Search Results

Overview

Uniprot IDQ13263
Protein NameTranscription intermediary factor 1-beta
Gene NameTRIM28
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
188 HQRVKYTKDHTVRST
199 VRSTGPAKSRDGERT
213 TVYCNVHKHEPLVLF
254 DAVRNQRKLLASLVK
261 KLLASLVKRLGDKHA
272 DKHATLQKSTKEVRS
289 RQVSDVQKRVQVDVK
31 EGSAGGEKRSTAPSA
319 VLVNDAQKVTEGQQE
366 TALLLSKKLIYFQLH
434 RAPGPLSKQGSGSSQ
469 EPHVSGVKRSRSGEG
484 EVSGLMRKVPRVSLE

Function

E3 SUMO and ubiquitin ligase that plays a pivotal role in embryonic development, genomic imprinting, and maintenance of genomic stability through repression of repetitive and retroviral elements. Also involved in DNA repair, regulation of innate immunity or cellular energy homeostasis. Acts as a scaffold for assembling transcriptional repression complexes containing methyltransferases, histone deacetylases, and chromatin remodelers. Serves as a nuclear corepressor for KRAB domain-containing zinc finger proteins (KRAB-ZFPs), mediating gene silencing by recruiting CHD3, a subunit of the nucleosome remodeling and deacetylation (NuRD) complex, and SETDB1, which methylates histone H3 at Lys-9 (H3K9me), leading to heterochromatin formation. In collaboration with SETDB1, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway (By similarity). Functions as a coactivator for CEBPB and NR3C1 (glucocorticoid receptor) in transcriptional activation of ORM1, and as a corepressor for ERBB4. Inhibits E2F1 activity by promoting E2F1-HDAC1 complex formation and preventing E2F1 acetylation. This contributes to CDKN1A/p21(CIP1) regulation and provides a partial backup to suppress E2F1-mediated apoptosis in the absence of RB1. Mediates the nuclear localization of several KRAB-ZFP transcription factors including KOX1, ZNF268, and ZNF300 among others. In association with isoform 2 of ZFP90, is required for the transcriptional repressor activity of FOXP3 and the suppressive function of regulatory T-cells (Treg)(PubMed:23543754). Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306). Acts as a corepressor for ZFP568. Beyond its nuclear functions, acts as a positive regulator of type I interferon (IFN-I) signaling by promoting Lys-63-linked ubiquitination of TBK1, facilitating TBK1-IRF3 complex formation (PubMed:38495890). Mediates TRAF6 SUMOylation to regulate its nucleo-cytoplasmic shuttling and modulate activation of the canonical NF-kappa-B signaling pathway (PubMed:39920527). Facilitates SUMOylation of NLRP3, protecting it from 'Lys-48'-linked ubiquitination and proteasomal degradation and thereby enhancing inflammasome activation (PubMed:34373456)

Protein Sequence

10 MAASAAAASA 20 AAASAASGSP 30 GPGEGSAGGE 40 KRSTAPSAAA 50 SASASAAASS 60 PAGGGAEALE 70 LLEHCGVCRE 80 RLRPEREPRL 90 LPCLHSACSA 100 CLGPAAPAAA 110 NSSGDGGAAG 120 DGTVVDCPVC 130 KQQCFSKDIV 140 ENYFMRDSGS 150 KAATDAQDAN 160 QCCTSCEDNA 170 PATSYCVECS 180 EPLCETCVEA 190 HQRVKYTKDH 200 TVRSTGPAKS 210 RDGERTVYCN 220 VHKHEPLVLF 230 CESCDTLTCR 240 DCQLNAHKDH 250 QYQFLEDAVR 260 NQRKLLASLV 270 KRLGDKHATL 280 QKSTKEVRSS 290 IRQVSDVQKR 300 VQVDVKMAIL 310 QIMKELNKRG 320 RVLVNDAQKV 330 TEGQQERLER 340 QHWTMTKIQK 350 HQEHILRFAS 360 WALESDNNTA 370 LLLSKKLIYF 380 QLHRALKMIV 390 DPVEPHGEMK 400 FQWDLNAWTK 410 SAEAFGKIVA 420 ERPGTNSTGP 430 APMAPPRAPG 440 PLSKQGSGSS 450 QPMEVQEGYG 460 FGSGDDPYSS 470 AEPHVSGVKR 480 SRSGEGEVSG 490 LMRKVPRVSL 500 ERLDLDLTAD 510 SQPPVFKVFP 520 GSTTEDYNLI 530 VIERGAAAAA 540 TGQPGTAPAG 550 TPGAPPLAGM 560 AIVKEEETEA 570 AIGAPPTATE 580 GPETKPVLMA 590 LAEGPGAEGP 600 RLASPSGSTS 610 SGLEVVAPEG 620 TSAPGGGPGT 630 LDDSATICRV 640 CQKPGDLVMC 650 NQCEFCFHLD 660 CHLPALQDVP 670 GEEWSCSLCH 680 VLPDLKEEDG 690 SLSLDGADST 700 GVVAKLSPAN 710 QRKCERVLLA 720 LFCHEPCRPL 730 HQLATDSTFS 740 LDQPGGTLDL 750 TLIRARLQEK 760 LSPPYSSPQE 770 FAQDVGRMFK 780 QFNKLTEDKA 790 DVQSIIGLQR 800 FFETRMNEAF 810 GDTKFSAVLV 820 EPPPMSLPGA 830 GLSSQELSGG PGDGP

