SETX_HUMAN
ID SETX_HUMAN Reviewed; 2677 AA.
AC Q7Z333; A2A396; B2RPB2; B5ME16; C9JQ10; O75120; Q3KQX4; Q5JUJ1; Q68DW5;
AC Q6AZD7; Q7Z3J6; Q8WX33; Q9H9D1; Q9NVP9;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 4.
DT 03-AUG-2022, entry version 180.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, VARIANT
RP CYS-1152, VARIANTS SCAN2 CYS-305; TRP-332; LEU-413; SER-1756 AND LEU-2213,
RP 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., Moniz J.-C.,
RA Tranchant C., Aubourg P., Tazir M., Schoels L., Pandolfo M., Schulz J.B.,
RA Pouget J., Calvas P., Shizuka-Ikeda M., Shoji M., Tanaka M., Izatt L.,
RA Shaw C.E., M'Zahem A., Dunne E., Bomont P., Benhassine T., Bouslam N.,
RA Stevanin G., Brice A., Guimaraes J., Mendonca P., Barbot C., Coutinho P.,
RA Sequeiros J., 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 SEQUENCE
RP [LARGE SCALE MRNA] OF 447-2677 (ISOFORM 3), AND VARIANTS GLU-1192;
RP 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., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA 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., 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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS GLU-1192;
RP 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 project:
RT 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. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT 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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1621, 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 [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., Nakamura J.,
RA Gatei M., Criscuolo C., Filla A., Chessa L., Fusser M., Epe B., Gueven N.,
RA Lavin M.F.;
RT "Senataxin, defective in ataxia oculomotor apraxia type 2, is involved in
RT 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 SER-1019,
RP AND IDENTIFICATION BY 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 [11]
RP FUNCTION, AND INTERACTION WITH NCL; PABPN1; PABPC1; POLR2A; SF3B1 AND 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 type
RT 2, in transcriptional regulation.";
RL Hum. Mol. Genet. 18:3384-3396(2009).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1017, AND IDENTIFICATION BY
RP 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., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT 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., 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 [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 pause
RT 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., 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 [19]
RP FUNCTION, INTERACTION WITH EXOSC9 AND UBE2I, SUMOYLATION, SUBCELLULAR
RP LOCATION, CHARACTERIZATION OF VARIANTS SCAN2 CYS-305 AND LEU-413,
RP CHARACTERIZATION OF VARIANTS ALS4 ILE-3 AND SER-389, AND MUTAGENESIS OF
RP 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, disrupted
RT in the neurodegenerative disease AOA2, targets the exosome to sites of
RT 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, AND
RP 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 DNA
RT 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., 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 [23]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-339, AND IDENTIFICATION BY MASS
RP 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 MASS
RP 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 replication
RT stress reveals novel small ubiquitin-like modified target proteins and
RT 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., Schmitges F.W.,
RA Zhong G., Liu K., Li W., Moffat J., Vedadi M., Min J., Pawson T.J.,
RA Blencowe B.J., Greenblatt J.F.;
RT "SMN and symmetric arginine dimethylation of RNA polymerase II C-terminal
RT domain control termination.";
RL Nature 529:48-53(2016).
RN [26]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-894; LYS-1056; LYS-1340; LYS-1341
RP AND LYS-1415, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [27]
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., Fischbeck K.H.,
RA Timmerman V., Cornblath D.R., Chance P.F.;
RT "DNA/RNA helicase gene mutations in a form of juvenile amyotrophic lateral
RT sclerosis (ALS4).";
RL Am. J. Hum. Genet. 74:1128-1135(2004).
RN [28]
RP VARIANT SCAN2 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 mutations
RT cause motor neuron disease.";
RL Neurobiol. Dis. 23:97-108(2006).
RN [29]
RP VARIANTS SCAN2 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 AFP:
RT novel mutations in SETX.";
RL Neurology 66:1580-1581(2006).
