ID ASCC3_HUMAN Reviewed; 2202 AA. AC Q8N3C0; E7EW23; O43738; Q4G1A0; Q5VTN2; Q9H1I9; Q9H5A2; Q9NTR0; DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot. DT 11-SEP-2007, sequence version 3. DT 09-APR-2025, entry version 198. DE RecName: Full=Activating signal cointegrator 1 complex subunit 3; DE EC=3.6.4.12 {ECO:0000269|PubMed:22055184, ECO:0000269|PubMed:32579943, ECO:0000269|PubMed:36302773}; DE AltName: Full=ASC-1 complex subunit p200 {ECO:0000303|PubMed:12077347}; DE Short=ASC1p200; DE AltName: Full=Helicase, ATP binding 1; DE AltName: Full=Trip4 complex subunit p200 {ECO:0000303|PubMed:12077347}; GN Name=ASCC3; Synonyms=HELIC1, RQT2 {ECO:0000303|PubMed:32099016}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT PHE-146. RC TISSUE=Melanoma; 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 [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Thymus; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3). RC TISSUE=Skin, and Testis; 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 [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 277-2202, PARTIAL PROTEIN SEQUENCE, FUNCTION, RP VARIANT CYS-1995, IDENTIFICATION OF THE ASC-1 COMPLEX, SUBCELLULAR RP LOCATION, AND TISSUE SPECIFICITY. RC TISSUE=Cervix carcinoma; RX PubMed=12077347; DOI=10.1128/mcb.22.14.5203-5211.2002; RA Jung D.-J., Sung H.-S., Goo Y.-W., Lee H.M., Park O.K., Jung S.-Y., Lim J., RA Kim H.-J., Lee S.-K., Kim T.S., Lee J.W., Lee Y.C.; RT "Novel transcription coactivator complex containing activating signal RT cointegrator 1."; RL Mol. Cell. Biol. 22:5203-5211(2002). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1012-2202, AND VARIANT CYS-1995. RC TISSUE=Melanoma; RA Baurain J.-F.; RT "The immunodominant antigen recognized by autologous CTL on a human RT melanoma is generated by a point mutation in a new member of the RNA RT helicase gene family."; RL Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases. RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Lymphoblast; RX PubMed=14654843; DOI=10.1038/nature02166; RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.; RT "Proteomic characterization of the human centrosome by protein correlation RT profiling."; RL Nature 426:570-574(2003). RN [9] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-572, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [10] 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 [11] RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH ALKBH3, AND MUTAGENESIS OF RP GLY-1354. RX PubMed=22055184; DOI=10.1016/j.molcel.2011.08.039; RA Dango S., Mosammaparast N., Sowa M.E., Xiong L.J., Wu F., Park K., RA Rubin M., Gygi S., Harper J.W., Shi Y.; RT "DNA unwinding by ASCC3 helicase is coupled to ALKBH3-dependent DNA RT alkylation repair and cancer cell proliferation."; RL Mol. Cell 44:373-384(2011). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12 AND SER-2195, 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 [13] 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 [14] RP SUBCELLULAR LOCATION, IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION RP IN A COMPLEX WITH ASCC1 AND ASCC2, AND INTERACTION WITH ASCC2 AND ALKBH3. RX PubMed=29144457; DOI=10.1038/nature24484; RA Brickner J.R., Soll J.M., Lombardi P.M., Vaagboe C.B., Mudge M.C., RA Oyeniran C., Rabe R., Jackson J., Sullender M.E., Blazosky E., Byrum A.K., RA Zhao Y., Corbett M.A., Gecz J., Field M., Vindigni A., Slupphaug G., RA Wolberger C., Mosammaparast N.; RT "A ubiquitin-dependent signalling axis specific for ALKBH-mediated DNA RT dealkylation repair."; RL Nature 551:389-393(2017). RN [15] RP FUNCTION, INTERACTION WITH ZNF598 AND RPS3, AND SUBCELLULAR LOCATION. RX PubMed=28757607; DOI=10.1038/s41467-017-00188-1; RA Matsuo Y., Ikeuchi K., Saeki Y., Iwasaki S., Schmidt C., Udagawa T., RA Sato F., Tsuchiya H., Becker T., Tanaka K., Ingolia N.T., Beckmann R., RA Inada T.; RT "Ubiquitination of stalled ribosome triggers ribosome-associated quality RT control."; RL Nat. Commun. 8:159-159(2017). RN [16] RP INTERACTION WITH ASCC1 AND ASCC2, IDENTIFICATION IN THE ASCC COMPLEX, AND RP SUBCELLULAR LOCATION. RX PubMed=29997253; DOI=10.1074/jbc.ra117.000114; RA Soll J.M., Brickner J.R., Mudge M.C., Mosammaparast N.; RT "RNA ligase-like domain in activating signal cointegrator 1 complex subunit RT 1 (ASCC1) regulates ASCC complex function during alkylation damage."; RL J. Biol. Chem. 293:13524-13533(2018). RN [17] RP INTERACTION WITH ZCCHC4. RX PubMed=31799605; DOI=10.1093/nar/gkz1147; RA Pinto R., Vaagboe C.B., Jakobsson M.E., Kim Y., Baltissen M.P., RA O'Donohue M.F., Guzman U.H., Malecki J.M., Wu J., Kirpekar F., Olsen J.V., RA Gleizes P.E., Vermeulen M., Leidel S.A., Slupphaug G., Falnes P.O.; RT "The