P22681 · CBL_HUMAN
- ProteinE3 ubiquitin-protein ligase CBL
- GeneCBL
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids906 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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 (PubMed:17094949).
Ubiquitinates SPRY2 (PubMed:17094949, PubMed:17974561).
Ubiquitinates EGFR (PubMed:17974561).
Recognizes activated receptor tyrosine kinases, including KIT, FLT1, FGFR1, FGFR2, PDGFRA, PDGFRB, 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).
Ubiquitinates SPRY2 (PubMed:17094949, PubMed:17974561).
Ubiquitinates EGFR (PubMed:17974561).
Recognizes activated receptor tyrosine kinases, including KIT, FLT1, FGFR1, FGFR2, PDGFRA, PDGFRB, 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).
Miscellaneous
This protein has one functional calcium-binding site.
Catalytic activity
Pathway
Protein modification; protein ubiquitination.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 229 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 231 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 233 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 235 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 240 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 294 | 4-O-phospho-L-tyrosine (UniProtKB | ChEBI) | ||||
Sequence: R |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameE3 ubiquitin-protein ligase CBL
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP22681
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Colocalizes with FGFR2 in lipid rafts at the cell membrane.
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia (NSLL)
- Note
- DescriptionA syndrome characterized by a phenotype reminiscent of Noonan syndrome. Clinical features are highly variable, including facial dysmorphism, short neck, developmental delay, hyperextensible joints and thorax abnormalities with widely spaced nipples. The facial features consist of triangular face with hypertelorism, large low-set ears, ptosis, and flat nasal bridge. Some patients manifest cardiac defects. Some have an increased risk for certain malignancies, particularly juvenile myelomonocytic leukemia.
- See alsoMIM:613563
Natural variants in NSLL
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_064332 | 367 | Q>P | in NSLL; dbSNP:rs267606704 | |
VAR_064333 | 382 | K>E | in NSLL; dominant-negative; impairs CBL-mediated ubiquitination, internalization and degradation of the EGF receptor/EGFR; decreases the ability to negatively regulate EGFR signaling; dbSNP:rs267606705 | |
VAR_064334 | 390 | D>Y | in NSLL; dominant-negative; impairs CBL-mediated ubiquitination, internalization and degradation of the EGF receptor/EGFR; decreases the ability to negatively regulate EGFR signaling; dbSNP:rs267606707 | |
VAR_064335 | 420 | R>Q | in NSLL; dominant-negative; impairs CBL-mediated ubiquitination, internalization and degradation of the EGF receptor/EGFR; decreases the ability to negatively regulate EGFR signaling; dbSNP:rs267606708 |
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 80 | Abolishes interaction with ZAP70. | ||||
Sequence: S → D | ||||||
Mutagenesis | 82 | Abolishes interaction with ZAP70. | ||||
Sequence: P → A | ||||||
Mutagenesis | 229 | Abolishes interaction with ZAP70. | ||||
Sequence: D → Q | ||||||
Mutagenesis | 240 | Abolishes interaction with ZAP70. | ||||
Sequence: E → S | ||||||
Natural variant | VAR_071040 | 287 | found in patients with acute myeloid leukemia; uncertain significance | |||
Sequence: K → R | ||||||
Mutagenesis | 294 | Abolishes interaction with ZAP70. | ||||
Sequence: R → K | ||||||
Mutagenesis | 306 | Abolishes interaction with ZAP70 and EPHB1, but does not affect interaction with SLA. Reduces ubiquitination and therefore proteasomal degradation of SPRED2. | ||||
Sequence: G → E | ||||||
Natural variant | VAR_071041 | 365 | found in patients with acute myeloid leukemia; uncertain significance; loss of the ability to negatively regulate signaling pathways; promotes cell cycle progression; decreases apoptosis | |||
Sequence: Q → QSK | ||||||
Natural variant | VAR_064332 | 367 | in NSLL; dbSNP:rs267606704 | |||
Sequence: Q → P | ||||||
