UniProt Accession

 TIF1B_HUMAN; Q13263; O00677; Q7Z632; Q93040; Q96IM1 

Genbank Protein ID

 U78773; X97548; U95040; BC004978; BC007390; BC052986; U31657 

Genbank Nucleotide ID

 AAB37341.1; CAA66150.1; AAB51517.1; AAH04978.1; AAH07390.2; AAH52986.1; AAA74954.1 

Protein Name

 Transcription intermediary factor 1-beta 

Protein Synonyms/Alias

 TIF1-beta; E3 SUMO-protein ligase TRIM28; KRAB-associated protein 1; KAP-1; KRAB-interacting protein 1; KRIP-1; Nuclear corepressor KAP-1; RING finger protein 96; Tripartite motif-containing protein 28 

Gene Name

 TRIM28 

Gene Synonyms/Alias

 KAP1; RNF96; TIF1B 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
31	EGSAGGEKRSTAPSA	acetylation	[1]
31	EGSAGGEKRSTAPSA	ubiquitination	[1, 2, 3]
127	CKQQCFSKDIVENYF	ubiquitination	[4, 5]
213	TVYCNVHKHEPLVLF	ubiquitination	[3, 6]
238	DCQLNAHKDHQYQFL	ubiquitination	[2, 3, 6]
254	DAVRNQRKLLASLVK	ubiquitination	[3, 4, 5]
261	KLLASLVKRLGDKHA	ubiquitination	[3, 4, 5, 6]
266	LVKRLGDKHATLQKS	acetylation	[7]
266	LVKRLGDKHATLQKS	ubiquitination	[3, 6]
272	DKHATLQKSTKEVRS	ubiquitination	[4, 5, 6]
275	ATLQKSTKEVRSSIR	ubiquitination	[6]
289	RQVSDVQKRVQVDVK	ubiquitination	[6]
296	KRVQVDVKMAILQIM	ubiquitination	[3, 6]
304	MAILQIMKELNKRGR	acetylation	[7]
304	MAILQIMKELNKRGR	ubiquitination	[3, 4, 5, 6]
319	VLVNDAQKVTEGQQE	ubiquitination	[1, 2, 3, 4, 5, 6, 8, 9]
337	RQHWTMTKIQKHQEH	ubiquitination	[3, 4, 5]
340	WTMTKIQKHQEHILR	acetylation	[1, 7]
340	WTMTKIQKHQEHILR	ubiquitination	[1, 3, 4, 5, 6]
365	NTALLLSKKLIYFQL	ubiquitination	[4, 5, 6, 9]
366	TALLLSKKLIYFQLH	ubiquitination	[2, 3, 4, 5]
377	FQLHRALKMIVDPVE	acetylation	[7]
377	FQLHRALKMIVDPVE	ubiquitination	[2, 3, 4, 5, 6]
390	VEPHGEMKFQWDLNA	ubiquitination	[6]
400	WDLNAWTKSAEAFGK	ubiquitination	[4, 5, 6, 10]
407	KSAEAFGKIVAERPG	ubiquitination	[2, 3, 4, 5, 6]
434	RAPGPLSKQGSGSSQ	ubiquitination	[1, 2, 3, 4, 5, 6, 8]
469	EPHVSGVKRSRSGEG	ubiquitination	[1, 2, 3, 4, 5, 6, 8]
507	DSQPPVFKVFPGSTT	ubiquitination	[6]
554	LAGMAIVKEEETEAA	sumoylation	[11, 12, 13]
575	ATEGPETKPVLMALA	sumoylation	[11, 12]
575	ATEGPETKPVLMALA	ubiquitination	[6]
676	CHVLPDLKEEDGSLS	sumoylation	[11, 12]
750	IRARLQEKLSPPYSS	sumoylation	[11, 12, 14, 15, 16]
750	IRARLQEKLSPPYSS	ubiquitination	[2, 3, 4, 5, 6]
770	QDVGRMFKQFNKLTE	acetylation	[7]
770	QDVGRMFKQFNKLTE	ubiquitination	[3, 4, 5, 6]
774	RMFKQFNKLTEDKAD	acetylation	[7]
774	RMFKQFNKLTEDKAD	ubiquitination	[3, 4, 5, 6]
779	FNKLTEDKADVQSII	sumoylation	[11, 12, 13, 14, 15, 16, 17]
779	FNKLTEDKADVQSII	ubiquitination	[3, 4, 5, 6]
804	NEAFGDTKFSAVLVE	sumoylation	[11, 12, 13, 14]

