UniProtKB/Swiss-Prot P51681: Variant p.Tyr10Asp

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 10 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: US 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 Aspartate (D) at position 10 (Y10D, p.Tyr10Asp). 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 acidic (D) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: -3 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 INCCR5-71A; results in absent sulfation and greatly decreased binding CCL4 and CCL5 when associated with D-3, D-10 and D-15; restored most CCL4 binding when associated with D-3 and D-15. Any additional useful information about the variant.

Sequence information

Variant position: 10 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 352 The length of the canonical sequence.
Location on the sequence: MDYQVSSPI Y DINYYTSEPCQKINVKQIAA 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 – 352	C-C chemokine receptor type 5
Topological domain	1 – 30	Extracellular
Modified residue	3 – 3	Sulfotyrosine
Modified residue	10 – 10	Sulfotyrosine
Modified residue	14 – 14	Sulfotyrosine
Modified residue	15 – 15	Sulfotyrosine
Glycosylation	6 – 6	O-linked (GalNAc...) serine
Glycosylation	7 – 7	O-linked (GalNAc...) serine
Mutagenesis	3 – 3	Y -> D. No sulfation and strongly decreases binding with CCL4 and CCL5; when associated with D-10; D-14 and D-15. Restores most CCL4 binding; when associated with D-10 and D-15.
Mutagenesis	3 – 3	Y -> F. No sulfation and strongly decreases binding with CCL4 and CCL5; when associated with F-10; F-14 and F-15.
Mutagenesis	6 – 6	S -> A. Strongly decreases CCL4 binding. No change in glycosylation status.
Mutagenesis	7 – 7	S -> A. No change in glycosylation status and binds CCL4 as efficiently as wild type.
Mutagenesis	10 – 10	Y -> F. No sulfation and greatly decreases binding of CCL4 and CCL5; when associated with F-3; F-14 and F-15. Small loss of sulfation; when associated with F-14 and F-15.
Mutagenesis	14 – 14	Y -> D. No sulfation and greatly decreased binding of CCL4 and CCL5; when associated with D-3; D-10 and D-14. No restoration of CCL4 binding; when associated with D-10 and D-15.
Mutagenesis	14 – 14	Y -> F. No sulfation and greatly decreases binding of CCL4 and CCL5; when associated with F-3; F-10; and F-15. Small loss of sulfation; when associated with F-10 and F-15.
Mutagenesis	15 – 15	Y -> D. No sulfation and greatly decreased binding of CCL4 and CCL5; when associated with D-3; D-10 and D-14. Restored most CCL4 binding; when associated with D-3 and D-10.
Mutagenesis	15 – 15	Y -> F. No sulfation and greatly decreases binding of CCL4 and CCL5; when associated with F-3; F-10 and F-14. Small loss of sulfation; when associated with F-10 and F-14.
Mutagenesis	20 – 20	C -> A. Decreases to 40% surface expression. No effect on conformational integrity. Disrupts binding of CCL4. Decreases cell HIV infection.
Helix	10 – 13

Literature citations

Sialylated O-glycans and sulfated tyrosines in the NH2-terminal domain of CC chemokine receptor 5 contribute to high affinity binding of chemokines.
Bannert N.; Craig S.; Farzan M.; Sogah D.; Santo N.V.; Choe H.; Sodroski J.;
J. Exp. Med. 194:1661-1673(2001)
Cited for: SULFATION; GLYCOSYLATION AT SER-6 AND SER-7; INTERACTION WITH CCL3; CCL4 AND CCL5; MUTAGENESIS OF TYR-3; 6-SER-SER-7; SER-6; SER-7; TYR-10; TYR-14; TYR-15 AND 16-THR-SER-17; CHARACTERIZATION OF VARIANT ASP-10;