UniProtKB/Swiss-Prot P16442: Variant p.Met214Arg

Histo-blood group ABO system transferase
Gene: ABO
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Variant information Variant position:

214 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

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:

From Methionine (M) to Arginine (R) at position 214 (M214R, p.Met214Arg). 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 large size and basic (R) 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:

Genetic variations in ABO define the ABO blood group system [MIM:616093]. The ABO blood group system is one of the most important blood group systems in transfusion medicine. The ABO blood group involves 3 carbohydrate antigens: A, B, and H. A, B, and AB individuals express a glycosyltransferase activity that converts the H antigen to the A antigen (by addition of UDP-GalNAc) or to the B antigen (by addition of UDP-Gal). There are only 4 amino acid differences between A and B transferases in the catalytic domain, two of which (Leu266Met and Gly268Ala) are primarily responsible for the substrate specificity. The group O phenotype results from variations in ABO that cause a loss of glycosyltransferase activity. The most common group O allele results from a single nucleotide deletion near the 5' end of the gene (NM_020469.2:c.261del) that causes a frameshift and early termination with no active enzyme production (p.Thr88Profs*31). Additional information on the polymorphism described.
Variant description:

In allele Bel01; loss of manganese binding and reduced catalytic activity. Any additional useful information about the variant.

Sequence information Variant position:

214 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

354 The length of the canonical sequence.
Location on the sequence:

DFCERRFLSEVDYLVCVDVD M EFRDHVGVEILTPLFGTLHP 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                         DFCERRFLSEVDYLVCVDVDMEFRDHVGVEILTPLFGTLHP

Mouse                         HFSERRFLREVDYLVCADADMKFSDHVGVEILSTFFGTLHP

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 – 354	Histo-blood group ABO system transferase
Chain	54 – 354	Fucosylglycoprotein alpha-N-acetylgalactosaminyltransferase soluble form
Topological domain	54 – 354	Lumenal
Binding site	211 – 211
Binding site	213 – 213
Binding site	233 – 233
Mutagenesis	214 – 214	M -> TV. Alters substrate specificity so that both UDP-N-acetyl-D-galactosamine and UDP-galactose are utilized.
Mutagenesis	234 – 234	P -> S. Altered substrate specificity in group B transferase.
Beta strand	212 – 216

Literature citations
Molecular genetic analysis of variant phenotypes of the ABO blood group system.
Ogasawara K.; Yabe R.; Uchikawa M.; Saitou N.; Bannai M.; Nakata K.; Takenaka M.; Fujisawa K.; Ishikawa Y.; Juji T.; Tokunaga K.;
Blood 88:2732-2737(1996)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 81-354; POLYMORPHISM; VARIANTS LEU-156; GLY-176; ARG-214; ILE-216; ASP-223; SER-235; MET-266; ALA-268; MET-277; ASN-291; GLY-352 AND TRP-352; Structural effects of naturally occurring human blood group B galactosyltransferase mutations adjacent to the DXD motif.
Persson M.; Letts J.A.; Hosseini-Maaf B.; Borisova S.N.; Palcic M.M.; Evans S.V.; Olsson M.L.;
J. Biol. Chem. 282:9564-9570(2007)
Cited for: X-RAY CRYSTALLOGRAPHY (1.67 ANGSTROMS) OF 64-354 OF MUTANTS ARG-214 AND THR-214; COFACTOR; CHARACTERIZATION OF VARIANT ARG-214; MUTAGENESIS OF MET-214; 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.