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Q9H9Q4 (NHEJ1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 102. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Non-homologous end-joining factor 1
Alternative name(s):
Protein cernunnos
XRCC4-like factor
Gene names
Name:NHEJ1
Synonyms:XLF
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length299 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.7 Ref.11

Subunit structure

Exists mainly as a homodimer. Interacts with XRCC4 and the XRCC4-LIG4 complex. Binds DNA in a length-dependent manner. Ref.7 Ref.8 Ref.10 Ref.12

Subcellular location

Nucleus Ref.1 Ref.7.

Tissue specificity

Ubiquitously expressed. Ref.1

Domain

The coiled-coil region mediates homodimerization.

Involvement in disease

Severe combined immunodeficiency due to NHEJ1 deficiency (NHEJ1-SCID) [MIM:611291]: SCID 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.6 Ref.7 Ref.10

A chromosomal aberration involving NHEJ1 is found in a patient with polymicrogyria. Translocation t(2;7)(q35;p22). Ref.6

Miscellaneous

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

Sequence similarities

Belongs to the XLF family.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

LIG4P499174EBI-847807,EBI-847896
XRCC4Q134268EBI-847807,EBI-717592

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9H9Q4-1)

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.
Isoform 2 (identifier: Q9H9Q4-2)

The sequence of this isoform differs from the canonical sequence as follows:
     276-299: GTSGPLQRPQLSKVKRKKPRGLFS → ALCRDLSCQRSRGRSQGVSSVNLLWPQLLRMDLENSFQASP
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 299299Non-homologous end-joining factor 1
PRO_0000228654

Regions

Region1 – 135135Globular head
Coiled coil128 – 17043 Ref.12

Natural variations

Alternative sequence276 – 29924GTSGP…RGLFS → ALCRDLSCQRSRGRSQGVSS VNLLWPQLLRMDLENSFQAS P in isoform 2.
VSP_017689
Natural variant141A → T.
Corresponds to variant rs34689457 [ dbSNP | Ensembl ].
VAR_038790
Natural variant571R → G in NHEJ1-SCID; fails to translocate to the nucleus. Ref.1 Ref.10
VAR_025704
Natural variant891H → R.
Corresponds to variant rs1056296 [ dbSNP | Ensembl ].
VAR_038791
Natural variant1231C → R in NHEJ1-SCID. Ref.1
VAR_025705
Natural variant2561Q → L.
Corresponds to variant rs35270667 [ dbSNP | Ensembl ].
VAR_038792

Experimental info

Sequence conflict2561Q → R in CAG33572. Ref.3

Secondary structure

................................ 299
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 1, 2001. Version 1.
Checksum: BC5C68076A5E7A96

FASTA29933,337
        10         20         30         40         50         60 
MEELEQGLLM QPWAWLQLAE NSLLAKVFIT KQGYALLVSD LQQVWHEQVD TSVVSQRAKE 

        70         80         90        100        110        120 
LNKRLTAPPA AFLCHLDNLL RPLLKDAAHP SEATFSCDCV ADALILRVRS ELSGLPFYWN 

       130        140        150        160        170        180 
FHCMLASPSL VSQHLIRPLM GMSLALQCQV RELATLLHMK DLEIQDYQES GATLIRDRLK 

       190        200        210        220        230        240 
TEPFEENSFL EQFMIEKLPE ACSIGDGKPF VMNLQDLYMA VTTQEVQVGQ KHQGAGDPHT 

       250        260        270        280        290 
SNSASLQGID SQCVNQPEQL VSSAPTLSAP EKESTGTSGP LQRPQLSKVK RKKPRGLFS 

« Hide

Isoform 2 [UniParc].

Checksum: 11CAF1C6543580CE
Show »

