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UniProtKB/Swiss-Prot O00255: Variant p.Ala314Pro

Menin
Gene: MEN1
Variant information

Variant position:  314
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 Alanine (A) to Proline (P) at position 314 (A314P, p.Ala314Pro).
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 small size and hydrophobic (A) to medium size and hydrophobic (P)
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; no effect on histone methylation; almost no effect on JUND-binding.
Any additional useful information about the variant.



Sequence information

Variant position:  314
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:   LEPTPGRPDPLTLYHKGIAS  A KTYYRDEHIYPYMYLAGYHC
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                         LEPTPGRPDPLTLYHKGIASAKTYYRDEHIYPYMYLAGYHC

                              LEPTPGRPDPLTLYHKGIASAKTYYRDEHIYPYMYLAGYHC

Mouse                         LEPTPGRPDPLTLYHKGIASAKTYYQDEHIYPYMYLAGYHC

Rat                           LEPTPGRPDPLTLYHKGIASAKTYYQDEHIYPYMYLAGYHC

Bovine                        LEPTPGRPDPLTLYHKGIASAKTYYRDEHIYPYMYLAGYHC

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
Mutagenesis 295 – 295 E -> R. Reduced interaction with KMT2A; when associated with R-290 and R-293.
Mutagenesis 324 – 324 Y -> A. Reduced interaction with KMT2A.
Mutagenesis 328 – 328 Y -> A. Reduced interaction with KMT2A.
Helix 303 – 317


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;

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.