MEN1_RAT
ID MEN1_RAT Reviewed; 610 AA.
AC Q9WVR8; D3ZCA2;
DT 31-MAY-2011, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Menin;
GN Name=Men1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC STRAIN=Wistar; TISSUE=Brain;
RX PubMed=10612420; DOI=10.1016/s0303-7207(99)00150-1;
RA Maruyama K., Tsukada T., Hosono T., Ohkura N., Kishi M., Honda M.,
RA Nara-Ashizawa N., Nagasaki K., Yamaguchi K.;
RT "Structure and distribution of rat menin mRNA.";
RL Mol. Cell. Endocrinol. 156:25-33(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC STRAIN=Wistar;
RX PubMed=10524203; DOI=10.1016/s0167-4781(99)00089-5;
RA Karges W., Maier S., Wissmann A., Dralle H., Dosch H.M., Boehm B.O.;
RT "Primary structure, gene expression and chromosomal mapping of rodent
RT homologs of the MEN1 tumor suppressor gene.";
RL Biochim. Biophys. Acta 1446:286-294(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION, INTERACTION WITH SMAD3, AND INDUCTION BY TGFB1.
RX PubMed=11274402; DOI=10.1073/pnas.061358098;
RA Kaji H., Canaff L., Lebrun J.J., Goltzman D., Hendy G.N.;
RT "Inactivation of menin, a Smad3-interacting protein, blocks transforming
RT growth factor type beta signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:3837-3842(2001).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-543, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Essential component of a MLL/SET1 histone methyltransferase
CC (HMT) complex, a complex that specifically methylates 'Lys-4' of
CC histone H3 (H3K4). Functions as a transcriptional regulator. Binds to
CC the TERT promoter and represses telomerase expression. Represses JUND-
CC mediated transcriptional activation on AP1 sites, as well as that
CC mediated by NFKB subunit RELA. Positively regulates HOXC8 and HOXC6
CC gene expression. May be involved in normal hematopoiesis through the
CC activation of HOXA9 expression. May be involved in DNA repair (By
CC similarity). Plays a role in TGFB1-mediated inhibition of cell-
CC proliferation, possibly regulating SMAD3 transcriptional activity.
CC {ECO:0000250|UniProtKB:O00255, ECO:0000250|UniProtKB:O88559,
CC ECO:0000269|PubMed:11274402}.
CC -!- SUBUNIT: Component of the MLL-HCF complex, at least composed of
CC KMT2A/MLL1, MEN1, ASH2L, RBBP5, DPY30, WDR5, HCFC1 and HCFC2 (By
CC similarity). Component of the menin-associated histone
CC methyltransferase complex, at least composed of KMT2B/MLL4, MEN1,
CC ASH2L, RBBP5, DPY30 and WDR5 (By similarity). Interacts with POLR2B (By
CC similarity). Interacts with POLR2A phosphorylated at 'Ser-5', but not
CC with the unphosphorylated, nor 'Ser-2' phosphorylated POLR2A forms (By
CC similarity). Interacts with FANCD2 and DBF4 (By similarity). Interacts
CC with SMAD3, but not with SMAD2, nor SMAD4 (PubMed:11274402). Directly
CC interacts with NFKB1, NFKB2 and RELA (By similarity). Interacts with
CC JUND (via MBM motif); inhibits the interaction of JUND with MAPK10 and
CC the phosphorylation of JUND by MAP kinases MAPK8 and MAPK10 (By
CC similarity). Interacts with KMT2A (via MBM motif) (By similarity). The
CC KMT2A-MEN1 complex interacts with PSIP1 with a greater affinity as MEN1
CC enhances interaction of KMT2A with PSIP1 (By similarity).
CC {ECO:0000250|UniProtKB:O00255, ECO:0000269|PubMed:11274402}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10612420}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9WVR8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9WVR8-2; Sequence=VSP_041103;
CC -!- TISSUE SPECIFICITY: Widely expressed, including in the pituitary,
CC brain, large intestine, spleen, kidney, adrenal gland, ovary, testis,
CC thymus, lung, epididymis, bone marrow, pancreatic islets and placenta.
CC {ECO:0000269|PubMed:10524203, ECO:0000269|PubMed:10612420}.
CC -!- DEVELOPMENTAL STAGE: In the brain, highest expression at E16 to 18.
CC Expression decreases from E20 onward. {ECO:0000269|PubMed:10612420}.
CC -!- INDUCTION: By TGFB1. {ECO:0000269|PubMed:11274402}.
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DR EMBL; AB023400; BAA82134.1; -; mRNA.
