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Protein Page:
Cbl-b (human)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitination
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylylation
sn S-Nitrosylation
ca Caspase cleavage
sc Succinylation

Overview
Cbl-b E3 ubiquitin-protein ligase which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and transfers it to substrates, generally promoting their degradation by the proteasome. Negatively regulates TCR (T-cell receptor), BCR (B- cell receptor) and FCER1 (high affinity immunoglobulin epsilon receptor) signal transduction pathways. In naive T-cells, inhibits VAV1 activation upon TCR engagement and imposes a requirement for CD28 costimulation for proliferation and IL-2 production. Also acts by promoting PIK3R1/p85 ubiquitination, which impairs its recruitment to the TCR and subsequent activation. In activated T- cells, inhibits PLCG1 activation and calcium mobilization upon restimulation and promotes anergy. In B-cells, acts by ubiquitinating SYK and promoting its proteasomal degradation. May also be involved in EGFR ubiquitination and internalization. Interacts with SH3 domain-containing proteins LCK, CRK and SORBS1. Interacts with LCP2 and ZAP70. May interact with CBL. Interacts with SH3 domain-containing proteins VAV1, FYN, FGR, PLCG1, GRB2, CRKL, PIK3R1 and SH3KBP1/CIN85. Identified in heterotrimeric complexes with SH3KBP1/CIN85, CD2AP and ARHGEF7, where one CBLB peptide binds two copies of the other protein. Interacts with poly-ubiquitinated proteins. Dimerization is required for the binding of poly-ubiquitin, but not for the binding of mono-ubiquitin. Expressed in placenta, heart, lung, kidney, spleen, ovary and testis, as well as fetal brain and liver and hematopoietic cell lines, but not in adult brain, liver, pancreas, salivary gland, or skeletal muscle. Present in lymphocytes. 4 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: Calcium-binding protein; Ubiquitin ligase; EC 6.3.2.-; Ligase; Ubiquitin conjugating system; Adaptor/scaffold
Cellular Component: cytoplasm; nucleolus; plasma membrane; nucleus; cytosol
Molecular Function: signal transducer activity; protein binding; phosphotyrosine binding; zinc ion binding; ubiquitin-protein ligase activity; calcium ion binding; ligase activity
Biological Process: cell surface receptor linked signal transduction; T cell activation; positive regulation of protein catabolic process; protein ubiquitination; negative regulation of T cell receptor signaling pathway; negative regulation of alpha-beta T cell proliferation; immune response; NLS-bearing substrate import into nucleus; signal transduction; positive regulation of T cell anergy
Reference #:  Q13191 (UniProtKB)
Alt. Names/Synonyms: Cas-Br-M (murine) ecotropic retroviral transforming sequence b; Cas-Br-M (murine) ectropic retroviral transforming sequence b; Casitas B-lineage lymphoma proto-oncogene b; Cbl-b; CBLB; DKFZp686J10223; DKFZp779A0729; DKFZp779F1443; E3 ubiquitin-protein ligase CBL-B; FLJ36865; FLJ41152; Nbla00127; RING finger protein 56; RNF56; SH3-binding protein CBL-B; Signal transduction protein CBL-B
Gene Symbols: CBLB
Molecular weight: 109,450 Da
Basal Isoelectric point: 8.15  Predict pI for various phosphorylation states
CST Pathways:  B Cell Receptor Signaling  |  Insulin Receptor Signaling
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
Select Structure to View Below

Cbl-b

Protein Structure Not Found.


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Sites Implicated In
molecular association, regulation: Y665‑p, Y709‑p

Modification Sites and Domains Show Modification Legend
Click here to view phosphorylation modifications only

Modification Sites in Parent Protein, Orthologs, and Isoforms Show Modification Legend
 

Show Multiple Sequence Alignment


 SS 

SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.


 MS 

MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       human

 
0 1 R8-m1 MANSMNGrNPGGRGG
0 1 R18-m1 GGRGGNPrKGRILGI
0 2 Y92-p LRLILSKyDDNQKLA
0 2 Y106-p AQLSENEyFKIYIDS
0 1 Y276-p VKARLQKysTKPGsY
0 1 S277-p KARLQKysTKPGsYI
1 0 S282-p KysTKPGsYIFRLSC
0 3 Y337-p LYPDGRSyNPDLTGL
0 3 Y360-p IKVTQEQyELyCEMG
1 76 Y363-p TQEQyELyCEMGSTF
0 1 T471-p LANVRKCtDRQNsPV
0 10 S476-p KCtDRQNsPVtsPGS
0 2 T479-p DRQNsPVtsPGSsPL
0 9 S480-p RQNsPVtsPGSsPLA
0 10 S484-p PVtsPGSsPLAQRRK
0 1 R520 LIQKGIVRsPCGsPt
0 11 S521-p IQKGIVRsPCGsPtG
0 10 S525-p IVRsPCGsPtGsPKS
0 1 T527-p RsPCGsPtGsPKSSP
0 9 S529-p PCGsPtGsPKSSPCM
0 1 T601-p CPRDVFGtNQLVGCR
0 3 S614-p CRLLGEGsPKPGItA
0 1 T620-p GsPKPGItASSNVNG
0 3 S634-p GRHSRVGsDPVLMRK
0 3 S662-p FSNGHLGsEEyDVPP
2 118 Y665-p GHLGsEEyDVPPRLs
0 92 S672-p yDVPPRLsPPPPVTT
0 1 T678 LsPPPPVTTLLPSIK
0 1 T679 sPPPPVTTLLPSIKC
0 1 T698-p ANSLSEKtRDPVEED
2 113 Y709-p VEEDDDEyKIPSSHP
0 1 S735-p NVKPPVRsCDNGHCM
0 17 Y763-p NIPDLSIyLKGDVFD
0 1 N788 ARPPTRDNPKHGSSL
0 1 T798-p HGSSLNRtPSDyDLL
0 1 Y802-p LNRtPSDyDLLIPPL
0 4 T882-p LPGENVKtNRtsQDy
0 10 T885-p ENVKtNRtsQDyDQL
0 23 S886-p NVKtNRtsQDyDQLP
1 441 Y889-p tNRtsQDyDQLPsCs
0 9 S894-p QDyDQLPsCsDGsQA
0 1 C895 DyDQLPsCsDGsQAP
0 8 S896-p yDQLPsCsDGsQAPA
0 1 S899-p LPsCsDGsQAPARPP
0 1 S977-p FAFPPPVsPRLNL__
  mouse

