UniProtKB/Swiss-Prot Q15796: Variant p.Pro445His

Mothers against decapentaplegic homolog 2
Gene: SMAD2
Chromosomal location: 18q21.1
Variant information

Variant position:  445
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 implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Proline (P) to Histidine (H) at position 445 (P445H, p.Pro445His).
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 (P) to medium size and polar (H)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
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 a colorectal carcinoma sample.
Any additional useful information about the variant.



Sequence information

Variant position:  445
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  467
The length of the canonical sequence.

Location on the sequence:   EYRRQTVTSTPCWIELHLNG  P LQWLDKVLTQMGSPSVRCSS
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                         EYRRQTVTSTPCWIELHLNGPLQWLDKVLTQMGSPSVRCSS

Mouse                         EYRRQTVTSTPCWIELHLNGPLQWLDKVLTQMGSPSVRCSS

Rat                           EYRRQTVTSTPCWIELHLNGPLQWLDKVLTQMGSPSVRCSS

Bovine                        EYRRQTVTSTPCWIELHLNGPLQWLDKVLTQMGSPSVRCSS

Zebrafish                     EYRRQTVTSTPCWIELHLNGPLQWLDKVLTQMGSPSVRCSS

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 – 467 Mothers against decapentaplegic homolog 2
Domain 274 – 467 MH2
Modified residue 458 – 458 Phosphoserine
Modified residue 460 – 460 Phosphoserine
Modified residue 464 – 464 Phosphoserine
Modified residue 465 – 465 Phosphoserine; by TGFBR1
Mutagenesis 464 – 464 S -> A. Loss of phosphorylation by TGFBR1; when associated with A-465 and A-467.
Mutagenesis 465 – 465 S -> A. No change in binding to PPM1A. Loss of phosphorylation by TGFBR1; when associated with A-464 and A-467.
Mutagenesis 465 – 465 S -> D. No change in binding to PPM1A.
Helix 443 – 453


Literature citations

MADR2 maps to 18q21 and encodes a TGFbeta-regulated MAD-related protein that is functionally mutated in colorectal carcinoma.
Eppert K.; Scherer S.W.; Ozcelik H.; Pirone R.; Hoodless P.; Kim H.; Tsui L.-C.; Bapat B.; Gallinger S.; Andrulis I.L.; Thomsen G.H.; Wrana J.L.; Attisano L.;
Cell 86:543-552(1996)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG); PHOSPHORYLATION BY TGFBR1; VARIANTS CYS-133; ARG-440; HIS-445 AND GLU-450;

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.