ID SETX_HUMAN Reviewed; 2677 AA.
AC Q7Z333; A2A396; B2RPB2; B5ME16; C9JQ10; O75120; Q3KQX4; Q5JUJ1;
AC Q68DW5; Q6AZD7; Q7Z3J6; Q8WX33; Q9H9D1; Q9NVP9;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 4.
DT 30-NOV-2016, entry version 142.
DE RecName: Full=Probable helicase senataxin {ECO:0000305};
DE EC=3.6.4.-;
DE AltName: Full=Amyotrophic lateral sclerosis 4 protein;
DE AltName: Full=SEN1 homolog {ECO:0000305};
DE AltName: Full=Senataxin {ECO:0000303|PubMed:14770181, ECO:0000312|HGNC:HGNC:445};
GN Name=SETX {ECO:0000303|PubMed:14770181, ECO:0000312|HGNC:HGNC:445};
GN Synonyms=ALS4, KIAA0625, SCAR1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, VARIANT
RP CYS-1152, VARIANTS SCAR1 CYS-305; TRP-332; LEU-413; SER-1756 AND
RP LEU-2213, AND INVOLVEMENT IN ALS4.
RX PubMed=14770181; DOI=10.1038/ng1303;
RA Moreira M.-C., Klur S., Watanabe M., Nemeth A.H., Le Ber I.,
RA Moniz J.-C., Tranchant C., Aubourg P., Tazir M., Schoels L.,
RA Pandolfo M., Schulz J.B., Pouget J., Calvas P., Shizuka-Ikeda M.,
RA Shoji M., Tanaka M., Izatt L., Shaw C.E., M'Zahem A., Dunne E.,
RA Bomont P., Benhassine T., Bouslam N., Stevanin G., Brice A.,
RA Guimaraes J., Mendonca P., Barbot C., Coutinho P., Sequeiros J.,
RA Duerr A., Warter J.-M., Koenig M.;
RT "Senataxin, the ortholog of a yeast RNA helicase, is mutant in ataxia-
RT ocular apraxia 2.";
RL Nat. Genet. 36:225-227(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 447-2677 (ISOFORM 3), AND VARIANTS
RP GLU-1192; ARG-1252; VAL-1386 AND VAL-2587.
RC TISSUE=Amygdala, Fetal kidney, and Retina;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
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.,
RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA 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.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA 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.,
RA Rogers J., Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS
RP GLU-1192; ARG-1252; VAL-1386; ALA-1855; VAL-2587 AND GLY-2612.
RC TISSUE=Peripheral nerve, Retinoblastoma, Testis, and Uterus;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 15-2677 (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=9734811; DOI=10.1093/dnares/5.3.169;
RA Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H.,
RA Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. X.
RT The complete sequences of 100 new cDNA clones from brain which can
RT code for large proteins in vitro.";
RL DNA Res. 5:169-176(1998).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1762-2677 (ISOFORM 1), AND
RP VARIANT VAL-2587.
RC TISSUE=Teratocarcinoma;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1017 AND SER-1019, AND
RP IDENTIFICATION BY 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.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1621, AND IDENTIFICATION
RP BY 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
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [9]
RP FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=17562789; DOI=10.1083/jcb.200701042;
RA Suraweera A., Becherel O.J., Chen P., Rundle N., Woods R.,
RA Nakamura J., Gatei M., Criscuolo C., Filla A., Chessa L., Fusser M.,
RA Epe B., Gueven N., Lavin M.F.;
RT "Senataxin, defective in ataxia oculomotor apraxia type 2, is involved
RT in the defense against oxidative DNA damage.";
RL J. Cell Biol. 177:969-979(2007).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-615; SER-1017 AND
RP SER-1019, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 [11]
RP FUNCTION, AND INTERACTION WITH NCL; PABPN1; PABPC1; POLR2A; SF3B1 AND
RP SMN1.
RX PubMed=19515850; DOI=10.1093/hmg/ddp278;
RA Suraweera A., Lim Y., Woods R., Birrell G.W., Nasim T., Becherel O.J.,
RA Lavin M.F.;
RT "Functional role for senataxin, defective in ataxia oculomotor apraxia
RT type 2, in transcriptional regulation.";
RL Hum. Mol. Genet. 18:3384-3396(2009).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1017, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1017 AND SER-1019, AND
RP IDENTIFICATION BY 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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [14]
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.,
RA Buerckstuemmer T., 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 [15]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=21576111; DOI=10.1093/brain/awr084;
RA Vantaggiato C., Bondioni S., Airoldi G., Bozzato A., Borsani G.,
RA Rugarli E.I., Bresolin N., Clementi E., Bassi M.T.;
RT "Senataxin modulates neurite growth through fibroblast growth factor 8
RT signalling.";
RL Brain 134:1808-1828(2011).
RN [16]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=21112256; DOI=10.1016/j.dnarep.2010.10.012;
RA De Amicis A., Piane M., Ferrari F., Fanciulli M., Delia D., Chessa L.;
RT "Role of senataxin in DNA damage and telomeric stability.";
RL DNA Repair 10:199-209(2011).
RN [17]
RP FUNCTION.
RX PubMed=21700224; DOI=10.1016/j.molcel.2011.04.026;
RA Skourti-Stathaki K., Proudfoot N.J., Gromak N.;
RT "Human senataxin resolves RNA/DNA hybrids formed at transcriptional
RT pause sites to promote Xrn2-dependent termination.";
RL Mol. Cell 42:794-805(2011).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1017 AND SER-1019, 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.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [19]
RP FUNCTION, INTERACTION WITH EXOSC9 AND UBE2I, SUMOYLATION, SUBCELLULAR
RP LOCATION, CHARACTERIZATION OF VARIANTS SCAR1 CYS-305 AND LEU-413,
RP CHARACTERIZATION OF VARIANTS ALS4 ILE-3 AND SER-389, AND MUTAGENESIS
RP OF GLU-65.
RX PubMed=24105744; DOI=10.1101/gad.224923.113;
RA Richard P., Feng S., Manley J.L.;
RT "A SUMO-dependent interaction between Senataxin and the exosome,
RT disrupted in the neurodegenerative disease AOA2, targets the exosome
RT to sites of transcription-induced DNA damage.";
RL Genes Dev. 27:2227-2232(2013).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-642; SER-911; SER-947;
RP SER-956; SER-1330; SER-1366; SER-1623; SER-1663 AND THR-2474, 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 [21]
RP INTERACTION WITH CHD4; POLR2A; PRKDC AND TRIM28, SUBCELLULAR LOCATION,
RP AND DOMAIN.
RX PubMed=23149945; DOI=10.1128/MCB.01195-12;
RA Yuce O., West S.C.;
RT "Senataxin, defective in the neurodegenerative disorder ataxia with
RT oculomotor apraxia 2, lies at the interface of transcription and the
RT DNA damage response.";
RL Mol. Cell. Biol. 33:406-417(2013).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1017 AND SER-1019, AND
RP IDENTIFICATION BY 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.,
RA Wang L., Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human
RT liver phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [23]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-339, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25114211; DOI=10.1073/pnas.1413825111;
RA Impens F., Radoshevich L., Cossart P., Ribet D.;
RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by
RT external stimuli.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014).
RN [24]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-1063, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25755297; DOI=10.1074/mcp.O114.044792;
RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V.,
RA Vertegaal A.C.;
RT "System-wide analysis of SUMOylation dynamics in response to
RT replication stress reveals novel small ubiquitin-like modified target
RT proteins and acceptor lysines relevant for genome stability.";
RL Mol. Cell. Proteomics 14:1419-1434(2015).
RN [25]
RP FUNCTION, AND INTERACTION WITH POLR2A AND SMN1.
RX PubMed=26700805; DOI=10.1038/nature16469;
RA Yanling Zhao D., Gish G., Braunschweig U., Li Y., Ni Z.,
RA Schmitges F.W., Zhong G., Liu K., Li W., Moffat J., Vedadi M., Min J.,
RA Pawson T.J., Blencowe B.J., Greenblatt J.F.;
RT "SMN and symmetric arginine dimethylation of RNA polymerase II C-
RT terminal domain control termination.";
RL Nature 529:48-53(2016).
RN [26]
RP VARIANTS ALS4 SER-389 AND HIS-2136, AND TISSUE SPECIFICITY.
RX PubMed=15106121; DOI=10.1086/421054;
RA Chen Y.-Z., Bennett C.L., Huynh H.M., Blair I.P., Puls I., Irobi J.,
RA Dierick I., Abel A., Kennerson M.L., Rabin B.A., Nicholson G.A.,
RA Auer-Grumbach M., Wagner K., De Jonghe P., Griffin J.W.,
RA Fischbeck K.H., Timmerman V., Cornblath D.R., Chance P.F.;
RT "DNA/RNA helicase gene mutations in a form of juvenile amyotrophic
RT lateral sclerosis (ALS4).";
RL Am. J. Hum. Genet. 74:1128-1135(2004).
RN [27]
RP VARIANT SCAR1 ARG-2368, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16644229; DOI=10.1016/j.nbd.2006.02.007;
RA Chen Y.-Z., Hashemi S.H., Anderson S.K., Huang Y., Moreira M.-C.,
RA Lynch D.R., Glass I.A., Chance P.F., Bennett C.L.;
RT "Senataxin, the yeast Sen1p orthologue: characterization of a unique
RT protein in which recessive mutations cause ataxia and dominant
RT mutations cause motor neuron disease.";
RL Neurobiol. Dis. 23:97-108(2006).
RN [28]
RP VARIANTS SCAR1 ILE-274 AND CYS-1294.
RX PubMed=16717225; DOI=10.1212/01.wnl.0000216135.59699.9b;
RA Asaka T., Yokoji H., Ito J., Yamaguchi K., Matsushima A.;
RT "Autosomal recessive ataxia with peripheral neuropathy and elevated
RT AFP: novel mutations in SETX.";
RL Neurology 66:1580-1581(2006).
RN [29]
RP VARIANTS SCAR1 ASP-603 AND LYS-653.
RX PubMed=17096168; DOI=10.1007/s10048-006-0067-8;
RA Bassuk A.G., Chen Y.Z., Batish S.D., Nagan N., Opal P., Chance P.F.,
RA Bennett C.L.;
RT "In cis autosomal dominant mutation of Senataxin associated with
RT tremor/ataxia syndrome.";
RL Neurogenetics 8:45-49(2007).
RN [30]
RP VARIANTS ALS4 GLY-1554; GLU-2029 AND THR-2547.
RX PubMed=21190393; DOI=10.3109/17482968.2010.545952;
RA Hirano M., Quinzii C.M., Mitsumoto H., Hays A.P., Roberts J.K.,
RA Richard P., Rowland L.P.;
RT "Senataxin mutations and amyotrophic lateral sclerosis.";
RL Amyotroph. Lateral Scler. 12:223-227(2011).
RN [31]
RP VARIANTS SCAR1 VAL-274 AND ARG-1976.
RX PubMed=23566282; DOI=10.3109/00207454.2013.787616;
RA Datta N., Hohler A.;
RT "A new SETX mutation producing AOA2 in two siblings.";
RL Int. J. Neurosci. 123:670-673(2013).
RN [32]
RP INVOLVEMENT IN SCAR1.
RX PubMed=23786967; DOI=10.1016/j.jns.2013.05.018;
RA Ichikawa Y., Ishiura H., Mitsui J., Takahashi Y., Kobayashi S.,
RA Takuma H., Kanazawa I., Doi K., Yoshimura J., Morishita S., Goto J.,
RA Tsuji S.;
RT "Exome analysis reveals a Japanese family with spinocerebellar ataxia,
RT autosomal recessive 1.";
RL J. Neurol. Sci. 331:158-160(2013).
RN [33]
RP VARIANTS SCAR1 LYS-331; LEU-496 AND THR-2229, AND VARIANT ARG-992.
RX PubMed=23941260; DOI=10.1186/1750-1172-8-123;
RA Nanetti L., Cavalieri S., Pensato V., Erbetta A., Pareyson D.,
RA Panzeri M., Zorzi G., Antozzi C., Moroni I., Gellera C., Brusco A.,
RA Mariotti C.;
RT "SETX mutations are a frequent genetic cause of juvenile and adult
RT onset cerebellar ataxia with neuropathy and elevated serum alpha-
RT fetoprotein.";
RL Orphanet J. Rare Dis. 8:123-123(2013).
RN [34]
RP VARIANT SER-389, CHARACTERIZATION OF VARIANT ALS4 SER-389, SUBUNIT,
RP ABSENCE OF INTERACTION WITH C14ORF178, UBIQUITINATION, AND
RP SUMOYLATION.
RX PubMed=24244371; DOI=10.1371/journal.pone.0078837;
RA Bennett C.L., Chen Y., Vignali M., Lo R.S., Mason A.G., Unal A.,
RA Huq Saifee N.P., Fields S., La Spada A.R.;
RT "Protein interaction analysis of senataxin and the ALS4 L389S mutant
RT yields insights into senataxin post-translational modification and
RT uncovers mutant-specific binding with a brain cytoplasmic RNA-encoded
RT peptide.";
RL PLoS ONE 8:E78837-E78837(2013).
CC -!- FUNCTION: Probable RNA/DNA helicase involved in diverse aspects of
CC RNA metabolism and genomic integrity. Plays a role in
CC transcription regulation by its ability to modulate RNA Polymerase
CC II (Pol II) binding to chromatin and through its interaction with
CC proteins involved in transcription (PubMed:19515850,
CC PubMed:21700224). Contributes to the mRNA splicing efficiency and
CC splice site selection (PubMed:19515850). Required for the
CC resolution of R-loop RNA-DNA hybrid formation at G-rich pause
CC sites located downstream of the poly(A) site, allowing XRN2
CC recruitment and XRN2-mediated degradation of the downstream
CC cleaved RNA and hence efficient RNA polymerase II (RNAp II)
CC transcription termination (PubMed:19515850, PubMed:21700224,
CC PubMed:26700805). Required for the 3' transcriptional termination
CC of PER1 and CRY2, thus playing an important role in the circadian
CC rhythm regulation (By similarity). Involved in DNA double-strand
CC breaks damage response generated by oxidative stress
CC (PubMed:17562789). In association with RRP45, targets the RNA
CC exosome complex to sites of transcription-induced DNA damage
CC (PubMed:24105744). Plays a role in the development and maturation
CC of germ cells: essential for male meiosis, acting at the interface
CC of transcription and meiotic recombination, and in the process of
CC gene silencing during meiotic sex chromosome inactivation (MSCI)
CC (By similarity). May be involved in telomeric stability through
CC the regulation of telomere repeat-containing RNA (TERRA)
CC transcription (PubMed:21112256). Plays a role in neurite outgrowth
CC in hippocampal cells through FGF8-activated signaling pathways.
CC Inhibits retinoic acid-induced apoptosis (PubMed:21576111).
CC {ECO:0000250|UniProtKB:A2AKX3, ECO:0000269|PubMed:17562789,
CC ECO:0000269|PubMed:19515850, ECO:0000269|PubMed:21112256,
CC ECO:0000269|PubMed:21576111, ECO:0000269|PubMed:21700224,
CC ECO:0000269|PubMed:24105744, ECO:0000269|PubMed:26700805}.
CC -!- SUBUNIT: Homodimer (PubMed:24244371). Interacts with PER2; the
CC interaction inhibits termination of circadian target genes (By
CC similarity). Interacts with CHD4, POLR2A, PRKDC and TRIM28
CC (PubMed:23149945). Does not interact with C14orf178
CC (PubMed:24244371). Interacts with UBE2I (PubMed:24105744).
CC Interacts (via N-terminus domain) with EXOSC9 (via C-terminus
CC region); the interaction enhances SETX sumoylation
CC (PubMed:24105744). Interacts with NCL (via N-terminus domain)
CC (PubMed:19515850). Interacts with PABPN1, PABPC1 and SF3B1
CC (PubMed:19515850). Interacts with SMN1/SMN2 and POLR2A; SMN1/SMN2
CC recruits SETX to POLR2A (PubMed:19515850, PubMed:26700805).
CC {ECO:0000250|UniProtKB:A2AKX3, ECO:0000269|PubMed:19515850,
CC ECO:0000269|PubMed:23149945, ECO:0000269|PubMed:24105744,
CC ECO:0000269|PubMed:24244371, ECO:0000269|PubMed:26700805}.
CC -!- INTERACTION:
CC Self; NbExp=4; IntAct=EBI-1220123, EBI-1220123;
CC P63279:UBE2I; NbExp=3; IntAct=EBI-1220123, EBI-80168;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17562789,
CC ECO:0000269|PubMed:21576111, ECO:0000269|PubMed:24105744}.
CC Nucleus, nucleoplasm {ECO:0000269|PubMed:17562789}. Nucleus,
CC nucleolus {ECO:0000269|PubMed:17562789}. Cytoplasm
CC {ECO:0000269|PubMed:17562789, ECO:0000269|PubMed:21576111}.
CC Chromosome {ECO:0000269|PubMed:23149945}. Chromosome, telomere
CC {ECO:0000269|PubMed:21112256}. Cell projection, axon
CC {ECO:0000269|PubMed:21576111}. Cell projection, growth cone
CC {ECO:0000269|PubMed:21576111}. Note=May be detected in the
CC nucleolus only in cycling cells. At pachytene stage, colocalizes
CC predominantly to the heterochromatic XY-body of sex chromosomes
CC with DNA damage response proteins in a BRCA1-dependent manner (By
CC similarity). Localizes with telomeric DNA in a transcription-
CC dependent manner (PubMed:21112256). Under replication stress,
CC colocalizes with a variety of DNA damage signaling and repair
CC response proteins at distinct nuclear foci in mitotic S/G2- and
CC G1-phase cells in a transcription- and RNA/DNA hybrid-dependent
CC manner (PubMed:23149945). Localizes at limited number of nuclear
CC foci (PubMed:24105744). Colocalizes with EXOSC9 in nuclear foci
CC upon induction of transcription-related DNA damage at the S phase
CC (PubMed:24105744). Most abundant in the nucleus. Detected in
CC granules. Colocalized in cycling cells with FBL in the nucleolus.
CC {ECO:0000250|UniProtKB:A2AKX3, ECO:0000269|PubMed:17562789,
CC ECO:0000269|PubMed:21112256, ECO:0000269|PubMed:21576111,
CC ECO:0000269|PubMed:23149945, ECO:0000269|PubMed:24105744}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q7Z333-1; Sequence=Displayed;
CC Name=3;
CC IsoId=Q7Z333-3; Sequence=VSP_017124;
CC Note=No experimental confirmation available.;
CC Name=4;
CC IsoId=Q7Z333-4; Sequence=VSP_028826;
CC Note=No experimental confirmation available.;
CC -!- TISSUE SPECIFICITY: Highly expressed in skeletal muscle. Expressed
CC in heart, fibroblast, placenta and liver. Weakly expressed in
CC brain and lung. Expressed in the cortex of the kidney (highly
CC expressed in tubular epithelial cells but low expression in the
CC glomerulus). {ECO:0000269|PubMed:14770181,
CC ECO:0000269|PubMed:15106121, ECO:0000269|PubMed:16644229,
CC ECO:0000269|PubMed:17562789}.
CC -!- DOMAIN: The N-terminus domain is necessary for S/G2 nuclear foci
CC localization (PubMed:23149945). {ECO:0000269|PubMed:23149945}.
CC -!- PTM: Ubiquitinated. {ECO:0000269|PubMed:24244371}.
CC -!- PTM: Sumoylated preferentially with SUMO2 or SUMO3
CC (PubMed:24105744, PubMed:24244371). {ECO:0000269|PubMed:24105744,
CC ECO:0000269|PubMed:24244371}.
CC -!- DISEASE: Spinocerebellar ataxia, autosomal recessive, 1 (SCAR1)
CC [MIM:606002]: Spinocerebellar ataxia is a clinically and
CC genetically heterogeneous group of cerebellar disorders. Patients
CC show progressive incoordination of gait and often poor
CC coordination of hands, speech and eye movements, due to
CC degeneration of the cerebellum with variable involvement of the
CC brainstem and spinal cord. SCAR1 is an autosomal recessive form
CC associated with peripheral neuropathy and elevated serum alpha-
CC fetoprotein, immunoglobulins and, less commonly, creatine kinase
CC levels. Some SCAR1 patients manifest oculomotor apraxia.
CC {ECO:0000269|PubMed:14770181, ECO:0000269|PubMed:16644229,
CC ECO:0000269|PubMed:16717225, ECO:0000269|PubMed:17096168,
CC ECO:0000269|PubMed:23566282, ECO:0000269|PubMed:23786967,
CC ECO:0000269|PubMed:23941260, ECO:0000269|PubMed:24105744}.
CC Note=The disease is caused by mutations affecting the gene
CC represented in this entry.
CC -!- DISEASE: Amyotrophic lateral sclerosis 4 (ALS4) [MIM:602433]: A
CC form of amyotrophic lateral sclerosis with childhood- or
CC adolescent-onset, and characterized by slow disease progression
CC and the sparing of bulbar and respiratory muscles. Amyotrophic
CC lateral sclerosis is a neurodegenerative disorder affecting upper
CC motor neurons in the brain and lower motor neurons in the brain
CC stem and spinal cord, resulting in fatal paralysis. Sensory
CC abnormalities are absent. The pathologic hallmarks of the disease
CC include pallor of the corticospinal tract due to loss of motor
CC neurons, presence of ubiquitin-positive inclusions within
CC surviving motor neurons, and deposition of pathologic aggregates.
CC The etiology of amyotrophic lateral sclerosis is likely to be
CC multifactorial, involving both genetic and environmental factors.
CC The disease is inherited in 5-10% of the cases.
CC {ECO:0000269|PubMed:14770181, ECO:0000269|PubMed:15106121,
CC ECO:0000269|PubMed:21190393, ECO:0000269|PubMed:24105744,
CC ECO:0000269|PubMed:24244371}. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the DNA2/NAM7 helicase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA91701.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
CC Sequence=BAB14299.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
CC Sequence=CAD97857.1; Type=Frameshift; Positions=1626; Evidence={ECO:0000305};
DR EMBL; AY362728; AAR13367.1; -; mRNA.
DR EMBL; BX537849; CAD97857.1; ALT_FRAME; mRNA.
DR EMBL; BX538166; CAD98045.1; -; mRNA.
DR EMBL; CR749249; CAH18105.1; -; mRNA.
DR EMBL; AL159997; CAI40854.1; -; Genomic_DNA.
DR EMBL; AL353701; CAI40854.1; JOINED; Genomic_DNA.
DR EMBL; AL159997; CAI40857.1; -; Genomic_DNA.
DR EMBL; AL353701; CAM14151.1; -; Genomic_DNA.
DR EMBL; AL159997; CAM14151.1; JOINED; Genomic_DNA.
DR EMBL; BC032600; AAH32600.2; -; mRNA.
DR EMBL; BC032622; AAH32622.2; -; mRNA.
DR EMBL; BC078166; AAH78166.1; -; mRNA.
DR EMBL; BC106017; AAI06018.1; -; mRNA.
DR EMBL; BC137350; AAI37351.1; -; mRNA.
DR EMBL; AB014525; BAA31600.2; -; mRNA.
DR EMBL; AK001456; BAA91701.1; ALT_INIT; mRNA.
DR EMBL; AK022902; BAB14299.1; ALT_INIT; mRNA.
DR CCDS; CCDS6947.1; -. [Q7Z333-1]
DR RefSeq; NP_055861.3; NM_015046.5. [Q7Z333-1]
DR RefSeq; XP_005272228.1; XM_005272171.1. [Q7Z333-4]
DR RefSeq; XP_005272229.1; XM_005272172.2. [Q7Z333-4]
DR RefSeq; XP_005272230.1; XM_005272173.2. [Q7Z333-4]
DR RefSeq; XP_011516706.1; XM_011518404.2. [Q7Z333-4]
DR RefSeq; XP_011516707.1; XM_011518405.2. [Q7Z333-4]
DR RefSeq; XP_016869984.1; XM_017014495.1. [Q7Z333-1]
DR RefSeq; XP_016869986.1; XM_017014497.1.
DR UniGene; Hs.460317; -.
DR ProteinModelPortal; Q7Z333; -.
DR SMR; Q7Z333; -.
DR BioGrid; 116699; 41.
DR DIP; DIP-38360N; -.
DR IntAct; Q7Z333; 29.
DR MINT; MINT-4649968; -.
DR STRING; 9606.ENSP00000224140; -.
DR iPTMnet; Q7Z333; -.
DR PhosphoSitePlus; Q7Z333; -.
DR BioMuta; SETX; -.
DR DMDM; 296453021; -.
DR EPD; Q7Z333; -.
DR MaxQB; Q7Z333; -.
DR PaxDb; Q7Z333; -.
DR PeptideAtlas; Q7Z333; -.
DR PRIDE; Q7Z333; -.
DR Ensembl; ENST00000224140; ENSP00000224140; ENSG00000107290. [Q7Z333-1]
DR GeneID; 23064; -.
DR KEGG; hsa:23064; -.
DR UCSC; uc004cbk.4; human. [Q7Z333-1]
DR CTD; 23064; -.
DR DisGeNET; 23064; -.
DR GeneCards; SETX; -.
DR GeneReviews; SETX; -.
DR HGNC; HGNC:445; SETX.
DR HPA; HPA024105; -.
DR HPA; HPA057269; -.
DR MalaCards; SETX; -.
DR MIM; 602433; phenotype.
DR MIM; 606002; phenotype.
DR MIM; 608465; gene.
DR neXtProt; NX_Q7Z333; -.
DR OpenTargets; ENSG00000107290; -.
DR Orphanet; 357043; Amyotrophic lateral sclerosis type 4.
DR Orphanet; 64753; Spinocerebellar ataxia with axonal neuropathy type 2.
DR PharmGKB; PA24751; -.
DR eggNOG; KOG1801; Eukaryota.
DR eggNOG; COG1112; LUCA.
DR GeneTree; ENSGT00810000125415; -.
DR HOVERGEN; HBG108476; -.
DR InParanoid; Q7Z333; -.
DR KO; K10706; -.
DR OMA; PEDMDLC; -.
DR OrthoDB; EOG091G01EA; -.
DR PhylomeDB; Q7Z333; -.
DR TreeFam; TF324634; -.
DR ChiTaRS; SETX; human.
DR GeneWiki; SETX; -.
DR GenomeRNAi; 23064; -.
DR PRO; PR:Q7Z333; -.
DR Proteomes; UP000005640; Chromosome 9.
DR Bgee; ENSG00000107290; -.
DR ExpressionAtlas; Q7Z333; baseline and differential.
DR Genevisible; Q7Z333; HS.
DR GO; GO:0030424; C:axon; IDA:UniProtKB.
DR GO; GO:0000781; C:chromosome, telomeric region; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0030426; C:growth cone; IDA:UniProtKB.
DR GO; GO:0000228; C:nuclear chromosome; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003677; F:DNA binding; IC:UniProtKB.
DR GO; GO:0003678; F:DNA helicase activity; TAS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0001147; F:transcription termination site sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0044344; P:cellular response to fibroblast growth factor stimulus; IDA:UniProtKB.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IDA:UniProtKB.
DR GO; GO:0034599; P:cellular response to oxidative stress; IDA:UniProtKB.
DR GO; GO:0071300; P:cellular response to retinoic acid; IDA:UniProtKB.
DR GO; GO:0007623; P:circadian rhythm; IEA:Ensembl.
DR GO; GO:0006310; P:DNA recombination; IEA:UniProtKB-KW.
DR GO; GO:0006353; P:DNA-templated transcription, termination; IMP:UniProtKB.
DR GO; GO:0006302; P:double-strand break repair; IDA:UniProtKB.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0000165; P:MAPK cascade; IDA:UniProtKB.
DR GO; GO:0006376; P:mRNA splice site selection; IMP:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:2000144; P:positive regulation of DNA-templated transcription, initiation; IMP:UniProtKB.
DR GO; GO:0060566; P:positive regulation of DNA-templated transcription, termination; IMP:UniProtKB.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IDA:UniProtKB.
DR GO; GO:0033120; P:positive regulation of RNA splicing; IMP:UniProtKB.
DR GO; GO:2000806; P:positive regulation of termination of RNA polymerase II transcription, poly(A)-coupled; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IMP:UniProtKB.
DR GO; GO:0043491; P:protein kinase B signaling; IDA:UniProtKB.
DR GO; GO:0006396; P:RNA processing; TAS:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; IEA:UniProtKB-KW.
DR GO; GO:0006369; P:termination of RNA polymerase II transcription; IEA:Ensembl.
DR Gene3D; 3.40.50.300; -; 3.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR026121; Senataxin.
DR PANTHER; PTHR10887:SF377; PTHR10887:SF377; 3.
DR SUPFAM; SSF52540; SSF52540; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Amyotrophic lateral sclerosis; ATP-binding;
KW Biological rhythms; Cell projection; Chromosome; Coiled coil;
KW Complete proteome; Cytoplasm; Differentiation; Disease mutation;
KW DNA damage; DNA recombination; DNA repair; Helicase; Hydrolase;
KW Isopeptide bond; Neurodegeneration; Neurogenesis; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Polymorphism; Reference proteome;
KW Spermatogenesis; Telomere; Ubl conjugation.
FT CHAIN 1 2677 Probable helicase senataxin.
FT /FTId=PRO_0000080724.
FT NP_BIND 1963 1970 ATP. {ECO:0000255}.
FT REGION 2661 2677 Necessary for nuclear localization.
FT COILED 2105 2136 {ECO:0000255}.
FT MOTIF 2070 2087 Bipartite nuclear localization signal.
FT {ECO:0000255}.
FT MOD_RES 615 615 Phosphoserine.
FT {ECO:0000244|PubMed:18669648}.
FT MOD_RES 642 642 Phosphoserine.
FT {ECO:0000244|PubMed:23186163}.
