Menin

Function

Essential component of a MLL/SET1 histone methyltransferase (HMT) complex, a complex that specifically methylates 'Lys-4' of histone H3 (H3K4). Functions as a transcriptional regulator. Binds to the TERT promoter and represses telomerase expression. Plays a role in TGFB1-mediated inhibition of cell-proliferation, possibly regulating SMAD3 transcriptional activity. Represses JUND-mediated transcriptional activation on AP1 sites, as well as that mediated by NFKB subunit RELA. Positively regulates HOXC8 and HOXC6 gene expression. May be involved in normal hematopoiesis through the activation of HOXA9 expression (By similarity). May be involved in DNA repair.

Classification

Family (Pfam)

PF05053 Menin

InterPro

Menin

Functional cluster

Membrane Channels & Lipid-Anchored Proteins

Experimental structures · PDB · 61

• 3U84 X-ray 2.50A
• 3U85 X-ray 3.00A
• 3U86 X-ray 2.84A
• 3U88 X-ray 3.00A
• 4GPQ X-ray 1.46A
• 4GQ3 X-ray 1.56A
• 4GQ4 X-ray 1.27A
• 4GQ6 X-ray 1.55A
• 4I80 X-ray 3.10A
• 4OG3 X-ray 2.01A
• 4OG4 X-ray 1.45A
• 4OG5 X-ray 1.63A
• … and 49 more

A predicted model is available from AlphaFold.

Gene Ontology · 35

• GO:0000785 chromatin
• GO:0000781 chromosome, telomeric region
• GO:0032154 cleavage furrow
• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0005788 endoplasmic reticulum lumen
• GO:0035097 histone methyltransferase complex
• GO:0016363 nuclear matrix
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0032991 protein-containing complex
• GO:0003682 chromatin binding
• GO:0003690 double-stranded DNA binding
• GO:0000400 four-way junction DNA binding
• GO:0051219 phosphoprotein binding
• GO:0030674 protein-macromolecule adaptor activity
• GO:0070412 R-SMAD binding
• GO:0000976 transcription cis-regulatory region binding
• GO:0000403 Y-form DNA binding
• GO:0006974 DNA damage response
• GO:0006281 DNA repair
• GO:0045786 negative regulation of cell cycle
• GO:0008285 negative regulation of cell population proliferation
• GO:0045892 negative regulation of DNA-templated transcription
• GO:0046329 negative regulation of JNK cascade
• GO:0045668 negative regulation of osteoblast differentiation
• GO:0000122 negative regulation of transcription by RNA polymerase II
• GO:0002076 osteoblast development
• GO:0045944 positive regulation of transcription by RNA polymerase II
• GO:0030511 positive regulation of transforming growth factor beta receptor signaling pathway
• GO:0006357 regulation of transcription by RNA polymerase II
• GO:0010332 response to gamma radiation
• GO:0009411 response to UV
• GO:0045064 T-helper 2 cell differentiation
• GO:0045815 transcription initiation-coupled chromatin remodeling

Disease associations

• multiple endocrine neoplasia type 1 MONDO:0007540

Drugs targeting this protein · 2

• REVUMENIB SESQUIFUMARATE inhibitor
• REVUMENIB CITRATE inhibitor

Related proteins · sequence + function similarity

• Menin 1.00
• Menin 1.00
• Menin 1.00
• Menin 1.00
• Nonsense-mediated mRNA decay factor SMG5 0.72
• Nonsense-mediated mRNA decay factor SMG5 0.70
• FHF complex subunit HOOK-interacting protein 1B 0.70
• FHF complex subunit HOOK-interacting protein 1B 0.70
• FHF complex subunit HOOK-interacting protein 1B 0.70
• FHF complex subunit HOOK-interacting protein 1B 0.70
• Differentially expressed in FDCP 8 homolog 0.69
• Ras-associating and dilute domain-containing protein 0.69

Co-cited proteins · studied together in the literature

• Max dimerization protein 1 1 shared papers
• Protein DBF4 homolog A 1 shared papers
• Transcription factor JunD 1 shared papers
• Parafibromin 1 shared papers
• Transcription factor JunD 2 shared papers
• Protein AF-9 2 shared papers
• Histone-lysine N-methyltransferase 2A 5 shared papers
• Menin 1 shared papers
• Menin 1 shared papers
• Fanconi anemia group D2 protein 1 shared papers
• SMAD family member 3 1 shared papers
• Host cell factor 2 1 shared papers

Literature · 69 cited papers

• The same site on the integrase-binding domain of lens epithelium-derived growth factor is a therapeutic target for MLL leukemia and HIV. Blood · 2014
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• Structural insights into inhibition of the bivalent menin-MLL interaction by small molecules in leukemia. Blood · 2012
• The same pocket in menin binds both MLL and JUND but has opposite effects on transcription. Nature · 2012
• Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci. Signal. · 2010
• Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci. Signal. · 2009
• Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal. Chem. · 2009
• A quantitative atlas of mitotic phosphorylation. Proc. Natl. Acad. Sci. U.S.A. · 2008
• Identification of MEN1 and HRPT2 somatic mutations in paraffin-embedded (sporadic) parathyroid carcinomas. Clin. Endocrinol. (Oxf.) · 2007
• Novel MEN1 germline mutations in Brazilian families with multiple endocrine neoplasia type 1. Clin. Endocrinol. (Oxf.) · 2007
• ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science · 2007
• … and 57 more in the literature graph