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Protein

E3 SUMO-protein ligase CBX4

Gene

CBX4

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

Functioni

E3 SUMO-protein ligase which facilitates SUMO1 conjugation by UBE2I (PubMed:12679040). Involved in the sumoylation of HNRNPK, a p53/TP53 transcriptional coactivator, hence indirectly regulates p53/TP53 transcriptional activation resulting in p21/CDKN1A expression. Monosumoylates ZNF131 (PubMed:22825850).2 Publications
Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development (PubMed:12167701, PubMed:19636380, PubMed:21282530). PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility (PubMed:12167701, PubMed:19636380, PubMed:21282530). Binds to histone H3 trimethylated at 'Lys-9' (H3K9me3) (By similarity). Plays a role in the lineage differentiation of the germ layers in embryonic development (By similarity).By similarity3 Publications

Miscellaneous

The human orthologs of the Drosophila Polycomb group protein Pc are CBX2, CBX4, CBX6, CBX7 and CBX8. These show distinct nuclear localizations, contribute differently to transcriptional repression, and appear to be part of distinct PRC1-like protein complexes. The hPRC-H complex purified in PubMed:12167701 probably presents a mixture of different complexes containing different Polycomb group proteins.

Pathwayi: protein sumoylation

This protein is involved in the pathway protein sumoylation, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein sumoylation and in Protein modification.

GO - Molecular functioni

  • chromatin binding Source: Ensembl
  • enzyme binding Source: UniProtKB
  • methylated histone binding Source: Ensembl
  • phosphoprotein binding Source: Ensembl
  • single-stranded RNA binding Source: Ensembl
  • SUMO binding Source: MGI
  • SUMO transferase activity Source: Reactome
  • transcription corepressor activity Source: ProtInc
  • transcription regulatory region DNA binding Source: Ensembl

GO - Biological processi

Keywordsi

Molecular functionChromatin regulator, Repressor, Transferase
Biological processTranscription, Transcription regulation, Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-HSA-2559580 Oxidative Stress Induced Senescence
R-HSA-3108214 SUMOylation of DNA damage response and repair proteins
R-HSA-3899300 SUMOylation of transcription cofactors
R-HSA-4551638 SUMOylation of chromatin organization proteins
R-HSA-4570464 SUMOylation of RNA binding proteins
R-HSA-4655427 SUMOylation of DNA methylation proteins
R-HSA-8939243 RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known
R-HSA-8943724 Regulation of PTEN gene transcription
SIGNORiO00257
UniPathwayi
UPA00886

Names & Taxonomyi

Protein namesi
Recommended name:
E3 SUMO-protein ligase CBX4 (EC:2.3.2.-)
Alternative name(s):
Chromobox protein homolog 4
Polycomb 2 homolog
Short name:
Pc2
Short name:
hPc2
Gene namesi
Name:CBX4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000141582.14
HGNCiHGNC:1554 CBX4
MIMi603079 gene
neXtProtiNX_O00257

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

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi16I → F: Reduced interaction with HIST2H3A, HIST1H3A and RNF2. 1 Publication1
Mutagenesisi434S → A: Abolishes interaction with YWHAZ and YWHAE; impairs interaction with PCGF6 and BMI1; no effect on interaction with RNF2. 1 Publication1
Mutagenesisi494K → R: No effect on ZNF131 sumoylation. 1 Publication1
Mutagenesisi497T → A: Small decrease in ZNF131 sumoylation. 1 Publication1

Organism-specific databases

DisGeNETi8535
OpenTargetsiENSG00000141582
PharmGKBiPA26129

Chemistry databases

ChEMBLiCHEMBL3232685

Polymorphism and mutation databases

BioMutaiCBX4

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000802061 – 560E3 SUMO-protein ligase CBX4Add BLAST560

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki77Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki106Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki114Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki125Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei149N6-acetyllysine; alternateCombined sources1
Cross-linki149Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Cross-linki157Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki167Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki178Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei182PhosphoserineCombined sources1
Cross-linki191Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki205Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki212Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki223Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki249Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki268Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki278Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki280Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki320Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki352Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki365Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei467PhosphoserineCombined sources1
Cross-linki494Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate1 Publication
Cross-linki494Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei497Phosphothreonine; by HIPK21 Publication1

