Reviewed, UniProtKB/Swiss-Prot Q13185 (CBX3_HUMAN)

Names and origin

Protein names

Recommended name:
    Chromobox protein homolog 3
Alternative name(s):
    Heterochromatin protein 1 homolog gamma
      Short name=HP1 gamma
    Modifier 2 protein
    HECH

Gene names

Name:

CBX3

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	183 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Seems to be involved in transcriptional silencing in heterochromatin-like complexes. Recognizes and binds histone H3 tails methylated at 'Lys-9', leading to epigenetic repression. May contribute to the association of the heterochromatin with the inner nuclear membrane through its interaction with lamin B receptor (LBR). Involved in the formation of functional kinetochore through interaction with MIS12 complex proteins.
Subunit structure	Binds directly to CHAF1A. Interacts with histone H3 methylated at 'Lys-9'. Part of the E2F6.com-1 complex in G0 phase composed of E2F6, MGA, MAX, TFDP1, CBX3, BAT8, EUHMTASE1, RING1, RNF2, MBLR, L3MBTL2 and YAF2. Interacts with LBR, INCENP, TRIM28/TIF1B, SUV420H1, SUV420H2 and SP100. Interacts with TIF1A By similarity. Interacts with MIS12 and C20orf127. Can interact directly with CBX5 via the chromoshadow domain.
Subcellular location	Nucleus Potential. Note: Associates with euchromatin and is largely excluded from constitutive heterochromatin. May be associated with microtubules and mitotic poles during mitosis Potential.
Post-translational modification	Phosphorylated by PIM1. Phosphorylated during interphase and possibly hyper-phosphorylated during mitosis. Ref.3 Ref.10 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21
Sequence similarities	Contains 2 chromo domains.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Domain	Repeat
Molecular function	Chromatin regulator Repressor
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	chromatin assembly or disassembly Inferred from electronic annotation. Source: InterPro chromatin remodeling Ref.1 Non-traceable author statement. Source: UniProtKB negative regulation of transcription Inferred from direct assay. Source: UniProtKB regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	condensed chromosome, centromeric region Inferred from sequence or structural similarity. Source: UniProtKB nuclear centromeric heterochromatin Inferred from sequence or structural similarity. Source: UniProtKB nuclear euchromatin Inferred from direct assay. Source: UniProtKB nuclear inner membrane Ref.1 Non-traceable author statement. Source: UniProtKB polytene chromosome chromocenter Inferred from sequence or structural similarity. Source: UniProtKB spindle Inferred from direct assay. Source: UniProtKB
Molecular function	chromatin binding Inferred from electronic annotation. Source: InterPro general transcriptional repressor activity Inferred from mutant phenotype. Source: UniProtKB protein domain specific binding Ref.1 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
LBR	Q14739	1	EBI-78176,EBI-1055147
TRIM28	Q13263	1	EBI-78176,EBI-78139