human methyltransferase ZCCHC4 catalyses N6-methyladenosine RT modification of 28S ribosomal RNA."; RL Nucleic Acids Res. 48:830-846(2020). RN [18] RP FUNCTION, CATALYTIC ACTIVITY, IDENTIFICATION IN THE RQT COMPLEX, AND RP MUTAGENESIS OF LYS-505. RX PubMed=32579943; DOI=10.1016/j.molcel.2020.06.006; RA Juszkiewicz S., Speldewinde S.H., Wan L., Svejstrup J.Q., Hegde R.S.; RT "The ASC-1 complex disassembles collided ribosomes."; RL Mol. Cell 79:603-614(2020). RN [19] RP FUNCTION, IDENTIFICATION IN THE RQT COMPLEX, AND MUTAGENESIS OF LYS-505. RX PubMed=32099016; DOI=10.1038/s41598-020-60241-w; RA Hashimoto S., Sugiyama T., Yamazaki R., Nobuta R., Inada T.; RT "Identification of a novel trigger complex that facilitates ribosome- RT associated quality control in mammalian cells."; RL Sci. Rep. 10:3422-3422(2020). RN [20] RP FUNCTION, CATALYTIC ACTIVITY, IDENTIFICATION IN THE RQT COMPLEX, AND RP MUTAGENESIS OF LYS-505. RX PubMed=36302773; DOI=10.1038/s41467-022-34097-9; RA Narita M., Denk T., Matsuo Y., Sugiyama T., Kikuguchi C., Ito S., Sato N., RA Suzuki T., Hashimoto S., Machova I., Tesina P., Beckmann R., Inada T.; RT "A distinct mammalian disome collision interface harbors K63-linked RT polyubiquitination of uS10 to trigger hRQT-mediated subunit dissociation."; RL Nat. Commun. 13:6411-6411(2022). RN [21] RP VARIANT MRT81 PRO-1564, AND INVOLVEMENT IN MRT81. RX PubMed=21937992; DOI=10.1038/nature10423; RA Najmabadi H., Hu H., Garshasbi M., Zemojtel T., Abedini S.S., Chen W., RA Hosseini M., Behjati F., Haas S., Jamali P., Zecha A., Mohseni M., RA Puettmann L., Vahid L.N., Jensen C., Moheb L.A., Bienek M., Larti F., RA Mueller I., Weissmann R., Darvish H., Wrogemann K., Hadavi V., RA Lipkowitz B., Esmaeeli-Nieh S., Wieczorek D., Kariminejad R., RA Firouzabadi S.G., Cohen M., Fattahi Z., Rost I., Mojahedi F., Hertzberg C., RA Dehghan A., Rajab A., Banavandi M.J., Hoffer J., Falah M., Musante L., RA Kalscheuer V., Ullmann R., Kuss A.W., Tzschach A., Kahrizi K., Ropers H.H.; RT "Deep sequencing reveals 50 novel genes for recessive cognitive RT disorders."; RL Nature 478:57-63(2011). RN [22] RP VARIANTS MRT81 1211-GLN--LYS-2202 DEL; MET-1427; GLN-1472; HIS-1518; RP ASP-1652; PHE-1662; 1761-ARG--LYS-2202 DEL AND ARG-1898, AND INVOLVEMENT IN RP MRT81. RX PubMed=35047834; DOI=10.1016/j.xhgg.2021.100024; RA Nair D., Li D., Erdogan H., Yoon A., Harr M.H., Bergant G., Peterlin B., RA Skrjanec Pusenjak M., Jayakar P., Pfundt R., Jansen S., McWalter K., RA Sidhu A., Saliganan S., Agolini E., Jacob A., Pasquier J., Arash R., RA Kahrizi K., Najmabadi H., Ropers H.H., Bhoj E.J.; RT "Discovery of a neuromuscular syndrome caused by biallelic variants in RT ASCC3."; RL HGG Adv. 2:100024-100024(2021). RN [23] RP ERRATUM OF PUBMED:35047834. RX PubMed=35860725; DOI=10.1016/j.xhgg.2022.100122; RA Nair D., Li D., Erdogan H., Yoon A., Harr M.H., Bergant G., Peterlin B., RA Pusenjak M.S., Jayakar P., Pfundt R., Jansen S., McWalter K., Sidhu A., RA Saliganan S., Agolini E., Jacob A., Pasquier J., Arash R., Kahrizi K., RA Najmabadi H., Ropers H.H., Bhoj E.J.; RL HGG Adv. 3:100122-100122(2022). CC -!- FUNCTION: ATPase involved both in DNA repair and rescue of stalled CC ribosomes (PubMed:22055184, PubMed:28757607, PubMed:32099016, CC PubMed:32579943, PubMed:36302773). 3'-5' DNA helicase involved in CC repair of alkylated DNA: promotes DNA unwinding to generate single- CC stranded substrate needed for ALKBH3, enabling ALKBH3 to process CC alkylated N3-methylcytosine (3mC) within double-stranded regions CC (PubMed:22055184). Also involved in activation of the ribosome quality CC control (RQC) pathway, a pathway that degrades nascent peptide chains CC during problematic translation (PubMed:28757607, PubMed:32099016, CC PubMed:32579943, PubMed:36302773). Drives the splitting of stalled CC ribosomes that are ubiquitinated in a ZNF598-dependent manner, as part CC of the ribosome quality control trigger (RQT) complex (PubMed:28757607, CC PubMed:32099016, PubMed:32579943, PubMed:36302773). Part of the ASC-1 CC complex that enhances NF-kappa-B, SRF and AP1 transactivation CC (PubMed:12077347). {ECO:0000269|PubMed:12077347, CC ECO:0000269|PubMed:22055184, ECO:0000269|PubMed:28757607, CC ECO:0000269|PubMed:32099016, ECO:0000269|PubMed:32579943, CC ECO:0000269|PubMed:36302773}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H2O = ADP + phosphate + H(+); Xref=Rhea:RHEA:13065, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.12; CC Evidence={ECO:0000269|PubMed:22055184, ECO:0000269|PubMed:32579943, CC ECO:0000269|PubMed:36302773}; CC -!