UniProtKB/Swiss-Prot P35222: Variant p.Thr41Ala

Catenin beta-1
Gene: CTNNB1
Chromosomal location: 3p21.3
Variant information

Variant position:  41
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Unclassified
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Threonine (T) to Alanine (A) at position 41 (T41A, p.Thr41Ala).
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 polar (T) to small size and hydrophobic (A)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  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

Variant description:  In hepatoblastoma and hepatocellular carcinoma; also in a desmoid tumor; strongly reduces phosphorylation and degradation; abolishes phosphorylation on Ser-33 and Ser-37 and enhances transactivation of target genes.
Any additional useful information about the variant.



Sequence information

Variant position:  41
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  781
The length of the canonical sequence.

Location on the sequence:   AVSHWQQQSYLDSGIHSGAT  T TAPSLSGKGNPEEEDVDTSQ
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                         AVSHWQQQSYLDSGIHSGATTTAPSLSGKGNPEEEDVDTSQ

Mouse                         AVSHWQQQSYLDSGIHSGATTTAPSLSGKGNPEEEDVDTSQ

Rat                           AVSHWQQQSYLDSGIHSGATTTAPSLSGKGNPEEEDVDTSQ

Bovine                        AVSHWQQQSYLDSGIHSGATTTAPSLSGKGNPEEEDVDTTQ

Dog                           AVSHWQQQSYLDSGIHSGATTTAPSLSGKGNPEEEDVDTTQ

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.

TypePositionsDescription
Chain 2 – 781 Catenin beta-1
Modified residue 23 – 23 Phosphoserine; by GSK3-beta
Modified residue 29 – 29 Phosphoserine; by GSK3-beta
Modified residue 33 – 33 Phosphoserine; by GSK3-beta and HIPK2
Modified residue 37 – 37 Phosphoserine; by GSK3-beta and HIPK2
Modified residue 41 – 41 Phosphothreonine; by GSK3-beta
Modified residue 45 – 45 Phosphoserine
Alternative sequence 1 – 565 Missing. In isoform 2.
Mutagenesis 29 – 29 S -> F. No effect.


Literature citations

Characterisation of the phosphorylation of beta-catenin at the GSK-3 priming site Ser45.
Hagen T.; Vidal-Puig A.;
Biochem. Biophys. Res. Commun. 294:324-328(2002)
Cited for: PHOSPHORYLATION AT SER-45; CHARACTERIZATION OF VARIANT HEPATOCELLULAR CARCINOMA ALA-41; CHARACTERIZATION OF VARIANT DESMOID TUMOR ALA-41; CHARACTERIZATION OF VARIANT HEPATOBLASTOMA ALA-41;

Identification of two novel regulated serines in the N-terminus of beta-catenin.
van Noort M.; van de Wetering M.; Clevers H.;
Exp. Cell Res. 276:264-272(2002)
Cited for: PHOSPHORYLATION AT SER-23 AND SER-29 BY GSK3B; PHOSPHORYLATION AT THR-41; MUTAGENESIS OF SER-29; CHARACTERIZATION OF VARIANTS HEPATOCELLULAR CARCINOMA ARG-23; ALA-37 AND ALA-41; CHARACTERIZATION OF VARIANT PTR TYR-33; CHARACTERIZATION OF VARIANT MDB ALA-37; CHARACTERIZATION OF VARIANT DESMOID TUMOR ALA-41; CHARACTERIZATION OF VARIANT HEPATOBLASTOMA ALA-41;

Childhood hepatoblastomas frequently carry a mutated degradation targeting box of the beta-catenin gene.
Koch A.; Denkhaus D.; Albrecht S.; Leuschner I.; von Schweinitz D.; Pietsch T.;
Cancer Res. 59:269-273(1999)
Cited for: VARIANTS HEPATOBLASTOMA TYR-32; VAL-34; CYS-37 AND ALA-41;

Beta-catenin accumulation and mutation of the CTNNB1 gene in hepatoblastoma.
Blaeker H.; Hofmann W.J.; Rieker R.J.; Penzel R.; Graf M.; Otto H.F.;
Genes Chromosomes Cancer 25:399-402(1999)
Cited for: VARIANT HEPATOBLASTOMA ALA-41;

Mutational analysis of beta-catenin gene in Japanese ovarian carcinomas: frequent mutations in endometrioid carcinomas.
Sagae S.; Kobayashi K.; Nishioka Y.; Sugimura M.; Ishioka S.; Nagata M.; Terasawa K.; Tokino T.; Kudo R.;
Jpn. J. Cancer Res. 90:510-515(1999)
Cited for: VARIANTS OVARIAN CANCER CYS-37; ILE-41 AND ALA-41;

A novel case of a sporadic desmoid tumour with mutation of the beta catenin gene.
Shitoh K.; Konishi F.; Iijima T.; Ohdaira T.; Sakai K.; Kanazawa K.; Miyaki M.;
J. Clin. Pathol. 52:695-696(1999)
Cited for: VARIANT DESMOID TUMOR ALA-41;

Beta-catenin mutations in hepatocellular carcinoma correlate with a low rate of loss of heterozygosity.
Legoix P.; Bluteau O.; Bayer J.; Perret C.; Balabaud C.; Belghiti J.; Franco D.; Thomas G.; Laurent-Puig P.; Zucman-Rossi J.;
Oncogene 18:4044-4046(1999)
Cited for: VARIANTS HEPATOCELLULAR CARCINOMA ARG-23; 25-TRP--SER-33 DEL; ALA-32; GLY-32; TYR-32; LEU-33; PHE-33; ARG-34; SER-35; ALA-37; 37-SER-GLY-38 DELINS TRP; TYR-37; ALA-41; ILE-41; PHE-45 AND PRO-45;

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.