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UniProtKB/Swiss-Prot O60828: Variant p.Tyr65Cys

Polyglutamine-binding protein 1
Gene: PQBP1
Variant information

Variant position:  65
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Tyrosine (Y) to Cysteine (C) at position 65 (Y65C, p.Tyr65Cys).
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 (Y) to medium size and polar (C)
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

Involvement in disease:  Renpenning syndrome 1 (RENS1) [MIM:309500]: A X-linked mental retardation syndrome characterized by mental retardation, microcephaly, short stature, and small testes. The craniofacies tends to be narrow and tall with upslanting palpebral fissures, abnormal nasal configuration, cupped ears, and short philtrum. The nose may appear long or bulbous, with overhanging columella. Less consistent manifestations include ocular colobomas, cardiac malformations, cleft palate, and anal anomalies. {ECO:0000269|PubMed:14634649, ECO:0000269|PubMed:16740914, ECO:0000269|PubMed:20410308, ECO:0000269|PubMed:21315190, ECO:0000269|PubMed:23512658, ECO:0000269|PubMed:26046437}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In RENS1; impairs interaction with WBP11, CGAS, SF3B1 and ATN1.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  65
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  265
The length of the canonical sequence.

Location on the sequence:   LEGLPPSWYKVFDPSCGLPY  Y WNADTDLVSWLSPHDPNSVV
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                         LEGLPPSWYKVFDPSCGLPYYWNADTDLVSWLSPHDPNSVV

Gorilla                       LEGLPPSWYKVFDPSCGLPYYWNADTDLVSWLSPHDPNSVV

Mouse                         IEGLPPSWYKVFDPSCGLPYYWNVETDLVSWLSPHDPNFVV

Rat                           IEGLPPSWYKVFDPSCGLPYYWNVETDLVSWLSPHDPNFVV

Bovine                        LEGLPPSWYKVFDPSCGLPYYWNVDTDLVSWLSPHDPNSVV

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.

TypePositionsDescription
Chain 2 – 265 Polyglutamine-binding protein 1
Domain 46 – 80 WW
Alternative sequence 55 – 73 VFDPSCGLPYYWNADTDLV -> RAPLLLECRHRPCILALPT. In isoform 8.
Alternative sequence 60 – 60 C -> W. In isoform 10.
Alternative sequence 61 – 265 Missing. In isoform 10.
Alternative sequence 61 – 67 GLPYYWN -> PGWSAMV. In isoform 9.
Mutagenesis 52 – 52 W -> A. Enhances transcriptional activation. Reduces transcriptional activation; when associated with A-75. Markedly reduced transcriptional activation; when associated with A-64; A-65 and A-66. Abolishes transcriptional activation; when associated with A-64; A-65; A-66 and A-75.
Mutagenesis 64 – 64 Y -> A. No effect on transcriptional activation; when associated with A-65 and A-66. Markedly reduced transcriptional activation; when associated with A-52; A-65 and A-66. Abolishes transcriptional activation; when associated with A-52; A-65; A-66 and A-75.
Mutagenesis 65 – 65 Y -> A. No effect on transcriptional activation; when associated with A-64 and A-66. Markedly reduced transcriptional activation; when associated with A-52; A-64 and A-66. Abolishes transcriptional activation; when associated with A-52; A-64; A-66 and A-75.
Mutagenesis 66 – 66 W -> A. No effect on transcriptional activation; when associated with A-64 and A-65. Markedly reduced transcriptional activation; when associated with A-52; A-64 and A-65. Abolishes transcriptional activation; when associated with A-52; A-64; A-65 and A-75.
Mutagenesis 75 – 75 W -> A. No effect on transcriptional activation. Reduces transcriptional activation; when associated with A-52. Abolishes transcriptional activation; when associated with A-52; A-64; A-65 and A-66.
Mutagenesis 78 – 78 P -> G. No effect on transcriptional activation.


Literature citations

PQBP1, a factor linked to intellectual disability, affects alternative splicing associated with neurite outgrowth.
Wang Q.; Moore M.J.; Adelmant G.; Marto J.A.; Silver P.A.;
Genes Dev. 27:615-626(2013)
Cited for: FUNCTION; INTERACTION WITH SF3B1 AND WBP11; SUBUNIT; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANT RENS1 CYS-65;

PQBP1 is a proximal sensor of the cGAS-dependent innate response to HIV-1.
Yoh S.M.; Schneider M.; Seifried J.; Soonthornvacharin S.; Akleh R.E.; Olivieri K.C.; De Jesus P.D.; Ruan C.; de Castro E.; Ruiz P.A.; Germanaud D.; des Portes V.; Garcia-Sastre A.; Koenig R.; Chanda S.K.;
Cell 161:1293-1305(2015)
Cited for: FUNCTION; INTERACTION WITH CGAS; CHARACTERIZATION OF VARIANT RENS1 CYS-65;

Golabi-Ito-Hall syndrome results from a missense mutation in the WW domain of the PQBP1 gene.
Lubs H.; Abidi F.E.; Echeverri R.; Holloway L.; Meindl A.; Stevenson R.E.; Schwartz C.E.;
J. Med. Genet. 43:E30-E30(2006)
Cited for: VARIANT RENS1 CYS-65;

Y65C missense mutation in the WW domain of the Golabi-Ito-Hall syndrome protein PQBP1 affects its binding activity and deregulates pre-mRNA splicing.
Tapia V.E.; Nicolaescu E.; McDonald C.B.; Musi V.; Oka T.; Inayoshi Y.; Satteson A.C.; Mazack V.; Humbert J.; Gaffney C.J.; Beullens M.; Schwartz C.E.; Landgraf C.; Volkmer R.; Pastore A.; Farooq A.; Bollen M.; Sudol M.;
J. Biol. Chem. 285:19391-19401(2010)
Cited for: CHARACTERIZATION OF VARIANT RENS1 CYS-65; INTERACTION WITH WBP11 AND ATN1; DOMAIN; FUNCTION;

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.