FASTA31635,291

References

« Hide 'large scale' references
[1]"Cernunnos, a novel nonhomologous end-joining factor, is mutated in human immunodeficiency with microcephaly."
Buck D., Malivert L., de Chasseval R., Barraud A., Fondaneche M.-C., Sanal O., Plebani A., Stephan J.-L., Hufnagel M., le Deist F., Fischer A., Durandy A., de Villartay J.-P., Revy P.
Cell 124:287-299(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, VARIANTS NHEJ1-SCID GLY-57 AND ARG-123.
Tissue: Thymus.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[3]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 177-299 (ISOFORM 2).
Tissue: Bone marrow and Skin.
[6]"Nonhomologous end joining and V(D)J recombination require an additional factor."
Dai Y., Kysela B., Hanakahi L.A., Manolis K., Riballo E., Stumm M., Harville T.O., West S.C., Oettinger M.A., Jeggo P.A.
Proc. Natl. Acad. Sci. U.S.A. 100:2462-2467(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: DISEASE.
[7]"XLF interacts with the XRCC4-DNA ligase IV complex to promote DNA nonhomologous end-joining."
Ahnesorg P., Smith P., Jackson S.P.
Cell 124:301-313(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH XRCC4, INVOLVEMENT IN NHEJ1-SCID.
[8]"Cernunnos interacts with the XRCC4 x DNA-ligase IV complex and is homologous to the yeast nonhomologous end-joining factor Nej1."
Callebaut I., Malivert L., Fischer A., Mornon J.P., Revy P., de Villartay J.P.
J. Biol. Chem. 281:13857-13860(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH XRCC4-LIG4 COMPLEX.
[9]"Truncation of NHEJ1 in a patient with polymicrogyria."
Cantagrel V., Lossi A.M., Lisgo S., Missirian C., Borges A., Philip N., Fernandez C., Cardoso C., Figarella-Branger D., Moncla A., Lindsay S., Dobyns W.B., Villard L.
Hum. Mutat. 28:356-364(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: CHROMOSOMAL TRANSLOCATION.
[10]"Length-dependent binding of human XLF to DNA and stimulation of XRCC4.DNA ligase IV activity."
Lu H., Pannicke U., Schwarz K., Lieber M.R.
J. Biol. Chem. 282:11155-11162(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH XRCC4-LIG4 COMPLEX, DNA-BINDING, CHARACTERIZATION OF VARIANT NHEJ1-SCID GLY-57.
[11]"Cernunnos/XLF promotes the ligation of mismatched and noncohesive DNA ends."
Tsai C.J., Kim S.A., Chu G.
Proc. Natl. Acad. Sci. U.S.A. 104:7851-7856(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[12]"Crystal structure of human XLF/Cernunnos reveals unexpected differences from XRCC4 with implications for NHEJ."
Li Y., Chirgadze D.Y., Bolanos-Garcia V.M., Sibanda B.L., Davies O.R., Ahnesorg P., Jackson S.P., Blundell T.L.
EMBO J. 27:290-300(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1-233, COILED-COIL REGION, SUBUNIT.
+Additional computationally mapped references.

Web resources

NHEJ1base

NHEJ1 mutation db

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_079058.1. NM_024782.2.
UniGeneHs.225988.

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
ProteinModelPortalQ9H9Q4.
SMRQ9H9Q4. Positions 1-230.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid122931. 4 interactions.
DIPDIP-37959N.
IntActQ9H9Q4. 4 interactions.
MINTMINT-5003574.
STRING9606.ENSP00000349313.

PTM databases

PhosphoSiteQ9H9Q4.

Polymorphism databases

DMDM74734059.

Proteomic databases

PaxDbQ9H9Q4.
PRIDEQ9H9Q4.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000356853; ENSP00000349313; ENSG00000187736. [Q9H9Q4-1]
ENST00000409720; ENSP00000387290; ENSG00000187736. [Q9H9Q4-2]
GeneID79840.
KEGGhsa:79840.
UCSCuc002vjp.4. human. [Q9H9Q4-1]

Organism-specific databases

CTD79840.
GeneCardsGC02M219941.
HGNCHGNC:25737. NHEJ1.
HPACAB012334.
MIM611290. gene.
611291. phenotype.
neXtProtNX_Q9H9Q4.
Orphanet208447. Bilateral generalized polymicrogyria.
169079. Cernunnos-XLF deficiency.
PharmGKBPA144596401.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG47408.
HOGENOMHOG000089974.
HOVERGENHBG080703.
KOK10980.
OMAYWNFHCI.
OrthoDBEOG7Z0JXT.
PhylomeDBQ9H9Q4.
TreeFamTF328567.

Gene expression databases

BgeeQ9H9Q4.
CleanExHS_NHEJ1.
GenevestigatorQ9H9Q4.

Family and domain databases

Gene3D2.170.210.10. 1 hit.
InterProIPR015381. XLF/Cernunnos.
IPR009089. XRCC4_N.
[Graphical view]
PfamPF09302. XLF. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ9H9Q4.
GeneWikiXLF_(protein).
GenomeRNAi79840.
NextBio69516.
PROQ9H9Q4.
SOURCESearch...

Entry information

Entry nameNHEJ1_HUMAN
AccessionPrimary (citable) accession number: Q9H9Q4
Secondary accession number(s): B8ZZA4 expand/collapse secondary AC list , Q4ZFW7, Q6IA64, Q96JS9
Entry history
Integrated into UniProtKB/Swiss-Prot: March 21, 2006
Last sequence update: March 1, 2001
Last modified: April 16, 2014
This is version 102 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM