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UniProtKB/Swiss-Prot O00255: Variant p.Thr349Arg

Menin
Gene: MEN1
Variant information

Variant position:  349
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 Threonine (T) to Arginine (R) at position 349 (T349R, p.Thr349Arg).
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 (T) to large size and basic (R)
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; almost no effect on JUND-binding; yields insoluble protein.
Any additional useful information about the variant.



Sequence information

Variant position:  349
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:   LAGYHCRNRNVREALQAWAD  T ATVIQDYNYCREDEEIYKEF
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                         LAGYHCRNRNVREALQAWADTATVIQDYNYCREDEEIYKEF

                              LAGYHCRNRNVREALQAWADTATVIQDYNYCREDEEIYKEF

Mouse                         LAGYHCRNRNVREALQAWADTATVIQDYNYCREDEEIYKEF

Rat                           LAGYHCRNRNVREALQAWADTATVIQDYNYCREDEEIYKEF

Bovine                        LAGYHCRNRNVREALQAWADTATVIQDYNYCREDEEIYKEF

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 – 615 Menin
Region 219 – 395 Interaction with FANCD2
Helix 339 – 353


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;

MEN1 gene mutation analysis in Italian patients with multiple endocrine neoplasia type 1.
Morelli A.; Falchetti A.; Martineti V.; Becherini L.; Mark M.; Friedman E.; Brandi M.L.;
Eur. J. Endocrinol. 142:131-137(2000)
Cited for: VARIANTS MEN1 LYS-45; MET-220 AND ARG-349;

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.