MPHOSPH8
entrez
54737
canonical
uniprot
Q99549
canonical
ensembl
ENSG00000196199
resolver
ensp
ENSP00000355388
resolver
ensp
ENSP00000684860
resolver
ensp
ENSP00000684862
resolver
genesymbol
MPHOSPH8
resolver
genesymbol_syn
MPP8
resolver
hgnc
HGNC:29810
resolver
uniprot
B7Z6F9
resolver
uniprot
Q5JPE5
resolver
uniprot
Q5JTQ0
resolver
uniprot
Q86TK3
resolver
uniprot
Q96MK4
resolver
uniprot
Q9BTP1
resolver
uniprot_entry
MPP8_HUMAN
resolver
uniprot_sec
B7Z6F9
resolver
uniprot_sec
Q5JPE5
resolver
uniprot_sec
Q5JTQ0
resolver
uniprot_sec
Q86TK3
resolver
uniprot_sec
Q96MK4
resolver
uniprot_sec
Q9BTP1
resolver
amino_acid_sequence
MEQVAEGARVTAVPVSAADSTEELAEVEEGVGVVGEDNDAAARGAEAFGDSEEDGEDVFEVEKILDMKTEGGKVLYKVRWKGYTSDDDTWEPEIHLEDCKEVLLEFRKKIAENKAKAVRKDIQRLSLNNDIFEANSDSDQQSETKEDTSPKKKKKKLRQREEKSPDDLKKKKAKAGKLKDKSKPDLESSLESLVFDLRTKKRISEAKEELKESKKPKKDEVKETKELKKVKKGEIRDLKTKTREDPKENRKTKKEKFVESQVESESSVLNDSPFPEDDSEGLHSDSREEKQNTKSARERAGQDMGLEHGFEKPLDSAMSAEEDTDVRGRRKKKTPRKAEDTRENRKLENKNAFLEKKTVPKKQRNQDRSKSAAELEKLMPVSAQTPKGRRLSGEERGLWSTDSAEEDKETKRNESKEKYQKRHDSDKEEKGRKEPKGLKTLKEIRNAFDLFKLTPEEKNDVSENNRKREEIPLDFKTIDDHKTKENKQSLKERRNTRDETDTWAYIAAEGDQEVLDSVCQADENSDGRQQILSLGMDLQLEWMKLEDFQKHLDGKDENFAATDAIPSNVLRDAVKNGDYITVKVALNSNEEYNLDQEDSSGMTLVMLAAAGGQDDLLRLLITKGAKVNGRQKNGTTALIHAAEKNFLTTVAILLEAGAFVNVQQSNGETALMKACKRGNSDIVRLVIECGADCNILSKHQNSALHFAKQSNNVLVYDLLKNHLETLSRVAEETIKDYFEARLALLEPVFPIACHRLCEGPDFSTDFNYKPPQNIPEGSGILLFIFHANFLGKEVIARLCGPCSVQAVVLNDKFQLPVFLDSHFVYSFSPVAGPNKLFIRLTEAPSAKVKLLIGAYRVQLQ
uniprot
proteins
function
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). {ECO:0000269|PubMed:20871592, ECO:0000269|PubMed:26022416, ECO:0000269|PubMed:28581500, ECO:0000269|PubMed:29211708, ECO:0000269|PubMed:30487602, ECO:0000269|PubMed:33144593, ECO:0000269|PubMed:39013473}.
uniprot
proteins
mass_dalton
97182
uniprot
proteins
mutagenesis
MUTAGEN 80; /note="W->A: Abolishes interaction with histone H3K9me3 and prevents recruitment of the HUSH complex to heterochromatin. Impaired ability to mediate silencing of unintegrated retroviral DNA."; /evidence="ECO:0000269|PubMed:20871592, ECO:0000269|PubMed:26022416, ECO:0000269|PubMed:30487602"; MUTAGEN 149; /note="S->A: In STA mutant; fails to dissociate from chromatin during early mitosis; when associated with A-164; A-334 and A-385."; /evidence="ECO:0000269|PubMed:23416073"; MUTAGEN 164; /note="S->A: In STA mutant; fails to dissociate from chromatin during early mitosis; when associated with A-149; A-334 and A-385."; /evidence="ECO:0000269|PubMed:23416073"; MUTAGEN 334; /note="T->A: In STA mutant; fails to dissociate from chromatin during early mitosis; when associated with A-149; A-164 and A-385."; /evidence="ECO:0000269|PubMed:23416073"; MUTAGEN 385; /note="T->A: In STA mutant; fails to dissociate from chromatin during early mitosis; when associated with A-149; A-164; and A-334."; /evidence="ECO:0000269|PubMed:23416073
uniprot
proteins
post_translational_modification
PTM: Phosphorylated in M (mitotic) phase. Phosphorylation by CDK1 promotes dissociation from chromatin. {ECO:0000269|PubMed:23416073, ECO:0000269|PubMed:8885239}.
uniprot
proteins
pubmed
12559565
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15057823
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18318008
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20871592
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
21419134
uniprot
proteins
pubmed
22022377
uniprot
proteins
pubmed
22086334
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23416073
uniprot
proteins
pubmed
23532874
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
26022416
uniprot
proteins
pubmed
28581500
uniprot
proteins
pubmed
29211708
uniprot
proteins
pubmed
30487602
uniprot
proteins
pubmed
33144593
uniprot
proteins
pubmed
34415726
uniprot
proteins
pubmed
39013473
uniprot
proteins
pubmed
39489739
uniprot
proteins
pubmed
39638237
uniprot
proteins
pubmed
8885239
uniprot
proteins
sequence_length
860
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20871592, ECO:0000269|PubMed:23416073, ECO:0000269|PubMed:26022416, ECO:0000269|PubMed:28581500, ECO:0000269|PubMed:39013473, ECO:0000269|PubMed:39489739, ECO:0000269|PubMed:8885239}. Chromosome {ECO:0000269|PubMed:23416073, ECO:0000269|PubMed:26022416, ECO:0000269|PubMed:28581500, ECO:0000269|PubMed:34415726, ECO:0000269|PubMed:39013473, ECO:0000269|PubMed:39489739}. Note=Detected on heterochromatin (PubMed:20871592, PubMed:26022416, PubMed:34415726). Dissociates from chromatin during interphase and early mitosis (PubMed:23416073). Detected on nucleosomes (PubMed:20871592). {ECO:0000269|PubMed:20871592, ECO:0000269|PubMed:23416073, ECO:0000269|PubMed:26022416}.
uniprot
proteins