DR EMBL; AF130369; AAF01353.1; -; mRNA.
DR EMBL; AF130370; AAF01354.1; -; mRNA.
DR EMBL; CH473953; EDM12593.1; -; Genomic_DNA.
DR EMBL; CH473953; EDM12594.1; -; Genomic_DNA.
DR EMBL; CH473953; EDM12595.1; -; Genomic_DNA.
DR RefSeq; NP_062081.1; NM_019208.3. [Q9WVR8-1]
DR RefSeq; XP_006230832.1; XM_006230770.3. [Q9WVR8-1]
DR RefSeq; XP_006230833.1; XM_006230771.3. [Q9WVR8-1]
DR RefSeq; XP_006230834.1; XM_006230772.3. [Q9WVR8-1]
DR AlphaFoldDB; Q9WVR8; -.
DR SMR; Q9WVR8; -.
DR STRING; 10116.ENSRNOP00000028592; -.
DR iPTMnet; Q9WVR8; -.
DR PhosphoSitePlus; Q9WVR8; -.
DR PaxDb; Q9WVR8; -.
DR PRIDE; Q9WVR8; -.
DR Ensembl; ENSRNOT00000099846; ENSRNOP00000076697; ENSRNOG00000021054. [Q9WVR8-2]
DR GeneID; 29417; -.
DR KEGG; rno:29417; -.
DR UCSC; RGD:3078; rat. [Q9WVR8-1]
DR CTD; 4221; -.
DR RGD; 3078; Men1.
DR VEuPathDB; HostDB:ENSRNOG00000021054; -.
DR eggNOG; ENOG502QUYK; Eukaryota.
DR GeneTree; ENSGT00390000014237; -.
DR HOGENOM; CLU_018646_0_0_1; -.
DR InParanoid; Q9WVR8; -.
DR OMA; GVNERSW; -.
DR OrthoDB; 799417at2759; -.
DR PhylomeDB; Q9WVR8; -.
DR Reactome; R-RNO-201722; Formation of the beta-catenin:TCF transactivating complex.
DR Reactome; R-RNO-2173796; SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
DR Reactome; R-RNO-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-RNO-5626467; RHO GTPases activate IQGAPs.
DR Reactome; R-RNO-8957275; Post-translational protein phosphorylation.
DR PRO; PR:Q9WVR8; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Proteomes; UP000234681; Chromosome 1.
DR Bgee; ENSRNOG00000021054; Expressed in cerebellum and 20 other tissues.
DR Genevisible; Q9WVR8; RN.
DR GO; GO:0000785; C:chromatin; ISO:RGD.
DR GO; GO:0000781; C:chromosome, telomeric region; ISO:RGD.
DR GO; GO:0032154; C:cleavage furrow; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0035097; C:histone methyltransferase complex; ISO:RGD.
DR GO; GO:0071339; C:MLL1 complex; ISO:RGD.
DR GO; GO:0044665; C:MLL1/2 complex; ISO:RGD.
DR GO; GO:0016363; C:nuclear matrix; ISO:RGD.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR GO; GO:0017053; C:transcription repressor complex; ISO:RGD.
DR GO; GO:0003682; F:chromatin binding; IDA:RGD.
DR GO; GO:0003677; F:DNA binding; ISO:RGD.
DR GO; GO:0001216; F:DNA-binding transcription activator activity; ISO:RGD.
DR GO; GO:0003690; F:double-stranded DNA binding; ISO:RGD.
DR GO; GO:0000400; F:four-way junction DNA binding; ISO:RGD.
DR GO; GO:0051219; F:phosphoprotein binding; ISO:RGD.
DR GO; GO:0047485; F:protein N-terminus binding; ISO:RGD.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; ISO:RGD.
DR GO; GO:0070412; F:R-SMAD binding; ISO:RGD.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:RGD.
DR GO; GO:0000403; F:Y-form DNA binding; ISO:RGD.
DR GO; GO:0007420; P:brain development; IEP:RGD.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISO:RGD.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IEP:RGD.
DR GO; GO:0071375; P:cellular response to peptide hormone stimulus; IEP:RGD.
DR GO; GO:0006338; P:chromatin remodeling; ISO:RGD.
DR GO; GO:0046697; P:decidualization; IEP:RGD.
DR GO; GO:0048704; P:embryonic skeletal system morphogenesis; ISO:RGD.
DR GO; GO:0030097; P:hemopoiesis; ISO:RGD.
DR GO; GO:0051568; P:histone H3-K4 methylation; ISO:RGD.
DR GO; GO:0016571; P:histone methylation; ISO:RGD.
