UniProtKB/Swiss-Prot P12821: Variant p.Pro1228Leu

Angiotensin-converting enzyme
Gene: ACE
Chromosomal location: 17q23
Variant information

Variant position:  1228
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Unclassified
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Proline (P) to Leucine (L) at position 1228 (P1228L, p.Pro1228Leu).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
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:  No effect on activity; increases secretion; rate of solubilization is 2.5-fold higher than wild-type.
Any additional useful information about the variant.



Sequence information

Variant position:  1228
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1306
The length of the canonical sequence.

Location on the sequence:   LRTENELHGEKLGWPQYNWT  P NSARSEGPLPDSGRVSFLGL
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.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         LRTENELHGEKLGWPQYNWTPNSARSEGPLPDSGRVSFLGL

Chimpanzee                    LRTENELHGEKLGWPQYNWTPNSARSEGPLPDSGRVSFLGL

Mouse                         LVTENRRHGETLGWPEYNWAPNTARAEGSTAESNRVNFLGL

Rat                           LVTENRRHGETLGWPEYTWTPNTARAEGSLPESSRVNFLGM

Rabbit                        LLTENGRHGEKLGWPQYTWTPNSARSEGSLPDSGRVNFLGM

Drosophila                    LEAENIKNNVHIGWTTSNKCVSS------------------

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 30 – 1306 Angiotensin-converting enzyme
Chain 30 – 1232 Angiotensin-converting enzyme, soluble form
Topological domain 30 – 1256 Extracellular
Region 631 – 1232 Peptidase M2 2
Site 1225 – 1225 Not glycosylated
Alternative sequence 1146 – 1306 Missing. In isoform Somatic-2.


Literature citations

Increased shedding of angiotensin-converting enzyme by a mutation identified in the stalk region.
Eyries M.; Michaud A.; Deinum J.; Agrapart M.; Chomilier J.; Kramers C.; Soubrier F.;
J. Biol. Chem. 276:5525-5532(2001)
Cited for: BIOPHYSICOCHEMICAL PROPERTIES; CHARACTERIZATION OF VARIANT LEU-1228;

Point mutation in the stalk of angiotensin-converting enzyme causes a dramatic increase in serum angiotensin-converting enzyme but no cardiovascular disease.
Kramers C.; Danilov S.M.; Deinum J.; Balyasnikova I.V.; Scharenborg N.; Looman M.; Boomsma F.; de Keijzer M.H.; van Duijn C.; Martin S.; Soubrier F.; Adema G.J.;
Circulation 104:1236-1240(2001)
Cited for: VARIANT LEU-1228; ASSOCIATION WITH BENIGN SERUM INCREASE OF ANGIOTENSIN-CONVERTING ENZYME;

Hereditary elevation of angiotensin converting enzyme suggesting neurosarcoidosis.
Linnebank M.; Kesper K.; Jeub M.; Urbach H.; Wuellner U.; Klockgether T.; Schmidt S.;
Neurology 61:1819-1820(2003)
Cited for: VARIANT LEU-1228; ASSOCIATION WITH BENIGN SERUM INCREASE OF ANGIOTENSIN-CONVERTING ENZYME;

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.