UniProtKB/SwissProt variant VAR

Variant information

Variant position:

323

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

Type of variant:

LP/P [Disclaimer]

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 Glutamate (E) to Lysine (K) at position 323 (E323K, p.Glu323Lys).

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 large size and basic (K)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

1

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:

In GLC1A; inhibits endoproteolytic processing; mainly accumulates as insoluble aggregates inside the endoplasmic reticulum.

Any additional useful information about the variant.

Sequence information

Variant position:

323

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

Protein sequence length:

504

The length of the canonical sequence.

Location on the sequence:

LISQFMQGYPSKVHILPRPL E STGAVVYSGSLYFQGAESRT

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                         LISQFMQGY-----------------------------------------------------------------PSKVHILPRPLESTGA------VVYSGSLYF---------------------------------------QGAESRT

                              LASQFLQGY--------------------------------

Mouse                         QISQFEQGY--------------------------------

Rat                           QISQFEQGY--------------------------------

Bovine                        HIRKFTQGY--------------------------------

Rabbit                        RISQFVQGY--------------------------------

Cat                           LSSQFLQGY--------------------------------

Slime mold                    RCAQTIQGYFRAWKQASPFFDLRMQNEQLFQGRKERNRFSM

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	33 – 504	Myocilin
Chain	227 – 504	Myocilin, C-terminal fragment
Domain	244 – 503	Olfactomedin-like
Disulfide bond	245 – 433
Beta strand	322 – 325

Literature citations

Myocilin mutations causing glaucoma inhibit the intracellular endoproteolytic cleavage of myocilin between amino acids Arg226 and Ile227.
Aroca-Aguilar J.D.; Sanchez-Sanchez F.; Ghosh S.; Coca-Prados M.; Escribano J.;
J. Biol. Chem. 280:21043-21051(2005)
Cited for: PROTEIN SEQUENCE OF 227-233; SUBCELLULAR LOCATION; TISSUE SPECIFICITY; CHARACTERIZATION OF VARIANTS GLC1A LYS-323; LEU-370 AND GLY-380; PROTEOLYTIC PROCESSING;

Age-dependent prevalence of mutations at the GLC1A locus in primary open-angle glaucoma.
Shimizu S.; Lichter P.R.; Johnson A.T.; Zhou Z.; Higashi M.; Gottfredsdottir M.; Othman M.; Moroi S.E.; Rozsa F.W.; Schertzer R.M.; Clarke M.S.; Schwartz A.L.; Downs C.A.; Vollrath D.; Richards J.E.;
Am. J. Ophthalmol. 130:165-177(2000)
Cited for: VARIANTS GLC1A ARG-252; GLY-272; LYS-323; LEU-370; MET-377; PHE-426; ASN-477 AND SER-499; VARIANTS ASP-57; LYS-76; MET-329 AND ARG-398; CHARACTERIZATION OF VARIANTS GLC1A ARG-252; GLY-272; LYS-323; LEU-370; MET-377; PHE-426; ASN-477 AND SER-499; CHARACTERIZATION OF VARIANTS ASP-57; LYS-76; MET-329 AND ARG-398;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q99972: Variant p.Glu323Lys