RN [30]
RP VARIANTS SCAN2 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 [31]
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., Richard P.,
RA Rowland L.P.;
RT "Senataxin mutations and amyotrophic lateral sclerosis.";
RL Amyotroph. Lateral Scler. 12:223-227(2011).
RN [32]
RP VARIANTS SCAN2 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 [33]
RP INVOLVEMENT IN SCAN2.
RX PubMed=23786967; DOI=10.1016/j.jns.2013.05.018;
RA Ichikawa Y., Ishiura H., Mitsui J., Takahashi Y., Kobayashi S., Takuma H.,
RA Kanazawa I., Doi K., Yoshimura J., Morishita S., Goto J., 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 [34]
RP VARIANTS SCAN2 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., Panzeri M.,
RA Zorzi G., Antozzi C., Moroni I., Gellera C., Brusco A., Mariotti C.;
RT "SETX mutations are a frequent genetic cause of juvenile and adult onset
RT cerebellar ataxia with neuropathy and elevated serum alpha-fetoprotein.";
RL Orphanet J. Rare Dis. 8:123-123(2013).
RN [35]
RP VARIANT SER-389, CHARACTERIZATION OF VARIANT ALS4 SER-389, SUBUNIT, LACK OF
RP INTERACTION WITH C14ORF178, UBIQUITINATION, AND 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 yields
RT insights into senataxin post-translational modification and uncovers
RT mutant-specific binding with a brain cytoplasmic RNA-encoded peptide.";
RL PLoS ONE 8:E78837-E78837(2013).
CC -!- FUNCTION: Probable RNA/DNA helicase involved in diverse aspects of RNA
CC metabolism and genomic integrity. Plays a role in transcription
CC regulation by its ability to modulate RNA Polymerase II (Pol II)
CC binding to chromatin and through its interaction with proteins involved
CC in transcription (PubMed:19515850, PubMed:21700224). Contributes to the
CC mRNA splicing efficiency and splice site selection (PubMed:19515850).
CC Required for the resolution of R-loop RNA-DNA hybrid formation at G-
CC rich pause sites located downstream of the poly(A) site, allowing XRN2
CC recruitment and XRN2-mediated degradation of the downstream cleaved RNA
CC and hence efficient RNA polymerase II (RNAp II) transcription
CC termination (PubMed:19515850, PubMed:21700224, PubMed:26700805).
CC Required for the 3' transcriptional termination of PER1 and CRY2, thus
CC playing an important role in the circadian rhythm regulation (By
CC similarity). Involved in DNA double-strand breaks damage response
CC generated by oxidative stress (PubMed:17562789). In association with
CC RRP45, targets the RNA exosome complex to sites of transcription-
CC induced DNA damage (PubMed:24105744). Plays a role in the development
CC and maturation of germ cells: essential for male meiosis, acting at the
CC interface of transcription and meiotic recombination, and in the
CC process of gene silencing during meiotic sex chromosome inactivation
CC (MSCI) (By similarity). May be involved in telomeric stability through
CC the regulation of telomere repeat-containing RNA (TERRA) transcription
CC (PubMed:21112256). Plays a role in neurite outgrowth in hippocampal
CC cells through FGF8-activated signaling pathways. Inhibits retinoic
CC 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 (PubMed:24244371).
