMed:18158905"; MUTAGEN 174; /note="L->A: Impaired ability to repair double-strand breaks (DSBs). Does not affect interaction with XRCC4."; /evidence="ECO:0000269|PubMed:18158905"; MUTAGEN 178; /note="R->A: Impaired ability to repair double-strand breaks (DSBs). Does not affect interaction with XRCC4. Does not affect ability to participate in V(D)J recombination."; /evidence="ECO:0000269|PubMed:18158905, ECO:0000269|PubMed:20558749"; MUTAGEN 179; /note="L->A: Impaired ability to repair double-strand breaks (DSBs). Does not affect interaction with XRCC4."; /evidence="ECO:0000269|PubMed:18158905"; MUTAGEN 182; /note="E->A: Does not affect ability to participate in V(D)J recombination."; /evidence="ECO:0000269|PubMed:20558749"; MUTAGEN 185; /note="E->A: Does not affect ability to repair double-strand breaks (DSBs). Does not affect interaction with XRCC4."; /evidence="ECO:0000269|PubMed:18158905"; MUTAGEN 189..190; /note="FL->DD: Does not affect ability to participate in V(D)J recombination."; /evidence="ECO:0000269|PubMed:20558749"; MUTAGEN 195; /note="I->A: Does not affect ability to repair double-strand breaks (DSBs). Does not affect interaction with XRCC4."; /evidence="ECO:0000269|PubMed:18158905"; MUTAGEN 203; /note="S->A: In 6A mutant; abolished phosphorylation; does not affect ability to repair double-strand breaks (DSBs), possibly because of redundancy with XRCC4 phosphorylation sites; when associated with A-132, A-245, A-251, A-263 and A-266. In XLF-Ala mutant; abolished phosphorylation by PRKDC; does not affect ability to bridge DNA when associated with XRCC4 phosphorylation-defective mutant; when associated with A-132, A-245 and A-251."; /evidence="ECO:0000269|PubMed:18644470, ECO:0000269|PubMed:22228831, ECO:0000269|PubMed:28500754"; MUTAGEN 203; /note="S->D: In XLF-Asp mutant; phospho-mimetic mutant; abolished ability to bridge DNA when associated with XRCC4 phospho-mimetic mutant; when associated with D-132, D-245 and D-251."; /evidence="ECO:0000269|PubMed:28500754"; MUTAGEN 245; /note="S->A: In 6A mutant; abolished phosphorylation; does not affect ability to repair double-strand breaks (DSBs), possibly because of redundancy with XRCC4 phosphorylation sites; when associated with A-132, A-203, A-251, A-263 and A-266. In XLF-Ala mutant; abolished phosphorylation by PRKDC; does not affect ability to bridge DNA when associated with XRCC4 phosphorylation-defective mutant; when associated with A-132, A-203 and A-251."; /evidence="ECO:0000269|PubMed:18644470, ECO:0000269|PubMed:22228831, ECO:0000269|PubMed:28500754"; MUTAGEN 245; /note="S->D: In XLF-Asp mutant; phospho-mimetic mutant; abolished ability to bridge DNA when associated with XRCC4 phospho-mimetic mutant; when associated with D-132, D-203 and D-251."; /evidence="ECO:0000269|PubMed:28500754"; MUTAGEN 251; /note="S->A: In 6A mutant; abolished phosphorylation; does not affect ability to repair double-strand breaks (DSBs), possibly because of redundancy with XRCC4 phosphorylation sites; when associated with A-132, A-203, A-245, A-263 and A-266. In XLF-Ala mutant; abolished phosphorylation by PRKDC; does not affect ability to bridge DNA when associated with XRCC4 phosphorylation-defective mutant; when associated with A-132, A-203 and A-245."; /evidence="ECO:0000269|PubMed:18644470, ECO:0000269|PubMed:22228831, ECO:0000269|PubMed:28500754"; MUTAGEN 251; /note="S->D: In XLF-Asp mutant; phospho-mimetic mutant; abolished ability to bridge DNA when associated with XRCC4 phospho-mimetic mutant; when associated with D-132, D-203 and