PAXX_HUMAN
ID PAXX_HUMAN Reviewed; 204 AA.
AC Q9BUH6; Q8IY19;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2004, sequence version 2.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Protein PAXX {ECO:0000305};
DE AltName: Full=Paralog of XRCC4 and XLF {ECO:0000303|PubMed:25574025};
DE AltName: Full=XRCC4-like small protein {ECO:0000303|PubMed:25941166};
GN Name=PAXX {ECO:0000303|PubMed:25574025, ECO:0000312|HGNC:HGNC:27849};
GN Synonyms=C9orf142 {ECO:0000312|HGNC:HGNC:27849},
GN XLS {ECO:0000303|PubMed:25941166};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 17-204 (ISOFORM 2).
RC TISSUE=Brain;
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-148, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-148, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-148, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-152, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-148, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-148 AND SER-152, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-148 AND SER-152, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-152, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [13]
RP FUNCTION, AND SUBUNIT.
RX PubMed=25941166; DOI=10.1038/cdd.2015.22;
RA Craxton A., Somers J., Munnur D., Jukes-Jones R., Cain K., Malewicz M.;
RT "XLS (c9orf142) is a new component of mammalian DNA double-stranded break
RT repair.";
RL Cell Death Differ. 22:890-897(2015).
RN [14]
RP INTERACTION WITH XRCC5 AND XRCC6, AND MUTAGENESIS OF SER-184 AND
RP 199-VAL--PHE-201.
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 [15]
RP FUNCTION, INTERACTION WITH XRCC6, PHOSPHORYLATION AT SER-134; THR-145;
RP SER-148 AND SER-152, AND MUTAGENESIS OF SER-134; 145-THR--SER-152;
RP 177-ARG--ARG-179 AND 199-VAL--PHE-201.
RX PubMed=27705800; DOI=10.1016/j.celrep.2016.09.026;
RA Tadi S.K., Tellier-Lebegue C., Nemoz C., Drevet P., Audebert S., Roy S.,
RA Meek K., Charbonnier J.B., Modesti M.;
RT "PAXX is an accessory c-NHEJ factor that associates with Ku70 and has
RT overlapping functions with XLF.";
RL Cell Rep. 17:541-555(2016).
RN [16]
RP FUNCTION.
RX PubMed=27703001; DOI=10.1074/jbc.m116.752329;
RA Chang H.H.Y., Watanabe G., Gerodimos C.A., Ochi T., Blundell T.L.,
RA Jackson S.P., Lieber M.R.;
RT "Different DNA End Configurations Dictate Which NHEJ Components Are Most
RT Important for Joining Efficiency.";
RL J. Biol. Chem. 291:24377-24389(2016).
RN [17]
RP XLM MOTIF.
RX PubMed=27063109; DOI=10.1038/ncomms11242;
RA Grundy G.J., Rulten S.L., Arribas-Bosacoma R., Davidson K., Kozik Z.,
RA Oliver A.W., Pearl L.H., Caldecott K.W.;
RT "The Ku-binding motif is a conserved module for recruitment and stimulation
RT of non-homologous end-joining proteins.";
RL Nat. Commun. 7:11242-11242(2016).
RN [18]
RP FUNCTION (MICROBIAL INFECTION), AND SUBCELLULAR LOCATION (MICROBIAL
RP INFECTION).
RX PubMed=29144403; DOI=10.3390/v9110342;
RA Trigg B.J., Lauer K.B., Fernandes Dos Santos P., Coleman H., Balmus G.,
RA Mansur D.S., Ferguson B.J.;
RT "The Non-Homologous End Joining Protein PAXX Acts to Restrict HSV-1
RT Infection.";
RL Viruses 9:0-0(2017).
RN [19]
RP FUNCTION, AND INTERACTION WITH POLL.