CC Interacts with UBE2I (PubMed:24105744). Interacts (via N-terminus
CC domain) with EXOSC9 (via C-terminus region); the interaction enhances
CC SETX sumoylation (PubMed:24105744). Interacts with NCL (via N-terminus
CC domain) (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 Q7Z333; P24928: POLR2A; NbExp=7; IntAct=EBI-1220123, EBI-295301;
CC Q7Z333; Q8N6K7-2: SAMD3; NbExp=3; IntAct=EBI-1220123, EBI-11528848;
CC Q7Z333; Q7Z333: SETX; NbExp=4; IntAct=EBI-1220123, EBI-1220123;
CC Q7Z333; Q16637: SMN2; NbExp=3; IntAct=EBI-1220123, EBI-395421;
CC Q7Z333; P63279: UBE2I; NbExp=3; IntAct=EBI-1220123, EBI-80168;
CC Q7Z333; O75604-3: USP2; NbExp=3; IntAct=EBI-1220123, EBI-10696113;
CC Q7Z333; Q9GZS3: WDR61; NbExp=3; IntAct=EBI-1220123, EBI-358545;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17562789,
CC ECO:0000269|PubMed:21576111, ECO:0000269|PubMed:24105744}. Nucleus,
CC nucleoplasm {ECO:0000269|PubMed:17562789}. Nucleus, nucleolus
CC {ECO:0000269|PubMed:17562789}. Cytoplasm {ECO:0000269|PubMed:17562789,
CC ECO:0000269|PubMed:21576111}. Chromosome {ECO:0000269|PubMed:23149945}.
CC Chromosome, telomere {ECO:0000269|PubMed:21112256}. Cell projection,
CC axon {ECO:0000269|PubMed:21576111}. Cell projection, growth cone
CC {ECO:0000269|PubMed:21576111}. Note=May be detected in the nucleolus
CC only in cycling cells. At pachytene stage, colocalizes predominantly to
CC the heterochromatic XY-body of sex chromosomes with DNA damage response
CC proteins in a BRCA1-dependent manner (By similarity). Localizes with
CC telomeric DNA in a transcription-dependent manner (PubMed:21112256).
CC Under replication stress, colocalizes with a variety of DNA damage
CC signaling and repair response proteins at distinct nuclear foci in
CC mitotic S/G2- and G1-phase cells in a transcription- and RNA/DNA
CC hybrid-dependent manner (PubMed:23149945). Localizes at limited number
CC of nuclear foci (PubMed:24105744). Colocalizes with EXOSC9 in nuclear
CC foci upon induction of transcription-related DNA damage at the S phase
CC (PubMed:24105744). Most abundant in the nucleus. Detected in granules.
CC 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 Name=4;
CC IsoId=Q7Z333-4; Sequence=VSP_028826;
CC -!- TISSUE SPECIFICITY: Highly expressed in skeletal muscle. Expressed in
CC heart, fibroblast, placenta and liver. Weakly expressed in brain and
CC lung. Expressed in the cortex of the kidney (highly expressed in
CC tubular epithelial cells but low expression in the glomerulus).
CC {ECO:0000269|PubMed:14770181, ECO:0000269|PubMed:15106121,
CC ECO:0000269|PubMed:16644229, 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 (PubMed:24105744,
CC PubMed:24244371). {ECO:0000269|PubMed:24105744,
CC ECO:0000269|PubMed:24244371}.
CC -!- DISEASE: Spinocerebellar ataxia, autosomal recessive, with axonal
CC neuropathy 2 (SCAN2) [MIM:606002]: A form of spinocerebellar ataxia, a
CC clinically and genetically heterogeneous group of cerebellar disorders.
CC Patients show progressive incoordination of gait and often poor
CC coordination of hands, speech and eye movements, due to degeneration of
CC the cerebellum with variable involvement of the brainstem and spinal
CC cord. SCAN2 is an autosomal recessive form associated with peripheral
CC neuropathy and elevated serum alpha-fetoprotein, immunoglobulins and,
CC less commonly, creatine kinase levels. Some SCAN2 patients manifest
CC oculomotor apraxia. {ECO:0000269|PubMed:14770181,
CC ECO:0000269|PubMed:16644229, ECO:0000269|PubMed:16717225,
CC ECO:0000269|PubMed:17096168, ECO:0000269|PubMed:23566282,
CC ECO:0000269|PubMed:23786967, ECO:0000269|PubMed:23941260,
CC ECO:0000269|PubMed:24105744}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Amyotrophic lateral sclerosis 4 (ALS4) [MIM:602433]: A form of
CC amyotrophic lateral sclerosis with childhood- or adolescent-onset, and
CC characterized by slow disease progression and the sparing of bulbar and
CC respiratory muscles. Amyotrophic lateral sclerosis is a
CC neurodegenerative disorder affecting upper motor neurons in the brain
CC and lower motor neurons in the brain stem and spinal cord, resulting in
CC fatal paralysis. Sensory abnormalities are absent. The pathologic
CC hallmarks of the disease include pallor of the corticospinal tract due
CC to loss of motor neurons, presence of ubiquitin-positive inclusions
CC within surviving motor neurons, and deposition of pathologic
CC aggregates. The etiology of amyotrophic lateral sclerosis is likely to
CC be 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 variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the DNA2/NAM7 helicase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA91701.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB14299.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAD97857.1; Type=Frameshift; Evidence={ECO:0000305};
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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; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL353701; -; NOT_ANNOTATED_CDS; 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.
