O08629 (TIF1B_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transcription intermediary factor 1-beta
Short name=TIF1-beta

Alternative name(s):
E3 SUMO-protein ligase TRIM28
EC=6.3.2.-
KRAB-associated protein 1
Nuclear corepressor KAP-1
Tripartite motif-containing protein 28

Gene names

Name:	Trim28
Synonyms:	Kap1, Tif1b

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	835 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Nuclear corepressor for KRAB domain-containing zinc finger proteins (KRAB-ZFPs). Mediates gene silencing by recruiting CHD3, a subunit of the nucleosome remodeling and deacetylation (NuRD) complex, and SETDB1 (which specifically methylates histone H3 at 'Lys-9' (H3K9me)) to the promoter regions of KRAB target genes. Enhances transcriptional repression by coordinating the increase in H3K9me, the decrease in histone H3 'Lys-9 and 'Lys-14' acetylation (H3K9ac and H3K14ac, respectively) and the disposition of HP1 proteins to silence gene expression. Recruitment of SETDB1 induces heterochromatinization. May play a role as a coactivator for CEBPB and NR3C1 in the transcriptional activation of ORM1. Also corepressor for ERBB4. Inhibits E2F1 activity by stimulating E2F1-HDAC1 complex formation and inhibiting E2F1 acetylation. May serve as a partial backup to prevent E2F1-mediated apoptosis in the absence of RB1. Important regulator of CDKN1A/p21(CIP1). Has E3 SUMO-protein ligase activity toward itself via its PHD-type zinc finger. Specifically sumoylates IRF7, thereby inhibiting its transactivation activity. Ubiquitinates p53/TP53 leading to its proteosomal degradation; the function is enhanced by MAGEC2 and MAGEA2, and possibly MAGEA3 and MAGEA6 By similarity.
Pathway	Protein modification; protein sumoylation.
Subunit structure	Oligomer; the RBCC domain homotrimerizes and interacts with one molecule of KRAB to form the KRAB-KAP1 corepressor complex By similarity. Binding to a KRAB domain is an absolute requirement for silencing gene expression By similarity. Interacts with CEBPB and NR3C1. Interacts with a number of KRAB-ZFP proteins including ZNF10, ZFP53, ZFP68, ZNF382 and ZNF256. Interacts with NCOR1, NR3C1 and CHD3. Interacts with CEBPB (via the RING-type and PHD-type zinc fingers). Component of a ternary complex that includes TRIM28, a HP1 protein (CBX1, CBX3 OR CBX5), a KRAB domain-containing protein, and DNA. Interacts with CBX5 (via the PxVxL motif); the interaction occurs in interphase nuclei and competes for binding POGZ. Interacts with POGZ; the interaction competes for interaction with CBX5. Interacts with SETDB1; the interaction is enhanced by KAP1 sumoylation, stimulates SETB1 histone methyltransferase activity and gene silencing. Interacts (via the PHD-type zinc finger) with UBE2I; the interaction is required for sumoylation and repressor activity. Component of the TRIM28/KAP1-ERBB4-MDM2 complex involved in connecting growth factor and DNA damage responses. Interacts directly with ERBB4; the interaction represses ERBB4-mediated transcription activity. Interacts