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Protein

Non-homologous end-joining factor 1

Gene

NHEJ1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

DNA repair protein involved in DNA nonhomologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination. May serve as a bridge between XRCC4 and the other NHEJ factors located at DNA ends, or may participate in reconfiguration of the end bound NHEJ factors to allow XRCC4 access to the DNA termini. It may act in concert with XRCC6/XRCC5 (Ku) to stimulate XRCC4-mediated joining of blunt ends and several types of mismatched ends that are noncomplementary or partially complementary (PubMed:16439204, PubMed:16439205, PubMed:17470781). Binds DNA in a length-dependent manner (PubMed:17317666).4 Publications

GO - Molecular functioni

GO - Biological processi

  • B cell differentiation Source: UniProtKB
  • central nervous system development Source: UniProtKB
  • DNA recombination Source: InterPro
  • double-strand break repair via nonhomologous end joining Source: UniProtKB
  • positive regulation of ligase activity Source: UniProtKB
  • response to ionizing radiation Source: UniProtKB
  • T cell differentiation Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

DNA damage, DNA repair

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

BioCyciZFISH:G66-31270-MONOMER.
ReactomeiR-HSA-5693571. Nonhomologous End-Joining (NHEJ).
SIGNORiQ9H9Q4.

Names & Taxonomyi

Protein namesi
Recommended name:
Non-homologous end-joining factor 1
Alternative name(s):
Protein cernunnos
XRCC4-like factor
Gene namesi
Name:NHEJ1
Synonyms:XLF
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:25737. NHEJ1.

Subcellular locationi

GO - Cellular componenti

  • DNA ligase IV complex Source: GO_Central
  • nonhomologous end joining complex Source: UniProtKB
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Severe combined immunodeficiency due to NHEJ1 deficiency (NHEJ1-SCID)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionSCID refers to 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. NHEJ1-SCID is characterized by a profound T- and B-lymphocytopenia associated with increased cellular sensitivity to ionizing radiation, 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 mutations.
See also OMIM:611291
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02570457R → G in NHEJ1-SCID; fails to translocate to the nucleus. 2 PublicationsCorresponds to variant rs118204451dbSNPEnsembl.1
Natural variantiVAR_025705123C → R in NHEJ1-SCID. 1 PublicationCorresponds to variant rs118204452dbSNPEnsembl.1

A chromosomal aberration involving NHEJ1 is found in a patient with polymicrogyria. Translocation t(2;7)(q35;p22).

Keywords - Diseasei

Disease mutation, SCID

Organism-specific databases

DisGeNETi79840.
MalaCardsiNHEJ1.
MIMi611291. phenotype.
OpenTargetsiENSG00000187736.
Orphaneti208447. Bilateral generalized polymicrogyria.
169079. Cernunnos-XLF deficiency.
PharmGKBiPA144596401.

Polymorphism and mutation databases

BioMutaiNHEJ1.
DMDMi74734059.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002286541 – 299Non-homologous end-joining factor 1Add BLAST299

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei245PhosphoserineBy similarity1
Modified residuei287PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9H9Q4.
MaxQBiQ9H9Q4.
PaxDbiQ9H9Q4.
PeptideAtlasiQ9H9Q4.
PRIDEiQ9H9Q4.

PTM databases

iPTMnetiQ9H9Q4.
PhosphoSitePlusiQ9H9Q4.

Expressioni

Tissue specificityi

Ubiquitously expressed.1 Publication

Gene expression databases

BgeeiENSG00000187736.
CleanExiHS_NHEJ1.
ExpressionAtlasiQ9H9Q4. baseline and differential.
GenevisibleiQ9H9Q4. HS.

Organism-specific databases

HPAiCAB012334.

Interactioni

Subunit structurei

Exists mainly as a homodimer. Associates with the non-homologous end joining (NHEJ) complex which is at least composed of the core proteins XRCC5/Ku80, XRCC6/Ku70, PRKDC/DNA-PKcs, LIG4 and XRCC4.7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
LIG4P499174EBI-847807,EBI-847896
XRCC4Q134268EBI-847807,EBI-717592

Protein-protein interaction databases

BioGridi122931. 7 interactors.
DIPiDIP-37959N.
IntActiQ9H9Q4. 7 interactors.
MINTiMINT-5003574.
STRINGi9606.ENSP00000349313.