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.
DR RefSeq; XP_016869986.1; XM_017014497.1.
DR AlphaFoldDB; Q7Z333; -.
DR SMR; Q7Z333; -.
DR BioGRID; 116699; 173.
DR DIP; DIP-38360N; -.
DR ELM; Q7Z333; -.
DR IntAct; Q7Z333; 57.
DR MINT; Q7Z333; -.
DR STRING; 9606.ENSP00000224140; -.
DR GlyGen; Q7Z333; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q7Z333; -.
DR PhosphoSitePlus; Q7Z333; -.
DR BioMuta; SETX; -.
DR DMDM; 296453021; -.
DR EPD; Q7Z333; -.
DR jPOST; Q7Z333; -.
DR MassIVE; Q7Z333; -.
DR MaxQB; Q7Z333; -.
DR PaxDb; Q7Z333; -.
DR PeptideAtlas; Q7Z333; -.
DR PRIDE; Q7Z333; -.
DR ProteomicsDB; 69001; -. [Q7Z333-1]
DR ProteomicsDB; 69002; -. [Q7Z333-3]
DR ProteomicsDB; 69003; -. [Q7Z333-4]
DR Antibodypedia; 31672; 367 antibodies from 22 providers.
DR DNASU; 23064; -.
DR Ensembl; ENST00000224140.6; ENSP00000224140.5; ENSG00000107290.14. [Q7Z333-1]
DR GeneID; 23064; -.
DR KEGG; hsa:23064; -.
DR MANE-Select; ENST00000224140.6; ENSP00000224140.5; NM_015046.7; NP_055861.3.
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; ENSG00000107290; Low tissue specificity.
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 VEuPathDB; HostDB:ENSG00000107290; -.
DR eggNOG; KOG1801; Eukaryota.
DR GeneTree; ENSGT00940000160918; -.
DR HOGENOM; CLU_000967_0_0_1; -.
DR InParanoid; Q7Z333; -.
DR OMA; KQEPLGN; -.
DR OrthoDB; 220934at2759; -.
DR PhylomeDB; Q7Z333; -.
DR TreeFam; TF324634; -.
DR PathwayCommons; Q7Z333; -.
DR SignaLink; Q7Z333; -.
DR BioGRID-ORCS; 23064; 21 hits in 1081 CRISPR screens.
DR ChiTaRS; SETX; human.
DR GeneWiki; SETX; -.
DR GenomeRNAi; 23064; -.
DR Pharos; Q7Z333; Tbio.
DR PRO; PR:Q7Z333; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q7Z333; protein.
DR Bgee; ENSG00000107290; Expressed in right testis and 184 other tissues.
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:0045171; C:intercellular bridge; IDA:HPA.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
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:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0003723; F:RNA binding; IBA:GO_Central.
DR GO; GO:0001147; F:transcription termination site sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
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:0007399; P:nervous system development; IEA:UniProtKB-KW.
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 by RNA polymerase II; 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; IBA:GO_Central.
DR CDD; cd18808; SF1_C_Upf1; 1.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR045055; DNA2/NAM7-like.
DR InterPro; IPR041679; DNA2/NAM7-like_C.