RX PubMed=30250067; DOI=10.1038/s41467-018-06127-y;
RA Craxton A., Munnur D., Jukes-Jones R., Skalka G., Langlais C., Cain K.,
RA Malewicz M.;
RT "PAXX and its paralogs synergistically direct DNA polymerase lambda
RT activity in DNA repair.";
RL Nat. Commun. 9:3877-3877(2018).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 1-145, SUBUNIT, SUBCELLULAR
RP LOCATION, MUTAGENESIS OF 96-LEU--LEU-109; 177-ARG--ARG-179; 186-ILE-ASN-187
RP AND PHE-201, AND REGION.
RX PubMed=25670504; DOI=10.1038/ncomms7233;
RA Xing M., Yang M., Huo W., Feng F., Wei L., Jiang W., Ning S., Yan Z.,
RA Li W., Wang Q., Hou M., Dong C., Guo R., Gao G., Ji J., Zha S., Lan L.,
RA Liang H., Xu D.;
RT "Interactome analysis identifies a new paralogue of XRCC4 in non-homologous
RT end joining DNA repair pathway.";
RL Nat. Commun. 6:6233-6233(2015).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS), FUNCTION, HOMODIMERIZATION,
RP SUBCELLULAR LOCATION, DOMAIN, INTERACTION WITH XRCC5 AND XRCC6, AND
RP MUTAGENESIS OF 199-VAL--PHE-201.
RX PubMed=25574025; DOI=10.1126/science.1261971;
RA Ochi T., Blackford A.N., Coates J., Jhujh S., Mehmood S., Tamura N.,
RA Travers J., Wu Q., Draviam V.M., Robinson C.V., Blundell T.L.,
RA Jackson S.P.;
RT "DNA repair. PAXX, a paralog of XRCC4 and XLF, interacts with Ku to promote
RT DNA double-strand break repair.";
RL Science 347:185-188(2015).
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:25574025, PubMed:25670504,
CC PubMed:25941166, PubMed:27705800). May act as a scaffold required for
CC accumulation of the Ku heterodimer, composed of XRCC5/Ku80 and
CC XRCC6/Ku70, at double-strand break sites and promote the assembly
CC and/or stability of the NHEJ machinery (PubMed:25574025,
CC PubMed:25670504, PubMed:25941166). Involved in NHEJ by promoting the
CC ligation of blunt-ended DNA ends (PubMed:27703001). Together with
CC NHEJ1/XLF, collaborates with DNA polymerase lambda (POLL) to promote
CC joining of non-cohesive DNA ends (PubMed:30250067, PubMed:25670504).
CC Constitutes a non-essential component of classical NHEJ: has a
CC complementary but distinct function with NHEJ1/XLF in DNA repair
CC (PubMed:27705800). Able to restrict infection by herpesvirus 1 (HSV-1)
CC via an unknown mechanism (PubMed:29144403).
CC {ECO:0000269|PubMed:25574025, ECO:0000269|PubMed:25670504,
CC ECO:0000269|PubMed:25941166, ECO:0000269|PubMed:27703001,
CC ECO:0000269|PubMed:27705800, ECO:0000269|PubMed:29144403,
CC ECO:0000269|PubMed:30250067}.
CC -!- SUBUNIT: Homodimer (PubMed:25574025). Interacts with the DNA-bound
CC XRCC5/Ku80 and XRCC6/Ku70 heterodimer (Ku complex); the interaction is
CC direct (PubMed:27601299, PubMed:27705800, PubMed:25574025). Associated
CC component of the non-homologous end joining (NHEJ) complex, composed of
CC the core proteins PRKDC, LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and
CC NHEJ1/XLF (PubMed:25670504, PubMed:25941166). Interacts with POLL (DNA
CC polymerase lambda); promoting POLL recruitment to double-strand breaks
CC (DSBs) and stimulation of the end-filling activity of POLL
CC (PubMed:30250067). {ECO:0000269|PubMed:25574025,
CC ECO:0000269|PubMed:25670504, ECO:0000269|PubMed:25941166,
CC ECO:0000269|PubMed:27601299, ECO:0000269|PubMed:27705800,
CC ECO:0000269|PubMed:30250067}.
