MEN1 encodes menin, a 610-amino-acid, predominantly nuclear scaffold protein without a recognized enzymatic or sequence-specific DNA-binding domain. Its structure resembles a curved hand with a deep central pocket that binds short motifs of partner proteins. Through this pocket menin binds the N-terminus of the H3K4 methyltransferases KMT2A/MLL1 and KMT2B/MLL2, and with MLL1 forms a composite surface for the chromatin-anchoring protein LEDGF/PSIP1. As a subunit of MLL1/MLL2 complexes it targets H3K4 methylation to genes such as the HOX cluster, CDKN1B (p27) and CDKN2C (p18), acting as a transcriptional coactivator; MLL fusion oncoproteins depend on this interaction, which is the target of menin-MLL inhibitors in acute leukemia. The same pocket binds the AP-1 factor JunD, where menin blocks JNK-mediated JunD phosphorylation and represses JunD-driven transcription; menin also represses NF-kB (RELA) and TERT transcription and acts as a cofactor for SMAD3 in TGF-beta signaling. Menin binds double-stranded and branched DNA in a sequence-independent manner through basic residues of its C-terminal nuclear localization signals. It also takes part in DNA damage responses, relocating to chromatin after UV irradiation and associating with FANCD2. Germline loss-of-function mutations cause multiple endocrine neoplasia type 1, with tumors of the parathyroid, pancreatic islets and anterior pituitary.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:12837246 Multiple tumor suppressor pathways negatively regulate telom... | ACCEPT | Summary: Lin and Elledge identified menin in a genetic screen as a direct repressor of the hTERT promoter. Reason: Menin-dependent repression of RNA polymerase II target genes (hTERT, JunD/AP-1 targets) is a well-supported function, carried out as a corepressor bound to DNA-binding partners such as JunD. Supporting Evidence: PMID:12837246 The third, the tumor suppressor Menin, is a direct repressor of hTERT. file:human/MEN1/MEN1-uniprot.txt Binds to the TERT promoter and represses telomerase expression. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:22327296 The same pocket in menin binds both MLL and JUND but has opp... | ACCEPT | Summary: Huang et al. show that menin binds JunD through the same pocket that binds MLL1 and suppresses JunD-induced transcription. Reason: Direct structural and functional evidence that menin represses JunD-dependent Pol II transcription; consistent with the corepressor role. Supporting Evidence: PMID:22327296 The menin-JUND interaction blocks JUN N-terminal kinase (JNK)-mediated JUND phosphorylation and suppresses JUND-induced transcription. PMID:9989505 Menin repressed transcriptional activation mediated by JunD fused to the Gal4 DNA-binding domain from a Gal4 responsive reporter, or by JunD from an AP1-responsive reporter. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:23784080 HTLV-1 bZIP factor impedes the menin tumor suppressor and up... | ACCEPT | Summary: Borowiak et al. show JunD and menin form a repressor complex on the hTERT promoter, antagonised by HTLV-1 HBZ. Reason: Supports menin as part of a JunD-containing repressor complex at a Pol II promoter. Supporting Evidence: PMID:23784080 we report that JunD and menin form a repressor complex of hTERT transcription in HBZ-negative cells PMID:12837246 The third, the tumor suppressor Menin, is a direct repressor of hTERT. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:9989505 Menin interacts with the AP1 transcription factor JunD and r... | ACCEPT | Summary: Agarwal et al. identified JunD as a direct menin partner and showed menin represses JunD-activated transcription from Gal4 and AP-1 reporters. Reason: Founding evidence for menin as a repressor of JunD-mediated Pol II transcription. Supporting Evidence: PMID:9989505 Menin repressed transcriptional activation mediated by JunD fused to the Gal4 DNA-binding domain from a Gal4 responsive reporter, or by JunD from an AP1-responsive reporter. |
| GO:0000400 four-way junction DNA binding | IDA PMID:15331604 Direct binding of DNA by tumor suppressor menin. | KEEP AS NON CORE | Summary: La et al. showed by gel shift that purified menin binds 4-way junction DNA as well as dsDNA, Y-form and branched DNA. Reason: The in vitro binding is real, but it is part of a sequence-independent, structure-tolerant DNA binding mediated by basic NLS residues; there is no evidence that menin acts specifically on Holliday junctions in vivo. Kept as a precise but peripheral activity. Supporting Evidence: PMID:15331604 It also binds a variety of DNA structures, including Y-structures, branched structures, and 4-way junction structures. PMID:15331604 These results indicate that menin not only binds to DNA in a non-sequence specific fashion |
| GO:0000403 Y-form DNA binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT propagation of Y-form DNA binding, grounded in the human menin IDA (PMID:15331604). Reason: Consistent with the experimental IDA row; the activity is real in vitro but its in vivo role is unclear, so it is kept as non-core. Supporting Evidence: PMID:15331604 It also binds a variety of DNA structures, including Y-structures, branched structures, and 4-way junction structures. |
| GO:0000403 Y-form DNA binding | IDA PMID:15331604 Direct binding of DNA by tumor suppressor menin. | KEEP AS NON CORE | Summary: La et al. showed purified menin binds Y-structure DNA in gel shift assays. Reason: Supported in vitro, part of the general non-sequence-specific DNA binding by the C-terminal basic region; peripheral to menin's scaffold/coregulator role. Supporting Evidence: PMID:15331604 It also binds a variety of DNA structures, including Y-structures, branched structures, and 4-way junction structures. PMID:15331604 These results indicate that menin not only binds to DNA in a non-sequence specific fashion |
| GO:0000781 chromosome, telomeric region | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara transfer from mouse menin, whose source is an IDA (PMID:12203793) showing menin at telomeres of meiotic cells. Reason: Telomere localization was seen only in meiotic cells and explicitly not in somatic cells; the localization is plausible for human but is restricted and peripheral. Supporting Evidence: PMID:12203793 We used immunocytochemistry to explore its role in meiosis and found that it localizes exclusively at telomeres. PMID:12203793 menin does not specifically associate with telomeres in somatic cells |
| GO:0000781 chromosome, telomeric region | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Curator-judged similarity transfer from mouse menin meiotic telomere localization. Reason: As for the IEA row: meiosis-restricted localization, not seen in somatic cells; kept as non-core. Supporting Evidence: PMID:12203793 We used immunocytochemistry to explore its role in meiosis and found that it localizes exclusively at telomeres. PMID:12203793 menin does not specifically associate with telomeres in somatic cells |
| GO:0000785 chromatin | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT propagation of chromatin localization across the menin family. Reason: Menin acts on chromatin at target loci with MLL1/MLL2 and LEDGF; well supported by ChIP and fractionation. Supporting Evidence: PMID:12874027 menin is localized to chromatin and nuclear matrix, and the association with nuclear matrix is enhanced by gamma-irradiation PMID:15640349 Menin activates transcription by means of a mechanism involving recruitment of MLL to the p27Kip1 and p18Ink4c promoters and coding regions. |
| GO:0000785 chromatin | IDA PMID:12837246 Multiple tumor suppressor pathways negatively regulate telom... | ACCEPT | Summary: Lin and Elledge describe menin as a direct repressor of the hTERT promoter, implying promoter-bound chromatin localization. Reason: Chromatin association of menin is well established; consistent with core function as a chromatin-bound coregulator. Supporting Evidence: PMID:12837246 The third, the tumor suppressor Menin, is a direct repressor of hTERT. file:human/MEN1/MEN1-uniprot.txt Binds to the TERT promoter and represses telomerase expression. |
| GO:0000785 chromatin | IDA PMID:12874027 Menin associates with FANCD2, a protein involved in repair o... | ACCEPT | Summary: Jin et al. found menin in chromatin and nuclear-matrix fractions. Reason: Direct fractionation evidence for chromatin localization. Supporting Evidence: PMID:12874027 menin is localized to chromatin and nuclear matrix, and the association with nuclear matrix is enhanced by gamma-irradiation |
