UniProtKB/Swiss-Prot P06870: Variant p.Arg77His

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 77 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 77 (R77H, p.Arg77His). 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
Polymorphism: Genetic variations in KLK1 are the cause of a decreased in urinary kallikrein activity [MIM:615953]. The His-77 mutation dramatically reduces the activity of the enzyme in the urine. There is a 50 to 60% reduction in urinary kallikrein activity in His-77 individuals, but renal and hormonal adaptation to dietary changes in sodium and potassium are unaffected. However, in studies of brachial artery function, His-77 individuals consistently exhibited an increase in wall shear stress and a paradoxical reduction in artery diameter and lumen compared to Arg-77 individuals. This partial genetic deficiency in kallikrein activity is associated with a form of arterial dysfunction involving inappropriate inward remodeling of the brachial artery despite a chronic increase in shear stress. Additional information on the polymorphism described.
Variant description: Associated with a significant decrease in urinary kallikrein activity. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs5515 [ dbSNP | Ensembl ]

Sequence information

Variant position: 77 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 262 The length of the canonical sequence.
Location on the sequence: RQWVLTAAHCISDNYQLWLG R HNLFDDENTAQFVHVSESFP 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	25 – 262	Kallikrein-1
Domain	25 – 259	Peptidase S1
Active site	65 – 65	Charge relay system
Glycosylation	93 – 93	O-linked (GalNAc...) serine
Disulfide bond	31 – 174

Literature citations

Loss-of-function polymorphism of the human kallikrein gene with reduced urinary kallikrein activity.
Slim R.; Torremocha F.; Moreau T.; Pizard A.; Hunt S.C.; Vuagnat A.; Williams G.H.; Gauthier F.; Jeunemaitre X.; Alhenc-Gelas F.;
J. Am. Soc. Nephrol. 13:968-976(2002)
Cited for: CHARACTERIZATION OF VARIANTS HIS-77 AND GLN-145; POLYMORPHISM;