Natural variant | VAR_071042 | 371 | found in patients with acute myeloid leukemia; uncertain significance; loss of the ability to negatively regulate signaling pathways; promotes cell cycle progression; decreases apoptosis; dbSNP:rs267606706 | |||
Sequence: Y → H | ||||||
Mutagenesis | 371 | Strongly reduces tyrosine phosphorylation by INSR; when associated with F-700 and F-774. | ||||
Sequence: Y → F | ||||||
Mutagenesis | 381 | Loss of ubiquitin ligase activity. | ||||
Sequence: C → A | ||||||
Natural variant | VAR_064333 | 382 | in NSLL; dominant-negative; impairs CBL-mediated ubiquitination, internalization and degradation of the EGF receptor/EGFR; decreases the ability to negatively regulate EGFR signaling; dbSNP:rs267606705 | |||
Sequence: K → E | ||||||
Natural variant | VAR_064334 | 390 | in NSLL; dominant-negative; impairs CBL-mediated ubiquitination, internalization and degradation of the EGF receptor/EGFR; decreases the ability to negatively regulate EGFR signaling; dbSNP:rs267606707 | |||
Sequence: D → Y | ||||||
Natural variant | VAR_064335 | 420 | in NSLL; dominant-negative; impairs CBL-mediated ubiquitination, internalization and degradation of the EGF receptor/EGFR; decreases the ability to negatively regulate EGFR signaling; dbSNP:rs267606708 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_071043 | 499 | found in patients with acute myeloid leukemia; uncertain significance | |||
Sequence: R → L | ||||||
Natural variant | VAR_057211 | 620 | in dbSNP:rs2227988 | |||
Sequence: L → F | ||||||
Mutagenesis | 674 | Does not affect interaction with TNS4 following EGF stimulation. | ||||
Sequence: Y → F | ||||||
Mutagenesis | 700 | Does not affect interaction with TNS4 following EGF stimulation. Strongly reduces tyrosine phosphorylation by INSR; when associated with F-371 and F-774. | ||||
Sequence: Y → F | ||||||
Mutagenesis | 731 | No effect on tyrosine phosphorylation by INSR. Loss of phosphorylation by SRC. Inhibition of bone resorption. Abolishes interaction with PIK3R1. Does not affect interaction with TNS4 following EGF stimulation. | ||||
Sequence: Y → F | ||||||
Mutagenesis | 774 | Loss of interaction with TNS4 following EGF stimulation. Strongly reduces tyrosine phosphorylation by INSR; when associated with F-371 and F-700. | ||||
Sequence: Y → F | ||||||
Natural variant | VAR_057212 | 782 | in dbSNP:rs2229073 | |||
Sequence: P → L | ||||||
Natural variant | VAR_057213 | 904 | in dbSNP:rs17122769 | |||
Sequence: V → I |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1,898 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data), modified residue.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000055858 | 1-906 | UniProt | E3 ubiquitin-protein ligase CBL | |||
Sequence: MAGNVKKSSGAGGGSGSGGSGSGGLIGLMKDAFQPHHHHHHHLSPHPPGTVDKKMVEKCWKLMDKVVRLCQNPKLALKNSPPYILDLLPDTYQHLRTILSRYEGKMETLGENEYFRVFMENLMKKTKQTISLFKEGKERMYEENSQPRRNLTKLSLIFSHMLAELKGIFPSGLFQGDTFRITKADAAEFWRKAFGEKTIVPWKSFRQALHEVHPISSGLEAMALKSTIDLTCNDYISVFEFDIFTRLFQPWSSLLRNWNSLAVTHPGYMAFLTYDEVKARLQKFIHKPGSYIFRLSCTRLGQWAIGYVTADGNILQTIPHNKPLFQALIDGFREGFYLFPDGRNQNPDLTGLCEPTPQDHIKVTQEQYELYCEMGSTFQLCKICAENDKDVKIEPCGHLMCTSCLTSWQESEGQGCPFCRCEIKGTEPIVVDPFDPRGSGSLLRQGAEGAPSPNYDDDDDERADDTLFMMKELAGAKVERPPSPFSMAPQASLPPVPPRLDLLPQRVCVPSSASALGTASKAASGSLHKDKPLPVPPTLRDLPPPPPPDRPYSVGAESRPQRRPLPCTPGDCPSRDKLPPVPSSRLGDSWLPRPIPKVPVSAPSSSDPWTGRELTNRHSLPFSLPSQMEPRPDVPRLGSTFSLDTSMSMNSSPLVGPECDHPKIKPSSSANAIYSLAARPLPVPKLPPGEQCEGEEDTEYMTPSSRPLRPLDTSQSSRACDCDQQIDSCTYEAMYNIQSQAPSITESSTFGEGNLAAAHANTGPEESENEDDGYDVPKPPVPAVLARRTLSDISNASSSFGWLSLDGDPTTNVTEGSQVPERPPKPFPRRINSERKAGSCQQGSGPAASAATASPQLSSEIENLMSQGYSYQDIQKALVIAQNNIEMAKNILREFVSISSPAHVAT | |||||||
Modified residue (large scale data) | 8 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 15 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 17 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 20 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 22 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 141 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 371 | UniProt | Phosphotyrosine; by INSR | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 371 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 439 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 439 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 441 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 