MOR2A_MOUSE
ID MOR2A_MOUSE Reviewed; 1030 AA.
AC Q69ZX6; Q5QNQ7; Q6P547;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-SEP-2006, sequence version 2.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=ATPase MORC2A {ECO:0000305};
DE EC=3.6.1.- {ECO:0000250|UniProtKB:Q9Y6X9};
DE AltName: Full=MORC family CW-type zinc finger protein 2A;
DE AltName: Full=Zinc finger CW-type coiled-coil domain protein 1;
GN Name=Morc2a {ECO:0000312|MGI:MGI:1921772};
GN Synonyms=Kiaa0852 {ECO:0000312|EMBL:BAD32320.1},
GN Zcwcc1 {ECO:0000312|MGI:MGI:1921772};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1] {ECO:0000312|EMBL:BAD32320.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryonic intestine {ECO:0000312|EMBL:BAD32320.1};
RX PubMed=15368895; DOI=10.1093/dnares/11.3.205;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H.,
RA Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: IV.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 11:205-218(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3] {ECO:0000305, ECO:0000312|EMBL:AAH63082.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 337-1030.
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:AAH63082.1};
RC TISSUE=Brain {ECO:0000312|EMBL:AAH63082.1};
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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-854, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT "Large scale localization of protein phosphorylation by use of electron
RT capture dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 8:904-912(2009).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-737; SER-741; SER-775;
RP THR-834; SER-854 AND SER-859, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP TISSUE SPECIFICITY.
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 [7]
RP FUNCTION, MUTAGENESIS OF 68-ASP-ASP-69, INTERACTION WITH HISTONE H3, AND
RP SUBCELLULAR LOCATION.
RX PubMed=29728365; DOI=10.1101/gr.227280.117;
RA Fukuda K., Okuda A., Yusa K., Shinkai Y.;
RT "A CRISPR knockout screen identifies SETDB1-target retroelement silencing
RT factors in embryonic stem cells.";
RL Genome Res. 28:846-858(2018).
RN [8]
RP INTERACTION WITH MORC2A.
RX PubMed=29329290; DOI=10.1371/journal.pgen.1007175;
RA Shi B., Xue J., Zhou J., Kasowitz S.D., Zhang Y., Liang G., Guan Y.,
RA Shi Q., Liu M., Sha J., Huang X., Wang P.J.;
RT "MORC2B is essential for meiotic progression and fertility.";
RL PLoS Genet. 14:E1007175-E1007175(2018).
CC -!- FUNCTION: Essential for epigenetic silencing by the HUSH complex.
CC Recruited by HUSH to target site in heterochromatin, the ATPase
CC activity and homodimerization are critical for HUSH-mediated silencing
CC (By similarity). 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 (PubMed:29728365). Silencing events often occur within
CC introns of transcriptionally active genes, and lead to the down-
CC regulation of host gene expression. During DNA damage response,
CC regulates chromatin remodeling through ATP hydrolysis (By similarity).
CC During DNA damage response, may regulate chromatin remodeling through
CC ATP hydrolysis (By similarity). {ECO:0000250|UniProtKB:Q9Y6X9,
CC ECO:0000269|PubMed:29728365}.
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:0000250|UniProtKB:Q9Y6X9};
CC -!- ACTIVITY REGULATION: ATPase activity is dependent of phosphorylation by
CC PAK1 and presence of DNA. {ECO:0000250|UniProtKB:Q9Y6X9}.
CC -!- SUBUNIT: Homodimerizes upon ATP-binding and dissociate upon ATP
CC hydrolysis; homodimerization is required for gene silencing (By
CC similarity). Binds histone H3 independently of the methylation status
CC at 'Lys-9' (PubMed:29728365). Interacts with HDAC4. Interacts with
CC FAM208A/TASOR and MPHOSPH8; the interactions associate MORC2 with the
CC HUSH complex which recruits MORC2 to heterochromatic loci (By
CC similarity). Interacts with Morc2b (PubMed:29329290).