Post-translational modificationi

Phosphorylated on Thr-497 by HIPK2 upon DNA damage. This phosphorylation stimulates E3 SUMO-protein ligase activity and promotes sumoylation on Lys-494, as well as sumoylation of other target proteins, such as HNRNPK.3 Publications

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO00257
MaxQBiO00257
PaxDbiO00257
PeptideAtlasiO00257
PRIDEiO00257
ProteomicsDBi47811
47812 [O00257-3]

PTM databases

iPTMnetiO00257
PhosphoSitePlusiO00257

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

BgeeiENSG00000141582 Expressed in 209 organ(s), highest expression level in bone marrow
CleanExiHS_CBX4
ExpressionAtlasiO00257 baseline and differential
GenevisibleiO00257 HS

Organism-specific databases

HPAiHPA008228
HPA012021

Interactioni

Subunit structurei

Interacts with histone H3-K9Me3 (By similarity). Interacts with CHTOP (By similarity). Component of a PRC1-like complex (PubMed:12167701, PubMed:19636380, PubMed:21282530). The composition of the PRC1 complex differs between the PRC1 complex in pluripotent embryonic stem cells containing RNF2, CBX7 and PCGF2, and the PRC1 complex in differentiating cells containing RNF2, CBX2, CBX4 and BMI1 (By similarity). Self-associates (PubMed:21282530). Interacts with SUV39H1 and HIPK2 (PubMed:12101246, PubMed:17018294). Interacts with CSNK2B (PubMed:21282530). May interact with HIST2H3A, HIST1H3A and RNF2 (PubMed:18927235). Interacts with SUMO1P1/SUMO5 (PubMed:27211601).By similarity7 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114105, 103 interactors
CORUMiO00257
DIPiDIP-42042N
ELMiO00257
IntActiO00257, 88 interactors
MINTiO00257
STRINGi9606.ENSP00000269397

Chemistry databases

BindingDBiO00257

Structurei

Secondary structure

1560
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO00257
SMRiO00257
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO00257

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini11 – 69ChromoPROSITE-ProRule annotationAdd BLAST59

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 539Interaction with BMI1Add BLAST539
Regioni1 – 75Involved in interaction with HIST2H3A and HIST1H3A1 PublicationAdd BLAST75
Regioni531 – 556Involved in interaction with HIST2H3A and RNF21 PublicationAdd BLAST26
Regioni540 – 560Interaction with RNF2Add BLAST21

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi378 – 400His-richAdd BLAST23
Compositional biasi389 – 400Poly-HisAdd BLAST12
Compositional biasi499 – 510Poly-AlaAdd BLAST12

Domaini

The polyhistidine repeat may act as a targeting signal to nuclear speckles.1 Publication

Phylogenomic databases

eggNOGiENOG410IPQ6 Eukaryota
ENOG410ZQCR LUCA
GeneTreeiENSGT00530000063056
HOGENOMiHOG000206923
HOVERGENiHBG005257
InParanoidiO00257
KOiK11452
OMAiVLQQKWV
OrthoDBiEOG091G06XV
PhylomeDBiO00257
TreeFamiTF106456

