UniProtKB/Swiss-Prot Q01523: Variant p.Arg71His

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 71 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 Arginine (R) to Histidine (H) at position 71 (R71H, p.Arg71His). 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 basic (R) to medium size and polar (H) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: 0 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: Impairs antimicrobial activity against S.aureus. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs7839771 [ dbSNP | Ensembl ]

Sequence information

Variant position: 71 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 94 The length of the canonical sequence.
Location on the sequence: LSALRTSGSQARATCYCRTG R CATRESLSGVCEISGRLYRL 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
Peptide	20 – 94	Defensin alpha 5
Peptide	23 – 94	HD5(23-94)
Peptide	29 – 94	HD5(29-94)
Peptide	56 – 94	HD5(56-94)
Peptide	63 – 94	HD5(63-94)
Disulfide bond	65 – 93
Disulfide bond	67 – 82
Mutagenesis	67 – 67	C -> S. Prohibits tetramer formation; when associated with S-93.
Mutagenesis	69 – 69	T -> R. Enhanced antibacterial activity against both E.coli and S.aureus. Enhanced membrane binding and membrane disintegration abilities, as well as further increased antibacterial activity; when associated with R-83.
Mutagenesis	71 – 71	R -> A. Reduced killing of S.aureus and E.coli. Impairs antimicrobial activity against E.coli, E.aerogenes, S.aureus and B.cereus; when associated with A-90. Reduced induction of IL-8 secretion; when associated with A-90.
Mutagenesis	71 – 71	R -> K. Impairs antimicrobial activity against S. aureus; when associated with K-90. Reduced induction of IL-8 secretion; when associated with K-90.
Mutagenesis	72 – 72	C -> S. Prohibits tetramer formation; when associated with S-92.
Mutagenesis	75 – 75	R -> A. Impairs antimicrobial activity against E.coli, E.aerogenes, S.aureus and B.cereus; when associated with A-94. Reduced induction of IL-8 secretion; when associated with A-94.
Mutagenesis	75 – 75	R -> K. Does not impair antimicrobial activity against E.coli, E.aerogenes, S.aureus and B.cereus; when associated with K-94. Reduced induction of IL-8 secretion; when associated with K-90.
Mutagenesis	77 – 77	S -> A. Increased interaction with B.antracis lef/lethal factor.
Mutagenesis	83 – 83	E -> R. Enhanced antibacterial activity against both E.coli and S.aureus. Disrupts homodimerization. Enhanced membrane binding and membrane disintegration abilities, as well further increased antibacterial activity; when associated with R-69.
Mutagenesis	85 – 85	S -> R. Enhanced antibacterial activity against both E.coli and S.aureus.
Mutagenesis	86 – 86	G -> R. Enhanced antibacterial activity against both E.coli and S.aureus.
Mutagenesis	88 – 88	L -> A. Reduced interaction with B.antracis lef/lethal factor. Reduced enhancement of S.flexneri infection.
Mutagenesis	89 – 89	Y -> A. Disrupts homodimer-formation. Reduced interaction with B.antracis lef/lethal factor and reduced killing of S.aureus. Reduced enhancement of S.flexneri infection.
Mutagenesis	90 – 90	R -> A. Does not disrupt homodimer-formation. Reduced enhancement of S.flexneri infection. Impairs antimicrobial activity against E.coli, E.aerogenes, S.aureus and B.cereus; when associated with A-71. Reduced induction of IL-8 secretion; when associated with A-71.
Mutagenesis	90 – 90	R -> K. Impairs antimicrobial activity against S. aureus; when associated with K-71. Reduced induction of IL-8 secretion; when associated with K-71.
Mutagenesis	91 – 91	L -> A. Reduced interaction with B.antracis lef/lethal factor and decreased bactericidal activity against E.coli and S.aureus. Reduced enhancement of S.flexneri infection.

Literature citations

Selective arginines are important for the antibacterial activity and host cell interaction of human alpha-defensin 5.
de Leeuw E.; Rajabi M.; Zou G.; Pazgier M.; Lu W.;
FEBS Lett. 583:2507-2512(2009)
Cited for: X-RAY CRYSTALLOGRAPHY (1.63 ANGSTROMS) OF 63-94 OF MUTANT HIS-71; FUNCTION; DISULFIDE BONDS; VARIANT HIS-71; MUTAGENESIS OF ARG-71; ARG-75; ARG-90 AND ARG-94;