Search Results

Overview

Uniprot ID	Q9UPN9
Protein Name	E3 ubiquitin-protein ligase TRIM33
Gene Name	TRIM33
Organism	Homo sapiens

Kla Sites from experimental identification

Position	Flanking peptide
1118	QPRRKRLKSDERPVH
763	SSGRTAEKTSLSFKS
769	EKTSLSFKSDQVKVK
861	LSSLVNGKSPIRSLM
950	CDNLQHSKKGKTAQG
951	DNLQHSKKGKTAQGL
953	LQHSKKGKTAQGLSP

Function

Acts as an E3 ubiquitin-protein ligase. Promotes SMAD4 ubiquitination, nuclear exclusion and degradation via the ubiquitin proteasome pathway. According to PubMed:16751102, does not promote a decrease in the level of endogenous SMAD4. May act as a transcriptional repressor. Inhibits the transcriptional response to TGF-beta/BMP signaling cascade. Plays a role in the control of cell proliferation. Its association with SMAD2 and SMAD3 stimulates erythroid differentiation of hematopoietic stem/progenitor (By similarity). Monoubiquitinates SMAD4 and acts as an inhibitor of SMAD4-dependent TGF-beta/BMP signaling cascade (Monoubiquitination of SMAD4 hampers its ability to form a stable complex with activated SMAD2/3 resulting in inhibition of TGF-beta/BMP signaling cascade)

Protein Sequence

10 MAENKGGGEA 20 ESGGGGSGSA 30 PVTAGAAGPA 40 AQEAEPPLTA 50 VLVEEEEEEG 60 GRAGAEGGAA 70 GPDDGGVAAA 80 SSGSAQAASS 90 PAASVGTGVA 100 GGAVSTPAPA 110 PASAPAPGPS 120 AGPPPGPPAS 130 LLDTCAVCQQ 140 SLQSRREAEP 150 KLLPCLHSFC 160 LRCLPEPERQ 170 LSVPIPGGSN 180 GDIQQVGVIR 190 CPVCRQECRQ 200 IDLVDNYFVK 210 DTSEAPSSSD 220 EKSEQVCTSC 230 EDNASAVGFC 240 VECGEWLCKT 250 CIEAHQRVKF 260 TKDHLIRKKE 270 DVSESVGASG 280 QRPVFCPVHK 290 QEQLKLFCET 300 CDRLTCRDCQ 310 LLEHKEHRYQ 320 FLEEAFQNQK 330 GAIENLLAKL 340 LEKKNYVHFA 350 ATQVQNRIKE 360 VNETNKRVEQ 370 EIKVAIFTLI 380 NEINKKGKSL 390 LQQLENVTKE 400 RQMKLLQQQN 410 DITGLSRQVK 420 HVMNFTNWAI 430 ASGSSTALLY 440 SKRLITFQLR 450 HILKARCDPV 460 PAANGAIRFH 470 CDPTFWAKNV 480 VNLGNLVIES 490 KPAPGYTPNV 500 VVGQVPPGTN 510 HISKTPGQIN 520 LAQLRLQHMQ 530 QQVYAQKHQQ 540 LQQMRMQQPP 550 APVPTTTTTT 560 QQHPRQAAPQ 570 MLQQQPPRLI 580 SVQTMQRGNM 590 NCGAFQAHQM 600 RLAQNAARIP 610 GIPRHSGPQY 620 SMMQPHLQRQ 630 HSNPGHAGPF 640 PVVSVHNTTI 650 NPTSPTTATM 660 ANANRGPTSP 670 SVTAIELIPS 680 VTNPENLPSL 690 PDIPPIQLED 700 AGSSSLDNLL 710 SRYISGSHLP 720 PQPTSTMNPS 730 PGPSALSPGS 740 SGLSNSHTPV 750 RPPSTSSTGS 760 RGSCGSSGRT 770 AEKTSLSFKS 780 DQVKVKQEPG 790 TEDEICSFSG 800 GVKQEKTEDG 810 RRSACMLSSP 820 ESSLTPPLST 830 NLHLESELDA 840 LASLENHVKI 850 EPADMNESCK 860 QSGLSSLVNG 870 KSPIRSLMHR 880 SARIGGDGNN 890 KDDDPNEDWC 900 AVCQNGGDLL 910 CCEKCPKVFH 920 LTCHVPTLLS 930 FPSGDWICTF 940 CRDIGKPEVE 950 YDCDNLQHSK 960 KGKTAQGLSP 970 VDQRKCERLL 980 LYLYCHELSI 990 EFQEPVPASI 1000 PNYYKIIKKP 1010 MDLSTVKKKL 1020 QKKHSQHYQI 1030 PDDFVADVRL 1040 IFKNCERFNE 1050 MMKVVQVYAD 1060 TQEINLKADS 1070 EVAQAGKAVA 1080 LYFEDKLTEI 1090 YSDRTFAPLP 1100 EFEQEEDDGE 1110 VTEDSDEDFI 1120 QPRRKRLKSD ERPVHIK

Gene Ontology

Classification	GO ID	Description
Cellular Component	GO:0000785	chromatin
Cellular Component	GO:0005654	nucleoplasm
Cellular Component	GO:0005634	nucleus
Molecular Function	GO:0070410	co-SMAD binding
Molecular Function	GO:0003677	DNA binding
Molecular Function	GO:0070412	R-SMAD binding
Molecular Function	GO:0061630	ubiquitin protein ligase activity
Molecular Function	GO:0004842	ubiquitin-protein transferase activity
Molecular Function	GO:0008270	zinc ion binding
Biological Process	GO:0006351	DNA-templated transcription
Biological Process	GO:0030514	negative regulation of BMP signaling pathway
Biological Process	GO:0045892	negative regulation of DNA-templated transcription
Biological Process	GO:0000122	negative regulation of transcription by RNA polymerase II
Biological Process	GO:0016567	protein ubiquitination
Biological Process	GO:0017015	regulation of transforming growth factor beta receptor signaling pathway

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] 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.

[4] 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.

[5] 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.

[6] Chao L, Xu Y, Yang Y, Ao X, Liang J. Identification of lactylation-related biomarkers for diagnosis, prognosis, and treatment responsiveness in triple-negative breast cancer.. World J Surg Oncol 24(1):77. 2026 Jan 22. PMID: 41566505.

[7] 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.