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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P22681: Variant p.Asp390Tyr

E3 ubiquitin-protein ligase CBL
Gene: CBL
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Variant information Variant position: help 390 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance

Residue change: help From Aspartate (D) to Tyrosine (Y) at position 390 (D390Y, p.Asp390Tyr). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties: help Change from medium size and acidic (D) to large size and aromatic (Y) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -3 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Variant description: help In NSLL; dominant-negative; impairs CBL-mediated ubiquitination, internalization and degradation of the EGF receptor/EGFR; decreases the ability to negatively regulate EGFR signaling. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 390 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 906 The length of the canonical sequence.
Location on the sequence: help LYCEMGSTFQLCKICAENDK D VKIEPCGHLMCTSCLTSWQE The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation: help The multiple alignment of the region surrounding the variant against various orthologous sequences.
Human                         LYCEMGSTFQLCKICAENDKDVKIEPCGHLMCTSCLTSWQE

Mouse                         LYCEMGSTFQLCKICAENDKDVKIEPCGHLMCTSCLTSWQE

Fission yeast                 ------SALDMILRCCKSNSHV---VAGHDLYG--------

Sequence annotation in neighborhood: help The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.
TypePositionsDescription
Chain 1 – 906 E3 ubiquitin-protein ligase CBL
Zinc finger 381 – 420 RING-type
Region 358 – 906 Required for ubiquitination of SPRED2
Modified residue 371 – 371 Phosphotyrosine; by INSR
Mutagenesis 371 – 371 Y -> F. Strongly reduces tyrosine phosphorylation by INSR; when associated with F-700 and F-774.
Mutagenesis 381 – 381 C -> A. Loss of ubiquitin ligase activity.



Literature citations
Heterozygous germline mutations in the CBL tumor-suppressor gene cause a Noonan syndrome-like phenotype.
Martinelli S.; De Luca A.; Stellacci E.; Rossi C.; Checquolo S.; Lepri F.; Caputo V.; Silvano M.; Buscherini F.; Consoli F.; Ferrara G.; Digilio M.C.; Cavaliere M.L.; van Hagen J.M.; Zampino G.; van der Burgt I.; Ferrero G.B.; Mazzanti L.; Screpanti I.; Yntema H.G.; Nillesen W.M.; Savarirayan R.; Zenker M.; Dallapiccola B.; Gelb B.D.; Tartaglia M.;
Am. J. Hum. Genet. 87:250-257(2010)
Cited for: VARIANTS NSLL PRO-367; GLU-382; TYR-390 AND GLN-420; CHARACTERIZATION OF VARIANTS NSLL TYR-390 AND GLN-420; RASopathy-associated CBL germline mutations cause aberrant ubiquitylation and trafficking of EGFR.
Brand K.; Kentsch H.; Glashoff C.; Rosenberger G.;
Hum. Mutat. 35:1372-1381(2014)
Cited for: CHARACTERIZATION OF VARIANTS NSLL GLU-382; TYR-390 AND GLN-420;
Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.