ID   MEN1_CANLF              Reviewed;         610 AA.
AC   A2SXS5; E2RDP0;
DT   31-MAY-2011, integrated into UniProtKB/Swiss-Prot.
DT   08-NOV-2023, sequence version 2.
DT   27-MAR-2024, entry version 102.
DE   RecName: Full=Menin;
GN   Name=MEN1;
OS   Canis lupus familiaris (Dog) (Canis familiaris).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX   NCBI_TaxID=9615;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX   PubMed=17338170; DOI=10.1892/0891-6640(2007)21[199:imoiac]2.0.co;2;
RA   Goldstein R.E., Atwater D.Z., Cazolli D.M., Goldstein O., Wade C.M.,
RA   Lindblad-Toh K.;
RT   "Inheritance, mode of inheritance, and candidate genes for primary
RT   hyperparathyroidism in Keeshonden.";
RL   J. Vet. Intern. Med. 21:199-203(2007).
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. Plays a role in
CC       TGFB1-mediated inhibition of cell-proliferation, possibly regulating
CC       SMAD3 transcriptional activity. Represses JUND-mediated transcriptional
CC       activation on AP1 sites, as well as that mediated by NFKB subunit RELA.
CC       Positively regulates HOXC8 and HOXC6 gene expression. May be involved
CC       in normal hematopoiesis through the activation of HOXA9 expression. May
CC       be involved in DNA repair (By similarity).
CC       {ECO:0000250|UniProtKB:O00255, ECO:0000250|UniProtKB:O88559}.
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 (By similarity). 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}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O00255}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=A2SXS5-2; Sequence=Displayed;
CC       Name=2;
CC         IsoId=A2SXS5-1; Sequence=VSP_062034;
CC       Name=3;
CC         IsoId=A2SXS5-3; Sequence=VSP_041102;
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DR   EMBL; DQ366289; ABD16380.1; -; mRNA.
DR   RefSeq; NP_001074977.1; NM_001081508.2. [A2SXS5-1]
DR   AlphaFoldDB; A2SXS5; -.
DR   STRING; 9615.ENSCAFP00000020909; -.
DR   PaxDb; 9612-ENSCAFP00000020910; -.
DR   Ensembl; ENSCAFT00030010270.1; ENSCAFP00030008996.1; ENSCAFG00030005512.1. [A2SXS5-2]
DR   Ensembl; ENSCAFT00040041016.1; ENSCAFP00040035760.1; ENSCAFG00040022015.1. [A2SXS5-2]
DR   GeneID; 483758; -.
DR   KEGG; cfa:483758; -.
DR   CTD; 4221; -.
DR   eggNOG; ENOG502QUYK; Eukaryota.
DR   HOGENOM; CLU_018646_0_0_1; -.
DR   InParanoid; A2SXS5; -.
DR   OMA; SDVIWNG; -.
DR   OrthoDB; 2903812at2759; -.
DR   TreeFam; TF323888; -.
DR   Reactome; R-CFA-201722; Formation of the beta-catenin:TCF transactivating complex.
DR   Reactome; R-CFA-2173796; SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
DR   Reactome; R-CFA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR   Reactome; R-CFA-5626467; RHO GTPases activate IQGAPs.
DR   Reactome; R-CFA-8957275; Post-translational protein phosphorylation.
DR   Reactome; R-CFA-9772755; Formation of WDR5-containing histone-modifying complexes.
DR   Proteomes; UP000002254; Unplaced.
DR   Proteomes; UP000694429; Chromosome 18.
DR   Proteomes; UP000694542; Chromosome 18.
DR   Proteomes; UP000805418; Unplaced.
DR   Bgee; ENSCAFG00000014185; Expressed in thymus and 47 other cell types or tissues.
DR   GO; GO:0000785; C:chromatin; IBA:GO_Central.
DR   GO; GO:0035097; C:histone methyltransferase complex; IBA:GO_Central.
DR   GO; GO:0003682; F:chromatin binding; IBA:GO_Central.
DR   GO; GO:0000976; F:transcription cis-regulatory region binding; IBA:GO_Central.
DR   GO; GO:0000403; F:Y-form DNA binding; IBA:GO_Central.
DR   GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR   GO; GO:0045786; P:negative regulation of cell cycle; IBA:GO_Central.
DR   GO; GO:0008285; P:negative regulation of cell population proliferation; IBA:GO_Central.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   CDD; cd14456; Menin; 1.
DR   InterPro; IPR007747; Menin.
DR   PANTHER; PTHR12693; MENIN; 1.
DR   PANTHER; PTHR12693:SF3; MENIN; 1.
DR   Pfam; PF05053; Menin; 2.
PE   2: Evidence at transcript 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_0000408472"
FT   REGION          214..390
FT                   /note="Interaction with FANCD2"
FT                   /evidence="ECO:0000250|UniProtKB:O00255"
FT   REGION          462..552
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        462..497
FT                   /note="Basic and acidic 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:0000250|UniProtKB:O00255"
FT   MOD_RES         594
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:O00255"
FT   VAR_SEQ         149
FT                   /note="G -> GWSPTG (in isoform 2)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_062034"
FT   VAR_SEQ         401..455
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_041102"
SQ   SEQUENCE   610 AA;  67434 MW;  071D4C293176D637 CRC64;
     MGLKAAQKTL FPLRSIDDVV RLFAAELGRE EPDLVLLSLV LGFVEHFLAV NRVIPTNVPE
     LTFQPSPAPD PPGGLTYFPV ADLSIIAALY ARFTAQIRGA VDLSLYPREG GVSSRELVKK
     VSDVIWNSLS RSYFKDRAHI QSLFSFITGT KLDSSGVAFA VVGACQALGL RDVHLALSED
     HAWVVFGPNG EQTAEVTWHG KGNEDRRGQT VNAGVAERSW LYLKGSYMRC DRKMEVAFMV
     CAINPSIDLH TDSLELLQLQ QKLLWLLYDL GHLERYPMAL GNLADLEELE PTPGRPDPLT
     LYHKGIASAK TYYRDEHIYP YMYLAGYHCR NRNVREALQA WADTATVIQD YNYCREDEEI
     YKEFFEVAND VIPNLLKEAA SLLEAGEERP GEQTQGVQSQ GSALQDPECF AHLLRFYDGI
     CKWEEGSPTP VLHVGWATFL VQSLGRFEGQ VRQKVRIVSR EAEAAEAEEL WGEEAREGRR
     RGPRRESKPE EPPPPKKPAL DKGPGGGQGA MSGPPRKPPG TVPGTARGPE GGSTAPAPAP
     AASPPPEGPV LTFQSEKMKG MKELLVATKI NSSAIKLQLT AQSQVQMKKQ KVSTPSDYTL
     SFLKRQRKGL
//