UniProtKB/Swiss-Prot P55072: Variant p.Ala232Glu

Transitional endoplasmic reticulum ATPase
Gene: VCP
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Variant information Variant position:

232 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 Alanine (A) to Glutamate (E) at position 232 (A232E, p.Ala232Glu). 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 small size and hydrophobic (A) to medium size and acidic (E) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-1 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 IBMPFD1; increased ATPase activity; no defect in ubiquitin-dependent protein degradation by the proteasome; impaired autophagic function; defect in maturation of ubiquitin-containing autophagosomes; decreased interaction with CAV1 and UBXN6. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs121909331 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

QLAQIKEMVELPLRHPALFK A IGVKPPRGILLYGPPGTGKT 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                         QLAQIKEMVELPLRHPALFKAIGVKPPRGILLYGPPGTGKT

Mouse                         QLAQIKEMVELPLRHPALFKAIGVKPPRGILLYGPPGTGKT

Rat                           QLAQIKEMVELPLRHPALFKAIGVKPPRGILLYGPPGTGKT

Pig                           QLAQIKEMVELPLRHPALFKAIGVKPPRGILLYGPPGTGKT

Bovine                        QLAQIKEMVELPLRHPALFKAIGVKPPRGILLYGPPGTGKT

Xenopus laevis                QLAQIKEMVELPLRHPALFKAIGVKPPRGILLYGPPGTGKT

Xenopus tropicalis            QLAQIKEMVELPLRHPALFKAIGVKPPRGILLYGPPGTGKT

Zebrafish                     QLAQIKEMVELPLRHPALFKAIGVKPPRGILLYGPPGTGKT

Drosophila                    QLAQIKEMVELPLRHPSLFKAIGVKPPRGILMYGPPGTGKT

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	2 – 806	Transitional endoplasmic reticulum ATPase
Mutagenesis	251 – 251	K -> Q. Impairs ERAD degradation of HMGCR and does not inhibit interaction with RHBDD1; when associated with Q-524.
Helix	227 – 233

Literature citations
Endolysosomal sorting of ubiquitylated caveolin-1 is regulated by VCP and UBXD1 and impaired by VCP disease mutations.
Ritz D.; Vuk M.; Kirchner P.; Bug M.; Schuetz S.; Hayer A.; Bremer S.; Lusk C.; Baloh R.H.; Lee H.; Glatter T.; Gstaiger M.; Aebersold R.; Weihl C.C.; Meyer H.;
Nat. Cell Biol. 13:1116-1123(2011)
Cited for: FUNCTION; INTERACTION WITH CAV1 AND UBXN6; CHARACTERIZATION OF VARIANTS IBMPFD1 GLY-95; HIS-155 AND GLU-232; MUTAGENESIS OF GLU-578; Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein.
Watts G.D.J.; Wymer J.; Kovach M.J.; Mehta S.G.; Mumm S.; Darvish D.; Pestronk A.; Whyte M.P.; Kimonis V.E.;
Nat. Genet. 36:377-381(2004)
Cited for: VARIANTS IBMPFD1 GLY-95; CYS-155; HIS-155; PRO-155; GLN-191 AND GLU-232; VCP/p97 is essential for maturation of ubiquitin-containing autophagosomes and this function is impaired by mutations that cause IBMPFD.
Tresse E.; Salomons F.A.; Vesa J.; Bott L.C.; Kimonis V.; Yao T.P.; Dantuma N.P.; Taylor J.P.;
Autophagy 6:217-227(2010)
Cited for: CHARACTERIZATION OF VARIANTS IBMPFD1 HIS-155; SER-155 AND GLU-232; MUTAGENESIS OF GLU-305 AND GLU-578; FUNCTION; A novel mutation in VCP causes Charcot-Marie-Tooth Type 2 disease.
Gonzalez M.A.; Feely S.M.; Speziani F.; Strickland A.V.; Danzi M.; Bacon C.; Lee Y.; Chou T.F.; Blanton S.H.; Weihl C.C.; Zuchner S.; Shy M.E.;
Brain 137:2897-2902(2014)
Cited for: VARIANT CMT2Y LYS-185; CHARACTERIZATION OF VARIANT CMT2Y LYS-185; CHARACTERIZATION OF VARIANTS IBMPFD1 HIS-155 AND GLU-232; Rare Manifestation of a c.290 C>T, p.Gly97Glu VCP Mutation.
Jerath N.U.; Crockett C.D.; Moore S.A.; Shy M.E.; Weihl C.C.; Chou T.F.; Grider T.; Gonzalez M.A.; Zuchner S.; Swenson A.;
Case Rep. Genet. 2015:239167-239167(2015)
Cited for: VARIANT CMT2Y GLU-97; CHARACTERIZATION OF VARIANT CMT2Y GLU-97; CHARACTERIZATION OF VARIANTS IBMPFD1 HIS-155; TRP-198 AND GLU-232; VCP/p97 cooperates with YOD1, UBXD1 and PLAA to drive clearance of ruptured lysosomes by autophagy.
Papadopoulos C.; Kirchner P.; Bug M.; Grum D.; Koerver L.; Schulze N.; Poehler R.; Dressler A.; Fengler S.; Arhzaouy K.; Lux V.; Ehrmann M.; Weihl C.C.; Meyer H.;
EMBO J. 36:135-150(2017)
Cited for: FUNCTION; INTERACTION WITH PLAA; UBXN6 AND YOD1; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS IBMPFD1 HIS-155; TRP-198 AND GLU-232; MUTAGENESIS OF GLU-578;

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.