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UniProtKB/Swiss-Prot P06870: Variant p.Glu145Gln

Kallikrein-1
Gene: KLK1
Chromosomal location: 19q13.4
Variant information

Variant position:  145
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Polymorphism
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Glutamate (E) to Glutamine (Q) at position 145 (E145Q, p.Glu145Gln).
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 acidic (E) to medium size and polar (Q)
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

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:  Polymorphism; not associated with changes in urinary kallikrein activity.
Any additional useful information about the variant.

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



Sequence information

Variant position:  145
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:   RLTEPADTITDAVKVVELPT  E EPEVGSTCLASGWGSIEPEN
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.

TypePositionsDescription
Chain 25 – 262 Kallikrein-1
Domain 25 – 259 Peptidase S1
Glycosylation 165 – 165 N-linked (GlcNAc...) asparagine; partial
Disulfide bond 31 – 174


Literature citations

Nucleotide sequence of cloned cDNA for human pancreatic kallikrein.
Fukushima D.; Kitamura N.; Nakanishi S.;
Biochemistry 24:8037-8043(1985)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); VARIANTS GLN-145 AND GLU-186;

Structure and chromosomal localization of the human renal kallikrein gene.
Evans B.A.; Yun Z.X.; Close J.A.; Tregear G.W.; Kitamura N.; Nakanishi S.; Callen D.F.; Baker E.; Hyland V.J.; Sutherland G.R.; Richards R.I.;
Biochemistry 27:3124-3129(1988)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANT GLN-145;

Kallikrein cDNA from the pancreas of a Chinese patient.
Li T.; Du G.; Dai Y.;
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); VARIANTS GLN-145 AND GLU-186;

Cloning of human full-length CDSs in BD Creator(TM) system donor vector.
Kalnine N.; Chen X.; Rolfs A.; Halleck A.; Hines L.; Eisenstein S.; Koundinya M.; Raphael J.; Moreira D.; Kelley T.; LaBaer J.; Lin Y.; Phelan M.; Farmer A.;
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1); VARIANT GLN-145;

Submission
SeattleSNPs variation discovery resource;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANT GLN-145;

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] (ISOFORM 1); VARIANT GLN-145;

Human kidney kallikrein: cDNA cloning and sequence analysis.
Baker A.R.; Shine J.;
DNA 4:445-450(1985)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 18-262 (ISOFORM 1); VARIANTS GLN-145 AND GLU-186;

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;

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.