CC -!- INTERACTION:
CC Q9BUH6; Q96CV9: OPTN; NbExp=3; IntAct=EBI-2839993, EBI-748974;
CC Q9BUH6; P13010: XRCC5; NbExp=2; IntAct=EBI-2839993, EBI-357997;
CC Q9BUH6-1; Q9BUH6-1: PAXX; NbExp=4; IntAct=EBI-16137878, EBI-16137878;
CC Q9BUH6-1; P13010: XRCC5; NbExp=5; IntAct=EBI-16137878, EBI-357997;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:25574025,
CC ECO:0000269|PubMed:25670504, ECO:0000269|PubMed:29144403}. Chromosome
CC {ECO:0000269|PubMed:25574025, ECO:0000269|PubMed:25670504}.
CC Note=Predominantly localizes to the nucleus. Accumulates at sites of
CC DNA damage generated by laser microirradiation.
CC {ECO:0000269|PubMed:25574025, ECO:0000269|PubMed:25670504}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:29144403}.
CC Note=(Microbial infection) Upon infection by herpesvirus 1 (HSV-1), it
CC is partially translocated into the cytoplasm in an HSV-1-dependent
CC manner. {ECO:0000269|PubMed:29144403}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9BUH6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BUH6-2; Sequence=VSP_024996, VSP_024997;
CC -!- DOMAIN: The N-terminus (residues 1-113) forms a head domain that is
CC structurally related to those of XRCC4, XLF/NHEJ1, and SASS6.
CC {ECO:0000269|PubMed:25574025}.
CC -!- PTM: Phosphorylation may inhibit interaction with the DNA-bound
CC XRCC5/Ku80 and XRCC6/Ku70 heterodimer (Ku complex).
CC {ECO:0000269|PubMed:27705800}.
CC -!- SIMILARITY: Belongs to the XRCC4-XLF family. PAXX subfamily.
CC {ECO:0000305}.
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DR EMBL; AL807752; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC002613; AAH02613.2; -; mRNA.
DR EMBL; BC038191; AAH38191.1; -; mRNA.
DR CCDS; CCDS7020.1; -. [Q9BUH6-1]
DR RefSeq; NP_899064.1; NM_183241.2. [Q9BUH6-1]
DR PDB; 3WTD; X-ray; 2.35 A; A/B=1-166.
DR PDB; 3WTF; X-ray; 3.45 A; A/B=1-204.
DR PDB; 4WJA; X-ray; 2.60 A; A/B=1-145.
DR PDBsum; 3WTD; -.
DR PDBsum; 3WTF; -.
DR PDBsum; 4WJA; -.
DR AlphaFoldDB; Q9BUH6; -.
DR SMR; Q9BUH6; -.
DR BioGRID; 130343; 45.
DR DIP; DIP-61486N; -.
DR IntAct; Q9BUH6; 13.
DR MINT; Q9BUH6; -.
DR STRING; 9606.ENSP00000360682; -.
DR GlyGen; Q9BUH6; 2 sites, 2 O-linked glycans (2 sites).
DR iPTMnet; Q9BUH6; -.
DR PhosphoSitePlus; Q9BUH6; -.
DR BioMuta; PAXX; -.
DR DMDM; 74752355; -.
DR EPD; Q9BUH6; -.
DR jPOST; Q9BUH6; -.
DR MassIVE; Q9BUH6; -.
DR MaxQB; Q9BUH6; -.
DR PaxDb; Q9BUH6; -.
DR PeptideAtlas; Q9BUH6; -.
DR PRIDE; Q9BUH6; -.
DR ProteomicsDB; 79085; -. [Q9BUH6-1]
DR ProteomicsDB; 79086; -. [Q9BUH6-2]
DR Antibodypedia; 51856; 52 antibodies from 13 providers.
DR DNASU; 286257; -.
