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UniProtKB/Swiss-Prot P30566: Variant p.Arg303Cys

Adenylosuccinate lyase
Gene: ADSL
Variant information

Variant position:  303
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 Arginine (R) to Cysteine (C) at position 303 (R303C, p.Arg303Cys).
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

Involvement in disease:  Adenylosuccinase deficiency (ADSLD) [MIM:103050]: An autosomal recessive disorder characterized by the accumulation in the body fluids of succinylaminoimidazole-carboxamide riboside (SAICA-riboside) and succinyladenosine (S-Ado). Most children display marked psychomotor delay, often accompanied by epilepsy or autistic features, or both, although some patients may be less profoundly retarded. Occasionally, growth retardation and muscular wasting are also present. {ECO:0000269|PubMed:10090474, ECO:0000269|PubMed:10888601, ECO:0000269|PubMed:10958654, ECO:0000269|PubMed:12368987, ECO:0000269|PubMed:12833398, ECO:0000269|PubMed:1302001, ECO:0000269|PubMed:19405474, ECO:0000269|PubMed:22812634, ECO:0000269|PubMed:9266401, ECO:0000269|PubMed:9545543}. 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 ADSLD; mild; strongly reduced activity with SAMP, but only slightly reduced activity with SAICAR; abolishes cooperativity.
Any additional useful information about the variant.

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



Sequence information

Variant position:  303
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  484
The length of the canonical sequence.

Location on the sequence:   EKQQIGSSAMPYKRNPMRSE  R CCSLARHLMTLVMDPLQTAS
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                         EKQQIGSSAMPYKRNPMRSERCCSLARHLMTLVMDPLQTAS

Mouse                         EKQQIGSSAMPYKRNPMRSERCCSLARHLMALTMDPLQTAS

Bovine                        EKQQIGSSAMPYKRNPMRSERCCSLARHLMALVMDPLQTAS

Chicken                       EKDQIGSSAMPYKRNPMRSERCCSLARHLMTLVLDPLQTAS

Caenorhabditis elegans        EKDQIGSSAMPYKKNPMKSERCCALSRKLINAPQEALTILA

Slime mold                    VKGEVGSSTMPHKVNPIDFENAEGNMGVANALYEHLSAKLP

Baker's yeast                 EKSQIGSSAMAYKRNPMRCERVCSLARHLGSLFSDAVQTAS

Fission yeast                 EAGQIGSSAMAYKRNPMRCERICSQARYIMNLIPNALNTAS

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 2 – 484 Adenylosuccinate lyase
Active site 289 – 289 Proton donor/acceptor
Binding site 303 – 303 Substrate; shared with neighboring subunit
Modified residue 295 – 295 N6-acetyllysine
Helix 299 – 313


Literature citations

Structural and biochemical characterization of human adenylosuccinate lyase (ADSL) and the R303C ADSL deficiency-associated mutation.
Ray S.P.; Deaton M.K.; Capodagli G.C.; Calkins L.A.; Sawle L.; Ghosh K.; Patterson D.; Pegan S.D.;
Biochemistry 51:6701-6713(2012)
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF WILD-TYPE AND VARIANT ADSLD CYS-303; CATALYTIC ACTIVITY; CHARACTERIZATION OF VARIANT ADSLD CYS-303; ACTIVE SITE; ACTIVITY REGULATION; SUBUNIT;

Mutation analysis in adenylosuccinate lyase deficiency: eight novel mutations in the re-evaluated full ADSL coding sequence.
Marie S.; Cuppens H.; Heuterspreute M.; Jaspers M.; Tola E.Z.; Gu X.X.; Legius E.; Vincent M.-F.; Jaeken J.; Cassiman J.-J.; van den Berghe G.;
Hum. Mutat. 13:197-202(1999)
Cited for: VARIANTS ADSLD VAL-72; TRP-141; GLN-190; GLU-246; CYS-303; ARG-395 AND HIS-426;

Clinical, biochemical and molecular genetic correlations in adenylosuccinate lyase deficiency.
Race V.; Marie S.; Vincent M.-F.; Van den Berghe G.;
Hum. Mol. Genet. 9:2159-2165(2000)
Cited for: CHARACTERIZATION OF VARIANTS ADSLD VAL-2; LEU-26; TRP-141; CYS-303; ARG-395; HIS-426 AND SER-450;

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.