ID MPP8_HUMAN Reviewed; 860 AA. AC Q99549; B7Z6F9; Q5JPE5; Q5JTQ0; Q86TK3; Q96MK4; Q9BTP1; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-2005, sequence version 2. DT 27-MAR-2024, entry version 186. DE RecName: Full=M-phase phosphoprotein 8; DE AltName: Full=Two hybrid-associated protein 3 with RanBPM {ECO:0000303|PubMed:12559565}; DE Short=Twa3 {ECO:0000303|PubMed:12559565}; GN Name=MPHOSPH8 {ECO:0000312|HGNC:HGNC:29810}; Synonyms=MPP8; 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 2), AND NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 619-860 (ISOFORM 1). RC TISSUE=Placenta; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Lymph node; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057823; DOI=10.1038/nature02379; RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L., RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., RA Frankish A.G., Frankland J., French L., Garner P., Garnett J., RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., RA Rogers J., Ross M.T.; RT "The DNA sequence and analysis of human chromosome 13."; RL Nature 428:522-528(2004). 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 1). RC TISSUE=Pancreas, and PNS; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 228-532 (ISOFORMS 1/2), SUBCELLULAR LOCATION, RP AND PHOSPHORYLATION. RC TISSUE=Lymphoblast; RX PubMed=8885239; DOI=10.1091/mbc.7.9.1455; RA Matsumoto-Taniura N., Pirollet F., Monroe R., Gerace L., Westendorf J.M.; RT "Identification of novel M phase phosphoproteins by expression cloning."; RL Mol. Biol. Cell 7:1455-1469(1996). RN [7] RP IDENTIFICATION. RX PubMed=12559565; DOI=10.1016/s0378-1119(02)01153-8; RA Umeda M., Nishitani H., Nishimoto T.; RT "A novel nuclear protein, Twa1, and Muskelin comprise a complex with RT RanBPM."; RL Gene 303:47-54(2003). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-51; SER-319 AND SER-392, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-136; SER-138; SER-149 AND RP SER-189, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-51, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=18318008; DOI=10.1002/pmic.200700884; RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D., RA Zou H., Gu J.; RT "Large-scale phosphoproteome analysis of human liver tissue by enrichment RT and fractionation of phosphopeptides with strong anion exchange RT chromatography."; RL Proteomics 8:1346-1361(2008). RN [11] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP 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 [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-51; SER-136; SER-138; RP SER-149; SER-188; SER-189; SER-192 AND SER-403, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [13] RP FUNCTION, INTERACTION WITH HISTONE H3K9ME3; DNMT3A; EHMT1 AND SETDB1, RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF TRP-80. RX PubMed=20871592; DOI=10.1038/emboj.2010.239; RA Kokura K., Sun L., Bedford M.T., Fang J.; RT "Methyl-H3K9-binding protein MPP8 mediates E-cadherin gene silencing and RT promotes tumour cell motility and invasion."; RL EMBO J. 29:3673-3687(2010). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-51; SER-136; SER-138; RP SER-392; SER-400; SER-403 AND THR-454, AND IDENTIFICATION BY MASS RP 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 [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-51; SER-136; SER-138; RP SER-319; SER-392 AND SER-403, AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [16] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [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 [17] RP PHOSPHORYLATION AT SER-149; SER-164; THR-334 AND THR-385, AND MUTAGENESIS RP OF SER-149; SER-164; THR-334 AND THR-385. RX PubMed=23416073; DOI=10.1016/j.bbrc.2013.02.027; RA Nishigaki M., Kawada Y., Misaki T., Murata K., Goshima T., Hirokawa T., RA Yamada C., Shimada M., Nakanishi M.; RT "Mitotic phosphorylation of MPP8 by cyclin-dependent kinases regulates RT chromatin dissociation."; RL Biochem. Biophys. Res. Commun. 432:654-659(2013). RN [18] RP INTERACTION WITH HUMANIN. RX PubMed=23532874; DOI=10.1002/psc.2500; RA Maximov V.V., Martynenko A.V., Arman I.P., Tarantul V.Z.; RT "Humanin binds MPP8: mapping interaction sites of the peptide and RT protein."; RL J. Pept. Sci. 19:301-307(2013). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-51; SER-403 AND THR-454, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-51; SER-272 AND SER-279, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [21] RP FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION IN THE HUSH COMPLEX, AND RP MUTAGENESIS OF TRP-80. RX PubMed=26022416; DOI=10.1126/science.aaa7227; RA Tchasovnikarova I.A., Timms R.T., Matheson N.J., Wals K., Antrobus R., RA Goettgens B., Dougan G., Dawson M.A., Lehner P.J.; RT "Epigenetic silencing by the HUSH complex mediates position-effect RT variegation in human cells."; RL Science 348:1481-1485(2015). RN [22] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH MORC2. 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 [23] 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 [24] RP FUNCTION, INTERACTION WITH ZNF638, AND MUTAGENESIS OF TRP-80. RX PubMed=30487602; DOI=10.1038/s41586-018-0750-6; RA Zhu Y., Wang G.Z., Cingoez O., Goff S.P.; RT "NP220 mediates silencing of unintegrated retroviral DNA."; RL Nature 564:278-282(2018). RN [25] RP X-RAY CRYSTALLOGRAPHY (2.49 ANGSTROMS) OF 55-116 IN COMPLEX WITH HISTONE RP H3K9ME3 PEPTIDE, DOMAIN CHROMO, AND SUBUNIT. RX PubMed=21419134; DOI=10.1016/j.jmb.2011.03.018; RA Chang Y., Horton J.R., Bedford M.T., Zhang X., Cheng X.; RT "Structural insights for MPP8 chromodomain interaction with histone H3 RT lysine 9: potential effect of phosphorylation on methyl-lysine binding."; RL J. Mol. Biol. 408:807-814(2011). RN [26] RP X-RAY CRYSTALLOGRAPHY (2.31 ANGSTROMS) OF 55-116 IN COMPLEX WITH DNMT3A. RX PubMed=22086334; DOI=10.1038/ncomms1549; RA Chang Y., Sun L., Kokura K., Horton J.R., Fukuda M., Espejo A., Izumi V., RA Koomen J.M., Bedford M.T., Zhang X., Shinkai Y., Fang J., Cheng X.; RT "MPP8 mediates the interactions between DNA methyltransferase Dnmt3a and RT H3K9 methyltransferase GLP/G9a."; RL Nat. Commun. 2:533-533(2011). RN [27] RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 55-116 IN COMPLEX WITH HISTONE RP H3K9ME3 PEPTIDE, DOMAIN CHROMO, AND SUBUNIT. RX PubMed=22022377; DOI=10.1371/journal.pone.0025104; RA Li J., Li Z., Ruan J., Xu C., Tong Y., Pan P.W., Tempel W., Crombet L., RA Min J., Zang J.; RT "Structural basis for specific binding of human MPP8 chromodomain to RT histone H3 methylated at lysine 9."; RL PLoS ONE 6:E25104-E25104(2011). CC -!