FT MOD_RES 878 878 Phosphoserine.
FT {ECO:0000250|UniProtKB:A2AKX3}.
FT MOD_RES 911 911 Phosphoserine.
FT {ECO:0000244|PubMed:23186163}.
FT MOD_RES 947 947 Phosphoserine.
FT {ECO:0000244|PubMed:23186163}.
FT MOD_RES 956 956 Phosphoserine.
FT {ECO:0000244|PubMed:23186163}.
FT MOD_RES 1017 1017 Phosphoserine.
FT {ECO:0000244|PubMed:17081983,
FT ECO:0000244|PubMed:18669648,
FT ECO:0000244|PubMed:19690332,
FT ECO:0000244|PubMed:20068231,
FT ECO:0000244|PubMed:21406692,
FT ECO:0000244|PubMed:24275569}.
FT MOD_RES 1019 1019 Phosphoserine.
FT {ECO:0000244|PubMed:17081983,
FT ECO:0000244|PubMed:18669648,
FT ECO:0000244|PubMed:20068231,
FT ECO:0000244|PubMed:21406692,
FT ECO:0000244|PubMed:24275569}.
FT MOD_RES 1330 1330 Phosphoserine.
FT {ECO:0000244|PubMed:23186163}.
FT MOD_RES 1366 1366 Phosphoserine.
FT {ECO:0000244|PubMed:23186163}.
FT MOD_RES 1489 1489 Phosphoserine.
FT {ECO:0000250|UniProtKB:A2AKX3}.
FT MOD_RES 1621 1621 Phosphoserine.
FT {ECO:0000244|PubMed:16964243}.
FT MOD_RES 1623 1623 Phosphoserine.
FT {ECO:0000244|PubMed:23186163}.
FT MOD_RES 1663 1663 Phosphoserine.
FT {ECO:0000244|PubMed:23186163}.
FT MOD_RES 2474 2474 Phosphothreonine.
FT {ECO:0000244|PubMed:23186163}.
FT CROSSLNK 339 339 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO1).
FT {ECO:0000244|PubMed:25114211}.
FT CROSSLNK 1063 1063 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO2).
FT {ECO:0000244|PubMed:25755297}.
FT VAR_SEQ 2367 2399 Missing (in isoform 3).
FT {ECO:0000303|PubMed:17974005}.
FT /FTId=VSP_017124.
FT VAR_SEQ 2429 2429 M -> MQLLPRSFCVHVNHSPFFSPEPKYLHWALK (in
FT isoform 4). {ECO:0000305}.
FT /FTId=VSP_028826.
FT VARIANT 3 3 T -> I (in ALS4; heterozygous; does not
FT affect the interaction with EXOSC9 and
FT UBE2I; does not decrease sumoylation;
FT dbSNP:rs28941475).
FT {ECO:0000269|PubMed:24105744}.
FT /FTId=VAR_018776.
FT VARIANT 274 274 M -> I (in SCAR1).
FT {ECO:0000269|PubMed:16717225}.
FT /FTId=VAR_036646.
FT VARIANT 274 274 M -> V (in SCAR1; dbSNP:rs753713810).
FT {ECO:0000269|PubMed:23566282}.
FT /FTId=VAR_072587.
FT VARIANT 305 305 W -> C (in SCAR1; abolishes interaction
FT with EXOSC9; does not abolish interaction
FT with UBE2I; decreases sumoylation).
FT {ECO:0000269|PubMed:14770181,
FT ECO:0000269|PubMed:24105744}.
FT /FTId=VAR_018777.
FT VARIANT 331 331 I -> K (in SCAR1).
FT {ECO:0000269|PubMed:23941260}.
FT /FTId=VAR_071682.
FT VARIANT 332 332 R -> W (in SCAR1; dbSNP:rs29001665).
FT {ECO:0000269|PubMed:14770181}.
FT /FTId=VAR_018778.
FT VARIANT 389 389 L -> S (in ALS4; does not affect the
FT interaction with EXOSC9 and UBE2I; does
FT not decrease sumoylation and
FT ubiquitination; does not inhibit
FT homodimerization; unlike the wild-type
FT protein the mutant induces interaction
FT with C14orf178; dbSNP:rs29001584).
FT {ECO:0000269|PubMed:15106121,
FT ECO:0000269|PubMed:24105744,
FT ECO:0000269|PubMed:24244371}.
FT /FTId=VAR_018779.
FT VARIANT 413 413 P -> L (in SCAR1; abolishes interaction
FT with EXOSC9; does not abolish interaction
FT with UBE2I; decreases sumoylation).
FT {ECO:0000269|PubMed:14770181,
FT ECO:0000269|PubMed:24105744}.
FT /FTId=VAR_018780.
FT VARIANT 496 496 P -> L (in SCAR1).
FT {ECO:0000269|PubMed:23941260}.
FT /FTId=VAR_071683.
FT VARIANT 603 603 N -> D (in SCAR1; atypical; associated
FT with K-653; dbSNP:rs116205032).
FT {ECO:0000269|PubMed:17096168}.
FT /FTId=VAR_036647.
FT VARIANT 653 653 Q -> K (in SCAR1; atypical; associated
FT with D-603; dbSNP:rs116333061).
FT {ECO:0000269|PubMed:17096168}.
FT /FTId=VAR_036648.
FT VARIANT 660 660 A -> G (in dbSNP:rs882709).
FT /FTId=VAR_018781.
FT VARIANT 992 992 K -> R (in dbSNP:rs61742937).
FT {ECO:0000269|PubMed:23941260}.
FT /FTId=VAR_071684.
FT VARIANT 1061 1061 P -> L (in dbSNP:rs12352982).
FT /FTId=VAR_018782.
FT VARIANT 1152 1152 F -> C (in dbSNP:rs3739922).
FT {ECO:0000269|PubMed:14770181}.
FT /FTId=VAR_018783.
FT VARIANT 1192 1192 D -> E (in dbSNP:rs1185193).
FT {ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17974005}.
FT /FTId=VAR_018784.
FT VARIANT 1221 1221 K -> N (in dbSNP:rs12344006).
FT /FTId=VAR_056208.