452 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 452 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 455 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 483 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 483 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 486 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 492 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 552 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 553 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 568 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 615 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 619 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 619 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 623 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 639 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 642 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 642 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 652 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 667 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 668 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 668 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 669 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 669 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 674 | UniProt | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 674 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 675 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 698 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 700 | UniProt | Phosphotyrosine; by ABL1 | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 700 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 702 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 714 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 731 | UniProt | Phosphotyrosine; by SRC | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 767 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 774 | UniProt | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 789 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 791 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 799 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 900 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 900 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
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
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 (PubMed:11896602, PubMed:20094046).
Ubiquitination is negatively regulated by IFT20 (PubMed:29237719).
Ubiquitination is negatively regulated by IFT20 (PubMed:29237719).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Forms homodimers; IFT20 promotes the formation of stable homodimers (PubMed:29237719).
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 (PubMed:29237719).
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 ATX2 (By similarity).
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 (PubMed:29237719).
Interacts with SPRY2; the interaction inhibits CBL-mediated ubiquitination of EGFR (PubMed:17974561).
Interacts (phosphorylated at Tyr-774) with tensin TNS4 (via SH2 domain); the interaction is enhanced in the presence of EGF and reduces interaction of CBL with EGFR (PubMed:23774213).
Interacts with EGFR; the interaction is reduced in the presence of TNS4 (PubMed:23774213).
Interacts with CD5 (PubMed:23376399).
Interacts with CD93 (PubMed:26848865).
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 (PubMed:29237719).
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 ATX2 (By similarity).
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 (PubMed:29237719).
Interacts with SPRY2; the interaction inhibits CBL-mediated ubiquitination of EGFR (PubMed:17974561).
Interacts (phosphorylated at Tyr-774) with tensin TNS4 (via SH2 domain); the interaction is enhanced in the presence of EGF and reduces interaction of CBL with EGFR (PubMed:23774213).
Interacts with EGFR; the interaction is reduced in the presence of TNS4 (PubMed:23774213).
Interacts with CD5 (PubMed:23376399).
Interacts with CD93 (PubMed:26848865).
(Microbial infection) Interacts with M.tuberculosis LpqN, which influences the balance between intrinsic antibacterial and antiviral defense.
