UniProtKB/SwissProt variant VAR

Variant information

Variant position:

22

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 Leucine (L) to Arginine (R) at position 22 (L22R, p.Leu22Arg).

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 (L) to large size and basic (R)

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 MEN1; no effect on histone methylation; almost no effect on JUND-binding; no repression of JUND transactivation.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs104894256 [ dbSNP | Ensembl ]

Sequence information

Variant position:

22

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

Protein sequence length:

615

The length of the canonical sequence.

Location on the sequence:

GLKAAQKTLFPLRSIDDVVR L FAAELGREEPDLVLLSLVLG

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                         GLKAAQKTLFPLRSIDDVVRLFAAELGREEPDLVLLSLVLG

Mouse                         GLKAAQKTLFPLRSIDDVVRLFAAELGREEPDLVLLSLVLG

Rat                           GLKAAQKTLFPLRSIDDVVRLFAAELGREEPDLVLLSLVLG

Bovine                        GLKAAQKTLFPLRSIDDVVRLFAAELGREEPDLVLLSLVLG

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 – 615	Menin
Helix	16 – 27

Literature citations

Positional cloning of the gene for multiple endocrine neoplasia-type 1.
Chandrasekharappa S.C.; Guru S.C.; Manickam P.; Olufemi S.-E.; Collins F.S.; Emmert-Buck M.R.; Debelenko L.V.; Zhuang Z.; Lubensky I.A.; Liotta L.A.; Crabtree J.S.; Wang Y.; Roe B.A.; Weisemann J.; Boguski M.S.; Agarwal S.K.; Kester M.B.; Kim Y.S.; Heppner C.; Dong Q.; Spiegel A.M.; Burns A.L.; Marx S.J.;
Science 276:404-407(1997)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2); VARIANTS MEN1 ARG-22; LYS-119 DEL; GLU-368 DEL AND ARG-441; VARIANTS GLN-176 AND ALA-546;

Menin interacts with the AP1 transcription factor JunD and represses JunD-activated transcription.
Agarwal S.K.; Guru S.C.; Heppner C.; Erdos M.R.; Collins R.M.; Park S.Y.; Saggar S.; Chandrasekharappa S.C.; Collins F.S.; Spiegel A.M.; Marx S.J.; Burns A.L.;
Cell 96:143-152(1999)
Cited for: INTERACTION WITH JUND; VARIANTS MEN1 LEU-12; ARG-22; ASP-139; TYR-139; PRO-165; PRO-181; VAL-247; PRO-291; PRO-314; ARG-349 AND ARG-441;

Menin associates with a trithorax family histone methyltransferase complex and with the hoxc8 locus.
Hughes C.M.; Rozenblatt-Rosen O.; Milne T.A.; Copeland T.D.; Levine S.S.; Lee J.C.; Hayes D.N.; Shanmugam K.S.; Bhattacharjee A.; Biondi C.A.; Kay G.F.; Hayward N.K.; Hess J.L.; Meyerson M.;
Mol. Cell 13:587-597(2004)
Cited for: FUNCTION IN H3K4 METHYLATION; IDENTIFICATION IN THE MEN1-ASSOCIATED HISTONE METHYLTRANSFERASE COMPLEX; INTERACTION WITH POLR2A AND POLR2B; VARIANTS MEN1 LEU-12; ARG-22; ASP-139; VAL-247; PRO-314; ARG-349 AND ARG-441;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O00255: Variant p.Leu22Arg