- SUBUNIT: Identified in the ASCC complex that contains ASCC1, ASCC2 and CC ASCC3 (PubMed:12077347, PubMed:29144457, PubMed:29997253). Functions as CC scaffolding subunit that interacts directly with both ASCC1 and ASCC2 CC (PubMed:29144457, PubMed:29997253). Interacts directly with ALKBH3, and CC thereby recruits ALKBH3 to the ASCC complex (PubMed:22055184, CC PubMed:29144457). Part of the ASC-1/TRIP4 complex, that contains TRIP4, CC ASCC1, ASCC2 and ASCC3 (PubMed:12077347). Part of the RQT (ribosome CC quality control trigger) complex, that contains ASCC2, ASCC3 and TRIP4 CC (PubMed:32099016, PubMed:32579943, PubMed:36302773). Associates with CC ribosomes; recruited to collided ribosomes (PubMed:32099016, CC PubMed:32579943, PubMed:36302773). Interacts with ZCCHC4 CC (PubMed:31799605). Interacts with ZNF598 (PubMed:28757607). Interacts CC with RPS3 (PubMed:28757607). {ECO:0000269|PubMed:12077347, CC ECO:0000269|PubMed:22055184, ECO:0000269|PubMed:28757607, CC ECO:0000269|PubMed:29144457, ECO:0000269|PubMed:29997253, CC ECO:0000269|PubMed:31799605, ECO:0000269|PubMed:32099016, CC ECO:0000269|PubMed:32579943, ECO:0000269|PubMed:36302773}. CC -!- INTERACTION: CC Q8N3C0; Q8N9N2: ASCC1; NbExp=3; IntAct=EBI-1210710, EBI-10268317; CC Q8N3C0; Q8N9N2-2: ASCC1; NbExp=4; IntAct=EBI-1210710, EBI-10962548; CC Q8N3C0; Q9H1I8: ASCC2; NbExp=9; IntAct=EBI-1210710, EBI-711197; CC Q8N3C0; P53701: HCCS; NbExp=2; IntAct=EBI-1210710, EBI-10763431; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12077347, CC ECO:0000269|PubMed:29144457}. Nucleus speckle CC {ECO:0000269|PubMed:29144457, ECO:0000269|PubMed:29997253}. Cytoplasm, CC cytosol {ECO:0000269|PubMed:28757607}. Note=Colocalizes with ALKBH3 and CC ASCC2 in nuclear foci when cells have been exposed to alkylating agents CC that cause DNA damage. {ECO:0000269|PubMed:29144457}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q8N3C0-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8N3C0-3; Sequence=VSP_042955, VSP_042956; CC Name=3; CC IsoId=Q8N3C0-4; Sequence=VSP_042957, VSP_042958; CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:12077347}. CC -!- DISEASE: Intellectual developmental disorder, autosomal recessive 81 CC (MRT81) [MIM:620700]: An autosomal recessive disorder characterized by CC variable features including mild to severe developmental delay, CC hypotonia, feeding difficulties, extreme fatigue, and neurobehavioral CC abnormalities. {ECO:0000269|PubMed:21937992, CC ECO:0000269|PubMed:35047834}. Note=The disease may be caused by CC variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the helicase family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAG45474.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=CAA11679.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=CAA11679.1; 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; AL834463; CAD39122.1; -; mRNA. DR EMBL; AK315197; BAG37637.1; -; mRNA. DR EMBL; AL121965; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL133338; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL356122; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL591585; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; Z86062; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471051; EAW48449.1; -; Genomic_DNA. DR EMBL; BC050681; AAH50681.1; -; mRNA. DR EMBL; BC125211; AAI25212.1; -; mRNA. DR EMBL; BC125212; AAI25213.1; -; mRNA. DR EMBL; BC026066; AAH26066.1; -; mRNA. DR EMBL; AY013288; AAG45474.1; ALT_FRAME; mRNA. DR EMBL; AJ223948; CAA11679.1; ALT_SEQ; mRNA. DR CCDS; CCDS5046.1; -. [Q8N3C0-1] DR CCDS; CCDS5047.1; -. [Q8N3C0-3] DR CCDS; CCDS75497.1; -. [Q8N3C0-4] DR RefSeq; NP_001271200.1; NM_001284271.2. [Q8N3C0-4] DR RefSeq; NP_006819.2; NM_006828.4. [Q8N3C0-1] DR RefSeq; NP_071374.1; NM_022091.5. [Q8N3C0-3] DR PDB; 6YXQ; X-ray; 2.70 A; A=1-207. DR PDB; 8ALZ; EM; 3.40 A; B=401-2202. DR PDBsum; 6YXQ; -. DR PDBsum; 8ALZ; -. DR AlphaFoldDB; Q8N3C0; -. DR EMDB; EMD-15521; -. DR SMR; Q8N3C0; -. DR BioGRID; 116170; 233. DR ComplexPortal; CPX-6641; ASCC DNA alkylation repair complex. DR ComplexPortal; CPX-6642; RQT ribosome-associated quality control trigger complex. DR CORUM; Q8N3C0; -. DR IntAct; Q8N3C0; 104. DR MINT; Q8N3C0; -. DR STRING; 9606.ENSP00000358159; -. DR CarbonylDB; Q8N3C0; -. DR GlyGen; Q8N3C0; 4 sites, 3 N-linked glycans (3 sites), 1 O-linked glycan (1 site). DR iPTMnet; Q8N3C0; -. DR MetOSite; Q8N3C0; -. DR PhosphoSitePlus; Q8N3C0; -. DR SwissPalm; Q8N3C0; -. DR BioMuta; ASCC3; -. DR DMDM; 158518649; -. DR jPOST; Q8N3C0; -. DR MassIVE; Q8N3C0; -. DR PaxDb; 9606-ENSP00000358159; -. DR PeptideAtlas; Q8N3C0; -. DR ProteomicsDB; 71786; -. [Q8N3C0-1] DR ProteomicsDB; 71787; -. [Q8N3C0-3] DR ProteomicsDB; 71788; -. [Q8N3C0-4] DR Pumba; Q8N3C0; -. DR Antibodypedia; 32044; 105 antibodies from 19 providers. DR DNASU; 10973; -. DR Ensembl; ENST00000369143.2; ENSP00000358139.2; ENSG00000112249.14. [Q8N3C0-3] DR