Binary interactions
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, domain, zinc finger, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-21 | Disordered | ||||
Sequence: MAGNVKKSSGAGGGSGSGGSG | ||||||
Region | 1-357 | Sufficient for interaction with EPHB1 | ||||
Sequence: MAGNVKKSSGAGGGSGSGGSGSGGLIGLMKDAFQPHHHHHHHLSPHPPGTVDKKMVEKCWKLMDKVVRLCQNPKLALKNSPPYILDLLPDTYQHLRTILSRYEGKMETLGENEYFRVFMENLMKKTKQTISLFKEGKERMYEENSQPRRNLTKLSLIFSHMLAELKGIFPSGLFQGDTFRITKADAAEFWRKAFGEKTIVPWKSFRQALHEVHPISSGLEAMALKSTIDLTCNDYISVFEFDIFTRLFQPWSSLLRNWNSLAVTHPGYMAFLTYDEVKARLQKFIHKPGSYIFRLSCTRLGQWAIGYVTADGNILQTIPHNKPLFQALIDGFREGFYLFPDGRNQNPDLTGLCEPTP | ||||||
Region | 47-175 | 4H | ||||
Sequence: PPGTVDKKMVEKCWKLMDKVVRLCQNPKLALKNSPPYILDLLPDTYQHLRTILSRYEGKMETLGENEYFRVFMENLMKKTKQTISLFKEGKERMYEENSQPRRNLTKLSLIFSHMLAELKGIFPSGLFQ | ||||||
Domain | 47-351 | Cbl-PTB | ||||
Sequence: PPGTVDKKMVEKCWKLMDKVVRLCQNPKLALKNSPPYILDLLPDTYQHLRTILSRYEGKMETLGENEYFRVFMENLMKKTKQTISLFKEGKERMYEENSQPRRNLTKLSLIFSHMLAELKGIFPSGLFQGDTFRITKADAAEFWRKAFGEKTIVPWKSFRQALHEVHPISSGLEAMALKSTIDLTCNDYISVFEFDIFTRLFQPWSSLLRNWNSLAVTHPGYMAFLTYDEVKARLQKFIHKPGSYIFRLSCTRLGQWAIGYVTADGNILQTIPHNKPLFQALIDGFREGFYLFPDGRNQNPDLTG | ||||||
Region | 176-248 | EF-hand-like | ||||
Sequence: GDTFRITKADAAEFWRKAFGEKTIVPWKSFRQALHEVHPISSGLEAMALKSTIDLTCNDYISVFEFDIFTRLF | ||||||
Region | 249-351 | SH2-like | ||||
Sequence: QPWSSLLRNWNSLAVTHPGYMAFLTYDEVKARLQKFIHKPGSYIFRLSCTRLGQWAIGYVTADGNILQTIPHNKPLFQALIDGFREGFYLFPDGRNQNPDLTG | ||||||
Region | 352-380 | Linker | ||||
Sequence: LCEPTPQDHIKVTQEQYELYCEMGSTFQL | ||||||
Region | 358-906 | Required for ubiquitination of SPRED2 | ||||
Sequence: QDHIKVTQEQYELYCEMGSTFQLCKICAENDKDVKIEPCGHLMCTSCLTSWQESEGQGCPFCRCEIKGTEPIVVDPFDPRGSGSLLRQGAEGAPSPNYDDDDDERADDTLFMMKELAGAKVERPPSPFSMAPQASLPPVPPRLDLLPQRVCVPSSASALGTASKAASGSLHKDKPLPVPPTLRDLPPPPPPDRPYSVGAESRPQRRPLPCTPGDCPSRDKLPPVPSSRLGDSWLPRPIPKVPVSAPSSSDPWTGRELTNRHSLPFSLPSQMEPRPDVPRLGSTFSLDTSMSMNSSPLVGPECDHPKIKPSSSANAIYSLAARPLPVPKLPPGEQCEGEEDTEYMTPSSRPLRPLDTSQSSRACDCDQQIDSCTYEAMYNIQSQAPSITESSTFGEGNLAAAHANTGPEESENEDDGYDVPKPPVPAVLARRTLSDISNASSSFGWLSLDGDPTTNVTEGSQVPERPPKPFPRRINSERKAGSCQQGSGPAASAATASPQLSSEIENLMSQGYSYQDIQKALVIAQNNIEMAKNILREFVSISSPAHVAT | ||||||
Zinc finger | 381-420 | RING-type | ||||
Sequence: CKICAENDKDVKIEPCGHLMCTSCLTSWQESEGQGCPFCR | ||||||
Region | 432-462 | Disordered | ||||
Sequence: DPFDPRGSGSLLRQGAEGAPSPNYDDDDDER | ||||||
Region | 477-498 | Disordered | ||||
Sequence: KVERPPSPFSMAPQASLPPVPP | ||||||
Region | 519-667 | Disordered | ||||
Sequence: ASKAASGSLHKDKPLPVPPTLRDLPPPPPPDRPYSVGAESRPQRRPLPCTPGDCPSRDKLPPVPSSRLGDSWLPRPIPKVPVSAPSSSDPWTGRELTNRHSLPFSLPSQMEPRPDVPRLGSTFSLDTSMSMNSSPLVGPECDHPKIKPS | ||||||
