Overview
| Uniprot ID | P22681 |
|---|
| Protein Name | E3 ubiquitin-protein ligase CBL |
|---|
| Gene Name | CBL |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 521 |
SALGTASKAASGSLH |
| 577 |
GDCPSRDKLPPVPSS |
Function
E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors (PubMed:10514377, PubMed:11896602, PubMed:14661060, PubMed:14739300, PubMed:15190072, PubMed:17509076, PubMed:18374639, PubMed:19689429, PubMed:21596750, PubMed:28381567, PubMed:40101708). Accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their degradation by the proteasome (PubMed:10514377, PubMed:14661060, PubMed:14739300, PubMed:17094949, PubMed:17509076, PubMed:17974561). Recognizes activated receptor tyrosine kinases, including KIT, FLT1, FGFR1, FGFR2, PDGFRA, PDGFRB, CSF1R, EPHA8 and KDR and mediates their ubiquitination to terminate signaling (PubMed:15190072, PubMed:18374639, PubMed:21596750). Recognizes membrane-bound HCK, SRC and other kinases of the SRC family and mediates their ubiquitination and degradation (PubMed:11896602). Ubiquitinates EGFR and SPRY2 (PubMed:17094949, PubMed:17974561). Involved in LAG3-mediated inhibition of TCR signaling: following ligand-binding to LAG3, catalyzes 'Lys-63'-linked ubiquitination of LAG3, unleashing the LAG3 C-terminus from the membrane, and initiating a signaling that prevents TCR activation (PubMed:40101708). Ubiquitinates NECTIN1 following association between NECTIN1 and herpes simplex virus 1/HHV-1 envelope glycoprotein D, leading to NECTIN1 removal from cell surface (PubMed:28381567). Participates in signal transduction in hematopoietic cells. Plays an important role in the regulation of osteoblast differentiation and apoptosis (PubMed:15190072, PubMed:18374639). Essential for osteoclastic bone resorption (PubMed:14739300). The 'Tyr-731' phosphorylated form induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function (PubMed:14739300). In association with CBLB, required for proper feedback inhibition of ciliary platelet-derived growth factor receptor-alpha (PDGFRA) signaling pathway via ubiquitination and internalization of PDGFRA (By similarity)
Protein Sequence
10
MAGNVKKSSG
20
AGGGSGSGGS
30
GSGGLIGLMK
40
DAFQPHHHHH
50
HHLSPHPPGT
60
VDKKMVEKCW
70
KLMDKVVRLC
80
QNPKLALKNS
90
PPYILDLLPD
100
TYQHLRTILS
110
RYEGKMETLG
120
ENEYFRVFME
130
NLMKKTKQTI
140
SLFKEGKERM
150
YEENSQPRRN
160
LTKLSLIFSH
170
MLAELKGIFP
180
SGLFQGDTFR
190
ITKADAAEFW
200
RKAFGEKTIV
210
PWKSFRQALH
220
EVHPISSGLE
230
AMALKSTIDL
240
TCNDYISVFE
250
FDIFTRLFQP
260
WSSLLRNWNS
270
LAVTHPGYMA
280
FLTYDEVKAR
290
LQKFIHKPGS
300
YIFRLSCTRL
310
GQWAIGYVTA
320
DGNILQTIPH
330
NKPLFQALID
340
GFREGFYLFP
350
DGRNQNPDLT
360
GLCEPTPQDH
370
IKVTQEQYEL
380
YCEMGSTFQL
390
CKICAENDKD
400
VKIEPCGHLM
410
CTSCLTSWQE
420
SEGQGCPFCR
430
CEIKGTEPIV
440
VDPFDPRGSG
450
SLLRQGAEGA
460
PSPNYDDDDD
470
ERADDTLFMM
480
KELAGAKVER
490
PPSPFSMAPQ
500
ASLPPVPPRL
510
DLLPQRVCVP
520
SSASALGTAS
530
KAASGSLHKD
540
KPLPVPPTLR
550
DLPPPPPPDR
560
PYSVGAESRP
570
QRRPLPCTPG
580
DCPSRDKLPP
590
VPSSRLGDSW
600
LPRPIPKVPV
610
SAPSSSDPWT
620
GRELTNRHSL
630
PFSLPSQMEP
640
RPDVPRLGST
650
FSLDTSMSMN
660
SSPLVGPECD
670
HPKIKPSSSA
680
NAIYSLAARP
690
LPVPKLPPGE
700
QCEGEEDTEY
710
MTPSSRPLRP
720
LDTSQSSRAC
730
DCDQQIDSCT
740
YEAMYNIQSQ
750
APSITESSTF
760
GEGNLAAAHA
770
NTGPEESENE
780
DDGYDVPKPP
790
VPAVLARRTL
800
SDISNASSSF
810
GWLSLDGDPT
820
TNVTEGSQVP
830
ERPPKPFPRR
840
INSERKAGSC
850
QQGSGPAASA
860
ATASPQLSSE
870
IENLMSQGYS
880
YQDIQKALVI
890
AQNNIEMAKN
900
ILREFVSISS
PAHVAT
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005929 |
cilium |
| Biological Process |
GO:0042594 |
response to starvation |
| Biological Process |
GO:0033574 |
response to testosterone |
| Biological Process |
GO:0007165 |
signal transduction |
| Biological Process |
GO:0046718 |
symbiont entry into host cell |
| Biological Process |
GO:0070086 |
ubiquitin-dependent endocytosis |
| Biological Process |
GO:0006511 |
ubiquitin-dependent protein catabolic process |
| Cellular Component |
GO:0005829 |
cytosol |
| Cellular Component |
GO:0016600 |
flotillin complex |
| Cellular Component |
GO:0005925 |
focal adhesion |
| Cellular Component |
GO:0005794 |
Golgi apparatus |
| Cellular Component |
GO:0030426 |
growth cone |
| Cellular Component |
GO:0045121 |
membrane raft |
| Cellular Component |
GO:0048471 |
perinuclear region of cytoplasm |
| Cellular Component |
GO:0005886 |
plasma membrane |
| Molecular Function |
GO:0045296 |
cadherin binding |
| Molecular Function |
GO:0005509 |
calcium ion binding |
| Molecular Function |
GO:0046875 |
ephrin receptor binding |
| Molecular Function |
GO:0036312 |
phosphatidylinositol 3-kinase regulatory subunit binding |
| Molecular Function |
GO:0001784 |
phosphotyrosine residue binding |
| Molecular Function |
GO:0030971 |
receptor tyrosine kinase binding |
| Molecular Function |
GO:0017124 |
SH3 domain binding |
| Molecular Function |
GO:0061630 |
ubiquitin protein ligase activity |
| Molecular Function |
GO:0004842 |
ubiquitin-protein transferase activity |
| Molecular Function |
GO:0008270 |
zinc ion binding |
| Biological Process |
GO:0071456 |
cellular response to hypoxia |
| Biological Process |
GO:1990090 |
cellular response to nerve growth factor stimulus |
| Biological Process |
GO:0036120 |
cellular response to platelet-derived growth factor stimulus |
| Biological Process |
GO:0019221 |
cytokine-mediated signaling pathway |
| Biological Process |
GO:0006974 |
DNA damage response |
| Biological Process |
GO:0008584 |
male gonad development |
| Biological Process |
GO:0043303 |
mast cell degranulation |
| Biological Process |
GO:0043066 |
negative regulation of apoptotic process |
| Biological Process |
GO:0042059 |
negative regulation of epidermal growth factor receptor signaling pathway |
| Biological Process |
GO:0050868 |
negative regulation of T cell activation |
| Biological Process |
GO:0050860 |
negative regulation of T cell receptor signaling pathway |
| Biological Process |
GO:0045742 |
positive regulation of epidermal growth factor receptor signaling pathway |
| Biological Process |
GO:0051897 |
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction |
| Biological Process |
GO:0048260 |
positive regulation of receptor-mediated endocytosis |
| Biological Process |
GO:0051865 |
protein autoubiquitination |
| Biological Process |
GO:0070534 |
protein K63-linked ubiquitination |
| Biological Process |
GO:0006513 |
protein monoubiquitination |
| Biological Process |
GO:0050821 |
protein stabilization |
| Biological Process |
GO:0016567 |
protein ubiquitination |
| Biological Process |
GO:2000583 |
regulation of platelet-derived growth factor receptor-alpha signaling pathway |
| Biological Process |
GO:0014823 |
response to activity |
| Biological Process |
GO:0045471 |
response to ethanol |
| Biological Process |
GO:0010332 |
response to gamma radiation |
Reference
[1] 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.