Search Results

Overview

Uniprot ID	Q93034
Protein Name	Cullin-5
Gene Name	CUL5
Organism	Homo sapiens

Kla Sites from experimental identification

Position	Flanking peptide
10	TSNLLKNKGSLQFED
8	MATSNLLKNKGSLQF

Function

Core component of multiple cullin-5-RING E3 ubiquitin-protein ligase complexes (ECS complexes, also named CRL5 complexes), which mediate the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:11384984, PubMed:15601820, PubMed:21199876, PubMed:21980433, PubMed:23897481, PubMed:25505247, PubMed:27910872, PubMed:32200094, PubMed:33268465, PubMed:35512830, PubMed:38418882, PubMed:40963025). Acts a scaffold protein that contributes to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme (PubMed:11384984, PubMed:15601820, PubMed:33268465). The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable SOCS box-containing substrate recognition component (PubMed:11384984, PubMed:15601820, PubMed:33268465). Acts as a key regulator of neuron positioning during cortex development: component of various SOCS-containing ECS complexes, such as the ECS(SOCS7) complex, that regulate reelin signaling by mediating ubiquitination and degradation of DAB1 (By similarity). ECS(SOCS1) seems to direct ubiquitination of JAK2 (PubMed:11384984). The ECS(SOCS2) complex mediates the ubiquitination and subsequent proteasomal degradation of phosphorylated EPOR and GHR (PubMed:21980433, PubMed:25505247). The ECS(SPSB3) complex catalyzes ubiquitination of nuclear CGAS (PubMed:38418882). ECS(KLHDC1) complex is part of the DesCEND (destruction via C-end degrons) pathway and mediates ubiquitination and degradation of truncated SELENOS selenoprotein produced by failed UGA/Sec decoding, which ends with a glycine (PubMed:32200094). The ECS(ASB9) complex mediates ubiquitination and degradation of CKB (PubMed:33268465). As part of some ECS complex, promotes 'Lys-11'-linked ubiquitination and degradation of BTRC (PubMed:27910872). As part of a multisubunit ECS complex, polyubiquitinates monoubiquitinated POLR2A (PubMed:19920177). As part of the ECS(RAB40C) complex, mediates ANKRD28 ubiquitination and degradation, thereby inhibiting protein phosphatase 6 (PP6) complex activity and focal adhesion assembly during cell migration (PubMed:35512830). As part of the ECS(RAB40A) complex, mediates RHOU 'Lys-48'-linked ubiquitination and degradation, thus inhibiting focal adhesion disassembly during cell migration (PubMed:26598620). As part of the ECS(RAB40B) complex, mediates LIMA1/EPLIN and RAP2 ubiquitination, thereby regulating actin cytoskeleton dynamics and stress fiber formation during cell migration (PubMed:33999101, PubMed:35293963). The ECS(ASB7) complex acts a negative regulator of H3K9me3 histone mark by mediating ubiquitination and degradation of SUV39H1 (PubMed:40440427). As part of the ECS(LRRC58) complex, mediates CDO1 ubiquitination and degradation, regulating cysteine catabolism (PubMed:40963025). May form a cell surface vasopressin receptor (PubMed:9037604)

Protein Sequence

10 MATSNLLKNK 20 GSLQFEDKWD 30 FMRPIVLKLL 40 RQESVTKQQW 50 FDLFSDVHAV 60 CLWDDKGPAK 70 IHQALKEDIL 80 EFIKQAQARV 90 LSHQDDTALL 100 KAYIVEWRKF 110 FTQCDILPKP 120 FCQLEITLMG 130 KQGSNKKSNV 140 EDSIVRKLML 150 DTWNESIFSN 160 IKNRLQDSAM 170 KLVHAERLGE 180 AFDSQLVIGV 190 RESYVNLCSN 200 PEDKLQIYRD 210 NFEKAYLDST 220 ERFYRTQAPS 230 YLQQNGVQNY 240 MKYADAKLKE 250 EEKRALRYLE 260 TRRECNSVEA 270 LMECCVNALV 280 TSFKETILAE 290 CQGMIKRNET 300 EKLHLMFSLM 310 DKVPNGIEPM 320 LKDLEEHIIS 330 AGLADMVAAA 340 ETITTDSEKY 350 VEQLLTLFNR 360 FSKLVKEAFQ 370 DDPRFLTARD 380 KAYKAVVNDA 390 TIFKLELPLK 400 QKGVGLKTQP 410 ESKCPELLAN 420 YCDMLLRKTP 430 LSKKLTSEEI 440 EAKLKEVLLV 450 LKYVQNKDVF 460 MRYHKAHLTR 470 RLILDISADS 480 EIEENMVEWL 490 REVGMPADYV 500 NKLARMFQDI 510 KVSEDLNQAF 520 KEMHKNNKLA 530 LPADSVNIKI 540 LNAGAWSRSS 550 EKVFVSLPTE 560 LEDLIPEVEE 570 FYKKNHSGRK 580 LHWHHLMSNG 590 IITFKNEVGQ 600 YDLEVTTFQL 610 AVLFAWNQRP 620 REKISFENLK 630 LATELPDAEL 640 RRTLWSLVAF 650 PKLKRQVLLY 660 EPQVNSPKDF 670 TEGTLFSVNQ 680 EFSLIKNAKV 690 QKRGKINLIG 700 RLQLTTERMR 710 EEENEGIVQL 720 RILRTQEAII 730 QIMKMRKKIS 740 NAQLQTELVE 750 ILKNMFLPQK 760 KMIKEQIEWL 770 IEHKYIRRDE 780 SDINTFIYMA

Gene Ontology

Classification	GO ID	Description
Cellular Component	GO:0031466	Cul5-RING ubiquitin ligase complex
Cellular Component	GO:0005737	cytoplasm
Cellular Component	GO:0005829	cytosol
Cellular Component	GO:0005634	nucleus
Cellular Component	GO:0019005	SCF ubiquitin ligase complex
Cellular Component	GO:0090734	site of DNA damage
Molecular Function	GO:0005262	calcium channel activity
Molecular Function	GO:0038023	signaling receptor activity
Molecular Function	GO:0160072	ubiquitin ligase complex scaffold activity
Molecular Function	GO:0031625	ubiquitin protein ligase binding
Molecular Function	GO:0004842	ubiquitin-protein transferase activity
Biological Process	GO:0016477	cell migration
Biological Process	GO:0038128	ERBB2 signaling pathway
Biological Process	GO:0000082	G1/S transition of mitotic cell cycle
Biological Process	GO:0097193	intrinsic apoptotic signaling pathway
Biological Process	GO:0051895	negative regulation of focal adhesion assembly
Biological Process	GO:0120184	negative regulation of focal adhesion disassembly
Biological Process	GO:0030335	positive regulation of cell migration
Biological Process	GO:0043161	proteasome-mediated ubiquitin-dependent protein catabolic process
Biological Process	GO:0070979	protein K11-linked ubiquitination
Biological Process	GO:0016567	protein ubiquitination
Biological Process	GO:0038026	reelin-mediated signaling pathway
Biological Process	GO:2001222	regulation of neuron migration
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] 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] 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.

[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.