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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9H3L0: Variant p.Leu259Pro

Cobalamin trafficking protein CblD
Gene: MMADHC
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Variant information Variant position: help 259 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] 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: help From Leucine (L) to Proline (P) at position 259 (L259P, p.Leu259Pro). 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: help Similar physico-chemical property. Both residues are medium size and hydrophobic. The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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: help In MAHCD; cblD variant 1; decreases methylcobalamin levels and increases adenosylcobalamin levels; no effect on interaction with MMACHC. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 259 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 296 The length of the canonical sequence.
Location on the sequence: help NNTLFETDERYRHLGFSVDD L GCCKVIRHSLWGTHVVVGSI 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences.
Human                         NNTLFETDERYRHLGFSVDDLGCCKVIRHSLWGTHVVVGSI

Mouse                         NNTLFETDERYRHLGFSVDDLGCCKVIRHSLWGTHVVVGSI

Rat                           NNTLFETDERYRHLGFSVDDLGCCKVIRHGLWGTHVVVGSI

Chicken                       NNTLFETDERYRHFGFSVDDLGCCKVIRHNIWGTHVVVGSI

Sequence annotation in neighborhood: help 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 39 – 296 Cobalamin trafficking protein CblD
Mutagenesis 266 – 266 R -> A. Mildly decreases methylcobalamin levels and strongly increases adenosylcobalamin levels.
Mutagenesis 270 – 270 W -> A. Decreases methylcobalamin levels.
Mutagenesis 278 – 278 S -> A. Marginally decreases methylcobalamin levels and strongly increases adenosylcobalamin levels.



Literature citations
Gene identification for the cblD defect of vitamin B12 metabolism.
Coelho D.; Suormala T.; Stucki M.; Lerner-Ellis J.P.; Rosenblatt D.S.; Newbold R.F.; Baumgartner M.R.; Fowler B.;
N. Engl. J. Med. 358:1454-1464(2008)
Cited for: FUNCTION; TISSUE SPECIFICITY; VARIANTS MAHCD LEU-ALA-GLU-PRO-LEU-SER-108 INS; ASN-182; 204-PHE--ALA-232 DEL; CYS-249 AND PRO-259; Characterization of functional domains of the cblD (MMADHC) gene product.
Jusufi J.; Suormala T.; Burda P.; Fowler B.; Froese D.S.; Baumgartner M.R.;
J. Inherit. Metab. Dis. 37:841-849(2014)
Cited for: FUNCTION; CHARACTERIZATION OF VARIANT MAHCD PRO-259; MUTAGENESIS OF PHE-165; MET-186; TRP-189; ARG-197; PHE-204; CYS-212; ASP-226; TYR-237; ARG-266; TRP-270; SER-278 AND PHE-280; Structural insights into the MMACHC-MMADHC protein complex involved in vitamin B12 trafficking.
Froese D.S.; Kopec J.; Fitzpatrick F.; Schuller M.; McCorvie T.J.; Chalk R.; Plessl T.; Fettelschoss V.; Fowler B.; Baumgartner M.R.; Yue W.W.;
J. Biol. Chem. 290:29167-29177(2015)
Cited for: INTERACTION WITH MMACHC; CHARACTERIZATION OF VARIANTS MAHCD ASN-182 AND PRO-259; MUTAGENESIS OF TRP-189 AND ASP-226;
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.