- FUNCTION: Heterochromatin component that specifically recognizes and CC binds methylated 'Lys-9' of histone H3 (H3K9me) and promotes CC recruitment of proteins that mediate epigenetic repression CC (PubMed:20871592, PubMed:26022416). Mediates recruitment of the HUSH CC complex to H3K9me3 sites: the HUSH complex is recruited to genomic loci CC rich in H3K9me3 and is required to maintain transcriptional silencing CC by promoting recruitment of SETDB1, a histone methyltransferase that CC mediates further deposition of H3K9me3, as well as MORC2 CC (PubMed:26022416, PubMed:28581500). Binds H3K9me and promotes DNA CC methylation by recruiting DNMT3A to target CpG sites; these can be CC situated within the coding region of the gene (PubMed:20871592). CC Mediates down-regulation of CDH1 expression (PubMed:20871592). Also CC represses L1 retrotransposons in collaboration with MORC2 and, CC probably, SETDB1, the silencing is dependent of repressive epigenetic CC modifications, such as H3K9me3 mark. Silencing events often occur CC within introns of transcriptionally active genes, and lead to the down- CC regulation of host gene expression (PubMed:29211708). The HUSH complex CC is also involved in the silencing of unintegrated retroviral DNA by CC being recruited by ZNF638: some part of the retroviral DNA formed CC immediately after infection remains unintegrated in the host genome and CC is transcriptionally repressed (PubMed:30487602). CC {ECO:0000269|PubMed:20871592, ECO:0000269|PubMed:26022416, CC ECO:0000269|PubMed:28581500, ECO:0000269|PubMed:29211708, CC ECO:0000269|PubMed:30487602}. CC -!- SUBUNIT: Homodimer (PubMed:21419134, PubMed:22022377, PubMed:22086334). CC Interacts (via chromo domain) with histone H3K9me3 (PubMed:20871592). CC Has the highest affinity for H3K9me3, and lesser affinity for H3K9me2 CC and H3K9me1 (PubMed:20871592). Component of the HUSH complex; at least CC composed of TASOR, PPHLN1 and MPHOSPH8 (PubMed:26022416). Interacts CC with DNMT3, EHMT1 and SETDB1 (PubMed:20871592, PubMed:22086334). CC Interacts with MORC2; the interaction associateS MORC2 with the HUSH CC complex which recruits MORC2 to heterochromatic loci (PubMed:28581500). CC Interacts with ZNF638; leading to recruitment of the HUSH complex to CC unintegrated retroviral DNA (PubMed:30487602). Interacts with TASOR (By CC similarity). Interacts with humanin (PubMed:23532874). CC {ECO:0000250|UniProtKB:Q3TYA6, ECO:0000269|PubMed:20871592, CC ECO:0000269|PubMed:21419134, ECO:0000269|PubMed:22022377, CC ECO:0000269|PubMed:22086334, ECO:0000269|PubMed:23532874, CC ECO:0000269|PubMed:26022416, ECO:0000269|PubMed:28581500, CC ECO:0000269|PubMed:30487602}. CC -!- INTERACTION: CC Q99549; Q9H9B1: EHMT1; NbExp=3; IntAct=EBI-2653928, EBI-766087; CC Q99549; P68431: H3C12; NbExp=5; IntAct=EBI-2653928, EBI-79722; CC Q99549; Q15047: SETDB1; NbExp=3; IntAct=EBI-2653928, EBI-79691; CC Q99549; Q9UK61: TASOR; NbExp=3; IntAct=EBI-2653928, EBI-308354; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20871592, CC ECO:0000269|PubMed:23416073, ECO:0000269|PubMed:26022416, CC ECO:0000269|PubMed:28581500, ECO:0000269|PubMed:8885239}. Chromosome CC {ECO:0000269|PubMed:23416073, ECO:0000269|PubMed:26022416, CC ECO:0000269|PubMed:28581500}. Note=Detected on heterochromatin CC (PubMed:20871592, PubMed:26022416). Dissociates from chromatin during CC interphase and early mitosis (PubMed:23416073). Detected on nucleosomes CC (PubMed:20871592). {ECO:0000269|PubMed:20871592, CC ECO:0000269|PubMed:23416073, ECO:0000269|PubMed:26022416}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q99549-1; Sequence=Displayed; CC Name=2; CC IsoId=Q99549-2; Sequence=VSP_031523; CC -!- DOMAIN: The chromo domain mediates interaction with methylated 'Lys-9' CC of histone H3 (H3K9me), with the highest affinity for the trimethylated CC form (H3K9me3). {ECO:0000269|PubMed:21419134, CC ECO:0000269|PubMed:22022377}. CC -!