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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P10275: Variant p.Thr878Ala

Androgen receptor
Gene: AR
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Variant information Variant position: help 878 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Threonine (T) to Alanine (A) at position 878 (T878A, p.Thr878Ala). 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 small size and hydrophobic (A) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 0 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: help The poly-Gln region of AR is highly polymorphic and the number of Gln varies in the population (from 17 to 26). A smaller size of the poly-Gln region may be associated with the development of prostate cancer. Long poly-Gln alleles (>23) may be associated with higher testosterone levels and severe clinical outcome in COVID-19 disease (PubMed:33647767).The poly-Gly region of AR is polymorphic and ranges from 24 to 31 Gly. A poly-Gly region shorter or equal to 23 may be associated with the development of androgenetic alopecia. - Additional information on the polymorphism described.
Variant description: help Found in prostate cancer; found in bone metastases; alters receptor specificity so that transcription is activated by antiandrogens such as cyproterone acetate. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 878 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 920 The length of the canonical sequence.
Location on the sequence: help YQLTKLLDSVQPIARELHQF T FDLLIKSHMVSVDFPEMMAE 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                         YQLTKLLDSVQPIARELHQFTFDLLIKSHMVSVDFPEMMAE

                              YQLTKLLDSVQPIARELHQFTFDLLIKSHMVSVDFPEMMAE

Rhesus macaque                YQLTKLLDSVQPIARELHQFTFDLLIKSHMVSVDFPEMMAE

Chimpanzee                    YQLTKLLDSVQPIARELHQFTFDLLIKSHMVSVDFPEMMAE

Mouse                         YQLTKLLDSVQPIARELHQFTFDLLIKSHMVSVDFPEMMAE

Rat                           YQLTKLLDSVQPIARELHQFTFDLLIKSHMVSVDFPEMMAE

Pig                           YQLTKLLDSVQPIARELHQFTFDLLIKSHMVSVDFPEMMAE

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 – 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
Site 898 – 898 Interaction with coactivator FXXLF and FXXFY motifs
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.
Helix 850 – 883



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; Crystal structure of the T877A human androgen receptor ligand-binding domain complexed to cyproterone acetate provides insight for ligand-induced conformational changes and structure-based drug design.
Bohl C.E.; Wu Z.; Miller D.D.; Bell C.E.; Dalton J.T.;
J. Biol. Chem. 282:13648-13655(2007)
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 671-919 OF MUTANT ALA-878 IN COMPLEX WITH THE ANTIANDROGEN CYPROTERONE ACETATE; CHARACTERIZATION OF VARIANT PROSTATE CANCER ALA-878; MUTAGENESIS OF LEU-702; Identification of a new androgen receptor (AR) co-regulator BUD31 and related peptides to suppress wild-type and mutated AR-mediated prostate cancer growth via peptide screening and X-ray structure analysis.
Hsu C.L.; Liu J.S.; Wu P.L.; Guan H.H.; Chen Y.L.; Lin A.C.; Ting H.J.; Pang S.T.; Yeh S.D.; Ma W.L.; Chen C.J.; Wu W.G.; Chang C.;
Mol. Oncol. 8:1575-1587(2014)
Cited for: X-RAY CRYSTALLOGRAPHY (1.42 ANGSTROMS) OF 671-920 OF VARIANT PROSTATE CANCER ALA-878 AND WILD-TYPE IN COMPLEX WITH DIHYDROTESTOSTERONE AND BUD31 PEPTIDES; INTERACTION WITH BUD31; FUNCTION; SUBCELLULAR LOCATION; DOMAIN; A mutation in the ligand binding domain of the androgen receptor of human LNCaP cells affects steroid binding characteristics and response to anti-androgens.
Veldscholte J.; Ris-Stalpers C.; Kuiper G.G.J.M.; Jenster G.; Berrevoets C.A.; Claassen E.; van Rooij H.C.J.; Trapman J.; Brinkmann A.O.; Mulder E.;
Biochem. Biophys. Res. Commun. 173:534-540(1990)
Cited for: VARIANT LNCAP ALA-878; The androgen receptor in LNCaP cells contains a mutation in the ligand binding domain which affects steroid binding characteristics and response to antiandrogens.
Veldscholte J.; Berrevoets C.A.; Ris-Stalpers C.; Kuiper G.G.J.M.; Jenster G.; Trapman J.; Brinkmann A.O.; Mulder E.;
J. Steroid Biochem. Mol. Biol. 41:665-669(1992)
Cited for: VARIANT PROSTATE CANCER ALA-878; Androgen receptor gene mutations in human prostate cancer.
Suzuki H.; Sato N.; Watabe Y.; Masai M.; Seino S.; Shimazaki J.;
J. Steroid Biochem. Mol. Biol. 46:759-765(1993)
Cited for: VARIANTS HIS-702 AND ALA-878; Frequent detection of codon 877 mutation in the androgen receptor gene in advanced prostate cancers.
Gaddipati J.P.; McLeod D.G.; Heidenberg H.B.; Sesterhenn I.A.; Finger M.J.; Moul J.W.; Srivastava S.;
Cancer Res. 54:2861-2864(1994)
Cited for: VARIANT PROSTATE CANCER ALA-878; Codon 877 mutation in the androgen receptor gene in advanced prostate cancer: relation to antiandrogen withdrawal syndrome.
Suzuki H.; Akakura K.; Komiya A.; Aida S.; Akimoto S.; Shimazaki J.;
Prostate 29:153-158(1996)
Cited for: VARIANT PROSTATE CANCER ALA-878; Selection for androgen receptor mutations in prostate cancers treated with androgen antagonist.
Taplin M.-E.; Bubley G.J.; Ko Y.J.; Small E.J.; Upton M.; Rajeshkumar B.; Balk S.P.;
Cancer Res. 59:2511-2515(1999)
Cited for: VARIANTS PROSTATE CANCER ALA-878 AND ASN-891; Two mutations identified in the androgen receptor of the new human prostate cancer cell line MDA PCa 2a.
Zhao X.Y.; Boyle B.; Krishnan A.V.; Navone N.M.; Peehl D.M.; Feldman D.;
J. Urol. 162:2192-2199(1999)
Cited for: VARIANTS HIS-702 AND ALA-878;
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.