| GO:0000976 transcription cis-regulatory region binding | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: PAINT propagation of transcription cis-regulatory region binding, seeded by mouse and human ChIP-based annotations. Reason: Menin is found at specific regulatory regions (Hoxc8, CDKN1B, CDKN2C, GATA3) by ChIP, but its own DNA binding is sequence-independent and its targeting is attributed to DNA-binding partners (JunD, c-Myb/GATA-3, SMADs) and to the MLL1-LEDGF chromatin anchor. GO:0000976 asserts binding to a specific regulatory DNA sequence by the gene product, which overstates what menin does; its activity at these regions is better described by transcription coactivator/corepressor and adaptor terms. The IBA node inherits this interpretation of ChIP occupancy rather than evidence of sequence-specific binding. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: PANTHER:PTN000976222 SOURCE WEAK OR INFERRED Menin-family ancestral node. Menin descendants carry this term from ChIP occupancy at target loci; the related biology (recruitment to regulatory regions) is sound, but the term assigns sequence-specific regulatory-DNA binding to a protein that binds DNA only sequence-independently and is targeted by partners. MGI:MGI:1316736 SOURCE WEAK OR INFERRED Mouse menin descendant evidence is locus-occupancy (ChIP) data, which shows a menin-containing complex at regulatory regions rather than sequence-specific DNA binding by menin. UniProtKB:O00255 SOURCE WEAK OR INFERRED Human menin ChIP-based annotations (e.g. PMID:20484083) are among the descendant evidences; the same scoping issue applies. Supporting Evidence: PMID:15640349 Menin has been shown to bind nonspecifically to DNA; however, the mechanisms responsible for its recruitment to specific chromosomal sites are not known. PMID:15331604 These results indicate that menin not only binds to DNA in a non-sequence specific fashion PMID:14992727 Chromatin immunoprecipitation experiments reveal that menin is bound to the Hoxc8 locus. |
| GO:0000976 transcription cis-regulatory region binding | IDA PMID:20484083 c-Myb, Menin, GATA-3, and MLL form a dynamic transcription c... | MARK AS OVER ANNOTATED | Summary: Nakata et al. found menin in a c-Myb/GATA-3/MLL complex at the GATA-3 promoter in human T cells. Reason: Menin is found at specific regulatory regions (Hoxc8, CDKN1B, CDKN2C, GATA3) by ChIP, but its own DNA binding is sequence-independent and its targeting is attributed to DNA-binding partners (JunD, c-Myb/GATA-3, SMADs) and to the MLL1-LEDGF chromatin anchor. GO:0000976 asserts binding to a specific regulatory DNA sequence by the gene product, which overstates what menin does; its activity at these regions is better described by transcription coactivator/corepressor and adaptor terms. In this paper the DNA-binding components are c-Myb and GATA-3; menin is the bridging component. Supporting Evidence: PMID:20484083 c-Myb, GATA-3, and Menin form a core transcription complex that regulates GATA-3 expression PMID:20484083 we have recently shown that Menin recruits c-Myb into the MLL complex in human leukemia cells PMID:15640349 Menin has been shown to bind nonspecifically to DNA; however, the mechanisms responsible for its recruitment to specific chromosomal sites are not known. |
| GO:0000976 transcription cis-regulatory region binding | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl Compara transfer from mouse menin (source: UniProt IDA from PMID:14992727, Hoxc8 ChIP). Reason: Menin is found at specific regulatory regions (Hoxc8, CDKN1B, CDKN2C, GATA3) by ChIP, but its own DNA binding is sequence-independent and its targeting is attributed to DNA-binding partners (JunD, c-Myb/GATA-3, SMADs) and to the MLL1-LEDGF chromatin anchor. GO:0000976 asserts binding to a specific regulatory DNA sequence by the gene product, which overstates what menin does; its activity at these regions is better described by transcription coactivator/corepressor and adaptor terms. Supporting Evidence: PMID:14992727 Chromatin immunoprecipitation experiments reveal that menin is bound to the Hoxc8 locus. PMID:15640349 Menin has been shown to bind nonspecifically to DNA; however, the mechanisms responsible for its recruitment to specific chromosomal sites are not known. PMID:15331604 These results indicate that menin not only binds to DNA in a non-sequence specific fashion |
| GO:0001216 DNA-binding transcription activator activity | IEA GO_REF:0000107 | MODIFY | Summary: Ensembl Compara transfer of DNA-binding transcription activator activity from mouse menin O88559. The mouse source row is GO:0001216 IDA PMID:14992727 assigned by UniProt (QuickGO, 2026-10-24); Hughes et al. 2004 show menin in an MLL2/Ash2L H3K4 methyltransferase complex, ChIP at Hoxc8, and loss of Hoxc6/Hoxc8 expression in Men1-null cells. Reason: Menin has no sequence-specific DNA-binding domain. Its only demonstrated direct DNA binding is sequence-independent (dsDNA and branched structures, via basic NLS residues), and locus targeting depends on DNA-binding partners and the MLL1-LEDGF chromatin anchor. The source paper shows menin activates Hox transcription by recruiting histone methyltransferase activity, i.e. a coactivator, not a DNA-binding transcription factor. The essence (menin activates transcription of target genes) is sound, so the term is replaced by transcription coactivator activity, which captures menin's activity in MLL-dependent activation of Hox, CDKN1B/CDKN2C and GATA3. Proposed replacements: transcription coactivator activity Supporting Evidence: PMID:14992727 menin activates the transcription of differentiation-regulating genes by covalent histone modification PMID:14992727 Chromatin immunoprecipitation experiments reveal that menin is bound to the Hoxc8 locus. PMID:15640349 Menin has been shown to bind nonspecifically to DNA; however, the mechanisms responsible for its recruitment to specific chromosomal sites are not known. PMID:15331604 These results indicate that menin not only binds to DNA in a non-sequence specific fashion PMID:15640349 Menin activates transcription by means of a mechanism involving recruitment of MLL to the p27Kip1 and p18Ink4c promoters and coding regions. PMID:20484083 c-Myb, GATA-3, and Menin form a core transcription complex that regulates GATA-3 expression |
| GO:0002076 osteoblast development | IGI PMID:15563473 Menin suppresses osteoblast differentiation by antagonizing ... | KEEP AS NON CORE | Summary: Naito et al. studied menin-JunD interplay in mouse MC3T3-E1 osteoblastic cells; menin restrains later osteoblast maturation by antagonizing JunD. Reason: A tissue-specific consequence of menin's JunD corepressor activity; kept as non-core. The full text was not available, so the curator's IGI judgement is deferred to. Supporting Evidence: PMID:15563473 the data suggest that menin suppresses osteoblast maturation, in part, by inhibiting the differentiation actions of JunD |
| GO:0003677 DNA binding | IEA GO_REF:0000107 | MODIFY | Summary: Ensembl Compara transfer of generic DNA binding from mouse menin. Reason: Menin does bind DNA directly, but the evidence specifies double-stranded DNA binding in a sequence-independent manner (human IDA, PMID:15331604), a term this gene already carries. The generic term is refined to that descendant. Proposed replacements: double-stranded DNA binding Supporting Evidence: PMID:15331604 Here we show that menin directly binds to double stranded DNA in a sequence-independent manner. PMID:15331604 These results indicate that menin not only binds to DNA in a non-sequence specific fashion |
| GO:0003682 chromatin binding | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT propagation of chromatin binding across the menin family. Reason: Menin binds chromatin at target loci, both through direct non-specific DNA contacts and through the menin-MLL1-LEDGF ternary complex; this is as specific as the evidence supports. Supporting Evidence: PMID:15640349 Menin activates transcription by means of a mechanism involving recruitment of MLL to the p27Kip1 and p18Ink4c promoters and coding regions. PMID:22327296 menin promotes gene transcription by binding the transcription activator MLL1 through the peptide pocket while still interacting with the chromatin-anchoring protein LEDGF at a distinct surface formed by both menin and MLL1. PMID:15331604 Here we show that menin directly binds to double stranded DNA in a sequence-independent manner. |
| GO:0003682 chromatin binding | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara transfer of chromatin binding from mouse menin (source MGI IDAs, e.g. PMID:15640349). Reason: Consistent with the IBA row and with ChIP evidence of menin at target loci. Supporting Evidence: PMID:15640349 Menin activates transcription by means of a mechanism involving recruitment of MLL to the p27Kip1 and p18Ink4c promoters and coding regions. PMID:12874027 menin is localized to chromatin and nuclear matrix, and the association with nuclear matrix is enhanced by gamma-irradiation |
| GO:0003690 double-stranded DNA binding | IDA PMID:15331604 Direct binding of DNA by tumor suppressor menin. | ACCEPT | Summary: La et al. showed purified menin binds dsDNA, but not ssDNA, in a sequence-independent manner through basic residues of its two C-terminal NLSs; disease truncations that lose DNA binding fail to repress proliferation. Reason: Well-supported direct activity of menin. It is non-sequence-specific and distinct from transcription factor activity, but it is the precise description of menin's direct DNA contact. Supporting Evidence: PMID:15331604 Here we show that menin directly binds to double stranded DNA in a sequence-independent manner. PMID:15331604 These results indicate that menin not only binds to DNA in a non-sequence specific fashion PMID:15331604 these MEN1 disease-related menin mutants also fail to repress cell proliferation as well as cell cycle progression at the G2/M phase |
| GO:0005515 protein binding | IPI O00255-2 PMID:11302744 Menin, a gene product responsible for multiple endocrine neo... | REMOVE | Summary: Yeast two-hybrid and GST pull-down interaction of menin with nm23 (NME1). Reason: Generic protein binding is uninformative about molecular function. The reported interaction is not disputed; removal only reflects that GO:0005515 carries no functional information and the cited work does not establish a more specific activity for menin in this interaction. Supporting Evidence: PMID:11302744 we identified a putative tumor metastasis suppressor nm23/nucleoside diphosphate (NDP) kinase as an associated protein |
| GO:0005515 protein binding | IPI PMID:11500056 Menin interacts directly with the homeobox-containing protei... | REMOVE | Summary: Yeast two-hybrid interaction of menin with the homeobox protein Pem. Reason: Generic protein binding is uninformative about molecular function. The reported interaction is not disputed; removal only reflects that GO:0005515 carries no functional information and the cited work does not establish a more specific activity for menin in this interaction. Supporting Evidence: PMID:11500056 Both proteins colocalised predominantly in the nucleus but were occasionally also found in the cytoplasm. |
| GO:0005515 protein binding | IPI PMID:11526476 The tumor suppressor protein menin interacts with NF-kappaB ... | MODIFY | Summary: Heppner et al. showed menin binds NF-kB p50, p52 and p65 directly and represses p65-mediated transactivation on NF-kB sites. Reason: The paper supports a functional consequence of the binding: menin represses transcription activated by the DNA-binding NF-kB subunits. Transcription corepressor activity captures this better than generic protein binding. Proposed replacements: transcription corepressor activity Supporting Evidence: PMID:11526476 Menin represses p65-mediated transcriptional activation on NF-kappaB sites in a dose-dependent and specific manner. file:human/MEN1/MEN1-uniprot.txt Represses JUND-mediated transcriptional activation on AP1 sites, as well as that mediated by NFKB subunit RELA. |
| GO:0005515 protein binding | IPI PMID:11526476 The tumor suppressor protein menin interacts with NF-kappaB ... | MODIFY | Summary: Heppner et al. showed menin binds NF-kB p50, p52 and p65 directly and represses p65-mediated transactivation on NF-kB sites. Reason: The paper supports a functional consequence of the binding: menin represses transcription activated by the DNA-binding NF-kB subunits. Transcription corepressor activity captures this better than generic protein binding. Proposed replacements: transcription corepressor activity Supporting Evidence: PMID:11526476 Menin represses p65-mediated transcriptional activation on NF-kappaB sites in a dose-dependent and specific manner. file:human/MEN1/MEN1-uniprot.txt Represses JUND-mediated transcriptional activation on AP1 sites, as well as that mediated by NFKB subunit RELA. |
| GO:0005515 protein binding | IPI PMID:11526476 The tumor suppressor protein menin interacts with NF-kappaB ... | MODIFY | Summary: Heppner et al. showed menin binds NF-kB p50, p52 and p65 directly and represses p65-mediated transactivation on NF-kB sites. Reason: The paper supports a functional consequence of the binding: menin represses transcription activated by the DNA-binding NF-kB subunits. Transcription corepressor activity captures this better than generic protein binding. Proposed replacements: transcription corepressor activity Supporting Evidence: PMID:11526476 Menin represses p65-mediated transcriptional activation on NF-kappaB sites in a dose-dependent and specific manner. file:human/MEN1/MEN1-uniprot.txt Represses JUND-mediated transcriptional activation on AP1 sites, as well as that mediated by NFKB subunit RELA. |
| GO:0005515 protein binding | IPI O00255-2 PMID:11526476 The tumor suppressor protein menin interacts with NF-kappaB ... | MODIFY | Summary: Heppner et al. showed menin binds NF-kB p50, p52 and p65 directly and represses p65-mediated transactivation on NF-kB sites. Reason: The paper supports a functional consequence of the binding: menin represses transcription activated by the DNA-binding NF-kB subunits. Transcription corepressor activity captures this better than generic protein binding. Proposed replacements: transcription corepressor activity Supporting Evidence: PMID:11526476 Menin represses p65-mediated transcriptional activation on NF-kappaB sites in a dose-dependent and specific manner. file:human/MEN1/MEN1-uniprot.txt Represses JUND-mediated transcriptional activation on AP1 sites, as well as that mediated by NFKB subunit RELA. |
| GO:0005515 protein binding | IPI O00255-2 PMID:11526476 The tumor suppressor protein menin interacts with NF-kappaB ... | MODIFY | Summary: Heppner et al. showed menin binds NF-kB p50, p52 and p65 directly and represses p65-mediated transactivation on NF-kB sites. Reason: The paper supports a functional consequence of the binding: menin represses transcription activated by the DNA-binding NF-kB subunits. Transcription corepressor activity captures this better than generic protein binding. Proposed replacements: transcription corepressor activity Supporting Evidence: PMID:11526476 Menin represses p65-mediated transcriptional activation on NF-kappaB sites in a dose-dependent and specific manner. file:human/MEN1/MEN1-uniprot.txt Represses JUND-mediated transcriptional activation on AP1 sites, as well as that mediated by NFKB subunit RELA. |
| GO:0005515 protein binding | IPI PMID:12509449 The 32-kilodalton subunit of replication protein A interacts... | REMOVE | Summary: Menin binds RPA2 directly but had no detectable effect on RPA-DNA binding. Reason: Generic protein binding is uninformative about molecular function. The reported interaction is not disputed; removal only reflects that GO:0005515 carries no functional information and the cited work does not establish a more specific activity for menin in this interaction. Supporting Evidence: PMID:12509449 menin had no detectable effect on RPA-DNA binding in vitro |
| GO:0005515 protein binding | IPI PMID:12874027 Menin associates with FANCD2, a protein involved in repair o... | REMOVE | Summary: Menin associates with FANCD2; the association increases after gamma irradiation. Reason: Generic protein binding is uninformative about molecular function. The reported interaction is not disputed; removal only reflects that GO:0005515 carries no functional information and the cited work does not establish a more specific activity for menin in this interaction. Supporting Evidence: PMID:12874027 The interaction between menin and FANCD2 is enhanced by gamma-irradiation. |
| GO:0005515 protein binding | IPI PMID:14508515 Menin, a tumor suppressor, associates with nonmuscle myosin ... | REMOVE | Summary: Menin associates with nonmuscle myosin II-A heavy chain and colocalises with it at the cleavage furrow. Reason: Generic protein binding is uninformative about molecular function. The reported interaction is not disputed; removal only reflects that GO:0005515 carries no functional information and the cited work does not establish a more specific activity for menin in this interaction. Supporting Evidence: PMID:14508515 menin was seen to colocalize with this myosin isoform in the cleavage furrow of dividing cells by indirect immunofluoresence |
| GO:0005515 protein binding | IPI PMID:14992727 Menin associates with a trithorax family histone methyltrans... | REMOVE | Summary: Menin co-purifies with MLL-family H3K4 methyltransferase complexes. Reason: Generic protein binding is uninformative about molecular function. The reported interaction is not disputed; removal only reflects that GO:0005515 carries no functional information and the cited work does not establish a more specific activity for menin in this interaction. Supporting Evidence: PMID:14992727 menin is associated with a histone methyltransferase complex containing two trithorax family proteins, MLL2 and Ash2L |
| GO:0005515 protein binding | IPI PMID:14992727 Menin associates with a trithorax family histone methyltrans... | REMOVE | Summary: Menin co-purifies with RBBP5 as part of the MLL2/Ash2L methyltransferase complex. Reason: Generic protein binding is uninformative about molecular function. The reported interaction is not disputed; removal only reflects that GO:0005515 carries no functional information and the cited work does not establish a more specific activity for menin in this interaction. Supporting Evidence: PMID:14992727 menin is associated with a histone methyltransferase complex containing two trithorax family proteins, MLL2 and Ash2L |
| GO:0005515 protein binding | IPI PMID:14992727 Menin associates with a trithorax family histone methyltrans... | REMOVE | Summary: Menin co-purifies with ASH2L as part of the MLL2 methyltransferase complex. Reason: Generic protein binding is uninformative about molecular function. The reported interaction is not disputed; removal only reflects that GO:0005515 carries no functional information and the cited work does not establish a more specific activity for menin in this interaction. Supporting Evidence: PMID:14992727 menin is associated with a histone methyltransferase complex containing two trithorax family proteins, MLL2 and Ash2L |
| GO:0005515 protein binding | IPI PMID:15199122 Leukemia proto-oncoprotein MLL forms a SET1-like histone met... | REMOVE | Summary: Menin is a component of the 1-MDa MLL1 complex purified by Yokoyama et al. Reason: Generic protein binding is uninformative about molecular function. The reported interaction is not disputed; removal only reflects that GO:0005515 carries no functional information and the cited work does not establish a more specific activity for menin in this interaction. Supporting Evidence: PMID:15199122 Menin, a product of the MEN1 tumor suppressor gene, is also a component of the 1-MDa MLL complex. |
| GO:0005515 protein binding | IPI PMID:15960975 Physical association and coordinate function of the H3 K4 me... | REMOVE | Summary: Menin co-purifies with WDR5 in the MLL1-MOF complex. Reason: Generic protein binding is uninformative about molecular function. The reported interaction is not disputed; removal only reflects that GO:0005515 carries no functional information and the cited work does not establish a more specific activity for menin in this interaction. |
| GO:0005515 protein binding | IPI PMID:16951149 Multiple endocrine neoplasia type 1 interacts with forkhead ... | REMOVE | Summary: Menin interacts with the forkhead factor CHES1 (FOXN3) in a DNA damage S-phase checkpoint pathway. Reason: Generic protein binding is uninformative about molecular function. The reported interaction is not disputed; removal only reflects that GO:0005515 carries no functional information and the cited work does not establish a more specific activity for menin in this interaction. Supporting Evidence: PMID:16951149 Our data indicate that menin is involved in the activation of S-phase arrest in response to ionizing radiation. |
| GO:0005515 protein binding | IPI PMID:20484083 c-Myb, Menin, GATA-3, and MLL form a dynamic transcription c... | MODIFY | Summary: Nakata et al. show menin assembles with c-Myb and GATA-3 into a core complex that activates GATA-3 expression and recruits MLL. Reason: c-Myb is a DNA-binding transcription factor; the paper shows the menin-containing complex activates GATA-3 transcription and that menin recruits c-Myb to MLL. This is transcription coactivator activity. Proposed replacements: transcription coactivator activity Supporting Evidence: PMID:20484083 c-Myb, GATA-3, and Menin form a core transcription complex that regulates GATA-3 expression PMID:20484083 we have recently shown that Menin recruits c-Myb into the MLL complex in human leukemia cells |
| GO:0005515 protein binding | IPI PMID:20484083 c-Myb, Menin, GATA-3, and MLL form a dynamic transcription c... | MODIFY | Summary: Menin co-immunoprecipitates with GATA-3 in a c-Myb/GATA-3/menin/MLL complex at the GATA-3 locus. Reason: GATA-3 is a DNA-binding transcription factor, and the menin-containing complex activates GATA-3 transcription; transcription coactivator activity is the informative replacement. Proposed replacements: transcription coactivator activity Supporting Evidence: PMID:20484083 c-Myb, GATA-3, and Menin form a core transcription complex that regulates GATA-3 expression PMID:20484083 Immunoprecipitation revealed that the c-Myb/GATA-3 complex contained Menin and mixed lineage leukemia (MLL). |
| GO:0005515 protein binding | IPI O00255-2 PMID:22327296 The same pocket in menin binds both MLL and JUND but has opp... | MODIFY | Summary: Crystal structure of menin bound to the JunD menin-binding motif; menin blocks JNK-mediated JunD phosphorylation and suppresses JunD-induced transcription. Reason: The binding represses transcription driven by the DNA-binding factor JunD, i.e. transcription corepressor activity. Proposed replacements: transcription corepressor activity Supporting Evidence: PMID:22327296 The menin-JUND interaction blocks JUN N-terminal kinase (JNK)-mediated JUND phosphorylation and suppresses JUND-induced transcription. PMID:9989505 Menin repressed transcriptional activation mediated by JunD fused to the Gal4 DNA-binding domain from a Gal4 responsive reporter, or by JunD from an AP1-responsive reporter. |
| GO:0005515 protein binding | IPI O00255-2 PMID:22327296 The same pocket in menin binds both MLL and JUND but has opp... | MODIFY | Summary: Crystal structures of menin with MLL1 and with an MLL1-LEDGF heterodimer show that menin binds MLL1 in a deep pocket and assembles a menin-MLL1-LEDGF ternary complex. Reason: The paper explicitly describes menin as a scaffold bringing MLL1 and the chromatin anchor LEDGF together; protein-macromolecule adaptor activity is the informative function. Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:22327296 Our findings also provides concrete evidence that menin acts as a scaffold protein to assemble a menin-MLL1-LEDGF ternary complex to coordinating gene transcription PMID:22327296 menin promotes gene transcription by binding the transcription activator MLL1 through the peptide pocket while still interacting with the chromatin-anchoring protein LEDGF at a distinct surface formed by both menin and MLL1. |
| GO:0005515 protein binding | IPI PMID:22936661 Structural insights into inhibition of the bivalent menin-ML... | REMOVE | Summary: Structure of menin with the menin-MLL inhibitor MI-2; documents the bivalent menin-MLL interaction. Reason: Generic protein binding is uninformative about molecular function. The reported interaction is not disputed; removal only reflects that GO:0005515 carries no functional information and the cited work does not establish a more specific activity for menin in this interaction. Supporting Evidence: PMID:22936661 MLL interacts with menin in a bivalent mode involving 2 N-terminal fragments of MLL. |