Compositional bias | 536-553 | Pro residues | ||||
Sequence: PPTLRDLPPPPPPDRPYS | ||||||
Compositional bias | 603-623 | Polar residues | ||||
Sequence: PSSSDPWTGRELTNRHSLPFS | ||||||
Compositional bias | 639-653 | Polar residues | ||||
Sequence: STFSLDTSMSMNSSP | ||||||
Region | 648-906 | Interaction with CD2AP | ||||
Sequence: SMNSSPLVGPECDHPKIKPSSSANAIYSLAARPLPVPKLPPGEQCEGEEDTEYMTPSSRPLRPLDTSQSSRACDCDQQIDSCTYEAMYNIQSQAPSITESSTFGEGNLAAAHANTGPEESENEDDGYDVPKPPVPAVLARRTLSDISNASSSFGWLSLDGDPTTNVTEGSQVPERPPKPFPRRINSERKAGSCQQGSGPAASAATASPQLSSEIENLMSQGYSYQDIQKALVIAQNNIEMAKNILREFVSISSPAHVAT | ||||||
Region | 680-719 | Disordered | ||||
Sequence: PLPVPKLPPGEQCEGEEDTEYMTPSSRPLRPLDTSQSSRA | ||||||
Region | 743-781 | Disordered | ||||
Sequence: SITESSTFGEGNLAAAHANTGPEESENEDDGYDVPKPPV | ||||||
Compositional bias | 799-818 | Polar residues | ||||
Sequence: SFGWLSLDGDPTTNVTEGSQ | ||||||
Region | 799-854 | Disordered | ||||
Sequence: SFGWLSLDGDPTTNVTEGSQVPERPPKPFPRRINSERKAGSCQQGSGPAASAATAS | ||||||
Compositional bias | 835-854 | Polar residues | ||||
Sequence: RKAGSCQQGSGPAASAATAS | ||||||
Domain | 856-895 | UBA | ||||
Sequence: QLSSEIENLMSQGYSYQDIQKALVIAQNNIEMAKNILREF |
Domain
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.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length906
- Mass (Da)99,633
- Last updated2009-07-07 v2
- Checksum1AA6BF67377322CA
Computationally mapped potential isoform sequences
There are 5 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A0U1RQX8 | A0A0U1RQX8_HUMAN | CBL | 882 | ||
A0A0U1RR39 | A0A0U1RR39_HUMAN | CBL | 862 | ||
A0A0U1RRJ5 | A0A0U1RRJ5_HUMAN | CBL | 89 | ||
A0A1B0GW38 | A0A1B0GW38_HUMAN | CBL | 869 | ||
A0A8V8TQA9 | A0A8V8TQA9_HUMAN | CBL | 99 |
Features
Showing features for sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 15 | in Ref. 1; CAA40393 | ||||
Sequence: S → T | ||||||
Compositional bias | 536-553 | Pro residues | ||||
Sequence: PPTLRDLPPPPPPDRPYS | ||||||
Compositional bias | 603-623 | Polar residues | ||||
Sequence: PSSSDPWTGRELTNRHSLPFS | ||||||
Compositional bias | 639-653 | Polar residues | ||||
Sequence: STFSLDTSMSMNSSP | ||||||
Compositional bias | 799-818 | Polar residues | ||||
Sequence: SFGWLSLDGDPTTNVTEGSQ | ||||||
Compositional bias | 835-854 | Polar residues | ||||
Sequence: RKAGSCQQGSGPAASAATAS |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X57110 EMBL· GenBank· DDBJ | CAA40393.1 EMBL· GenBank· DDBJ | mRNA | ||
AP002956 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC132733 EMBL· GenBank· DDBJ | AAI32734.1 EMBL· GenBank· DDBJ | mRNA | ||
BC136463 EMBL· GenBank· DDBJ | AAI36464.1 EMBL· GenBank· DDBJ | mRNA |