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UniProtKB/Swiss-Prot P20594: Variant p.Tyr708Cys

Atrial natriuretic peptide receptor 2
Gene: NPR2
Variant information

Variant position:  708
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 Tyrosine (Y) to Cysteine (C) at position 708 (Y708C, p.Tyr708Cys).
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

Variant description:  In AMDM; no effect on subcellular location; changed glycosylation; no effect on C-type natriuretic peptide binding; decreased guanylate cyclase activity.
Any additional useful information about the variant.

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



Sequence information

Variant position:  708
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1047
The length of the canonical sequence.

Location on the sequence:   APELLSGNPLPTTGMQKADV  Y SFGIILQEIALRSGPFYLEG
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                         APELLSGNPLPTTGMQKADVYSFGIILQEIALRSGPFYLEG

Mouse                         APELLSGNPLPTTGMQKADVYSFAIILQEIALRSGPFYLEG

Rat                           APELLSGNPLPTTGMQKADVYSFAIILQEIALRSGPFYLEG

Bovine                        APELLSGNPLPTTGMQKADVYSFGIILQEIALRSGPFYLEG

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 – 1047 Atrial natriuretic peptide receptor 2
Topological domain 479 – 1047 Cytoplasmic
Domain 513 – 786 Protein kinase


Literature citations

Mutations in the transmembrane natriuretic peptide receptor NPR-B impair skeletal growth and cause acromesomelic dysplasia, type Maroteaux.
Bartels C.F.; Buekuelmez H.; Padayatti P.; Rhee D.K.; van Ravenswaaij-Arts C.; Pauli R.M.; Mundlos S.; Chitayat D.; Shih L.-Y.; Al-Gazali L.I.; Kant S.; Cole T.; Morton J.; Cormier-Daire V.; Faivre L.; Lees M.; Kirk J.; Mortier G.R.; Leroy J.; Zabel B.; Kim C.A.; Crow Y.; Braverman N.E.; van den Akker F.; Warman M.L.;
Am. J. Hum. Genet. 75:27-34(2004)
Cited for: FUNCTION; VARIANTS AMDM THR-32; GLY-115; GLU-176; MET-297; CYS-338; THR-409; GLU-413; CYS-708; TRP-776; CYS-957 AND ALA-959; CHARACTERIZATION OF VARIANTS AMDM GLY-115; MET-297 AND GLU-413;

Catalytically active guanylyl cyclase b requires endoplasmic reticulum-mediated glycosylation, and mutations that inhibit this process cause dwarfism.
Dickey D.M.; Edmund A.B.; Otto N.M.; Chaffee T.S.; Robinson J.W.; Potter L.R.;
J. Biol. Chem. 291:11385-11393(2016)
Cited for: CHARACTERIZATION OF VARIANTS AMDM PHE-658; CYS-708; TRP-776 AND ALA-959; FUNCTION; CATALYTIC ACTIVITY; SUBCELLULAR LOCATION; TOPOLOGY; GLYCOSYLATION; PHOSPHORYLATION; MUTAGENESIS OF ASN-24;

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.