Ensembl; ENST00000369162.7; ENSP00000358159.2; ENSG00000112249.14. [Q8N3C0-1] DR Ensembl; ENST00000522650.5; ENSP00000430769.1; ENSG00000112249.14. [Q8N3C0-4] DR GeneID; 10973; -. DR KEGG; hsa:10973; -. DR MANE-Select; ENST00000369162.7; ENSP00000358159.2; NM_006828.4; NP_006819.2. DR UCSC; uc003pqk.5; human. [Q8N3C0-1] DR AGR; HGNC:18697; -. DR CTD; 10973; -. DR DisGeNET; 10973; -. DR GeneCards; ASCC3; -. DR HGNC; HGNC:18697; ASCC3. DR HPA; ENSG00000112249; Low tissue specificity. DR MalaCards; ASCC3; -. DR MIM; 614217; gene. DR MIM; 620700; phenotype. DR neXtProt; NX_Q8N3C0; -. DR OpenTargets; ENSG00000112249; -. DR PharmGKB; PA134890913; -. DR VEuPathDB; HostDB:ENSG00000112249; -. DR eggNOG; KOG0952; Eukaryota. DR GeneTree; ENSGT00940000155377; -. DR HOGENOM; CLU_000335_2_1_1; -. DR InParanoid; Q8N3C0; -. DR OMA; MCSATEF; -. DR OrthoDB; 5575at2759; -. DR PhylomeDB; Q8N3C0; -. DR TreeFam; TF105778; -. DR PathwayCommons; Q8N3C0; -. DR Reactome; R-HSA-112126; ALKBH3 mediated reversal of alkylation damage. DR SignaLink; Q8N3C0; -. DR BioGRID-ORCS; 10973; 193 hits in 1172 CRISPR screens. DR CD-CODE; 232F8A39; P-body. DR CD-CODE; 804901D1; Nuclear speckle. DR CD-CODE; DEE660B4; Stress granule. DR ChiTaRS; ASCC3; human. DR GeneWiki; ASCC3; -. DR GenomeRNAi; 10973; -. DR Pharos; Q8N3C0; Tbio. DR PRO; PR:Q8N3C0; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; Q8N3C0; protein. DR Bgee; ENSG00000112249; Expressed in decidua and 194 other cell types or tissues. DR ExpressionAtlas; Q8N3C0; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0022626; C:cytosolic ribosome; IDA:UniProt. DR GO; GO:1990391; C:DNA repair complex; IPI:ComplexPortal. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0180022; C:RQC-trigger complex; IDA:UniProtKB. DR GO; GO:0043138; F:3'-5' DNA helicase activity; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0016887; F:ATP hydrolysis activity; IDA:UniProtKB. DR GO; GO:0036121; F:double-stranded DNA helicase activity; IEA:UniProtKB-EC. DR GO; GO:0061749; F:forked DNA-dependent helicase activity; IEA:UniProtKB-EC. DR GO; GO:0009378; F:four-way junction helicase activity; IEA:UniProtKB-EC. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:1990518; F:single-stranded 3'-5' DNA helicase activity; IEA:UniProtKB-EC. DR GO; GO:0006307; P:DNA alkylation repair; IDA:UniProtKB. DR GO; GO:0072344; P:rescue of stalled ribosome; IDA:UniProtKB. DR GO; GO:0032790; P:ribosome disassembly; IDA:UniProtKB. DR GO; GO:1990116; P:ribosome-associated ubiquitin-dependent protein catabolic process; IMP:UniProtKB. DR CDD; cd18020; DEXHc_ASCC3_1; 1. DR CDD; cd18022; DEXHc_ASCC3_2; 1. DR CDD; cd18795; SF2_C_Ski2; 2. DR FunFam; 3.40.50.300:FF:000198; Activating signal cointegrator 1 complex subunit; 1. DR FunFam; 1.10.3380.10:FF:000002; Activating signal cointegrator 1 complex subunit 3; 1. DR FunFam; 3.40.50.300:FF:000231; Activating signal cointegrator 1 complex subunit 3; 1. DR FunFam; 1.10.150.20:FF:000028; activating signal cointegrator 1 complex subunit 3; 1. DR FunFam; 2.60.40.150:FF:000113; activating signal cointegrator 1 complex subunit 3; 1. DR FunFam; 2.60.40.150:FF:000004; RNA helicase, activating signal cointegrator 1; 1. DR FunFam; 3.40.50.300:FF:000102; RNA helicase, activating signal cointegrator 1; 1. DR FunFam; 1.10.10.10:FF:000012; U5 small nuclear ribonucleoprotein helicase; 1. DR FunFam; 1.10.10.10:FF:000024; U5 small nuclear ribonucleoprotein helicase; 1. DR FunFam; 1.10.3380.10:FF:000001; U5 small nuclear ribonucleoprotein helicase; 1. DR FunFam; 3.40.50.300:FF:000062; U5 small nuclear ribonucleoprotein helicase; 1. DR Gene3D; 1.10.150.20; 5' to 3' exonuclease, C-terminal subdomain; 1. DR Gene3D; 2.60.40.150; C2 domain; 2. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 4. DR Gene3D; 1.10.3380.10; Sec63 N-terminal domain-like domain; 2. DR Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 2. DR InterPro; IPR003593; AAA+_ATPase. DR InterPro; IPR035892; C2_domain_sf. DR InterPro; IPR011545; DEAD/DEAH_box_helicase_dom. DR InterPro; IPR050474; Hel308_SKI2-like. DR InterPro; IPR014001; Helicase_ATP-bd. DR InterPro; IPR001650; Helicase_C-like. DR InterPro; IPR014756; Ig_E-set. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR004179; Sec63-dom. DR InterPro; IPR036388; WH-like_DNA-bd_sf. DR InterPro; IPR036390; WH_DNA-bd_sf. DR PANTHER; PTHR47961:SF13; ACTIVATING SIGNAL COINTEGRATOR 1 COMPLEX SUBUNIT 3; 1. DR PANTHER; PTHR47961; DNA POLYMERASE THETA, PUTATIVE (AFU_ORTHOLOGUE AFUA_1G05260)-RELATED; 1. DR Pfam; PF00270; DEAD; 2. DR Pfam; PF00271; Helicase_C; 2. DR Pfam; PF02889; Sec63; 2. DR Pfam; PF23445; SNRNP200_wHTH; 2. DR PIRSF; PIRSF039073; BRR2; 1. DR SMART; SM00382; AAA; 2. DR SMART; SM00487; DEXDc; 2. DR SMART; SM00490; HELICc; 2. DR SMART; SM00973; Sec63; 2. DR SUPFAM; SSF81296; E set domains; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 4. DR SUPFAM; SSF158702; Sec63 N-terminal domain-like; 2. DR SUPFAM; SSF46785; Winged helix' DNA-binding domain; 2. DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 2. DR PROSITE; PS51194; HELICASE_CTER; 2. