Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

M-phase phosphoprotein 8

Gene

MPHOSPH8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Heterochromatin component that specifically recognizes and binds methylated 'Lys-9' of histone H3 (H3K9me) and promotes recruitment of proteins that mediate epigenetic repression (PubMed:20871592, PubMed:26022416). Mediates recruitment of the HUSH complex to H3K9me3 sites: the HUSH complex is recruited to genomic loci rich in H3K9me3 and is probably required to maintain transcriptional silencing by promoting recruitment of SETDB1, a histone methyltransferase that mediates further deposition of H3K9me3 (PubMed:26022416). 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 down-regulation of CDH1 expression (PubMed:20871592).2 Publications

GO - Molecular functioni

GO - Biological processi

  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • regulation of DNA methylation Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Enzyme and pathway databases

BioCyciZFISH:G66-33226-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
M-phase phosphoprotein 8
Alternative name(s):
Two hybrid-associated protein 3 with RanBPM1 Publication
Short name:
Twa31 Publication
Gene namesi
Name:MPHOSPH8Imported
Synonyms:MPP8
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 13

Organism-specific databases

HGNCiHGNC:29810. MPHOSPH8.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • nuclear heterochromatin Source: UniProtKB
  • nuclear nucleosome Source: UniProtKB
  • nucleolus Source: HPA
  • nucleus Source: UniProtKB
  • plasma membrane Source: HPA
  • ubiquitin ligase complex Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi80W → A: Abolishes interaction with histone H3K9me3 and prevents recruitment of the HUSH complex to heterochromatin. 2 Publications1
Mutagenesisi149S → A in STA mutant; fails to dissociate from chromatin during early mitosis; when associated with A-164; A-334 and A-385. 1 Publication1
Mutagenesisi164S → A in STA mutant; fails to dissociate from chromatin during early mitosis; when associated with A-149; A-334 and A-385. 1 Publication1
Mutagenesisi334T → A in STA mutant; fails to dissociate from chromatin during early mitosis; when associated with A-149; A-164 and A-385. 1 Publication1
Mutagenesisi385T → A in STA mutant; fails to dissociate from chromatin during early mitosis; when associated with A-149; A-164; and A-334. 1 Publication1

Organism-specific databases

DisGeNETi54737.
OpenTargetsiENSG00000196199.
PharmGKBiPA162396090.

Chemistry databases

ChEMBLiCHEMBL1741210.

Polymorphism and mutation databases

BioMutaiMPHOSPH8.
DMDMi93204602.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000802441 – 860M-phase phosphoprotein 8Add BLAST860

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei51PhosphoserineCombined sources1
Modified residuei85PhosphoserineBy similarity1
Modified residuei136PhosphoserineCombined sources1
Modified residuei138PhosphoserineCombined sources1
Modified residuei144PhosphothreonineBy similarity1
Modified residuei149Phosphoserine; by CDK1Combined sources1 Publication1
Modified residuei164Phosphoserine; by CDK11 Publication1
Modified residuei188PhosphoserineCombined sources1
Modified residuei189PhosphoserineCombined sources1
Modified residuei192PhosphoserineCombined sources1
Modified residuei266PhosphoserineBy similarity1
Modified residuei272PhosphoserineCombined sources1
Modified residuei279PhosphoserineCombined sources1
Modified residuei319PhosphoserineCombined sources1
Modified residuei334Phosphothreonine; by CDK11 Publication1
Modified residuei385Phosphothreonine; by CDK11 Publication1
Modified residuei392PhosphoserineCombined sources1
Modified residuei400PhosphoserineCombined sources1
Modified residuei403PhosphoserineCombined sources1
Modified residuei454PhosphothreonineCombined sources1

Post-translational modificationi

Phosphorylated in M (mitotic) phase. Phosphorylation by CDK1 promotes dissociation from chromatin.2 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ99549.
MaxQBiQ99549.
PaxDbiQ99549.
PeptideAtlasiQ99549.
PRIDEiQ99549.

PTM databases

iPTMnetiQ99549.
PhosphoSitePlusiQ99549.

