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UniProtKB/Swiss-Prot Q16637: Variant p.Gly279Val

Survival motor neuron protein
Gene: SMN2
Variant information

Variant position:  279
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 Glycine (G) to Valine (V) at position 279 (G279V, p.Gly279Val).
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 glycine (G) to medium size and hydrophobic (V)
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:  Spinal muscular atrophy 1 (SMA1) [MIM:253300]: A form of spinal muscular atrophy, a group of neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. Autosomal recessive forms are classified according to the age of onset, the maximum muscular activity achieved, and survivorship. The severity of the disease is mainly determined by the copy number of SMN2, a copy gene which predominantly produces exon 7-skipped transcripts and only low amount of full-length transcripts that encode for a protein identical to SMN1. Only about 4% of SMA patients bear one SMN1 copy with an intragenic mutation. SMA1 is a severe form, with onset before 6 months of age. SMA1 patients never achieve the ability to sit. {ECO:0000269|PubMed:10732817, ECO:0000269|PubMed:14715275, ECO:0000269|PubMed:15249625, ECO:0000269|PubMed:15580564, ECO:0000269|PubMed:21088113, ECO:0000269|PubMed:21389246, ECO:0000269|PubMed:7813012, ECO:0000269|PubMed:9147655}. 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 SMA1; slightly reduces SMN binding to RPP20/POP7. Impairs dimerization and axon localization.
Any additional useful information about the variant.

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



Sequence information

Variant position:  279
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  294
The length of the canonical sequence.

Location on the sequence:   ALGSMLISWYMSGYHTGYYM  G FRQNQKEGRCSHSLN
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                         A----LGSMLISWYMSGYHTGYYMGFRQ-NQKEGR-CSHSLN

                              A----LGSMLISWYMSGYHTGYYMGFKQ-NQKEGR-

Mouse                         A----LGSMLISWYMSGYHTGYYMGFRQ-NKKEGK-

Rat                           A----LGSMLISWYMSGYHTGYYMGFRQ-NKKEGKK

Bovine                        A----LGSMLISWYMSGYHTGYYMGFKQ-SQKEGR-

Cat                           A----LGSMLISWYMSGYHTGYYMGFKQ-NQKEGR-

Drosophila                    GAEQDFVAMLTAWYMSGYYTGLYQGKKEASTTSGKK

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 – 294 Survival motor neuron protein
Region 279 – 294 Required for interaction with SYNCRIP
Alternative sequence 279 – 282 GFRQ -> EMLA. In isoform SMN-delta7 and isoform SMN-delta57.
Helix 263 – 280


Literature citations

Rpp20 interacts with SMN and is re-distributed into SMN granules in response to stress.
Hua Y.; Zhou J.;
Biochem. Biophys. Res. Commun. 314:268-276(2004)
Cited for: SUBUNIT; INTERACTION WITH RPP20/POP7; SUBCELLULAR LOCATION; MUTAGENESIS OF GLU-134; CHARACTERIZATION OF VARIANTS SMA1 CYS-272 AND VAL-279; CHARACTERIZATION OF VARIANT SMA2 AND SMA3 ILE-274; CHARACTERIZATION OF VARIANT SMA3 ILE-262;

Missense mutation clustering in the survival motor neuron gene: a role for a conserved tyrosine and glycine rich region of the protein in RNA metabolism?
Talbot K.; Ponting C.P.; Theodosiou A.M.; Rodriques N.R.; Surtees R.; Mountford R.; Davies K.E.;
Hum. Mol. Genet. 6:497-500(1997)
Cited for: VARIANT SMA1 VAL-279;

The survival of motor neuron (SMN) protein interacts with the mRNA-binding protein HuD and regulates localization of poly(A) mRNA in primary motor neuron axons.
Fallini C.; Zhang H.; Su Y.; Silani V.; Singer R.H.; Rossoll W.; Bassell G.J.;
J. Neurosci. 31:3914-3925(2011)
Cited for: INTERACTION WITH ELAVL4; VARIANT SMA1 VAL-279; MUTAGENESIS OF GLU-134;

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.