D-245."; /evidence="ECO:0000269|PubMed:28500754"; MUTAGEN 263; /note="S->A: In 6A mutant; abolished phosphorylation; does not affect ability to repair double-strand breaks (DSBs), possibly because of redundancy with XRCC4 phosphorylation sites; when associated with A-132, A-203, A-245, A-251 and A-266."; /evidence="ECO:0000269|PubMed:18644470, ECO:0000269|PubMed:22228831"; MUTAGEN 266; /note="T->A: In 6A mutant; abolished phosphorylation; does not affect ability to repair double-strand breaks (DSBs), possibly because of redundancy with XRCC4 phosphorylation sites; when associated with A-132, A-203, A-245, A-251 and A-263."; /evidence="ECO:0000269|PubMed:18644470, ECO:0000269|PubMed:22228831"; MUTAGEN 278; /note="S->A: Does not affect ability to repair double-strand breaks (DSBs). Does not affect interaction with XRCC4."; /evidence="ECO:0000269|PubMed:18158905"; MUTAGEN 293; /note="K->A: Abolished DNA-binding."; /evidence="ECO:0000269|PubMed:22287571
uniprot
proteins
post_translational_modification
PTM: Phosphorylated by PRKDC at the C-terminus in response to DNA damage (PubMed:18644470, PubMed:22228831, PubMed:28500754). Phosphorylations by PRKDC at the C-terminus of XRCC4 and NHEJ1/XLF are highly redundant and regulate ability of the XRCC4-NHEJ1/XLF subcomplex to bridge DNA (PubMed:22228831, PubMed:28500754). Phosphorylation does not prevent interaction with XRCC4 but disrupts ability to bridge DNA and promotes detachment from DNA (PubMed:22228831, PubMed:28500754). {ECO:0000269|PubMed:18644470, ECO:0000269|PubMed:22228831, ECO:0000269|PubMed:28500754}.
uniprot
proteins
protein_family
XLF subfamily
uniprot
proteins
protein_family
XRCC4-XLF family
uniprot
proteins
pubmed
12604777
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15815621
uniprot
proteins
pubmed
16439204
uniprot
proteins
pubmed
16439205
uniprot
proteins
pubmed
16571728
uniprot
proteins
pubmed
17191205
uniprot
proteins
pubmed
17317666
uniprot
proteins
pubmed
17470781
uniprot
proteins
pubmed
17567543
uniprot
proteins
pubmed
17717001
uniprot
proteins
pubmed
18046455
uniprot
proteins
pubmed
18064046
uniprot
proteins
pubmed
18158905
uniprot
proteins
pubmed
18644470
uniprot
proteins
pubmed
19056826
uniprot
proteins
pubmed
20558749
uniprot
proteins
pubmed
20597108
uniprot
proteins
pubmed
21768349
uniprot
proteins
pubmed
21775435
uniprot
proteins
pubmed
21936820
uniprot
proteins
pubmed
22102241
uniprot
proteins
pubmed
22228831
uniprot
proteins
pubmed
22287571
uniprot
proteins
pubmed
22658747
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24511403
uniprot
proteins
pubmed
25574025
uniprot
proteins
pubmed
25670504
uniprot
proteins
pubmed
25941166
uniprot
proteins
pubmed
26100018
uniprot
proteins
pubmed
27063109
uniprot
proteins
pubmed
27437582
uniprot
proteins
pubmed
28369633
uniprot
proteins
pubmed
28500754
uniprot
proteins
pubmed
30177755
uniprot
proteins
pubmed
30250067
uniprot
proteins
pubmed
33289484
uniprot
proteins
pubmed
33854234
uniprot
proteins
pubmed
34352203
uniprot
proteins
pubmed
35812385
uniprot
proteins
pubmed
37580330
uniprot
proteins
pubmed
37703920
uniprot
proteins
sequence_length
299
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16439204, ECO:0000269|PubMed:16439205, ECO:0000269|PubMed:20558749}. Chromosome {ECO:0000269|PubMed:18064046, ECO:0000269|PubMed:18644470, ECO:0000269|PubMed:27437582}. Note=Localizes to site of double-strand breaks; recruitment is dependent on XRCC5-XRCC6 (Ku) heterodimer. {ECO:0000269|PubMed:18064046, ECO:0000269|PubMed:18644470, ECO:0000269|PubMed:27437582}.
uniprot
proteins