Expressioni

Gene expression databases

BgeeiENSG00000196199.
CleanExiHS_MPHOSPH8.
ExpressionAtlasiQ99549. baseline and differential.
GenevisibleiQ99549. HS.

Organism-specific databases

HPAiHPA039701.
HPA040035.

Interactioni

Subunit structurei

Homodimer (PubMed:21419134, PubMed:22022377, PubMed:22086334). 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; at least composed of FAM208A/TASOR, PPHLN1 and MPHOSPH8 (PubMed:26022416). Interacts with DNMT3, EHMT1 and SETDB1 (PubMed:20871592, PubMed:22086334).5 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei59Interaction with histone H3K9me31 Publication1

Binary interactionsi

WithEntry#Exp.IntActNotes
EHMT1Q9H9B13EBI-2653928,EBI-766087
HIST1H3DP684315EBI-2653928,EBI-79722
SETDB1Q150472EBI-2653928,EBI-79691

GO - Molecular functioni

  • methylated histone binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: GO_Central

Protein-protein interaction databases

BioGridi120119. 62 interactors.
DIPiDIP-56224N.
IntActiQ99549. 51 interactors.
MINTiMINT-6943098.
STRINGi9606.ENSP00000355388.

Structurei

Secondary structure

1860
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi61 – 70Combined sources10
Beta strandi73 – 80Combined sources8
Helixi85 – 87Combined sources3
Beta strandi89 – 92Combined sources4
Helixi93 – 96Combined sources4
Helixi100 – 114Combined sources15

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3LWEX-ray2.05A/B55-116[»]
3QO2X-ray2.49A/B/C/D55-116[»]
3R93X-ray2.06A/B/C/D55-116[»]
3SVMX-ray2.31A55-116[»]
ProteinModelPortaliQ99549.
SMRiQ99549.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ99549.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini59 – 118ChromoPROSITE-ProRule annotationAdd BLAST60
Repeati600 – 629ANK 1Add BLAST30
Repeati633 – 662ANK 2Add BLAST30
Repeati666 – 695ANK 3Add BLAST30
Repeati699 – 728ANK 4Add BLAST30

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni80 – 87Histone H3K9me3 binding1 Publication8

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi151 – 256Lys-richAdd BLAST106

Domaini

The chromo domain mediates interaction with methylated 'Lys-9' of histone H3 (H3K9me), with the highest affinity for the trimethylated form (H3K9me3).2 Publications

Sequence similaritiesi

Contains 4 ANK repeats.PROSITE-ProRule annotation
Contains 1 chromo domain.PROSITE-ProRule annotation

Keywords - Domaini

ANK repeat, Repeat

Phylogenomic databases

eggNOGiKOG0504. Eukaryota.
KOG1911. Eukaryota.
COG0666. LUCA.
GeneTreeiENSGT00730000111087.
HOGENOMiHOG000290641.
HOVERGENiHBG052503.
InParanoidiQ99549.
OMAiKYQKRHD.
OrthoDBiEOG091G02M0.
PhylomeDBiQ99549.
TreeFamiTF106394.

