CYREN_MOUSE
ID CYREN_MOUSE Reviewed; 157 AA.
AC Q8BHZ5; Q8K0Y5;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=Cell cycle regulator of non-homologous end joining {ECO:0000303|PubMed:31795137};
DE Short=Cell cycle regulator of NHEJ {ECO:0000303|PubMed:31795137};
DE AltName: Full=Modulator of retrovirus infection homolog {ECO:0000303|PubMed:30017584};
GN Name=Cyren {ECO:0000303|PubMed:31795137, ECO:0000312|MGI:MGI:1925662};
GN Synonyms=Mri {ECO:0000303|PubMed:30017584};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=FVB/N; TISSUE=Salivary gland;
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).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, MOTIFS KBM AND KLM, DOMAIN, INTERACTION
RP WITH XRCC5; XRCC6; TRIM28/KAP1; ATM; MRE11; NBN AND RAD50, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=30017584; DOI=10.1016/j.molcel.2018.06.018;
RA Hung P.J., Johnson B., Chen B.R., Byrum A.K., Bredemeyer A.L.,
RA Yewdell W.T., Johnson T.E., Lee B.J., Deivasigamani S., Hindi I.,
RA Amatya P., Gross M.L., Paull T.T., Pisapia D.J., Chaudhuri J.,
RA Petrini J.J.H., Mosammaparast N., Amarasinghe G.K., Zha S., Tyler J.K.,
RA Sleckman B.P.;
RT "MRI is a DNA damage response adaptor during classical non-homologous end
RT joining.";
RL Mol. Cell 71:332-342(2018).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=31795137; DOI=10.3390/biom9120798;
RA Castaneda-Zegarra S., Huse C., Roesand O., Sarno A., Xing M.,
RA Gago-Fuentes R., Zhang Q., Alirezaylavasani A., Werner J., Ji P.,
RA Liabakk N.B., Wang W., Bjoeraas M., Oksenych V.;
RT "Generation of a Mouse Model Lacking the Non-Homologous End-Joining Factor
RT Mri/Cyren.";
RL Biomolecules 9:0-0(2019).
CC -!- FUNCTION: Cell-cycle-specific regulator of classical non-homologous end
CC joining (NHEJ) of DNA double-strand break (DSB) repair, which can act
CC both as an activator or inhibitor of NHEJ, depending on the cell cycle
CC phase (PubMed:30017584). Acts as a regulator of DNA repair pathway
CC choice by specifically inhibiting classical NHEJ during the S and G2
CC phases, thereby promoting error-free repair by homologous recombination
CC during cell cycle phases when sister chromatids are present (By
CC similarity). Preferentially protects single-stranded overhangs at break
CC sites by inhibiting classical NHEJ, thereby creating a local
CC environment that favors homologous recombination (By similarity). Acts
CC via interaction with XRCC5/Ku80 and XRCC6/Ku70 (By similarity). In
CC contrast, acts as an activator of NHEJ during G1 phase of the cell
CC cycle: promotes classical NHEJ in G1 phase cells via multivalent
CC interactions that increase the affinity of DNA damage response proteins
CC for DSB-associated chromatin (PubMed:30017584). Also involved in
CC immunoglobulin V(D)J recombination (PubMed:30017584, PubMed:31795137).
CC May also act as an indirect regulator of proteasome (By similarity).
CC {ECO:0000250|UniProtKB:Q09HN1, ECO:0000250|UniProtKB:Q9BWK5,
CC ECO:0000269|PubMed:30017584, ECO:0000269|PubMed:31795137}.
CC -!- SUBUNIT: Interacts (via KBM motif) with XRCC5/Ku80 and XRCC6/Ku70
CC heterodimer (PubMed:30017584). Interacts (via XLF motif) with
CC TRIM28/KAP1, ATM, MRE11, NBN and RAD50 (PubMed:30017584).
CC {ECO:0000269|PubMed:30017584}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9BWK5}. Nucleus
CC {ECO:0000250|UniProtKB:Q9BWK5}. Chromosome
CC {ECO:0000269|PubMed:30017584}. Note=Nuclear localization may depend
CC upon interaction with XRCC5/Ku80 and XRCC6/Ku70 heterodimer (By
CC similarity). Localizes to DNA damage sites (PubMed:30017584).
CC {ECO:0000250|UniProtKB:Q9BWK5, ECO:0000269|PubMed:30017584}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8BHZ5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8BHZ5-2; Sequence=VSP_031769;
CC -!- DOMAIN: The KBM (Ku-binding motif) mediates interaction with XRCC5/Ku80
CC and XRCC6/Ku70 and recruitment to DNA damage sites.
CC {ECO:0000269|PubMed:30017584}.
CC -!- DOMAIN: The XLM (XLF-like motif) mediates interaction with DNA damage
CC response proteins TRIM28/KAP1, ATM and members of the MRN complex
CC (MRE11, NBN and RAD50). {ECO:0000269|PubMed:30017584}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype in normal conditions: mice
CC are fertile, do not show any gross abnormalities and do not develop
CC spontaneous cancers (PubMed:30017584, PubMed:31795137). Mice have
CC normal numbers of B- and T-cells, but show defects in class switch
CC recombination in primary B-cells (PubMed:30017584, PubMed:31795137).
