MEN1_CANLF
ID MEN1_CANLF Reviewed; 615 AA.
AC A2SXS5; E2RDP0;
DT 31-MAY-2011, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 1.
DT 03-AUG-2022, entry version 93.
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 1).
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=4;
CC Name=1;
CC IsoId=A2SXS5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A2SXS5-2; Sequence=VSP_041101;
CC Name=3;
CC IsoId=A2SXS5-3; Sequence=VSP_041102;
CC Name=4;
CC IsoId=A2SXS5-4; Sequence=VSP_041101, VSP_041102;
CC -!- MISCELLANEOUS: [Isoform 4]: Gene prediction. {ECO:0000305}.
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DR EMBL; DQ366289; ABD16380.1; -; mRNA.
DR RefSeq; NP_001074977.1; NM_001081508.2. [A2SXS5-1]
DR AlphaFoldDB; A2SXS5; -.
DR SMR; A2SXS5; -.
DR STRING; 9615.ENSCAFP00000020909; -.
DR PaxDb; A2SXS5; -.
DR Ensembl; ENSCAFT00030010270; ENSCAFP00030008996; ENSCAFG00030005512. [A2SXS5-2]
DR Ensembl; ENSCAFT00030010300; ENSCAFP00030009023; ENSCAFG00030005512. [A2SXS5-4]
DR Ensembl; ENSCAFT00040041016; ENSCAFP00040035760; ENSCAFG00040022015. [A2SXS5-2]
DR Ensembl; ENSCAFT00040041061; ENSCAFP00040035879; ENSCAFG00040022015. [A2SXS5-4]
DR Ensembl; ENSCAFT00845051126; ENSCAFP00845040089; ENSCAFG00845028814. [A2SXS5-4]
DR GeneID; 483758; -.
DR KEGG; cfa:483758; -.
DR CTD; 4221; -.
DR eggNOG; ENOG502QUYK; Eukaryota.
DR GeneTree; ENSGT00390000014237; -.
DR HOGENOM; CLU_018646_0_0_1; -.
DR InParanoid; A2SXS5; -.
DR OMA; GVNERSW; -.
DR OrthoDB; 799417at2759; -.
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 Proteomes; UP000002254; Chromosome 18.
DR Bgee; ENSCAFG00000014185; Expressed in thymus and 47 other 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; PTHR12693; 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..615
FT /note="Menin"
FT /id="PRO_0000408472"
FT REGION 219..395
FT /note="Interaction with FANCD2"
FT /evidence="ECO:0000250|UniProtKB:O00255"
FT REGION 467..557
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 467..502
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 492
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00255"
FT MOD_RES 548
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00255"
FT MOD_RES 599
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O00255"
FT VAR_SEQ 150..154
FT /note="Missing (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_041101"
FT VAR_SEQ 401..455
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_041102"
SQ SEQUENCE 615 AA; 67962 MW; 52FB0491302AC165 CRC64;
MGLKAAQKTL FPLRSIDDVV RLFAAELGRE EPDLVLLSLV LGFVEHFLAV NRVIPTNVPE
LTFQPSPAPD PPGGLTYFPV ADLSIIAALY ARFTAQIRGA VDLSLYPREG GVSSRELVKK
VSDVIWNSLS RSYFKDRAHI QSLFSFITGW SPTGTKLDSS GVAFAVVGAC QALGLRDVHL
ALSEDHAWVV FGPNGEQTAE VTWHGKGNED RRGQTVNAGV AERSWLYLKG SYMRCDRKME
VAFMVCAINP SIDLHTDSLE LLQLQQKLLW LLYDLGHLER YPMALGNLAD LEELEPTPGR
PDPLTLYHKG IASAKTYYRD EHIYPYMYLA GYHCRNRNVR EALQAWADTA TVIQDYNYCR
EDEEIYKEFF EVANDVIPNL LKEAASLLEA GEERPGEQTQ GVQSQGSALQ DPECFAHLLR
FYDGICKWEE GSPTPVLHVG WATFLVQSLG RFEGQVRQKV RIVSREAEAA EAEELWGEEA
REGRRRGPRR ESKPEEPPPP KKPALDKGPG GGQGAMSGPP RKPPGTVPGT ARGPEGGSTA
PAPAPAASPP PEGPVLTFQS EKMKGMKELL VATKINSSAI KLQLTAQSQV QMKKQKVSTP
SDYTLSFLKR QRKGL
