UniProtKB/SwissProt variant VAR

Variant information

Variant position:

116

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

Type of variant:

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:

From Tryptophan (W) to Glycine (G) at position 116 (W116G, p.Trp116Gly).

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 aromatic (W) to glycine (G)

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

Variant description:

In CMT1C; decreases protein stability and association with early endosome membranes; impaired function in targeting endocytosed proteins for lysosomal degradation; does not abolish interaction with NEDD4 and TSG101.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs104894521 [ dbSNP | Ensembl ]

Sequence information

Variant position:

116

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

Protein sequence length:

161

The length of the canonical sequence.

Location on the sequence:

CPSCNKMIVSQLSYNAGALT W LSCGSLCLLGCIAGCCFIPF

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                         CPSCNKMIVSQLSYNAGALTWLSCGSLCLLGCIAGCCFIPF

Mouse                         CPSCSKMIVTQLSYNAGALTWLSCGSLCLLGCVAGCCFIPF

Rat                           CPSCNKMIVTQLSYNAGALTWLSCGSLCLLGCVAGCCFIPF

Chicken                       CPSCNQMIVTRLCYESGALTWLSCGGLFLLGCIAGCCLIPF

Xenopus tropicalis            CRSCNSMITTRLEYSSGALAWLSCGGLCLLGCIGGCCLIPF

Zebrafish                     CPVCSQSVITRLEYSSGPLVWLSCAGLAVFGCIYGCCLIPF

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.

Type	Positions	Description
Chain	1 – 161	Lipopolysaccharide-induced tumor necrosis factor-alpha factor
Domain	76 – 160	LITAF
Region	111 – 134	Membrane-binding amphipathic helix
Metal binding	96 – 96	Zinc
Metal binding	99 – 99	Zinc
Mutagenesis	96 – 96	C -> A. Abolishes association with cytoplasmic vesicle membranes.
Mutagenesis	135 – 135	P -> T. Decreases protein stability and association with early endosome membranes. Impaired function in targeting endocytosed proteins for lysosomal degradation.

Literature citations

SIMPLE interacts with NEDD4 and TSG101: evidence for a role in lysosomal sorting and implications for Charcot-Marie-Tooth disease.
Shirk A.J.; Anderson S.K.; Hashemi S.H.; Chance P.F.; Bennett C.L.;
J. Neurosci. Res. 82:43-50(2005)
Cited for: INTERACTION WITH NEDD4 AND TSG101; CHARACTERIZATION OF VARIANTS CMT1C SER-112; ASN-115 AND GLY-116; MUTAGENESIS OF 17-PRO--ALA-19 AND TYR-23;

Mutations associated with Charcot-Marie-Tooth disease cause SIMPLE protein mislocalization and degradation by the proteasome and aggresome-autophagy pathways.
Lee S.M.; Olzmann J.A.; Chin L.S.; Li L.;
J. Cell Sci. 124:3319-3331(2011)
Cited for: SUBCELLULAR LOCATION; MUTAGENESIS OF PRO-135; CHARACTERIZATION OF VARIANT CMT1C GLY-116;

Charcot-Marie-Tooth disease-linked protein SIMPLE functions with the ESCRT machinery in endosomal trafficking.
Lee S.M.; Chin L.S.; Li L.;
J. Cell Biol. 199:799-816(2012)
Cited for: FUNCTION; SUBCELLULAR LOCATION; DOMAIN; INTERACTION WITH TSG101; STAM AND HGS; PHOSPHORYLATION; MUTAGENESIS OF 17-PRO--PRO-20 AND PRO-135; CHARACTERIZATION OF VARIANT CMT1C GLY-116;

Mutation of a putative protein degradation gene LITAF/SIMPLE in Charcot-Marie-Tooth disease 1C.
Street V.A.; Bennett C.L.; Goldy J.D.; Shirk A.J.; Kleopa K.A.; Tempel B.L.; Lipe H.P.; Scherer S.S.; Bird T.D.; Chance P.F.;
Neurology 60:22-26(2003)
Cited for: VARIANTS CMT1C SER-112; ASN-115 AND GLY-116;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q99732: Variant p.Trp116Gly