DR GO; GO:0001776; P:leukocyte homeostasis; ISO:RGD.
DR GO; GO:0000165; P:MAPK cascade; ISO:RGD.
DR GO; GO:0060135; P:maternal process involved in female pregnancy; ISO:RGD.
DR GO; GO:0000278; P:mitotic cell cycle; IEP:RGD.
DR GO; GO:0045786; P:negative regulation of cell cycle; ISO:RGD.
DR GO; GO:1902807; P:negative regulation of cell cycle G1/S phase transition; IMP:RGD.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0010812; P:negative regulation of cell-substrate adhesion; IMP:RGD.
DR GO; GO:0045736; P:negative regulation of cyclin-dependent protein serine/threonine kinase activity; ISO:RGD.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IMP:RGD.
DR GO; GO:0046329; P:negative regulation of JNK cascade; ISO:RGD.
DR GO; GO:0046621; P:negative regulation of organ growth; ISO:RGD.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; ISO:RGD.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:0051974; P:negative regulation of telomerase activity; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:RGD.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0001503; P:ossification; ISO:RGD.
DR GO; GO:0002076; P:osteoblast development; ISO:RGD.
DR GO; GO:0002051; P:osteoblast fate commitment; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:RGD.
DR GO; GO:0045597; P:positive regulation of cell differentiation; ISO:RGD.
DR GO; GO:0051781; P:positive regulation of cell division; ISO:RGD.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0031062; P:positive regulation of histone methylation; ISO:RGD.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; ISO:RGD.
DR GO; GO:0032092; P:positive regulation of protein binding; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0030511; P:positive regulation of transforming growth factor beta receptor signaling pathway; ISO:RGD.
DR GO; GO:0032925; P:regulation of activin receptor signaling pathway; IMP:RGD.
DR GO; GO:2000045; P:regulation of G1/S transition of mitotic cell cycle; ISO:RGD.
DR GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0061469; P:regulation of type B pancreatic cell proliferation; IMP:RGD.
DR GO; GO:0010332; P:response to gamma radiation; ISO:RGD.
DR GO; GO:0071559; P:response to transforming growth factor beta; IMP:RGD.
DR GO; GO:0009411; P:response to UV; ISO:RGD.
DR GO; GO:0060021; P:roof of mouth development; ISO:RGD.
DR GO; GO:0003309; P:type B pancreatic cell differentiation; IMP:RGD.
DR CDD; cd14456; Menin; 1.
DR InterPro; IPR007747; Menin.
DR PANTHER; PTHR12693; PTHR12693; 1.
DR Pfam; PF05053; Menin; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Chromatin regulator; DNA-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1..610
FT /note="Menin"
FT /id="PRO_0000408473"
FT REGION 214..390
FT /note="Interaction with FANCD2"
FT /evidence="ECO:0000250|UniProtKB:O00255"
FT REGION 460..552
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 460..497
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 511..532
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 487
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00255"
FT MOD_RES 543
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 594
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O00255"
FT VAR_SEQ 396..450
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_041103"
SQ SEQUENCE 610 AA; 67335 MW; F9D2078B02363E32 CRC64;
MGLKAAQKTL FPLRSIDDVV RLFAAELGRE EPDLVLLSLV LGFVEHFLAV NRVIPTNVPE
LTFQPSPAPD PPGGLTYFPV ADLSIIAALY ARFTAQIRGA VDLSLYPREG GVSSRELVKK
VSDVIWNSLS RSYFKDRAHI QSLFSFITGT KLDSSGVAFA VVGACQALGL RDVHLALSED
HAWVVFGSNG EQTAEVTWHG KGNEDRRGQT VNAGVAERSW LYLKGSYMRC DRKMEVAFMV
CAINPSIDLH TDSLELLQLQ QKLLWLLYDL GHLERYPMAL GNLADLEELE PTPGRPDPLT
LYHKGIASAK TYYQDEHIYP YMYLAGYHCR NRNVREALQA WADTATVIQD YNYCREDEEI
YKEFFEVAND VIPNLLKEAA SLLEAGEERP GEQAQGTQGQ GSALQDPECF AHLLRFYDGI
CKWEEGSPTP VLHVGWATFL VQSLGRFEGQ VRQKVHIVSR EAEAAEAEEP WGDEAREGRR
RGPRRESKPE EPPPPKKPAL DKGPGSGQSA GSGPPRKTSG TVSGTARGTE VSSAAQAPAP
AASPPPEGPV LTFQSEKMKG MKELLVATKI NSSAIKLQLT AQSQVQMKKQ KVSTPSDYTL
SFLKRQRKGL
