UniProtKB/SwissProt variant VAR

Variant information

Variant position:

462

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 Isoleucine (I) to Valine (V) at position 462 (I462V, p.Ile462Val).

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:

Similar physico-chemical property. Both residues are medium size and hydrophobic.

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

BLOSUM score:

3

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 allele CYP1A1*2B and allele CYP1A1*2C; displays 5.7- and 12-fold increase in catalytic efficiency in the formation of 2-hydroxylated estrogens, 17beta-estradiol and estrone respectively..

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs1048943 [ dbSNP | Ensembl ]

Sequence information

Variant position:

462

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

Protein sequence length:

512

The length of the canonical sequence.

Location on the sequence:

VLSEKVIIFGMGKRKCIGET I ARWEVFLFLAILLQRVEFSV

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                         VLSEKVIIFGMGKRKCIGETIARWEVFLFLAILLQRVEFSV

                              ALSEKVILFGLGKRKCIGETIARLEVFLFLAILLQQVEFSV

Rhesus macaque                VLSEKVILFGLGKRKCIGETIARWEVFLFLAILLQRVEFSV

Mouse                         RLSEKVTLFGLGKRKCIGETIGRSEVFLFLAILLQQIEFKV

Rat                           HLSEKVILFGLGKRKCIGETIGRLEVFLFLAILLQQMEFNV

Rabbit                        ALTEKVLLFGLGKRKCIGETIGRLEVFLFLATLLQQVEFSV

Sheep                         VLSEKVIIFGLGKRQCIGEIIARLEVFLFLAILLHQVEFHV

Cat                           ALSEKVILFGLGKRKCIGETIARLEVFLFLAILLQQVEFSV

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 – 512	Cytochrome P450 1A1
Metal binding	457 – 457	Iron (heme axial ligand)
Alternative sequence	190 – 512	Missing. In isoform 2.
Alternative sequence	419 – 512	Missing. In isoform 3.
Helix	460 – 477

Literature citations

Association of CYP1A1 polymorphisms with differential metabolic activation of 17beta-estradiol and estrone.
Kisselev P.; Schunck W.H.; Roots I.; Schwarz D.;
Cancer Res. 65:2972-2978(2005)
Cited for: FUNCTION; CATALYTIC ACTIVITY; CHARACTERIZATION OF VARIANT ASN-461 AND VARIANT VAL-462; BIOPHYSICOCHEMICAL PROPERTIES; PATHWAY;

Genetic linkage of lung cancer-associated MspI polymorphisms with amino acid replacement in the heme binding region of the human cytochrome P450IA1 gene.
Hayashi S.; Watanabe J.; Nakachi K.; Kawajiri K.;
J. Biochem. 110:407-411(1991)
Cited for: VARIANT VAL-462;

Toward the evaluation of function in genetic variability: characterizing human SNP frequencies and establishing BAC-transgenic mice carrying the human CYP1A1_CYP1A2 locus.
Jiang Z.; Dalton T.P.; Jin L.; Wang B.; Tsuneoka Y.; Shertzer H.G.; Deka R.; Nebert D.W.;
Hum. Mutat. 25:196-206(2005)
Cited for: VARIANTS ASP-45; THR-78; ASN-461 AND VAL-462;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P04798: Variant p.Ile462Val