MPP8_RAT
ID MPP8_RAT Reviewed; 851 AA.
AC G3V8T1; Q4KLM1;
DT 21-MAR-2012, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2011, sequence version 1.
DT 03-AUG-2022, entry version 66.
DE RecName: Full=M-phase phosphoprotein 8 {ECO:0000250|UniProtKB:Q99549};
GN Name=Mphosph8 {ECO:0000312|RGD:1305133};
GN Synonyms=Mpp8 {ECO:0000250|UniProtKB:Q99549};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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).
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 (By similarity).
CC {ECO:0000250|UniProtKB:Q3TYA6, ECO:0000250|UniProtKB:Q99549}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q99549}.
CC Chromosome {ECO:0000250|UniProtKB:Q99549}. Note=Detected on
CC heterochromatin. Dissociates from chromatin during interphase and early
CC mitosis. Detected on nucleosomes. {ECO:0000250|UniProtKB:Q99549}.
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=AAH99116.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; CH474049; EDM14330.1; -; Genomic_DNA.
DR EMBL; BC099116; AAH99116.1; ALT_INIT; mRNA.
DR RefSeq; NP_001017375.2; NM_001017375.2.
DR AlphaFoldDB; G3V8T1; -.
DR SMR; G3V8T1; -.
DR STRING; 10116.ENSRNOP00000028145; -.
DR iPTMnet; G3V8T1; -.
DR PhosphoSitePlus; G3V8T1; -.
DR PaxDb; G3V8T1; -.
DR PRIDE; G3V8T1; -.
DR Ensembl; ENSRNOT00000028145; ENSRNOP00000028145; ENSRNOG00000061152.
DR GeneID; 290270; -.
DR KEGG; rno:290270; -.
DR CTD; 54737; -.
DR RGD; 1305133; Mphosph8.
DR eggNOG; KOG0504; Eukaryota.
DR eggNOG; KOG1911; Eukaryota.
DR GeneTree; ENSGT00940000160555; -.
DR HOGENOM; CLU_332588_0_0_1; -.
DR InParanoid; G3V8T1; -.
DR OrthoDB; 1628171at2759; -.
DR PRO; PR:G3V8T1; -.
DR Proteomes; UP000002494; Chromosome 15.
DR Proteomes; UP000234681; Chromosome 15.
DR Bgee; ENSRNOG00000051238; Expressed in ovary and 20 other tissues.
DR Genevisible; G3V8T1; RN.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0000792; C:heterochromatin; ISS:UniProtKB.
DR GO; GO:0000786; C:nucleosome; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0003682; F:chromatin binding; ISO:RGD.
DR GO; GO:0035064; F:methylated histone binding; 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:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0090309; P:positive regulation of DNA methylation-dependent heterochromatin assembly; ISS:UniProtKB.
DR GO; GO:0044030; P:regulation of DNA methylation; ISS:UniProtKB.
DR Gene3D; 1.25.40.20; -; 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 Pfam; PF12796; Ank_2; 2.
DR Pfam; PF00385; Chromo; 1.
DR SMART; SM00248; ANK; 3.
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 2: Evidence at transcript level;
KW ANK repeat; Chromosome; Nucleus; Phosphoprotein; Reference proteome;
KW Repeat; Transcription; Transcription regulation.
FT CHAIN 1..851
FT /note="M-phase phosphoprotein 8"
FT /id="PRO_0000415977"
FT DOMAIN 59..118
FT /note="Chromo"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00053"
FT REPEAT 591..620
FT /note="ANK 1"
FT REPEAT 624..653
FT /note="ANK 2"
FT REPEAT 657..686
FT /note="ANK 3"
FT REPEAT 690..719
FT /note="ANK 4"
FT REGION 21..54
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 133..174
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 240..302
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 315..428
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 159..174
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 240..259
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 275..302
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 329..364
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 386..428
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:0000250|UniProtKB:Q99549"
FT MOD_RES 85
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3TYA6"
FT MOD_RES 136
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99549"
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: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 263
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3TYA6"
FT MOD_RES 267
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99549"
FT MOD_RES 274
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99549"
FT MOD_RES 313
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99549"
FT MOD_RES 379
FT /note="Phosphothreonine; by CDK1"
FT /evidence="ECO:0000250|UniProtKB:Q99549"
FT MOD_RES 386
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99549"
FT MOD_RES 394
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99549"
FT MOD_RES 447
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q99549"
SQ SEQUENCE 851 AA; 96784 MW; A5DFDBCC343479A3 CRC64;
MAAATEENMS VAALVMSVPD NIGRSPEVEG GGAAGEEKDA ATKGTVAVGD SEEDGEDVFE
VERILDMKCE GGKNLYKVRW KGYTSDDDTW EPEVHLEDCK EVLLEFRKKV AENKAKAVRK
DIQKLSLNND IFEADSDIDQ QGDTKEDTSP RKKKKKIKYK EDKSPDDLRK KRAKMGKLKD
KFKTELESTS EILGFDVKTK KRILEVKEEL KDSKKPKKDE IKETKKTKRA DIRDLKIKIR
EDVKDNRKTK KERYIDSPLE SESPNDSFTL EDESEDFLSD NKEKQNVRTA KDKTGQDTVQ
ESIFEKHLDD LISIEEAGTR VRRKKKQPRK FEEPKEIKKL ENTNNFLERK MIPKKQRNQD
KGRSNPELSK LPSPVFAQTM KSLRLSGEEK GLKSSDLAEE EKERKNEPKE KYQKRYDFDK
EEKARKEPKG LKSFKEIRNA FDLFKKTAEE KNDLENNSKR EEISLDYKIT HDNKTKDKCS
LREERNTRDE TDTWAYIAAE GDQEVSDSVC QTDESSDGKQ PILSLGMDLQ LEWMKLEDFQ
KHLDGEDEPF ITANRIPSNL LRDAVKNGDY IAVKVALNSN EEYNLDQEDS TGMTLVMLAA
AGGQDDLLRL LITKGAKVNG RQKNGTTALI HAAEKNFLTT VAILLEAGAF VNVQQSNGET
ALMKACKRGN SDIVRLVIEC GADCNILSKH QNSALYFAKQ CNNVLVYELL KSHLETLSRV
AEETIRDYFE SRLALLEPVF PIACHRLCEG PDFSTDFNYM PPQNMPEGSG VLLFIFHANF
LGKDVIARLC GPCSVQAVVL NDKFQLPVFL DSHFVYSFSP VAGPNKLFIR LTEAPFAKVK
LLIGAYRVQL Q