FT VARIANT 1252 1252 G -> R (in dbSNP:rs1183768).
FT {ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17974005}.
FT /FTId=VAR_018785.
FT VARIANT 1294 1294 R -> C (in SCAR1; dbSNP:rs267607044).
FT {ECO:0000269|PubMed:16717225}.
FT /FTId=VAR_036649.
FT VARIANT 1331 1331 P -> L (in dbSNP:rs11243731).
FT /FTId=VAR_018786.
FT VARIANT 1386 1386 I -> V (in dbSNP:rs543573).
FT {ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17974005}.
FT /FTId=VAR_018787.
FT VARIANT 1554 1554 C -> G (in ALS4; dbSNP:rs112089123).
FT {ECO:0000269|PubMed:21190393}.
FT /FTId=VAR_071685.
FT VARIANT 1756 1756 F -> S (in SCAR1; heterozygous in a
FT British family; dbSNP:rs762175796).
FT {ECO:0000269|PubMed:14770181}.
FT /FTId=VAR_018788.
FT VARIANT 1855 1855 T -> A (in dbSNP:rs2296871).
FT {ECO:0000269|PubMed:15489334}.
FT /FTId=VAR_018789.
FT VARIANT 1855 1855 T -> P (in dbSNP:rs2296871).
FT /FTId=VAR_059458.
FT VARIANT 1976 1976 L -> R (in SCAR1; dbSNP:rs121434379).
FT {ECO:0000269|PubMed:23566282}.
FT /FTId=VAR_072588.
FT VARIANT 2029 2029 K -> E (in ALS4; dbSNP:rs746525639).
FT {ECO:0000269|PubMed:21190393}.
FT /FTId=VAR_071686.
FT VARIANT 2136 2136 R -> H (in ALS4; dbSNP:rs121434378).
FT {ECO:0000269|PubMed:15106121}.
FT /FTId=VAR_018790.
FT VARIANT 2213 2213 P -> L (in SCAR1; dbSNP:rs28940290).
FT {ECO:0000269|PubMed:14770181}.
FT /FTId=VAR_018791.
FT VARIANT 2229 2229 M -> T (in SCAR1).
FT {ECO:0000269|PubMed:23941260}.
FT /FTId=VAR_071687.
FT VARIANT 2368 2368 P -> R (in SCAR1).
FT {ECO:0000269|PubMed:16644229}.
FT /FTId=VAR_036650.
FT VARIANT 2547 2547 I -> T (in ALS4; dbSNP:rs151117904).
FT {ECO:0000269|PubMed:21190393}.
FT /FTId=VAR_071688.
FT VARIANT 2587 2587 I -> V (in dbSNP:rs1056899).
FT {ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17974005}.
FT /FTId=VAR_018792.
FT VARIANT 2612 2612 S -> G (in dbSNP:rs3739927).
FT {ECO:0000269|PubMed:15489334}.
FT /FTId=VAR_018793.
FT MUTAGEN 65 65 E->K: Abolishes interaction with EXOSC9
FT and UBE2I and decreases sumoylation.
FT {ECO:0000269|PubMed:24105744}.
FT CONFLICT 657 657 L -> S (in Ref. 2; CAD98045).
FT {ECO:0000305}.
FT CONFLICT 866 866 E -> G (in Ref. 2; CAD97857).
FT {ECO:0000305}.
FT CONFLICT 894 894 K -> E (in Ref. 2; CAH18105).
FT {ECO:0000305}.
FT CONFLICT 895 895 E -> G (in Ref. 2; CAD98045 and 5;
FT BAA31600). {ECO:0000305}.
FT CONFLICT 977 977 P -> T (in Ref. 2; CAD97857).
FT {ECO:0000305}.
FT CONFLICT 1073 1073 F -> C (in Ref. 2; CAD97857).
FT {ECO:0000305}.
FT CONFLICT 1276 1276 Q -> E (in Ref. 5; BAA31600).
FT {ECO:0000305}.
FT CONFLICT 1593 1593 R -> G (in Ref. 2; CAH18105).
FT {ECO:0000305}.
FT CONFLICT 1626 1626 N -> K (in Ref. 2; CAD97857).
FT {ECO:0000305}.
FT CONFLICT 1634 1634 I -> V (in Ref. 2; CAH18105).
FT {ECO:0000305}.
FT CONFLICT 1648 1650 PVG -> TRP (in Ref. 4; AAH32622).
FT {ECO:0000305}.
FT CONFLICT 1725 1725 L -> P (in Ref. 2; CAD97857).
FT {ECO:0000305}.
FT CONFLICT 1826 1826 E -> K (in Ref. 2; CAD98045 and 4;
FT AAH32600/AAH32622). {ECO:0000305}.
FT CONFLICT 1867 1867 F -> L (in Ref. 1; AAR13367 and 4;
FT AAH32622). {ECO:0000305}.
FT CONFLICT 2078 2078 Q -> L (in Ref. 2; CAD97857).
FT {ECO:0000305}.
FT CONFLICT 2324 2324 M -> E (in Ref. 6; BAB14299).
FT {ECO:0000305}.
FT CONFLICT 2423 2423 G -> E (in Ref. 2; CAH18105).
FT {ECO:0000305}.
FT CONFLICT 2458 2458 D -> G (in Ref. 2; CAH18105).
FT {ECO:0000305}.
FT CONFLICT 2539 2539 P -> S (in Ref. 2; CAD97857).
FT {ECO:0000305}.
FT CONFLICT 2565 2565 H -> R (in Ref. 2; CAD97857).
FT {ECO:0000305}.
FT CONFLICT 2577 2577 F -> L (in Ref. 6; BAB14299).
FT {ECO:0000305}.
SQ SEQUENCE 2677 AA; 302880 MW; 552FFE4A23A83868 CRC64;
MSTCCWCTPG GASTIDFLKR YASNTPSGEF QTADEDLCYC LECVAEYHKA RDELPFLHEV
LWELETLRLI NHFEKSMKAE IGDDDELYIV DNNGEMPLFD ITGQDFENKL RVPLLEILKY
PYLLLHERVN ELCVEALCRM EQANCSFQVF DKHPGIYLFL VHPNEMVRRW AILTARNLGK
VDRDDYYDLQ EVLLCLFKVI ELGLLESPDI YTSSVLEKGK LILLPSHMYD TTNYKSYWLG
ICMLLTILEE QAMDSLLLGS DKQNDFMQSI LHTMEREADD DSVDPFWPAL HCFMVILDRL
GSKVWGQLMD PIVAFQTIIN NASYNREIRH IRNSSVRTKL EPESYLDDMV TCSQIVYNYN
PEKTKKDSGW RTAICPDYCP NMYEEMETLA SVLQSDIGQD MRVHNSTFLW FIPFVQSLMD
LKDLGVAYIA QVVNHLYSEV KEVLNQTDAV CDKVTEFFLL ILVSVIELHR NKKCLHLLWV
SSQQWVEAVV KCAKLPTTAF TRSSEKSSGN CSKGTAMISS LSLHSMPSNS VQLAYVQLIR
SLLKEGYQLG QQSLCKRFWD KLNLFLRGNL SLGWQLTSQE THELQSCLKQ IIRNIKFKAP
PCNTFVDLTS ACKISPASYN KEESEQMGKT SRKDMHCLEA SSPTFSKEPM KVQDSVLIKA
DNTIEGDNNE QNYIKDVKLE DHLLAGSCLK QSSKNIFTER AEDQIKISTR KQKSVKEISS
YTPKDCTSRN GPERGCDRGI IVSTRLLTDS STDALEKVST SNEDFSLKDD ALAKTSKRKT
KVQKDEICAK LSHVIKKQHR KSTLVDNTIN LDENLTVSNI ESFYSRKDTG VQKGDGFIHN
LSLDPSGVLD DKNGEQKSQN NVLPKEKQLK NEELVIFSFH ENNCKIQEFH VDGKELIPFT
EMTNASEKKS SPFKDLMTVP ESRDEEMSNS TSVIYSNLTR EQAPDISPKS DTLTDSQIDR
DLHKLSLLAQ ASVITFPSDS PQNSSQLQRK VKEDKRCFTA NQNNVGDTSR GQVIIISDSD
DDDDERILSL EKLTKQDKIC LEREHPEQHV STVNSKEEKN PVKEEKTETL FQFEESDSQC
FEFESSSEVF SVWQDHPDDN NSVQDGEKKC LAPIANTTNG QGCTDYVSEV VKKGAEGIEE
HTRPRSISVE EFCEIEVKKP KRKRSEKPMA EDPVRPSSSV RNEGQSDTNK RDLVGNDFKS
IDRRTSTPNS RIQRATTVSQ KKSSKLCTCT EPIRKVPVSK TPKKTHSDAK KGQNRSSNYL
SCRTTPAIVP PKKFRQCPEP TSTAEKLGLK KGPRKAYELS QRSLDYVAQL RDHGKTVGVV
DTRKKTKLIS PQNLSVRNNK KLLTSQELQM QRQIRPKSQK NRRRLSDCES TDVKRAGSHT
AQNSDIFVPE SDRSDYNCTG GTEVLANSNR KQLIKCMPSE PETIKAKHGS PATDDACPLN
QCDSVVLNGT VPTNEVIVST SEDPLGGGDP TARHIEMAAL KEGEPDSSSD AEEDNLFLTQ
NDPEDMDLCS QMENDNYKLI ELIHGKDTVE VEEDSVSRPQ LESLSGTKCK YKDCLETTKN
QGEYCPKHSE VKAADEDVFR KPGLPPPASK PLRPTTKIFS SKSTSRIAGL SKSLETSSAL
SPSLKNKSKG IQSILKVPQP VPLIAQKPVG EMKNSCNVLH PQSPNNSNRQ GCKVPFGESK
YFPSSSPVNI LLSSQSVSDT FVKEVLKWKY EMFLNFGQCG PPASLCQSIS RPVPVRFHNY
GDYFNVFFPL MVLNTFETVA QEWLNSPNRE NFYQLQVRKF PADYIKYWEF AVYLEECELA
KQLYPKENDL VFLAPERINE EKKDTERNDI QDLHEYHSGY VHKFRRTSVM RNGKTECYLS
IQTQENFPAN LNELVNCIVI SSLVTTQRKL KAMSLLGSRN QLARAVLNPN PMDFCTKDLL
TTTSERIIAY LRDFNEDQKK AIETAYAMVK HSPSVAKICL IHGPPGTGKS KTIVGLLYRL
LTENQRKGHS DENSNAKIKQ NRVLVCAPSN AAVDELMKKI ILEFKEKCKD KKNPLGNCGD
INLVRLGPEK SINSEVLKFS LDSQVNHRMK KELPSHVQAM HKRKEFLDYQ LDELSRQRAL
CRGGREIQRQ ELDENISKVS KERQELASKI KEVQGRPQKT QSIIILESHI ICCTLSTSGG
LLLESAFRGQ GGVPFSCVIV DEAGQSCEIE TLTPLIHRCN KLILVGDPKQ LPPTVISMKA
QEYGYDQSMM ARFCRLLEEN VEHNMISRLP ILQLTVQYRM HPDICLFPSN YVYNRNLKTN
RQTEAIRCSS DWPFQPYLVF DVGDGSERRD NDSYINVQEI KLVMEIIKLI KDKRKDVSFR
NIGIITHYKA QKTMIQKDLD KEFDRKGPAE VDTVDAFQGR QKDCVIVTCV RANSIQGSIG
FLASLQRLNV TITRAKYSLF ILGHLRTLME NQHWNQLIQD AQKRGAIIKT CDKNYRHDAV
KILKLKPVLQ RSLTHPPTIA PEGSRPQGGL PSSKLDSGFA KTSVAASLYH TPSDSKEITL
TVTSKDPERP PVHDQLQDPR LLKRMGIEVK GGIFLWDPQP SSPQHPGATP PTGEPGFPVV
HQDLSHIQQP AAVVAALSSH KPPVRGEPPA ASPEASTCQS KCDDPEEELC HRREARAFSE
GEQEKCGSET HHTRRNSRWD KRTLEQEDSS SKKRKLL
//
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