UniProtKB/Swiss-Prot P22681: Variant p.Arg499Leu

E3 ubiquitin-protein ligase CBL
Gene: CBL
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Variant information Variant position:

499 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

US 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:

From Arginine (R) to Leucine (L) at position 499 (R499L, p.Arg499Leu). 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:

Change from large size and basic (R) to medium size and hydrophobic (L) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-2 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:

Found in patients with acute myeloid leukemia; uncertain significance. Any additional useful information about the variant.

Sequence information Variant position:

499 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

906 The length of the canonical sequence.
Location on the sequence:

ERPPSPFSMAPQASLPPVPP R LDLLPQRVCVPSSASALGTA 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:

The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         ERPPSPFSMAPQASLPPVPPRLDLLPQRVCVPSSASALGTA

Mouse                         ERPSSPFSMAPQASLPPVPPRLDLLQQRAPVPASTSVLGTA

Fission yeast                 LRPDTNLVLIE----SPTNPRISICDIRAIVKI------TR

Sequence annotation in neighborhood:

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.

Type	Positions	Description
Chain	1 – 906	E3 ubiquitin-protein ligase CBL
Region	358 – 906	Required for ubiquitination of SPRED2
Modified residue	483 – 483	Phosphoserine

Literature citations
Novel oncogenic mutations of CBL in human acute myeloid leukemia that activate growth and survival pathways depend on increased metabolism.
Fernandes M.S.; Reddy M.M.; Croteau N.J.; Walz C.; Weisbach H.; Podar K.; Band H.; Carroll M.; Reiter A.; Larson R.A.; Salgia R.; Griffin J.D.; Sattler M.;
J. Biol. Chem. 285:32596-32605(2010)
Cited for: VARIANTS ARG-287; SER-LYS-365 INS; HIS-371 AND LEU-499; CHARACTERIZATION OF VARIANTS SER-LYS-365 INS AND HIS-371; PHOSPHORYLATION AT TYR-674; TYR-700 AND TYR-774;

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.