Reference

 [1] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [2] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [3] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [4] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [5] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [6] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [7] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [8] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [9] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [10] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [11] Doxorubicin down-regulates Kruppel-associated box domain-associated protein 1 sumoylation that relieves its transcription repression on p21WAF1/CIP1 in breast cancer MCF-7 cells.
 Lee YK, Thomas SN, Yang AJ, Ann DK.
 J Biol Chem. 2007 Jan 19;282(3):1595-606. [PMID: 17079232]
 [12] Sumoylation of the transcriptional intermediary factor 1beta (TIF1beta), the Co-repressor of the KRAB Multifinger proteins, is required for its transcriptional activity and is modulated by the KRAB domain.
 Mascle XH, Germain-Desprez D, Huynh P, Estephan P, Aubry M.
 J Biol Chem. 2007 Apr 6;282(14):10190-202. [PMID: 17298944]
 [13] KAP-1 phosphorylation regulates CHD3 nucleosome remodeling during the DNA double-strand break response.
 Goodarzi AA, Kurka T, Jeggo PA.
 Nat Struct Mol Biol. 2011 Jun 5;18(7):831-9. [PMID: 21642969]
 [14] Site-specific identification of SUMO-2 targets in cells reveals an inverted SUMOylation motif and a hydrophobic cluster SUMOylation motif.
 Matic I, Schimmel J, Hendriks IA, van Santen MA, van de Rijke F, van Dam H, Gnad F, Mann M, Vertegaal AC.
 Mol Cell. 2010 Aug 27;39(4):641-52. [PMID: 20797634]
 [15] A novel proteomics approach to identify SUMOylated proteins and their modification sites in human cells.
 Galisson F, Mahrouche L, Courcelles M, Bonneil E, Meloche S, Chelbi-Alix MK, Thibault P.
 Mol Cell Proteomics. 2011 Feb;10(2):M110.004796. [PMID: 21098080]
 [16] Targeted identification of SUMOylation sites in human proteins using affinity enrichment and paralog-specific reporter ions.
 Lamoliatte F, Bonneil E, Durette C, Caron-Lizotte O, Wildemann D, Zerweck J, Wenschuh H, Thibault P.
 Mol Cell Proteomics. 2013 Jun 7;. [PMID: 23750026]
 [17] In vivo identification of sumoylation sites by a signature tag and cysteine-targeted affinity purification.
 Blomster HA, Imanishi SY, Siimes J, Kastu J, Morrice NA, Eriksson JE, Sistonen L.
 J Biol Chem. 2010 Jun 18;285(25):19324-9. [PMID: 20388717] 

Functional Description

 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. Also 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. 

