UniProtKB/Swiss-Prot P13569: Variant p.Gly551Asp

Cystic fibrosis transmembrane conductance regulator
Gene: CFTR
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Variant information Variant position:

551 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 Aspartate (D) at position 551 (G551D, p.Gly551Asp). 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 medium size and acidic (D) 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 CF; decrease in the frequency of channel opening in vitro; decrease in channel activity and ATPase activity; complete loss of bicarbonate transport; no effect on trafficking to the cell membrane, protein stability, nor on the maturation of glycans. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs75527207 [ dbSNP | Ensembl ]

Sequence information Variant position:

551 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

1480 The length of the canonical sequence.
Location on the sequence:

SKFAEKDNIVLGEGGITLSG G QRARISLARAVYKDADLYLL 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                         SKFAEKDNIVLGEGGITLSGGQRARISLARAVYKDADLYLL

Gorilla                       SKFAEKDNIVLGEGGITLSGGQRARISLARAVYKDADLYLL

                              SKFAEKDNIVLGEGGVTLSGGQRARISLARAVYKDADLYLL

Rhesus macaque                SKFAEKDNIVLGEGGITLSGGQRARISLARAVYKDADLYLL

Chimpanzee                    SKFAEKDNIVLGEGGITLSGGQRARISLARAVYKDADLYLL

Mouse                         TKFAEQDNTVLGEGGVTLSGGQRARISLARAVYKDADLYLL

Rat                           TKFAEQDNTVLGEGGVTLSGGQRARISLARAVYKDADLYLL

Pig                           SKFAEKDNIVLGEGGITLSGGQRARISLARAVYKDADLYLL

Bovine                        SKFAEKDNVVLGEGGITLSGGQRARISLARAVYKDADLYLL

Rabbit                        SKFTEKDNTVLGEGGITLSGGQRARISLARAVYKDADLYLL

Sheep                         SKFSEKDNIVLGEGGITLSGGQRARISLARAVYKDADLYLL

Horse                         SKFAEKDNIVLGEGGIQLSGGQRARISLARAVYKDADLYLL

Xenopus laevis                SKFPEKDNTVLGEGGITLSGGQRARISLARAVYKDADLYLL

Zebrafish                     AALPEKDKTPMAEGGLNLSGGQKARVALARAVYRDADLYLL

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 – 1480	Cystic fibrosis transmembrane conductance regulator
Topological domain	359 – 858	Cytoplasmic
Domain	423 – 646	ABC transporter 1
Modified residue	549 – 549	Phosphoserine
Mutagenesis	539 – 539	I -> T. Enhances trafficking from the endoplasmic reticulum to the cell membrane.
Helix	550 – 563

