MPP8_HUMAN
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 03-AUG-2022, entry version 177.
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};
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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; 76.
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 BioMuta; MPHOSPH8; -.
DR DMDM; 93204602; -.
DR EPD; Q99549; -.
DR jPOST; Q99549; -.
DR MassIVE; Q99549; -.
DR MaxQB; Q99549; -.
DR PaxDb; Q99549; -.
DR PeptideAtlas; Q99549; -.
DR PRIDE; Q99549; -.
DR ProteomicsDB; 78321; -. [Q99549-1]
DR ProteomicsDB; 78322; -. [Q99549-2]
DR ABCD; Q99549; 2 sequenced antibodies.
DR Antibodypedia; 22243; 103 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 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; FAISCEF; -.
DR OrthoDB; 1628171at2759; -.
DR PhylomeDB; Q99549; -.
DR TreeFam; TF106394; -.
DR PathwayCommons; Q99549; -.
DR SignaLink; Q99549; -.
DR BioGRID-ORCS; 54737; 111 hits in 1082 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 194 other tissues.
DR ExpressionAtlas; Q99549; baseline and differential.
DR Genevisible; Q99549; 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: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:0035064; F:methylated histone binding; IDA: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:0045892; P:negative regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0090309; P:positive regulation of DNA methylation-dependent heterochromatin assembly; IDA:UniProtKB.
DR GO; GO:0044030; P:regulation of DNA methylation; IMP:UniProtKB.
DR Gene3D; 1.25.40.20; -; 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 Pfam; PF12796; Ank_2; 2.
DR Pfam; PF00385; Chromo; 1.
DR SMART; SM00248; ANK; 4.
DR SMART; SM00298; CHROMO; 1.
DR SUPFAM; SSF48403; SSF48403; 1.
DR SUPFAM; SSF54160; SSF54160; 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.
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
