UniProtKB/SwissProt variant VAR

Variant information

Variant position:

1580

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 Leucine (L) to Proline (P) at position 1580 (L1580P, p.Leu1580Pro).

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:

In SMDP3; does not affect location in intracellular vesicle membrane; does not affect proteolytic cleavage; does not affect N-glycosylation; loss of ATP hydrolysis activity; decreases ATP binding in vitro; affects the intracellular vesicles development; decreases phosphatidylcholine transport.

Any additional useful information about the variant.

Sequence information

Variant position:

1580

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

Protein sequence length:

1704

The length of the canonical sequence.

Location on the sequence:

ARESGKAIIITSHSMEECEA L CTRLAIMVQGQFKCLGSPQH

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                         ARESGKAIIITSHSMEECEALCTRLAIMVQGQFKCLGSPQH

Mouse                         ARESGKAIVITSHSMEECEALCTRLAIMVQGQFKCLGSPQH

Slime mold                    LKK-DKVIILTTHSMLECSAVCDRLTIMKSGKMMCLGSIQH

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	1 – 1704	Phospholipid-transporting ATPase ABCA3
Chain	175 – 1704	150 Kda mature form
Domain	1381 – 1614	ABC transporter 2
Alternative sequence	210 – 1704	Missing. In isoform 2.
Mutagenesis	1580 – 1580	L -> A. Decreases ATP hydrolysis activity of 13% compared to the wild-type.
Mutagenesis	1580 – 1580	L -> F. Decreases ATP hydrolysis activity of 13% compared to the wild-type.
Mutagenesis	1580 – 1580	L -> V. Decreases ATP hydrolysis activity of 56% compared to the wild-type.

Literature citations

Characterization and classification of ATP-binding cassette transporter ABCA3 mutants in fatal surfactant deficiency.
Matsumura Y.; Ban N.; Ueda K.; Inagaki N.;
J. Biol. Chem. 281:34503-34514(2006)
Cited for: FUNCTION; PROTEOLYTIC CLEAVAGE; GLYCOSYLATION; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS SMDP3 PRO-101; ASP-568; PRO-982; SER-1221; PRO-1553; PRO-1580 AND PRO-1591; MUTAGENESIS OF GLY-1221 AND LEU-1580;

Metabolic labelling of choline phospholipids probes ABCA3 transport in lamellar bodies.
Li Y.; Kinting S.; Hoeppner S.; Forstner M.E.; Uhl O.; Koletzko B.; Griese M.;
Biochim. Biophys. Acta 1864:158516-158516(2019)
Cited for: CATALYTIC ACTIVITY; FUNCTION; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS SMDP3 ASP-568 AND PRO-1580; ACTIVITY REGULATION;

ABCA3 gene mutations in newborns with fatal surfactant deficiency.
Shulenin S.; Nogee L.M.; Annilo T.; Wert S.E.; Whitsett J.A.; Dean M.;
N. Engl. J. Med. 350:1296-1303(2004)
Cited for: VARIANTS SMDP3 PRO-101; ASP-568; PRO-982; SER-1221; PRO-1553; PRO-1580 AND PRO-1591;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q99758: Variant p.Leu1580Pro