with MDM2; the interaction contributes to p53/TP53 inactivation. Component of the TRIM28/KAP1-MDM2-p53/TP53; involved in regulating p53/TP53 stabilization and activity. Interacts (via the leucine zipper alpha helical coiled-coil) with E2F1 (central region); the interaction inhibits E2F1 acetylation and transcriptional activity. Interacts with PPP1CA; the interaction dephosphorylates TRIM28 at Ser-824 and forms a complex at the p21 promoter site. Interacts with PPP1CB; the interaction is weak but is increased on dephosphorylation at Ser-824 By similarity. Interacts with SMARCAD1. Interacts with, and sumoylates IRF7. Interacts with MAGEC2 By similarity. Part of a complex composed of TRIM28, HDAC1, HDAC2 and EHMT2 By similarity. Ref.3
Subcellular location	Nucleus By similarity. Note: Associated with centromeric heterochromatin during cell differentiation through CBX1 By similarity.
Domain	The HP1 box is both necessary and sufficient for HP1 binding By similarity. The PHD-type zinc finger enhances CEBPB transcriptional activity. The PHD-type zinc finger, the HP1 box and the bromo domain, function together to assemble the machinery required for repression of KRAB domain-containing proteins. Acts as an intramolecular SUMO E3 ligase for autosumoylation of bromodomain By similarity. The RING-finger-B Box-coiled-coil/tripartite motif (RBCC/TRIM motif) is required for interaction with the KRAB domain of KRAB-zinc finger proteins. Binds four zinc ions per molecule. The RING finger and the N-terminal of the leucine zipper alpha helical coiled-coil region of RBCC are required for oligomerization By similarity. Contains one Pro-Xaa-Val-Xaa-Leu (PxVxL) motif, which is required for interaction with chromoshadow domains. This motif requires additional residues -7, -6, +4 and +5 of the central Val which contact the chromoshadow domain By similarity.
Post-translational modification	ATM-induced phosphorylation on Ser-825 represses sumoylation leading to the de-repression of expression of a subset of genes involved in cell cycle control and apoptosis in response to genotoxic stress. Dephosphorylation by the phosphatases, PPP1CA and PP1CB forms, allows sumoylation and expression of TRIM28 target genes By similarity. Sumoylation/desumoylation events regulate TRIM28-mediated transcriptional repression. Sumoylation is required for interaction with CHD3 and SETDB1 and the corepressor activity. Represses and is repressed by Ser-824 phosphorylation. Enhances the TRIM28 corepressor activity, inhibiting transcriptional activity of a number of genes including GADD45A and CDKN1A/p21. Lys-555, Lys-780 and Lys-805 are the major sites of sumoylation. In response to Dox-induced DNA damage, enhanced phosphorylation on Ser-825 prevents sumoylation and allows de-repression of CDKN1A/p21 By similarity. Auto-ubiquitinated; enhanced by MAGEA2 and MAGEC2 By similarity.
Sequence similarities	Belongs to the TRIM/RBCC family. Contains 2 B box-type zinc fingers. Contains 1 bromo domain. Contains 1 PHD-type zinc finger. Contains 1 RING-type zinc finger.

