UniProtKB/Swiss-Prot P46527: Variant p.Pro69Leu

Cyclin-dependent kinase inhibitor 1B
Gene: CDKN1B
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Variant information Variant position:

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

LB/B 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 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.
Other resources:

Links to websites of interest for the variant.

Variant rs777354267 [ dbSNP | Ensembl ]

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

                              CIDMEEASQNKWNFDFQNHKPLEGKYEWQEVEKGSLPEFYY

Mouse                         CRDMEEASQRKWNFDFQNHKPLEGRYEWQEVERGSLPEFYY

Cat                           CRDMEEASQRKWNFDFQNHKPLEGKYEWQEVEKGSLPEFYY

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 – 198	Cyclin-dependent kinase inhibitor 1B
Region	51 – 91	Interaction with CDK2
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.