ID MORC2_HUMAN Reviewed; 1032 AA. AC Q9Y6X9; B2RNB1; Q9UF28; Q9Y6V2; DT 26-JUL-2002, integrated into UniProtKB/Swiss-Prot. DT 05-SEP-2006, sequence version 2. DT 27-MAR-2024, entry version 198. DE RecName: Full=ATPase MORC2 {ECO:0000305}; DE EC=3.6.1.- {ECO:0000269|PubMed:23260667, ECO:0000269|PubMed:28581500, ECO:0000269|PubMed:29440755}; DE AltName: Full=MORC family CW-type zinc finger protein 2 {ECO:0000305}; DE AltName: Full=Zinc finger CW-type coiled-coil domain protein 1; GN Name=MORC2 {ECO:0000312|HGNC:HGNC:23573}; Synonyms=KIAA0852, ZCWCC1; 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). RC TISSUE=Brain; RX PubMed=10048485; DOI=10.1093/dnares/5.6.355; RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., RA Tanaka A., Kotani H., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XII. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 5:355-364(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84; RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., RA Beare D.M., Dunham I.; RT "A genome annotation-driven approach to cloning the human ORFeome."; RL Genome Biol. 5:R84.1-R84.11(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10591208; DOI=10.1038/990031; RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C., RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., RA Wright H.; RT "The DNA sequence of human chromosome 22."; RL Nature 402:489-495(1999). 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Cerebellum, and Neuroblastoma; 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 [LARGE SCALE MRNA] OF 712-1032. RC TISSUE=Testis; 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 [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-615, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-696; SER-705; SER-725; RP SER-730; THR-733; SER-777 AND SER-779, AND IDENTIFICATION BY MASS RP 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 [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-739 AND SER-743, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [11] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=20225202; DOI=10.1002/ar.21119; RA Wang G.L., Wang C.Y., Cai X.Z., Chen W., Wang X.H., Li F.; RT "Identification and expression analysis of a novel CW-type zinc finger RT protein MORC2 in cancer cells."; RL Anat. Rec. 293:1002-1009(2010). RN [12] RP FUNCTION, AND INTERACTION WITH HDAC4. RX PubMed=20110259; DOI=10.1093/nar/gkq006; RA Shao Y., Li Y., Zhang J., Liu D., Liu F., Zhao Y., Shen T., Li F.; RT "Involvement of histone deacetylation in MORC2-mediated down-regulation of RT carbonic anhydrase IX."; RL Nucleic Acids Res. 38:2813-2824(2010). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-615; SER-743; SER-777 AND RP SER-779, AND 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-615; SER-739; SER-743; RP SER-777 AND SER-779, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP 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 [16] RP FUNCTION, PHOSPHORYLATION AT SER-739, MUTAGENESIS OF ASP-68; ASP-69; RP SER-725; SER-730; SER-739 AND SER-773, AND SUBCELLULAR LOCATION. RX PubMed=23260667; DOI=10.1016/j.celrep.2012.11.018; RA Li D.Q., Nair S.S., Ohshiro K., Kumar A., Nair V.S., Pakala S.B., RA Reddy S.D., Gajula R.P., Eswaran J., Aravind L., Kumar R.; RT "MORC2 signaling integrates phosphorylation-dependent, ATPase-coupled RT chromatin remodeling during the DNA damage response."; RL Cell Rep. 2:1657-1669(2012). RN [17] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [18] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-582; SER-602; SER-615; RP SER-696; SER-705; SER-725; SER-730; THR-733; SER-739; SER-743; SER-777 AND RP SER-779, AND 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 [20] RP FUNCTION IN LIPID HOMEOSTASIS, SUBCELLULAR LOCATION, AND INTERACTION WITH RP ACLY. RX PubMed=24286864; DOI=10.1016/j.bbamcr.2013.11.012; RA Sanchez-Solana B., Li D.Q., Kumar R.; RT "Cytosolic functions of MORC2 in lipogenesis and adipogenesis."; RL Biochim. Biophys. Acta 1843:316-326(2014). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-615, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [22] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-767, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25218447; DOI=10.1038/nsmb.2890; RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M., RA Vertegaal A.C.; RT "Uncovering global SUMOylation signaling networks in a site-specific RT manner."; RL Nat. Struct. Mol. Biol. 21:927-936(2014). RN [23] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-652; LYS-704; LYS-716; LYS-767; RP LYS-819 AND LYS-932, 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 [24] RP FUNCTION. RX PubMed=29211708; DOI=10.1038/nature25179; RA Liu N., Lee C.H., Swigut T., Grow E., Gu B., Bassik M.C., Wysocka J.; RT "Selective silencing of euchromatic L1s revealed by genome-wide screens for RT L1 regulators."; RL Nature 553:228-232(2018). RN [25] RP VARIANTS CMT2Z GLU-96; GLY-236; TRP-252 AND ARG-444, AND VARIANTS CYS-248; RP HIS-283; HIS-466; CYS-585 AND GLY-757. RX PubMed=26659848; DOI=10.1002/ana.24575; RA Albulym O.M., Kennerson M.L., Harms M.B., Drew A.P., Siddell A.H., RA Auer-Grumbach M., Pestronk A., Connolly A., Baloh R.H., Zuchner S., RA Reddel S.W., Nicholson G.A.; RT "MORC2 mutations cause axonal Charcot-Marie-Tooth disease with pyramidal RT signs."; RL Ann. Neurol. 79:419-427(2016). RN [26] RP VARIANTS CMT2Z LEU-87 AND TRP-252. RX PubMed=26497905; DOI=10.1093/brain/awv311; RA Sevilla T., Lupo V., Martinez-Rubio D., Sancho P., Sivera R., RA Chumillas M.J., Garcia-Romero M., Pascual-Pascual S.I., Muelas N., RA Dopazo J., Vilchez J.J., Palau F., Espinos C.; RT "Mutations in the MORC2 gene cause axonal Charcot-Marie-Tooth disease."; RL Brain 139:62-72(2016). RN [27] RP VARIANTS CMT2Z ARG-400; ASN-466 AND ARG-798, AND VARIANTS ASP-163 AND RP SER-209. RX PubMed=27329773; DOI=10.1093/brain/aww156; RA Zhao X., Li X., Hu Z., Liu L., Xie Y., Tian T., Man J., Wang J., Zi X., RA Xia K., Tang B., Wei X., Zhang R.; RT "MORC2 mutations in a cohort of Chinese patients with Charcot-Marie-Tooth RT disease type 2."; RL Brain 139:e56-e56(2016). RN [28] RP VARIANT ARG-424. RX PubMed=27794525; DOI=10.1093/brain/aww252; RA Schottmann G., Wagner C., Seifert F., Stenzel W., Schuelke M.; RT "MORC2 mutation causes severe spinal muscular atrophy-phenotype, cerebellar RT atrophy, and diaphragmatic paralysis."; RL Brain 139:E70-E70(2016). RN [29] RP VARIANT ARG-424. RX PubMed=28402445; DOI=10.1093/brain/awx083; RA Zanni G., Nardella M., Barresi S., Bellacchio E., Niceta M., Ciolfi A., RA Pro S., D'Arrigo S., Tartaglia M., Bertini E.; RT "De novo p.T362R mutation in MORC2 causes early onset cerebellar ataxia, RT axonal polyneuropathy and nocturnal hypoventilation."; RL Brain 140:E34-E34(2017). RN [30] RP VARIANTS CMT2Z TRP-252; CYS-394; ARG-400; TYR-407 AND VAL-431, AND VARIANTS RP SER-209; MET-228 AND LYS-906. RX PubMed=28771897; DOI=10.1111/ene.13360; RA Ando M., Okamoto Y., Yoshimura A., Yuan J.H., Hiramatsu Y., Higuchi Y., RA Hashiguchi A., Mitsui J., Ishiura H., Fukumura S., Matsushima M., Ochi N., RA Tsugawa J., Morishita S., Tsuji S., Takashima H.; RT "Clinical and mutational spectrum of Charcot-Marie-Tooth disease type 2Z RT caused by MORC2 variants in Japan."; RL Eur. J. Neurol. 24:1274-1282(2017). RN [31] RP CHARACTERIZATION OF VARIANT CMT2Z TRP-252, FUNCTION, SUBCELLULAR LOCATION, RP INTERACTION WITH TASOR AND MPHOSPH8, MUTAGENESIS OF ASN-39 AND ASP-68, RP CATALYTIC ACTIVITY, AND DSDNA-BINDING. RX PubMed=28581500; DOI=10.1038/ng.3878; RA Tchasovnikarova I.A., Timms R.T., Douse C.H., Roberts R.C., Dougan G., RA Kingston R.E., Modis Y., Lehner P.J.; RT "Hyperactivation of HUSH complex function by Charcot-Marie-Tooth disease RT mutation in MORC2."; RL Nat. Genet. 49:1035-1044(2017). RN [32] RP INVOLVEMENT IN DIGFAN, VARIANTS DIGFAN ILE-24; LYS-27; LEU-87; VAL-88; RP CYS-132; SER-266; ARG-388; CYS-394 AND PHE-413, CHARACTERIZATION OF RP VARIANTS DIGFAN ILE-24; LYS-27; LEU-87; CYS-132; SER-266, CHARACTERIZATION RP OF VARIANTS CMT2Z GLY-236; TRP-252, AND FUNCTION. RX PubMed=32693025; DOI=10.1016/j.ajhg.2020.06.013; RG Undiagnosed Diseases Network; RA Guillen Sacoto M.J., Tchasovnikarova I.A., Torti E., Forster C., RA Andrew E.H., Anselm I., Baranano K.W., Briere L.C., Cohen J.S., RA Craigen W.J., Cytrynbaum C., Ekhilevitch N., Elrick M.J., Fatemi A., RA Fraser J.L., Gallagher R.C., Guerin A., Haynes D., High F.A., Inglese C.N., RA Kiss C., Koenig M.K., Krier J., Lindstrom K., Marble M., Meddaugh H., RA Moran E.S., Morel C.F., Mu W., Muller E.A. II, Nance J., Natowicz M.R., RA Numis A.L., Ostrem B., Pappas J., Stafstrom C.E., Streff H., Sweetser D.A., RA Szybowska M., Walker M.A., Wang W., Weiss K., Weksberg R., Wheeler P.G., RA Yoon G., Kingston R.E., Juusola J.; RT "De Novo Variants in the ATPase Module of MORC2 Cause a Neurodevelopmental RT Disorder with Growth Retardation and Variable Craniofacial Dysmorphism."; RL Am. J. Hum. Genet. 107:352-363(2020). RN [33] {ECO:0007744|PDB:5OF9, ECO:0007744|PDB:5OFA, ECO:0007744|PDB:5OFB} RP X-RAY CRYSTALLOGRAPHY (1.81 ANGSTROMS) OF 1-603 OF WILD-TYPE, X-RAY RP CRYSTALLOGRAPHY (1.81 ANGSTROMS) OF 1-603 OF, X-RAY CRYSTALLOGRAPHY (1.81 RP ANGSTROMS) OF 1-603 OF VARIANT CMT2Z LEU-87, X-RAY CRYSTALLOGRAPHY (1.81 RP ANGSTROMS) OF 1-603 OF VARIANT ARG-424 IN COMPLEX WITH ATP; MAGNESIUM AND RP ZINC, CHARACTERIZATION OF VARIANTS CMT2Z LEU-87 AND TRP-252, RP CHARACTERIZATION OF VARIANT ARG-424, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, RP AND MUTAGENESIS OF TYR-18; ASN-39; ARG-266; ARG-319; ARG-326; ARG-329; RP ARG-333; ARG-344; ARG-351 AND ARG-358. RX PubMed=29440755; DOI=10.1038/s41467-018-03045-x; RA Douse C.H., Bloor S., Liu Y., Shamin M., Tchasovnikarova I.A., Timms R.T., RA Lehner P.J., Modis Y.; RT "Neuropathic MORC2 mutations perturb GHKL ATPase dimerization dynamics and RT epigenetic silencing by multiple structural mechanisms."; RL Nat. Commun. 9:651-651(2018). CC -!- FUNCTION: Essential for epigenetic silencing by the HUSH (human CC silencing hub) complex. Recruited by HUSH to target site in CC heterochromatin, the ATPase activity and homodimerization are critical CC for HUSH-mediated silencing (PubMed:28581500, PubMed:29440755, CC PubMed:32693025). Represses germ cell-related genes and L1 CC retrotransposons in collaboration with SETDB1 and the HUSH complex, the CC silencing is dependent of repressive epigenetic modifications, such as CC H3K9me3 mark. Silencing events often occur within introns of CC transcriptionally active genes, and lead to the down-regulation of host CC gene expression (PubMed:29211708). During DNA damage response, CC regulates chromatin remodeling through ATP hydrolysis. Upon DNA damage, CC is phosphorylated by PAK1, both colocalize to chromatin and induce H2AX CC expression. ATPase activity is required and dependent of CC phosphorylation by PAK1 and presence of DNA (PubMed:23260667). Recruits CC histone deacetylases, such as HDAC4, to promoter regions, causing local CC histone H3 deacetylation and transcriptional repression of genes such CC as CA9 (PubMed:20225202, PubMed:20110259). Exhibits a cytosolic CC function in lipogenesis, adipogenic differentiation, and lipid CC homeostasis by increasing the activity of ACLY, possibly preventing its CC dephosphorylation (PubMed:24286864). {ECO:0000269|PubMed:20110259, CC ECO:0000269|PubMed:20225202, ECO:0000269|PubMed:23260667, CC ECO:0000269|PubMed:24286864, ECO:0000269|PubMed:28581500, CC ECO:0000269|PubMed:29211708, ECO:0000269|PubMed:29440755, CC ECO:0000269|PubMed:32693025}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; CC Evidence={ECO:0000269|PubMed:23260667, ECO:0000269|PubMed:28581500, CC ECO:0000269|PubMed:29440755}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13066; CC Evidence={ECO:0000269|PubMed:23260667}; CC -!- ACTIVITY REGULATION: ATPase activity is dependent of phosphorylation by CC PAK1 and presence of DNA. {ECO:0000269|PubMed:23260667}. CC -!- SUBUNIT: Homodimerizes upon ATP-binding and dissociate upon ATP CC hydrolysis; homodimerization is required for gene silencing CC (PubMed:29440755). Interacts with HDAC4 (PubMed:20110259). Interacts CC with ACLY (PubMed:24286864). Interacts with TASOR and MPHOSPH8; the CC interactions associate MORC2 with the HUSH complex which recruits MORC2 CC to heterochromatic loci (PubMed:28581500). CC {ECO:0000269|PubMed:20110259, ECO:0000269|PubMed:24286864, CC ECO:0000269|PubMed:28581500, ECO:0000269|PubMed:29440755}. CC -!- INTERACTION: CC Q9Y6X9-1; Q9Y6X9-1: MORC2; NbExp=2; IntAct=EBI-26959886, EBI-26959886; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20225202, CC ECO:0000269|PubMed:23260667, ECO:0000269|PubMed:28581500}. Cytoplasm, CC cytosol {ECO:0000269|PubMed:20225202, ECO:0000269|PubMed:24286864}. CC Chromosome {ECO:0000269|PubMed:23260667, ECO:0000269|PubMed:28581500}. CC Nucleus matrix {ECO:0000269|PubMed:23260667}. Note=Mainly located in CC the nucleus (PubMed:20225202). Upon phosphorylation at Ser-739, CC recruited to damaged chromatin (PubMed:23260667). CC {ECO:0000269|PubMed:20225202, ECO:0000269|PubMed:23260667}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9Y6X9-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9Y6X9-2; Sequence=VSP_041759; CC -!