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Overview

Uniprot IDO08629
Protein NameTranscription intermediary factor 1-beta
Gene NameTrim28
OrganismRattus norvegicus

Kla Sites from experimental identification

Position Flanking peptide
780 FNKLTEDKADVQSII

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). Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs). 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. Mediates TRAF6 SUMOylation to regulate its nucleo-cytoplasmic shuttling and modulate activation of the canonical NF-kappa-B signaling pathway. Facilitates SUMOylation of NLRP3, protecting it from 'Lys-48'-linked ubiquitination and proteasomal degradation and thereby enhancing inflammasome activation (By similarity)

Protein Sequence

10 MAASAAAATA 20 AASAATAASA 30 ASGSPGSGEG 40 SAGGEKRPAA 50 SSAAAASASA 60 SSPAGGGGEA 70 QELLEHCGVC 80 RERLRPERDP 90 RLLPCLHSAC 100 SACLGPATPA 110 AANNSGDGGS 120 AGDGAMVDCP 130 VCKQQCYSKD 140 IVENYFMRDS 150 GSKASSDSQD 160 ANQCCTSCED 170 NAPATSYCVE 180 CSEPLCETCV 190 EAHQRVKYTK 200 DHTVRSTGPA 210 KTRDGERTVY 220 CNVHKHEPLV 230 LFCESCDTLT 240 CRDCQLNAHK 250 DHQYQFLEDA 260 VRNQRKLLAS 270 LVKRLGDKHA 280 TLQKNTKEVR 290 SSIRQVSDVQ 300 KRVQVDVKMA 310 ILQIMKELNK 320 RGRVLVNDAQ 330 KVTEGQQERL 340 ERQHWTMTKI 350 QKHQEHILRF 360 ASWALESDNN 370 TALLLSKKLI 380 YFQLHRALKM 390 IVDPVEPHGE 400 MKFQWDLNAW 410 TKSAEAFGKI 420 VAERPGTNST 430 GPGPMAPPRA 440 PGPLSKQGSG 450 SSQPMEVQEG 460 YGFGTDDPYS 470 SAEPHVSGMK 480 RSRSGEGEVS 490 GLMRKVPRVS 500 LERLDLDLTS 510 DSQPPVFKVF 520 PGSTTEDYNL 530 IVIERGAAAA 540 AAGQAGTVPP 550 GAPGAPPLPG 560 MAIVKEEETE 570 AAIGAPPAAP 580 EGPETKPVLM 590 ALTEGPGAEG 600 PRLASPSGST 610 SSGLEVVAPE 620 VTSAPVSGPG 630 ILDDSATICR 640 VCQKPGDLVM 650 CNQCEFCFHL 660 DCHLPSLQDV 670 PGEEWSCSLC 680 HVLPDLKEED 690 GSLSLDGADS 700 TGVVAKLSPA 710 NQRKCERVLL 720 ALFCHEPCRP 730 LHQLATDSTF 740 SMEQPGGTLD 750 LTLIRARLQE 760 KLSPPYSSPQ 770 EFAQDVGRMF 780 KQFNKLTEDK 790 ADVQSIIGLQ 800 RFFETRMNDA 810 FGDTKFSAVL 820 VEPPPLNLPS 830 AGLSSQELSG 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: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:0060028 convergent extension involved in axis elongation
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:0007566 embryo implantation
Biological Process GO:0060669 embryonic placenta morphogenesis
Biological Process GO:0043045 epigenetic programming of gene expression
Biological Process GO:0001837 epithelial to mesenchymal transition
Biological Process GO:0071514 genomic imprinting
Biological Process GO:0001701 in utero embryonic development
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:0045869 negative regulation of single stranded viral RNA replication via double stranded DNA intermediate
Biological Process GO:0000122 negative regulation of transcription by RNA polymerase II
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:0046777 protein autophosphorylation
Biological Process GO:0006468 protein phosphorylation
Biological Process GO:0016925 protein sumoylation
Biological Process GO:0016567 protein ubiquitination
Biological Process GO:0044790 suppression of viral release by host

Reference

[1] Sheng L, Xu H, Wang Y, Ni J, Xiang T et al.. Systematic analysis of lysine lactylation in nucleus pulposus cells.. iScience 27(11):111157. 2024 Nov 15. PMID: 39524337.