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Protein

E3 SUMO-protein ligase CBX4

Gene

CBX4

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

Functioni

E3 SUMO-protein ligase which facilitates SUMO1 conjugation by UBE2I. 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.
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. 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.

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
  • ligase activity Source: UniProtKB-KW
  • 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

  • chromatin modification Source: UniProtKB-KW
  • negative regulation of apoptotic process Source: ProtInc
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • protein sumoylation Source: Reactome
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Ligase, Repressor

Keywords - Biological processi

Transcription, Transcription regulation, Ubl conjugation pathway

Enzyme and pathway databases

BioCyciZFISH:ENSG00000141582-MONOMER.
ReactomeiR-HSA-2559580. Oxidative Stress Induced Senescence.
R-HSA-3108214. SUMOylation of DNA damage response and repair proteins.
R-HSA-4570464. SUMOylation of RNA binding proteins.
SIGNORiO00257.
UniPathwayiUPA00886.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 SUMO-protein ligase CBX4 (EC:6.3.2.-)
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

HGNCiHGNC:1554. CBX4.

Subcellular locationi

GO - Cellular componenti

  • nuclear speck Source: UniProtKB-SubCell
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
  • PcG protein complex Source: UniProtKB
  • PRC1 complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
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-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
Modified residuei149N6-acetyllysine; alternateCombined sources1
Cross-linki149Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei182PhosphoserineCombined sources1
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-linki280Glycyl 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)1 Publication
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.

PTM databases

iPTMnetiO00257.
PhosphoSitePlusiO00257.

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

BgeeiENSG00000141582.
CleanExiHS_CBX4.
ExpressionAtlasiO00257. baseline and differential.
GenevisibleiO00257. HS.

Organism-specific databases

HPAiHPA008228.
HPA012021.

Interactioni

Subunit structurei

Interacts with histone H3-K9Me3. Interacts with CHTOP (By similarity). Component of a PRC1-like complex. Self-associates. Interacts with SUV39H1 and HIPK2. Interacts with CSNK2B.By similarity5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BMI1P352267EBI-722425,EBI-2341576
CBX8Q9HC523EBI-722425,EBI-712912
CSNK2A1P684002EBI-4392727,EBI-347804
CSNK2BP678702EBI-4392727,EBI-348169
HIF1AQ1666515EBI-722425,EBI-447269
PCGF6Q9BYE72EBI-4392727,EBI-1048026
RNF2Q994965EBI-722425,EBI-722416
YWHABP319462EBI-722425,EBI-359815
YWHAEP622582EBI-4392727,EBI-356498
YWHAZP631042EBI-4392727,EBI-347088

GO - Molecular functioni

  • enzyme binding Source: UniProtKB
  • SUMO binding Source: MGI

Protein-protein interaction databases

BioGridi114105. 99 interactors.
DIPiDIP-42042N.
IntActiO00257. 81 interactors.
MINTiMINT-1196265.
STRINGi9606.ENSP00000269397.

Chemistry databases

BindingDBiO00257.

Structurei

Secondary structure

1560
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi13 – 22Combined sources10
Beta strandi25 – 32Combined sources8
Helixi37 – 39Combined sources3
Beta strandi41 – 44Combined sources4
Helixi45 – 48Combined sources4
Helixi51 – 53Combined sources3

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...

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
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

Sequence similaritiesi

Contains 1 chromo domain.PROSITE-ProRule annotation

Phylogenomic databases

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

Family and domain databases

InterProiIPR033773. CBX7_C.
IPR000953. Chromo/shadow_dom.
IPR017984. Chromo_dom_subgr.
IPR023780. Chromo_domain.
IPR016197. Chromodomain-like.
IPR023779. Chromodomain_CS.
[Graphical view]
PfamiPF17218. CBX7_C. 1 hit.
PF00385. Chromo. 1 hit.
[Graphical view]
PRINTSiPR00504. CHROMODOMAIN.
SMARTiSM00298. CHROMO. 1 hit.
[Graphical view]
SUPFAMiSSF54160. SSF54160. 1 hit.
PROSITEiPS00598. 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: 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

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

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. 99 interactors.
DIPiDIP-42042N.
IntActiO00257. 81 interactors.
MINTiMINT-1196265.
STRINGi9606.ENSP00000269397.

Chemistry databases

BindingDBiO00257.
ChEMBLiCHEMBL3232685.

PTM databases

iPTMnetiO00257.
PhosphoSitePlusiO00257.

Polymorphism and mutation databases

BioMutaiCBX4.

Proteomic databases

EPDiO00257.
MaxQBiO00257.
PaxDbiO00257.
PeptideAtlasiO00257.
PRIDEiO00257.

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.
GeneCardsiCBX4.
H-InvDBHIX0014237.
HGNCiHGNC:1554. CBX4.
HPAiHPA008228.
HPA012021.
MIMi603079. gene.
neXtProtiNX_O00257.
OpenTargetsiENSG00000141582.
PharmGKBiPA26129.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

UniPathwayiUPA00886.
BioCyciZFISH:ENSG00000141582-MONOMER.
ReactomeiR-HSA-2559580. Oxidative Stress Induced Senescence.
R-HSA-3108214. SUMOylation of DNA damage response and repair proteins.
R-HSA-4570464. SUMOylation of RNA binding proteins.
SIGNORiO00257.

Miscellaneous databases

ChiTaRSiCBX4. human.
EvolutionaryTraceiO00257.
GenomeRNAii8535.
PROiO00257.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000141582.
CleanExiHS_CBX4.
ExpressionAtlasiO00257. baseline and differential.
GenevisibleiO00257. HS.

Family and domain databases

InterProiIPR033773. CBX7_C.
IPR000953. Chromo/shadow_dom.
IPR017984. Chromo_dom_subgr.
IPR023780. Chromo_domain.
IPR016197. Chromodomain-like.
IPR023779. Chromodomain_CS.
[Graphical view]
PfamiPF17218. CBX7_C. 1 hit.
PF00385. Chromo. 1 hit.
[Graphical view]
PRINTSiPR00504. CHROMODOMAIN.
SMARTiSM00298. CHROMO. 1 hit.
[Graphical view]
SUPFAMiSSF54160. SSF54160. 1 hit.
PROSITEiPS00598. CHROMO_1. 1 hit.
PS50013. CHROMO_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCBX4_HUMAN
AccessioniPrimary (citable) accession number: O00257
Secondary accession number(s): B1PJR7, Q6TPI8, Q96C04
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 24, 2001
Last sequence update: July 28, 2009
Last modified: November 30, 2016
This is version 165 of the entry and version 3 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

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.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: 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. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. 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.