- TISSUE SPECIFICITY: Highly expressed in smooth muscle, pancreas and CC testis. CC -!- PTM: Phosphorylated by PAK1 at Ser-739 upon DNA damage. Phosphorylation CC is required for ATPase activity and recruitment to damaged chromatin. CC {ECO:0000269|PubMed:23260667}. CC -!- DISEASE: Charcot-Marie-Tooth disease, axonal, 2Z (CMT2Z) [MIM:616688]: CC An autosomal dominant, axonal form of Charcot-Marie-Tooth disease, a CC disorder of the peripheral nervous system, characterized by progressive CC weakness and atrophy, initially of the peroneal muscles and later of CC the distal muscles of the arms. Charcot-Marie-Tooth disease is CC classified in two main groups on the basis of electrophysiologic CC properties and histopathology: primary peripheral demyelinating CC neuropathies (designated CMT1 when they are dominantly inherited) and CC primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 CC group are characterized by signs of axonal degeneration in the absence CC of obvious myelin alterations, normal or slightly reduced nerve CC conduction velocities, and progressive distal muscle weakness and CC atrophy. {ECO:0000269|PubMed:26497905, ECO:0000269|PubMed:26659848, CC ECO:0000269|PubMed:27329773, ECO:0000269|PubMed:28581500, CC ECO:0000269|PubMed:28771897, ECO:0000269|PubMed:29440755, CC ECO:0000269|PubMed:32693025}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Developmental delay, impaired growth, dysmorphic facies, and CC axonal neuropathy (DIGFAN) [MIM:619090]: An autosomal dominant disease CC characterized by developmental delay, intellectual disability, CC hypotonia, poor growth, short stature, microcephaly, and variable CC craniofacial dysmorphism. Patients often present weakness, CC hyporeflexia, and electrophysiologic abnormalities consistent with an CC axonal sensorimotor peripheral neuropathy. Additional features may CC include hearing loss, pigmentary retinopathy, and abnormalities on CC brain imaging, including cerebral or cerebellar atrophy, CC hypomyelination, and lesions in the basal ganglia or brainstem. Disease CC severity is highly variable. {ECO:0000269|PubMed:32693025}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SEQUENCE CAUTION: CC Sequence=AAC12954.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC Sequence=BAA74875.2; Type=Miscellaneous discrepancy; Note=Intron retention.; 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; AB020659; BAA74875.2; ALT_SEQ; mRNA. DR EMBL; CR456469; CAG30355.1; -; mRNA. DR EMBL; AC004542; AAC12954.1; ALT_SEQ; Genomic_DNA. DR EMBL; AL133637; CAB63760.1; -; mRNA. DR EMBL; CH471095; EAW59921.1; -; Genomic_DNA. DR EMBL; BC019257; AAH19257.3; -; mRNA. DR EMBL; BC136782; AAI36783.1; -; mRNA. DR CCDS; CCDS33636.1; -. [Q9Y6X9-2] DR CCDS; CCDS77668.1; -. [Q9Y6X9-1] DR PIR; T02436; T02436. DR PIR; T43455; T43455. DR RefSeq; NP_001290185.1; NM_001303256.2. [Q9Y6X9-1] DR RefSeq; NP_001290186.1; NM_001303257.2. DR RefSeq; NP_055756.1; NM_014941.3. [Q9Y6X9-2] DR RefSeq; XP_016884157.1; XM_017028668.1. DR PDB; 5OF9; X-ray; 1.81 A; A/B=1-603. DR PDB; 5OFA; X-ray; 2.57 A; A/B=1-603. DR PDB; 5OFB; X-ray; 2.02 A; A/B=1-603. DR PDBsum; 5OF9; -. DR PDBsum; 5OFA; -. DR PDBsum; 5OFB; -. DR AlphaFoldDB; Q9Y6X9; -. DR SMR; Q9Y6X9; -. DR BioGRID; 116547; 75. DR IntAct; Q9Y6X9; 20. DR MINT; Q9Y6X9; -. DR STRING; 9606.ENSP00000380763; -. DR GlyGen; Q9Y6X9; 3 sites, 1 O-linked glycan (3 sites). DR iPTMnet; Q9Y6X9; -. DR PhosphoSitePlus; Q9Y6X9; -. DR SwissPalm; Q9Y6X9; -. DR BioMuta; MORC2; -. DR DMDM; 114152840; -. DR EPD; Q9Y6X9; -. DR jPOST; Q9Y6X9; -. DR MassIVE; Q9Y6X9; -. DR MaxQB; Q9Y6X9; -. DR PaxDb; 9606-ENSP00000215862; -. DR PeptideAtlas; Q9Y6X9; -. DR ProteomicsDB; 86822; -. [Q9Y6X9-1] DR ProteomicsDB; 86823; -. [Q9Y6X9-2] DR Pumba; Q9Y6X9; -. DR Antibodypedia; 235; 166 antibodies from 18 providers. DR DNASU; 22880; -. DR Ensembl; ENST00000215862.8; ENSP00000215862.4; ENSG00000133422.14. [Q9Y6X9-2] DR