Search Results

Overview

Uniprot IDQ99549
Protein NameM-phase phosphoprotein 8
Gene NameMPHOSPH8
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
350 ENRKLENKNAFLEKK
356 NKNAFLEKKTVPKKQ
357 KNAFLEKKTVPKKQR
387 PVSAQTPKGRRLSGE

Function

Heterochromatin component that specifically recognizes and binds methylated 'Lys-9' of histone H3 (H3K9me) and promotes recruitment of proteins that mediate epigenetic repression (PubMed:26022416, PubMed:28581500, PubMed:29211708). As part of the HUSH complex, promotes epigenetic repression of mobile genetic elements, such as retroviruses and transposable elements: the HUSH complex mainly represses LINE-1 (L1) retrotransposons that are still capable of transposition (PubMed:29211708). Silencing events often occur within introns of transcriptionally active genes, and lead to the down-regulation of host gene expression (PubMed:29211708). MPHOSPH8 mediates recruitment of the HUSH complex to H3K9me3 sites: the HUSH complex is recruited to genomic loci rich in H3K9me3 and is required to maintain transcriptional silencing by promoting recruitment of SETDB1, a histone methyltransferase that mediates further deposition of H3K9me3, as well as MORC2, a chromatin remodeler that compacts chromatin (PubMed:26022416, PubMed:28581500). The HUSH complex is also involved in the silencing of unintegrated retroviral DNA by being recruited by ZNF638: some part of the retroviral DNA formed immediately after infection remains unintegrated in the host genome and is transcriptionally repressed (PubMed:30487602). As part of the HUSH2 complex, promotes epigenetic repression of interferon-stimulated genes (PubMed:33144593, PubMed:39013473). Binds H3K9me and promotes DNA methylation by recruiting DNMT3A to target CpG sites; these can be situated within the coding region of the gene (PubMed:20871592). Mediates silencing of E-cadherin (CDH1) and protocadherin genes in the nervous system (PubMed:20871592)

Protein Sequence

10 MEQVAEGARV 20 TAVPVSAADS 30 TEELAEVEEG 40 VGVVGEDNDA 50 AARGAEAFGD 60 SEEDGEDVFE 70 VEKILDMKTE 80 GGKVLYKVRW 90 KGYTSDDDTW 100 EPEIHLEDCK 110 EVLLEFRKKI 120 AENKAKAVRK 130 DIQRLSLNND 140 IFEANSDSDQ 150 QSETKEDTSP 160 KKKKKKLRQR 170 EEKSPDDLKK 180 KKAKAGKLKD 190 KSKPDLESSL 200 ESLVFDLRTK 210 KRISEAKEEL 220 KESKKPKKDE 230 VKETKELKKV 240 KKGEIRDLKT 250 KTREDPKENR 260 KTKKEKFVES 270 QVESESSVLN 280 DSPFPEDDSE 290 GLHSDSREEK 300 QNTKSARERA 310 GQDMGLEHGF 320 EKPLDSAMSA 330 EEDTDVRGRR 340 KKKTPRKAED 350 TRENRKLENK 360 NAFLEKKTVP 370 KKQRNQDRSK 380 SAAELEKLMP 390 VSAQTPKGRR 400 LSGEERGLWS 410 TDSAEEDKET 420 KRNESKEKYQ 430 KRHDSDKEEK 440 GRKEPKGLKT 450 LKEIRNAFDL 460 FKLTPEEKND 470 VSENNRKREE 480 IPLDFKTIDD 490 HKTKENKQSL 500 KERRNTRDET 510 DTWAYIAAEG 520 DQEVLDSVCQ 530 ADENSDGRQQ 540 ILSLGMDLQL 550 EWMKLEDFQK 560 HLDGKDENFA 570 ATDAIPSNVL 580 RDAVKNGDYI 590 TVKVALNSNE 600 EYNLDQEDSS 610 GMTLVMLAAA 620 GGQDDLLRLL 630 ITKGAKVNGR 640 QKNGTTALIH 650 AAEKNFLTTV 660 AILLEAGAFV 670 NVQQSNGETA 680 LMKACKRGNS 690 DIVRLVIECG 700 ADCNILSKHQ 710 NSALHFAKQS 720 NNVLVYDLLK 730 NHLETLSRVA 740 EETIKDYFEA 750 RLALLEPVFP 760 IACHRLCEGP 770 DFSTDFNYKP 780 PQNIPEGSGI 790 LLFIFHANFL 800 GKEVIARLCG 810 PCSVQAVVLN 820 DKFQLPVFLD 830 SHFVYSFSPV 840 AGPNKLFIRL 850 TEAPSAKVKL 860 LIGAYRVQLQ

Gene Ontology

Classification GO ID Description
Biological Process GO:0044027 negative regulation of gene expression via chromosomal CpG island methylation
Cellular Component GO:0000785 chromatin
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0000792 heterochromatin
Cellular Component GO:0140283 HUSH complex
Cellular Component GO:0140286 HUSH2 complex
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0000786 nucleosome
Cellular Component GO:0005634 nucleus
Molecular Function GO:0003682 chromatin binding
Molecular Function GO:0062072 histone H3K9me2/3 reader activity
Biological Process GO:0140719 constitutive heterochromatin formation
Biological Process GO:0006351 DNA-templated transcription
Biological Process GO:0045814 negative regulation of gene expression, epigenetic
Biological Process GO:0032480 negative regulation of type I interferon production
Biological Process GO:0141005 transposable element silencing by heterochromatin formation

Reference

[1] Yang D, Yin J, Shan L, Yi X, Zhang W et al.. Identification of lysine-lactylated substrates in gastric cancer cells.. iScience 25(7):104630. 2022 Jul 15. PMID: 35800753.

[2] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.