UniProtKB/SwissProt variant VAR

Variant information

Variant position:

7

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 Valine (V) at position 7 (E7V, p.Glu7Val).

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 medium size and hydrophobic (V)

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 SKCA; Hb S; at heterozygosity confers resistance to malaria.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs334 [ dbSNP | Ensembl ]

Sequence information

Variant position:

7

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

Protein sequence length:

147

The length of the canonical sequence.

Location on the sequence:

MVHLTP E EKSAVTALWGKVNVDEVGGE

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                         MVHLTPEEKSAVTALWGKVNVDEVGGE

Gorilla                       MVHLTPEEKSAVTALWGKVNVDEVGGE

Rhesus macaque                -VHLTPEEKNAVTTLWGKVNVDEVGGE

Chimpanzee                    MVHLTPEEKSAVTALWGKVNVDEVGGE

Pig                           MVHLSAEEKEAVLGLWGKVNVDEVGGE

Bovine                        --MLTAEEKAAVTAFWGKVKVDEVGGE

Rabbit                        MVHLSSEEKSAVTALWGKVNVEEVGGE

Sheep                         --MLTAEEKAAVTGFWGKVKVDEVGAE

Cat                           -GFLTAEEKGLVNGLWGKVNVDEVGGE

Horse                         -VQLSGEEKAAVLALWDKVNEEEVGGE

Chicken                       MVHWTAEEKQLITGLWGKVNVAECGAE

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
Initiator methionine	1 – 1	Removed
Chain	2 – 147	Hemoglobin subunit beta
Binding site	2 – 2
Binding site	3 – 3
Modified residue	2 – 2	N-acetylvaline
Modified residue	2 – 2	N-pyruvate 2-iminyl-valine; in Hb A1b
Modified residue	10 – 10	Phosphoserine
Modified residue	13 – 13	Phosphothreonine
Glycosylation	2 – 2	N-linked (Glc) (glycation) valine; in Hb A1c
Glycosylation	9 – 9	N-linked (Glc) (glycation) lysine
Glycosylation	18 – 18	N-linked (Glc) (glycation) lysine
Helix	6 – 17

Literature citations

A new hemoglobin, beta chain variant 'Hb S-Wake' confirmed to be on the same chromosome with hemoglobin S mutation, detected in an African-American family.
Kutlar F.; Lallinger R.R.; Holley L.; Glendenning M.; Kutlar A.;
Cited for: NUCLEOTIDE SEQUENCE [MRNA]; VARIANT SKCA VAL-7; VARIANT SER-140;

Gene mutations in human haemoglobin: the chemical difference between normal and sickle cell haemoglobin.
Ingram V.M.;
Nature 180:326-328(1957)
Cited for: PROTEIN SEQUENCE OF 3-9; INVOLVEMENT IN SKCA; VARIANT SKCA VAL-7;

How malaria has affected the human genome and what human genetics can teach us about malaria.
Kwiatkowski D.P.;
Am. J. Hum. Genet. 77:171-192(2005)
Cited for: POLYMORPHISM; ASSOCIATION OF VARIANT SKCA VAL-7 WITH RESISTANCE TO MALARIA;

Crystal structure of sickle-cell deoxyhemoglobin at 5 A resolution.
Wishner B.C.; Ward K.B.; Lattman E.E.; Love W.E.;
J. Mol. Biol. 98:179-194(1975)
Cited for: X-RAY CRYSTALLOGRAPHY (5 ANGSTROMS) OF VARIANT SKCA VAL-7;

Structure of fully liganded Hb zeta2beta2s trapped in a tense conformation.
Safo M.K.; Ko T.P.; Abdulmalik O.; He Z.; Wang A.H.; Schreiter E.R.; Russell J.E.;
Acta Crystallogr. D 69:2061-2071(2013)
Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF VARIANT SKCA VAL-7 IN COMPLEX WITH HEME AND HBZ; SUBUNIT;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P68871: Variant p.Glu7Val