 
R8 MANSMNGRNPGGRGG
R18 GGRGGNPRKGRILGI
Y92 LRLILSKYDDNQKLA
Y106 AQLSENEYFKIYIDS
Y276 VKARLQKYSTKPGSY
S277 KARLQKYSTKPGSYI
S282 KYSTKPGSYIFRLSC
Y337 LYPDGRSYNPDLTGL
Y360 IKVTQEQYELYCEMG
Y363 TQEQYELYCEMGSTF
T471-p LASVRKCtDRQNsPV
S476-p KCtDRQNsPVtsPGS
T479-p DRQNsPVtsPGSsPL
S480-p RQNsPVtsPGSsPLA
S484-p PVtsPGSsPLAQRRK
R520-m2 LIQKGIVrsPCGsPT
S521-p IQKGIVrsPCGsPTG
S525-p IVrsPCGsPTGsPKS
T527 rsPCGsPTGsPKSSP
S529-p PCGsPTGsPKSSPCM
T600 CPRDAFGTNQVMGCR
S613 CRILGDGSPKPGVTA
T619 GSPKPGVTANSSLNG
S633 GRHSRMGSEQVLMRK
T661 FSNGHLATEEyDVPP
Y664-p GHLATEEyDVPPRLs
S671-p yDVPPRLsPPPPVtt
T677-p LsPPPPVttLLPSIK
T678-p sPPPPVttLLPSIKC
T697 ANCLSEKTRDTVEDD
Y708-p VEDDDDEyKIPSSHP
S734 NVKAPVRSCDNGHCI
Y763-p NIPDLGIyLKGGGSD
S788-p ARPPPRDsPKHGSSV
T798 HGSSVNRTPSDYDLL
Y802 VNRTPSDYDLLIPPL
A882 AAGDSGKANRAsQDy
A885 DSGKANRAsQDyDQL
S886-p SGKANRAsQDyDQLP
Y889-p ANRAsQDyDQLPSss
S894 QDyDQLPSssDGSQA
S895-p DyDQLPSssDGSQAP
S896-p yDQLPSssDGSQAPA
S899 LPSssDGSQAPARPP
S977-p FAFPPPVsPRLNL__
  rat

 
R8 MANSMNGRNPGGRGG
R18 GGRGGNPRKGRILGI
Y92 LRLILSKYDDNQKLA
Y106 AQLSENEYFKIYIDS
Y276 VKARLQKYSTKPGSY
S277 KARLQKYSTKPGSYI
S282 KYSTKPGSYIFRLSC
Y337 LYPDGRSYNPDLTGL
Y360 IKVTQEQYELYCEMG
Y363 TQEQYELYCEMGSTF
T471 LASVRKCTDRQNSPV
S476 KCTDRQNSPVTSPGS
T479 DRQNSPVTSPGSSPL
S480 RQNSPVTSPGSSPLA
S484 PVTSPGSSPLAQRRK
R520 LIQKGIVRSPCGSPT
S521 IQKGIVRSPCGSPTG
S525 IVRSPCGSPTGSPKS
T527 RSPCGSPTGSPKSSP
S529 PCGSPTGSPKSSPCM
T600 CPRDAFGTNQVMGCR
S613 CRILGDGSPKPGVTA
T619 GSPKPGVTANSNLNG
S633-p GRHSRMGsDQVLMRK
P661 FSNGHLAPEEYDVPP
Y664 GHLAPEEYDVPPRLS
S671 YDVPPRLSPPPPVTA
T677 LSPPPPVTALLPSIK
A678 SPPPPVTALLPSIKC
T697 ANCLSEKTRDTVEED
Y708-p VEEDDDEyKIPSSHP
S734 NVKPPVRSCDNGHCI
Y763 NIPDLGIYLKGEDAF
- gap
- gap
- gap
S838-p APGDGVKsNRAsQDy
A841 DGVKsNRAsQDyDQL
S842-p GVKsNRAsQDyDQLP
Y845-p sNRAsQDyDQLPSSS
S850 QDyDQLPSSSDGSQA
S851 DyDQLPSSSDGSQAP
S852 yDQLPSSSDGSQAPA
S855 LPSSSDGSQAPARPP
S933 FAFPPPVSPRLNL__
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