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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O00255: Variant p.His139Asp

Menin
Gene: MEN1
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Variant information Variant position: help 139 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help 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: help 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: help -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: help 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: help Links to websites of interest for the variant.


Sequence information Variant position: help 139 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 610 The length of the canonical sequence.
Location on the sequence: help KKVSDVIWNSLSRSYFKDRA H IQSLFSFITGTKLDSSGVAF 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         KKVSDVIWNSLSRSYFKDRAHIQSLFSFITGTKLDSSGVAF

                              KKVSDVIWNSLSRSYFKDRAHIQSLFSFITGTKLDSSGVAF

Mouse                         KKVSDVIWNSLSRSYFKDRAHIQSLFSFITGTKLDSSGVAF

Rat                           KKVSDVIWNSLSRSYFKDRAHIQSLFSFITGTKLDSSGVAF

Bovine                        KKVSDVIWNSLSRSYFKDRAHIQSLFSFITGTKLDSSGVAF
Sequence annotation in neighborhood: help 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 – 610 Menin
Alternative sequence 148 – 148 T -> TGWSPV. In isoform 2.
Alternative sequence 148 – 148 Missing. In isoform 3.
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-160; PRO-176; VAL-242; PRO-286; PRO-309; ARG-344 AND ARG-436; 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-242; PRO-309; ARG-344 AND ARG-436; 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-241; VAL-242; ARG-281 AND ARG-344; CHARACTERIZATION OF VARIANT GLN-284; MUTAGENESIS OF ALA-182; MET-278; ASP-285; GLU-288; GLU-290; TYR-319; TYR-323; GLU-366 AND ASP-370; 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-152; 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;
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.