ID MPP8_MOUSE Reviewed; 858 AA.
AC Q3TYA6; A6H600; Q3TWY7;
DT 21-MAR-2012, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 27-MAR-2024, entry version 143.
DE RecName: Full=M-phase phosphoprotein 8 {ECO:0000250|UniProtKB:Q99549};
GN Name=Mphosph8 {ECO:0000250|UniProtKB:Q99549, ECO:0000312|MGI:MGI:1922589};
GN Synonyms=Mpp8 {ECO:0000250|UniProtKB:Q99549};
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]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Visual cortex;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
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]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-51, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-51; SER-85; SER-136; SER-138;
RP THR-144; SER-267 AND SER-271, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Lung, Pancreas, 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 [7]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
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 [8]
RP INTERACTION WITH TASOR, AND TISSUE SPECIFICITY.
RX PubMed=31112734; DOI=10.1016/j.yexcr.2019.05.018;
RA Gresakova V., Novosadova V., Prochazkova M., Bhargava S., Jenickova I.,
RA Prochazka J., Sedlacek R.;
RT "Fam208a orchestrates interaction protein network essential for early
RT embryonic development and cell division.";
RL Exp. Cell Res. 382:111437-111437(2019).
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. Mediates
CC recruitment of the HUSH complex to H3K9me3 sites: the HUSH complex is
CC recruited to genomic loci rich in H3K9me3 and is required to maintain
CC transcriptional silencing by promoting recruitment of SETDB1, a histone
CC methyltransferase that mediates further deposition of H3K9me3, as well
CC as MORC2. Binds H3K9me and promotes DNA methylation by recruiting
CC DNMT3A to target CpG sites; these can be situated within the coding
CC region of the gene. Mediates down-regulation of CDH1 expression. 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. The HUSH complex is also involved
CC in the silencing of unintegrated retroviral DNA by being recruited by
CC ZNF638: some part of the retroviral DNA formed immediately after
CC infection remains unintegrated in the host genome and is
CC transcriptionally repressed. {ECO:0000250|UniProtKB:Q99549}.
CC -!- SUBUNIT: Homodimer. Interacts (via chromo domain) with histone H3K9me3.
CC Has the highest affinity for H3K9me3, and lesser affinity for H3K9me2
CC and H3K9me1. Component of the HUSH complex; at least composed of TASOR,
CC PPHLN1 and MPHOSPH8. Interacts with DNMT3, EHMT1 and SETDB1. Interacts
CC with MORC2; the interaction associateS MORC2 with the HUSH complex
CC which recruits MORC2 to heterochromatic loci. Interacts with ZNF638;
CC leading to recruitment of the HUSH complex to unintegrated retroviral
CC DNA (By similarity). Interacts with TASOR (PubMed:31112734).
CC {ECO:0000250|UniProtKB:Q99549, ECO:0000269|PubMed:31112734}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:23416073}. Chromosome
CC {ECO:0000269|PubMed:23416073}. Note=Detected on heterochromatin
CC (PubMed:23416073). Dissociates from chromatin during interphase and
CC early mitosis (PubMed:23416073). Detected on nucleosomes (By
CC similarity). {ECO:0000250|UniProtKB:Q99549,
CC ECO:0000269|PubMed:23416073}.
CC -!- TISSUE SPECIFICITY: Expressed in the spermatogonia, spermatocytes and
CC granular cells within the cerebellum. {ECO:0000269|PubMed:31112734}.
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:0000250|UniProtKB:Q99549}.
CC -!- PTM: Phosphorylated in M (mitotic) phase. Phosphorylation by CDK1
CC promotes dissociation from chromatin. {ECO:0000250|UniProtKB:Q99549}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI45701.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK158773; BAE34657.1; -; mRNA.
DR EMBL; AK159495; BAE35129.1; -; mRNA.
DR EMBL; AC154731; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466535; EDL36192.1; -; Genomic_DNA.
DR EMBL; BC145700; AAI45701.1; ALT_INIT; mRNA.
DR CCDS; CCDS49504.1; -.
DR RefSeq; NP_076262.2; NM_023773.2.
DR AlphaFoldDB; Q3TYA6; -.
DR SMR; Q3TYA6; -.
DR BioGRID; 217406; 3.
DR STRING; 10090.ENSMUSP00000112170; -.
DR iPTMnet; Q3TYA6; -.
DR PhosphoSitePlus; Q3TYA6; -.
DR SwissPalm; Q3TYA6; -.
DR EPD; Q3TYA6; -.
DR jPOST; Q3TYA6; -.
DR MaxQB; Q3TYA6; -.
DR PaxDb; 10090-ENSMUSP00000112170; -.
DR PeptideAtlas; Q3TYA6; -.
DR ProteomicsDB; 291437; -.
DR Pumba; Q3TYA6; -.
DR Antibodypedia; 22243; 125 antibodies from 29 providers.
DR DNASU; 75339; -.
DR Ensembl; ENSMUST00000116468.2; ENSMUSP00000112170.2; ENSMUSG00000079184.11.
DR GeneID; 75339; -.
DR KEGG; mmu:75339; -.
DR UCSC; uc011zmc.1; mouse.
DR AGR; MGI:1922589; -.
DR CTD; 54737; -.
DR MGI; MGI:1922589; Mphosph8.
DR VEuPathDB; HostDB:ENSMUSG00000079184; -.