DR InterPro; IPR041677; DNA2/NAM7_AAA_11.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR10887; PTHR10887; 1.
DR Pfam; PF13086; AAA_11; 1.
DR Pfam; PF13087; AAA_12; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Amyotrophic lateral sclerosis; ATP-binding;
KW Biological rhythms; Cell projection; Chromosome; Coiled coil; Cytoplasm;
KW Differentiation; Disease variant; DNA damage; DNA recombination;
KW DNA repair; Helicase; Hydrolase; Isopeptide bond; Neurodegeneration;
KW Neurogenesis; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Spermatogenesis; Telomere; Ubl conjugation.
FT CHAIN 1..2677
FT /note="Probable helicase senataxin"
FT /id="PRO_0000080724"
FT REGION 1158..1219
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1237..1258
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1351..1385
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1579..1604
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2474..2496
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2556..2577
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2597..2677
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2661..2677
FT /note="Necessary for nuclear localization"
FT COILED 2105..2136
FT /evidence="ECO:0000255"
FT MOTIF 2070..2087
FT /note="Bipartite nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 1185..1199
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1200..1219
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1237..1251
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1360..1374
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2620..2677
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 1963..1970
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT MOD_RES 615
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 642
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 878
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A2AKX3"
FT MOD_RES 911
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 947
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 956
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1017
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 1019
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:24275569"
FT MOD_RES 1330
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1366
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1489
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A2AKX3"
FT MOD_RES 1621
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243"
FT MOD_RES 1623
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1663
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 2474
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 339
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1)"
FT /evidence="ECO:0007744|PubMed:25114211"
FT CROSSLNK 894
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 1056
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 1063
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25755297"
FT CROSSLNK 1340
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 1341
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 1415
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 2367..2399
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_017124"
FT VAR_SEQ 2429
FT /note="M -> MQLLPRSFCVHVNHSPFFSPEPKYLHWALK (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_028826"
FT VARIANT 3
FT /note="T -> I (in ALS4; heterozygous; does not affect the
FT interaction with EXOSC9 and UBE2I; does not decrease
FT sumoylation; dbSNP:rs28941475)"
FT /evidence="ECO:0000269|PubMed:24105744"
FT /id="VAR_018776"
FT VARIANT 274
FT /note="M -> I (in SCAN2; dbSNP:rs997473183)"
FT /evidence="ECO:0000269|PubMed:16717225"
FT /id="VAR_036646"
FT VARIANT 274
FT /note="M -> V (in SCAN2; dbSNP:rs753713810)"
FT /evidence="ECO:0000269|PubMed:23566282"
FT /id="VAR_072587"
FT VARIANT 305
FT /note="W -> C (in SCAN2; abolishes interaction with EXOSC9;
FT does not abolish interaction with UBE2I; decreases
FT sumoylation; dbSNP:rs1564548971)"
FT /evidence="ECO:0000269|PubMed:14770181,
FT ECO:0000269|PubMed:24105744"
FT /id="VAR_018777"
FT VARIANT 331
FT /note="I -> K (in SCAN2; dbSNP:rs1422277504)"
