Q9H9Q4 (NHEJ1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Non-homologous end-joining factor 1

Alternative name(s):
Protein cernunnos
XRCC4-like factor

Gene names

Name:	NHEJ1
Synonyms:	XLF

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	299 AA.
Sequence status	Complete.
Protein existence	Evidence 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	Interacts with XRCC4 and the XRCC4-LIG4 complex. Binds DNA in a length-dependent manner. Ref.7 Ref.8 Ref.10
Subcellular location	Nucleus Ref.1 Ref.7.
Tissue specificity	Ubiquitously expressed. Ref.1
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.

Ontologies

Keywords
Biological process	DNA damage DNA repair
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Chromosomal rearrangement Polymorphism
Disease	Disease mutation SCID
Ligand	DNA-binding
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	B cell differentiation Inferred from mutant phenotype Ref.1. Source: UniProtKB DNA recombination Inferred from electronic annotation. Source: InterPro T cell differentiation Inferred from mutant phenotype Ref.1. Source: UniProtKB central nervous system development Non-traceable author statement Ref.1. Source: UniProtKB double-strand break repair via nonhomologous end joining Inferred from mutant phenotype Ref.1Ref.7. Source: UniProtKB positive regulation of ligase activity Non-traceable author statement Ref.7. Source: UniProtKB response to ionizing radiation Inferred from direct assay Ref.7. Source: UniProtKB
Cellular_component	nonhomologous end joining complex Inferred from direct assay PubMed 20383123. Source: UniProtKB nucleus Inferred from direct assay Ref.1Ref.7. Source: UniProtKB
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
LIG4	P49917	4	EBI-847807,EBI-847896
XRCC4	Q13426	5	EBI-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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 299

299

Non-homologous end-joining factor 1

PRO_0000228654

Natural variations

Alternative sequence

276 – 299

24

GTSGP…RGLFS → ALCRDLSCQRSRGRSQGVSS VNLLWPQLLRMDLENSFQAS P in isoform 2.

VSP_017689

Natural variant

14

1

A → T.
Corresponds to variant rs34689457 [ dbSNP | Ensembl ].

VAR_038790

Natural variant

57

1

R → G in NHEJ1-SCID; fails to translocate to the nucleus. Ref.1 Ref.10

VAR_025704

Natural variant

89

1

H → R.
Corresponds to variant rs1056296 [ dbSNP | Ensembl ].

VAR_038791

Natural variant

123

1

C → R in NHEJ1-SCID. Ref.1

VAR_025705

Natural variant

256

1

Q → L.
Corresponds to variant rs35270667 [ dbSNP | Ensembl ].

VAR_038792

Experimental info

Sequence conflict

256

1

Q → R in CAG33572. Ref.3

Secondary structure

1

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299

Helix Strand Turn

Details...

Helix

1 – 9

9

Beta strand

14 – 17

4

Beta strand

19 – 30

12

Beta strand

33 – 39

7

Beta strand

44 – 49

6

Helix

51 – 61

11

Helix

69 – 85

17

Beta strand

94 – 100

7

Beta strand

103 – 112

10

Beta strand

115 – 125

11

Helix

128 – 134

7

Helix

136 – 169

34

Helix

186 – 196

11

Helix

198 – 201

4

Helix

208 – 213

6

Helix

215 – 228

14

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: BC5C68076A5E7A96	FASTA	299	33,337
	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
	Isoform 2 [UniParc]. Checksum: 11CAF1C6543580CE	FASTA	316	35,291
	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 250 260 270 280 290 300 SNSASLQGID SQCVNQPEQL VSSAPTLSAP EKESTALCRD LSCQRSRGRS QGVSSVNLLW 310 PQLLRMDLEN SFQASP

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.
+	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.

IPI

IPI00549762.
IPI00735288.

RefSeq

NP_079058.1. NM_024782.2.

UniGene

Hs.225988.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2QM4	X-ray	2.30	A/B/C/D	1-233	[»]
2R9A	X-ray	2.50	A/B	1-224	[»]
3Q4F	X-ray	5.50	A/B/E/F	1-224	[»]
3RWR	X-ray	3.94	D/E/H/I/L/M/O/Q/S/T/W/X	1-224	[»]
3SR2	X-ray	3.97	C/D/G/H	1-224	[»]
3W03	X-ray	8.49	A/B	1-233	[»]

ProteinModelPortal

Q9H9Q4.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-37959N.

IntAct

Q9H9Q4. 2 interactions.

MINT

MINT-5003574.

STRING

9606.ENSP00000349313.

PTM databases

PhosphoSite

Q9H9Q4.

Polymorphism databases

DMDM

74734059.

Proteomic databases

PaxDb

Q9H9Q4.

PRIDE

Q9H9Q4.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000356853; ENSP00000349313; ENSG00000187736.
ENST00000409720; ENSP00000387290; ENSG00000187736.

GeneID

79840.

KEGG

hsa:79840.

UCSC

uc002vjp.4. human.

Organism-specific databases

CTD

79840.

GeneCards

GC02M219941.

HGNC

HGNC:25737. NHEJ1.

HPA

CAB012334.

MIM

611290. gene.
611291. phenotype.

neXtProt

NX_Q9H9Q4.

Orphanet

208447. Bilateral generalized polymicrogyria.
169079. Severe combined immunodeficiency - microcephaly - growth retardation - sensitivity to ionizing radiation.

PharmGKB

PA144596401.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG47408.

HOGENOM

HOG000089974.

HOVERGEN

HBG080703.

KO

K10980.

OMA

YWNFHCI.

Gene expression databases

ArrayExpress

Q9H9Q4.

Bgee

Q9H9Q4.

CleanEx

HS_NHEJ1.

Genevestigator

Q9H9Q4.

GermOnline

ENSG00000187736. Homo sapiens.

Family and domain databases

Gene3D

2.170.210.10. 1 hit.

InterPro

IPR015381. XLF/Cernunnos.
IPR009089. XRCC4_N.
[Graphical view]

Pfam

PF09302. XLF. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9H9Q4.

GenomeRNAi

79840.

NextBio

69516.

SOURCE

Search...

Entry information

Entry name

NHEJ1_HUMAN

Accession

Primary (citable) accession number: Q9H9Q4
Secondary accession number(s): B8ZZA4 , Q4ZFW7, Q6IA64, Q96JS9

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 21, 2006
Last sequence update:	March 1, 2001
Last modified:	May 1, 2013
This is version 93 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.