Family and domain databases

CDDicd00024 CHROMO, 1 hit
InterProiView protein in InterPro
IPR033773 CBX7_C
IPR016197 Chromo-like_dom_sf
IPR000953 Chromo/chromo_shadow_dom
IPR017984 Chromo_dom_subgr
IPR023780 Chromo_domain
IPR023779 Chromodomain_CS
PfamiView protein in Pfam
PF17218 CBX7_C, 1 hit
PF00385 Chromo, 1 hit
PRINTSiPR00504 CHROMODOMAIN
SMARTiView protein in SMART
SM00298 CHROMO, 1 hit
SUPFAMiSSF54160 SSF54160, 1 hit
PROSITEiView protein in PROSITE
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: O00257-1) [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
MELPAVGEHV FAVESIEKKR IRKGRVEYLV KWRGWSPKYN TWEPEENILD
60 70 80 90 100
PRLLIAFQNR ERQEQLMGYR KRGPKPKPLV VQVPTFARRS NVLTGLQDSS
110 120 130 140 150
TDNRAKLDLG AQGKGQGHQY ELNSKKHHQY QPHSKERAGK PPPPGKSGKY
160 170 180 190 200
YYQLNSKKHH PYQPDPKMYD LQYQGGHKEA PSPTCPDLGA KSHPPDKWAQ
210 220 230 240 250
GAGAKGYLGA VKPLAGAAGA PGKGSEKGPP NGMMPAPKEA VTGNGIGGKM
260 270 280 290 300
KIVKNKNKNG RIVIVMSKYM ENGMQAVKIK SGEVAEGEAR SPSHKKRAAD
310 320 330 340 350
ERHPPADRTF KKAAGAEEKK VEAPPKRREE EVSGVSDPQP QDAGSRKLSP
360 370 380 390 400
TKEAFGEQPL QLTTKPDLLA WDPARNTHPP SHHPHPHPHH HHHHHHHHHH
410 420 430 440 450
AVGLNLSHVR KRCLSETHGE REPCKKRLTA RSISTPTCLG GSPAAERPAD
460 470 480 490 500
LPPAAALPQP EVILLDSDLD EPIDLRCVKT RSEAGEPPSS LQVKPETPAS
510 520 530 540 550
AAVAVAAAAA PTTTAEKPPA EAQDEPAESL SEFKPFFGNI IITDVTANCL
560
TVTFKEYVTV
Length:560
Mass (Da):61,368
Last modified:July 28, 2009 - v3
Checksum:iDF5C8C4C0CCB1F31
GO
Isoform 2 (identifier: O00257-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     127-396: Missing.

Show »
Length:290
Mass (Da):31,987
Checksum:iB1E71D5122A7B7FA
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F8WCW6F8WCW6_HUMAN
E3 SUMO-protein ligase CBX4
CBX4
60Annotation score:
I3L4F1I3L4F1_HUMAN
E3 SUMO-protein ligase CBX4
CBX4
90Annotation score:

Sequence cautioni

The sequence AAH14967 differs from that shown. Aberrant splicing.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti137 – 138Missing in AAB80718 (PubMed:9315667).Curated2
Sequence conflicti142P → R in AAB80718 (PubMed:9315667).Curated1
Sequence conflicti458P → R in AAB80718 (PubMed:9315667).Curated1
Sequence conflicti458P → R in AAB62734 (PubMed:15489334).Curated1
Sequence conflicti477C → S in AAB80718 (PubMed:9315667).Curated1
Sequence conflicti477C → S in AAB62734 (PubMed:15489334).Curated1
Sequence conflicti480T → S in AAB80718 (PubMed:9315667).Curated1
Sequence conflicti480T → S in AAB62734 (PubMed:15489334).Curated1
Sequence conflicti505V → VAA in ACA49234 (Ref. 3) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_041599127 – 396Missing in isoform 2. 1 PublicationAdd BLAST270

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF013956 mRNA Translation: AAB80718.1
EU439707 mRNA Translation: ACA49234.1
AY390430 mRNA Translation: AAQ97596.1
AC100791 Genomic DNA No translation available.
BC014967 mRNA Translation: AAH14967.1 Sequence problems.
U94344 mRNA Translation: AAB62734.1
CCDSiCCDS32758.1 [O00257-1]
RefSeqiNP_003646.2, NM_003655.2 [O00257-1]
UniGeneiHs.405046

Genome annotation databases

EnsembliENST00000269397; ENSP00000269397; ENSG00000141582 [O00257-1]
GeneIDi8535
KEGGihsa:8535
UCSCiuc002jxe.4 human [O00257-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF013956 mRNA Translation: AAB80718.1
EU439707 mRNA Translation: ACA49234.1
AY390430 mRNA Translation: AAQ97596.1
AC100791 Genomic DNA No translation available.
BC014967 mRNA Translation: AAH14967.1 Sequence problems.
U94344 mRNA Translation: AAB62734.1
CCDSiCCDS32758.1 [O00257-1]
RefSeqiNP_003646.2, NM_003655.2 [O00257-1]
UniGeneiHs.405046