CC Mice lacking both Cyren and Nhej1/Xlf show embryonic lethality caused
CC by severe defects in classical non-homologous end joining (NHEJ)
CC (PubMed:30017584). {ECO:0000269|PubMed:30017584,
CC ECO:0000269|PubMed:31795137}.
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DR EMBL; AK042380; BAC31243.1; -; mRNA.
DR EMBL; AK170119; BAE41576.1; -; mRNA.
DR EMBL; BC029235; AAH29235.1; -; mRNA.
DR CCDS; CCDS19997.1; -. [Q8BHZ5-1]
DR CCDS; CCDS85030.1; -. [Q8BHZ5-2]
DR RefSeq; NP_001129083.1; NM_001135611.1. [Q8BHZ5-1]
DR RefSeq; NP_001334030.1; NM_001347101.1. [Q8BHZ5-2]
DR RefSeq; NP_954596.1; NM_199145.2. [Q8BHZ5-1]
DR AlphaFoldDB; Q8BHZ5; -.
DR STRING; 10090.ENSMUSP00000053349; -.
DR PhosphoSitePlus; Q8BHZ5; -.
DR EPD; Q8BHZ5; -.
DR PaxDb; Q8BHZ5; -.
DR PRIDE; Q8BHZ5; -.
DR ProteomicsDB; 277937; -. [Q8BHZ5-1]
DR ProteomicsDB; 277938; -. [Q8BHZ5-2]
DR Antibodypedia; 18116; 54 antibodies from 17 providers.
DR Ensembl; ENSMUST00000055097; ENSMUSP00000053349; ENSMUSG00000046806. [Q8BHZ5-1]
DR Ensembl; ENSMUST00000115006; ENSMUSP00000110658; ENSMUSG00000046806. [Q8BHZ5-2]
DR Ensembl; ENSMUST00000115007; ENSMUSP00000110659; ENSMUSG00000046806. [Q8BHZ5-1]
DR GeneID; 78412; -.
DR KEGG; mmu:78412; -.
DR UCSC; uc009bhv.1; mouse. [Q8BHZ5-1]
DR UCSC; uc009bhx.2; mouse. [Q8BHZ5-2]
DR CTD; 78996; -.
DR MGI; MGI:1925662; Cyren.
DR VEuPathDB; HostDB:ENSMUSG00000046806; -.
DR eggNOG; ENOG502SEX2; Eukaryota.
DR GeneTree; ENSGT00390000013192; -.
DR HOGENOM; CLU_126072_0_0_1; -.
DR InParanoid; Q8BHZ5; -.
DR OMA; AKAPKRM; -.
DR PhylomeDB; Q8BHZ5; -.
DR TreeFam; TF336925; -.
DR BioGRID-ORCS; 78412; 1 hit in 71 CRISPR screens.
DR PRO; PR:Q8BHZ5; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q8BHZ5; protein.
DR Bgee; ENSMUSG00000046806; Expressed in granulocyte and 61 other tissues.
DR ExpressionAtlas; Q8BHZ5; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0035861; C:site of double-strand break; IDA:UniProtKB.
DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; IMP:UniProtKB.
DR GO; GO:0033152; P:immunoglobulin V(D)J recombination; IMP:UniProtKB.
DR GO; GO:2001033; P:negative regulation of double-strand break repair via nonhomologous end joining; ISS:UniProtKB.
DR DisProt; DP01754; -.
DR InterPro; IPR028278; MRI.
DR PANTHER; PTHR14566; PTHR14566; 1.
DR Pfam; PF15325; MRI; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Chromosome; Cytoplasm; DNA damage;
KW DNA repair; Nucleus; Reference proteome.
FT CHAIN 1..157
FT /note="Cell cycle regulator of non-homologous end joining"
FT /id="PRO_0000320949"
FT REGION 80..148
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1..21
FT /note="KBM"
FT /evidence="ECO:0000250|UniProtKB:Q9BWK5"
FT MOTIF 147..157
FT /note="XLM"
FT /evidence="ECO:0000250|UniProtKB:Q9BWK5"
FT COMPBIAS 89..113
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 134..148
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q9BWK5"
FT VAR_SEQ 74
FT /note="E -> EVTSVLSLVSPMPGDSSWVGTSTGPPLL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_031769"
FT CONFLICT 137
FT /note="S -> I (in Ref. 2; AAH29235)"
FT /evidence="ECO:0000305"
FT CONFLICT 142
FT /note="Missing (in Ref. 2; AAH29235)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 157 AA; 17287 MW; F4F36C5F855B2288 CRC64;
METLKSKTKT RVLPSWMTAP VDERKVVSVK TATRKQTAAW AQRVGAATRA PATETVYCMN
EAEMVDVALG ILIEGRKQEK PWEQRSLEAT DKLQLSPPCS SSPGSSSEEE DSRISSLAPG
LSPPRGPEAS DSPCSRSPEE EKEEEDALKY VREIFFS
