Product: CBL Antibody
Catalog: AF6225
Description: Rabbit polyclonal antibody to CBL
Application: WB IHC IF/ICC
Reactivity: Human, Mouse, Rat
Prediction: Pig, Zebrafish, Bovine, Horse, Sheep, Rabbit, Dog, Chicken, Xenopus
Mol.Wt.: 120kDa; 100kD(Calculated).
Uniprot: P22681
RRID: AB_2835099

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 100ul $280 In stock
 200ul $350 In stock

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Product Info

Source:
Rabbit
Application:
WB 1:500-1:2000, IHC 1:50-1:200, IF/ICC 1:100-1:500
*The optimal dilutions should be determined by the end user.
*Tips:

WB: For western blot detection of denatured protein samples. IHC: For immunohistochemical detection of paraffin sections (IHC-p) or frozen sections (IHC-f) of tissue samples. IF/ICC: For immunofluorescence detection of cell samples. ELISA(peptide): For ELISA detection of antigenic peptide.

Reactivity:
Human,Mouse,Rat
Prediction:
Pig(92%), Zebrafish(92%), Bovine(92%), Horse(92%), Sheep(92%), Rabbit(92%), Dog(92%), Chicken(100%), Xenopus(92%)
Clonality:
Polyclonal
Specificity:
CBL Antibody detects endogenous levels of total CBL.
RRID:
AB_2835099
Cite Format: Affinity Biosciences Cat# AF6225, RRID:AB_2835099.
Conjugate:
Unconjugated.
Purification:
The antiserum was purified by peptide affinity chromatography using SulfoLink™ Coupling Resin (Thermo Fisher Scientific).
Storage:
Rabbit IgG in phosphate buffered saline , pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol. Store at -20 °C. Stable for 12 months from date of receipt.
Alias:

Fold/Unfold

4732447J05Rik; C CBL; Cas Br M (murine) ecotropic retroviral transforming sequence; Casitas B lineage lymphoma proto oncogene; Casitas B-lineage lymphoma proto-oncogene; CBL 2; cbl; CBL_HUMAN; CBL2; E3 ubiquitin protein ligase CBL; E3 ubiquitin-protein ligase CBL; Oncogene CBL2; Proto oncogene c CBL; Proto-oncogene c-CBL; RGD1561386; RING finger protein 55; RNF55; Signal transduction protein CBL;

Immunogens

Immunogen:
Uniprot:
Gene(ID):
Description:
Cbl an adapter protein that functions as a negative regulator of many signaling pathways that start from receptors at the cell surface.
Sequence:
MAGNVKKSSGAGGGSGSGGSGSGGLIGLMKDAFQPHHHHHHHLSPHPPGTVDKKMVEKCWKLMDKVVRLCQNPKLALKNSPPYILDLLPDTYQHLRTILSRYEGKMETLGENEYFRVFMENLMKKTKQTISLFKEGKERMYEENSQPRRNLTKLSLIFSHMLAELKGIFPSGLFQGDTFRITKADAAEFWRKAFGEKTIVPWKSFRQALHEVHPISSGLEAMALKSTIDLTCNDYISVFEFDIFTRLFQPWSSLLRNWNSLAVTHPGYMAFLTYDEVKARLQKFIHKPGSYIFRLSCTRLGQWAIGYVTADGNILQTIPHNKPLFQALIDGFREGFYLFPDGRNQNPDLTGLCEPTPQDHIKVTQEQYELYCEMGSTFQLCKICAENDKDVKIEPCGHLMCTSCLTSWQESEGQGCPFCRCEIKGTEPIVVDPFDPRGSGSLLRQGAEGAPSPNYDDDDDERADDTLFMMKELAGAKVERPPSPFSMAPQASLPPVPPRLDLLPQRVCVPSSASALGTASKAASGSLHKDKPLPVPPTLRDLPPPPPPDRPYSVGAESRPQRRPLPCTPGDCPSRDKLPPVPSSRLGDSWLPRPIPKVPVSAPSSSDPWTGRELTNRHSLPFSLPSQMEPRPDVPRLGSTFSLDTSMSMNSSPLVGPECDHPKIKPSSSANAIYSLAARPLPVPKLPPGEQCEGEEDTEYMTPSSRPLRPLDTSQSSRACDCDQQIDSCTYEAMYNIQSQAPSITESSTFGEGNLAAAHANTGPEESENEDDGYDVPKPPVPAVLARRTLSDISNASSSFGWLSLDGDPTTNVTEGSQVPERPPKPFPRRINSERKAGSCQQGSGPAASAATASPQLSSEIENLMSQGYSYQDIQKALVIAQNNIEMAKNILREFVSISSPAHVAT

