UniProtKB/Swiss-Prot P46527: Variant p.Pro69Leu

Cyclin-dependent kinase inhibitor 1B
Gene: CDKN1B
Chromosomal location: 12p12-p13.1
Variant information

Variant position:  69
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Unclassified
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Proline (P) to Leucine (L) at position 69 (P69L, p.Pro69Leu).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -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:  Found in a patient with multiple endocrine tumors; germline mutation; reduced expression levels; shows impaired binding to CDK2.
Any additional useful information about the variant.



Sequence information

Variant position:  69
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  198
The length of the canonical sequence.

Location on the sequence:   CRDMEEASQRKWNFDFQNHK  P LEGKYEWQEVEKGSLPEFYY
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                         CRDMEEASQRKWNFDFQNHKPLEGKYEWQEVEKGSLPEFYY

Mouse                         CRDMEEASQRKWNFDFQNHKPLEGRYEWQEVERGSLPEFYY

Cat                           CRDMEEASQRKWNFDFQNHKPLEGKYEWQEVEKGSLPEFYY

Dog                           CIDMEEASQNKWNFDFQNHKPLEGKYEWQEVEKGSLPEFYY

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.

TypePositionsDescription
Chain 1 – 198 Cyclin-dependent kinase inhibitor 1B
Modified residue 74 – 74 Phosphotyrosine; by SRC
Modified residue 88 – 88 Phosphotyrosine; by ABL, LYN, SRC and JAK2
Modified residue 89 – 89 Phosphotyrosine
Mutagenesis 74 – 74 Y -> F. No change in binding CDK4 and no inhibition of CDK4 activity. Translocates to nucleus. No effect on in vitro phosphorylation of CDK4 by CCNH-CDK7.
Mutagenesis 88 – 88 Y -> F. Abolishes LYN-mediated phosphorylation, reduceS CDK2-mediated phosphorylation on T-187, has greater cell cycle arrest into S-phase, no effect on binding CDK2 complexes, reduced CDK4 binding and inhibits CDK4 enzyme activity. No nuclear translocation. No effect on in vitro phosphorylation of CDK4 by CCNH-CDK7. Completely abolishes CDK4 binding; when associated with F-89.
Mutagenesis 89 – 89 Y -> F. No effect on binding CDK2 complexes, reduced CDK4 binding and greatly inhibits CDK4 enzyme activity. No nuclear translocation. Inhibits in vitro phosphorylation of CDK4 by CCNH-CDK7. Completely abolishes CDK4 binding; when associated with F-88.


Literature citations

A novel germline CDKN1B mutation causing multiple endocrine tumors: clinical, genetic and functional characterization.
Molatore S.; Marinoni I.; Lee M.; Pulz E.; Ambrosio M.R.; degli Uberti E.C.; Zatelli M.C.; Pellegata N.S.;
Hum. Mutat. 31:E1825-E1835(2010)
Cited for: VARIANT LEU-69; CHARACTERIZATION OF VARIANT LEU-69;

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.