PAXX_MOUSE
ID PAXX_MOUSE Reviewed; 205 AA.
AC Q8K0Y7; Q8C6V7;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 105.
DE RecName: Full=Protein PAXX {ECO:0000305};
DE AltName: Full=Paralog of XRCC4 and XLF {ECO:0000303|PubMed:29511619, ECO:0000303|PubMed:29511621};
GN Name=Paxx {ECO:0000303|PubMed:29511619, ECO:0000303|PubMed:29511621};
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 GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 70-205.
RC STRAIN=C57BL/6J; TISSUE=Head;
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27601299; DOI=10.1016/j.celrep.2016.08.069;
RA Lescale C., Lenden Hasse H., Blackford A.N., Balmus G., Bianchi J.J.,
RA Yu W., Bacoccina L., Jarade A., Clouin C., Sivapalan R.,
RA Reina-San-Martin B., Jackson S.P., Deriano L.;
RT "Specific roles of XRCC4 paralogs PAXX and XLF during V(D)J
RT recombination.";
RL Cell Rep. 16:2967-2979(2016).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27798842; DOI=10.1101/gad.290510.116;
RA Balmus G., Barros A.C., Wijnhoven P.W., Lescale C., Hasse H.L.,
RA Boroviak K., le Sage C., Doe B., Speak A.O., Galli A., Jacobsen M.,
RA Deriano L., Adams D.J., Blackford A.N., Jackson S.P.;
RT "Synthetic lethality between PAXX and XLF in mammalian development.";
RL Genes Dev. 30:2152-2157(2016).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27601633; DOI=10.1073/pnas.1611882113;
RA Kumar V., Alt F.W., Frock R.L.;
RT "PAXX and XLF DNA repair factors are functionally redundant in joining DNA
RT breaks in a G1-arrested progenitor B-cell line.";
RL Proc. Natl. Acad. Sci. U.S.A. 113:10619-10624(2016).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27830975; DOI=10.1080/15384101.2016.1253640;
RA Hung P.J., Chen B.R., George R., Liberman C., Morales A.J., Colon-Ortiz P.,
RA Tyler J.K., Sleckman B.P., Bredemeyer A.L.;
RT "Deficiency of XLF and PAXX prevents DNA double-strand break repair by non-
RT homologous end joining in lymphocytes.";
RL Cell Cycle 16:286-295(2017).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=28051062; DOI=10.1038/ncomms13816;
RA Liu X., Shao Z., Jiang W., Lee B.J., Zha S.;
RT "PAXX promotes KU accumulation at DNA breaks and is essential for end-
RT joining in XLF-deficient mice.";
RL Nat. Commun. 8:13816-13816(2017).
RN [10]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=29077092; DOI=10.1038/cdd.2017.184;
RA Abramowski V., Etienne O., Elsaid R., Yang J., Berland A., Kermasson L.,
RA Roch B., Musilli S., Moussu J.P., Lipson-Ruffert K., Revy P., Cumano A.,
RA Boussin F.D., de Villartay J.P.;
RT "PAXX and Xlf interplay revealed by impaired CNS development and
RT immunodeficiency of double KO mice.";
RL Cell Death Differ. 25:444-452(2018).
RN [11]
RP DISRUPTION PHENOTYPE.
RX PubMed=29511619; DOI=10.1002/2211-5463.12381;
RA Gago-Fuentes R., Xing M., Saeterstad S., Sarno A., Dewan A., Beck C.,
RA Bradamante S., Bjoeraas M., Oksenych V.;
RT "Normal development of mice lacking PAXX, the paralogue of XRCC4 and XLF.";
RL FEBS Open Bio 8:426-434(2018).
RN [12]
RP DISRUPTION PHENOTYPE.
RX PubMed=29511621; DOI=10.1002/2211-5463.12380;
RA Dewan A., Xing M., Lundbaek M.B., Gago-Fuentes R., Beck C., Aas P.A.,
RA Liabakk N.B., Saeterstad S., Chau K.T.P., Kavli B.M., Oksenych V.;
RT "Robust DNA repair in PAXX-deficient mammalian cells.";
RL FEBS Open Bio 8:442-448(2018).