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; Coiled coil; KW Cytoplasm; Direct protein sequencing; DNA damage; DNA repair; Helicase; KW Hydrolase; Intellectual disability; Nucleotide-binding; Nucleus; KW Phosphoprotein; Proteomics identification; Reference proteome; Repeat. FT CHAIN 1..2202 FT /note="Activating signal cointegrator 1 complex subunit 3" FT /id="PRO_0000102093" FT DOMAIN 486..669 FT /note="Helicase ATP-binding 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541" FT DOMAIN 728..914 FT /note="Helicase C-terminal 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542" FT DOMAIN 978..1287 FT /note="SEC63 1" FT DOMAIN 1336..1511 FT /note="Helicase ATP-binding 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541" FT DOMAIN 1544..1739 FT /note="Helicase C-terminal 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542" FT DOMAIN 1812..2176 FT /note="SEC63 2" FT REGION 1..400 FT /note="Required for interaction with ASCC2" FT /evidence="ECO:0000269|PubMed:29997253" FT COILED 18..79 FT /evidence="ECO:0000255" FT COILED 328..356 FT /evidence="ECO:0000255" FT MOTIF 611..614 FT /note="DEVH box" FT MOTIF 1453..1456 FT /note="DEIH box" FT BINDING 499..506 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541" FT BINDING 1349..1356 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541" FT MOD_RES 12 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 572 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 2195 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 81..111 FT /note="VGTDNGREAIESGAAFLFMTFHLKDSVGHKE -> EVNCPFQKRRLDGKEED FT EKMSRASDRFRGLR (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_042955" FT VAR_SEQ 112..2202 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_042956" FT VAR_SEQ 719..731 FT /note="MVFVHARNATVRT -> HLFYLLLHLFICF (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_042957" FT VAR_SEQ 732..2202 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_042958" FT VARIANT 146 FT /note="L -> F (in dbSNP:rs9390698)" FT /evidence="ECO:0000269|PubMed:17974005" FT /id="VAR_034859" FT VARIANT 344 FT /note="E -> K (in dbSNP:rs6918004)" FT /id="VAR_049339" FT VARIANT 478 FT /note="N -> S (in dbSNP:rs7750940)" FT /id="VAR_049340" FT VARIANT 1016 FT /note="S -> C (in dbSNP:rs57534235)" FT /id="VAR_061212" FT VARIANT 1050 FT /note="V -> I (in dbSNP:rs9497983)" FT /id="VAR_034860" FT VARIANT 1211..2202 FT /note="Missing (in MRT81; uncertain significance; FT dbSNP:rs372947820)" FT /evidence="ECO:0000269|PubMed:35047834" FT /id="VAR_089330" FT VARIANT 1425 FT /note="V -> A (in dbSNP:rs17246013)" FT /id="VAR_049341" FT VARIANT 1427 FT /note="T -> M (in MRT81; uncertain significance; FT dbSNP:rs1483972453)" FT /evidence="ECO:0000269|PubMed:35047834" FT /id="VAR_089331" FT VARIANT 1472 FT /note="R -> Q (in MRT81; uncertain significance; FT dbSNP:rs1051651433)" FT /evidence="ECO:0000269|PubMed:35047834" FT /id="VAR_089332" FT VARIANT 1497 FT /note="R -> T (in dbSNP:rs17305382)" FT /id="VAR_049342" FT VARIANT 1518 FT /note="R -> H (in MRT81; uncertain significance; FT dbSNP:rs148742449)" FT /evidence="ECO:0000269|PubMed:35047834" FT /id="VAR_089333" FT VARIANT 1564 FT /note="S -> P (in MRT81; uncertain significance; FT dbSNP:rs1414695401)" FT /evidence="ECO:0000269|PubMed:21937992" FT /id="VAR_089334" FT VARIANT 1652 FT /note="G -> D (in MRT81; uncertain significance; FT dbSNP:rs749948570)" FT /evidence="ECO:0000269|PubMed:35047834" FT /id="VAR_089335" FT VARIANT 1662 FT /note="I -> F (in MRT81; uncertain significance)" FT /evidence="ECO:0000269|PubMed:35047834" FT /id="VAR_089336" FT VARIANT 1761..2202 FT /note="Missing (in MRT81; uncertain significance; FT dbSNP:rs1045124261)" FT /evidence="ECO:0000269|PubMed:35047834" FT /id="VAR_089337" FT VARIANT 1800 FT /note="C -> W (in dbSNP:rs35011147)" FT /id="VAR_034861" FT VARIANT 1898 FT /note="H -> R (in MRT81; uncertain significance; FT dbSNP:rs1381176199)" FT /evidence="ECO:0000269|PubMed:35047834" FT /id="VAR_089338" FT VARIANT 1930 FT /note="V -> M (in dbSNP:rs3213542)" FT /id="VAR_034862" FT VARIANT 1995 FT /note="S -> C (in dbSNP:rs240780)" FT /evidence="ECO:0000269|PubMed:12077347, ECO:0000269|Ref.7" FT /id="VAR_034863" FT VARIANT 2176 FT /note="Y -> C (in dbSNP:rs240768)" FT /id="VAR_034864" FT MUTAGEN 505 FT /note="K->R: Defective activation of the ribosome quality