UniProtKB/SwissProt variant VAR

Variant information

Variant position:

297

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 Glycine (G) at position 297 (E297G, p.Glu297Gly).

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 glycine (G)

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

BLOSUM score:

-2

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 PFIC2 and BRIC2; reduces transport capacity for taurocholate; decreases protein expression; affects maturation of protein in the reticulum endoplasmic; does not affect apical membrane localization; does not affect cell surface expression of the mature form; does not affect transport of taurocholate and glycocholate; enhances ubiquitination susceptibility; reduces transport activity of taurocholate in a low cholesterol environment; increases transport activity of taurocholate in a high cholesterol environment; does not affect protein expression; does not affect cell membrane localization.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs11568372 [ dbSNP | Ensembl ]

Sequence information

Variant position:

297

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

Protein sequence length:

1321

The length of the canonical sequence.

Location on the sequence:

AGVVADEVISSMRTVAAFGG E KREVERYEKNLVFAQRWGIR

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                         AGVVADEVISSMRTVAAFGGEKREVERYEKNLVFAQRWGIR

Mouse                         AGSIADEVLSSIRTVAAFGGENKEVERYEKNLMFAQRWGIW

Rat                           AGSIADEVLSSIRTVAAFGGENKEVERYEKNLVFAQRWGIW

Rabbit                        AGSVADEVISSMRTVAAFGGEKKEVERYEKNLVFAQRWGIR

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 – 1321	Bile salt export pump
Topological domain	262 – 319	Cytoplasmic
Domain	62 – 385	ABC transmembrane type-1 1
Mutagenesis	1 – 441	Missing. Does not affect ATPase-coupled bile acid transport activity. Decreases protein stability.
Turn	294 – 308

Literature citations

A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis.
Strautnieks S.S.; Bull L.N.; Knisely A.S.; Kocoshis S.A.; Dahl N.; Arnell H.; Sokal E.M.; Dahan K.; Childs S.; Ling V.; Tanner M.S.; Kagalwalla A.F.; Nemeth A.; Pawlowska J.; Baker A.; Mieli-Vergani G.; Freimer N.B.; Gardiner R.M.; Thompson R.J.;
Nat. Genet. 20:233-238(1998)
Cited for: NUCLEOTIDE SEQUENCE [MRNA]; VARIANTS PFIC2 GLY-297; GLU-461; GLY-482; ARG-982; CYS-1153 AND GLN-1268;

Benign recurrent intrahepatic cholestasis type 2 is caused by mutations in ABCB11.
van Mil S.W.C.; van der Woerd W.L.; van der Brugge G.; Sturm E.; Jansen P.L.M.; Bull L.N.; van den Berg I.E.T.; Berger R.; Houwen R.H.J.; Klomp L.W.J.;
Gastroenterology 127:379-384(2004)
Cited for: VARIANTS BRIC2 GLY-186; GLY-297; THR-570; PRO-923; PRO-926; CYS-1050 AND HIS-1128;

Two common PFIC2 mutations are associated with the impaired membrane trafficking of BSEP/ABCB11.
Hayashi H.; Takada T.; Suzuki H.; Akita H.; Sugiyama Y.;
Hepatology 41:916-924(2005)
Cited for: CHARACTERIZATION OF VARIANTS PFIC2 GLY-297 AND GLY-482; CATALYTIC ACTIVITY; FUNCTION; SUBCELLULAR LOCATION; BIOPHYSICOCHEMICAL PROPERTIES; GLYCOSYLATION;

Impaired expression and function of the bile salt export pump due to three novel ABCB11 mutations in intrahepatic cholestasis.
Noe J.; Kullak-Ublick G.A.; Jochum W.; Stieger B.; Kerb R.; Haberl M.; Muellhaupt B.; Meier P.J.; Pauli-Magnus C.;
J. Hepatol. 43:536-543(2005)
Cited for: VARIANTS BRIC2 GLY-297 AND THR-432; CHARACTERIZATION OF VARIANTS BRIC2 GLY-297 AND THR-432;

Short-chain ubiquitination is associated with the degradation rate of a cell-surface-resident bile salt export pump (BSEP/ABCB11).
Hayashi H.; Sugiyama Y.;
Mol. Pharmacol. 75:143-150(2009)
Cited for: CHARACTERIZATION OF VARIANT PFIC2 GLY-297; UBIQUITINATION;

Polymorphic variants in the human bile salt export pump (BSEP; ABCB11): functional characterization and interindividual variability.
Ho R.H.; Leake B.F.; Kilkenny D.M.; Meyer Zu Schwabedissen H.E.; Glaeser H.; Kroetz D.L.; Kim R.B.;
Pharmacogenet. Genomics 20:45-57(2010)
Cited for: VARIANTS LEU-56; VAL-206; ALA-444; HIS-558; SER-591; GLN-592; VAL-677 AND LYS-1186; CHARACTERIZATION OF VARIANTS LEU-56; VAL-206; ALA-444; HIS-558; SER-591; GLN-592; VAL-677 AND LYS-1186; VARIANT PFIC2 GLY-297; CHARACTERIZATION OF VARIANTS PFIC2 GLY-297; ARG-982 AND CYS-1153; FUNCTION; CATALYTIC ACTIVITY; SUBCELLULAR LOCATION;

Differential effects of membrane cholesterol content on the transport activity of multidrug resistance-associated protein 2 (ABCC2) and of the bile salt export pump (ABCB11).
Guyot C.; Hofstetter L.; Stieger B.;
Mol. Pharmacol. 85:909-920(2014)
Cited for: CHARACTERIZATION OF VARIANTS BRIC2 GLY-297 AND THR-432; CHARACTERIZATION VARIANT ALA-444; FUNCTION; CATALYTIC ACTIVITY; ACTIVITY REGULATION;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O95342: Variant p.Glu297Gly