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Protein

M-phase phosphoprotein 8

Gene

MPHOSPH8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

  • methylated histone binding Source: UniProtKB

GO - Biological processi

  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • regulation of DNA methylation Source: UniProtKB

Keywordsi

Molecular functionRepressor
Biological processTranscription, Transcription regulation

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

EuPathDBiHostDB:ENSG00000196199.13
HGNCiHGNC:29810 MPHOSPH8
MIMi611626 gene
neXtProtiNX_Q99549

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
ProteomicsDBi78321
78322 [Q99549-2]

PTM databases

iPTMnetiQ99549
PhosphoSitePlusiQ99549

Expressioni

Gene expression databases

BgeeiENSG00000196199 Expressed in 223 organ(s), highest expression level in frontal cortex
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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi120119, 64 interactors
CORUMiQ99549
DIPiDIP-56224N
IntActiQ99549, 51 interactors
MINTiQ99549
STRINGi9606.ENSP00000355388

Structurei

Secondary structure

1860
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Keywords - Domaini

ANK repeat, Repeat

Phylogenomic databases

eggNOGiKOG0504 Eukaryota
KOG1911 Eukaryota
COG0666 LUCA
GeneTreeiENSGT00730000111087
HOGENOMiHOG000290641
HOVERGENiHBG052503
InParanoidiQ99549
KOiK21871
OMAiKYQKRHD
OrthoDBiEOG091G02M0
PhylomeDBiQ99549
TreeFamiTF106394

Family and domain databases

CDDicd00204 ANK, 1 hit
cd00024 CHROMO, 1 hit
Gene3Di1.25.40.20, 1 hit
InterProiView protein in InterPro
IPR002110 Ankyrin_rpt
IPR020683 Ankyrin_rpt-contain_dom
IPR036770 Ankyrin_rpt-contain_sf
IPR016197 Chromo-like_dom_sf
IPR000953 Chromo/chromo_shadow_dom
IPR023780 Chromo_domain
IPR023779 Chromodomain_CS
PfamiView protein in Pfam
PF12796 Ank_2, 2 hits
PF00385 Chromo, 1 hit
SMARTiView protein in SMART
SM00248 ANK, 4 hits
SM00298 CHROMO, 1 hit
SUPFAMiSSF48403 SSF48403, 1 hit
SSF54160 SSF54160, 1 hit
PROSITEiView protein in PROSITE
PS50297 ANK_REP_REGION, 1 hit
PS50088 ANK_REPEAT, 3 hits
PS00598 CHROMO_1, 1 hit
PS50013 CHROMO_2, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

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

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0A0MT47A0A0A0MT47_HUMAN
M-phase phosphoprotein 8
MPHOSPH8
311Annotation score:
H0Y6J1H0Y6J1_HUMAN
M-phase phosphoprotein 8
MPHOSPH8
150Annotation score:

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.
AL354808 Genomic DNA No translation available.
AL359457 Genomic DNA No translation available.
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

Similar proteinsi

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.
AL354808 Genomic DNA No translation available.
AL359457 Genomic DNA No translation available.
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, 64 interactors
CORUMiQ99549
DIPiDIP-56224N
IntActiQ99549, 51 interactors
MINTiQ99549
STRINGi9606.ENSP00000355388

Chemistry databases

ChEMBLiCHEMBL1741210

PTM databases

iPTMnetiQ99549
PhosphoSitePlusiQ99549

Polymorphism and mutation databases

BioMutaiMPHOSPH8
DMDMi93204602

Proteomic databases

EPDiQ99549
MaxQBiQ99549
PaxDbiQ99549
PeptideAtlasiQ99549
PRIDEiQ99549
ProteomicsDBi78321
78322 [Q99549-2]

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
EuPathDBiHostDB:ENSG00000196199.13
GeneCardsiMPHOSPH8
H-InvDBiHIX0171874
HGNCiHGNC:29810 MPHOSPH8
HPAiHPA039701
HPA040035
MIMi611626 gene
neXtProtiNX_Q99549
OpenTargetsiENSG00000196199
PharmGKBiPA162396090
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0504 Eukaryota
KOG1911 Eukaryota
COG0666 LUCA
GeneTreeiENSGT00730000111087
HOGENOMiHOG000290641
HOVERGENiHBG052503
InParanoidiQ99549
KOiK21871
OMAiKYQKRHD
OrthoDBiEOG091G02M0
PhylomeDBiQ99549
TreeFamiTF106394

Miscellaneous databases

ChiTaRSiMPHOSPH8 human
EvolutionaryTraceiQ99549
GeneWikiiMPHOSPH8
GenomeRNAii54737
PROiPR:Q99549
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000196199 Expressed in 223 organ(s), highest expression level in frontal cortex
CleanExiHS_MPHOSPH8
ExpressionAtlasiQ99549 baseline and differential
GenevisibleiQ99549 HS

Family and domain databases

CDDicd00204 ANK, 1 hit
cd00024 CHROMO, 1 hit
Gene3Di1.25.40.20, 1 hit
InterProiView protein in InterPro
IPR002110 Ankyrin_rpt
IPR020683 Ankyrin_rpt-contain_dom
IPR036770 Ankyrin_rpt-contain_sf
IPR016197 Chromo-like_dom_sf
IPR000953 Chromo/chromo_shadow_dom
IPR023780 Chromo_domain
IPR023779 Chromodomain_CS
PfamiView protein in Pfam
PF12796 Ank_2, 2 hits
PF00385 Chromo, 1 hit
SMARTiView protein in SMART
SM00248 ANK, 4 hits
SM00298 CHROMO, 1 hit
SUPFAMiSSF48403 SSF48403, 1 hit
SSF54160 SSF54160, 1 hit
PROSITEiView protein in PROSITE
PS50297 ANK_REP_REGION, 1 hit
PS50088 ANK_REPEAT, 3 hits
PS00598 CHROMO_1, 1 hit
PS50013 CHROMO_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiMPP8_HUMAN
AccessioniPrimary (citable) accession number: Q99549
Secondary accession number(s): B7Z6F9
, Q5JPE5, Q5JTQ0, Q86TK3, Q96MK4, Q9BTP1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: February 1, 2005
Last modified: November 7, 2018
This is version 154 of the entry and version 2 of the sequence. See 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. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Human chromosome 13
    Human chromosome 13: entries, gene names and cross-references to MIM
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