UniProtKB/SwissProt variant VAR

Variant information

Variant position:

757

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 Glutamate (E) to Lysine (K) at position 757 (E757K, p.Glu757Lys).

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 large size and basic (K)

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:

10% reduced expression level compared to wild-type; transport properties comparable to wild-type.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs3765534 [ dbSNP | Ensembl ]

Sequence information

Variant position:

757

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

Protein sequence length:

1325

The length of the canonical sequence.

Location on the sequence:

YWANKQSMLNVTVNGGGNVT E KLDLNWYLGIYSGLTVATVL

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                         YWANKQSMLNVTVNGGGNVTEKLDLNWYLGIYSGLTVATVL

Mouse                         HWANKQGALNNTRNANGNITETLDLSWYLGIYAGLTAVTVL

Rat                           HWANRQGALNDTKNANGNVTGTLDLSWYLGIYTGLTAVTVL

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 – 1325	ATP-binding cassette sub-family C member 4
Domain	714 – 1005	ABC transmembrane type-1 2
Glycosylation	746 – 746	N-linked (GlcNAc...) asparagine
Glycosylation	754 – 754	N-linked (GlcNAc...) asparagine
Mutagenesis	746 – 746	N -> Q. Does not affect plasma membrane localization; 1.5 fold increase in PEG2 transport; does not affect estradiol 17-beta-D-glucuronide transport.
Mutagenesis	754 – 754	N -> Q. Does not affect plasma membrane localization; PEG2 transport is decreased by 50%; does not affect estradiol 17-beta-D-glucuronide transport.

Literature citations

6-mercaptopurine and 9-(2-phosphonyl-methoxyethyl) adenine (PMEA) transport altered by two missense mutations in the drug transporter gene ABCC4.
Janke D.; Mehralivand S.; Strand D.; Goedtel-Armbrust U.; Habermeier A.; Gradhand U.; Fischer C.; Toliat M.R.; Fritz P.; Zanger U.M.; Schwab M.; Fromm M.F.; Nuernberg P.; Wojnowski L.; Closs E.I.; Lang T.;
Hum. Mutat. 29:659-669(2008)
Cited for: VARIANTS CYS-556; ILE-776; ILE-820; PHE-854 AND VAL-866; CHARACTERIZATION OF VARIANTS TRP-187; ASN-304; GLU-487; CYS-556; LYS-757; ILE-776; ILE-820; PHE-854; VAL-866 AND MET-1142; CATALYTIC ACTIVITY; FUNCTION;

A Japanese-specific allele in the GALNT11 gene.
Yuasa I.; Umetsu K.; Matsusue A.; Nishimukai H.; Harihara S.; Fukumori Y.; Saitou N.; Jin F.; Chattopadhyay P.K.; Henke L.; Henke J.;
Leg. Med. 12:208-211(2010)
Cited for: VARIANT LYS-757;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O15439: Variant p.Glu757Lys