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Overview

Uniprot IDQ01105
Protein NameProtein SET
Gene NameSET
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
13 QSPLPPQKKKPRPPP
132 VTEFEDIKSGYRIDF
14 SPLPPQKKKPRPPPA
15 PLPPQKKKPRPPPAL
154 FENKVLSKEFHLNES
167 ESGDPSSKSTEIKWK
174 KSTEIKWKSGKDLTK
189 RSSQTQNKASRKRQH
35 SASAGLPKKGEKEQQ
68 QASEEILKVEQKYNK
72 EILKVEQKYNKLRQP
83 LRQPFFQKRSELIAK

Function

Multitasking protein, involved in apoptosis, transcription, nucleosome assembly and histone chaperoning. Isoform 2 anti-apoptotic activity is mediated by inhibition of the GZMA-activated DNase, NME1. In the course of cytotoxic T-lymphocyte (CTL)-induced apoptosis, GZMA cleaves SET, disrupting its binding to NME1 and releasing NME1 inhibition. Isoform 1 and isoform 2 are potent inhibitors of protein phosphatase 2A. Isoform 1 and isoform 2 inhibit EP300/CREBBP and PCAF-mediated acetylation of histones (HAT) and nucleosomes, most probably by masking the accessibility of lysines of histones to the acetylases. The predominant target for inhibition is histone H4. HAT inhibition leads to silencing of HAT-dependent transcription and prevents active demethylation of DNA. Both isoforms stimulate DNA replication of the adenovirus genome complexed with viral core proteins; however, isoform 2 specific activity is higher

Protein Sequence

10 MAPKRQSPLP 20 PQKKKPRPPP 30 ALGPEETSAS 40 AGLPKKGEKE 50 QQEAIEHIDE 60 VQNEIDRLNE 70 QASEEILKVE 80 QKYNKLRQPF 90 FQKRSELIAK 100 IPNFWVTTFV 110 NHPQVSALLG 120 EEDEEALHYL 130 TRVEVTEFED 140 IKSGYRIDFY 150 FDENPYFENK 160 VLSKEFHLNE 170 SGDPSSKSTE 180 IKWKSGKDLT 190 KRSSQTQNKA 200 SRKRQHEEPE 210 SFFTWFTDHS 220 DAGADELGEV 230 IKDDIWPNPL 240 QYYLVPDMDD 250 EEGEGEEDDD 260 DDEEEEGLED 270 IDEEGDEDEG 280 EEDEDDDEGE 290 EGEEDEGEDD

Gene Ontology

Classification GO ID Description
Cellular Component GO:0000785 chromatin
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005829 cytosol
Cellular Component GO:0005783 endoplasmic reticulum
Cellular Component GO:0005811 lipid droplet
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0048471 perinuclear region of cytoplasm
Cellular Component GO:0032991 protein-containing complex
Molecular Function GO:0003682 chromatin binding
Molecular Function GO:0003677 DNA binding
Molecular Function GO:0042393 histone binding
Molecular Function GO:0004864 protein phosphatase inhibitor activity
Molecular Function GO:0019888 protein phosphatase regulator activity
Biological Process GO:0006260 DNA replication
Biological Process GO:0045892 negative regulation of DNA-templated transcription
Biological Process GO:0043524 negative regulation of neuron apoptotic process
Biological Process GO:0006334 nucleosome assembly
Biological Process GO:0006337 nucleosome disassembly

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] Cheng Z, Huang H, Li M, Chen Y. Proteomic analysis identifies PFKP lactylation in SW480 colon cancer cells.. iScience 27(1):108645. 2024 Jan 19. PMID: 38155775.

[7] 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.

[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] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.

[10] 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.