Ensembl; ENST00000397641.8; ENSP00000380763.2; ENSG00000133422.14. [Q9Y6X9-1] DR GeneID; 22880; -. DR KEGG; hsa:22880; -. DR MANE-Select; ENST00000397641.8; ENSP00000380763.2; NM_001303256.3; NP_001290185.1. DR UCSC; uc003aje.2; human. [Q9Y6X9-1] DR AGR; HGNC:23573; -. DR CTD; 22880; -. DR DisGeNET; 22880; -. DR GeneCards; MORC2; -. DR GeneReviews; MORC2; -. DR HGNC; HGNC:23573; MORC2. DR HPA; ENSG00000133422; Low tissue specificity. DR MalaCards; MORC2; -. DR MIM; 616661; gene. DR MIM; 616688; phenotype. DR MIM; 619090; phenotype. DR neXtProt; NX_Q9Y6X9; -. DR OpenTargets; ENSG00000133422; -. DR Orphanet; 466768; Autosomal dominant Charcot-Marie-Tooth disease type 2Z. DR PharmGKB; PA134986990; -. DR VEuPathDB; HostDB:ENSG00000133422; -. DR eggNOG; KOG1845; Eukaryota. DR GeneTree; ENSGT00940000153998; -. DR HOGENOM; CLU_011516_0_0_1; -. DR InParanoid; Q9Y6X9; -. DR OMA; GYLSARW; -. DR OrthoDB; 933627at2759; -. DR PhylomeDB; Q9Y6X9; -. DR TreeFam; TF329118; -. DR PathwayCommons; Q9Y6X9; -. DR Reactome; R-HSA-75105; Fatty acyl-CoA biosynthesis. DR SignaLink; Q9Y6X9; -. DR SIGNOR; Q9Y6X9; -. DR BioGRID-ORCS; 22880; 32 hits in 1163 CRISPR screens. DR ChiTaRS; MORC2; human. DR GeneWiki; MORC2; -. DR GenomeRNAi; 22880; -. DR Pharos; Q9Y6X9; Tbio. DR PRO; PR:Q9Y6X9; -. DR Proteomes; UP000005640; Chromosome 22. DR RNAct; Q9Y6X9; Protein. DR Bgee; ENSG00000133422; Expressed in cervix squamous epithelium and 207 other cell types or tissues. DR ExpressionAtlas; Q9Y6X9; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0000792; C:heterochromatin; IDA:UniProtKB. DR GO; GO:0016363; C:nuclear matrix; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB. DR GO; GO:0016887; F:ATP hydrolysis activity; IDA:UniProtKB. DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB. DR GO; GO:0006338; P:chromatin remodeling; IDA:UniProtKB. DR GO; GO:0006974; P:DNA damage response; IDA:UniProtKB. DR GO; GO:0006631; P:fatty acid metabolic process; IEA:UniProtKB-KW. DR GO; GO:0045814; P:negative regulation of gene expression, epigenetic; IDA:UniProtKB. DR GO; GO:0045869; P:negative regulation of single stranded viral RNA replication via double stranded DNA intermediate; IMP:UniProtKB. DR GO; GO:0090309; P:positive regulation of DNA methylation-dependent heterochromatin formation; IDA:UniProtKB. DR CDD; cd16931; HATPase_MORC-like; 1. DR Gene3D; 3.30.40.100; -; 1. DR Gene3D; 3.30.565.10; Histidine kinase-like ATPase, C-terminal domain; 1. DR InterPro; IPR036890; HATPase_C_sf. DR InterPro; IPR041006; Morc_S5. DR InterPro; IPR011124; Znf_CW. DR PANTHER; PTHR23337:SF7; ATPASE MORC2; 1. DR PANTHER; PTHR23337; ZINC FINGER CW-TYPE COILED-COIL DOMAIN PROTEIN 1; 1. DR Pfam; PF13589; HATPase_c_3; 1. DR Pfam; PF17942; Morc6_S5; 1. DR Pfam; PF07496; zf-CW; 1. DR SUPFAM; SSF55874; ATPase domain of HSP90 chaperone/DNA topoisomerase II/histidine kinase; 1. DR PROSITE; PS51050; ZF_CW; 1. DR Genevisible; Q9Y6X9; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; KW Charcot-Marie-Tooth disease; Chromosome; Coiled coil; Cytoplasm; KW Disease variant; Dwarfism; Fatty acid metabolism; Hydrolase; KW Intellectual disability; Isopeptide bond; Lipid metabolism; Magnesium; KW Metal-binding; Neurodegeneration; Neuropathy; Nucleotide-binding; Nucleus; KW Phosphoprotein; Reference proteome; Ubl conjugation; Zinc; Zinc-finger. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:22223895, FT ECO:0007744|PubMed:22814378" FT CHAIN 2..1032 FT /note="ATPase MORC2" FT /id="PRO_0000096537" FT ZN_FING 490..544 FT /note="CW-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00454, FT ECO:0000269|PubMed:29440755" FT REGION 530..563 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 577..793 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 850..870 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 282..362 FT /evidence="ECO:0000255" FT COILED 547..584 FT /evidence="ECO:0000255" FT COILED 741..761 FT /evidence="ECO:0000255" FT COILED 966..1016 FT /evidence="ECO:0000255" FT COMPBIAS 533..563 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 612..640 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 686..705 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 739..793 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 39 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:29440755" FT