Sequence Annotation

 DOMAIN 697 801 Bromo.
 ZN_FING 65 121 RING-type.
 ZN_FING 148 195 B box-type 1; atypical.
 ZN_FING 204 245 B box-type 2.
 ZN_FING 625 672 PHD-type.
 REGION 65 376 RBCC domain.
 REGION 246 376 Leucine zipper alpha helical coiled-coil
 REGION 247 376 Interaction with MAGEC2.
 REGION 366 370 Involved in binding PPP1CA.
 REGION 476 513 HP1 box.
 MOTIF 481 494 PxVxL motif.
 MOD_RES 2 2 N-acetylalanine.
 MOD_RES 19 19 Phosphoserine.
 MOD_RES 50 50 Phosphoserine.
 MOD_RES 304 304 N6-acetyllysine.
 MOD_RES 340 340 N6-acetyllysine.
 MOD_RES 377 377 N6-acetyllysine.
 MOD_RES 439 439 Phosphoserine.
 MOD_RES 471 471 Phosphoserine.
 MOD_RES 473 473 Phosphoserine.
 MOD_RES 479 479 Phosphoserine.
 MOD_RES 489 489 Phosphoserine.
 MOD_RES 501 501 Phosphoserine.
 MOD_RES 541 541 Phosphothreonine.
 MOD_RES 594 594 Phosphoserine.
 MOD_RES 683 683 Phosphoserine.
 MOD_RES 697 697 Phosphoserine.
 MOD_RES 752 752 Phosphoserine.
 MOD_RES 757 757 Phosphoserine.
 MOD_RES 770 770 N6-acetyllysine.
 MOD_RES 774 774 N6-acetyllysine.
 MOD_RES 824 824 Phosphoserine; by ATM and ATR and dsDNA
 CROSSLNK 554 554 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 676 676 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 750 750 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 779 779 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 804 804 Glycyl lysine isopeptide (Lys-Gly)  

Keyword

 3D-structure; Acetylation; Alternative splicing; Complete proteome; Direct protein sequencing; Isopeptide bond; Ligase; Metal-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; Repressor; Transcription; Transcription regulation; Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 835 AA 

Protein Sequence

Gene Ontology

 GO:0005719; C:nuclear euchromatin; IEA:Compara.
 GO:0005720; C:nuclear heterochromatin; IEA:Compara.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0003677; F:DNA binding; IDA:UniProtKB.
 GO:0004672; F:protein kinase activity; IEA:Compara.
 GO:0043565; F:sequence-specific DNA binding; IEA:Compara.
 GO:0003700; F:sequence-specific DNA binding transcription factor activity; IEA:Compara.
 GO:0003713; F:transcription coactivator activity; IEA:Compara.
 GO:0003714; F:transcription corepressor activity; IDA:UniProtKB.
 GO:0031625; F:ubiquitin protein ligase binding; IDA:UniProtKB.
 GO:0004842; F:ubiquitin-protein ligase activity; IDA:UniProtKB.
 GO:0008270; F:zinc ion binding; IDA:UniProtKB.
 GO:0060028; P:convergent extension involved in axis elongation; IEA:Compara.
 GO:0006281; P:DNA repair; IDA:UniProtKB.
 GO:0060669; P:embryonic placenta morphogenesis; IEA:Compara.
 GO:0001837; P:epithelial to mesenchymal transition; ISS:HGNC.
 GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IEA:Compara.
 GO:0045892; P:negative regulation of transcription, DNA-dependent; IDA:UniProtKB.
 GO:0045739; P:positive regulation of DNA repair; IDA:UniProtKB.
 GO:0045893; P:positive regulation of transcription, DNA-dependent; ISS:HGNC.
 GO:0046777; P:protein autophosphorylation; IEA:Compara.
 GO:0051259; P:protein oligomerization; IDA:UniProtKB.
 GO:0016925; P:protein sumoylation; IDA:UniProtKB.
 GO:0006367; P:transcription initiation from RNA polymerase II promoter; TAS:Reactome. 

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. 

Pfam

 PF00628; PHD
 PF00643; zf-B_box 

SMART

 SM00502; BBC
 SM00336; BBOX
 SM00297; BROMO
 SM00249; PHD
 SM00184; RING 

PROSITE

 PS00633; BROMODOMAIN_1
 PS50014; BROMODOMAIN_2
 PS50119; ZF_BBOX
 PS01359; ZF_PHD_1
 PS50016; ZF_PHD_2
 PS00518; ZF_RING_1
 PS50089; ZF_RING_2 

PRINTS