- PTM: Phosphorylated in M (mitotic) phase. Phosphorylation by CDK1 CC promotes dissociation from chromatin. {ECO:0000269|PubMed:23416073, CC ECO:0000269|PubMed:8885239}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH46214.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAB71284.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=CAI46172.1; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AK056785; BAB71284.1; ALT_INIT; mRNA. DR EMBL; AK300258; BAH13245.1; -; mRNA. DR EMBL; AL832864; CAI46172.1; ALT_FRAME; mRNA. DR EMBL; AL354808; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL359457; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471075; EAX08228.1; -; Genomic_DNA. DR EMBL; CH471075; EAX08230.1; -; Genomic_DNA. DR EMBL; BC003542; AAH03542.2; -; mRNA. DR EMBL; BC046214; AAH46214.1; ALT_INIT; mRNA. DR EMBL; X98259; CAA66912.1; -; mRNA. DR CCDS; CCDS9287.1; -. [Q99549-1] DR RefSeq; NP_059990.2; NM_017520.3. [Q99549-1] DR PDB; 3LWE; X-ray; 2.05 A; A/B=55-116. DR PDB; 3QO2; X-ray; 2.49 A; A/B/C/D=55-116. DR PDB; 3R93; X-ray; 2.06 A; A/B/C/D=55-116. DR PDB; 3SVM; X-ray; 2.31 A; A=55-116. DR PDB; 6V2S; X-ray; 1.60 A; A/B=55-116. DR PDB; 7M5U; X-ray; 2.02 A; A=55-116. DR PDBsum; 3LWE; -. DR PDBsum; 3QO2; -. DR PDBsum; 3R93; -. DR PDBsum; 3SVM; -. DR PDBsum; 6V2S; -. DR PDBsum; 7M5U; -. DR AlphaFoldDB; Q99549; -. DR SMR; Q99549; -. DR BioGRID; 120119; 89. DR ComplexPortal; CPX-2348; HUSH epigenetic repressor complex. DR CORUM; Q99549; -. DR DIP; DIP-56224N; -. DR IntAct; Q99549; 55. DR MINT; Q99549; -. DR STRING; 9606.ENSP00000355388; -. DR ChEMBL; CHEMBL1741210; -. DR iPTMnet; Q99549; -. DR PhosphoSitePlus; Q99549; -. DR SwissPalm; Q99549; -. DR BioMuta; MPHOSPH8; -. DR DMDM; 93204602; -. DR EPD; Q99549; -. DR jPOST; Q99549; -. DR MassIVE; Q99549; -. DR MaxQB; Q99549; -. DR PaxDb; 9606-ENSP00000355388; -. DR PeptideAtlas; Q99549; -. DR ProteomicsDB; 78321; -. [Q99549-1] DR ProteomicsDB; 78322; -. [Q99549-2] DR Pumba; Q99549; -. DR ABCD; Q99549; 2 sequenced antibodies. DR Antibodypedia; 22243; 125 antibodies from 29 providers. DR DNASU; 54737; -. DR Ensembl; ENST00000361479.10; ENSP00000355388.4; ENSG00000196199.14. [Q99549-1] DR GeneID; 54737; -. DR KEGG; hsa:54737; -. DR MANE-Select; ENST00000361479.10; ENSP00000355388.4; NM_017520.4; NP_059990.2. DR UCSC; uc001umh.4; human. [Q99549-1] DR AGR; HGNC:29810; -. DR CTD; 54737; -. DR DisGeNET; 54737; -. DR GeneCards; MPHOSPH8; -. DR HGNC; HGNC:29810; MPHOSPH8. DR HPA; ENSG00000196199; Low tissue specificity. DR MIM; 611626; gene. DR neXtProt; NX_Q99549; -. DR OpenTargets; ENSG00000196199; -. DR PharmGKB; PA162396090; -. DR VEuPathDB; HostDB:ENSG00000196199; -. DR eggNOG; KOG0504; Eukaryota. DR eggNOG; KOG1911; Eukaryota. DR GeneTree; ENSGT00730000111087; -. DR HOGENOM; CLU_332588_0_0_1; -. DR InParanoid; Q99549; -. DR OMA; QKNQDKG; -. DR OrthoDB; 3061686at2759; -. DR PhylomeDB; Q99549; -. DR TreeFam; TF106394; -. DR PathwayCommons; Q99549; -. DR SignaLink; Q99549; -. DR BioGRID-ORCS; 54737; 116 hits in 1165 CRISPR screens. DR ChiTaRS; MPHOSPH8; human. DR EvolutionaryTrace; Q99549; -. DR GeneWiki; MPHOSPH8; -. DR GenomeRNAi; 54737; -. DR Pharos; Q99549; Tbio. DR PRO; PR:Q99549; -. DR Proteomes; UP000005640; Chromosome 13. DR RNAct; Q99549; Protein. DR Bgee; ENSG00000196199; Expressed in tendon of biceps brachii and 196 other cell types or tissues. DR ExpressionAtlas; Q99549; 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:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0000786; C:nucleosome; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB. DR GO; GO:0140566; F:histone reader activity; IDA:GO_Central. DR GO; GO:0035064; F:methylated histone binding; IDA:UniProtKB. DR GO; GO:0044027; P:negative regulation of gene expression via CpG island methylation; IMP:UniProtKB. 