Structurei

Secondary structure

1299
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi1 – 9Combined sources9
Beta strandi14 – 17Combined sources4
Beta strandi19 – 30Combined sources12
Beta strandi33 – 39Combined sources7
Beta strandi44 – 49Combined sources6
Helixi51 – 61Combined sources11
Helixi69 – 85Combined sources17
Beta strandi94 – 100Combined sources7
Beta strandi103 – 112Combined sources10
Beta strandi115 – 125Combined sources11
Helixi128 – 134Combined sources7
Helixi136 – 169Combined sources34
Helixi186 – 196Combined sources11
Helixi198 – 201Combined sources4
Helixi208 – 213Combined sources6
Helixi215 – 228Combined sources14

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2QM4X-ray2.30A/B/C/D1-233[»]
2R9AX-ray2.50A/B1-224[»]
3Q4FX-ray5.50A/B/E/F1-224[»]
3RWRX-ray3.94D/E/H/I/L/M/O/Q/S/T/W/X1-224[»]
3SR2X-ray3.97C/D/G/H1-224[»]
3W03X-ray8.49A/B1-233[»]
ProteinModelPortaliQ9H9Q4.
SMRiQ9H9Q4.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9H9Q4.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 135Globular headAdd BLAST135

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili128 – 1701 PublicationAdd BLAST43

Domaini

The coiled-coil region mediates homodimerization.

Sequence similaritiesi

Belongs to the XLF family.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiENOG410IT7Y. Eukaryota.
ENOG411291V. LUCA.
GeneTreeiENSGT00390000009940.
HOGENOMiHOG000089974.
HOVERGENiHBG080703.
InParanoidiQ9H9Q4.
KOiK10980.
OMAiHQGTGDP.
OrthoDBiEOG091G1269.
PhylomeDBiQ9H9Q4.
TreeFamiTF328567.

Family and domain databases

Gene3Di2.170.210.10. 1 hit.
InterProiIPR015381. XLF_fam.
IPR009089. XRCC4_N.
[Graphical view]
PfamiPF09302. XLF. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9H9Q4-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEELEQGLLM QPWAWLQLAE NSLLAKVFIT KQGYALLVSD LQQVWHEQVD
60 70 80 90 100
TSVVSQRAKE LNKRLTAPPA AFLCHLDNLL RPLLKDAAHP SEATFSCDCV
110 120 130 140 150
ADALILRVRS ELSGLPFYWN FHCMLASPSL VSQHLIRPLM GMSLALQCQV
160 170 180 190 200
RELATLLHMK DLEIQDYQES GATLIRDRLK TEPFEENSFL EQFMIEKLPE
210 220 230 240 250
ACSIGDGKPF VMNLQDLYMA VTTQEVQVGQ KHQGAGDPHT SNSASLQGID
260 270 280 290
SQCVNQPEQL VSSAPTLSAP EKESTGTSGP LQRPQLSKVK RKKPRGLFS
Length:299
Mass (Da):33,337
Last modified:March 1, 2001 - v1
Checksum:iBC5C68076A5E7A96
GO
Isoform 2 (identifier: Q9H9Q4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     276-299: GTSGPLQRPQLSKVKRKKPRGLFS → ALCRDLSCQRSRGRSQGVSSVNLLWPQLLRMDLENSFQASP

Note: No experimental confirmation available.
Show »
Length:316
Mass (Da):35,291
Checksum:i11CAF1C6543580CE
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti256Q → R in CAG33572 (Ref. 3) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03879014A → T.Corresponds to variant rs34689457dbSNPEnsembl.1
Natural variantiVAR_02570457R → G in NHEJ1-SCID; fails to translocate to the nucleus. 2 PublicationsCorresponds to variant rs118204451dbSNPEnsembl.1
Natural variantiVAR_03879189H → R.Corresponds to variant rs1056296dbSNPEnsembl.1
Natural variantiVAR_025705123C → R in NHEJ1-SCID. 1 PublicationCorresponds to variant rs118204452dbSNPEnsembl.1
Natural variantiVAR_038792256Q → L.Corresponds to variant rs35270667dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_017689276 – 299GTSGP…RGLFS → ALCRDLSCQRSRGRSQGVSS VNLLWPQLLRMDLENSFQAS P in isoform 2. 1 PublicationAdd BLAST24

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ972687 mRNA. Translation: CAI99410.1.
AK022672 mRNA. Translation: BAB14168.1.
CR457291 mRNA. Translation: CAG33572.1.
AC020575 Genomic DNA. No translation available.
AC068946 Genomic DNA. No translation available.
AC097468 Genomic DNA. Translation: AAX88921.1.
BC008210 mRNA. Translation: AAH08210.2.
BC012732 mRNA. Translation: AAH12732.1.
BC030986 mRNA. Translation: AAH30986.1.
CCDSiCCDS2432.1. [Q9H9Q4-1]
RefSeqiNP_079058.1. NM_024782.2. [Q9H9Q4-1]
UniGeneiHs.225988.

