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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P04150: Variant p.Val575Gly

Glucocorticoid receptor
Gene: NR3C1
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Variant information Variant position: help 575 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Valine (V) to Glycine (G) at position 575 (V575G, p.Val575Gly). 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 hydrophobic (V) to glycine (G) 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 GCCR; uncertain significance; reduces transactivation activity; enhances transrepression activity; reduces affinity for ligand; delays nuclear translocation; does not exert a dominant negative effect; does not impair DNA binding. Any additional useful information about the variant.


Sequence information Variant position: help 575 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 777 The length of the canonical sequence.
Location on the sequence: help STWRIMTTLNMLGGRQVIAA V KWAKAIPGFRNLHLDDQMTL 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                         STWRIMTTLNMLGGRQVIAAVKWAKAIPGFRNLHLDDQMTL

Mouse                         SAWRIMTTLNMLGGRQVIAAVKWAKAIPGFRNLHLDDQMTL

Rat                           SAWRIMTTLNMLGGRQVIAAVKWAKAILGLRNLHLDDQMTL

Pig                           STWRIMTALNMLGGRQVIAAVKWAKAIPGFRNLHLDDQMTL

Rabbit                        STWRIMTTLNMLGGRQVIAAVKWAKAIPGFRNLHLDDQMTL

Xenopus laevis                TTRRLMSSLNMLGGRQVVSAVRWAKAIPGFRNLHLDDQMTL

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 – 777 Glucocorticoid receptor
Domain 524 – 758 NR LBD
Region 485 – 777 Interaction with CLOCK
Region 532 – 697 Interaction with CRY1
Alternative sequence 491 – 674 Missing. In isoform GR-A alpha and isoform GR-A beta.
Mutagenesis 585 – 585 R -> A. Reduces activation mediated by ligand binding domain; when associated with A-590.
Mutagenesis 590 – 590 D -> A. Reduces activation mediated by ligand binding domain; when associated with A-585.
Helix 556 – 579



Literature citations
A novel point mutation of the human glucocorticoid receptor gene causes primary generalized glucocorticoid resistance through impaired interaction with the LXXLL motif of the p160 coactivators: dissociation of the transactivating and transreppressive activities.
Nicolaides N.C.; Roberts M.L.; Kino T.; Braatvedt G.; Hurt D.E.; Katsantoni E.; Sertedaki A.; Chrousos G.P.; Charmandari E.;
J. Clin. Endocrinol. Metab. 99:E902-E907(2014)
Cited for: VARIANT GCCR GLY-575; CHARACTERIZATION OF VARIANT GCCR GLY-575;
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.