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Details on Person UniProt:Q99549 MPHOSPH8
| Class:Id | ReferenceGeneProduct:59529 |
|---|---|
| _chainChangeLog | chain:1-860 added on Fri February 6 2015 |
| _displayName | UniProt:Q99549 MPHOSPH8 |
| _timestamp | 2026-02-20 21:32:02 |
| chain | chain:1-860 |
| checksum | DD75D14C3DBF5E95 |
| comment | 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).SUBUNIT Homodimer (PubMed:21419134, PubMed:22022377, PubMed:22086334, PubMed:39638237). Interacts (via chromo domain) with histone H3K9me3 (PubMed:20871592). Has the highest affinity for H3K9me3, and lesser affinity for H3K9me2 and H3K9me1 (PubMed:20871592). Component of the HUSH complex; composed of TASOR, PPHLN1 and MPHOSPH8 (PubMed:26022416, PubMed:39013473, PubMed:39489739). Component of the HUSH2 complex; composed of TASOR2, PPHLN1 and MPHOSPH8 (PubMed:39013473, PubMed:39489739). Interacts with DNMT3, EHMT1 and SETDB1 (PubMed:20871592, PubMed:22086334). Interacts with MORC2; the interaction associates MORC2 with the HUSH complex which recruits MORC2 to heterochromatic loci (PubMed:28581500). Interacts with ZNF638; leading to recruitment of the HUSH complex to unintegrated retroviral DNA (PubMed:30487602). Interacts with humanin (PubMed:23532874). Interacts with HDGFL2 (PubMed:34415726).INTERACTION Detected on heterochromatin (PubMed:20871592, PubMed:26022416, PubMed:34415726). Dissociates from chromatin during interphase and early mitosis (PubMed:23416073). Detected on nucleosomes (PubMed:20871592).ALTERNATIVE PRODUCTS The chromo domain mediates interaction with methylated 'Lys-9' of histone H3 (H3K9me), with the highest affinity for the trimethylated form (H3K9me3).PTM Phosphorylated in M (mitotic) phase. Phosphorylation by CDK1 promotes dissociation from chromatin.SEQUENCE CAUTION Truncated N-terminus.SEQUENCE CAUTION Truncated N-terminus. |
| description | recommendedName: fullName evidence="23"M-phase phosphoprotein 8 alternativeName: fullName evidence="20"Two hybrid-associated protein 3 with RanBPM shortName evidence="20"Twa3 |
| geneName | MPHOSPH8 MPP8 |
| identifier | Q99549 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Acetylation Alternative splicing ANK repeat Chromosome Disulfide bond Nucleus Phosphoprotein Proteomics identification Reference proteome Repeat Repressor Transcription Transcription regulation |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | MPHOSPH8 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8962228] ENSEMBL:ENSG00000196199 MPHOSPH8 [Homo sapiens] |
| secondaryIdentifier | MPP8_HUMAN B7Z6F9 Q5JPE5 Q5JTQ0 Q86TK3 Q96MK4 Q9BTP1 |
| sequenceLength | 860 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:237809] UniProt:Q99549-2 MPHOSPH8 [Homo sapiens] [ReferenceIsoform:413149] UniProt:Q99549-1 MPHOSPH8 [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:9844052] MPHOSPH8 [nucleoplasm] [Homo sapiens] |
| [Change default viewing format] | |
No pathways have been reviewed or authored by UniProt:Q99549 MPHOSPH8 (59529)