FT control (RQC) pathway. Impairs its association with FT ribosomes." FT /evidence="ECO:0000269|PubMed:32099016, FT ECO:0000269|PubMed:32579943, ECO:0000269|PubMed:36302773" FT MUTAGEN 1354 FT /note="G->D: Abolishes 3'-5' DNA helicase activity and FT ability to promote DNA repair." FT /evidence="ECO:0000269|PubMed:22055184" FT CONFLICT 86 FT /note="G -> E (in Ref. 5; AAH26066)" FT /evidence="ECO:0000305" FT CONFLICT 444 FT /note="P -> S (in Ref. 1; CAD39122)" FT /evidence="ECO:0000305" FT CONFLICT 582 FT /note="V -> A (in Ref. 5; AAH26066)" FT /evidence="ECO:0000305" FT CONFLICT 750 FT /note="P -> S (in Ref. 1; CAD39122)" FT /evidence="ECO:0000305" FT CONFLICT 1187 FT /note="S -> F (in Ref. 7; CAA11679)" FT /evidence="ECO:0000305" FT CONFLICT 1343 FT /note="C -> S (in Ref. 7; CAA11679)" FT /evidence="ECO:0000305" FT HELIX 6..14 FT /evidence="ECO:0007829|PDB:6YXQ" FT HELIX 16..19 FT /evidence="ECO:0007829|PDB:6YXQ" FT HELIX 20..22 FT /evidence="ECO:0007829|PDB:6YXQ" FT HELIX 26..35 FT /evidence="ECO:0007829|PDB:6YXQ" FT TURN 36..39 FT /evidence="ECO:0007829|PDB:6YXQ" FT HELIX 47..57 FT /evidence="ECO:0007829|PDB:6YXQ" FT HELIX 60..81 FT /evidence="ECO:0007829|PDB:6YXQ" FT STRAND 83..85 FT /evidence="ECO:0007829|PDB:6YXQ" FT HELIX 87..101 FT /evidence="ECO:0007829|PDB:6YXQ" FT HELIX 109..119 FT /evidence="ECO:0007829|PDB:6YXQ" FT HELIX 124..138 FT /evidence="ECO:0007829|PDB:6YXQ" FT HELIX 143..159 FT /evidence="ECO:0007829|PDB:6YXQ" FT TURN 163..166 FT /evidence="ECO:0007829|PDB:6YXQ" FT STRAND 419..422 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 460..463 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 465..470 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 479..488 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 495..498 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 503..520 FT /evidence="ECO:0007829|PDB:8ALZ" FT TURN 522..526 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 533..536 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 540..553 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 565..567 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 572..577 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 580..583 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 585..593 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 597..599 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 607..609 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 615..618 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 621..638 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 643..649 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 655..660 FT /evidence="ECO:0007829|PDB:8ALZ" FT TURN 665..667 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 668..671 FT /evidence="ECO:0007829|PDB:8ALZ" FT TURN 674..676 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 677..679 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 693..714 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 718..720 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 725..740 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 741..743 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 745..747 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 754..765 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 770..774 FT /evidence="ECO:0007829|PDB:8ALZ" FT TURN 775..778 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 779..781 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 784..786 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 788..800 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 804..807 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 812..815 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 821..824 FT /evidence="ECO:0007829|PDB:8ALZ" FT TURN 833..835 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 843..851 FT /evidence="ECO:0007829|PDB:8ALZ" FT TURN 856..858 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 862..865 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 870..877 FT /evidence="ECO:0007829|PDB:8ALZ" FT TURN 878..880 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 894..904 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 910..919 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 921..928 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 931..933 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 937..942 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 947..962 FT /evidence="ECO:0007829|PDB:8ALZ" FT TURN 963..965 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 966..970 FT /evidence="ECO:0007829|PDB:8ALZ" FT TURN 971..974 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 975..978 