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UniProtKB/Swiss-Prot Q99758: Variant p.Gly1221Ser

Phospholipid-transporting ATPase ABCA3
Gene: ABCA3
Variant information

Variant position:  1221
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 Glycine (G) to Serine (S) at position 1221 (G1221S, p.Gly1221Ser).
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 glycine (G) to small size and polar (S)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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 intracellular vesicle membrane location; does not affect proteolytic cleavage; does not affect N-glycosylation; loss of ATP hydrolysis activity.
Any additional useful information about the variant.



Sequence information

Variant position:  1221
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:   FFFLGAATAYTRLTIFNILS  G IATFLMVTIMRIPAVKLEEL
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                         FFFL--GAATAYTRLTIFNILSGIATFLMVT--IMRIPAVK-----LEEL

Mouse                         FFFS--AASTAYTRLTIFNILSGIATFIMVT--IMRIPAVK

Rat                           FFFS--AASTAYTRLTIFNILSGIATFIVVT--IMRIPAVK

Slime mold                    YCWSSHGKATGF----IFGIHFGIGLLMTVTCFILRIWVIK

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 1 – 1704 Phospholipid-transporting ATPase ABCA3
Chain 175 – 1704 150 Kda mature form
Transmembrane 1213 – 1233 Helical
Alternative sequence 210 – 1704 Missing. In isoform 2.
Mutagenesis 1221 – 1221 G -> A. Decreases ATP hydrolysis activity of 15% compared to the wild-type.
Mutagenesis 1221 – 1221 G -> T. Decreases ATP hydrolysis activity of 36% compared to the wild-type.
Mutagenesis 1221 – 1221 G -> V. Decreases ATP hydrolysis activity of 18% 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;

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;

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.