FT /evidence="ECO:0000269|PubMed:23941260"
FT /id="VAR_071682"
FT VARIANT 332
FT /note="R -> W (in SCAN2; dbSNP:rs29001665)"
FT /evidence="ECO:0000269|PubMed:14770181"
FT /id="VAR_018778"
FT VARIANT 389
FT /note="L -> S (in ALS4; does not affect the interaction
FT with EXOSC9 and UBE2I; does not decrease sumoylation and
FT ubiquitination; does not inhibit homodimerization; unlike
FT the wild-type protein the mutant induces interaction with
FT C14orf178; dbSNP:rs29001584)"
FT /evidence="ECO:0000269|PubMed:15106121,
FT ECO:0000269|PubMed:24105744, ECO:0000269|PubMed:24244371"
FT /id="VAR_018779"
FT VARIANT 413
FT /note="P -> L (in SCAN2; abolishes interaction with EXOSC9;
FT does not abolish interaction with UBE2I; decreases
FT sumoylation; dbSNP:rs1564547645)"
FT /evidence="ECO:0000269|PubMed:14770181,
FT ECO:0000269|PubMed:24105744"
FT /id="VAR_018780"
FT VARIANT 496
FT /note="P -> L (in SCAN2; dbSNP:rs1320071128)"
FT /evidence="ECO:0000269|PubMed:23941260"
FT /id="VAR_071683"
FT VARIANT 603
FT /note="N -> D (in SCAN2; atypical; associated with K-653;
FT dbSNP:rs116205032)"
FT /evidence="ECO:0000269|PubMed:17096168"
FT /id="VAR_036647"
FT VARIANT 653
FT /note="Q -> K (in SCAN2; atypical; associated with D-603;
FT dbSNP:rs116333061)"
FT /evidence="ECO:0000269|PubMed:17096168"
FT /id="VAR_036648"
FT VARIANT 660
FT /note="A -> G (in dbSNP:rs882709)"
FT /id="VAR_018781"
FT VARIANT 992
FT /note="K -> R (in dbSNP:rs61742937)"
FT /evidence="ECO:0000269|PubMed:23941260"
FT /id="VAR_071684"
FT VARIANT 1061
FT /note="P -> L (in dbSNP:rs12352982)"
FT /id="VAR_018782"
FT VARIANT 1152
FT /note="F -> C (in dbSNP:rs3739922)"
FT /evidence="ECO:0000269|PubMed:14770181"
FT /id="VAR_018783"
FT VARIANT 1192
FT /note="D -> E (in dbSNP:rs1185193)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17974005"
FT /id="VAR_018784"
FT VARIANT 1221
FT /note="K -> N (in dbSNP:rs12344006)"
FT /id="VAR_056208"
FT VARIANT 1252
FT /note="G -> R (in dbSNP:rs1183768)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17974005"
FT /id="VAR_018785"
FT VARIANT 1294
FT /note="R -> C (in SCAN2; dbSNP:rs267607044)"
FT /evidence="ECO:0000269|PubMed:16717225"
FT /id="VAR_036649"
FT VARIANT 1331
FT /note="P -> L (in dbSNP:rs11243731)"
FT /id="VAR_018786"
FT VARIANT 1386
FT /note="I -> V (in dbSNP:rs543573)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17974005"
FT /id="VAR_018787"
FT VARIANT 1554
FT /note="C -> G (in ALS4; likely benign variant;
FT dbSNP:rs112089123)"
FT /evidence="ECO:0000269|PubMed:21190393"
FT /id="VAR_071685"
FT VARIANT 1756
FT /note="F -> S (in SCAN2; heterozygous in a British family;
FT dbSNP:rs762175796)"
FT /evidence="ECO:0000269|PubMed:14770181"
FT /id="VAR_018788"
FT VARIANT 1855
FT /note="T -> A (in dbSNP:rs2296871)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_018789"
FT VARIANT 1855
FT /note="T -> P (in dbSNP:rs2296871)"
FT /id="VAR_059458"
FT VARIANT 1976
FT /note="L -> R (in SCAN2; dbSNP:rs121434379)"
FT /evidence="ECO:0000269|PubMed:23566282"
FT /id="VAR_072588"
FT VARIANT 2029
FT /note="K -> E (in ALS4; dbSNP:rs746525639)"
FT /evidence="ECO:0000269|PubMed:21190393"
FT /id="VAR_071686"
FT VARIANT 2136
FT /note="R -> H (in ALS4; dbSNP:rs121434378)"
FT /evidence="ECO:0000269|PubMed:15106121"
FT /id="VAR_018790"
FT VARIANT 2213
FT /note="P -> L (in SCAN2; dbSNP:rs28940290)"
FT /evidence="ECO:0000269|PubMed:14770181"
FT /id="VAR_018791"
FT VARIANT 2229
FT /note="M -> T (in SCAN2; dbSNP:rs1471824334)"
FT /evidence="ECO:0000269|PubMed:23941260"
FT /id="VAR_071687"
FT VARIANT 2368
FT /note="P -> R (in SCAN2; dbSNP:rs1420833435)"
FT /evidence="ECO:0000269|PubMed:16644229"
FT /id="VAR_036650"
FT VARIANT 2547
FT /note="I -> T (in ALS4; dbSNP:rs151117904)"
FT /evidence="ECO:0000269|PubMed:21190393"
FT /id="VAR_071688"
FT VARIANT 2587
FT /note="I -> V (in dbSNP:rs1056899)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:17974005"
FT /id="VAR_018792"
FT VARIANT 2612
FT /note="S -> G (in dbSNP:rs3739927)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_018793"
FT MUTAGEN 65
FT /note="E->K: Abolishes interaction with EXOSC9 and UBE2I
FT and decreases sumoylation."
