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UniProtKB/Swiss-Prot Q9UNQ0: Variant p.Asn590Tyr

Broad substrate specificity ATP-binding cassette transporter ABCG2
Gene: ABCG2
Variant information

Variant position:  590
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Polymorphism
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Asparagine (N) to Tyrosine (Y) at position 590 (N590Y, p.Asn590Tyr).
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 polar (N) to large size and aromatic (Y)
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

Polymorphism:  Genetic variations in ABCG2 define the blood group Junior system (JR) [MIM:614490]. Individuals with Jr(a-) blood group lack the Jr(a) antigen on their red blood cells. These individuals may have anti-Jr(a) antibodies in their serum, which can cause transfusion reactions or hemolytic disease of the fetus or newborn. Although the clinical significance of the Jr(a-) blood group has been controversial, severe fatal hemolytic disease of the newborn has been reported. The Jr(a-) phenotype has a higher frequency in individuals of Asian descent, compared to those of European descent. The Jr(a-) phenotype is inherited as an autosomal recessive trait.Genetic variations in ABCG2 influence the variance in serum uric acid concentrations and define the serum uric acid concentration quantitative trait locus 1 (UAQTL1) [MIM:138900]. Excess serum accumulation of uric acid can lead to the development of gout, a common disorder characterized by tissue deposition of monosodium urate crystals as a consequence of hyperuricemia (PubMed:18834626, PubMed:19506252, PubMed:20368174). -
Additional information on the polymorphism described.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  590
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  655
The length of the canonical sequence.

Location on the sequence:   YFSIPRYGFTALQHNEFLGQ  N FCPGLNATGNNPCNYATCTG
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                         YFSIPRYGFTALQHNEFLGQNFC------------PGLNATGNNPC--NYATCT---G

Rhesus macaque                YFSIPRYGFTALQHNEFLGQNFC------------PGLNAT

Mouse                         YFSIPRYGFTALQYNEFLGQEFC------------PGFNVT

Rat                           YFSIPRYGFTALQHNEFLGQEFC------------PGLNVT

Pig                           YFSIPRYGFSALQYNEFLGQNFC------------PGLNVT

Bovine                        YLSIPRYGYAALQHNEFLGQNFC------------PGLNVT

Slime mold                    WISPIKYAFEGLMSNEHHGLIYSCDDSETIPPRNTPNFELP

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 – 655 Broad substrate specificity ATP-binding cassette transporter ABCG2
Topological domain 557 – 630 Extracellular
Domain 389 – 651 ABC transmembrane type-2
Glycosylation 596 – 596 N-linked (GlcNAc...) asparagine
Disulfide bond 603 – 603 Interchain
Alternative sequence 550 – 611 IFSGLLVNLTTIASWLSWLQYFSIPRYGFTALQHNEFLGQNFCPGLNATGNNPCNYATCTGE -> VCWSISQPLHLGCHGFSTSAFHDMDLRLCSIMNFWDKTSAQDSMQQETILVTMQHVLAKNIW. In isoform 2.
Mutagenesis 583 – 583 H -> A. Strongly reduced binding to hemin but not to PPIX.
Mutagenesis 596 – 596 N -> Q. Loss of glycosylation.
Mutagenesis 603 – 603 C -> A. Strongly reduced binding to hemin but not to PPIX.
Mutagenesis 605 – 605 Y -> A. No effect on hemin binding.


Literature citations

Natural allelic variants of breast cancer resistance protein (BCRP) and their relationship to BCRP expression in human intestine.
Zamber C.P.; Lamba J.K.; Yasuda K.; Farnum J.; Thummel K.; Schuetz J.D.; Schuetz E.G.;
Pharmacogenetics 13:19-28(2003)
Cited for: VARIANTS MET-12; LYS-141; LEU-206 AND TYR-590;

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.