Family and domain databases

Gene3Di1.25.40.20. 1 hit.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR000953. Chromo/shadow_dom.
IPR023780. Chromo_domain.
IPR016197. Chromodomain-like.
IPR023779. Chromodomain_CS.
[Graphical view]
PfamiPF12796. Ank_2. 2 hits.
PF00385. Chromo. 1 hit.
[Graphical view]
SMARTiSM00248. ANK. 4 hits.
SM00298. CHROMO. 1 hit.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 1 hit.
SSF54160. SSF54160. 1 hit.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 3 hits.
PS00598. CHROMO_1. 1 hit.
PS50013. CHROMO_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q99549-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEQVAEGARV TAVPVSAADS TEELAEVEEG VGVVGEDNDA AARGAEAFGD
60 70 80 90 100
SEEDGEDVFE VEKILDMKTE GGKVLYKVRW KGYTSDDDTW EPEIHLEDCK
110 120 130 140 150
EVLLEFRKKI AENKAKAVRK DIQRLSLNND IFEANSDSDQ QSETKEDTSP
160 170 180 190 200
KKKKKKLRQR EEKSPDDLKK KKAKAGKLKD KSKPDLESSL ESLVFDLRTK
210 220 230 240 250
KRISEAKEEL KESKKPKKDE VKETKELKKV KKGEIRDLKT KTREDPKENR
260 270 280 290 300
KTKKEKFVES QVESESSVLN DSPFPEDDSE GLHSDSREEK QNTKSARERA
310 320 330 340 350
GQDMGLEHGF EKPLDSAMSA EEDTDVRGRR KKKTPRKAED TRENRKLENK
360 370 380 390 400
NAFLEKKTVP KKQRNQDRSK SAAELEKLMP VSAQTPKGRR LSGEERGLWS
410 420 430 440 450
TDSAEEDKET KRNESKEKYQ KRHDSDKEEK GRKEPKGLKT LKEIRNAFDL
460 470 480 490 500
FKLTPEEKND VSENNRKREE IPLDFKTIDD HKTKENKQSL KERRNTRDET
510 520 530 540 550
DTWAYIAAEG DQEVLDSVCQ ADENSDGRQQ ILSLGMDLQL EWMKLEDFQK
560 570 580 590 600
HLDGKDENFA ATDAIPSNVL RDAVKNGDYI TVKVALNSNE EYNLDQEDSS
610 620 630 640 650
GMTLVMLAAA GGQDDLLRLL ITKGAKVNGR QKNGTTALIH AAEKNFLTTV
660 670 680 690 700
AILLEAGAFV NVQQSNGETA LMKACKRGNS DIVRLVIECG ADCNILSKHQ
710 720 730 740 750
NSALHFAKQS NNVLVYDLLK NHLETLSRVA EETIKDYFEA RLALLEPVFP
760 770 780 790 800
IACHRLCEGP DFSTDFNYKP PQNIPEGSGI LLFIFHANFL GKEVIARLCG
810 820 830 840 850
PCSVQAVVLN DKFQLPVFLD SHFVYSFSPV AGPNKLFIRL TEAPSAKVKL
860
LIGAYRVQLQ
Length:860
Mass (Da):97,182
Last modified:February 1, 2005 - v2
Checksum:iDD75D14C3DBF5E95
GO
Isoform 2 (identifier: Q99549-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     820-860: DSHFVYSFSP...LIGAYRVQLQ → TGSRSVVQAG...GLKMHATTSG

Show »
Length:867
Mass (Da):97,637
Checksum:i5638702150529EA3
GO

Sequence cautioni

The sequence AAH46214 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAB71284 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence CAI46172 differs from that shown. Reason: Frameshift at positions 248, 255 and 731.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti526 – 530DGRQQ → GEFGI in CAA66912 (PubMed:8885239).Curated5
Sequence conflicti860Q → QPNRRDWAEFS in AAH46214 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_031523820 – 860DSHFV…RVQLQ → TGSRSVVQAGVQWRGLQLTG VLTSQAQAILPPQPPNYLGL KMHATTSG in isoform 2. 2 PublicationsAdd BLAST41

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK056785 mRNA. Translation: BAB71284.1. Different initiation.
AK300258 mRNA. Translation: BAH13245.1.
AL832864 mRNA. Translation: CAI46172.1. Frameshift.
AL359457, AL354808 Genomic DNA. Translation: CAI16671.1.
AL354808, AL359457 Genomic DNA. Translation: CAI41002.1.
CH471075 Genomic DNA. Translation: EAX08228.1.
CH471075 Genomic DNA. Translation: EAX08230.1.
BC003542 mRNA. Translation: AAH03542.2.
BC046214 mRNA. Translation: AAH46214.1. Different initiation.
X98259 mRNA. Translation: CAA66912.1.
CCDSiCCDS9287.1. [Q99549-1]
RefSeqiNP_059990.2. NM_017520.3. [Q99549-1]
UniGeneiHs.269654.