Ontologies

Keywords
Biological process	Transcription Transcription regulation Ubl conjugation pathway
Cellular component	Nucleus
Domain	Bromodomain Repeat Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase Repressor
PTM	Acetylation Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA repair Inferred from electronic annotation. Source: Compara convergent extension involved in axis elongation Inferred from electronic annotation. Source: Compara embryonic placenta morphogenesis Inferred from electronic annotation. Source: Compara epithelial to mesenchymal transition Inferred from sequence or structural similarity. Source: HGNC negative regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara positive regulation of DNA repair Inferred from electronic annotation. Source: Compara positive regulation of transcription, DNA-dependent Inferred from sequence or structural similarity. Source: HGNC protein autophosphorylation Inferred from electronic annotation. Source: Compara protein oligomerization Inferred from electronic annotation. Source: Compara protein sumoylation Inferred from electronic annotation. Source: UniProtKB-UniPathway transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	nuclear euchromatin Inferred from electronic annotation. Source: Compara nuclear heterochromatin Inferred from electronic annotation. Source: Compara nucleoplasm Inferred from electronic annotation. Source: Compara nucleus Inferred from sequence or structural similarity. Source: HGNC
Molecular_function	protein kinase activity Inferred from electronic annotation. Source: Compara sequence-specific DNA binding Inferred from electronic annotation. Source: Compara sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: Compara transcription coactivator activity Inferred from electronic annotation. Source: Compara transcription corepressor activity Inferred from electronic annotation. Source: Compara ubiquitin-protein ligase activity Inferred from electronic annotation. Source: Compara zinc ion binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 835	835	Transcription intermediary factor 1-beta		PRO_0000056394
Regions
	Domain	698 – 802	105	Bromo
	Zinc finger	67 – 123	57	RING-type
	Zinc finger	150 – 197	48	B box-type 1; atypical
	Zinc finger	206 – 247	42	B box-type 2
	Zinc finger	626 – 673	48	PHD-type
	Region	248 – 378	131	Leucine zipper alpha helical coiled-coil region By similarity
	Region	249 – 378	130	Interaction with MAGEC2 By similarity
	Region	368 – 372	5	Involved in binding PPP1CA By similarity
	Region	477 – 514	38	HP1 box
	Motif	482 – 495	14	PxVxL motif
	Compositional bias	2 – 60	59	Ala-rich
	Compositional bias	55 – 58	4	Poly-Gly
	Compositional bias	527 – 532	6	Poly-Ala
Amino acid modifications
	Modified residue	24	1	Phosphoserine By similarity
	Modified residue	52	1	Phosphoserine By similarity
	Modified residue	306	1	N6-acetyllysine By similarity
	Modified residue	342	1	N6-acetyllysine By similarity
	Modified residue	379	1	N6-acetyllysine By similarity
	Modified residue	441	1	Phosphoserine By similarity
	Modified residue	472	1	Phosphoserine By similarity
	Modified residue	474	1	Phosphoserine By similarity
	Modified residue	480	1	Phosphoserine By similarity
	Modified residue	490	1	Phosphoserine By similarity
	Modified residue	502	1	Phosphoserine By similarity
	Modified residue	595	1	Phosphoserine By similarity
	Modified residue	684	1	Phosphoserine By similarity
	Modified residue	698	1	Phosphoserine By similarity
	Modified residue	753	1	Phosphoserine By similarity
	Modified residue	758	1	Phosphoserine By similarity
	Modified residue	771	1	N6-acetyllysine By similarity
	Modified residue	775	1	N6-acetyllysine By similarity
	Modified residue	825	1	Phosphoserine; by ATM and ATR and dsDNA kinase By similarity
	Cross-link	555		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
	Cross-link	677		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
	Cross-link	751		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
	Cross-link	780		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO-1) By similarity
	Cross-link	805		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO-1) By similarity