CC -!- FUNCTION: Non-essential DNA repair protein involved in DNA non-
CC homologous end joining (NHEJ); participates in double-strand break
CC (DSB) repair and V(D)J recombination (PubMed:27601299, PubMed:27798842,
CC PubMed:27601633, PubMed:27830975, PubMed:28051062, PubMed:29077092).
CC May act as a scaffold required for accumulation of the Ku heterodimer,
CC composed of XRCC5/Ku80 and XRCC6/Ku70, at double-strand break sites and
CC promote the assembly and/or stability of the NHEJ machinery
CC (PubMed:28051062). Involved in NHEJ by promoting the ligation of blunt-
CC ended DNA ends (By similarity). Together with NHEJ1/XLF, collaborates
CC with DNA polymerase lambda (POLL) to promote joining of non-cohesive
CC DNA ends (By similarity). Constitutes a non-essential component of
CC classical NHEJ: has a complementary but distinct function with
CC NHEJ1/XLF in DNA repair (PubMed:27601299, PubMed:27798842,
CC PubMed:27830975, PubMed:28051062). {ECO:0000250|UniProtKB:Q9BUH6,
CC ECO:0000269|PubMed:27601299, ECO:0000269|PubMed:27601633,
CC ECO:0000269|PubMed:27798842, ECO:0000269|PubMed:27830975,
CC ECO:0000269|PubMed:28051062, ECO:0000269|PubMed:29077092}.
CC -!- SUBUNIT: Homodimer (By similarity). Interacts with the DNA-bound
CC XRCC5/Ku80 and XRCC6/Ku70 heterodimer (Ku complex); the interaction is
CC direct (By similarity). Associated component of the non-homologous end
CC joining (NHEJ) complex, composed of the core proteins PRKDC, LIG4,
CC XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF (By similarity). Interacts
CC with POLL (DNA polymerase lambda); promoting POLL recruitment to
CC double-strand breaks (DSBs) and stimulation of the end-filling activity
CC of POLL (By similarity). {ECO:0000250|UniProtKB:Q9BUH6}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9BUH6}.
CC Chromosome {ECO:0000250|UniProtKB:Q9BUH6}. Note=Predominantly localizes
CC to the nucleus. Accumulates at sites of DNA damage generated by laser
CC microirradiation. {ECO:0000250|UniProtKB:Q9BUH6}.
CC -!- DOMAIN: The N-terminus (residues 1-115) forms a head domain that is
CC structurally related to those of XRCC4, XLF/NHEJ1, and SASS6.
CC {ECO:0000250|UniProtKB:Q9BUH6}.
CC -!- PTM: Phosphorylation may inhibit interaction with the DNA-bound
CC XRCC5/Ku80 and XRCC6/Ku70 heterodimer (Ku complex).
CC {ECO:0000250|UniProtKB:Q9BUH6}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype in normal conditions
CC (PubMed:27798842, PubMed:28051062, PubMed:29511619, PubMed:29511621).
CC Mice are viable, grow normally, are fertile and have normal lymphocyte
CC development (PubMed:27798842, PubMed:29511619, PubMed:29511621). They
CC however show mild radiosensitivity (PubMed:29511619, PubMed:29511621).
CC Mice lacking both Paxx and Nhej1/Xlf show embryonic lethality caused by
CC severe defects in classical non-homologous end joining (NHEJ)
CC (PubMed:27601299, PubMed:27798842, PubMed:27601633, PubMed:27830975,
CC PubMed:28051062, PubMed:29077092). {ECO:0000269|PubMed:27601299,
CC ECO:0000269|PubMed:27601633, ECO:0000269|PubMed:27798842,
CC ECO:0000269|PubMed:27830975, ECO:0000269|PubMed:28051062,
CC ECO:0000269|PubMed:29077092, ECO:0000269|PubMed:29511619,
CC ECO:0000269|PubMed:29511621}.
CC -!- SIMILARITY: Belongs to the XRCC4-XLF family. PAXX subfamily.
CC {ECO:0000305}.