FT /evidence="ECO:0000269|PubMed:24105744"
FT CONFLICT 657
FT /note="L -> S (in Ref. 2; CAD98045)"
FT /evidence="ECO:0000305"
FT CONFLICT 866
FT /note="E -> G (in Ref. 2; CAD97857)"
FT /evidence="ECO:0000305"
FT CONFLICT 894
FT /note="K -> E (in Ref. 2; CAH18105)"
FT /evidence="ECO:0000305"
FT CONFLICT 895
FT /note="E -> G (in Ref. 2; CAD98045 and 5; BAA31600)"
FT /evidence="ECO:0000305"
FT CONFLICT 977
FT /note="P -> T (in Ref. 2; CAD97857)"
FT /evidence="ECO:0000305"
FT CONFLICT 1073
FT /note="F -> C (in Ref. 2; CAD97857)"
FT /evidence="ECO:0000305"
FT CONFLICT 1276
FT /note="Q -> E (in Ref. 5; BAA31600)"
FT /evidence="ECO:0000305"
FT CONFLICT 1593
FT /note="R -> G (in Ref. 2; CAH18105)"
FT /evidence="ECO:0000305"
FT CONFLICT 1626
FT /note="N -> K (in Ref. 2; CAD97857)"
FT /evidence="ECO:0000305"
FT CONFLICT 1634
FT /note="I -> V (in Ref. 2; CAH18105)"
FT /evidence="ECO:0000305"
FT CONFLICT 1648..1650
FT /note="PVG -> TRP (in Ref. 4; AAH32622)"
FT /evidence="ECO:0000305"
FT CONFLICT 1725
FT /note="L -> P (in Ref. 2; CAD97857)"
FT /evidence="ECO:0000305"
FT CONFLICT 1826
FT /note="E -> K (in Ref. 2; CAD98045 and 4; AAH32600/
FT AAH32622)"
FT /evidence="ECO:0000305"
FT CONFLICT 1867
FT /note="F -> L (in Ref. 1; AAR13367 and 4; AAH32622)"
FT /evidence="ECO:0000305"
FT CONFLICT 2078
FT /note="Q -> L (in Ref. 2; CAD97857)"
FT /evidence="ECO:0000305"
FT CONFLICT 2324
FT /note="M -> E (in Ref. 6; BAB14299)"
FT /evidence="ECO:0000305"
FT CONFLICT 2423
FT /note="G -> E (in Ref. 2; CAH18105)"
FT /evidence="ECO:0000305"
FT CONFLICT 2458
FT /note="D -> G (in Ref. 2; CAH18105)"
FT /evidence="ECO:0000305"
FT CONFLICT 2539
FT /note="P -> S (in Ref. 2; CAD97857)"
FT /evidence="ECO:0000305"
FT CONFLICT 2565
FT /note="H -> R (in Ref. 2; CAD97857)"
FT /evidence="ECO:0000305"
FT CONFLICT 2577
FT /note="F -> L (in Ref. 6; BAB14299)"
FT /evidence="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
