MORC2_HUMAN
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 03-AUG-2022, entry version 189.
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,
CC PubMed:29440755,PubMed:32693025). Represses germ cell-related genes and
CC L1 retrotransposons in collaboration with SETDB1 and the HUSH complex,
CC the silencing is dependent of repressive epigenetic modifications, such
CC as 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 2Z (CMT2Z) [MIM:616688]: An
CC 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 ---------------------------------------------------------------------------
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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; 59.
DR IntAct; Q9Y6X9; 20.
DR MINT; Q9Y6X9; -.
DR STRING; 9606.ENSP00000215862; -.
DR GlyGen; Q9Y6X9; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9Y6X9; -.
DR PhosphoSitePlus; Q9Y6X9; -.
DR BioMuta; MORC2; -.
DR DMDM; 114152840; -.
DR EPD; Q9Y6X9; -.
DR jPOST; Q9Y6X9; -.
DR MassIVE; Q9Y6X9; -.
DR MaxQB; Q9Y6X9; -.
DR PaxDb; Q9Y6X9; -.
DR PeptideAtlas; Q9Y6X9; -.
DR PRIDE; Q9Y6X9; -.
DR ProteomicsDB; 86822; -. [Q9Y6X9-1]
DR ProteomicsDB; 86823; -. [Q9Y6X9-2]
DR Antibodypedia; 235; 143 antibodies from 17 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 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; DDTMTCL; -.
DR OrthoDB; 193855at2759; -.
DR PhylomeDB; Q9Y6X9; -.
DR TreeFam; TF329118; -.
DR PathwayCommons; Q9Y6X9; -.
DR Reactome; R-HSA-75105; Fatty acyl-CoA biosynthesis.
DR SignaLink; Q9Y6X9; -.
DR BioGRID-ORCS; 22880; 31 hits in 1078 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 205 other tissues.
DR ExpressionAtlas; Q9Y6X9; baseline and differential.
DR Genevisible; Q9Y6X9; HS.
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:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0006338; P:chromatin remodeling; 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 assembly; IDA:UniProtKB.
DR Gene3D; 3.30.565.10; -; 1.
DR InterPro; IPR036890; HATPase_C_sf.
DR InterPro; IPR041006; Morc_S5.
DR InterPro; IPR011124; Znf_CW.
DR Pfam; PF17942; Morc6_S5; 1.
DR Pfam; PF07496; zf-CW; 1.
DR SUPFAM; SSF55874; SSF55874; 1.
DR PROSITE; PS51050; ZF_CW; 1.
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 HUSH-
FT 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; unknown pathological 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)"
FT /evidence="ECO:0000269|PubMed:32693025"
FT /id="VAR_085379"
FT VARIANT 424
FT /note="T -> R (probable disease-associated variant found in
FT a child with spinal atrophy-phenotype, cerebellar atrophy
FT and diaphragmatic paralysis; also found in a second child
FT with early onset cerebellar ataxia, axonal polyneuropathy
FT and nocturanl hypoventilation; increased ATPase activity;
FT increased rate of dimer assembly and disassembly; decreased
FT 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)"
FT /evidence="ECO:0000269|PubMed:28771897"
FT /id="VAR_085380"
FT VARIANT 444
FT /note="G -> R (in CMT2Z; unknown pathological
FT 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; unknown pathological
FT 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; unknown pathological 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. Unables 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 E-
FT 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 E-
FT 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 E-
FT 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 Unables 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