DR Ensembl; ENST00000371620.4; ENSP00000360682.3; ENSG00000148362.11. [Q9BUH6-1]
DR GeneID; 286257; -.
DR KEGG; hsa:286257; -.
DR MANE-Select; ENST00000371620.4; ENSP00000360682.3; NM_183241.3; NP_899064.1.
DR UCSC; uc004cki.3; human. [Q9BUH6-1]
DR CTD; 286257; -.
DR DisGeNET; 286257; -.
DR GeneCards; PAXX; -.
DR HGNC; HGNC:27849; PAXX.
DR HPA; ENSG00000148362; Low tissue specificity.
DR MIM; 616315; gene.
DR neXtProt; NX_Q9BUH6; -.
DR OpenTargets; ENSG00000148362; -.
DR PharmGKB; PA143485344; -.
DR VEuPathDB; HostDB:ENSG00000148362; -.
DR eggNOG; ENOG502S6IF; Eukaryota.
DR GeneTree; ENSGT00390000000543; -.
DR HOGENOM; CLU_121226_0_0_1; -.
DR InParanoid; Q9BUH6; -.
DR OMA; VCYCEPE; -.
DR OrthoDB; 1347811at2759; -.
DR PhylomeDB; Q9BUH6; -.
DR TreeFam; TF337247; -.
DR PathwayCommons; Q9BUH6; -.
DR SignaLink; Q9BUH6; -.
DR BioGRID-ORCS; 286257; 6 hits in 1062 CRISPR screens.
DR GenomeRNAi; 286257; -.
DR Pharos; Q9BUH6; Tbio.
DR PRO; PR:Q9BUH6; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q9BUH6; protein.
DR Bgee; ENSG00000148362; Expressed in granulocyte and 146 other tissues.
DR Genevisible; Q9BUH6; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0070419; C:nonhomologous end joining complex; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0035861; C:site of double-strand break; IDA:UniProtKB.
DR GO; GO:0070182; F:DNA polymerase binding; IPI:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0060090; F:molecular adaptor activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; IDA:UniProtKB.
DR DisProt; DP01795; -.
DR InterPro; IPR027873; PAXX.
DR PANTHER; PTHR28586; PTHR28586; 1.
DR Pfam; PF15384; PAXX; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chromosome; Cytoplasm; DNA damage;
KW DNA repair; Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..204
FT /note="Protein PAXX"
FT /id="PRO_0000286104"
FT DOMAIN 37..79
FT /note="PISA"
FT /evidence="ECO:0000305"
FT REGION 143..204
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 171..204
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:0000269|PubMed:25574025,
FT ECO:0000269|PubMed:25670504"
FT MOTIF 190..204
FT /note="XLM"
FT /evidence="ECO:0000305|PubMed:27063109"
FT COMPBIAS 156..170
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 134
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:27705800"
FT MOD_RES 145
FT /note="Phosphothreonine"
FT /evidence="ECO:0000305|PubMed:27705800"
FT MOD_RES 148
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:27705800,
FT ECO:0007744|PubMed:16964243, ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 152
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:27705800,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT VAR_SEQ 61..106
FT /note="KARFGLSAAEDITPRFRAACEQQAVALTLQEDRASLTLSGGPSALA -> VG
FT NWAGLGAATPLLAVQIVYGATDIWDSPEGSDTLCPPCSCSPPIG (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_024996"
FT VAR_SEQ 107..204
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_024997"
FT MUTAGEN 96..109
FT /note="LTLSGGPSALAFDL->DTDSGGPSADAFDD: Loss of function in
FT DNA non-homologous end joining (NHEJ)."
FT /evidence="ECO:0000269|PubMed:25670504"
FT MUTAGEN 134
FT /note="S->A: Does not affect interaction with the DNA-bound
FT XRCC5/Ku80 and XRCC6/Ku70 heterodimer; when associated with
FT 145-D--152."
