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UniProtKB/Swiss-Prot P30038: Variant p.Ser352Leu

Delta-1-pyrroline-5-carboxylate dehydrogenase, mitochondrial
Gene: ALDH4A1
Chromosomal location: 1p36
Variant information

Variant position:  352
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
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 Serine (S) to Leucine (L) at position 352 (S352L, p.Ser352Leu).
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 polar (S) to medium size and hydrophobic (L)
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

Involvement in disease:  Hyperprolinemia 2 (HYRPRO2) [MIM:239510]: An inborn error of proline metabolism resulting in elevated plasma levels of proline and delta-1-pyrroline-5-carboxylate (P5C). The condition is considered to be benign, but affected individuals can exhibit neurological manifestations that vary in severity. Clinical signs include seizures, intellectual deficit and mild developmental delay. {ECO:0000269|PubMed:22516612, ECO:0000269|PubMed:9700195}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In HYRPRO2; allele ALDH4A1*3; loss of enzyme activity.
Any additional useful information about the variant.

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



Sequence information

Variant position:  352
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  563
The length of the canonical sequence.

Location on the sequence:   VVSGTLRSAFEYGGQKCSAC  S RLYVPHSLWPQIKGRLLEEH
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                         VVSGTLRSAFEYGGQKCSACSRLYVPHSLWPQIKGRLLEEH

Mouse                         VVSGTLRSAFEYGGQKCSACSRLYVPKSLWPQIKGRLLEEH

Rat                           VVSGTLRSAFEYGGQKCSACSRLYVPQSLWPQIKGRLLEEH

Bovine                        VVSGTLRSAFEYGGQKCSACSRLYAPRSLWPQIKGRLLEEL

Zebrafish                     VVTGTIRSAFEYGGQKCSACSRMYVPDSLWPQIRQGLLDVY

Slime mold                    FVNNTLRGAFEYQGQKCSACSRAYIPQSLWPQIKDRLVTGV

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 25 – 563 Delta-1-pyrroline-5-carboxylate dehydrogenase, mitochondrial
Active site 348 – 348 Nucleophile
Modified residue 347 – 347 N6-succinyllysine
Modified residue 365 – 365 N6-acetyllysine
Mutagenesis 352 – 352 S -> A. Reduced affinity for NAD. No effect on enzyme activity.
Beta strand 351 – 357


Literature citations

The three-dimensional structural basis of type II hyperprolinemia.
Srivastava D.; Singh R.K.; Moxley M.A.; Henzl M.T.; Becker D.F.; Tanner J.J.;
J. Mol. Biol. 420:176-189(2012)
Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 18-563 OF WILD-TYPE; MUTANT ALA-352 AND VARIANT HYRPRO2 LEU-352; CATALYTIC ACTIVITY; FUNCTION; PATHWAY; BIOPHYSICOCHEMICAL PROPERTIES; SUBUNIT; ACTIVE SITE; CHARACTERIZATION OF VARIANT HYRPRO2 LEU-352; MUTAGENESIS OF SER-352;

Mutations in the Delta1-pyrroline 5-carboxylate dehydrogenase gene cause type II hyperprolinemia.
Geraghty M.T.; Vaughn D.; Nicholson A.J.; Lin W.-W.; Jimenez-Sanchez G.; Obie C.; Flynn M.P.; Valle D.; Hu C.-A.A.;
Hum. Mol. Genet. 7:1411-1415(1998)
Cited for: VARIANT HYRPRO2 LEU-352; VARIANT LEU-16;

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.