BINDING 39 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:29440755" FT BINDING 87..89 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:29440755" FT BINDING 99..105 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:29440755" FT BINDING 427 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:29440755" FT BINDING 499 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00454" FT BINDING 502 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00454" FT BINDING 525 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00454" FT BINDING 536 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00454" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:22223895, FT ECO:0007744|PubMed:22814378" FT MOD_RES 582 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 602 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 615 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 696 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 705 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 725 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 730 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 733 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 739 FT /note="Phosphoserine; by PAK1" FT /evidence="ECO:0000269|PubMed:23260667, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 743 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 777 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 779 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT CROSSLNK 652 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 704 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 716 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 767 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:25218447, FT ECO:0007744|PubMed:28112733" FT CROSSLNK 819 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 932 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT VAR_SEQ 1..62 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15461802, FT ECO:0000303|PubMed:15489334" FT /id="VSP_041759" FT VARIANT 24 FT /note="T -> I (in DIGFAN; increases HUSH-dependent gene FT silencing; dbSNP:rs1602510214)" FT /evidence="ECO:0000269|PubMed:32693025" FT /id="VAR_085367" FT VARIANT 27 FT /note="E -> K (in DIGFAN; increases HUSH-dependent gene FT silencing; dbSNP:rs1602510200)" FT /evidence="ECO:0000269|PubMed:32693025" FT /id="VAR_085368" FT VARIANT 87 FT /note="S -> L (in CMT2Z and DIGFAN; decreased ATPase FT activity; ATP-independent homodimerization; increases FT HUSH-dependent gene silencing; dbSNP:rs864309504)" FT /evidence="ECO:0000269|PubMed:26497905, FT ECO:0000269|PubMed:29440755, ECO:0000269|PubMed:32693025" FT /id="VAR_076454" FT VARIANT 88 FT /note="A -> V (in DIGFAN; dbSNP:rs1602499659)" FT /evidence="ECO:0000269|PubMed:32693025" FT /id="VAR_085369" FT VARIANT 96 FT /note="Q -> E (in CMT2Z; uncertain significance; FT dbSNP:rs749060708)" FT /evidence="ECO:0000269|PubMed:26659848" FT /id="VAR_076455" FT VARIANT 132 FT /note="R -> C (in DIGFAN; increases HUSH-dependent gene FT silencing; dbSNP:rs1064795559)" FT /evidence="ECO:0000269|PubMed:32693025" FT /id="VAR_085370" FT VARIANT 163 FT /note="E -> D (in dbSNP:rs186458188)" FT /evidence="ECO:0000269|PubMed:27329773" FT /id="VAR_085371" FT VARIANT 209 FT /note="N -> S (in dbSNP:rs76273991)" FT /evidence="ECO:0000269|PubMed:27329773, FT ECO:0000269|PubMed:28771897" FT /id="VAR_085372" FT VARIANT 228 FT /note="T -> M (in dbSNP:rs774960940)" FT /evidence="ECO:0000269|PubMed:28771897" FT /id="VAR_085373" FT VARIANT 236 FT /note="E -> G (in CMT2Z; increases HUSH-dependent gene FT silencing; dbSNP:rs886037934)" FT /evidence="ECO:0000269|PubMed:26659848, FT ECO:0000269|PubMed:32693025" FT /id="VAR_076456" FT VARIANT 248 FT /note="Y -> C (in dbSNP:rs1355363942)" FT /evidence="ECO:0000269|PubMed:26659848" FT /id="VAR_076457" FT VARIANT 252 FT /note="R -> W (in CMT2Z; slightly decreased ATPase FT activity; increases HUSH-dependent gene silencing; FT dbSNP:rs864309503)" FT /evidence="ECO:0000269|PubMed:26497905, FT ECO:0000269|PubMed:26659848, ECO:0000269|PubMed:28581500, FT ECO:0000269|PubMed:28771897, ECO:0000269|PubMed:29440755, FT ECO:0000269|PubMed:32693025" FT /id="VAR_076458" FT VARIANT 266 FT /note="R -> S (in DIGFAN; increases HUSH-dependent gene FT