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UniProtKB/Swiss-Prot P63000: Variant p.Cys18Tyr

Ras-related C3 botulinum toxin substrate 1
Gene: RAC1
Variant information

Variant position:  18
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 Cysteine (C) to Tyrosine (Y) at position 18 (C18Y, p.Cys18Tyr).
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 polar (C) to large size and aromatic (Y)
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:  Mental retardation, autosomal dominant 48 (MRD48) [MIM:617751]: A form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD48 patients manifest global developmental delay and moderate to severe intellectual disability. {ECO:0000269|PubMed:28886345}. 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 MRD48; decreased substrate adhesion-dependent cell spreading; dominant-negative effect; reduced neuronal proliferation.
Any additional useful information about the variant.

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

Sequence information

Variant position:  18
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  192
The length of the canonical sequence.

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.

Chain 1 – 189 Ras-related C3 botulinum toxin substrate 1
Nucleotide binding 13 – 18 GTP
Modified residue 32 – 32 O-AMP-tyrosine; by Haemophilus IbpA; alternate
Modified residue 35 – 35 O-AMP-threonine; by Vibrio VopS
Glycosylation 32 – 32 O-linked (GlcNAc) tyrosine; by Photorhabdus PAU_02230; alternate
Mutagenesis 12 – 12 G -> V. Constitutively active. Interacts with PARD6 proteins. Increases nuclear localization and up-regulates transcriptional activity of NR3C2.
Mutagenesis 17 – 17 T -> N. Constitutively inactivated. Abolishes interaction with PARD6 proteins. No effect on NR3C2 transcriptional activity. No interaction with PPP5C. Doesn't activate PPP5C phosphatase activity and translocate PPP5C to the plasma membrane.
Mutagenesis 30 – 30 G -> V. No interaction with PPP5C; when associated with L-61. Translocates to the plasma membrane; also when associated with L-61.
Mutagenesis 32 – 32 Y -> F. Abolishes AMPylation by Haemophilus IbpA.
Mutagenesis 35 – 35 T -> A. Abolishes AMPylation by Vibrio VopS.
Mutagenesis 35 – 35 T -> S. No interaction with PPP5C; when associated with L-61. Translocates to the plasma membrane; also when associated with L-61.
Mutagenesis 37 – 37 F -> A. Strongly reduced interaction with PLCB2.
Helix 16 – 25

Literature citations

RAC1 Missense Mutations in Developmental Disorders with Diverse Phenotypes.
Reijnders M.R.F.; Ansor N.M.; Kousi M.; Yue W.W.; Tan P.L.; Clarkson K.; Clayton-Smith J.; Corning K.; Jones J.R.; Lam W.W.K.; Mancini G.M.S.; Marcelis C.; Mohammed S.; Pfundt R.; Roifman M.; Cohn R.; Chitayat D.; Millard T.H.; Katsanis N.; Brunner H.G.; Banka S.;
Am. J. Hum. Genet. 101:466-477(2017)

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.