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 980..987 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 992..1001 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1010..1016 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1019..1021 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1028..1040 FT /evidence="ECO:0007829|PDB:8ALZ" FT TURN 1047..1050 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1053..1065 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1073..1100 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1103..1118 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1126..1129 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 1131..1133 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1135..1143 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1148..1153 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1156..1163 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1166..1176 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 1182..1187 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 1192..1195 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 1198..1204 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1210..1213 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 1218..1225 FT /evidence="ECO:0007829|PDB:8ALZ" FT TURN 1227..1229 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 1233..1240 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1242..1247 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 1251..1255 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 1265..1276 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 1280..1286 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1310..1313 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1316..1319 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1329..1337 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 1345..1348 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1355..1369 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 1376..1378 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1382..1395 FT /evidence="ECO:0007829|PDB:8ALZ" FT TURN 1396..1399 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 1400..1402 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1411..1419 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 1424..1426 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1428..1434 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1444..1446 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 1449..1453 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1455..1458 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 1459..1462 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1465..1480 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 1485..1489 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1496..1502 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 1506..1512 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 1518..1520 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 1522..1525 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1535..1552 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 1559..1561 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 1564..1566 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1567..1578 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 1581..1583 FT /evidence="ECO:0007829|PDB:8ALZ" FT TURN 1585..1588 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1593..1602 FT /evidence="ECO:0007829|PDB:8ALZ" FT TURN 1609..1615 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1623..1625 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1627..1636 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 1643..1645 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 1651..1653 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 1658..1662 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 1666..1668 FT /evidence="ECO:0007829|PDB:8ALZ" FT TURN 1670..1672 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 1673..1677 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1680..1687 FT /evidence="ECO:0007829|PDB:8ALZ" FT TURN 1693..1695 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 1697..1703 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1707..1718 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1728..1730 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1731..1740 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 1741..1743 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1747..1753 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1754..1756 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1758..1765 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1768..1770 