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 183	183	Chromobox protein homolog 3		PRO_0000080203
Regions
	Domain	30 – 88	59	Chromo 1
	Domain	121 – 179	59	Chromo 2; shadow subtype
Amino acid modifications
	Modified residue	93	1	Phosphoserine Ref.15 Ref.16 Ref.17 Ref.18
	Modified residue	95	1	Phosphoserine Ref.15 Ref.16 Ref.18 Ref.20 Ref.21
	Modified residue	97	1	Phosphoserine Ref.19
	Modified residue	176	1	Phosphoserine Ref.19 Ref.20
Experimental info
	Sequence conflict	111	1	A → G in AAH14380. Ref.5
	Sequence conflict	111	1	A → V in AAF62370. Ref.4
	Sequence conflict	130	1	T → I Ref.1
	Sequence conflict	130	1	T → I Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q13185-1 [UniParc]. Last modified October 17, 2006. Version 4. Checksum: 5928C63E0C93A76A	FASTA	183	20,811
	10 20 30 40 50 60 MASNKTTLQK MGKKQNGKSK KVEEAEPEEF VVEKVLDRRV VNGKVEYFLK WKGFTDADNT 70 80 90 100 110 120 WEPEENLDCP ELIEAFLNSQ KAGKEKDGTK RKSLSDSESD DSKSKKKRDA ADKPRGFARG 130 140 150 160 170 180 LDPERIIGAT DSSGELMFLM KWKDSDEADL VLAKEANMKC PQIVIAFYEE RLTWHSCPED EAQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Interaction between an integral protein of the nuclear envelope inner membrane and human chromodomain proteins homologous to Drosophila HP1." Ye Q., Worman H.J. J. Biol. Chem. 271:14653-14656(1996) [PubMed: 8663349] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 11-183.
[2]	Ye Q., Worman H.J. Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[3]	"Identification of heterochromatin protein 1 (HP1) as a phosphorylation target by Pim-1 kinase and the effect of phosphorylation on the transcriptional repression function of HP1." Koike N., Maita H., Taira T., Ariga H., Iguchi-Ariga S.M.M. FEBS Lett. 467:17-21(2000) [PubMed: 10664448] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 11-183, PHOSPHORYLATION BY PIM1.
[4]	Chen J.H., Luo W.Q., Hu S.N., Zhou H.J., Huang X.W., Zhou Y., Yuan J.G., Qiang B.Q. Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Bone marrow and Placenta.
[6]	Lubec G., Afjehi-Sadat L. Submitted (MAR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 160-171, MASS SPECTROMETRY. Tissue: Brain and Cajal-Retzius cell.
[7]	"Domain-specific interactions of human HP1-type chromodomain proteins and inner nuclear membrane protein LBR." Ye Q., Callebaut I., Pezhman A., Courvalin J.-C., Worman H.J. J. Biol. Chem. 272:14983-14989(1997) [PubMed: 9169472] [Abstract] Cited for: INTERACTION WITH LBR AND CBX5.
[8]	"INCENP centromere and spindle targeting: identification of essential conserved motifs and involvement of heterochromatin protein HP1." Ainsztein A.M., Kandels-Lewis S.E., Mackay A.M., Earnshaw W.C. J. Cell Biol. 143:1763-1774(1998) [PubMed: 9864353] [Abstract] Cited for: INTERACTION WITH INCENP.
[9]	"Interaction of SP100 with HP1 proteins: a link between the promyelocytic leukemia-associated nuclear bodies and the chromatin compartment." Seeler J.-S., Marchio A., Sitterlin D., Transy C., Dejean A. Proc. Natl. Acad. Sci. U.S.A. 95:7316-7321(1998) [PubMed: 9636146] [Abstract] Cited for: INTERACTION WITH SP100.
[10]	"Localization and phosphorylation of HP1 proteins during the cell cycle in mammalian cells." Minc E., Allory Y., Worman H.J., Courvalin J.-C., Buendia B. Chromosoma 108:220-234(1999) [PubMed: 10460410] [Abstract] Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION.
[11]	"KAP-1 corepressor protein interacts and colocalizes with heterochromatic and euchromatic HP1 proteins: a potential role for Kruppel-associated box-zinc finger proteins in heterochromatin-mediated gene silencing." Ryan R.F., Schultz D.C., Ayyanathan K., Singh P.B., Friedman J.R., Fredericks W.J., Rauscher F.J. III Mol. Cell. Biol. 19:4366-4378(1999) [PubMed: 10330177] [Abstract] Cited for: INTERACTION WITH TRIM28.
[12]	"Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins." Lachner M., O'Carroll D., Rea S., Mechtler K., Jenuwein T. Nature 410:116-120(2001) [PubMed: 11242053] [Abstract] Cited for: INTERACTION WITH HISTONE H3 LYS-9.
[13]	"A complex with chromatin modifiers that occupies E2F- and Myc-responsive genes in G0 cells." Ogawa H., Ishiguro K., Gaubatz S., Livingston D.M., Nakatani Y. Science 296:1132-1136(2002) [PubMed: 12004135] [Abstract] Cited for: IDENTIFICATION IN COMPLEX WITH E2F6; TFDP1; MAX; MGA; BAT8; EUHMTASE1; RING1; RNF2; MBLR; L3MBTL2 AND YAF2.
[14]	"A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1." Obuse C., Iwasaki O., Kiyomitsu T., Goshima G., Toyoda Y., Yanagida M. Nat. Cell Biol. 6:1135-1141(2004) [PubMed: 15502821] [Abstract] Cited for: INTERACTION WITH MIS12 AND C20ORF127.
[15]	"Global phosphoproteome of HT-29 human colon adenocarcinoma cells." Kim J.-E., Tannenbaum S.R., White F.M. J. Proteome Res. 4:1339-1346(2005) [PubMed: 16083285] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-93 AND SER-95, MASS SPECTROMETRY.
[16]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-93 AND SER-95, MASS SPECTROMETRY. Tissue: Epithelium.
[17]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-93, MASS SPECTROMETRY. Tissue: Epithelium.
[18]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-93 AND SER-95, MASS SPECTROMETRY.
[19]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-97 AND SER-176, MASS SPECTROMETRY.
[20]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-95 AND SER-176, MASS SPECTROMETRY.
[21]	"Large-scale phosphoproteome analysis of human liver tissue by enrichment and fractionation of phosphopeptides with strong anion exchange chromatography." Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D., Zou H., Gu J. Proteomics 8:1346-1361(2008) [PubMed: 18318008] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-95, MASS SPECTROMETRY. Tissue: Liver.
[22]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

