UniProtKB/Swiss-Prot P03372: Variant p.Gly400Val

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 400 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: 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: From Glycine (G) to Valine (V) at position 400 (G400V, p.Gly400Val). 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 glycine (G) to medium size and hydrophobic (V) 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: Destabilizes the receptor and decreases its affinity for estradiol at 25 degrees Celsius, but not at 4 degrees Celsius. Any additional useful information about the variant.

Sequence information

Variant position: 400 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 595 The length of the canonical sequence.
Location on the sequence: ECAWLEILMIGLVWRSMEHP G KLLFAPNLLLDRNQGKCVEG 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.
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 – 595	Estrogen receptor
Domain	311 – 547	NR LBD
Region	262 – 595	Interaction with AKAP13
Region	264 – 595	Self-association
Region	311 – 595	Transactivation AF-2
Mutagenesis	386 – 386	I -> C. Loss of transmembrane localization, no effect on peripheral membrane localization. Impairs activation of estrogen-induced activation of NOS3 and production of nitric oxide. No effect on binding to ERES.

Literature citations

Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A.
Green S.; Walter P.; Kumar V.; Krust A.; Bornert J.-M.; Argos P.; Chambon P.;
Nature 320:134-139(1986)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); VARIANT VAL-400; Sequence and expression of human estrogen receptor complementary DNA.
Greene G.L.; Gilna P.; Waterfield M.; Baker A.; Hort Y.; Shine J.;
Science 231:1150-1154(1986)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); VARIANT VAL-400; The cloned human oestrogen receptor contains a mutation which alters its hormone binding properties.
Tora L.; Mullick A.; Metzger D.; Ponglikitmongkol M.; Park I.; Chambon P.;
EMBO J. 8:1981-1986(1989)
Cited for: VARIANT VAL-400;