UniProtKB/Swiss-Prot O95342: Variant p.Val444Ala

Bile salt export pump
Gene: ABCB11
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Variant information Variant position:

444 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B 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 Valine (V) to Alanine (A) at position 444 (V444A, p.Val444Ala). 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 hydrophobic (V) to small size and hydrophobic (A) 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:

Does not affect transport capacity for taurocholate; increases transport activity of taurocholate in a low cholesterol environment; increases transport activity of taurocholate in a high cholesterol environment; does not affect cell surface protein expression; does not affect protein expression. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs2287622 [ dbSNP | Ensembl ]

Sequence information Variant position:

444 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:

NVTFHYPSRPEVKILNDLNM V IKPGEMTALVGPSGAGKSTA 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                         NVTFHYPSRPEVKILNDLNMVIKPGEMTALVGPSGAGKSTA

Mouse                         NVTFHYPSRPEVKILNNLSMVIKPGETTAFVGSSGAGKSTA

Rat                           NVTFHYPSRPDVKILDNLSMVIKPGETTALVGSSGAGKSTA

Rabbit                        NVTFHYPSRPEVKILNNLSMVIKPGEMTALVGPSGAGKSTA

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	375 – 755	Cytoplasmic
Domain	420 – 656	ABC transporter 1

Literature citations
Cellular localization and functional characterization of the human bile salt export pump (BSEP).
Mol O.; Hooiveld G.J.E.J.; Jansen P.L.M.; Muller M.;
Cited for: NUCLEOTIDE SEQUENCE [MRNA]; VARIANT ALA-444; Three hundred twenty-six genetic variations in genes encoding nine members of ATP-binding cassette, subfamily B (ABCB/MDR/TAP), in the Japanese population.
Saito S.; Iida A.; Sekine A.; Miura Y.; Ogawa C.; Kawauchi S.; Higuchi S.; Nakamura Y.;
J. Hum. Genet. 47:38-50(2002)
Cited for: VARIANT ALA-444; Sequence analysis of bile salt export pump (ABCB11) and multidrug resistance p-glycoprotein 3 (ABCB4, MDR3) in patients with intrahepatic cholestasis of pregnancy.
Pauli-Magnus C.; Lang T.; Meier Y.; Zodan-Marin T.; Jung D.; Breymann C.; Zimmermann R.; Kenngott S.; Beuers U.; Reichel C.; Kerb R.; Penger A.; Meier P.J.; Kullak-Ublick G.A.;
Pharmacogenetics 14:91-102(2004)
Cited for: VARIANTS GLN-415; ALA-444; SER-591 AND VAL-677; Genetic variability, haplotype structures, and ethnic diversity of hepatic transporters MDR3 (ABCB4) and bile salt export pump (ABCB11).
Lang T.; Haberl M.; Jung D.; Drescher A.; Schlagenhaufer R.; Keil A.; Mornhinweg E.; Stieger B.; Kullak-Ublick G.A.; Kerb R.;
Drug Metab. Dispos. 34:1582-1599(2006)
Cited for: VARIANTS VAL-206; ALA-284; LYS-299; ALA-444; GLY-616; ALA-619; VAL-677; HIS-698; VAL-865 AND GLN-958; Interindividual variability of canalicular ATP-binding-cassette (ABC)-transporter expression in human liver.
Meier Y.; Pauli-Magnus C.; Zanger U.M.; Klein K.; Schaeffeler E.; Nussler A.K.; Nussler N.; Eichelbaum M.; Meier P.J.; Stieger B.;
Hepatology 44:62-74(2006)
Cited for: VARIANTS ALA-444 AND VAL-677; Mutations and polymorphisms in the bile salt export pump and the multidrug resistance protein 3 associated with drug-induced liver injury.
Lang C.; Meier Y.; Stieger B.; Beuers U.; Lang T.; Kerb R.; Kullak-Ublick G.A.; Meier P.J.; Pauli-Magnus C.;
Pharmacogenet. Genomics 17:47-60(2007)
Cited for: VARIANTS ALA-284; ALA-444; TYR-676; VAL-677; HIS-698 AND ARG-855; BIOPHYSICOCHEMICAL PROPERTIES; CHARACTERIZATION OF VARIANTS ALA-444; TYR-676; VAL-677 AND ARG-855; 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; Diagnosis of ABCB11 gene mutations in children with intrahepatic cholestasis using high resolution melting analysis and direct sequencing.
Hu G.; He P.; Liu Z.; Chen Q.; Zheng B.; Zhang Q.;
Mol. Med. Report. 10:1264-1274(2014)
Cited for: VARIANTS PFIC2 HIS-337; CYS-472; TRP-696; PRO-931; VAL-1131 AND ARG-1198; VARIANTS ALA-444 AND VAL-865; 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; Functional analysis of the correlation between ABCB11 gene mutation and primary intrahepatic stone.
Gan L.; Pan S.; Cui J.; Bai J.; Jiang P.; He Y.;
Mol. Med. Report. 19:195-204(2019)
Cited for: VARIANTS LYS-299; ALA-444 AND VAL-865; CHARACTERIZATION OF VARIANT VAL-865; SUBCELLULAR LOCATION;

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.