ID   NHEJ1_RAT               Reviewed;         304 AA.
AC   Q6AYI4;
DT   21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT   13-SEP-2004, sequence version 1.
DT   27-MAR-2024, entry version 110.
DE   RecName: Full=Non-homologous end-joining factor 1 {ECO:0000305};
DE   AltName: Full=Protein cernunnos {ECO:0000250|UniProtKB:Q9H9Q4};
DE   AltName: Full=XRCC4-like factor {ECO:0000250|UniProtKB:Q9H9Q4};
GN   Name=Nhej1 {ECO:0000312|RGD:1359338};
GN   Synonyms=Xlf {ECO:0000250|UniProtKB:Q9H9Q4};
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Testis;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
CC   -!- FUNCTION: DNA repair protein involved in DNA non-homologous end joining
CC       (NHEJ); required for double-strand break (DSB) repair and V(D)J
CC       recombination. Plays a key role in NHEJ by promoting the ligation of
CC       various mismatched and non-cohesive ends. Together with PAXX,
CC       collaborates with DNA polymerase lambda (POLL) to promote joining of
CC       non-cohesive DNA ends. May act in concert with XRCC5-XRCC6 (Ku) to
CC       stimulate XRCC4-mediated joining of blunt ends and several types of
CC       mismatched ends that are non-complementary or partially complementary.
CC       In some studies, has been shown to associate with XRCC4 to form
CC       alternating helical filaments that bridge DNA and act like a bandage,
CC       holding together the broken DNA until it is repaired. Alternatively, it
CC       has also been shown that rather than forming filaments, a single nhej1
CC       dimer interacts through both head domains with xrcc4 to promote the
CC       close alignment of DNA ends. The XRCC4-NHEJ1/XLF subcomplex binds to
CC       the DNA fragments of a DSB in a highly diffusive manner and robustly
CC       bridges two independent DNA molecules, holding the broken DNA fragments
CC       in close proximity to one other. The mobility of the bridges ensures
CC       that the ends remain accessible for further processing by other repair
CC       factors. Binds DNA in a length-dependent manner.
CC       {ECO:0000250|UniProtKB:A0A1L8ENT6, ECO:0000250|UniProtKB:Q9H9Q4}.
CC   -!- SUBUNIT: Homodimer; mainly exists as a homodimer when not associated
CC       with XRCC4. Interacts with XRCC4; the interaction is direct and is
CC       mediated via a head-to-head interaction between N-terminal head
CC       regions. Component of the core long-range non-homologous end joining
CC       (NHEJ) complex (also named DNA-PK complex) composed of PRKDC, LIG4,
CC       XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF. Additional component of
CC       the NHEJ complex includes PAXX. Following autophosphorylation, PRKDC
CC       dissociates from DNA, leading to formation of the short-range NHEJ
CC       complex, composed of LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF.
CC       Interacts with POLL (DNA polymerase lambda); promoting POLL recruitment
CC       to double-strand breaks (DSBs) and stimulation of the end-filling
CC       activity of POLL. {ECO:0000250|UniProtKB:Q9H9Q4}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9H9Q4}.
CC       Chromosome {ECO:0000250|UniProtKB:Q9H9Q4}. Note=Localizes to site of
CC       double-strand breaks; recruitment is dependent on XRCC5-XRCC6 (Ku)
CC       heterodimer. {ECO:0000250|UniProtKB:Q9H9Q4}.
CC   -!- DOMAIN: The coiled-coil region mediates homodimerization.
CC       {ECO:0000250|UniProtKB:Q9H9Q4}.
CC   -!- DOMAIN: The Leu-lock (Leu-120) site inserts into a hydrophobic pocket
CC       in XRCC4. {ECO:0000250|UniProtKB:Q9H9Q4}.
CC   -!- DOMAIN: The XLM motif (also called the KBM motif or KBMX motif) and the
CC       interior region of the C-terminal tail preceding the XLM motif are
CC       essential for DNA end joining. The sequence of the C-terminal tail is
CC       not critical for its role in end joining but it must be sufficiently
CC       long to interact with XRCC4 and to stabilize the interaction of XRCC4
CC       with LIG4. A single XLM motif and C-terminal tail is sufficient to
CC       promote end joining. {ECO:0000250|UniProtKB:A0A1L8ENT6}.
CC   -!- PTM: Phosphorylated by PRKDC at the C-terminus in response to DNA
CC       damage. Phosphorylation by PRKDC at the C-terminus of XRCC4 and
CC       NHEJ1/XLF are highly redundant and regulate ability of the XRCC4-
CC       NHEJ1/XLF subcomplex to bridge DNA. Phosphorylation does not prevent
CC       interaction with XRCC4 but disrupts ability to bridge DNA and promotes
CC       detachment from DNA. {ECO:0000250|UniProtKB:Q9H9Q4}.
CC   -!- SIMILARITY: Belongs to the XRCC4-XLF family. XLF subfamily.
CC       {ECO:0000305}.
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DR   EMBL; BC079033; AAH79033.1; -; mRNA.
DR   RefSeq; NP_001014239.1; NM_001014217.1.
DR   RefSeq; XP_006245302.1; XM_006245240.1.
DR   RefSeq; XP_006245303.1; XM_006245241.3.
DR   RefSeq; XP_006245304.1; XM_006245242.3.
DR   AlphaFoldDB; Q6AYI4; -.