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1777..1797 FT /evidence="ECO:0007829|PDB:8ALZ" FT TURN 1804..1806 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 1807..1809 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1814..1821 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1826..1834 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1842..1850 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1853..1855 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1864..1871 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 1873..1877 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1881..1883 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1887..1899 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1907..1934 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1938..1952 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 1956..1958 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1960..1963 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1969..1971 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1972..1976 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 1981..1985 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 1996..2003 FT /evidence="ECO:0007829|PDB:8ALZ" FT TURN 2004..2006 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 2008..2010 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 2011..2014 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 2016..2018 FT /evidence="ECO:0007829|PDB:8ALZ" FT HELIX 2023..2032 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 2036..2044 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 2056..2058 FT /evidence="ECO:0007829|PDB:8ALZ" FT TURN 2068..2070 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 2080..2088 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 2092..2094 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 2115..2121 FT /evidence="ECO:0007829|PDB:8ALZ" FT TURN 2122..2125 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 2126..2133 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 2137..2146 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 2154..2165 FT /evidence="ECO:0007829|PDB:8ALZ" FT STRAND 2171..2178 FT /evidence="ECO:0007829|PDB:8ALZ" SQ SEQUENCE 2202 AA; 251460 MW; 9F074E6E5853399C CRC64; MALPRLTGAL RSFSNVTKQD NYNEEVADLK IKRSKLHEQV LDLGLTWKKI IKFLNEKLEK SKMQSINEDL KDILHAAKQI VGTDNGREAI ESGAAFLFMT FHLKDSVGHK ETKAIKQMFG PFPSSSATAA CNATNRIISH FSQDDLTALV QMTEKEHGDR VFFGKNLAFS FDMHDLDHFD ELPINGETQK TISLDYKKFL NEHLQEACTP ELKPVEKTNG SFLWCEVEKY LNSTLKEMTE VPRVEDLCCT LYDMLASIKS GDELQDELFE LLGPEGLELI EKLLQNRITI VDRFLNSSND HRFQALQDNC KKILGENAKP NYGCQVTIQS EQEKQLMKQY RREEKRIARR EKKAGEDLEV SEGLMCFDPK ELRIQREQAL LNARSVPILS RQRDADVEKI HYPHVYDSQA EAMKTSAFIA GAKMILPEGI QRENNKLYEE VRIPYSEPMP LSFEEKPVYI QDLDEIGQLA FKGMKRLNRI QSIVFETAYN TNENMLICAP TGAGKTNIAM LTVLHEIRQH FQQGVIKKNE FKIVYVAPMK ALAAEMTDYF SRRLEPLGII VKELTGDMQL SKSEILRTQM LVTTPEKWDV VTRKSVGDVA LSQIVRLLIL DEVHLLHEDR GPVLESIVAR TLRQVESTQS MIRILGLSAT LPNYLDVATF LHVNPYIGLF FFDGRFRPVP LGQTFLGIKC ANKMQQLNNM DEVCYENVLK QVKAGHQVMV FVHARNATVR TAMSLIERAK NCGHIPFFFP TQGHDYVLAE KQVQRSRNKQ VRELFPDGFS IHHAGMLRQD RNLVENLFSN GHIKVLVCTA TLAWGVNLPA HAVIIKGTQI YAAKRGSFVD LGILDVMQIF GRAGRPQFDK FGEGIIITTH DKLSHYLTLL TQRNPIESQF LESLADNLNA EIALGTVTNV EEAVKWISYT YLYVRMRANP LAYGISHKAY QIDPTLRKHR EQLVIEVGRK LDKAQMIRFE ERTGYFSSTD LGRTASHYYI KYNTIETFNE LFDAHKTEGD IFAIVSKAEE FDQIKVREEE IEELDTLLSN FCELSTPGGV ENSYGKINIL LQTYISRGEM DSFSLISDSA YVAQNAARIV RALFEIALRK RWPTMTYRLL NLSKVIDKRL WGWASPLRQF SILPPHILTR LEEKKLTVDK LKDMRKDEIG HILHHVNIGL KVKQCVHQIP SVMMEASIQP ITRTVLRVTL SIYADFTWND QVHGTVGEPW WIWVEDPTND HIYHSEYFLA LKKQVISKEA QLLVFTIPIF EPLPSQYYIR AVSDRWLGAE AVCIINFQHL ILPERHPPHT ELLDLQPLPI TALGCKAYEA LYNFSHFNPV QTQIFHTLYH TDCNVLLGAP TGSGKTVAAE LAIFRVFNKY PTSKAVYIAP LKALVRERMD DWKVRIEEKL GKKVIELTGD VTPDMKSIAK ADLIVTTPEK WDGVSRSWQN RNYVQQVTIL IIDEIHLLGE ERGPVLEVIV SRTNFISSHT EKPVRIVGLS TALANARDLA DWLNIKQMGL FNFRPSVRPV PLEVHIQGFP GQHYCPRMAS MNKPAFQAIR SHSPAKPVLI FVSSRRQTRL TALELIAFLA TEEDPKQWLN MDEREMENII ATVRDSNLKL TLAFGIGMHH AGLHERDRKT VEELFVNCKV QVLIATSTLA WGVNFPAHLV IIKGTEYYDG KTRRYVDFPI TDVLQMMGRA GRPQFDDQGK AVILVHDIKK DFYKKFLYEP FPVESSLLGV LSDHLNAEIA GGTITSKQDA LDYITWTYFF RRLIMNPSYY NLGDVSHDSV NKFLSHLIEK SLIELELSYC IEIGEDNRSI EPLTYGRIAS YYYLKHQTVK MFKDRLKPEC STEELLSILS DAEEYTDLPV RHNEDHMNSE LAKCLPIESN PHSFDSPHTK AHLLLQAHLS RAMLPCPDYD TDTKTVLDQA LRVCQAMLDV AANQGWLVTV LNITNLIQMV IQGRWLKDSS LLTLPNIENH HLHLFKKWKP IMKGPHARGR TSIESLPELI HACGGKDHVF SSMVESELHA AKTKQAWNFL SHLPVINVGI SVKGSWDDLV EGHNELSVST LTADKRDDNK WIKLHADQEY VLQVSLQRVH FGFHKGKPES CAVTPRFPKS KDEGWFLILG EVDKRELIAL KRVGYIRNHH VASLSFYTPE IPGRYIYTLY FMSDCYLGLD QQYDIYLNVT QASLSAQVNT KVSDSLTDLA LK //