UniProtKB/Swiss-Prot P12821: Variant p.Pro1228Leu

Angiotensin-converting enzyme
Gene: ACE
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Variant information Variant position:

1228 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 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.
Other resources:

Links to websites of interest for the variant.

Variant rs121912703 [ dbSNP | Ensembl ]

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

Pig                           LVTENGRHGEKLGWPQYNWTPNSARLEGSFAGTGRVNFLGL

Bovine                        LVTENGRHGEKLGWPQYNWTPNSARLEGPFVGSGRVNFLGL

Rabbit                        LLTENGRHGEKLGWPQYTWTPNSARSEGSLPDSGRVNFLGM

Chicken                       LVKKNTENGEVLGWPEYSWTPYAV--TEFHAATDTADFLGM

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.

Type	Positions	Description
Chain	30 – 1306	Angiotensin-converting enzyme
Chain	30 – 1232	Angiotensin-converting enzyme, soluble form
Topological domain	30 – 1256	Extracellular
Region	1215 – 1256	Juxtamembrane stalk
Site	1225 – 1225	Not glycosylated
Alternative sequence	1146 – 1306	Missing. In isoform Somatic-2.
Mutagenesis	1229 – 1229	N -> Q. Increased cleavage and secretion of the soluble form by generating a new cleavage site.

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: CATALYTIC ACTIVITY; 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.