UniProtKB/Swiss-Prot P23526: Variant p.Arg49Cys

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 49 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: LP/P [Disclaimer: Variants classification is intended for research purposes only, not for clinical and diagnostic use. The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant.] 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 Arginine (R) to Cysteine (C) at position 49 (R49C, p.Arg49Cys). 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 large size and basic (R) to medium size and polar (C) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: -3 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 HMAHCHD; severely decreased adenosylhomocysteinase activity measured under reducing conditions; affects protein self-interaction and is able to form tetramers only under reducing conditions; does not affect nuclear-cytoplasmic protein distribution. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs369428934 [ dbSNP | Ensembl ]

Sequence information

Variant position: 49 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 432 The length of the canonical sequence.
Location on the sequence: MPGLMRMRERYSASKPLKGA R IAGCLHMTVETAVLIETLVT 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.
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	2 – 432	Adenosylhomocysteinase
Binding site	57 – 57
Mutagenesis	1 – 127	Missing. Affects nuclear-cytoplasmic protein distribution resulting in increased protein amount in the nucleus.
Beta strand	49 – 54

Literature citations

S-adenosylhomocysteine hydrolase (AHCY) deficiency: two novel mutations with lethal outcome.
Vugrek O.; Beluzic R.; Nakic N.; Mudd S.H.;
Hum. Mutat. 30:E555-E565(2009)
Cited for: VARIANTS HMAHCHD CYS-49 AND GLY-86; SUBUNIT; CHARACTERIZATION OF VARIANTS HMAHCHD CYS-49 AND GLY-86; S-adenosylhomocysteine hydrolase deficiency: two siblings with fetal hydrops and fatal outcomes.
Grubbs R.; Vugrek O.; Deisch J.; Wagner C.; Stabler S.; Allen R.; Baric I.; Rados M.; Mudd S.H.;
J. Inherit. Metab. Dis. 33:705-713(2010)
Cited for: VARIANTS HMAHCHD CYS-49 AND GLY-86; Clinical picture of S-adenosylhomocysteine hydrolase deficiency resembles phosphomannomutase 2 deficiency.
Honzik T.; Magner M.; Krijt J.; Sokolova J.; Vugrek O.; Beluzic R.; Baric I.; Hansikova H.; Elleder M.; Vesela K.; Bauerova L.; Ondruskova N.; Jesina P.; Zeman J.; Kozich V.;
Mol. Genet. Metab. 107:611-613(2012)
Cited for: VARIANTS HMAHCHD CYS-49 AND SER-71; Mutations in S-adenosylhomocysteine hydrolase (AHCY) affect its nucleocytoplasmic distribution and capability to interact with S-adenosylhomocysteine hydrolase-like 1 protein.
Grbesa I.; Kalo A.; Beluzic R.; Kovacevic L.; Lepur A.; Rokic F.; Hochberg H.; Kanter I.; Simunovic V.; Munoz-Torres P.M.; Shav-Tal Y.; Vugrek O.;
Eur. J. Cell Biol. 96:579-590(2017)
Cited for: CHARACTERIZATION OF VARIANTS HMAHCHD CYS-49; SER-71; GLY-86; VAL-89; CYS-143 AND ASP-328; MUTAGENESIS OF 1-MET--MET-127; TYR-7 AND 365-GLN--TYR-432; SUBCELLULAR LOCATION; INTERACTION WITH AHCYL1;