Genome annotation databases

EnsembliENST00000356853; ENSP00000349313; ENSG00000187736. [Q9H9Q4-1]
ENST00000409720; ENSP00000387290; ENSG00000187736. [Q9H9Q4-2]
GeneIDi79840.
KEGGihsa:79840.
UCSCiuc002vjp.5. human. [Q9H9Q4-1]

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement, Polymorphism

Cross-referencesi

Web resourcesi

NHEJ1base

NHEJ1 mutation db

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ972687 mRNA. Translation: CAI99410.1.
AK022672 mRNA. Translation: BAB14168.1.
CR457291 mRNA. Translation: CAG33572.1.
AC020575 Genomic DNA. No translation available.
AC068946 Genomic DNA. No translation available.
AC097468 Genomic DNA. Translation: AAX88921.1.
BC008210 mRNA. Translation: AAH08210.2.
BC012732 mRNA. Translation: AAH12732.1.
BC030986 mRNA. Translation: AAH30986.1.
CCDSiCCDS2432.1. [Q9H9Q4-1]
RefSeqiNP_079058.1. NM_024782.2. [Q9H9Q4-1]
UniGeneiHs.225988.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2QM4X-ray2.30A/B/C/D1-233[»]
2R9AX-ray2.50A/B1-224[»]
3Q4FX-ray5.50A/B/E/F1-224[»]
3RWRX-ray3.94D/E/H/I/L/M/O/Q/S/T/W/X1-224[»]
3SR2X-ray3.97C/D/G/H1-224[»]
3W03X-ray8.49A/B1-233[»]
ProteinModelPortaliQ9H9Q4.
SMRiQ9H9Q4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122931. 7 interactors.
DIPiDIP-37959N.
IntActiQ9H9Q4. 7 interactors.
MINTiMINT-5003574.
STRINGi9606.ENSP00000349313.

PTM databases

iPTMnetiQ9H9Q4.
PhosphoSitePlusiQ9H9Q4.

Polymorphism and mutation databases

BioMutaiNHEJ1.
DMDMi74734059.

Proteomic databases

EPDiQ9H9Q4.
MaxQBiQ9H9Q4.
PaxDbiQ9H9Q4.
PeptideAtlasiQ9H9Q4.
PRIDEiQ9H9Q4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000356853; ENSP00000349313; ENSG00000187736. [Q9H9Q4-1]
ENST00000409720; ENSP00000387290; ENSG00000187736. [Q9H9Q4-2]
GeneIDi79840.
KEGGihsa:79840.
UCSCiuc002vjp.5. human. [Q9H9Q4-1]

Organism-specific databases

CTDi79840.
DisGeNETi79840.
GeneCardsiNHEJ1.
HGNCiHGNC:25737. NHEJ1.
HPAiCAB012334.
MalaCardsiNHEJ1.
MIMi611290. gene.
611291. phenotype.
neXtProtiNX_Q9H9Q4.
OpenTargetsiENSG00000187736.
Orphaneti208447. Bilateral generalized polymicrogyria.
169079. Cernunnos-XLF deficiency.
PharmGKBiPA144596401.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IT7Y. Eukaryota.
ENOG411291V. LUCA.
GeneTreeiENSGT00390000009940.
HOGENOMiHOG000089974.
HOVERGENiHBG080703.
InParanoidiQ9H9Q4.
KOiK10980.
OMAiHQGTGDP.
OrthoDBiEOG091G1269.
PhylomeDBiQ9H9Q4.
TreeFamiTF328567.

Enzyme and pathway databases

BioCyciZFISH:G66-31270-MONOMER.
ReactomeiR-HSA-5693571. Nonhomologous End-Joining (NHEJ).
SIGNORiQ9H9Q4.

Miscellaneous databases

ChiTaRSiNHEJ1. human.
EvolutionaryTraceiQ9H9Q4.
GeneWikiiXLF_(protein).
GenomeRNAii79840.
PROiQ9H9Q4.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000187736.
CleanExiHS_NHEJ1.
ExpressionAtlasiQ9H9Q4. baseline and differential.
GenevisibleiQ9H9Q4. HS.

Family and domain databases

Gene3Di2.170.210.10. 1 hit.
InterProiIPR015381. XLF_fam.
IPR009089. XRCC4_N.
[Graphical view]
PfamiPF09302. XLF. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNHEJ1_HUMAN
AccessioniPrimary (citable) accession number: Q9H9Q4
Secondary accession number(s): B8ZZA4
, Q4ZFW7, Q6IA64, Q96JS9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 21, 2006
Last sequence update: March 1, 2001
Last modified: November 2, 2016
This is version 127 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

Was named 'Cernunnos' after the enigmatic Celtic god of hunting, the underworld and fertility.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.