Search Results

Overview

Uniprot IDQ13620
Protein NameCullin-4B
Gene NameCUL4B
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
158 TSQQQQLKNKSILIS
200 SAKKLVIKNFKDKPK
55 TTPPTSAKKRKLNSS
56 TPPTSAKKRKLNSSS
58 PTSAKKRKLNSSSSS
589 ELEKMLDKIMIIFRF
789 LQSLACGKARVLAKN

Function

Core component of multiple cullin-RING-based E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:14578910, PubMed:16322693, PubMed:16678110, PubMed:18593899, PubMed:22118460, PubMed:29779948, PubMed:30166453, PubMed:33854232, PubMed:33854239, PubMed:25970626). The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition subunit (PubMed:14578910, PubMed:16678110, PubMed:18593899, PubMed:22118460, PubMed:29779948). CUL4B may act within the complex as a scaffold protein, contributing to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme (PubMed:14578910, PubMed:16678110, PubMed:18593899, PubMed:22118460). Plays a role as part of the E3 ubiquitin-protein ligase complex in polyubiquitination of CDT1, histone H2A, histone H3 and histone H4 in response to radiation-induced DNA damage (PubMed:14578910, PubMed:16678110, PubMed:18593899). Targeted to UV damaged chromatin by DDB2 and may be important for DNA repair and DNA replication (PubMed:16678110). A number of DCX complexes (containing either TRPC4AP or DCAF12 as substrate-recognition component) are part of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation (PubMed:29779948). The DCX(AMBRA1) complex is a master regulator of the transition from G1 to S cell phase by mediating ubiquitination of phosphorylated cyclin-D (CCND1, CCND2 and CCND3) (PubMed:33854232, PubMed:33854239). The DCX(AMBRA1) complex also acts as a regulator of Cul5-RING (CRL5) E3 ubiquitin-protein ligase complexes by mediating ubiquitination and degradation of Elongin-C (ELOC) component of CRL5 complexes (PubMed:30166453). Required for ubiquitination of cyclin E (CCNE1 or CCNE2), and consequently, normal G1 cell cycle progression (PubMed:16322693, PubMed:19801544). Regulates the mammalian target-of-rapamycin (mTOR) pathway involved in control of cell growth, size and metabolism (PubMed:18235224). Specific CUL4B regulation of the mTORC1-mediated pathway is dependent upon 26S proteasome function and requires interaction between CUL4B and MLST8 (PubMed:18235224). With CUL4A, contributes to ribosome biogenesis (PubMed:26711351)

Protein Sequence

10 MMSQSSGSGD 20 GNDDEATTSK 30 DGGFSSPSPS 40 AAAAAQEVRS 50 ATDGNTSTTP 60 PTSAKKRKLN 70 SSSSSSSNSS 80 NEREDFDSTS 90 SSSSTPPLQP 100 RDSASPSTSS 110 FCLGVSVAAS 120 SHVPIQKKLR 130 FEDTLEFVGF 140 DAKMAEESSS 150 SSSSSSPTAA 160 TSQQQQLKNK 170 SILISSVASV 180 HHANGLAKSS 190 TTVSSFANSK 200 PGSAKKLVIK 210 NFKDKPKLPE 220 NYTDETWQKL 230 KEAVEAIQNS 240 TSIKYNLEEL 250 YQAVENLCSY 260 KISANLYKQL 270 RQICEDHIKA 280 QIHQFREDSL 290 DSVLFLKKID 300 RCWQNHCRQM 310 IMIRSIFLFL 320 DRTYVLQNSM 330 LPSIWDMGLE 340 LFRAHIISDQ 350 KVQNKTIDGI 360 LLLIERERNG 370 EAIDRSLLRS 380 LLSMLSDLQI 390 YQDSFEQRFL 400 EETNRLYAAE 410 GQKLMQEREV 420 PEYLHHVNKR 430 LEEEADRLIT 440 YLDQTTQKSL 450 IATVEKQLLG 460 EHLTAILQKG 470 LNNLLDENRI 480 QDLSLLYQLF 490 SRVRGGVQVL 500 LQQWIEYIKA 510 FGSTIVINPE 520 KDKTMVQELL 530 DFKDKVDHII 540 DICFLKNEKF 550 INAMKEAFET 560 FINKRPNKPA 570 ELIAKYVDSK 580 LRAGNKEATD 590 EELEKMLDKI 600 MIIFRFIYGK 610 DVFEAFYKKD 620 LAKRLLVGKS 630 ASVDAEKSML 640 SKLKHECGAA 650 FTSKLEGMFK 660 DMELSKDIMI 670 QFKQYMQNQN 680 VPGNIELTVN 690 ILTMGYWPTY 700 VPMEVHLPPE 710 MVKLQEIFKT 720 FYLGKHSGRK 730 LQWQSTLGHC 740 VLKAEFKEGK 750 KELQVSLFQT 760 LVLLMFNEGE 770 EFSLEEIKQA 780 TGIEDGELRR 790 TLQSLACGKA 800 RVLAKNPKGK 810 DIEDGDKFIC 820 NDDFKHKLFR 830 IKINQIQMKE 840 TVEEQASTTE 850 RVFQDRQYQI 860 DAAIVRIMKM 870 RKTLSHNLLV 880 SEVYNQLKFP 890 VKPADLKKRI 900 ESLIDRDYME 910 RDKENPNQYN YIA

Gene Ontology

Classification GO ID Description
Cellular Component GO:0080008 Cul4-RING E3 ubiquitin ligase complex
Cellular Component GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
Cellular Component GO:0031465 Cul4B-RING E3 ubiquitin ligase complex
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0070062 extracellular exosome
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0032991 protein-containing complex
Molecular Function GO:0160072 ubiquitin ligase complex scaffold activity
Molecular Function GO:0031625 ubiquitin protein ligase binding
Biological Process GO:0048708 astrocyte differentiation
Biological Process GO:0008283 cell population proliferation
Biological Process GO:0034644 cellular response to UV
Biological Process GO:0006974 DNA damage response
Biological Process GO:0040029 epigenetic regulation of gene expression
Biological Process GO:0000082 G1/S transition of mitotic cell cycle
Biological Process GO:0010467 gene expression
Biological Process GO:1904178 negative regulation of adipose tissue development
Biological Process GO:0006289 nucleotide-excision repair
Biological Process GO:0010498 proteasomal protein catabolic process
Biological Process GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
Biological Process GO:0000209 protein polyubiquitination
Biological Process GO:0016567 protein ubiquitination
Biological Process GO:0042981 regulation of apoptotic process
Biological Process GO:0010506 regulation of autophagy
Biological Process GO:1901987 regulation of cell cycle phase transition
Biological Process GO:0042127 regulation of cell population proliferation
Biological Process GO:0080135 regulation of cellular response to stress
Biological Process GO:0030174 regulation of DNA-templated DNA replication initiation
Biological Process GO:0045995 regulation of embryonic development
Biological Process GO:0060964 regulation of miRNA-mediated gene silencing
Biological Process GO:1902412 regulation of mitotic cytokinesis
Biological Process GO:0032814 regulation of natural killer cell activation
Biological Process GO:2000036 regulation of stem cell population maintenance
Biological Process GO:0031297 replication fork processing
Biological Process GO:0042254 ribosome biogenesis
Biological Process GO:0007283 spermatogenesis
Biological Process GO:0070914 UV-damage excision repair

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] 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.

[4] 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.

[5] 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.

[6] 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.