DR eggNOG; KOG0504; Eukaryota.
DR eggNOG; KOG1911; Eukaryota.
DR GeneTree; ENSGT00730000111087; -.
DR HOGENOM; CLU_332588_0_0_1; -.
DR InParanoid; Q3TYA6; -.
DR OMA; QKNQDKG; -.
DR OrthoDB; 3061686at2759; -.
DR PhylomeDB; Q3TYA6; -.
DR TreeFam; TF106394; -.
DR BioGRID-ORCS; 75339; 9 hits in 81 CRISPR screens.
DR ChiTaRS; Mphosph8; mouse.
DR PRO; PR:Q3TYA6; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q3TYA6; Protein.
DR Bgee; ENSMUSG00000079184; Expressed in animal zygote and 255 other cell types or tissues.
DR Genevisible; Q3TYA6; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0000792; C:heterochromatin; ISS:UniProtKB.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0000786; C:nucleosome; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0003682; F:chromatin binding; ISO:MGI.
DR GO; GO:0140566; F:histone reader activity; IEA:Ensembl.
DR GO; GO:0035064; F:methylated histone binding; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISO:MGI.
DR GO; GO:0044027; P:negative regulation of gene expression via CpG island methylation; 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; ISS:UniProtKB.
DR GO; GO:0090309; P:positive regulation of DNA methylation-dependent heterochromatin formation; ISS:UniProtKB.
DR GO; GO:0044030; P:regulation of DNA methylation; ISO:MGI.
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 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; 3.
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.
PE 1: Evidence at protein level;
KW ANK repeat; Chromosome; Nucleus; Phosphoprotein; Reference proteome;
KW Repeat; Transcription; Transcription regulation.
FT CHAIN 1..858
FT /note="M-phase phosphoprotein 8"
FT /id="PRO_0000415976"
FT DOMAIN 59..118
FT /note="Chromo"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00053"
FT REPEAT 598..627
FT /note="ANK 1"
FT REPEAT 631..660
FT /note="ANK 2"
FT REPEAT 664..693
FT /note="ANK 3"
FT REPEAT 697..726
FT /note="ANK 4"
FT REGION 18..55
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 80..87
FT /note="Histone H3K9me3 binding"
FT /evidence="ECO:0000250|UniProtKB:Q99549"
FT REGION 129..175
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 209..234
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 250..300
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 321..431
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 159..175
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 284..300
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 335..367
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 368..391
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 392..431
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:0000250|UniProtKB:Q99549"
FT MOD_RES 51
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 85
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 136
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 138
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 144
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 149
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000250|UniProtKB:Q99549"
FT MOD_RES 164
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000250|UniProtKB:Q99549"
FT MOD_RES 188
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99549"
FT MOD_RES 267
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 271
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 278
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99549"
FT MOD_RES 318
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99549"
FT MOD_RES 385
FT /note="Phosphothreonine; by CDK1"
FT /evidence="ECO:0000250|UniProtKB:Q99549"
FT MOD_RES 392
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99549"
FT MOD_RES 400
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99549"
FT MOD_RES 453
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q99549"
FT CONFLICT 158
FT /note="K -> E (in Ref. 1; BAE35129)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 858 AA; 97467 MW; 17C90A836A416964 CRC64;
MAAAAEEGMS AAALVMSVPD SIGRSPESEG VGAGDEEKDA ATKGTVAVGD SEEDGEDVFE
VERILDMKCE GGKNLYKVRW KGYTSEDDTW EPEVHLEDCK EVLLEFRKKL AENKAKAVRK
DIQRLSLNND IFEADSDSDQ QSDTKEDISP RKKKKKIKCK EETSPEDLRK KRTKMGKLKD
KFKTELESTS EIIGFDVKTK KRIWEVKEEL KDSKKPKKDE IKETKELKKA NKRAEVRDLK
IKIREDVKEN RKTKKERYIE SPLESESPND SLILEDDSED FISDNREENQ NVRSVRDKTA
QETVQEGIFE KHLDDLISIE EDAGTRVRRK KTKPRKFEEP KEIKKLESTN AFLERRAIPK
KQRNQDKGIS NLELNKLPSP VFAQTLKSSR LSGEEKSLKS PDLAEEEKEK KNEPKGKYQK
RYDLDKEEKA RKEPKVLKSF KEIRNAFDLF KKTTEEKNDV LENNSKREEI SLDSKIMNDN
KTKDKCSLKE KRNTRDETDT WAYIAAEGDQ EVSDSVCQTD ETSDGRQPVL SLGMDLQLEW
MKLEDFQKHL DGEDEPFITT NRIPNNLLRD AVKNGDYIAV KVALNSNEEY NLDQEDSTGM
TLVMLAAAGG QDDLLRLLIT KGAKVNGRQK NGTTALIHAA EKNFLTTVAI LLEAGAFVNV
QQSNGETALM KACKRGNSDI VRLVIECGAD CNILSKHQNS ALYFAKQCNN VLVYELLKSH
LETLSRVAEE TIRDYFESRL ALLEPVFPIA CHRLCEGPDF STDFNYMPPQ NMPEGSGVLL
FIFHANFLGK DVIARLCGPC SVQAVVLNDK FQLPVFLDSH FVYSFSPVAG PNKLFIRLTE
APFAKVKLLI GAYRVQLQ
//
