UniProtKB/SwissProt variant VAR

Variant information

Variant position:

896

The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:

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:

From Methionine (M) to Threonine (T) at position 896 (M896T, p.Met896Thr).

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 hydrophobic (M) to medium size and polar (T)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

-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:

In AIS; low androgen binding and transactivation.

Any additional useful information about the variant.

Sequence information

Variant position:

896

The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:

920

The length of the canonical sequence.

Location on the sequence:

QFTFDLLIKSHMVSVDFPEM M AEIISVQVPKILSGKVKPIY

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                         QFTFDLLIKSHMVSVDFPEMMAEIISVQVPKILSGKVKPIY

                              QFTFDLLIKSHMVSVDFPEMMAEIISVQVPKILSGKVKPIY

Rhesus macaque                QFTFDLLIKSHMVSVDFPEMMAEIISVQVPKILSGKVKPIY

Chimpanzee                    QFTFDLLIKSHMVSVDFPEMMAEIISVQVPKILSGKVKPIY

Mouse                         QFTFDLLIKSHMVSVDFPEMMAEIISVQVPKILSGKVKPIY

Rat                           QFTFDLLIKSHMVSVDFPEMMAEIISVQVPKILSGKVKPIY

Pig                           QFTFDLLIKSHMVSVDFPEMMAEIISVQVPKILSGKVKPIY

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 – 920	Androgen receptor
Domain	669 – 900	NR LBD
Region	552 – 919	Interaction with LPXN
Region	592 – 919	Interaction with CCAR1
Region	625 – 919	Interaction with KAT7
Binding site	878 – 878	17beta-hydroxy-5alpha-androstan-3-one
Site	898 – 898	Interaction with coactivator FXXLF and FXXFY motifs
Modified residue	916 – 916	Phosphotyrosine; by CSK
Alternative sequence	645 – 920	Missing. In isoform 3.
Alternative sequence	649 – 920	Missing. In isoform 4.
Mutagenesis	898 – 898	E -> AQ. Reduced transcription activation in the presence of androgen.
Mutagenesis	898 – 898	E -> KR. Loss of transcription activation in the presence of androgen.
Mutagenesis	916 – 916	Y -> F. Decrease in CSK-induced phosphorylation.
Helix	894 – 902

Literature citations

Structural basis for accommodation of nonsteroidal ligands in the androgen receptor.
Bohl C.E.; Miller D.D.; Chen J.; Bell C.E.; Dalton J.T.;
J. Biol. Chem. 280:37747-37754(2005)
Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 665-920 IN COMPLEXES WITH NONSTEROIDAL LIGANDS; MUTAGENESIS OF TRP-742; CHARACTERIZATION OF VARIANT PROSTATE CANCER ALA-878; CHARACTERIZATION OF VARIANT AIS THR-896;

Functional characterisation of mutations in the ligand-binding domain of the androgen receptor gene in patients with androgen insensitivity syndrome.
Lundberg Giwercman Y.; Nikoshkov A.; Lindsten K.; Bystroem B.; Pousette A.; Chibalin A.V.; Arvidsson S.; Tiulpakov A.; Semitcheva T.V.; Peterkova V.; Hagenfeldt K.; Ritzen E.M.; Wedell A.;
Hum. Genet. 103:529-531(1998)
Cited for: VARIANTS AIS THR-766; TYR-785 AND THR-896; VARIANT PAIS GLY-841;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P10275: Variant p.Met896Thr