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DR EMBL; AL732557; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC029214; AAH29214.1; -; mRNA.
DR EMBL; AK053101; BAC35265.1; -; mRNA.
DR CCDS; CCDS15775.1; -.
DR RefSeq; NP_705785.1; NM_153557.1.
DR AlphaFoldDB; Q8K0Y7; -.
DR SMR; Q8K0Y7; -.
DR STRING; 10090.ENSMUSP00000109899; -.
DR iPTMnet; Q8K0Y7; -.
DR PhosphoSitePlus; Q8K0Y7; -.
DR EPD; Q8K0Y7; -.
DR MaxQB; Q8K0Y7; -.
DR PaxDb; Q8K0Y7; -.
DR PRIDE; Q8K0Y7; -.
DR ProteomicsDB; 294164; -.
DR Antibodypedia; 51856; 52 antibodies from 13 providers.
DR DNASU; 227622; -.
DR Ensembl; ENSMUST00000114261; ENSMUSP00000109899; ENSMUSG00000047617.
DR GeneID; 227622; -.
DR KEGG; mmu:227622; -.
DR UCSC; uc008ise.1; mouse.
DR CTD; 286257; -.
DR MGI; MGI:2442831; Paxx.
DR VEuPathDB; HostDB:ENSMUSG00000047617; -.
DR eggNOG; ENOG502S6IF; Eukaryota.
DR GeneTree; ENSGT00390000000543; -.
DR HOGENOM; CLU_121226_0_0_1; -.
DR InParanoid; Q8K0Y7; -.
DR OMA; VCYCEPE; -.
DR OrthoDB; 1347811at2759; -.
DR PhylomeDB; Q8K0Y7; -.
DR TreeFam; TF337247; -.
DR BioGRID-ORCS; 227622; 3 hits in 108 CRISPR screens.
DR ChiTaRS; BC029214; mouse.
DR PRO; PR:Q8K0Y7; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q8K0Y7; protein.
DR Bgee; ENSMUSG00000047617; Expressed in granulocyte and 204 other tissues.
DR ExpressionAtlas; Q8K0Y7; baseline and differential.
DR Genevisible; Q8K0Y7; MM.
DR GO; GO:0043564; C:Ku70:Ku80 complex; ISO:MGI.
DR GO; GO:0070419; C:nonhomologous end joining complex; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0035861; C:site of double-strand break; ISS:UniProtKB.
DR GO; GO:0070182; F:DNA polymerase binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0060090; F:molecular adaptor activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; IMP:UniProtKB.
DR InterPro; IPR027873; PAXX.
DR PANTHER; PTHR28586; PTHR28586; 1.
DR Pfam; PF15384; PAXX; 1.
PE 1: Evidence at protein level;
KW Chromosome; DNA damage; DNA repair; Nucleus; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..205
FT /note="Protein PAXX"
FT /id="PRO_0000286105"
FT DOMAIN 39..81
FT /note="PISA"
FT /evidence="ECO:0000305"
FT REGION 147..205
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 172..205
FT /note="Mediates interaction with XRCC5/Ku80 and XRCC6/Ku70
FT and association with the non-homologous end joining core
FT complex"
FT /evidence="ECO:0000250|UniProtKB:Q9BUH6"
FT MOTIF 191..205
FT /note="XLM"
FT /evidence="ECO:0000250|UniProtKB:Q9BUH6"
FT COMPBIAS 148..162
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 147
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9BUH6"
FT MOD_RES 150
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BUH6"
SQ SEQUENCE 205 AA; 21977 MW; 77104C9D0A27C73A CRC64;
MAPPLLSLPL CILPPGSGSP RLVCYCERDS GGDGDRDDFN LYVTDAAELW STCFSPDSLA
RLKARFGLSG AEDIHSRFRA ACQQQAVTVS LQEDRALITL SGDTPALAFD LSKVPSPEAA
PRLQALTLSL AEHVCNLERR LAAAEETITS PKKNTQPAGT QFLPELDHQR GSSGPGVRRR
CPGESLINPG FKSKKPAAGV DFDET