Experimental info
	Sequence conflict	220	1	V → A in AAB51518. Ref.2
	Sequence conflict	263	1	K → R in AAB51518. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	O08629 [UniParc]. Last modified January 20, 2009. Version 2. Checksum: 0E4245EA6CA45CA0	FASTA	835	88,956
	10 20 30 40 50 60 MAASAAAATA AASAATAASA ASGSPGSGEG SAGGEKRPAA SSAAAASASA SSPAGGGGEA 70 80 90 100 110 120 QELLEHCGVC RERLRPERDP RLLPCLHSAC SACLGPATPA AANNSGDGGS AGDGAMVDCP 130 140 150 160 170 180 VCKQQCYSKD IVENYFMRDS GSKASSDSQD ANQCCTSCED NAPATSYCVE CSEPLCETCV 190 200 210 220 230 240 EAHQRVKYTK DHTVRSTGPA KTRDGERTVY CNVHKHEPLV LFCESCDTLT CRDCQLNAHK 250 260 270 280 290 300 DHQYQFLEDA VRNQRKLLAS LVKRLGDKHA TLQKNTKEVR SSIRQVSDVQ KRVQVDVKMA 310 320 330 340 350 360 ILQIMKELNK RGRVLVNDAQ KVTEGQQERL ERQHWTMTKI QKHQEHILRF ASWALESDNN 370 380 390 400 410 420 TALLLSKKLI YFQLHRALKM IVDPVEPHGE MKFQWDLNAW TKSAEAFGKI VAERPGTNST 430 440 450 460 470 480 GPGPMAPPRA PGPLSKQGSG SSQPMEVQEG YGFGTDDPYS SAEPHVSGMK RSRSGEGEVS 490 500 510 520 530 540 GLMRKVPRVS LERLDLDLTS DSQPPVFKVF PGSTTEDYNL IVIERGAAAA AAGQAGTVPP 550 560 570 580 590 600 GAPGAPPLPG MAIVKEEETE AAIGAPPAAP EGPETKPVLM ALTEGPGAEG PRLASPSGST 610 620 630 640 650 660 SSGLEVVAPE VTSAPVSGPG ILDDSATICR VCQKPGDLVM CNQCEFCFHL DCHLPSLQDV 670 680 690 700 710 720 PGEEWSCSLC HVLPDLKEED GSLSLDGADS TGVVAKLSPA NQRKCERVLL ALFCHEPCRP 730 740 750 760 770 780 LHQLATDSTF SMEQPGGTLD LTLIRARLQE KLSPPYSSPQ EFAQDVGRMF KQFNKLTEDK 790 800 810 820 830 ADVQSIIGLQ RFFETRMNDA FGDTKFSAVL VEPPPLNLPS AGLSSQELSG PGDGP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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]. Tissue: Lung.
[2]	Emison E.S., Lewis B.C., Shim H., Li Q., Dang C.V., Lee L.A. Submitted (MAR-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 197-281.
[3]	"Sequence-specific transcriptional repression by KS1, a multiple-zinc-finger-Kruppel-associated box protein." Gebelein B., Urrutia R. Mol. Cell. Biol. 21:928-939(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ZNF382.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	BC166843 mRNA. Translation: AAI66843.1. U95041 mRNA. Translation: AAB51518.1.
IPI	IPI00194567.
RefSeq	NP_446368.1. NM_053916.1.
UniGene	Rn.198494.
3D structure databases
ProteinModelPortal	O08629.
SMR	O08629. Positions 205-249, 625-813.
ModBase	Search...
PTM databases
PhosphoSite	O08629.
Proteomic databases
PaxDb	O08629.
PRIDE	O08629.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000029996; ENSRNOP00000031061; ENSRNOG00000027487.
GeneID	116698.
KEGG	rno:116698.
UCSC	RGD:620289. rat.
Organism-specific databases
CTD	10155.
RGD	620289. Trim28.
Phylogenomic databases
eggNOG	NOG284491.
GeneTree	ENSGT00530000062982.
HOGENOM	HOG000137674.
HOVERGEN	HBG055353.
InParanoid	O08629.
KO	K08882.
OrthoDB	EOG4320XK.
Enzyme and pathway databases
UniPathway	UPA00886.
Gene expression databases
Genevestigator	O08629.
GermOnline	ENSRNOG00000027487. Rattus norvegicus.
Family and domain databases
Gene3D	1.20.920.10. 1 hit. 3.30.40.10. 2 hits.
InterPro	IPR003649. Bbox_C. IPR001487. Bromodomain. IPR019786. Zinc_finger_PHD-type_CS. IPR000315. Znf_B-box. IPR011011. Znf_FYVE_PHD. IPR001965. Znf_PHD. IPR019787. Znf_PHD-finger. IPR001841. Znf_RING. IPR013083. Znf_RING/FYVE/PHD. [Graphical view]
Pfam	PF00628. PHD. 1 hit. PF00643. zf-B_box. 2 hits. [Graphical view]
SMART	SM00502. BBC. 1 hit. SM00336. BBOX. 2 hits. SM00297. BROMO. 1 hit. SM00249. PHD. 1 hit. SM00184. RING. 2 hits. [Graphical view]
SUPFAM	SSF57903. FYVE_PHD_ZnF. 1 hit.
PROSITE	PS00633. BROMODOMAIN_1. False negative. PS50014. BROMODOMAIN_2. False negative. PS50119. ZF_BBOX. 2 hits. PS01359. ZF_PHD_1. 1 hit. PS50016. ZF_PHD_2. 1 hit. PS00518. ZF_RING_1. False negative. PS50089. ZF_RING_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	619598.

Entry information

Entry name

TIF1B_RAT

Accession

Primary (citable) accession number: O08629
Secondary accession number(s): B2RYN5

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	January 20, 2009
Last modified:	April 3, 2013
This is version 100 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program