UniProt Accession

 CBL_MOUSE; P22682; Q3U527; Q8CEA1 

Genbank Protein ID

 X57111; AK028730; AK153915; BC125285 

Genbank Nucleotide ID

 CAA40394.1; BAC26087.1; BAE32253.1; AAI25286.1 

Protein Name

 E3 ubiquitin-protein ligase CBL 

Protein Synonyms/Alias

 Casitas B-lineage lymphoma proto-oncogene; Proto-oncogene c-Cbl; Signal transduction protein CBL 

Gene Name

 Cbl 

Gene Synonyms/Alias

  

Created Date

 July 27, 2013 

Organism

 Mus musculus (Mouse) 

NCBI Taxa ID

 10090 

Lysine Modification

Position	Peptide	Type	References
201	EKTIVPWKSFRQALH	ubiquitination	[1]
285	RLQKFIHKPGSYIFR	acetylation	[2]
285	RLQKFIHKPGSYIFR	succinylation	[2]

Reference

 [1] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023]
 [2] SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways.
 Park J, Chen Y, Tishkoff DX, Peng C, Tan M, Dai L, Xie Z, Zhang Y, Zwaans BM, Skinner ME, Lombard DB, Zhao Y.
 Mol Cell. 2013 Jun 27;50(6):919-30. [PMID: 23806337] 

Functional Description

 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 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-737 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. 

Sequence Annotation

 DOMAIN 45 349 Cbl-PTB.
 DOMAIN 863 902 UBA.
 ZN_FING 379 418 RING-type.
 REGION 1 355 Sufficient for interaction with EPHB1.
 REGION 45 173 4H.
 REGION 174 246 EF-hand-like.
 REGION 247 349 SH2-like.
 REGION 350 378 Linker.
 REGION 646 913 Interaction with CD2AP (By similarity).
 BINDING 292 292 Phosphotyrosine (By similarity).
 MOD_RES 139 139 Phosphotyrosine (By similarity).
 MOD_RES 195 195 N6-acetyllysine (By similarity).
 MOD_RES 369 369 Phosphotyrosine (By similarity).
 MOD_RES 450 450 Phosphoserine (By similarity).
 MOD_RES 453 453 Phosphotyrosine (By similarity).
 MOD_RES 550 550 Phosphotyrosine (By similarity).
 MOD_RES 665 665 Phosphoserine (By similarity).
 MOD_RES 666 666 Phosphoserine.
 MOD_RES 667 667 Phosphoserine.
 MOD_RES 672 672 Phosphotyrosine.
 MOD_RES 673 673 Phosphoserine (By similarity).
 MOD_RES 692 692 Phosphoserine.
 MOD_RES 698 698 Phosphotyrosine; by ABL1.
 MOD_RES 737 737 Phosphotyrosine; by SRC (By similarity).
 MOD_RES 780 780 Phosphotyrosine (By similarity).
 MOD_RES 907 907 Phosphoserine (By similarity).  

Keyword

 3D-structure; Acetylation; Calcium; Cell membrane; Complete proteome; Cytoplasm; Ligase; Membrane; Metal-binding; Phosphoprotein; Polymorphism; Proto-oncogene; Reference proteome; Repeat; Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 913 AA 

Protein Sequence

Gene Ontology

 GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
 GO:0005634; C:nucleus; IEA:InterPro.
 GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
 GO:0005509; F:calcium ion binding; IEA:InterPro.
 GO:0004871; F:signal transducer activity; IEA:InterPro.
 GO:0004842; F:ubiquitin-protein ligase activity; IEA:InterPro.
 GO:0008270; F:zinc ion binding; IEA:InterPro.
 GO:0045453; P:bone resorption; ISS:UniProtKB.
 GO:0007166; P:cell surface receptor signaling pathway; IEA:InterPro.
 GO:0043066; P:negative regulation of apoptotic process; IEA:Compara.
 GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase cascade; IEA:Compara.
 GO:0006468; P:protein phosphorylation; ISS:UniProtKB. 

Interpro

 IPR024162; Adaptor_Cbl.
 IPR014741; Adaptor_Cbl_EF_hand-like.
 IPR003153; Adaptor_Cbl_N_hlx.
 IPR014742; Adaptor_Cbl_SH2-like.
 IPR024159; Cbl_PTB.
 IPR011992; EF-hand-like_dom.
 IPR000980; SH2.
 IPR009060; UBA-like.
 IPR000449; UBA/transl_elong_EF1B_N.
 IPR015940; UBA/transl_elong_EF1B_N_euk.
 IPR001841; Znf_RING.
 IPR013083; Znf_RING/FYVE/PHD.
 IPR017907; Znf_RING_CS. 

Pfam

 PF02262; Cbl_N
 PF02761; Cbl_N2
 PF02762; Cbl_N3
 PF00627; UBA 

SMART

 SM00184; RING
 SM00165; UBA 

PROSITE

 PS51506; CBL_PTB
 PS50030; UBA
 PS00518; ZF_RING_1
 PS50089; ZF_RING_2 

PRINTS