silencing; dbSNP:rs1064796495)" FT /evidence="ECO:0000269|PubMed:32693025" FT /id="VAR_085374" FT VARIANT 283 FT /note="R -> H (in dbSNP:rs1482880426)" FT /evidence="ECO:0000269|PubMed:26659848" FT /id="VAR_076459" FT VARIANT 388 FT /note="S -> R (in DIGFAN; dbSNP:rs1602485958)" FT /evidence="ECO:0000269|PubMed:32693025" FT /id="VAR_085375" FT VARIANT 394 FT /note="Y -> C (in DIGFAN and CMT2Z; dbSNP:rs1555938796)" FT /evidence="ECO:0000269|PubMed:28771897, FT ECO:0000269|PubMed:32693025" FT /id="VAR_085376" FT VARIANT 400 FT /note="Q -> R (in CMT2Z)" FT /evidence="ECO:0000269|PubMed:27329773, FT ECO:0000269|PubMed:28771897" FT /id="VAR_085377" FT VARIANT 407 FT /note="C -> Y (in CMT2Z; dbSNP:rs1555938741)" FT /evidence="ECO:0000269|PubMed:28771897" FT /id="VAR_085378" FT VARIANT 413 FT /note="V -> F (in DIGFAN; increases HUSH-dependent gene FT silencing; dbSNP:rs1602485677)" FT /evidence="ECO:0000269|PubMed:32693025" FT /id="VAR_085379" FT VARIANT 424 FT /note="T -> R (found in early-onset spinal muscular FT atrophy-like disease with cerebellar atrophy, cerebellar FT ataxia and diaphragmatic paralysis; likely pathogenic; FT increased ATPase activity; increased rate of dimer assembly FT and disassembly; decreased HUSH-dependent gene silencing)" FT /evidence="ECO:0000269|PubMed:27794525, FT ECO:0000269|PubMed:28402445, ECO:0000269|PubMed:29440755" FT /id="VAR_081260" FT VARIANT 431 FT /note="A -> V (in CMT2Z; dbSNP:rs2040679845)" FT /evidence="ECO:0000269|PubMed:28771897" FT /id="VAR_085380" FT VARIANT 444 FT /note="G -> R (in CMT2Z; uncertain significance)" FT /evidence="ECO:0000269|PubMed:26659848" FT /id="VAR_076460" FT VARIANT 466 FT /note="D -> H" FT /evidence="ECO:0000269|PubMed:26659848" FT /id="VAR_076461" FT VARIANT 466 FT /note="D -> N (in CMT2Z; uncertain significance)" FT /evidence="ECO:0000269|PubMed:27329773" FT /id="VAR_085381" FT VARIANT 585 FT /note="R -> C (in dbSNP:rs548292999)" FT /evidence="ECO:0000269|PubMed:26659848" FT /id="VAR_076462" FT VARIANT 757 FT /note="E -> G (in dbSNP:rs774444542)" FT /evidence="ECO:0000269|PubMed:26659848" FT /id="VAR_076463" FT VARIANT 798 FT /note="H -> R (in CMT2Z; uncertain significance; FT dbSNP:rs1236354994)" FT /evidence="ECO:0000269|PubMed:27329773" FT /id="VAR_085382" FT VARIANT 906 FT /note="E -> K (in dbSNP:rs759328437)" FT /evidence="ECO:0000269|PubMed:28771897" FT /id="VAR_085383" FT MUTAGEN 18 FT /note="Y->A: Abolishes homodimerization. No effect on FT ATPase activity. Loss of HUSH-dependent gene silencing." FT /evidence="ECO:0000269|PubMed:29440755" FT MUTAGEN 39 FT /note="N->A: Loss of ATP-binding and ATPase activity. Does FT not homodimerizes. Seems to abolish chromatin compaction." FT /evidence="ECO:0000269|PubMed:28581500, FT ECO:0000269|PubMed:29440755" FT MUTAGEN 68 FT /note="D->A: Loss of ATP-binding and ATPase activity. Loss FT of binding to ATP and ATPase activity; when associated with FT A-69. Prevents chromatin remodeling." FT /evidence="ECO:0000269|PubMed:23260667, FT ECO:0000269|PubMed:28581500" FT MUTAGEN 69 FT /note="D->A: No effect on binding to ATP and ATPase FT activity; when associated with A-68." FT /evidence="ECO:0000269|PubMed:23260667" FT MUTAGEN 266 FT /note="R->A: Increases HUSH-dependent gene silencing." FT /evidence="ECO:0000269|PubMed:29440755" FT MUTAGEN 319 FT /note="R->E: No effect on HUSH-dependent gene silencing." FT /evidence="ECO:0000269|PubMed:29440755" FT MUTAGEN 326 FT /note="R->E: Loss of HUSH-dependent gene silencing. FT Decreases dsDNA-binding affinity; when associated with FT E-329 and E-333." FT /evidence="ECO:0000269|PubMed:29440755" FT MUTAGEN 329 FT /note="R->E: Loss of HUSH-dependent gene silencing. FT Decreases dsDNA-binding affinity; when associated with FT E-326 and E-333." FT /evidence="ECO:0000269|PubMed:29440755" FT MUTAGEN 333 FT /note="R->E: Loss of HUSH-dependent gene silencing. FT Decreases dsDNA-binding affinity; when associated with FT E-326 and E-329." FT /evidence="ECO:0000269|PubMed:29440755" FT MUTAGEN 344 FT /note="R->E: No effect on HUSH-dependent gene silencing." FT /evidence="ECO:0000269|PubMed:29440755" FT MUTAGEN 351 FT /note="R->E: No effect on HUSH-dependent gene silencing." FT /evidence="ECO:0000269|PubMed:29440755" FT MUTAGEN 358 FT /note="R->E: No effect on HUSH-dependent gene silencing." FT /evidence="ECO:0000269|PubMed:29440755" FT MUTAGEN 725 FT /note="S->A: No effect on phosphorylation by PAK1." FT /evidence="ECO:0000269|PubMed:23260667" FT MUTAGEN 730 FT /note="S->A: No effect on phosphorylation by PAK1." FT /evidence="ECO:0000269|PubMed:23260667" FT MUTAGEN 739 FT /note="S->A: Abolishes phosphorylation by PAK1. Not FT recruited on damaged chromatin. Loss of ATPase activity. FT Prevents chromatin remodeling. Upon irradiation, increases FT levels of damaged DNA." FT /evidence="ECO:0000269|PubMed:23260667" FT MUTAGEN 773 FT /note="S->A: No effect on phosphorylation by PAK1." FT /evidence="ECO:0000269|PubMed:23260667" FT HELIX 17..23 FT /evidence="ECO:0007829|PDB:5OF9" FT HELIX 29..42 FT /evidence="ECO:0007829|PDB:5OF9" FT STRAND 46..54 FT /evidence="ECO:0007829|PDB:5OF9" FT STRAND 61..68 FT /evidence="ECO:0007829|PDB:5OF9" FT HELIX 75..80 FT /evidence="ECO:0007829|PDB:5OF9" FT STRAND 83..85 FT /evidence="ECO:0007829|PDB:5OFB" FT HELIX 103..111 FT /evidence="ECO:0007829|PDB:5OF9" FT STRAND 112..121 FT /evidence="ECO:0007829|PDB:5OF9" FT STRAND 124..131 FT /evidence="ECO:0007829|PDB:5OF9" FT HELIX 132..138 FT /evidence="ECO:0007829|PDB:5OF9" FT STRAND 149..151 FT /evidence="ECO:0007829|PDB:5OF9" FT TURN 152..154 FT /evidence="ECO:0007829|PDB:5OF9" FT HELIX 162..175 FT /evidence="ECO:0007829|PDB:5OF9" FT HELIX 181..189 FT /evidence="ECO:0007829|PDB:5OF9" FT STRAND 193..204 FT /evidence="ECO:0007829|PDB:5OF9" FT STRAND 212..215 FT /evidence="ECO:0007829|PDB:5OF9" FT STRAND 217..219 FT /evidence="ECO:0007829|PDB:5OF9" FT STRAND 224..227 FT /evidence="ECO:0007829|PDB:5OF9" FT HELIX 235..237 FT /evidence="ECO:0007829|PDB:5OF9" FT HELIX 240..246 FT /evidence="ECO:0007829|PDB:5OF9" FT STRAND 247..250 FT /evidence="ECO:0007829|PDB:5OF9" FT STRAND 253..257 FT /evidence="ECO:0007829|PDB:5OF9" FT HELIX 267..269 FT /evidence="ECO:0007829|PDB:5OF9" FT STRAND 270..280 FT /evidence="ECO:0007829|PDB:5OF9" FT HELIX 282..320 FT /evidence="ECO:0007829|PDB:5OF9" FT HELIX 331..361 FT /evidence="ECO:0007829|PDB:5OF9" FT STRAND 365..372 FT /evidence="ECO:0007829|PDB:5OF9" FT STRAND 381..386 FT /evidence="ECO:0007829|PDB:5OF9" FT STRAND 389..395 FT /evidence="ECO:0007829|PDB:5OF9" FT HELIX 398..401 FT /evidence="ECO:0007829|PDB:5OF9" FT STRAND 402..405 FT /evidence="ECO:0007829|PDB:5OF9" FT TURN 406..409 FT /evidence="ECO:0007829|PDB:5OF9" FT STRAND 410..416 FT /evidence="ECO:0007829|PDB:5OF9" FT TURN 418..420 FT /evidence="ECO:0007829|PDB:5OF9" FT STRAND 427..431 FT /evidence="ECO:0007829|PDB:5OF9" FT HELIX 433..454 FT /evidence="ECO:0007829|PDB:5OF9" FT HELIX 456..459 FT /evidence="ECO:0007829|PDB:5OF9" FT HELIX 461..467 FT /evidence="ECO:0007829|PDB:5OF9" FT STRAND 472..474 FT /evidence="ECO:0007829|PDB:5OF9" FT HELIX 483..490 FT /evidence="ECO:0007829|PDB:5OF9" FT STRAND 495..498 FT /evidence="ECO:0007829|PDB:5OF9" FT TURN 500..502 FT /evidence="ECO:0007829|PDB:5OF9" FT STRAND 505..510 FT /evidence="ECO:0007829|PDB:5OF9" FT TURN 512..514 FT /evidence="ECO:0007829|PDB:5OFA" FT HELIX 525..527 FT /evidence="ECO:0007829|PDB:5OF9" FT HELIX 531..533 FT /evidence="ECO:0007829|PDB:5OFA" SQ SEQUENCE 1032 AA; 117823 MW; 7BEFA46E4150ABF5 CRC64; MAFTNYSSLN RAQLTFEYLH TNSTTHEFLF GALAELVDNA RDADATRIDI YAERREDLRG GFMLCFLDDG AGMDPSDAAS VIQFGKSAKR TPESTQIGQY GNGLKSGSMR IGKDFILFTK KEDTMTCLFL SRTFHEEEGI DEVIVPLPTW NARTREPVTD NVEKFAIETE LIYKYSPFRT EEEVMTQFMK IPGDSGTLVI IFNLKLMDNG EPELDIISNP RDIQMAETSP EGTKPERRSF RAYAAVLYID PRMRIFIHGH KVQTKRLSCC LYKPRMYKYT SSRFKTRAEQ EVKKAEHVAR IAEEKAREAE SKARTLEVRL GGDLTRDSRV MLRQVQNRAI TLRREADVKK RIKEAKQRAL KEPKELNFVF GVNIEHRDLD GMFIYNCSRL IKMYEKVGPQ LEGGMACGGV VGVVDVPYLV LEPTHNKQDF ADAKEYRHLL RAMGEHLAQY WKDIAIAQRG IIKFWDEFGY LSANWNQPPS SELRYKRRRA MEIPTTIQCD LCLKWRTLPF QLSSVEKDYP DTWVCSMNPD PEQDRCEASE QKQKVPLGTF RKDMKTQEEK QKQLTEKIRQ QQEKLEALQK TTPIRSQADL KKLPLEVTTR PSTEEPVRRP QRPRSPPLPA VIRNAPSRPP SLPTPRPASQ PRKAPVISST PKLPALAARE EASTSRLLQP PEAPRKPANT LVKTASRPAP LVQQLSPSLL PNSKSPREVP SPKVIKTPVV KKTESPIKLS PATPSRKRSV AVSDEEEVEE EAERRKERCK RGRFVVKEEK KDSNELSDSA GEEDSADLKR AQKDKGLHVE VRVNREWYTG RVTAVEVGKH VVRWKVKFDY VPTDTTPRDR WVEKGSEDVR LMKPPSPEHQ SLDTQQEGGE EEVGPVAQQA IAVAEPSTSE CLRIEPDTTA LSTNHETIDL LVQILRNCLR YFLPPSFPIS KKQLSAMNSD ELISFPLKEY FKQYEVGLQN LCNSYQSRAD SRAKASEESL RTSERKLRET EEKLQKLRTN IVALLQKVQE DIDINTDDEL DAYIEDLITK GD //