Search Results

Overview

Uniprot IDQ13616
Protein NameCullin-1
Gene NameCUL1
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
71 GAGVPPSKSKKGQTP
73 GVPPSKSKKGQTPGG
74 VPPSKSKKGQTPGGA

Function

Core component of multiple cullin-RING-based SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. SCF complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins (PubMed:22017875, PubMed:22017877, PubMed:27565346). In the SCF complex, serves as a rigid scaffold that organizes the SKP1-F-box protein and RBX1 subunits. May contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme (PubMed:38326650). The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and exchange of the substrate recognition component is mediated by TIP120A/CAND1 (PubMed:12609982, PubMed:38326650). The functional specificity of the SCF complex depends on the F-box protein as substrate recognition component (PubMed:38326650). SCF(BTRC) and SCF(FBXW11) direct ubiquitination of CTNNB1 and participate in Wnt signaling. SCF(FBXW11) directs ubiquitination of phosphorylated NFKBIA. SCF(BTRC) directs ubiquitination of NFKBIB, NFKBIE, ATF4, SMAD3, SMAD4, CDC25A, FBXO5 and probably NFKB2. SCF(BTRC) and/or SCF(FBXW11) direct ubiquitination of CEP68 (PubMed:25503564, PubMed:25704143). SCF(SKP2) directs ubiquitination of phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. SCF(SKP2) directs ubiquitination of ORC1, CDT1, RBL2, ELF4, CDKN1A, RAG2, FOXO1A, and probably MYC and TAL1. SCF(FBXW7) directs ubiquitination of CCNE1, NOTCH1 released notch intracellular domain (NICD), and probably PSEN1. SCF(FBXW2) directs ubiquitination of GCM1. SCF(FBXO32) directs ubiquitination of MYOD1. SCF(FBXO7) directs ubiquitination of BIRC2 and DLGAP5. SCF(FBXO33) directs ubiquitination of YBX1. SCF(FBXO1) directs ubiquitination of BCL6 and DTL but does not seem to direct ubiquitination of TP53. SCF(BTRC) mediates the ubiquitination of NFKBIA at 'Lys-21' and 'Lys-22'; the degradation frees the associated NFKB1-RELA dimer to translocate into the nucleus and to activate transcription. SCF(CCNF) directs ubiquitination of CCP110. SCF(FBXL3) and SCF(FBXL21) direct ubiquitination of CRY1 and CRY2. SCF(FBXO9) directs ubiquitination of TTI1 and TELO2. SCF(FBXO10) directs ubiquitination of BCL2. Neddylated CUL1-RBX1 ubiquitinates p53/TP53 recruited by Cul7-RING(FBXW8) complex (PubMed:35982156). SCF(BTRC) directs 'Lys-48'-linked ubiquitination of UBR2 in the T-cell receptor signaling pathway (PubMed:38225265). The SCF(FBXO31) protein ligase complex specifically mediates the ubiquitination of proteins amidated at their C-terminus in response to oxidative stress (PubMed:39880951)

Protein Sequence

10 MSSTRSQNPH 20 GLKQIGLDQI 30 WDDLRAGIQQ 40 VYTRQSMAKS 50 RYMELYTHVY 60 NYCTSVHQSN 70 QARGAGVPPS 80 KSKKGQTPGG 90 AQFVGLELYK 100 RLKEFLKNYL 110 TNLLKDGEDL 120 MDESVLKFYT 130 QQWEDYRFSS 140 KVLNGICAYL 150 NRHWVRRECD 160 EGRKGIYEIY 170 SLALVTWRDC 180 LFRPLNKQVT 190 NAVLKLIEKE 200 RNGETINTRL 210 ISGVVQSYVE 220 LGLNEDDAFA 230 KGPTLTVYKE 240 SFESQFLADT 250 ERFYTRESTE 260 FLQQNPVTEY 270 MKKAEARLLE 280 EQRRVQVYLH 290 ESTQDELARK 300 CEQVLIEKHL 310 EIFHTEFQNL 320 LDADKNEDLG 330 RMYNLVSRIQ 340 DGLGELKKLL 350 ETHIHNQGLA 360 AIEKCGEAAL 370 NDPKMYVQTV 380 LDVHKKYNAL 390 VMSAFNNDAG 400 FVAALDKACG 410 RFINNNAVTK 420 MAQSSSKSPE 430 LLARYCDSLL 440 KKSSKNPEEA 450 ELEDTLNQVM 460 VVFKYIEDKD 470 VFQKFYAKML 480 AKRLVHQNSA 490 SDDAEASMIS 500 KLKQACGFEY 510 TSKLQRMFQD 520 IGVSKDLNEQ 530 FKKHLTNSEP 540 LDLDFSIQVL 550 SSGSWPFQQS 560 CTFALPSELE 570 RSYQRFTAFY 580 ASRHSGRKLT 590 WLYQLSKGEL 600 VTNCFKNRYT 610 LQASTFQMAI 620 LLQYNTEDAY 630 TVQQLTDSTQ 640 IKMDILAQVL 650 QILLKSKLLV 660 LEDENANVDE 670 VELKPDTLIK 680 LYLGYKNKKL 690 RVNINVPMKT 700 EQKQEQETTH 710 KNIEEDRKLL 720 IQAAIVRIMK 730 MRKVLKHQQL 740 LGEVLTQLSS 750 RFKPRVPVIK 760 KCIDILIEKE 770 YLERVDGEKD TYSYLA

Gene Ontology

Classification GO ID Description
Cellular Component GO:0031461 cullin-RING ubiquitin ligase complex
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005829 cytosol
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:1990452 Parkin-FBXW7-Cul1 ubiquitin ligase complex
Cellular Component GO:0005886 plasma membrane
Cellular Component GO:0019005 SCF ubiquitin ligase complex
Molecular Function GO:0160072 ubiquitin ligase complex scaffold activity
Molecular Function GO:0031625 ubiquitin protein ligase binding
Biological Process GO:0034599 cellular response to oxidative stress
Biological Process GO:0051298 centrosome duplication
Biological Process GO:0060271 cilium assembly
Biological Process GO:0000082 G1/S transition of mitotic cell cycle
Biological Process GO:0006879 intracellular iron ion homeostasis
Biological Process GO:0097193 intrinsic apoptotic signaling pathway
Biological Process GO:0060173 limb development
Biological Process GO:0014033 neural crest cell differentiation
Biological Process GO:0043123 positive regulation of canonical NF-kappaB signal transduction
Biological Process GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
Biological Process GO:0070936 protein K48-linked ubiquitination
Biological Process GO:0016567 protein ubiquitination
Biological Process GO:0042981 regulation of apoptotic process
Biological Process GO:0030510 regulation of BMP signaling pathway
Biological Process GO:0051726 regulation of cell cycle
Biological Process GO:0010564 regulation of cell cycle process
Biological Process GO:0010824 regulation of centrosome duplication
Biological Process GO:0042752 regulation of circadian rhythm
Biological Process GO:2000001 regulation of DNA damage checkpoint
Biological Process GO:0006355 regulation of DNA-templated transcription
Biological Process GO:0050727 regulation of inflammatory response
Biological Process GO:1901524 regulation of mitophagy
Biological Process GO:0007346 regulation of mitotic cell cycle
Biological Process GO:0032006 regulation of TOR signaling
Biological Process GO:1904415 regulation of xenophagy
Biological Process GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process

Reference

[1] 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.

[2] 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.

[3] 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.

[4] 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.