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2K28NMR-A8-65[»]
3I8ZX-ray1.51A8-62[»]
5EPLX-ray1.81A/B8-65[»]
ProteinModelPortaliO00257
SMRiO00257
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114105, 103 interactors
CORUMiO00257
DIPiDIP-42042N
ELMiO00257
IntActiO00257, 88 interactors
MINTiO00257
STRINGi9606.ENSP00000269397

Chemistry databases

BindingDBiO00257
ChEMBLiCHEMBL3232685

PTM databases

iPTMnetiO00257
PhosphoSitePlusiO00257

Polymorphism and mutation databases

BioMutaiCBX4

Proteomic databases

EPDiO00257
MaxQBiO00257
PaxDbiO00257
PeptideAtlasiO00257
PRIDEiO00257
ProteomicsDBi47811
47812 [O00257-3]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000269397; ENSP00000269397; ENSG00000141582 [O00257-1]
GeneIDi8535
KEGGihsa:8535
UCSCiuc002jxe.4 human [O00257-1]

Organism-specific databases

CTDi8535
DisGeNETi8535
EuPathDBiHostDB:ENSG00000141582.14
GeneCardsiCBX4
H-InvDBiHIX0014237
HGNCiHGNC:1554 CBX4
HPAiHPA008228
HPA012021
MIMi603079 gene
neXtProtiNX_O00257
OpenTargetsiENSG00000141582
PharmGKBiPA26129
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IPQ6 Eukaryota
ENOG410ZQCR LUCA
GeneTreeiENSGT00530000063056
HOGENOMiHOG000206923
HOVERGENiHBG005257
InParanoidiO00257
KOiK11452
OMAiVLQQKWV
OrthoDBiEOG091G06XV
PhylomeDBiO00257
TreeFamiTF106456

Enzyme and pathway databases

UniPathwayi
UPA00886

ReactomeiR-HSA-2559580 Oxidative Stress Induced Senescence
R-HSA-3108214 SUMOylation of DNA damage response and repair proteins
R-HSA-3899300 SUMOylation of transcription cofactors
R-HSA-4551638 SUMOylation of chromatin organization proteins
R-HSA-4570464 SUMOylation of RNA binding proteins
R-HSA-4655427 SUMOylation of DNA methylation proteins
R-HSA-8939243 RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known
R-HSA-8943724 Regulation of PTEN gene transcription
SIGNORiO00257

Miscellaneous databases

ChiTaRSiCBX4 human
EvolutionaryTraceiO00257
GenomeRNAii8535
PROiPR:O00257
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000141582 Expressed in 209 organ(s), highest expression level in bone marrow
CleanExiHS_CBX4
ExpressionAtlasiO00257 baseline and differential
GenevisibleiO00257 HS

Family and domain databases

CDDicd00024 CHROMO, 1 hit
InterProiView protein in InterPro
IPR033773 CBX7_C
IPR016197 Chromo-like_dom_sf
IPR000953 Chromo/chromo_shadow_dom
IPR017984 Chromo_dom_subgr
IPR023780 Chromo_domain
IPR023779 Chromodomain_CS
PfamiView protein in Pfam
PF17218 CBX7_C, 1 hit
PF00385 Chromo, 1 hit
PRINTSiPR00504 CHROMODOMAIN
SMARTiView protein in SMART
SM00298 CHROMO, 1 hit
SUPFAMiSSF54160 SSF54160, 1 hit
PROSITEiView protein in PROSITE
PS00598 CHROMO_1, 1 hit
PS50013 CHROMO_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCBX4_HUMAN
AccessioniPrimary (citable) accession number: O00257
Secondary accession number(s): B1PJR7, Q6TPI8, Q96C04
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 24, 2001
Last sequence update: July 28, 2009
Last modified: October 10, 2018
This is version 182 of the entry and version 3 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. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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