CC {ECO:0000250|UniProtKB:Q9Y6X9, ECO:0000269|PubMed:29329290,
CC ECO:0000269|PubMed:29728365}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:29728365}. Cytoplasm,
CC cytosol {ECO:0000250|UniProtKB:Q9Y6X9}. Chromosome
CC {ECO:0000250|UniProtKB:Q9Y6X9}. Nucleus matrix
CC {ECO:0000250|UniProtKB:Q9Y6X9}. Note=Mainly located in the nucleus.
CC Upon phosphorylation at Ser-737, recruited to damaged chromatin.
CC {ECO:0000250|UniProtKB:Q9Y6X9}.
CC -!- TISSUE SPECIFICITY: Expressed in the axons and Schwann cells of
CC peripheral nerves. Expressed in testes (PubMed:29329290).
CC {ECO:0000269|PubMed:26497905, ECO:0000269|PubMed:29329290}.
CC -!- PTM: Phosphorylated by PAK1 at Ser-737 upon DNA damage. Phosphorylation
CC is required for ATPase activity and recruitment to damaged chromatin.
CC {ECO:0000250|UniProtKB:Q9Y6X9}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD32320.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK173042; BAD32320.1; ALT_INIT; mRNA.
DR EMBL; AL691413; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC063082; AAH63082.1; -; mRNA.
DR CCDS; CCDS48741.1; -.
DR RefSeq; NP_001152760.1; NM_001159288.1.
DR RefSeq; XP_011242078.1; XM_011243776.2.
DR AlphaFoldDB; Q69ZX6; -.
DR SMR; Q69ZX6; -.
DR BioGRID; 216819; 6.
DR IntAct; Q69ZX6; 1.
DR MINT; Q69ZX6; -.
DR STRING; 10090.ENSMUSP00000091087; -.
DR iPTMnet; Q69ZX6; -.
DR PhosphoSitePlus; Q69ZX6; -.
DR EPD; Q69ZX6; -.
DR jPOST; Q69ZX6; -.
DR MaxQB; Q69ZX6; -.
DR PaxDb; Q69ZX6; -.
DR PeptideAtlas; Q69ZX6; -.
DR PRIDE; Q69ZX6; -.
DR ProteomicsDB; 252591; -.
DR Ensembl; ENSMUST00000093389; ENSMUSP00000091087; ENSMUSG00000034543.
DR Ensembl; ENSMUST00000096441; ENSMUSP00000094176; ENSMUSG00000034543.
DR GeneID; 74522; -.
DR KEGG; mmu:74522; -.
DR UCSC; uc007htm.1; mouse.
DR CTD; 74522; -.
DR MGI; MGI:1921772; Morc2a.
DR VEuPathDB; HostDB:ENSMUSG00000034543; -.
DR eggNOG; KOG1845; Eukaryota.
DR GeneTree; ENSGT00940000153998; -.
DR HOGENOM; CLU_011516_0_0_1; -.
DR InParanoid; Q69ZX6; -.
DR OMA; DDTMTCL; -.
DR OrthoDB; 193855at2759; -.
DR PhylomeDB; Q69ZX6; -.
DR TreeFam; TF329118; -.
DR Reactome; R-MMU-75105; Fatty acyl-CoA biosynthesis.
DR BioGRID-ORCS; 74522; 5 hits in 72 CRISPR screens.
DR ChiTaRS; Morc2a; mouse.
DR PRO; PR:Q69ZX6; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q69ZX6; protein.
DR Bgee; ENSMUSG00000034543; Expressed in embryonic post-anal tail and 233 other tissues.
DR ExpressionAtlas; Q69ZX6; baseline and differential.
DR Genevisible; Q69ZX6; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0000792; C:heterochromatin; ISS:UniProtKB.
DR GO; GO:0016363; C:nuclear matrix; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0016887; F:ATP hydrolysis activity; ISO:MGI.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0042393; F:histone binding; IMP:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0006338; P:chromatin remodeling; ISS:UniProtKB.