Literature citations
Defective intracellular transport and processing of CFTR is the molecular basis of most cystic fibrosis.
Cheng S.H.; Gregory R.J.; Marshall J.; Paul S.; Souza D.W.; White G.A.; O'Riordan C.R.; Smith A.E.;
Cell 63:827-834(1990)
Cited for: CHARACTERIZATION OF VARIANT CF TRP-334; ILE-507 DEL; PHE-508 DEL; ASP-551 AND ILE-549; MUTAGENESIS OF LYS-464; PHE-508 AND LYS-1250; GLYCOSYLATION; A cluster of cystic fibrosis mutations in the first nucleotide-binding fold of the cystic fibrosis conductance regulator protein.
Cutting G.R.; Kasch L.M.; Rosenstein B.J.; Zielenski J.; Tsui L.-C.; Antonarakis S.E.; Kazazian H.H. Jr.;
Nature 346:366-369(1990)
Cited for: VARIANTS CF ASN-549; ASP-551 AND THR-559; Identification of mutations in regions corresponding to the two putative nucleotide (ATP)-binding folds of the cystic fibrosis gene.
Kerem B.-S.; Zielenski J.; Markiewicz D.; Bozon D.; Gazit E.; Yahav J.; Kennedy D.; Riordan J.R.; Collins F.S.; Rommens J.M.; Tsui L.-C.;
Proc. Natl. Acad. Sci. U.S.A. 87:8447-8451(1990)
Cited for: VARIANTS CF GLU-455; ARG-549; ILE-549; ASP-551; THR-560; ASN-563 AND HIS-574; Maturation and function of cystic fibrosis transmembrane conductance regulator variants bearing mutations in putative nucleotide-binding domains 1 and 2.
Gregory R.J.; Rich D.P.; Cheng S.H.; Souza D.W.; Paul S.; Manavalan P.; Anderson M.P.; Welsh M.J.; Smith A.E.;
Mol. Cell. Biol. 11:3886-3893(1991)
Cited for: CHARACTERIZATION OF CF VARIANTS ILE-507 DEL; PHE-508 DEL; ILE-549; ARG-549; ASP-551; THR-559; ASN-572; LYS-1303 AND ASP-1349; FUNCTION; SUBCELLULAR LOCATION; MUTAGENESIS OF PHE-508; Molecular characterization of cystic fibrosis: 16 novel mutations identified by analysis of the whole cystic fibrosis conductance transmembrane regulator (CFTR) coding regions and splice site junctions.
Fanen P.; Ghanem N.; Vidaud M.; Besmond C.; Martin J.; Costes B.; Plassa F.; Goossens M.;
Genomics 13:770-776(1992)
Cited for: VARIANTS VAL-44; MET-470; VAL-506; CYS-508; ALA-576; CYS-668; PHE-997; THR-1027 AND LEU-1162; VARIANTS CF GLY-44; ARG-178; ARG-225; TRP-334; PHE-508 DEL; 542-GLY--LEU-1480 DEL; ASP-551; ILE-562; ARG-628; 710-LYS--LEU-1480 DEL; 846-TRP--LEU-1480 DEL; CYS-913; 1063-TRP--LEU-1480 DEL; CYS-1066; 1092-TYR--LEU-1480 DEL; 1162-ARG--LEU-1480 DEL; GLU-1200; 1282-TRP--LEU-1480 DEL AND LYS-1303; Mislocalization of delta F508 CFTR in cystic fibrosis sweat gland.
Kartner N.; Augustinas O.; Jensen T.J.; Naismith A.L.; Riordan J.R.;
Nat. Genet. 1:321-327(1992)
Cited for: CHARACTERIZATION OF VARIANT CF PHE-508 DEL AND ASP-551; SUBCELLULAR LOCATION; TISSUE SPECIFICITY; ATPase activity of the cystic fibrosis transmembrane conductance regulator.
Li C.; Ramjeesingh M.; Wang W.; Garami E.; Hewryk M.; Lee D.; Rommens J.M.; Galley K.; Bear C.E.;
J. Biol. Chem. 271:28463-28468(1996)
Cited for: CHARACTERIZATION OF VARIANT CF ASP-551; CATALYTIC ACTIVITY; FUNCTION; SUBCELLULAR LOCATION; PHOSPHORYLATION; Cystic fibrosis mutation frequencies in upstate New York.
Shrimpton A.E.; Borowitz D.; Swender P.;
Hum. Mutat. 10:436-442(1997)
Cited for: VARIANTS CF GLU-85; HIS-117; TYR-287; GLU-455; ASP-551; PRO-1070 AND LYS-1303; Aberrant CFTR-dependent HCO3- transport in mutations associated with cystic fibrosis.
Choi J.Y.; Muallem D.; Kiselyov K.; Lee M.G.; Thomas P.J.; Muallem S.;
Nature 410:94-97(2001)
Cited for: CHARACTERIZATION OF VARIANTS CF HIS-117; THR-148; ARG-178; LYS-193; ASP-551; SER-551; GLN-620; VAL-648; GLY-800; TYR-949; THR-1067; GLN-1070; GLU-1244; PRO-1255 AND ASP-1349; Two small molecules restore stability to a sub-population of the cystic fibrosis transmembrane conductance regulator with the predominant disease-causing mutation.
Meng X.; Wang Y.; Wang X.; Wrennall J.A.; Rimington T.L.; Li H.; Cai Z.; Ford R.C.; Sheppard D.N.;
J. Biol. Chem. 292:3706-3719(2017)
Cited for: CHARACTERIZATION OF VARIANTS CF PHE-508 DEL AND ASP-551; SUBCELLULAR LOCATION; FUNCTION;

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.