UniProtKB/SwissProt variant VAR

Variant information

Variant position:

139

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 Histidine (H) to Aspartate (D) at position 139 (H139D, p.His139Asp).

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 (H) to medium size and acidic (D)

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:

In MEN1; almost complete loss of histone methylation; strong decrease in JUND-binding; no repression of JUND transactivation; reduced interaction with KMT2A.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs104894263 [ dbSNP | Ensembl ]

Sequence information

Variant position:

139

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:

KKVSDVIWNSLSRSYFKDRA H IQSLFSFITGWSPVGTKLDS

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                         KKVSDVIWNSLSRSYFKDRAHIQSLFSFITGWSPVGTKLDS

Mouse                         KKVSDVIWNSLSRSYFKDRAHIQSLFSFITG-----TKLDS

Rat                           KKVSDVIWNSLSRSYFKDRAHIQSLFSFITG-----TKLDS

Bovine                        KKVSDVIWNSLSRSYFKDRAHIQSLFSFITG-----TKLDS

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
Beta strand	137 – 139

Literature citations

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;

The same pocket in menin binds both MLL and JUND but has opposite effects on transcription.
Huang J.; Gurung B.; Wan B.; Matkar S.; Veniaminova N.A.; Wan K.; Merchant J.L.; Hua X.; Lei M.;
Nature 482:542-546(2012)
Cited for: X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 2-615 IN COMPLEX WITH KMT2A; PSIP1 AND JUND; INTERACTION WITH KMT2A AND JUND; INTERACTION OF KMT2A-MEN1 COMPLEX WITH PSIP1; CHARACTERIZATION OF VARIANTS MEN1 ASP-139; PHE-246; VAL-247; ARG-286 AND ARG-349; CHARACTERIZATION OF VARIANT GLN-289; MUTAGENESIS OF ALA-187; MET-283; ASP-290; GLU-293; GLU-295; TYR-324; TYR-328; GLU-371 AND ASP-375; FUNCTION;

Parathyroid MEN1 gene mutations in relation to clinical characteristics of nonfamilial primary hyperparathyroidism.
Carling T.; Correa P.; Hessman O.; Hedberg J.; Skogseid B.; Lindberg D.; Rastad J.; Westin G.; Akerstrom G.;
J. Clin. Endocrinol. Metab. 83:2960-2963(1998)
Cited for: VARIANT MEN1 ASP-139; VARIANT TRP-157;

Pituitary macroadenoma in a 5-year-old: an early expression of multiple endocrine neoplasia type 1.
Stratakis C.A.; Schussheim D.H.; Freedman S.M.; Keil M.F.; Pack S.D.; Agarwal S.K.; Skarulis M.C.; Weil R.J.; Lubensky I.A.; Zhuang Z.; Oldfield E.H.; Marx S.J.;
J. Clin. Endocrinol. Metab. 85:4776-4780(2000)
Cited for: VARIANT MEN1 ASP-139;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O00255: Variant p.His139Asp