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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P04150: Variant p.Thr556Ile

Glucocorticoid receptor
Gene: NR3C1
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Variant information Variant position: help 556 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] 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 Threonine (T) to Isoleucine (I) at position 556 (T556I, p.Thr556Ile). 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 polar (T) to medium size and hydrophobic (I) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -1 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; 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 556 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 LEVIEPEVLYAGYDSSVPDS T WRIMTTLNMLGGRQVIAAVK 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                         LEVIEPEVLYAGYDSSVPDSTWRIMTTLNMLGGRQVIAAVK

Mouse                         LEVIEPEVLYAGYDSSVPDSAWRIMTTLNMLGGRQVIAAVK

Rat                           LEVIEPEVLYAGYDSSVPDSAWRIMTTLNMLGGRQVIAAVK

Pig                           LEVIEPEVLYAGYDSSIPDSTWRIMTALNMLGGRQVIAAVK

Rabbit                        LEVIEPEVLYAGYDSSVPDSTWRIMTTLNMLGGRQVIAAVK

Xenopus laevis                LEVIEPEVLYSGYDSSIPDTTRRLMSSLNMLGGRQVVSAVR
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.
Helix 556 – 579



Literature citations
Generalized glucocorticoid resistance accompanied with an adrenocortical adenoma and caused by a novel point mutation of human glucocorticoid receptor gene.
Zhu H.J.; Dai Y.F.; Wang O.; Li M.; Lu L.; Zhao W.G.; Xing X.P.; Pan H.; Li N.S.; Gong F.Y.;
Chin. Med. J. 124:551-555(2011)
Cited for: VARIANT GCCR ILE-556; Functional characterization of the hGRalphaT556I causing Chrousos syndrome.
Nicolaides N.C.; Skyrla E.; Vlachakis D.; Psarra A.M.; Moutsatsou P.; Sertedaki A.; Kossida S.; Charmandari E.;
Eur. J. Clin. Invest. 46:42-49(2016)
Cited for: CHARACTERIZATION OF VARIANT GCCR ILE-556;
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.