DR   SMR; Q6AYI4; -.
DR   STRING; 10116.ENSRNOP00000024444; -.
DR   iPTMnet; Q6AYI4; -.
DR   PhosphoSitePlus; Q6AYI4; -.
DR   PaxDb; 10116-ENSRNOP00000024444; -.
DR   GeneID; 363251; -.
DR   KEGG; rno:363251; -.
DR   UCSC; RGD:1359338; rat.
DR   AGR; RGD:1359338; -.
DR   CTD; 79840; -.
DR   RGD; 1359338; Nhej1.
DR   VEuPathDB; HostDB:ENSRNOG00000018162; -.
DR   eggNOG; ENOG502S0R3; Eukaryota.
DR   HOGENOM; CLU_076115_1_0_1; -.
DR   InParanoid; Q6AYI4; -.
DR   OMA; VTRQEIQ; -.
DR   OrthoDB; 5390247at2759; -.
DR   PhylomeDB; Q6AYI4; -.
DR   TreeFam; TF328567; -.
DR   Reactome; R-RNO-5693571; Nonhomologous End-Joining (NHEJ).
DR   PRO; PR:Q6AYI4; -.
DR   Proteomes; UP000002494; Chromosome 9.
DR   Bgee; ENSRNOG00000018162; Expressed in testis and 19 other cell types or tissues.
DR   GO; GO:0032807; C:DNA ligase IV complex; IBA:GO_Central.
DR   GO; GO:0005958; C:DNA-dependent protein kinase-DNA ligase 4 complex; ISS:UniProtKB.
DR   GO; GO:0070419; C:nonhomologous end joining complex; ISS:UniProtKB.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0035861; C:site of double-strand break; ISS:UniProtKB.
DR   GO; GO:0045027; F:DNA end binding; ISS:UniProtKB.
DR   GO; GO:0070182; F:DNA polymerase binding; ISO:RGD.
DR   GO; GO:0030183; P:B cell differentiation; ISS:UniProtKB.
DR   GO; GO:0051103; P:DNA ligation involved in DNA repair; ISO:RGD.
DR   GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; ISS:UniProtKB.
DR   GO; GO:0033152; P:immunoglobulin V(D)J recombination; ISS:UniProtKB.
DR   GO; GO:0010212; P:response to ionizing radiation; ISS:UniProtKB.
DR   GO; GO:0030217; P:T cell differentiation; ISS:UniProtKB.
DR   CDD; cd22285; HD_XLF_N; 1.
DR   Gene3D; 2.170.210.10; DNA double-strand break repair and VJ recombination XRCC4, N-terminal; 1.
DR   Gene3D; 1.10.287.450; Helix hairpin bin; 1.
DR   InterPro; IPR015381; XLF_N.
DR   InterPro; IPR038051; XRCC4-like_N_sf.
DR   PANTHER; PTHR32235; NON-HOMOLOGOUS END-JOINING FACTOR 1; 1.
DR   PANTHER; PTHR32235:SF1; NON-HOMOLOGOUS END-JOINING FACTOR 1; 1.
DR   Pfam; PF09302; XLF; 1.
DR   Genevisible; Q6AYI4; RN.
PE   2: Evidence at transcript level;
KW   Chromosome; Coiled coil; DNA damage; DNA repair; DNA-binding; Nucleus;
KW   Phosphoprotein; Reference proteome.
FT   CHAIN           1..304
FT                   /note="Non-homologous end-joining factor 1"
FT                   /id="PRO_0000228656"
FT   REGION          1..140
FT                   /note="Globular head"
FT                   /evidence="ECO:0000250|UniProtKB:Q9H9Q4"
FT   REGION          229..293
FT                   /note="C-terminal tail"
FT                   /evidence="ECO:0000250|UniProtKB:A0A1L8ENT6"
FT   REGION          233..304
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          133..175
FT                   /evidence="ECO:0000250|UniProtKB:Q9H9Q4"
FT   MOTIF           294..304
FT                   /note="XLM"
FT                   /evidence="ECO:0000250|UniProtKB:Q9H9Q4"
FT   COMPBIAS        233..272
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        290..304
FT                   /note="Basic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            120
FT                   /note="Leu-lock"
FT                   /evidence="ECO:0000250|UniProtKB:Q9H9Q4"
FT   MOD_RES         137
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9H9Q4"
FT   MOD_RES         250
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q3KNJ2"
FT   MOD_RES         256
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9H9Q4"
FT   MOD_RES         271
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9H9Q4"
SQ   SEQUENCE   304 AA;  33885 MW;  DDB56676EB94B4DD CRC64;
     MEELEQGLLM QPWAWLQLAE NSLLAKASIT KHGYALLISD LQQVWHEQVD TLEVSQRAKE
     LNKRLTAPPA AFLHHLDEVL RPLFKDSAHQ DAAHPSKATF SCDRGEEVLI LRVRSELSGL
     PFNWHFHCLP ASSLLVSQHL ICPLMGVSLA LHSHVRELAA LLRMKDLEIQ AYQESGAVLS
     RGRLKTEPFE ENSFLEQFMV EKLPEACAVG DGRPFAMNLQ SLYVAVTKQQ VQARQKHKGS
     GEPQTSSSTS PQGTDSQLQN QPEQQISPTP TLSEPECEPM AASGPVHRAQ LVKAKRKKPR
     GLFS
//