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O00257 (CBX4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 136. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:CBX4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length560 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.9 Ref.11 Ref.12 Ref.16 Ref.17 Ref.18

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. Ref.9 Ref.11 Ref.12 Ref.16 Ref.17 Ref.18

Pathway

Protein modification; protein sumoylation.

Subunit structure

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. Ref.7 Ref.8 Ref.12 Ref.14 Ref.16

Subcellular location

Nucleus. Nucleus speckle. Note: Localization to nuclear polycomb bodies is required for ZNF131 sumoylation. Ref.2 Ref.9 Ref.12 Ref.16 Ref.17

Tissue specificity

Ubiquitous.

Domain

The polyhistidine repeat may act as a targeting signal to nuclear speckles (Ref.2).

Post-translational modification

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. Ref.12

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 Ref.8 probably presents a mixture of different complexes containing different Polycomb group proteins.

Sequence similarities

Contains 1 chromo domain.

Sequence caution

The sequence AAH14967.1 differs from that shown. Reason: Aberrant splicing.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
Ubl conjugation pathway
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   Molecular functionChromatin regulator
Ligase
Repressor
   PTMAcetylation
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processchromatin modification

Inferred from electronic annotation. Source: UniProtKB-KW

negative regulation of apoptotic process

Traceable author statement Ref.1. Source: ProtInc

negative regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype Ref.16. Source: UniProtKB

negative regulation of transcription, DNA-templated

Inferred from direct assay PubMed 18567530. Source: UniProtKB

protein sumoylation

Inferred from electronic annotation. Source: UniProtKB-UniPathway

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentPRC1 complex

Inferred from direct assay Ref.8Ref.14. Source: UniProtKB

PcG protein complex

Inferred from direct assay Ref.16. Source: UniProtKB

nuclear speck

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.16. Source: UniProtKB

   Molecular_functionSUMO binding

Inferred from direct assay PubMed 20176810. Source: MGI

chromatin binding

Inferred from electronic annotation. Source: Ensembl

enzyme binding

Inferred from physical interaction PubMed 17087506. Source: UniProtKB

ligase activity

Inferred from electronic annotation. Source: UniProtKB-KW

single-stranded RNA binding

Inferred from electronic annotation. Source: Ensembl

transcription corepressor activity

Traceable author statement Ref.1. Source: ProtInc

transcription regulatory region DNA binding

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O00257-1)

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.
Isoform 2 (identifier: O00257-3)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 560560E3 SUMO-protein ligase CBX4
PRO_0000080206

Regions

Domain11 – 6959Chromo
Region1 – 539539Interaction with BMI1
Region540 – 56021Interaction with RNF2
Compositional bias378 – 40023His-rich
Compositional bias389 – 40012Poly-His
Compositional bias499 – 51012Poly-Ala

Amino acid modifications

Modified residue1491N6-acetyllysine Ref.15
Modified residue4971Phosphothreonine; by HIPK2 Ref.12
Cross-link494Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.10

Natural variations

Alternative sequence127 – 396270Missing in isoform 2.
VSP_041599

Experimental info

Mutagenesis4341S → A: Abolishes interaction with YWHAZ and YWHAE; impairs interaction with PCGF6 and BMI1; no effect on interaction with RNF2. Ref.16
Mutagenesis4941K → R: No effect on ZNF131 sumoylation. Ref.17
Mutagenesis4971T → A: Small decrease in ZNF131 sumoylation. Ref.17
Sequence conflict137 – 1382Missing in AAB80718. Ref.1
Sequence conflict1421P → R in AAB80718. Ref.1
Sequence conflict4581P → R in AAB80718. Ref.1
Sequence conflict4581P → R in AAB62734. Ref.5
Sequence conflict4771C → S in AAB80718. Ref.1
Sequence conflict4771C → S in AAB62734. Ref.5
Sequence conflict4801T → S in AAB80718. Ref.1
Sequence conflict4801T → S in AAB62734. Ref.5
Sequence conflict5051V → VAA in ACA49234. Ref.3

Secondary structure

............ 560
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 28, 2009. Version 3.
Checksum: DF5C8C4C0CCB1F31

FASTA56061,368
        10         20         30         40         50         60 
MELPAVGEHV FAVESIEKKR IRKGRVEYLV KWRGWSPKYN TWEPEENILD PRLLIAFQNR 

        70         80         90        100        110        120 
ERQEQLMGYR KRGPKPKPLV VQVPTFARRS NVLTGLQDSS TDNRAKLDLG AQGKGQGHQY 

