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UniProtKB/Swiss-Prot P21964: Variant p.Ala72Ser

Catechol O-methyltransferase
Gene: COMT
Variant information

Variant position:  72
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Polymorphism
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 Alanine (A) to Serine (S) at position 72 (A72S, p.Ala72Ser).
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 small size and hydrophobic (A) to small size and polar (S)
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

Polymorphism:  Two alleles, COMT*1 or COMT*H with Val-158 and COMT*2 or COMT*L with Met-158 are responsible for a three to four-fold difference in enzymatic activity.Low enzyme activity alleles are associated with genetic susceptibility to alcoholism [MIM:103780]. -
Additional information on the polymorphism described.

Variant description:  Correlated with reduced enzyme activity; associated with increased risk for schizophrenia.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  72
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  271
The length of the canonical sequence.

Location on the sequence:   GDTKEQRILNHVLQHAEPGN  A QSVLEAIDTYCEQKEWAMNV
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                         GDTKEQRILNHVLQHAEPGNAQSVLEAIDTYCEQKEWAMNV

Mouse                         GGTKEQRILRHVQQHAKPGDPQSVLEAIDTYCSEKEWAMNV

Rat                           GDTKEQRILRYVQQNAKPGDPQSVLEAIDTYCTQKEWAMNV

Bovine                        GSSKEQRILQHVLQHAVAGDPQSVVAAIDSYSLEKEWAMHV

Horse                         GDSKEQRILRHVLQHAVAGDPQSVLETIDAYCSQKEWAMNV

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 1 – 271 Catechol O-methyltransferase
Topological domain 27 – 271 Extracellular
Binding site 92 – 92 S-adenosyl-L-methionine; via amide nitrogen
Helix 72 – 85


Literature citations

Submission
NIEHS SNPs program;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS SER-72 AND MET-158;

Characterization of single-nucleotide polymorphisms in coding regions of human genes.
Cargill M.; Altshuler D.; Ireland J.; Sklar P.; Ardlie K.; Patil N.; Shaw N.; Lane C.R.; Lim E.P.; Kalyanaraman N.; Nemesh J.; Ziaugra L.; Friedland L.; Rolfe A.; Warrington J.; Lipshutz R.; Daley G.Q.; Lander E.S.;
Nat. Genet. 22:231-238(1999)
Cited for: VARIANTS SER-34 AND SER-72;

Association of Ala72Ser polymorphism with COMT enzyme activity and the risk of schizophrenia in Koreans.
Lee S.-G.; Joo Y.; Kim B.; Chung S.; Kim H.-L.; Lee I.; Choi B.; Kim C.; Song K.;
Hum. Genet. 116:319-328(2005)
Cited for: CHARACTERIZATION OF VARIANT SER-72; INVOLVEMENT IN SCZD; CATALYTIC ACTIVITY;

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.