Gene Ontology

Classification GO ID Description
Cellular Component GO:0000785 chromatin
Cellular Component GO:0000791 euchromatin
Cellular Component GO:0000792 heterochromatin
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0032991 protein-containing complex
Cellular Component GO:0090575 RNA polymerase II transcription regulator complex
Molecular Function GO:0003682 chromatin binding
Molecular Function GO:0140463 chromatin-protein adaptor activity
Molecular Function GO:0070087 chromo shadow domain binding
Molecular Function GO:0003677 DNA binding
Molecular Function GO:0035851 Krueppel-associated box domain binding
Molecular Function GO:1990841 promoter-specific chromatin binding
Molecular Function GO:0004672 protein kinase activity
Molecular Function GO:0003723 RNA binding
Molecular Function GO:0061665 SUMO ligase activity
Molecular Function GO:0019789 SUMO transferase activity
Molecular Function GO:0003713 transcription coactivator activity
Molecular Function GO:0003714 transcription corepressor activity
Molecular Function GO:0061630 ubiquitin protein ligase activity
Molecular Function GO:0031625 ubiquitin protein ligase binding
Molecular Function GO:0004842 ubiquitin-protein transferase activity
Molecular Function GO:0008270 zinc ion binding
Biological Process GO:0006325 chromatin organization
Biological Process GO:0006974 DNA damage response
Biological Process GO:0006346 DNA methylation-dependent constitutive heterochromatin formation
Biological Process GO:0006281 DNA repair
Biological Process GO:0006351 DNA-templated transcription
Biological Process GO:0001837 epithelial to mesenchymal transition
Biological Process GO:0045087 innate immune response
Biological Process GO:0043124 negative regulation of canonical NF-kappaB signal transduction
Biological Process GO:0045892 negative regulation of DNA-templated transcription
Biological Process GO:0045739 positive regulation of DNA repair
Biological Process GO:0045893 positive regulation of DNA-templated transcription
Biological Process GO:0042307 positive regulation of protein import into nucleus
Biological Process GO:0032481 positive regulation of type I interferon production
Biological Process GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
Biological Process GO:0016925 protein sumoylation
Biological Process GO:0016567 protein ubiquitination
Biological Process GO:0044790 suppression of viral release by host

Reference

[1] Yang D, Yin J, Shan L, Yi X, Zhang W et al.. Identification of lysine-lactylated substrates in gastric cancer cells.. iScience 25(7):104630. 2022 Jul 15. PMID: 35800753.

[2] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[3] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.

[4] Lin Y, Chen M, Wang D, Yu Y, Chen R et al.. Multi-Proteomic Analysis Reveals the Effect of Protein Lactylation on Matrix and Cholesterol Metabolism in Tendinopathy.. J Proteome Res 22(6):1712-1722. 2023 Jun 2. PMID: 37159428.

[5] Yang YH, Wang QC, Kong J, Yang JT, Liu JF. Global profiling of lysine lactylation in human lungs.. Proteomics 23(15):e2200437. 2023 Aug. PMID: 37170646.

[6] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.

[7] Bao Q, Wan N, He Z, Cao J, Yuan W et al.. Subcellular Proteomic Mapping of Lysine Lactylation.. J Am Soc Mass Spectrom 35(12):3221-3232. 2024 Dec 4. PMID: 39569522.

[8] Guo X, Ren X, Yan C, Huang H. Quantitative Proteomics Reveals the Role of Lysine Lactylation in Lenalidomide-Resistance in Multiple Myeloma Cells.. ACS Chem Biol 20(7):1728-1738. 2025 Jul 18. PMID: 40590393.

[9] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.