Search Results

Overview

Uniprot ID	Q13619
Protein Name	Cullin-4A
Gene Name	CUL4A
Organism	Homo sapiens

Kla Sites from experimental identification

Position	Flanking peptide
46	GSKKLVIKNFRDRPR
8	MADEAPRKGSFSALV

Function

Core component of multiple cullin-RING-based E3 ubiquitin-protein ligase complexes which mediate the ubiquitination of target proteins (PubMed:14578910, PubMed:14739464, PubMed:15448697, PubMed:15548678, PubMed:15811626, PubMed:16678110, PubMed:17041588, PubMed:24209620, PubMed:30166453, PubMed:33854232, PubMed:33854239). As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme (PubMed:14578910, PubMed:14739464, PubMed:15448697, PubMed:15548678, PubMed:15811626, PubMed:16678110, PubMed:17041588, PubMed:24209620). The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1 (PubMed:14578910, PubMed:14739464, PubMed:15448697, PubMed:15548678, PubMed:15811626, PubMed:16678110, PubMed:17041588, PubMed:24209620). The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition component (PubMed:14578910, PubMed:14739464, PubMed:15448697, PubMed:15548678, PubMed:15811626, PubMed:16678110, PubMed:17041588, PubMed:24209620). DCX(DET1-COP1) directs ubiquitination of JUN (PubMed:14739464). DCX(DDB2) directs ubiquitination of XPC (PubMed:15811626). DCX(DDB2) ubiquitinates histones H3-H4 and is required for efficient histone deposition during replication-coupled (H3.1) and replication-independent (H3.3) nucleosome assembly, probably by facilitating the transfer of H3 from ASF1A/ASF1B to other chaperones involved in histone deposition (PubMed:16678110, PubMed:17041588, PubMed:24209620). DCX(DTL) plays a role in PCNA-dependent polyubiquitination of CDT1 and MDM2-dependent ubiquitination of p53/TP53 in response to radiation-induced DNA damage and during DNA replication (PubMed:14578910, PubMed:15448697, PubMed:15548678). DCX(DTL) directs autoubiquitination of DTL (PubMed:23478445). In association with DDB1 and SKP2 probably is involved in ubiquitination of CDKN1B/p27kip (PubMed:16537899). Is involved in ubiquitination of HOXA9 (PubMed:14609952). The DDB1-CUL4A-DTL E3 ligase complex regulates the circadian clock function by mediating the ubiquitination and degradation of CRY1 (PubMed:26431207). The DCX(ERCC8) complex (also named CSA complex) plays a role in transcription-coupled repair (TCR) (PubMed:12732143, PubMed:32355176, PubMed:38316879). 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). With CUL4B, contributes to ribosome biogenesis (PubMed:26711351)

Protein Sequence

10 MADEAPRKGS 20 FSALVGRTNG 30 LTKPAALAAA 40 PAKPGGAGGS 50 KKLVIKNFRD 60 RPRLPDNYTQ 70 DTWRKLHEAV 80 RAVQSSTSIR 90 YNLEELYQAV 100 ENLCSHKVSP 110 MLYKQLRQAC 120 EDHVQAQILP 130 FREDSLDSVL 140 FLKKINTCWQ 150 DHCRQMIMIR 160 SIFLFLDRTY 170 VLQNSTLPSI 180 WDMGLELFRT 190 HIISDKMVQS 200 KTIDGILLLI 210 ERERSGEAVD 220 RSLLRSLLGM 230 LSDLQVYKDS 240 FELKFLEETN 250 CLYAAEGQRL 260 MQEREVPEYL 270 NHVSKRLEEE 280 GDRVITYLDH 290 STQKPLIACV 300 EKQLLGEHLT 310 AILQKGLDHL 320 LDENRVPDLA 330 QMYQLFSRVR 340 GGQQALLQHW 350 SEYIKTFGTA 360 IVINPEKDKD 370 MVQDLLDFKD 380 KVDHVIEVCF 390 QKNERFVNLM 400 KESFETFINK 410 RPNKPAELIA 420 KHVDSKLRAG 430 NKEATDEELE 440 RTLDKIMILF 450 RFIHGKDVFE 460 AFYKKDLAKR 470 LLVGKSASVD 480 AEKSMLSKLK 490 HECGAAFTSK 500 LEGMFKDMEL 510 SKDIMVHFKQ 520 HMQNQSDSGP 530 IDLTVNILTM 540 GYWPTYTPME 550 VHLTPEMIKL 560 QEVFKAFYLG 570 KHSGRKLQWQ 580 TTLGHAVLKA 590 EFKEGKKEFQ 600 VSLFQTLVLL 610 MFNEGDGFSF 620 EEIKMATGIE 630 DSELRRTLQS 640 LACGKARVLI 650 KSPKGKEVED 660 GDKFIFNGEF 670 KHKLFRIKIN 680 QIQMKETVEE 690 QVSTTERVFQ 700 DRQYQIDAAI 710 VRIMKMRKTL 720 GHNLLVSELY 730 NQLKFPVKPG 740 DLKKRIESLI 750 DRDYMERDKD NPNQYHYVA

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:0005737	cytoplasm
Cellular Component	GO:0005654	nucleoplasm
Cellular Component	GO:0005634	nucleus
Molecular Function	GO:0160072	ubiquitin ligase complex scaffold activity
Molecular Function	GO:0061630	ubiquitin protein ligase activity
Molecular Function	GO:0031625	ubiquitin protein ligase binding
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:0001701	in utero embryonic development
Biological Process	GO:0097193	intrinsic apoptotic signaling pathway
Biological Process	GO:1904178	negative regulation of adipose tissue development
Biological Process	GO:0006289	nucleotide-excision repair
Biological Process	GO:0045732	positive regulation of protein catabolic process
Biological Process	GO:0043161	proteasome-mediated ubiquitin-dependent protein catabolic process
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:0048511	rhythmic process
Biological Process	GO:0042254	ribosome biogenesis
Biological Process	GO:0007283	spermatogenesis
Biological Process	GO:0042110	T cell activation
Biological Process	GO:0140627	ubiquitin-dependent protein catabolic process via the C-end degron rule pathway

Reference

[1] 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.

[2] 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.

[3] 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.