       130        140        150        160        170        180 
ELNSKKHHQY QPHSKERAGK PPPPGKSGKY YYQLNSKKHH PYQPDPKMYD LQYQGGHKEA 

       190        200        210        220        230        240 
PSPTCPDLGA KSHPPDKWAQ GAGAKGYLGA VKPLAGAAGA PGKGSEKGPP NGMMPAPKEA 

       250        260        270        280        290        300 
VTGNGIGGKM KIVKNKNKNG RIVIVMSKYM ENGMQAVKIK SGEVAEGEAR SPSHKKRAAD 

       310        320        330        340        350        360 
ERHPPADRTF KKAAGAEEKK VEAPPKRREE EVSGVSDPQP QDAGSRKLSP TKEAFGEQPL 

       370        380        390        400        410        420 
QLTTKPDLLA WDPARNTHPP SHHPHPHPHH HHHHHHHHHH AVGLNLSHVR KRCLSETHGE 

       430        440        450        460        470        480 
REPCKKRLTA RSISTPTCLG GSPAAERPAD LPPAAALPQP EVILLDSDLD EPIDLRCVKT 

       490        500        510        520        530        540 
RSEAGEPPSS LQVKPETPAS AAVAVAAAAA PTTTAEKPPA EAQDEPAESL SEFKPFFGNI 

       550        560 
IITDVTANCL TVTFKEYVTV 

« Hide

Isoform 2 [UniParc].

Checksum: B1E71D5122A7B7FA
Show »

FASTA29031,987

References

« Hide 'large scale' references
[1]"Interference with the expression of a novel human polycomb protein, hPc2, results in cellular transformation and apoptosis."
Satijn D.P.E., Olson D.J., van der Vlag J., Hamer K.M., Lambrechts C., Masselink H., Gunster M.J., Sewalt R.G.A.B., van Driel R., Otte A.P.
Mol. Cell. Biol. 17:6076-6086(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Fetal brain.
[2]"Genome-wide analysis of histidine repeats reveals their role in the localization of human proteins to the nuclear speckles compartment."
Salichs E., Ledda A., Mularoni L., Alba M.M., de la Luna S.
PLoS Genet. 5:E1000397-E1000397(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION.
[3]"Cloning and identification of NS5ATP1-binding protein 16."
Liu M., Cheng J., Wang L.
Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[4]"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. expand/collapse author list , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Colon.
[6]"RING1 is associated with the polycomb group protein complex and acts as a transcriptional repressor."
Satijn D.P.E., Gunster M.J., van der Vlag J., Hamer K.M., Schul W., Alkema M.J., Saurin A.J., Freemont P.S., van Driel R., Otte A.P.
Mol. Cell. Biol. 17:4105-4113(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 457-560 (ISOFORM 1).
[7]"Selective interactions between vertebrate polycomb homologs and the SUV39H1 histone lysine methyltransferase suggest that histone H3-K9 methylation contributes to chromosomal targeting of Polycomb group proteins."
Sewalt R.G.A.B., Lachner M., Vargas M., Hamer K.M., den Blaauwen J.L., Hendrix T., Melcher M., Schweizer D., Jenuwein T., Otte A.P.
Mol. Cell. Biol. 22:5539-5553(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SUV39H1.
[8]"The core of the polycomb repressive complex is compositionally and functionally conserved in flies and humans."
Levine S.S., Weiss A., Erdjument-Bromage H., Shao Z., Tempst P., Kingston R.E.
Mol. Cell. Biol. 22:6070-6078(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN A PRC1-LIKE HPRC-H COMPLEX WITH BMI1; CBX2; CBX8; PHC1; PHC2; PHC3; RING1 AND RNF2.
[9]"The polycomb protein Pc2 is a SUMO E3."
Kagey M.H., Melhuish T.A., Wotton D.
Cell 113:127-137(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUMOYLATION, SUBCELLULAR LOCATION.
[10]"Multiple activities contribute to Pc2 E3 function."
Kagey M.H., Melhuish T.A., Powers S.E., Wotton D.
EMBO J. 24:108-119(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUMOYLATION AT LYS-494.
[11]"Pc2-mediated sumoylation of Smad-interacting protein 1 attenuates transcriptional repression of E-cadherin."
Long J., Zuo D., Park M.
J. Biol. Chem. 280:35477-35489(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[12]"Phosphorylation-dependent control of Pc2 SUMO E3 ligase activity by its substrate protein HIPK2."
Roscic A., Moeller A., Calzado M.A., Renner F., Wimmer V.C., Gresko E., Luedi K.S., Schmitz M.L.
Mol. Cell 24:77-89(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH HIPK2, SUMOYLATION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT THR-497.
[13]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[14]"Several distinct polycomb complexes regulate and co-localize on the INK4a tumor suppressor locus."
Maertens G.N., El Messaoudi-Aubert S., Racek T., Stock J.K., Nicholls J., Rodriguez-Niedenfuhr M., Gil J., Peters G.
PLoS ONE 4:E6380-E6380(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A PRC1-LIKE COMPLEX.
[15]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-149, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]"Interaction proteomics analysis of polycomb proteins defines distinct PRC1 Complexes in mammalian cells."
Vandamme J., Volkel P., Rosnoblet C., Le Faou P., Angrand P.O.
Mol. Cell. Proteomics 0:0-0(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY (ISOFORM 2), IDENTIFICATION IN A PRC1-LIKE COMPLEX, SELF-ASSOCIATION, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-434.
[17]"Small ubiquitin-like modifier (SUMO) modification of zinc finger protein 131 potentiates its negative effect on estrogen signaling."
Oh Y., Chung K.C.
J. Biol. Chem. 287:17517-17529(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN ZNF131 SUMOYLATION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-494 AND THR-497.
[18]"DNA damage-induced heterogeneous nuclear ribonucleoprotein K SUMOylation regulates p53 transcriptional activation."
Pelisch F., Pozzi B., Risso G., Munoz M.J., Srebrow A.
J. Biol. Chem. 287:30789-30799(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[19]"Solution NMR structure of the chromo domain of the chromobox protein homolog 4."
Structural genomics consortium (SGC)
Submitted (FEB-2009) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 8-65.
[20]"Crystal structure of human chromobox homolog 4 (cbx4)."
Structural genomics consortium (SGC)
Submitted (SEP-2009) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (1.51 ANGSTROMS) OF 8-62.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_003646.2. NM_003655.2.
UniGeneHs.405046.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2K28NMR-A8-65[»]
3I8ZX-ray1.51A8-62[»]
ProteinModelPortalO00257.
SMRO00257. Positions 11-60.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114105. 71 interactions.
DIPDIP-42042N.
IntActO00257. 49 interactions.
MINTMINT-1196265.
STRING9606.ENSP00000269397.