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 GO; GO:0044030; P:regulation of DNA methylation; IBA:GO_Central. DR CDD; cd18633; CD_MMP8; 1. DR Gene3D; 2.40.50.40; -; 1. DR Gene3D; 1.25.40.20; Ankyrin repeat-containing domain; 1. DR IDEAL; IID00392; -. DR InterPro; IPR002110; Ankyrin_rpt. DR InterPro; IPR036770; Ankyrin_rpt-contain_sf. DR InterPro; IPR016197; Chromo-like_dom_sf. DR InterPro; IPR000953; Chromo/chromo_shadow_dom. DR InterPro; IPR023780; Chromo_domain. DR InterPro; IPR023779; Chromodomain_CS. DR PANTHER; PTHR24184:SF28; CHROMO DOMAIN-CONTAINING PROTEIN; 1. DR PANTHER; PTHR24184; SI:CH211-189E2.2; 1. DR Pfam; PF00023; Ank; 1. DR Pfam; PF12796; Ank_2; 1. DR Pfam; PF00385; Chromo; 1. DR SMART; SM00248; ANK; 4. DR SMART; SM00298; CHROMO; 1. DR SUPFAM; SSF48403; Ankyrin repeat; 1. DR SUPFAM; SSF54160; Chromo domain-like; 1. DR PROSITE; PS50297; ANK_REP_REGION; 1. DR PROSITE; PS50088; ANK_REPEAT; 3. DR PROSITE; PS00598; CHROMO_1; 1. DR PROSITE; PS50013; CHROMO_2; 1. DR Genevisible; Q99549; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; ANK repeat; Chromosome; KW Nucleus; Phosphoprotein; Reference proteome; Repeat; Repressor; KW Transcription; Transcription regulation. FT CHAIN 1..860 FT /note="M-phase phosphoprotein 8" FT /id="PRO_0000080244" FT DOMAIN 59..118 FT /note="Chromo" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00053" FT REPEAT 600..629 FT /note="ANK 1" FT REPEAT 633..662 FT /note="ANK 2" FT REPEAT 666..695 FT /note="ANK 3" FT REPEAT 699..728 FT /note="ANK 4" FT REGION 80..87 FT /note="Histone H3K9me3 binding" FT /evidence="ECO:0000269|PubMed:21419134" FT REGION 129..191 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 206..440 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 431..560 FT /note="Interaction with humanin" FT /evidence="ECO:0000269|PubMed:23532874" FT REGION 458..496 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 159..187 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 206..261 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 276..329 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 336..374 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 389..440 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 59 FT /note="Interaction with histone H3K9me3" FT /evidence="ECO:0000269|PubMed:21419134" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:22814378" FT MOD_RES 51 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18318008, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 85 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q3TYA6" FT MOD_RES 136 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692" FT MOD_RES 138 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692" FT MOD_RES 144 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q3TYA6" FT MOD_RES 149 FT /note="Phosphoserine; by CDK1" FT /evidence="ECO:0000305|PubMed:23416073, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332" FT MOD_RES 164 FT /note="Phosphoserine; by CDK1" FT /evidence="ECO:0000305|PubMed:23416073" FT MOD_RES 188 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 189 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332" FT MOD_RES 192 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 266 