UniProtKB/Swiss-Prot Q96LA9: Variant p.Leu83Ser

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 83 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: LB/B 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 Leucine (L) to Serine (S) at position 83 (L83S, p.Leu83Ser). 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 (L) to small size and polar (S) 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: Reduced activation by agonists; displays higher sensitivity to phosphate-modified drugs, such as fospropofol. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs2445179 [ dbSNP | Ensembl ]

Sequence information

Variant position: 83 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 322 The length of the canonical sequence.
Location on the sequence: IYILNLAAADFLFLSFQIIR L PLRLINISHLIRKILVSVMT 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.
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	1 – 322	Mas-related G-protein coupled receptor member X4
Transmembrane	63 – 87	Helical; Name=2
Glycosylation	89 – 89	N-linked (GlcNAc...) asparagine
Disulfide bond	23 – 251
Mutagenesis	82 – 82	R -> A. Decreased binding to 3-sulfated bile acids. Decreased activation by phosphate-modified drugs, such as fospropofol. Decreased activation by agonists.
Mutagenesis	86 – 86	R -> A. Decreased binding to 3-sulfated bile acids. Decreased activation by phosphate-modified drugs, such as fospropofol.
Mutagenesis	95 – 95	R -> A. Decreased binding to 3-sulfated bile acids. Decreased activation by phosphate-modified drugs, such as fospropofol. Decreased activation by agonists.
Mutagenesis	96 – 96	K -> A. Decreased binding to 3-sulfated bile acids. Decreased activation by agonists.
Mutagenesis	99 – 99	V -> A. Decreased binding to 3-sulfated bile acids.
Helix	62 – 85

Literature citations

A diverse family of GPCRs expressed in specific subsets of nociceptive sensory neurons.
Dong X.; Han S.-K.; Zylka M.J.; Simon M.I.; Anderson D.J.;
Cell 106:619-632(2001)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANT SER-83;
Proenkephalin A gene products activate a new family of sensory neuron-specific GPCRs.
Lembo P.M.C.; Grazzini E.; Groblewski T.; O'Donnell D.; Roy M.-O.; Zhang J.; Hoffert C.; Cao J.; Schmidt R.; Pelletier M.; Labarre M.; Gosselin M.; Fortin Y.; Banville D.; Shen S.; Stroem P.; Payza K.; Dray A.; Walker P.; Ahmad S.;
Nat. Neurosci. 5:201-209(2002)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS LEU-8; LYS-25; CYS-54; SER-83 AND VAL-182; TISSUE SPECIFICITY;
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
The MGC Project Team;
Genome Res. 14:2121-2127(2004)
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]; VARIANTS SER-83 AND VAL-182;
Structure, function and pharmacology of human itch GPCRs.
Cao C.; Kang H.J.; Singh I.; Chen H.; Zhang C.; Ye W.; Hayes B.W.; Liu J.; Gumpper R.H.; Bender B.J.; Slocum S.T.; Krumm B.E.; Lansu K.; McCorvy J.D.; Kroeze W.K.; English J.G.; DiBerto J.F.; Olsen R.H.J.; Huang X.P.; Zhang S.; Liu Y.; Kim K.; Karpiak J.; Jan L.Y.; Abraham S.N.; Jin J.; Shoichet B.K.; Fay J.F.; Roth B.L.;
Nature 600:170-175(2021)
Cited for: STRUCTURE BY ELECTRON MICROSCOPY (2.60 ANGSTROMS) OF 2-322 IN COMPLEX WITH GNB1 AND GNG2; FUNCTION; ACTIVITY REGULATION; DISULFIDE BOND; CHARACTERIZATION OF VARIANT SER-83; MUTAGENESIS OF ARG-82; ARG-95; LYS-96; TRP-158 AND TYR-240;
MRGPRX4 mediates phospho-drug-associated pruritus in a humanized mouse model.
Chien D.C.; Limjunyawong N.; Cao C.; Meixiong J.; Peng Q.; Ho C.Y.; Fay J.F.; Roth B.L.; Dong X.;
Sci. Transl. Med. 16:eadk8198-eadk8198(2024)
Cited for: STRUCTURE BY ELECTRON MICROSCOPY (3.14 ANGSTROMS) OF 2-322 IN COMPLEX WITH FOSPROPOFOL; GNB1 AND GNG2; FUNCTION; ACTIVITY REGULATION; MUTAGENESIS OF ARG-82; ARG-86; ARG-95; TRP-158; TYR-250 AND TYR-254; CHARACTERIZATION OF VARIANT SER-83;