DR GO; GO:0045814; P:negative regulation of gene expression, epigenetic; ISS: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; IMP: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 Acetylation; ATP-binding; Chromosome; Coiled coil; Cytoplasm; Hydrolase;
KW Isopeptide bond; Magnesium; Metal-binding; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Ubl conjugation; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6X9"
FT CHAIN 2..1030
FT /note="ATPase MORC2A"
FT /id="PRO_0000248243"
FT ZN_FING 490..544
FT /note="CW-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00454"
FT REGION 530..791
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 837..874
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 882..901
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 285..362
FT /evidence="ECO:0000255"
FT COILED 555..583
FT /evidence="ECO:0000255"
FT COILED 738..775
FT /evidence="ECO:0000255"
FT COILED 966..1011
FT /evidence="ECO:0000255"
FT COMPBIAS 533..574
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 596..610
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 633..668
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 672..695
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 737..791
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 837..852
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:0000250|UniProtKB:Q9Y6X9"
FT BINDING 39
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6X9"
FT BINDING 87..89
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6X9"
FT BINDING 99..105
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6X9"
FT BINDING 427
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6X9"
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:0000250|UniProtKB:Q9Y6X9"
FT MOD_RES 582
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6X9"
FT MOD_RES 614
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6X9"
FT MOD_RES 703
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6X9"
FT MOD_RES 728
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6X9"
FT MOD_RES 731
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6X9"
FT MOD_RES 737
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 741
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 775
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 777
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6X9"
FT MOD_RES 834
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 854
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19131326,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 859
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CROSSLNK 650
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6X9"
FT CROSSLNK 702
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6X9"
FT CROSSLNK 714
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6X9"
FT CROSSLNK 765
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6X9"
FT CROSSLNK 817
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6X9"
FT CROSSLNK 930
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6X9"
FT MUTAGEN 68..69
FT /note="DD->AA: Abolishes repression of germ cell-related
FT genes and L1 retrotransposons."
FT /evidence="ECO:0000269|PubMed:29728365"
SQ SEQUENCE 1030 AA; 117330 MW; 0EDD2D09F11C80A2 CRC64;
MAFTNYSSLN RAQLTFEYLH TNSTTHEFLF GALAELVDNA RDADATRIDI YAERREDLRG
GFMLCFLDDG AGMDPSDAAS VIQFGKSAKR TPESTQIGQY GNGLKSGSMR IGKDFILFTK
KEDTMTCLFL SRTFHEEEGI DEVIVPLPTW NARTREPITD NVEKFAIETE LVYKYSPFHT
EEQVMNQFMK IPGNSGTLVI IFNLKLMDNG EPELDIISNP KDIQMAETSP EGTKPERRSF
RAYAAVLYID PRMRIFIHGH KVQTKRLSCC LYKPRMYKYT SSRFKTRAEQ EVKKAEHVAR
IAEEKAREAE SKARTLEVRM GGDLTRDSRV MLRQVQNTAI TLRREADVKK RIKDAKQRAL
KEPKELNFVF GVNIEHRDLD GMFIYNCSRL IKMYEKVGPQ LEGGMACGGV VGVVDVPYLV
LEPTHNKQDF ADAKEYRHLL RAMGEHLAQY WKDIAIAQRG IIKFWDEFGY LSANWNQPPS
SELRFKRRRA MEIPTTIQCD LCLKWRTLPF QLSSVETDYP DTWVCSMNPD PEQDRCEASE
QKQKVPLGTL KKDPKTQEEK QKQLTEKIRQ QQEKLEALQK TTPIRSQADL KKLPLEVTTR
PIEEPVRRPQ RPRSPPLPAV IKNAPSRPPS IQTPRPSTQL RKTSVISLPK PPTTAARGET
STSRLLQPTE APRKPANPPI KTVPRPTPPV HTPPLSLIPS SKSLREVPAQ KAIKTPVVKK
PEPPVKQSVA TSGRKRSLAV SDEEEAEEEA EKRRERCKRG KLAVKEEKKE ANELSDSAGE
DHPAELRKAQ KDKGLHVEVR VNREWYTGRV TAVEVGKNAV RWKVKFDYVP TDTTPRDRWV
EKGSEDVRLM KPPSPEHQSP DTQQEGGEEE EAMVARQAVA LPEPSTSDGL PIEPDTTATS
PSHETIDLLV QILRNCLRYF LPPSFPISKK ELSVMNSEEL ISFPLKEYFK QYEVGLQNLC
HSYQSRADSR AKASEESLRT SEKKLRETEE KLQKLRTNIV ALLQKVQEDI DINTDDELDA
YIEDLITKGD