| GO:0005515 protein binding | IPI PMID:23784080 HTLV-1 bZIP factor impedes the menin tumor suppressor and up... | MODIFY | Summary: Borowiak et al. show JunD and menin form a repressor complex on the hTERT promoter. Reason: The binding represses JunD-dependent transcription; transcription corepressor activity is the informative replacement. Proposed replacements: transcription corepressor activity Supporting Evidence: PMID:23784080 we report that JunD and menin form a repressor complex of hTERT transcription in HBZ-negative cells |
| GO:0005515 protein binding | IPI PMID:24981860 Human-chromatin-related protein interactions identify a deme... | REMOVE | Summary: High-throughput AP-MS map of chromatin-related proteins recovering menin with WDR5. Reason: Generic protein binding is uninformative about molecular function. The reported interaction is not disputed; removal only reflects that GO:0005515 carries no functional information and the cited work does not establish a more specific activity for menin in this interaction. |
| GO:0005515 protein binding | IPI PMID:25305204 The same site on the integrase-binding domain of lens epithe... | REMOVE | Summary: Study of the LEDGF IBD-MLL interaction in the menin-MLL-LEDGF complex. Reason: Generic protein binding is uninformative about molecular function. The reported interaction is not disputed; removal only reflects that GO:0005515 carries no functional information and the cited work does not establish a more specific activity for menin in this interaction. Supporting Evidence: PMID:25305204 LEDGF associates with mixed-lineage leukemia (MLL) fusion proteins and menin and is required for leukemic transformation. |
| GO:0005515 protein binding | IPI PMID:27705803 A High-Density Map for Navigating the Human Polycomb Complex... | REMOVE | Summary: High-throughput Polycomb complexome AP-MS recovering menin with WDR5. Reason: Generic protein binding is uninformative about molecular function. The reported interaction is not disputed; removal only reflects that GO:0005515 carries no functional information and the cited work does not establish a more specific activity for menin in this interaction. |
| GO:0005515 protein binding | IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei... | REMOVE | Summary: High-throughput screen for mutation-directed neo-protein-protein interactions recording menin with BRAF. Reason: Generic protein binding is uninformative about molecular function. The reported interaction is not disputed; removal only reflects that GO:0005515 carries no functional information and the cited work does not establish a more specific activity for menin in this interaction. |
| GO:0005515 protein binding | IPI PMID:9989505 Menin interacts with the AP1 transcription factor JunD and r... | MODIFY | Summary: Agarwal et al. identified JunD as a direct menin partner; menin represses JunD-activated transcription. Reason: The interaction represses transcription driven by JunD, a DNA-binding AP-1 factor; transcription corepressor activity is the informative replacement. Proposed replacements: transcription corepressor activity Supporting Evidence: PMID:9989505 Menin repressed transcriptional activation mediated by JunD fused to the Gal4 DNA-binding domain from a Gal4 responsive reporter, or by JunD from an AP1-responsive reporter. |
| GO:0005515 protein binding | IPI PMID:9989505 Menin interacts with the AP1 transcription factor JunD and r... | REMOVE | Summary: Interaction with HSPE1 recorded from the JunD yeast two-hybrid paper. Reason: Generic protein binding is uninformative about molecular function. The reported interaction is not disputed; removal only reflects that GO:0005515 carries no functional information and the cited work does not establish a more specific activity for menin in this interaction. |
| GO:0005634 nucleus | IDA PMID:14508515 Menin, a tumor suppressor, associates with nonmuscle myosin ... | ACCEPT | Summary: Obungu et al. observed menin in the nucleus of interphase HeLa cells and at the cleavage furrow in dividing cells. Reason: Menin is a predominantly nuclear protein acting on chromatin; nucleus is a core location. Supporting Evidence: PMID:14508515 menin was seen to colocalize with this myosin isoform in the cleavage furrow of dividing cells by indirect immunofluoresence PMID:9465067 menin is located primarily in the nucleus |
| GO:0005634 nucleus | IDA PMID:15199122 Leukemia proto-oncoprotein MLL forms a SET1-like histone met... | ACCEPT | Summary: Menin purified from nuclear extracts as a component of the MLL complex. Reason: Menin is a predominantly nuclear protein acting on chromatin; nucleus is a core location. Supporting Evidence: PMID:15199122 Menin, a product of the MEN1 tumor suppressor gene, is also a component of the 1-MDa MLL complex. |
| GO:0005634 nucleus | IDA PMID:15640349 Menin and MLL cooperatively regulate expression of cyclin-de... | ACCEPT | Summary: Menin bound at target promoters and coding regions in the nucleus. Reason: Menin is a predominantly nuclear protein acting on chromatin; nucleus is a core location. Supporting Evidence: PMID:15640349 Menin activates transcription by means of a mechanism involving recruitment of MLL to the p27Kip1 and p18Ink4c promoters and coding regions. |
| GO:0005634 nucleus | IDA PMID:17500065 PTIP associates with MLL3- and MLL4-containing histone H3 ly... | ACCEPT | Summary: Menin detected in nuclear extracts as a subunit of MLL1/MLL2 complexes. Reason: Menin is a predominantly nuclear protein acting on chromatin; nucleus is a core location. Supporting Evidence: PMID:17500065 Menin is shared by MLL and MLL2 complexes only |
| GO:0005634 nucleus | IDA PMID:9465067 Menin, the product of the MEN1 gene, is a nuclear protein. | ACCEPT | Summary: Guru et al. showed menin is primarily nuclear and mapped two C-terminal NLSs. Reason: Menin is a predominantly nuclear protein acting on chromatin; nucleus is a core location. Supporting Evidence: PMID:9465067 menin is located primarily in the nucleus |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Combined automated annotation (InterPro menin family, UniProt subcellular location). Reason: Consistent with the experimental evidence that menin is primarily nuclear. Supporting Evidence: PMID:9465067 menin is located primarily in the nucleus file:human/MEN1/MEN1-uniprot.txt SUBCELLULAR LOCATION: Nucleus |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Human Protein Atlas immunofluorescence localization to the nucleoplasm. Reason: Consistent with menin's nuclear, chromatin-associated function. Supporting Evidence: PMID:9465067 menin is located primarily in the nucleus |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2186643 | ACCEPT | Summary: Reactome places menin in the nucleoplasm in reactions with MLL1/MLL2 complexes, LEDGF, SMAD or beta-catenin transcription complexes. Reason: Nucleoplasmic localization is consistent with menin's nuclear chromatin-associated function. Supporting Evidence: Reactome:R-HSA-2186643 binds SMAD2/3:SMAD4 heterotrimer through interaction with SMAD3 PMID:9465067 menin is located primarily in the nucleus |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-3364014 | ACCEPT | Summary: Reactome places menin in the nucleoplasm in reactions with MLL1/MLL2 complexes, LEDGF, SMAD or beta-catenin transcription complexes. Reason: Nucleoplasmic localization is consistent with menin's nuclear chromatin-associated function. Supporting Evidence: Reactome:R-HSA-3364014 A number of SET1-type complex proteins are pulled down from HeLa and SW480 extracts by a fragment of beta-catenin PMID:9465067 menin is located primarily in the nucleus |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-3364026 | ACCEPT | Summary: Reactome places menin in the nucleoplasm in reactions with MLL1/MLL2 complexes, LEDGF, SMAD or beta-catenin transcription complexes. Reason: Nucleoplasmic localization is consistent with menin's nuclear chromatin-associated function. Supporting Evidence: Reactome:R-HSA-3364026 The recruitment of SET1-type complex MLL2, in association with MEN1, at the MYC enhancer correlates with increased H3K4 trimethylation in vivo PMID:9465067 menin is located primarily in the nucleus |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-3364042 | ACCEPT | Summary: Reactome places menin in the nucleoplasm in reactions with MLL1/MLL2 