UniProtKB/Swiss-Prot P50570: Variant p.Arg465Trp

Dynamin-2
Gene: DNM2
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Variant information Variant position:

465 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 Arginine (R) to Tryptophan (W) at position 465 (R465W, p.Arg465Trp). 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 large size and aromatic (W) 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
Variant description:

In CNM1; reduced association with the centrosome; COS7 cells show a reduced uptake of transferrin and low-density lipoprotein complex; decreases autophagosome maturation; does not affect endocytosis; does not affect the trafficking of ATG9A and ATG16L1; does not affect SNX18 interaction; increases cell membrane localization; increases interaction with ITSN1; impairs recruitment to phagophore assembly site; increases GTPase-mediated membrane fission; inhibits GTPase-mediated membrane fission by BIN1 in a dose-dependent manner. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs121909091 [ dbSNP | Ensembl ]

Sequence information Variant position:

465 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

870 The length of the canonical sequence.
Location on the sequence:

KLSSYPRLREETERIVTTYI R EREGRTKDQILLLIDIEQSY 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                         KLSSYPRLREETERIVTTYIREREGRTKDQILLLIDIEQSY

Mouse                         KLSSYPRLREETERIVTTYIREREGRTKDQILLLIDIEQSY

Rat                           KLSSYPRLREETERIVTTYIREREGRTKDQILLLIDIEQSY

Bovine                        KLSSYPRLREETERIVTTYIREREGRTKDQILLLIDIEQSY

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 – 870	Dynamin-2

Literature citations
GSK3alpha phosphorylates dynamin-2 to promote GLUT4 endocytosis in muscle cells.
Laiman J.; Hsu Y.J.; Loh J.; Tang W.C.; Chuang M.C.; Liu H.K.; Yang W.S.; Chen B.C.; Chuang L.M.; Chang Y.C.; Liu Y.W.;
J. Cell Biol. 222:0-0(2023)
Cited for: FUNCTION; INTERACTION WITH BIN1; SUBUNIT; VARIANTS CNM1 TRP-465; THR-618; LEU-619 AND VAL-625 DEL; CHARACTERIZATION OF VARIANTS CNM1 TRP-465; THR-618; LEU-619 AND VAL-625 DEL; MUTAGENESIS OF SER-848; PHOSPHORYLATION AT SER-848; Mutations in dynamin 2 cause dominant centronuclear myopathy.
Bitoun M.; Maugenre S.; Jeannet P.-Y.; Lacene E.; Ferrer X.; Laforet P.; Martin J.-J.; Laporte J.; Lochmueller H.; Beggs A.H.; Fardeau M.; Eymard B.; Romero N.B.; Guicheney P.;
Nat. Genet. 37:1207-1209(2005)
Cited for: VARIANTS CNM1 LYS-368; TRP-369; GLN-369 AND TRP-465; CHARACTERIZATION OF VARIANTS CNM1 TRP-369 AND TRP-465; SUBCELLULAR LOCATION; Dynamin 2 mutations associated with human diseases impair clathrin-mediated receptor endocytosis.
Bitoun M.; Durieux A.-C.; Prudhon B.; Bevilacqua J.A.; Herledan A.; Sakanyan V.; Urtizberea A.; Cartier L.; Romero N.B.; Guicheney P.;
Hum. Mutat. 30:1419-1427(2009)
Cited for: VARIANT CNM1 LYS-650; CHARACTERIZATION OF VARIANTS CNM1 TRP-465; VAL-625 DEL AND LYS-650; CHARACTERIZATION OF VARIANT CMTDIB GLU-562; PATHOPHYSIOLOGICAL PATHWAY IN THE AUTOSOMAL FORMS OF CNM AND DNM2-CMT NEUROPATHY; FUNCTION; TISSUE SPECIFICITY; MUTAGENESIS OF LYS-44; Expanding the clinical, pathological and MRI phenotype of DNM2-related centronuclear myopathy.
Susman R.D.; Quijano-Roy S.; Yang N.; Webster R.; Clarke N.F.; Dowling J.; Kennerson M.; Nicholson G.; Biancalana V.; Ilkovski B.; Flanigan K.M.; Arbuckle S.; Malladi C.; Robinson P.; Vucic S.; Mayer M.; Romero N.B.; Urtizberea J.A.; Garcia-Bragado F.; Guicheney P.; Bitoun M.; Carlier R.Y.; North K.N.;
Neuromuscul. Disord. 20:229-237(2010)
Cited for: VARIANTS CNM1 LYS-368; TRP-465; HIS-522; THR-618; LEU-619 AND HIS-627; A DNM2 Centronuclear Myopathy Mutation Reveals a Link between Recycling Endosome Scission and Autophagy.
Puri C.; Manni M.M.; Vicinanza M.; Hilcenko C.; Zhu Y.; Runwal G.; Stamatakou E.; Menzies F.M.; Mamchaoui K.; Bitoun M.; Rubinsztein D.C.;
Dev. Cell 53:154.e6-168.e6(2020)
Cited for: VARIANT CNM1 TRP-465; CHARACTERIZATION OF VARIANT CNM1 TRP-465; FUNCTION; SUBCELLULAR LOCATION; INTERACTION WITH SNX18; ITSN1; MAP1LC3B; GABARAP; GABARAPL1 AND GABARAPL2; MUTAGENESIS OF TRP-525;

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.