Predictions

Predictions:

Score>80(red) has high confidence and is suggested to be used for WB detection. *The prediction model is mainly based on the alignment of immunogen sequences, the results are for reference only, not as the basis of quality assurance.

Species
Results
Score
Chicken
100
Pig
92
Horse
92
Bovine
92
Sheep
92
Dog
92
Xenopus
92
Zebrafish
92
Rabbit
92
Model Confidence:
High(score>80) Medium(80>score>50) Low(score<50) No confidence

PTMs - P22681 As Substrate

Site PTM Type Enzyme
K7 Ubiquitination
S8 Phosphorylation
S15 Phosphorylation
S17 Phosphorylation
S20 Phosphorylation
S22 Phosphorylation
K58 Ubiquitination
K74 Ubiquitination
K105 Ubiquitination
T126 Phosphorylation
K134 Acetylation
Y141 Phosphorylation
K183 Ubiquitination
K197 Acetylation
K203 Ubiquitination
Y337 Phosphorylation
Y368 Phosphorylation
Y371 Phosphorylation P06213 (INSR) , P07948 (LYN) , P00533 (EGFR)
K424 Ubiquitination
S439 Phosphorylation
S441 Phosphorylation
S452 Phosphorylation
Y455 Phosphorylation
S483 Phosphorylation
S486 Phosphorylation
S492 Phosphorylation
S511 Phosphorylation
S512 Phosphorylation
S514 Phosphorylation
S520 Phosphorylation
K521 Ubiquitination
Y552 Phosphorylation
T568 Phosphorylation
K577 Ubiquitination
S583 Phosphorylation
S584 Phosphorylation
S589 Phosphorylation
S601 Phosphorylation
S619 Phosphorylation P17252 (PRKCA)
S623 Phosphorylation P17252 (PRKCA)
S639 Phosphorylation P17252 (PRKCA)
T640 Phosphorylation
S642 Phosphorylation P17252 (PRKCA)
T645 Phosphorylation
S646 Phosphorylation
S652 Phosphorylation
S667 Phosphorylation
S668 Phosphorylation
S669 Phosphorylation
Y674 Phosphorylation
S675 Phosphorylation
T698 Phosphorylation
Y700 Phosphorylation P43405 (SYK) , P06241 (FYN) , P00533 (EGFR) , P06239 (LCK) , P06213 (INSR) , P00519 (ABL1)
T702 Phosphorylation
S704 Phosphorylation
S705 Phosphorylation
T713 Phosphorylation
S714 Phosphorylation
S716 Phosphorylation
S717 Phosphorylation
Y731 Phosphorylation P12931 (SRC) , P08631 (HCK) , P43405 (SYK) , P06239 (LCK) , P00533 (EGFR) , P06241 (FYN)
Y735 Phosphorylation
T762 Phosphorylation
S767 Phosphorylation
Y774 Phosphorylation P00533 (EGFR) , P06241 (FYN) , P12931 (SRC) , P06239 (LCK) , P43405 (SYK)
T789 Phosphorylation
S791 Phosphorylation
S794 Phosphorylation
S797 Phosphorylation
S799 Phosphorylation
S804 Phosphorylation
S833 Phosphorylation
S900 Phosphorylation

Research Backgrounds

Function:

Adapter protein that functions as a negative regulator of many signaling pathways that are triggered by activation of cell surface receptors. Acts as an E3 ubiquitin-protein ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their degradation by the proteasome. Recognizes activated receptor tyrosine kinases, including KIT, FLT1, FGFR1, FGFR2, PDGFRA, PDGFRB, EGFR, CSF1R, EPHA8 and KDR and terminates signaling. Recognizes membrane-bound HCK, SRC and other kinases of the SRC family and mediates their ubiquitination and degradation. Participates in signal transduction in hematopoietic cells. Plays an important role in the regulation of osteoblast differentiation and apoptosis. Essential for osteoclastic bone resorption. 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. May be functionally coupled with the E2 ubiquitin-protein ligase UB2D3. 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).

PTMs:

Phosphorylated on tyrosine residues by ALK, EGFR, SYK, FYN and ZAP70 (By similarity). Phosphorylated on tyrosine residues in response to FLT1 and KIT signaling. Phosphorylated on tyrosine residues by INSR and FGR. Phosphorylated on several tyrosine residues by constitutively activated FGFR3. Not phosphorylated at Tyr-731 by FGFR3. Phosphorylated on tyrosine residues by activated CSF1R, PDGFRA and PDGFRB. Phosphorylated on tyrosine residues by HCK.

Ubiquitinated, leading to its degradation via the proteasome. Ubiquitination is negatively regulated by IFT20.

Subcellular Location:

Cytoplasm. Cell membrane. Cell projection>Cilium. Golgi apparatus.
Note: Colocalizes with FGFR2 in lipid rafts at the cell membrane.

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
Subunit Structure:

Forms homodimers; IFT20 promotes the formation of stable homodimers. Interacts (phosphorylated at Tyr-731) with PIK3R1. Associates with NCK via its SH3 domain. The phosphorylated C-terminus interacts with CD2AP via its second SH3 domain. Binds to UBE2L3. Interacts with adapters SLA, SLA2 and with the phosphorylated C-terminus of SH2B2. Interacts with EGFR, SYK and ZAP70 via the highly conserved Cbl-N region. Also interacts with SORBS1 and INPPL1/SHIP2. Interacts with phosphorylated LAT2 (By similarity). Interacts with CBLB. Interacts with ALK, AXL, BLK, FGR and FGFR2. Interacts with CSF1R, EPHB1, FLT1, KDR, PDGFRA and PDGFRB; regulates receptor degradation through ubiquitination. Interacts with HCK and LYN. Interacts with TEK/TIE2 (tyrosine phosphorylated). Interacts with SH3KBP1 and this interaction is inhibited in the presence of SHKBP1 (By similarity). Interacts with SIGLEC10 (By similarity). Interacts with IFT20.

Family&Domains:

The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme.

The N-terminus is composed of the phosphotyrosine binding (PTB) domain, a short linker region and the RING-type zinc finger. The PTB domain, which is also called TKB (tyrosine kinase binding) domain, is composed of three different subdomains: a four-helix bundle (4H), a calcium-binding EF hand and a divergent SH2 domain.

Research Fields

· Cellular Processes > Transport and catabolism > Endocytosis.   (View pathway)

· Environmental Information Processing > Signal transduction > ErbB signaling pathway.   (View pathway)

· Genetic Information Processing > Folding, sorting and degradation > Ubiquitin mediated proteolysis.   (View pathway)

· Human Diseases > Infectious diseases: Bacterial > Bacterial invasion of epithelial cells.

· Human Diseases > Cancers: Overview > Pathways in cancer.   (View pathway)

· Human Diseases > Cancers: Overview > Proteoglycans in cancer.

· Human Diseases > Cancers: Specific types > Chronic myeloid leukemia.   (View pathway)

· Organismal Systems > Immune system > T cell receptor signaling pathway.   (View pathway)

· Organismal Systems > Endocrine system > Insulin signaling pathway.   (View pathway)

References

1). Li S et al. Fyn deficiency inhibits oxidative stress by decreasing c-Cbl-mediated ubiquitination of Sirt1 to attenuate diabetic renal fibrosis. Metabolism 2022 Dec 17; (PubMed: 36538986) [IF=9.8]

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