FT /evidence="ECO:0000269|PubMed:27705800"
FT MUTAGEN 134
FT /note="S->D: Phospho-mimetic mutant; abolished interaction
FT with DNA-bound the DNA-bound XRCC5/Ku80 and XRCC6/Ku70
FT heterodimer; when associated with 145-D--152."
FT /evidence="ECO:0000269|PubMed:27705800"
FT MUTAGEN 145..152
FT /note="TAVSPRKS->AAVAPRKA: Does not affect interaction with
FT the DNA-bound XRCC5/Ku80 and XRCC6/Ku70 heterodimer; when
FT associated with A-134."
FT /evidence="ECO:0000269|PubMed:27705800"
FT MUTAGEN 145..152
FT /note="TAVSPRKS->DAVDPRKD: Phospho-mimetic mutant;
FT abolished interaction with the DNA-bound XRCC5/Ku80 and
FT XRCC6/Ku70 heterodimer; when associated with D-134."
FT /evidence="ECO:0000269|PubMed:27705800"
FT MUTAGEN 177..179
FT /note="RRR->AAA: Abolishes the association with the non-
FT homologous end joining complex. Abolished interaction with
FT XRCC6/Ku70."
FT /evidence="ECO:0000269|PubMed:25670504,
FT ECO:0000269|PubMed:27705800"
FT MUTAGEN 184
FT /note="S->E: Abolished interaction with XRCC5/Ku80 and
FT XRCC6/Ku70."
FT /evidence="ECO:0000269|PubMed:27601299"
FT MUTAGEN 186..187
FT /note="IN->AA: Abolishes the association with the non-
FT homologous end joining complex."
FT /evidence="ECO:0000269|PubMed:25670504"
FT MUTAGEN 199..201
FT /note="VDF->ADA: Abolished interaction with XRCC5/Ku80 and
FT XRCC6/Ku70."
FT /evidence="ECO:0000269|PubMed:25574025,
FT ECO:0000269|PubMed:27601299"
FT MUTAGEN 201
FT /note="F->A: Abolishes the association with the non-
FT homologous end joining complex and localization to double-
FT strand break sites. Abolished interaction with XRCC6/Ku70."
FT /evidence="ECO:0000269|PubMed:25670504,
FT ECO:0000269|PubMed:27705800"
FT STRAND 8..12
FT /evidence="ECO:0007829|PDB:3WTD"
FT STRAND 14..16
FT /evidence="ECO:0007829|PDB:3WTD"
FT STRAND 20..25
FT /evidence="ECO:0007829|PDB:3WTD"
FT STRAND 30..32
FT /evidence="ECO:0007829|PDB:3WTD"
FT STRAND 38..42
FT /evidence="ECO:0007829|PDB:3WTD"
FT STRAND 44..49
FT /evidence="ECO:0007829|PDB:3WTD"
FT HELIX 54..64
FT /evidence="ECO:0007829|PDB:3WTD"
FT HELIX 73..82
FT /evidence="ECO:0007829|PDB:3WTD"
FT STRAND 85..90
FT /evidence="ECO:0007829|PDB:3WTD"
FT STRAND 93..98
FT /evidence="ECO:0007829|PDB:3WTD"
FT STRAND 100..103
FT /evidence="ECO:0007829|PDB:3WTD"
FT STRAND 105..111
FT /evidence="ECO:0007829|PDB:3WTD"
FT HELIX 114..140
FT /evidence="ECO:0007829|PDB:3WTD"
SQ SEQUENCE 204 AA; 21640 MW; 5F9737ED9463B6BE CRC64;
MDPLSPPLCT LPPGPEPPRF VCYCEGEESG EGDRGGFNLY VTDAAELWST CFTPDSLAAL
KARFGLSAAE DITPRFRAAC EQQAVALTLQ EDRASLTLSG GPSALAFDLS KVPGPEAAPR
LRALTLGLAK RVWSLERRLA AAEETAVSPR KSPRPAGPQL FLPDPDPQRG GPGPGVRRRC
PGESLINPGF KSKKPAGGVD FDET
