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 27-MAR-2024, entry version 189. 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; Q9GZS3: SKIC8; NbExp=3; IntAct=EBI-1220123, EBI-358545; 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 -!- 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 198. DR DIP; DIP-38360N; -. DR ELM; Q7Z333; -. DR IntAct; Q7Z333; 59. DR MINT; Q7Z333; -. DR STRING; 9606.ENSP00000224140; -. DR GlyCosmos; Q7Z333; 1 site, 1 glycan. DR GlyGen; Q7Z333; 2 sites, 1 O-linked glycan (2 sites). 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; 9606-ENSP00000224140; -. DR PeptideAtlas; Q7Z333; -. DR ProteomicsDB; 69001; -. [Q7Z333-1] DR ProteomicsDB; 69002; -. [Q7Z333-3] DR ProteomicsDB; 69003; -. [Q7Z333-4] DR Pumba; Q7Z333; -. DR Antibodypedia; 31672; 379 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 AGR; HGNC:445; -. 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; HTMEREA; -. DR OrthoDB; 170190at2759; -. DR PhylomeDB; Q7Z333; -. DR TreeFam; TF324634; -. DR PathwayCommons; Q7Z333; -. DR SignaLink; Q7Z333; -. DR BioGRID-ORCS; 23064; 23 hits in 1160 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 186 other cell types or tissues. DR ExpressionAtlas; Q7Z333; baseline and differential. 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:HPA. 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: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:0006974; P:DNA damage response; IDA:UniProtKB. 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 recognition; 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:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; IDA:UniProtKB. DR GO; GO:2000144; P:positive regulation of DNA-templated transcription initiation; 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:0060566; P:positive regulation of termination of DNA-templated transcription; 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: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; cd18042; DEXXQc_SETX; 1. DR CDD; cd18808; SF1_C_Upf1; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 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 InterPro; IPR047187; SF1_C_Upf1. DR PANTHER; PTHR10887; DNA2/NAM7 HELICASE FAMILY; 1. DR PANTHER; PTHR10887:SF525; HELICASE SENATAXIN-RELATED; 1. DR Pfam; PF13086; AAA_11; 1. DR Pfam; PF13087; AAA_12; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR Genevisible; Q7Z333; HS. 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; associated in cis 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; associated in cis 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; 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; FT AAH32600/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 //