Genome annotation databases

EnsembliENST00000361479; ENSP00000355388; ENSG00000196199. [Q99549-1]
GeneIDi54737.
KEGGihsa:54737.
UCSCiuc001umh.4. human. [Q99549-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK056785 mRNA. Translation: BAB71284.1. Different initiation.
AK300258 mRNA. Translation: BAH13245.1.
AL832864 mRNA. Translation: CAI46172.1. Frameshift.
AL359457, AL354808 Genomic DNA. Translation: CAI16671.1.
AL354808, AL359457 Genomic DNA. Translation: CAI41002.1.
CH471075 Genomic DNA. Translation: EAX08228.1.
CH471075 Genomic DNA. Translation: EAX08230.1.
BC003542 mRNA. Translation: AAH03542.2.
BC046214 mRNA. Translation: AAH46214.1. Different initiation.
X98259 mRNA. Translation: CAA66912.1.
CCDSiCCDS9287.1. [Q99549-1]
RefSeqiNP_059990.2. NM_017520.3. [Q99549-1]
UniGeneiHs.269654.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3LWEX-ray2.05A/B55-116[»]
3QO2X-ray2.49A/B/C/D55-116[»]
3R93X-ray2.06A/B/C/D55-116[»]
3SVMX-ray2.31A55-116[»]
ProteinModelPortaliQ99549.
SMRiQ99549.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120119. 62 interactors.
DIPiDIP-56224N.
IntActiQ99549. 51 interactors.
MINTiMINT-6943098.
STRINGi9606.ENSP00000355388.

Chemistry databases

ChEMBLiCHEMBL1741210.

PTM databases

iPTMnetiQ99549.
PhosphoSitePlusiQ99549.

Polymorphism and mutation databases

BioMutaiMPHOSPH8.
DMDMi93204602.

Proteomic databases

EPDiQ99549.
MaxQBiQ99549.
PaxDbiQ99549.
PeptideAtlasiQ99549.
PRIDEiQ99549.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000361479; ENSP00000355388; ENSG00000196199. [Q99549-1]
GeneIDi54737.
KEGGihsa:54737.
UCSCiuc001umh.4. human. [Q99549-1]

Organism-specific databases

CTDi54737.
DisGeNETi54737.
GeneCardsiMPHOSPH8.
H-InvDBHIX0171874.
HGNCiHGNC:29810. MPHOSPH8.
HPAiHPA039701.
HPA040035.
MIMi611626. gene.
neXtProtiNX_Q99549.
OpenTargetsiENSG00000196199.
PharmGKBiPA162396090.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0504. Eukaryota.
KOG1911. Eukaryota.
COG0666. LUCA.
GeneTreeiENSGT00730000111087.
HOGENOMiHOG000290641.
HOVERGENiHBG052503.
InParanoidiQ99549.
OMAiKYQKRHD.
OrthoDBiEOG091G02M0.
PhylomeDBiQ99549.
TreeFamiTF106394.

Enzyme and pathway databases

BioCyciZFISH:G66-33226-MONOMER.

Miscellaneous databases

ChiTaRSiMPHOSPH8. human.
EvolutionaryTraceiQ99549.
GeneWikiiMPHOSPH8.
GenomeRNAii54737.
PROiQ99549.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000196199.
CleanExiHS_MPHOSPH8.
ExpressionAtlasiQ99549. baseline and differential.
GenevisibleiQ99549. HS.

Family and domain databases

Gene3Di1.25.40.20. 1 hit.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR000953. Chromo/shadow_dom.
IPR023780. Chromo_domain.
IPR016197. Chromodomain-like.
IPR023779. Chromodomain_CS.
[Graphical view]
PfamiPF12796. Ank_2. 2 hits.
PF00385. Chromo. 1 hit.
[Graphical view]
SMARTiSM00248. ANK. 4 hits.
SM00298. CHROMO. 1 hit.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 1 hit.
SSF54160. SSF54160. 1 hit.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 3 hits.
PS00598. CHROMO_1. 1 hit.
PS50013. CHROMO_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMPP8_HUMAN
AccessioniPrimary (citable) accession number: Q99549
Secondary accession number(s): B7Z6F9
, Q5JPE5, Q5JTQ0, Q86TK3, Q96MK4, Q9BTP1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: February 1, 2005
Last modified: November 2, 2016
This is version 140 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 13
    Human chromosome 13: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.