UniProtKB/Swiss-Prot P04150: Variant p.Cys421Tyr

Glucocorticoid receptor
Gene: NR3C1
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Variant information Variant position:

421 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 Cysteine (C) to Tyrosine (Y) at position 421 (C421Y, p.Cys421Tyr). 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 medium size and polar (C) to large size and aromatic (Y) 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
Polymorphism:

Carriers of the 22-Glu-Lys-23 allele are relatively more resistant to the effects of GCs with respect to the sensitivity of the adrenal feedback mechanism than non-carriers, resulting in a better metabolic health profile. Carriers have a better survival than non-carriers, as well as lower serum CRP levels. The 22-Glu-Lys-23 polymorphism is associated with a sex-specific, beneficial body composition at young-adult age, as well as greater muscle strength in males. Additional information on the polymorphism described.

Sequence information Variant position:

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

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

DVSSPPSSSSTATTGPPPKL C LVCSDEASGCHYGVLTCGSC 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                         DVSSPPSSSSTATTGPPPKLCLVCSDEASGCHYGVLTCGSC

Mouse                         DVSSPPSSSSTA-TGPPPKLCLVCSDEASGCHYGVLTCGSC

Rat                           DVSSPPSSSSAA-TGPPPKLCLVCSDEASGCHYGVLTCGSC

Pig                           DVSSPPSSSSAA-TGPPPKLCLVCSDEASGCHYGVLTCGSC

Rabbit                        DVSSPPSNSTTA-AGPPPKLCLVCSDEASGCHYGVLTCGSC

Xenopus laevis                DASPSPSTSSTS-TGPPPKLCLVCSDEASGCHYGVLTCGSC

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 – 777	Glucocorticoid receptor
DNA binding	418 – 493	Nuclear receptor
Zinc finger	421 – 441	NR C4-type
Modified residue	404 – 404	Phosphoserine; by GSK3-beta
Cross	419 – 419	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Mutagenesis	404 – 404	S -> A. Abolishes phosphorylation. Does not affect translocation to the nucleus following ligand stimulation. Increases protein half-life and transcriptional repressor activity. Alters repertoire of regulated genes. Increases cell death.
Mutagenesis	404 – 404	S -> D. Does not affect translocation to the nucleus following ligand stimulation.

Literature citations
Cloning and expression of mutant glucocorticoid receptors from glucocorticoid-sensitive and -resistant human leukemic cells.
Powers J.H.; Hillmann A.G.; Tang D.C.; Harmon J.M.;
Cancer Res. 53:4059-4065(1993)
Cited for: VARIANTS TYR-421 AND PHE-753;

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.