PTM databases

PhosphoSiteO00257.

Proteomic databases

PaxDbO00257.
PRIDEO00257.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000269397; ENSP00000269397; ENSG00000141582. [O00257-1]
GeneID8535.
KEGGhsa:8535.
UCSCuc002jxe.3. human. [O00257-1]

Organism-specific databases

CTD8535.
GeneCardsGC17M077806.
H-InvDBHIX0014237.
HGNCHGNC:1554. CBX4.
HPAHPA008228.
MIM603079. gene.
neXtProtNX_O00257.
PharmGKBPA26129.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG281109.
HOGENOMHOG000206923.
HOVERGENHBG005257.
InParanoidO00257.
KOK11452.
OMAKWAHGAG.
OrthoDBEOG7PCJGP.
PhylomeDBO00257.
TreeFamTF106456.

Enzyme and pathway databases

ReactomeREACT_120956. Cellular responses to stress.
UniPathwayUPA00886.

Gene expression databases

ArrayExpressO00257.
BgeeO00257.
CleanExHS_CBX4.
GenevestigatorO00257.

Family and domain databases

InterProIPR017984. Chromo_dom_subgr.
IPR023780. Chromo_domain.
IPR000953. Chromo_domain/shadow.
IPR016197. Chromodomain-like.
IPR023779. Chromodomain_CS.
[Graphical view]
PfamPF00385. Chromo. 1 hit.
[Graphical view]
PRINTSPR00504. CHROMODOMAIN.
SMARTSM00298. CHROMO. 1 hit.
[Graphical view]
SUPFAMSSF54160. SSF54160. 1 hit.
PROSITEPS00598. CHROMO_1. 1 hit.
PS50013. CHROMO_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCBX4. human.
EvolutionaryTraceO00257.
GenomeRNAi8535.
NextBio31968.
PROO00257.
SOURCESearch...

Entry information

Entry nameCBX4_HUMAN
AccessionPrimary (citable) accession number: O00257
Secondary accession number(s): B1PJR7, Q6TPI8, Q96C04
Entry history
Integrated into UniProtKB/Swiss-Prot: January 24, 2001
Last sequence update: July 28, 2009
Last modified: April 16, 2014
This is version 136 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM