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:
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 CPSCNKMIVSQLSYNAGALT WLSCGSLCLLGCIAGCCFIPF
Mouse CPSCSKMIVTQLSYNAGALT WLSCGSLCLLGCVAGCCFIPF
Rat CPSCNKMIVTQLSYNAGALT WLSCGSLCLLGCVAGCCFIPF
Chicken CPSCNQMIVTRLCYESGALT WLSCGGLFLLGCIAGCCLIPF
Xenopus tropicalis CRSCNSMITTRLEYSSGALA WLSCGGLCLLGCIGGCCLIPF
Zebrafish CPVCSQSVITRLEYSSGPLV WLSCAGLAVFGCIYGCCLIPF
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
1 – 161 Lipopolysaccharide-induced tumor necrosis factor-alpha factor
76 – 160 LITAF
111 – 134 Membrane-binding amphipathic helix
96 – 96
99 – 99
96 – 96 C -> A. Abolishes association with cytoplasmic vesicle membranes.
135 – 135 P -> T. Decreases protein stability and association with early endosome membranes. Impaired function in targeting endocytosed proteins for lysosomal degradation.
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.;
Cited for: VARIANTS CMT1C SER-112; ASN-115 AND GLY-116;
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