UniProtKB/Swiss-Prot P55072: Variant p.Arg155His

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

155 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 Histidine (H) at position 155 (R155H, p.Arg155His). 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 medium size and polar (H) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

0 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 FTDALS6 and IBMPFD1; properly assembles into a hexameric structure; cultured cells expressing the mutant protein show a marked general increase in the level of ubiquitin-conjugated proteins and impaired protein degradation through the endoplasmic reticulum-associated degradation (ERAD) pathway; shows strongly reduced affinity for ADP and increased affinity for ATP; shows normal ATPase activity according to PubMed:16321991 while according to PubMed:25878907 and PubMed:25125609 shows increased ATPase activity; no defect in ubiquitin-dependent protein degradation by the proteasome; impaired autophagic function; defective maturation of ubiquitin-containing autophagosomes; decreased interaction with CAV1 and UBXN6; decreased endosome to lysosome transport via multivesicular body sorting pathway of CAV1; decreases the arsenite-induced stress granules (SGs) clearance process. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs121909329 [ dbSNP | Ensembl ]

Sequence information Variant position:

155 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:

LKPYFLEAYRPIRKGDIFLV R GGMRAVEFKVVETDPSPYCI 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                         LKPYFLEAYRPIRKGDIFLVRGGMRAVEFKVVETDPSPYCI

Mouse                         LKPYFLEAYRPIRKGDIFLVRGGMRAVEFKVVETDPSPYCI

Rat                           LKPYFLEAYRPIRKGDIFLVRGGMRAVEFKVVETDPSPYCI

Pig                           LKPYFLEAYRPIRKGDIFLVRGGMRAVEFKVVETDPSPYCI

Bovine                        LKPYFLEAYRPIRKGDIFLVRGGMRAVEFKVVETDPSPYCI

Xenopus laevis                LKPYFLEAYRPIRKGDIFLVRGGMRAVEFKVVETDPSPYCI

Xenopus tropicalis            LKPYFLEAYRPIRKGDIFLVRGGMRAVEFKVVETDPSPYCI

Zebrafish                     LKPYFLEAYRPIRKGDIFLVRGGMRAVEFKVVETDPSPYCI

Drosophila                    LKPYFLEAYRPIHMGDNFIVRAAMRPIEFKVVLTDPEPYCI

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	140 – 140	L -> D. Severely reduced binding to DERL1.

Literature citations
A newly uncovered group of distantly related lysine methyltransferases preferentially interact with molecular chaperones to regulate their activity.
Cloutier P.; Lavallee-Adam M.; Faubert D.; Blanchette M.; Coulombe B.;
PLoS Genet. 9:E1003210-E1003210(2013)
Cited for: PROTEIN SEQUENCE OF 314-322; IDENTIFICATION BY MASS SPECTROMETRY; METHYLATION AT LYS-315; MUTAGENESIS OF LYS-315; CHARACTERIZATION OF VARIANTS IBMPFD1 HIS-155 AND GLN-191; CHARACTERIZATION OF VARIANT FTDALS6 GLY-159; 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; A novel ATP-dependent conformation in p97 N-D1 fragment revealed by crystal structures of disease-related mutants.
Tang W.K.; Li D.; Li C.C.; Esser L.; Dai R.; Guo L.; Xia D.;
EMBO J. 29:2217-2229(2010)
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-481 IN COMPLEX WITH ATP ANALOG; CHARACTERIZATION OF VARIANTS IBMPFD1 GLY-95 AND HIS-155; MUTAGENESIS OF ARG-53 AND ARG-86; SUBUNIT; 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; Inclusion body myopathy-associated mutations in p97/VCP impair endoplasmic reticulum-associated degradation.
Weihl C.C.; Dalal S.; Pestronk A.; Hanson P.I.;
Hum. Mol. Genet. 15:189-199(2006)
Cited for: CHARACTERIZATION OF VARIANTS IBMPFD1 GLY-95 AND HIS-155; 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; ZFAND1 recruits p97 and the 26S proteasome to promote the clearance of arsenite-induced stress granules.
Turakhiya A.; Meyer S.R.; Marincola G.; Boehm S.; Vanselow J.T.; Schlosser A.; Hofmann K.; Buchberger A.;
Mol. Cell 70:906-919(2018)
Cited for: FUNCTION; INTERACTION WITH ZFAND1; MUTAGENESIS OF GLU-578; CHARACTERIZATION OF VARIANT IBMPFD1 HIS-155; Exome sequencing reveals VCP mutations as a cause of familial ALS.
Johnson J.O.; Mandrioli J.; Benatar M.; Abramzon Y.; Van Deerlin V.M.; Trojanowski J.Q.; Gibbs J.R.; Brunetti M.; Gronka S.; Wuu J.; Ding J.; McCluskey L.; Martinez-Lage M.; Falcone D.; Hernandez D.G.; Arepalli S.; Chong S.; Schymick J.C.; Rothstein J.; Landi F.; Wang Y.D.; Calvo A.; Mora G.; Sabatelli M.; Monsurro M.R.; Battistini S.; Salvi F.; Spataro R.; Sola P.; Borghero G.; Galassi G.; Scholz S.W.; Taylor J.P.; Restagno G.; Chio A.; Traynor B.J.;
Neuron 68:857-864(2010)
Cited for: VARIANTS FTDALS6 HIS-155; GLY-159; GLN-191 AND ASN-592; 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.