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q3TYA6" FT MOD_RES 272 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 279 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 319 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:21406692" FT MOD_RES 334 FT /note="Phosphothreonine; by CDK1" FT /evidence="ECO:0000305|PubMed:23416073" FT MOD_RES 385 FT /note="Phosphothreonine; by CDK1" FT /evidence="ECO:0000305|PubMed:23416073" FT MOD_RES 392 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692" FT MOD_RES 400 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 403 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 454 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT VAR_SEQ 820..860 FT /note="DSHFVYSFSPVAGPNKLFIRLTEAPSAKVKLLIGAYRVQLQ -> TGSRSVV FT QAGVQWRGLQLTGVLTSQAQAILPPQPPNYLGLKMHATTSG (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:17974005" FT /id="VSP_031523" FT MUTAGEN 80 FT /note="W->A: Abolishes interaction with histone H3K9me3 and FT prevents recruitment of the HUSH complex to FT heterochromatin. Impaired ability to mediate silencing of FT unintegrated retroviral DNA." FT /evidence="ECO:0000269|PubMed:20871592, FT ECO:0000269|PubMed:26022416, ECO:0000269|PubMed:30487602" FT MUTAGEN 149 FT /note="S->A: In STA mutant; fails to dissociate from FT chromatin during early mitosis; when associated with A-164; FT A-334 and A-385." FT /evidence="ECO:0000269|PubMed:23416073" FT MUTAGEN 164 FT /note="S->A: In STA mutant; fails to dissociate from FT chromatin during early mitosis; when associated with A-149; FT A-334 and A-385." FT /evidence="ECO:0000269|PubMed:23416073" FT MUTAGEN 334 FT /note="T->A: In STA mutant; fails to dissociate from FT chromatin during early mitosis; when associated with A-149; FT A-164 and A-385." FT /evidence="ECO:0000269|PubMed:23416073" FT MUTAGEN 385 FT /note="T->A: In STA mutant; fails to dissociate from FT chromatin during early mitosis; when associated with A-149; FT A-164; and A-334." FT /evidence="ECO:0000269|PubMed:23416073" FT CONFLICT 526..530 FT /note="DGRQQ -> GEFGI (in Ref. 6; CAA66912)" FT /evidence="ECO:0000305" FT CONFLICT 860 FT /note="Q -> QPNRRDWAEFS (in Ref. 5; AAH46214)" FT /evidence="ECO:0000305" FT STRAND 61..70 FT /evidence="ECO:0007829|PDB:6V2S" FT STRAND 73..80 FT /evidence="ECO:0007829|PDB:6V2S" FT HELIX 85..87 FT /evidence="ECO:0007829|PDB:6V2S" FT STRAND 89..92 FT /evidence="ECO:0007829|PDB:6V2S" FT HELIX 93..96 FT /evidence="ECO:0007829|PDB:6V2S" FT HELIX 100..113 FT /evidence="ECO:0007829|PDB:6V2S" SQ SEQUENCE 860 AA; 97182 MW; DD75D14C3DBF5E95 CRC64; MEQVAEGARV TAVPVSAADS TEELAEVEEG VGVVGEDNDA AARGAEAFGD SEEDGEDVFE VEKILDMKTE GGKVLYKVRW KGYTSDDDTW EPEIHLEDCK EVLLEFRKKI AENKAKAVRK DIQRLSLNND IFEANSDSDQ QSETKEDTSP KKKKKKLRQR EEKSPDDLKK KKAKAGKLKD KSKPDLESSL ESLVFDLRTK KRISEAKEEL KESKKPKKDE VKETKELKKV KKGEIRDLKT KTREDPKENR KTKKEKFVES QVESESSVLN DSPFPEDDSE GLHSDSREEK QNTKSARERA GQDMGLEHGF EKPLDSAMSA EEDTDVRGRR KKKTPRKAED TRENRKLENK NAFLEKKTVP KKQRNQDRSK SAAELEKLMP VSAQTPKGRR LSGEERGLWS TDSAEEDKET KRNESKEKYQ KRHDSDKEEK GRKEPKGLKT LKEIRNAFDL FKLTPEEKND VSENNRKREE IPLDFKTIDD HKTKENKQSL KERRNTRDET DTWAYIAAEG DQEVLDSVCQ ADENSDGRQQ ILSLGMDLQL EWMKLEDFQK HLDGKDENFA ATDAIPSNVL RDAVKNGDYI TVKVALNSNE EYNLDQEDSS GMTLVMLAAA GGQDDLLRLL ITKGAKVNGR QKNGTTALIH AAEKNFLTTV AILLEAGAFV NVQQSNGETA LMKACKRGNS DIVRLVIECG ADCNILSKHQ NSALHFAKQS NNVLVYDLLK NHLETLSRVA EETIKDYFEA RLALLEPVFP IACHRLCEGP DFSTDFNYKP PQNIPEGSGI LLFIFHANFL GKEVIARLCG PCSVQAVVLN DKFQLPVFLD SHFVYSFSPV AGPNKLFIRL TEAPSAKVKL LIGAYRVQLQ //