Overview
| Uniprot ID | Q13617 |
|---|
| Protein Name | Cullin-2 |
|---|
| Gene Name | CUL2 |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 404 |
NLLKKSAKGMTENEV |
Function
Core component of multiple cullin-RING-based ECS (ElonginB/C-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of target proteins (PubMed:11384984, PubMed:26138980, PubMed:29775578, PubMed:29779948, PubMed:37844242, PubMed:38326650). CUL2 serves as a rigid scaffold in the complex and may contribute to catalysis through positioning of the substrate and the E2 ubiquitin-conjugating enzyme (PubMed:10973499, PubMed:11384984, PubMed:12609982, PubMed:24076655, PubMed:9122164, PubMed:37844242, PubMed:38326650). 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:12609982, PubMed:24076655, PubMed:27565346, PubMed:38326650). The functional specificity of the ECS complex depends on the substrate recognition component (PubMed:10973499, PubMed:26138980, PubMed:29775578, PubMed:29779948, PubMed:9122164, PubMed:38326650). ECS(VHL) mediates the ubiquitination of hypoxia-inducible factor (HIF) (PubMed:10973499, PubMed:9122164). A number of ECS complexes (containing either KLHDC2, KLHDC3, KLHDC10, APPBP2, FEM1A, FEM1B or FEM1C 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:26138980, PubMed:29775578, PubMed:29779948, PubMed:37844242). ECS complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins (PubMed:27565346). ECS(LRR1) ubiquitinates MCM7 and promotes CMG replisome disassembly by VCP and chromatin extraction during S-phase (By similarity)
Protein Sequence
10
MSLKPRVVDF
20
DETWNKLLTT
30
IKAVVMLEYV
40
ERATWNDRFS
50
DIYALCVAYP
60
EPLGERLYTE
70
TKIFLENHVR
80
HLHKRVLESE
90
EQVLVMYHRY
100
WEEYSKGADY
110
MDCLYRYLNT
120
QFIKKNKLTE
130
ADLQYGYGGV
140
DMNEPLMEIG
150
ELALDMWRKL
160
MVEPLQAILI
170
RMLLREIKND
180
RGGEDPNQKV
190
IHGVINSFVH
200
VEQYKKKFPL
210
KFYQEIFESP
220
FLTETGEYYK
230
QEASNLLQES
240
NCSQYMEKVL
250
GRLKDEEIRC
260
RKYLHPSSYT
270
KVIHECQQRM
280
VADHLQFLHA
290
ECHNIIRQEK
300
KNDMANMYVL
310
LRAVSTGLPH
320
MIQELQNHIH
330
DEGLRATSNL
340
TQENMPTLFV
350
ESVLEVHGKF
360
VQLINTVLNG
370
DQHFMSALDK
380
ALTSVVNYRE
390
PKSVCKAPEL
400
LAKYCDNLLK
410
KSAKGMTENE
420
VEDRLTSFIT
430
VFKYIDDKDV
440
FQKFYARMLA
450
KRLIHGLSMS
460
MDSEEAMINK
470
LKQACGYEFT
480
SKLHRMYTDM
490
SVSADLNNKF
500
NNFIKNQDTV
510
IDLGISFQIY
520
VLQAGAWPLT
530
QAPSSTFAIP
540
QELEKSVQMF
550
ELFYSQHFSG
560
RKLTWLHYLC
570
TGEVKMNYLG
580
KPYVAMVTTY
590
QMAVLLAFNN
600
SETVSYKELQ
610
DSTQMNEKEL
620
TKTIKSLLDV
630
KMINHDSEKE
640
DIDAESSFSL
650
NMNFSSKRTK
660
FKITTSMQKD
670
TPQEMEQTRS
680
AVDEDRKMYL
690
QAAIVRIMKA
700
RKVLRHNALI
710
QEVISQSRAR
720
FNPSISMIKK
730
CIEVLIDKQY
740
IERSQASADE
YSYVA
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0031462 |
Cul2-RING ubiquitin ligase complex |
| Cellular Component |
GO:0005737 |
cytoplasm |
| Cellular Component |
GO:0005829 |
cytosol |
| Cellular Component |
GO:0005730 |
nucleolus |
| Cellular Component |
GO:0005654 |
nucleoplasm |
| Cellular Component |
GO:0005634 |
nucleus |
| 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 |
| Molecular Function |
GO:0004842 |
ubiquitin-protein transferase activity |
| Biological Process |
GO:0000082 |
G1/S transition of mitotic cell cycle |
| Biological Process |
GO:0097193 |
intrinsic apoptotic signaling pathway |
| Biological Process |
GO:0160276 |
negative regulation of beige fat cell differentiation |
| Biological Process |
GO:2000104 |
negative regulation of DNA-templated DNA replication |
| Biological Process |
GO:0000122 |
negative regulation of transcription by RNA polymerase II |
| Biological Process |
GO:0043161 |
proteasome-mediated ubiquitin-dependent protein catabolic process |
| Biological Process |
GO:0016567 |
protein ubiquitination |
| Biological Process |
GO:0072344 |
rescue of stalled cytosolic ribosome |
| Biological Process |
GO:1990116 |
ribosome-associated ubiquitin-dependent protein catabolic process |
| Biological Process |
GO:0031146 |
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process |
| Biological Process |
GO:0140627 |
ubiquitin-dependent protein catabolic process via the C-end degron rule pathway |
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.