U26312 mRNA. Translation: AAB48101.1.
AB030905 mRNA. Translation: BAA83340.1.
AF136630 mRNA. Translation: AAF62370.1.
BC000954 mRNA. Translation: AAH00954.1.
BC014380 mRNA. Translation: AAH14380.1.

IPI

IPI00297579.

RefSeq

NP_009207.2.
NP_057671.2.
XP_943872.1.

UniGene

Hs.381189

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3DM1	X-ray	2.40	A/C/E/G	29-86	[»]

SMR

Q13185. Positions 36-87, 113-178.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:5985N.

IntAct

Q13185. 4 interactions.

PTM databases

PhosphoSite

Q13185.

2-D gel databases

SWISS-2DPAGE

Q13185.

Proteomic databases

PeptideAtlas

Q13185.

PRIDE

Q13185.

Genome annotation databases

Ensembl

ENSG00000122565. Homo sapiens. [Contig view]

GeneID

11335.
653972.

KEGG

hsa:11335.
hsa:653972.

UCSC

uc003sxt.1. human.

Organism-specific databases

GeneCards

GC07P026207.
GC07P026208.

HGNC

HGNC:1553. CBX3.

HPA

CAB001973.
HPA004902.

MIM

604477. gene.

PharmGKB

PA26128.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q13185.

HOVERGEN

Q13185.

OMA

Q13185. VPAREAN.

Gene expression databases

ArrayExpress

Q13185.

Bgee

Q13185.

CleanEx

HS_CBX3.

GermOnline

ENSG00000122565. Homo sapiens.

Family and domain databases

InterPro

IPR017984. Chromo_dom_subgr.
IPR008251. Chromo_shadow.
IPR018125. Chromo_shadow_sbgrp.
IPR000953. Chromodomain.
[Graphical view]

Pfam

PF00385. Chromo. 1 hit.
PF01393. Chromo_shadow. 1 hit.
[Graphical view]

PRINTS

PR00504. CHROMODOMAIN.

SMART

SM00298. CHROMO. 2 hits.
SM00300. ChSh. 1 hit.
[Graphical view]

PROSITE

PS00598. CHROMO_1. 1 hit.
PS50013. CHROMO_2. 2 hits.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

43065.

SOURCE

Search...

Entry information

Entry name

CBX3_HUMAN

Accession

Primary (citable) accession number: Q13185
Secondary accession number(s): Q96CD7 , Q99409, Q9BVS3, Q9P0Z6

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	October 17, 2006
Last modified:	July 7, 2009
This is version 97 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)