complexes, LEDGF, SMAD or beta-catenin transcription complexes. Reason: Nucleoplasmic localization is consistent with menin's nuclear chromatin-associated function. Supporting Evidence: Reactome:R-HSA-3364026 The recruitment of SET1-type complex MLL2, in association with MEN1, at the MYC enhancer correlates with increased H3K4 trimethylation in vivo PMID:9465067 menin is located primarily in the nucleus |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9818682 | ACCEPT | Summary: Reactome places menin in the nucleoplasm in reactions with MLL1/MLL2 complexes, LEDGF, SMAD or beta-catenin transcription complexes. Reason: Nucleoplasmic localization is consistent with menin's nuclear chromatin-associated function. Supporting Evidence: Reactome:R-HSA-9818682 MEN1 (also known as Menin), a tumor suppressor protein mutated in multiple type I endocrine neoplasia, binds to the MLL2 complex. PMID:9465067 menin is located primarily in the nucleus |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9818937 | ACCEPT | Summary: Reactome places menin in the nucleoplasm in reactions with MLL1/MLL2 complexes, LEDGF, SMAD or beta-catenin transcription complexes. Reason: Nucleoplasmic localization is consistent with menin's nuclear chromatin-associated function. Supporting Evidence: Reactome:R-HSA-9818937 MEN1 (also known as Menin) associates with the MLL1 complex by binding to the N-terminal region of KMT2A PMID:9465067 menin is located primarily in the nucleus |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9818954 | ACCEPT | Summary: Reactome places menin in the nucleoplasm in reactions with MLL1/MLL2 complexes, LEDGF, SMAD or beta-catenin transcription complexes. Reason: Nucleoplasmic localization is consistent with menin's nuclear chromatin-associated function. Supporting Evidence: Reactome:R-HSA-9818954 PSIP1 (also known as LEDGF) conjointly binds to KMT2A (also known as MLL1 or MLL) and MEN1 (menin) PMID:9465067 menin is located primarily in the nucleus |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9821235 | ACCEPT | Summary: Reactome places menin in the nucleoplasm in reactions with MLL1/MLL2 complexes, LEDGF, SMAD or beta-catenin transcription complexes. Reason: Nucleoplasmic localization is consistent with menin's nuclear chromatin-associated function. Supporting Evidence: Reactome:R-HSA-9821235 Both HCFC1 (also known as Host cell factor 1 or HCF1) and HCFC2 (also known as Host cell factor 2 or HCF2) can associate with the complex of MLL1 and MEN1 PMID:9465067 menin is located primarily in the nucleus |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9821902 | ACCEPT | Summary: Reactome places menin in the nucleoplasm in reactions with MLL1/MLL2 complexes, LEDGF, SMAD or beta-catenin transcription complexes. Reason: Nucleoplasmic localization is consistent with menin's nuclear chromatin-associated function. Supporting Evidence: Reactome:R-HSA-9821902 PSIP1 (also known as LEDGF) is co-immunoprecipitated with MEN1-bound MLL2 complexes PMID:9465067 menin is located primarily in the nucleus |
| GO:0005737 cytoplasm | IDA PMID:11500056 Menin interacts directly with the homeobox-containing protei... | KEEP AS NON CORE | Summary: Menin and Pem colocalised mostly in the nucleus but occasionally in the cytoplasm. Reason: A minor cytoplasmic pool is reported; menin's function is nuclear, so this is non-core. Supporting Evidence: PMID:11500056 Both proteins colocalised predominantly in the nucleus but were occasionally also found in the cytoplasm. |
| GO:0005737 cytoplasm | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara transfer of cytoplasm from mouse menin. Reason: A minor cytoplasmic pool is plausible; non-core relative to the nuclear function. Supporting Evidence: PMID:11500056 Both proteins colocalised predominantly in the nucleus but were occasionally also found in the cytoplasm. PMID:9465067 menin is located primarily in the nucleus |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-8952289 | REMOVE | Summary: Reactome's generic reaction 'FAM20C phosphorylates FAM20C substrates' places all listed substrates, including menin, in the ER lumen. Reason: FAM20C acts on secreted proteins in the secretory pathway. Menin is a nuclear protein without a signal peptide and no study localises it to the ER lumen; the location is an artifact of including menin in a generic substrate set. Supporting Evidence: Reactome:R-HSA-8952289 Extracellular serine/threonine protein kinase FAM20C is an extracellular kinase that can phosphorylate a broad range of secreted protein. PMID:9465067 menin is located primarily in the nucleus |
| GO:0005829 cytosol | IDA PMID:14508515 Menin, a tumor suppressor, associates with nonmuscle myosin ... | KEEP AS NON CORE | Summary: Menin colocalises with nonmuscle myosin II-A in the cleavage furrow of dividing cells. Reason: Reflects a minor, cell-cycle-stage-specific extranuclear pool; non-core. Supporting Evidence: PMID:14508515 menin was seen to colocalize with this myosin isoform in the cleavage furrow of dividing cells by indirect immunofluoresence |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5672304 | KEEP AS NON CORE | Summary: Reactome places menin in the cytosol as corroborating IQGAP1 binding to the E-cadherin-catenin complex. Reason: Minor extranuclear role; non-core. Supporting Evidence: Reactome:R-HSA-5672304 this interaction is corroborated by menin (MEN1) |
| GO:0006281 DNA repair | NAS PMID:12874027 Menin associates with FANCD2, a protein involved in repair o... | MARK AS OVER ANNOTATED | Summary: Jin et al. proposed that menin acts in DNA repair with FANCD2, based on association with FANCD2 and DNA-damage sensitivity of Men1-null MEFs. Reason: Association with FANCD2 and damage sensitivity establish a role in the DNA damage response but do not show menin performing a DNA repair step; the NAS row overstates the evidence. DNA damage response is kept instead. Supporting Evidence: PMID:12874027 The interaction between menin and FANCD2 is enhanced by gamma-irradiation. PMID:12874027 loss of menin expression in mouse embryonic fibroblasts leads to increased sensitivity to DNA damage file:human/MEN1/MEN1-uniprot.txt May be involved in DNA repair. |
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT propagation of regulation of transcription by RNA polymerase II. Reason: Menin both activates (with MLL1/MLL2) and represses (with JunD, NF-kB) Pol II transcription, so the bidirectional parent term is an apt summary of its core process role at the family level; the directional children are also annotated. Supporting Evidence: PMID:22327296 menin promotes gene transcription by binding the transcription activator MLL1 through the peptide pocket while still interacting with the chromatin-anchoring protein LEDGF at a distinct surface formed by both menin and MLL1. PMID:22327296 The menin-JUND interaction blocks JUN N-terminal kinase (JNK)-mediated JUND phosphorylation and suppresses JUND-induced transcription. |
| GO:0006974 DNA damage response | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT propagation of DNA damage response, seeded by Drosophila Mnn1 and human menin. Reason: Menin participates in DNA-damage responses (S-phase checkpoint with CHES1, chromatin relocalization after UV, FANCD2 association), conserved to Drosophila; this is a real but secondary role. Supporting Evidence: PMID:16951149 Our data indicate that menin is involved in the activation of S-phase arrest in response to ionizing radiation. PMID:16690369 Menin localizes to the chromatin after UV irradiation. |
| GO:0006974 DNA damage response | IDA PMID:16690369 Menin localizes to chromatin through an ATR-CHK1 mediated pa... | KEEP AS NON CORE | Summary: Farley et al. showed menin relocalizes to chromatin after UV damage through an ATR-CHK1-dependent pathway. Reason: Supports involvement in the DNA damage response; peripheral to the core coregulator function. Supporting Evidence: PMID:16690369 Menin localizes to the chromatin after UV irradiation. |
| GO:0009411 response to UV | IDA PMID:16690369 Menin localizes to chromatin through an ATR-CHK1 mediated pa... | KEEP AS NON CORE | Summary: Menin chromatin association increases after UV irradiation in HEK293 cells. Reason: Valid but peripheral cellular response. Supporting Evidence: PMID:16690369 Menin localizes to the chromatin after UV irradiation. |
| GO:0010332 response to gamma radiation | IDA PMID:12874027 Menin associates with FANCD2, a protein involved in repair o... | KEEP AS NON CORE | Summary: Gamma irradiation enhances menin-FANCD2 interaction and menin association with the nuclear matrix. Reason: Valid but peripheral cellular response. Supporting Evidence: PMID:12874027 The interaction between menin and FANCD2 is enhanced by gamma-irradiation. PMID:12874027 menin is localized to chromatin and nuclear matrix, and the association with nuclear matrix is enhanced by gamma-irradiation |
| GO:0016363 nuclear matrix | IDA PMID:12874027 Menin associates with FANCD2, a protein involved in repair o... | KEEP AS NON CORE | Summary: Menin fractionates with the nuclear matrix, more so after gamma irradiation. Reason: Biochemical fractionation evidence; secondary to chromatin as the functional location. Supporting Evidence: PMID:12874027 menin is localized to chromatin and nuclear matrix, and the association with nuclear matrix is enhanced by gamma-irradiation |
| GO:0017053 transcription repressor complex | IPI PMID:22327296 The same pocket in menin binds both MLL and JUND but has opp... | ACCEPT | Summary: Menin binds JunD and represses JunD-induced transcription. Reason: Menin forms a repressive complex with JunD (also at the hTERT promoter, PMID:23784080); consistent with its corepressor activity. Supporting Evidence: PMID:22327296 The menin-JUND interaction blocks JUN N-terminal kinase (JNK)-mediated JUND phosphorylation and suppresses JUND-induced transcription. PMID:23784080 we report that JunD and menin form a repressor complex of hTERT transcription in HBZ-negative cells |
| GO:0030511 positive regulation of transforming growth factor beta receptor signaling pathway | IMP PMID:11274402 Inactivation of menin, a Smad3-interacting protein, blocks t... | KEEP AS NON CORE | Summary: Antisense menin blocks TGF-beta growth inhibition and Smad3-induced transcription by reducing Smad3/4-DNA binding. Reason: Menin acts as a SMAD3 transcriptional cofactor; the effect on TGF-beta signaling is real but context-dependent. Supporting Evidence: PMID:11274402 menin inactivation by antisense RNA antagonizes transforming growth factor type beta-mediated cell growth inhibition PMID:11274402 Menin interacts with Smad3, and antisense menin suppresses transforming growth factor type beta-induced and Smad3-induced transcriptional activity |
| GO:0030674 protein-macromolecule adaptor activity | IDA PMID:20484083 c-Myb, Menin, GATA-3, and MLL form a dynamic transcription c... | ACCEPT | Summary: Nakata et al. show menin bridges c-Myb/GATA-3 and the MLL complex at the GATA-3 locus. Reason: Menin's defining molecular activity is as a scaffold/adaptor that links DNA-binding factors and the chromatin anchor LEDGF to MLL1/MLL2 methyltransferase complexes, shown structurally by Huang et al. Supporting Evidence: PMID:20484083 we have recently shown that Menin recruits c-Myb into the MLL complex in human leukemia cells PMID:22327296 Our findings also provides concrete evidence that menin acts as a scaffold protein to assemble a menin-MLL1-LEDGF ternary complex to coordinating gene transcription |
| GO:0032154 cleavage furrow | IDA PMID:14508515 Menin, a tumor suppressor, associates with nonmuscle myosin ... | KEEP AS NON CORE | Summary: Menin colocalises with NMHC II-A at the cleavage furrow of dividing cells. Reason: Immunofluorescence-based, minor extranuclear localization; non-core. Supporting Evidence: PMID:14508515 menin was seen to colocalize with this myosin isoform in the cleavage furrow of dividing cells by indirect immunofluoresence |
| GO:0032991 protein-containing complex | IDA PMID:15199122 Leukemia proto-oncoprotein MLL forms a SET1-like histone met... | MODIFY | Summary: Menin co-purifies as a component of the 1-MDa MLL complex. Reason: Protein-containing complex is uninformative; the paper identifies the specific complex, so the annotation is refined to MLL1 complex. Proposed replacements: MLL1 complex Supporting Evidence: PMID:15199122 Menin, a product of the MEN1 tumor suppressor gene, is also a component of the 1-MDa MLL complex. |
| GO:0035097 histone methyltransferase complex | IDA PMID:17500065 PTIP associates with MLL3- and MLL4-containing histone H3 ly... | MODIFY | Summary: Cho et al. note menin as a subunit specific to the MLL1 and MLL2 histone methyltransferase complexes, absent from the PTIP (MLL3/MLL4) complex. Reason: The generic histone methyltransferase complex term is correct but the evidence specifies the MLL1/2 complex, which menin also carries. Proposed replacements: MLL1/2 complex Supporting Evidence: PMID:17500065 Menin is shared by MLL and MLL2 complexes only |
| GO:0043565 sequence-specific DNA binding | IEA GO_REF:0000107 | REMOVE | Summary: Ensembl Compara transfer of sequence-specific DNA binding from mouse menin; the mouse source is an MGI IDA from PMID:20956546 (QuickGO, 2026-10-24), a ChIP study of the menin-trithorax complex across the GATA3 locus in Th2 cells. Reason: Menin binds DNA sequence-independently (random-sequence probes, competition by poly dI/dC) and is targeted to loci through partner proteins; occupancy of a whole gene locus by a menin-containing complex is not evidence of sequence-specific DNA binding by menin. Supporting Evidence: PMID:15331604 These results indicate that menin not only binds to DNA in a non-sequence specific fashion PMID:15640349 Menin has been shown to bind nonspecifically to DNA; however, the mechanisms responsible for its recruitment to specific chromosomal sites are not known. PMID:20956546 TrxG complex associated with the TrxG component Menin binds to the whole GATA3 gene locus |
| GO:0044665 MLL1/2 complex | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT propagation of MLL1/2 complex membership, conserved to Drosophila menin. Reason: Menin is a defining subunit of MLL1/MLL2 complexes. Supporting Evidence: PMID:17500065 Menin is shared by MLL and MLL2 complexes only PMID:14992727 menin is associated with a histone methyltransferase complex containing two trithorax family proteins, MLL2 and Ash2L |
| GO:0044665 MLL1/2 complex | IPI PMID:23508102 Quantitative dissection and stoichiometry determination of t... | ACCEPT | Summary: Quantitative AP-MS of human SET1/MLL complexes found menin in MLL1/MLL2 complexes at substoichiometric levels. Reason: Core complex membership; Reactome notes menin is 4- to 5-fold less abundant than KMT2A/KMT2B in these complexes. Supporting Evidence: PMID:23508102 We applied label-free quantitative mass spectrometry to determine the subunit composition and stoichiometry of the human SET1/MLL complexes. Reactome:R-HSA-9818937 MEN1 has 4- to 5-fold-lower abundance in MLL1/MLL2 complexes than KMT2A/KMT2B |
| GO:0045064 T-helper 2 cell differentiation | IDA PMID:20484083 c-Myb, Menin, GATA-3, and MLL form a dynamic transcription c... | KEEP AS NON CORE | Summary: Menin is part of the c-Myb/GATA-3/MLL complex that maintains GATA-3 expression during human Th2 cell development. Reason: Menin contributes coactivator/scaffold activity to GATA-3 transcription in Th2 cells; a context-specific process, kept as non-core. Supporting Evidence: PMID:20484083 c-Myb, GATA-3, and Menin form a core transcription complex that regulates GATA-3 expression PMID:20484083 MLL recruitment into the c-Myb-GATA-3-Menin complex was associated with the formation Th2 memory cells. |
| GO:0045668 negative regulation of osteoblast differentiation | IGI PMID:15563473 Menin suppresses osteoblast differentiation by antagonizing ... | KEEP AS NON CORE | Summary: Menin suppresses osteoblast maturation, in part by inhibiting JunD. Reason: Developmental, context-specific outcome of menin's JunD corepressor activity; non-core. Supporting Evidence: PMID:15563473 the data suggest that menin suppresses osteoblast maturation, in part, by inhibiting the differentiation actions of JunD |
| GO:0045786 negative regulation of cell cycle | IDA PMID:15331604 Direct binding of DNA by tumor suppressor menin. | KEEP AS NON CORE | Summary: Menin expression in Men1-null MEFs represses proliferation and shifts cells toward G2/M; DNA-binding-defective mutants fail to do so. Reason: Menin restrains proliferation, largely through transcriptional control of CDK inhibitors; a downstream, non-core process. Supporting Evidence: PMID:15331604 these MEN1 disease-related menin mutants also fail to repress cell proliferation as well as cell cycle progression at the G2/M phase PMID:15640349 Menin activates transcription by means of a mechanism involving recruitment of MLL to the p27Kip1 and p18Ink4c promoters and coding regions. |
| GO:0045815 transcription initiation-coupled chromatin remodeling | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT propagation of transcription initiation-coupled chromatin remodeling (histone modification at target genes). Reason: Menin scaffolds the MLL1/MLL2 H3K4 methyltransferase complexes onto target loci, contributing the targeting that the methylation step depends on. Supporting Evidence: PMID:14992727 menin activates the transcription of differentiation-regulating genes by covalent histone modification PMID:15640349 Menin activates transcription by means of a mechanism involving recruitment of MLL to the p27Kip1 and p18Ink4c promoters and coding regions. |
| GO:0045815 transcription initiation-coupled chromatin remodeling | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara transfer from mouse menin. Reason: Consistent with the IBA and IMP rows. Supporting Evidence: PMID:14992727 menin activates the transcription of differentiation-regulating genes by covalent histone modification |
| GO:0045815 transcription initiation-coupled chromatin remodeling | IMP PMID:14992727 Menin associates with a trithorax family histone methyltrans... | ACCEPT | Summary: Hughes et al. showed the menin-associated complex methylates H3K4, tumor-derived menin mutants lose associated methyltransferase activity, and Men1 loss reduces Hoxc6/Hoxc8 expression. Reason: Menin brings H3K4 methyltransferase activity to target genes; accepted as a core process. Supporting Evidence: PMID:14992727 menin activates the transcription of differentiation-regulating genes by covalent histone modification PMID:14992727 Men1 knockout embryos and cells show decreased expression of the homeobox genes Hoxc6 and Hoxc8. |
| GO:0045892 negative regulation of DNA-templated transcription | IDA PMID:12226747 Menin uncouples Elk-1, JunD and c-Jun phosphorylation from M... | MODIFY | Summary: Gallo et al. showed menin represses the inducible activity of the c-fos promoter and inhibits JunD, c-Jun and Elk-1 phosphorylation. Reason: The repressed promoter (c-fos) is an RNA polymerase II promoter; the more specific term GO:0000122, which menin already carries, is appropriate. Proposed replacements: negative regulation of transcription by RNA polymerase II Supporting Evidence: PMID:12226747 We also show that Menin represses the inducible activity of the c-fos promoter. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:15199122 Leukemia proto-oncoprotein MLL forms a SET1-like histone met... | ACCEPT | Summary: Loss of menin phenocopies loss of MLL and reduces Hox gene expression. Reason: Menin is required for MLL-dependent activation of Hox and other target genes and contributes as the scaffold that recruits MLL; core process. Supporting Evidence: PMID:15199122 Abrogation of menin expression phenocopies loss of MLL and reveals a critical role for menin in the maintenance of Hox gene expression. PMID:15640349 Menin activates transcription by means of a mechanism involving recruitment of MLL to the p27Kip1 and p18Ink4c promoters and coding regions. |
| GO:0046329 negative regulation of JNK cascade | IDA PMID:12226747 Menin uncouples Elk-1, JunD and c-Jun phosphorylation from M... | MARK AS OVER ANNOTATED | Summary: Gallo et al. showed menin inhibits JNK-mediated phosphorylation of JunD and c-Jun. Reason: The same study shows menin does not affect activation of JNK1 or ERK2 and acts downstream of MAPK activation, at the level of the nuclear substrates. Menin blocks a JNK output on its bound partner rather than regulating the JNK cascade itself. Supporting Evidence: PMID:12226747 Kinase assays show that Menin overexpression does not interfere with activation of either ERK2 or JNK1, suggesting that Menin acts at a level downstream of MAPK activation. PMID:22327296 The menin-JUND interaction blocks JUN N-terminal kinase (JNK)-mediated JUND phosphorylation and suppresses JUND-induced transcription. |
| GO:0051219 phosphoprotein binding | IPI PMID:14992727 Menin associates with a trithorax family histone methyltrans... | MODIFY | Summary: Menin associates with RNA polymerase II whose CTD is phosphorylated on Ser5, but not with unphosphorylated or Ser2-phosphorylated Pol II. Reason: Phosphoprotein binding is generic; the evidence specifies selective binding to the Ser5-phosphorylated Pol II CTD. Proposed replacements: RNA polymerase II C-terminal domain phosphoserine binding Supporting Evidence: PMID:14992727 menin is associated with RNA polymerase II whose large subunit carboxyl-terminal domain is phosphorylated on Ser 5 file:human/MEN1/MEN1-uniprot.txt Interacts with POLR2A phosphorylated at 'Ser-5', but not with the unphosphorylated, nor 'Ser-2' phosphorylated POLR2A forms. |
| GO:0070412 R-SMAD binding | IPI PMID:11274402 Inactivation of menin, a Smad3-interacting protein, blocks t... | KEEP AS NON CORE | Summary: Menin interacts with Smad3. Reason: Informative binding term reflecting menin's role as a SMAD3 cofactor; peripheral to the MLL scaffold function. Supporting Evidence: PMID:11274402 Menin interacts with Smad3, and antisense menin suppresses transforming growth factor type beta-induced and Smad3-induced transcriptional activity Reactome:R-HSA-2186643 binds SMAD2/3:SMAD4 heterotrimer through interaction with SMAD3 |
| GO:0071339 MLL1 complex | IPI PMID:23508102 Quantitative dissection and stoichiometry determination of t... | ACCEPT | Summary: Menin is a subunit of the MLL1 complex. Reason: Supported by multiple purifications and the menin-MLL1 crystal structures; core. Supporting Evidence: PMID:15199122 Menin, a product of the MEN1 tumor suppressor gene, is also a component of the 1-MDa MLL complex. Reactome:R-HSA-9818937 MEN1 (also known as Menin) associates with the MLL1 complex by binding to the N-terminal region of KMT2A PMID:23508102 We applied label-free quantitative mass spectrometry to determine the subunit composition and stoichiometry of the human SET1/MLL complexes. |
| GO:0140608 cysteine-type endopeptidase activator activity | IEA GO_REF:0000107 | REMOVE | Summary: Ensembl Compara transfer from mouse menin; the mouse source is an MGI IDA from PMID:14688275 (QuickGO, 2026-10-24), which showed menin promotes apoptosis and increases procaspase-8 levels in MEFs. Reason: The paper shows menin raises expression of procaspase 8 and thereby caspase-8 activation after TNF-alpha; it does not show menin binding caspase 8 and increasing its activity. Cysteine-type endopeptidase activator activity is not supported. Supporting Evidence: PMID:14688275 loss of menin reduces the expression of procaspase 8 |
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Download this section (compressed HTML)Q: Does menin's sequence-independent dsDNA binding through its C-terminal NLS region contribute to recruiting or stabilizing MLL1/MLL2 complexes on chromatin in cells, or is targeting determined entirely by LEDGF and DNA-binding partners?
Q: Should UniProt's mouse menin GO:0001216 IDA (PMID:14992727), which Ensembl Compara projects to human, be reannotated as transcription coactivator activity, given that the paper shows recruitment of methyltransferase activity rather than sequence-specific DNA binding?
Q: How is the choice between menin's coactivator (MLL1/MLL2) and corepressor (JunD) roles regulated in a given cell, given that both partners compete for the same pocket?
Experiment: Compare genome-wide menin occupancy (CUT&RUN) in cells expressing wild-type menin, NLS1/NLS2 point mutants that lose dsDNA binding but stay nuclear, and pocket mutants that cannot bind MLL1/JunD, with and without LEDGF depletion or menin-MLL inhibitor treatment.
Hypothesis: Menin's chromatin occupancy depends on partner proteins rather than on its own DNA binding.
Type: genomics
Experiment: Run protein-binding microarray or HT-SELEX with purified full-length menin, with and without MLL1 N-terminal peptide, to test for any enriched motif beyond the sequence-independent binding reported in gel-shift assays.
Hypothesis: Menin has no intrinsic sequence preference for DNA.
Type: binding assay
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