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UniProtKB/Swiss-Prot Q12879: Variant p.Pro552Arg

Glutamate receptor ionotropic, NMDA 2A
Gene: GRIN2A
Variant information

Variant position:  552
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 Proline (P) to Arginine (R) at position 552 (P552R, p.Pro552Arg).
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 medium size and hydrophobic (P) to large size and basic (R)
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

Variant description:  In FESD; no effect on localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by increased glutamate and glycine potency with delay in rise time and slower deactivation time course.
Any additional useful information about the variant.

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



Sequence information

Variant position:  552
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1464
The length of the canonical sequence.

Location on the sequence:   GISVMVSRSNGTVSPSAFLE  P FSASVWVMMFVMLLIVSAIA
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                         GISVMVSRSNGTVSPSAFLEPFSASVWVMMFVMLLIVSAIA

Chimpanzee                    GISVMVSRSNGTVSPSAFLEPFSASVWVMMFVMLLIVSAIA

Mouse                         GISVMVSRSNGTVSPSAFLEPFSASVWVMMFVMLLIVSAIA

Rat                           GISVMVSRSNGTVSPSAFLEPFSASVWVMMFVMLLIVSAIA

Xenopus laevis                GISVMVSRSNGTVSPSAFLEPFSASVWVMMFVMLLLVSAMA

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 23 – 1464 Glutamate receptor ionotropic, NMDA 2A
Topological domain 23 – 555 Extracellular
Glycosylation 541 – 541 N-linked (GlcNAc...) asparagine
Mutagenesis 552 – 552 P -> A. Changed glutamate-gated calcium ion channel activity characterized by increased desensitization.
Mutagenesis 552 – 552 P -> G. Changed glutamate-gated calcium ion channel activity characterized by accelerated response activation time and increased desensitization.
Mutagenesis 552 – 552 P -> I. Changed glutamate-gated calcium ion channel activity characterized by increased desensitization.
Mutagenesis 552 – 552 P -> K. Changed glutamate-gated calcium ion channel activity characterized by increased glutamate and glycine potency with delay in rise time and slower deactivation time course.
Mutagenesis 552 – 552 P -> L. No effect on localization to the cell membrane. Changed glutamate-gated calcium ion channel activity characterized by increased desensitization.
Mutagenesis 552 – 552 P -> Q. No effect on localization to the cell membrane. Changed glutamate-gated calcium ion channel activity characterized by decreased response amplitude and changed desensitization without effect on response rise time or deactivation time course.


Literature citations

Diagnostic exome sequencing in persons with severe intellectual disability.
de Ligt J.; Willemsen M.H.; van Bon B.W.; Kleefstra T.; Yntema H.G.; Kroes T.; Vulto-van Silfhout A.T.; Koolen D.A.; de Vries P.; Gilissen C.; del Rosario M.; Hoischen A.; Scheffer H.; de Vries B.B.; Brunner H.G.; Veltman J.A.; Vissers L.E.;
N. Engl. J. Med. 367:1921-1929(2012)
Cited for: VARIANTS FESD ARG-552 AND VAL-649;

Molecular mechanism of disease-associated mutations in the pre-M1 helix of NMDA receptors and potential rescue pharmacology.
Ogden K.K.; Chen W.; Swanger S.A.; McDaniel M.J.; Fan L.Z.; Hu C.; Tankovic A.; Kusumoto H.; Kosobucki G.J.; Schulien A.J.; Su Z.; Pecha J.; Bhattacharya S.; Petrovski S.; Cohen A.E.; Aizenman E.; Traynelis S.F.; Yuan H.;
PLoS Genet. 13:E1006536-E1006536(2017)
Cited for: CHARACTERIZATION OF VARIANTS FESD THR-548 AND ARG-552; MUTAGENESIS OF PRO-552;

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.