MLXIP_HUMAN
ID MLXIP_HUMAN Reviewed; 919 AA.
AC Q9HAP2; A7MBN0; O94945; Q7LC47; Q8IXP1; Q8TAH9; Q8WVQ0; Q8WYA5;
DT 21-AUG-2007, integrated into UniProtKB/Swiss-Prot.
DT 21-AUG-2007, sequence version 2.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=MLX-interacting protein;
DE AltName: Full=Class E basic helix-loop-helix protein 36;
DE Short=bHLHe36;
DE AltName: Full=Transcriptional activator MondoA;
GN Name=MLXIP {ECO:0000312|HGNC:HGNC:17055};
GN Synonyms=BHLHE36, KIAA0867, MIR {ECO:0000312|EMBL:AAL55689.1}, MONDOA;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAG34121.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=11073985; DOI=10.1128/mcb.20.23.8845-8854.2000;
RA Billin A.N., Eilers A.L., Coulter K.L., Logan J.S., Ayer D.E.;
RT "MondoA, a novel basic helix-loop-helix-leucine zipper transcriptional
RT activator that constitutes a positive branch of a max-like network.";
RL Mol. Cell. Biol. 20:8845-8854(2000).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAL55689.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 4), AND VARIANT GLY-396.
RA Merla G., Cairo S., Reymond A.;
RT "Mir, a new bHLHZip protein interacting with Mlx.";
RL Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=10048485; DOI=10.1093/dnares/5.6.355;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 5:355-364(1998).
RN [4] {ECO:0000305, ECO:0000312|EMBL:AAH28309.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 5), NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 176-919 (ISOFORM 3), AND VARIANT GLY-396.
RC TISSUE=Pancreas {ECO:0000312|EMBL:AAH17656.1}, and
RC Placenta {ECO:0000312|EMBL:AAH28309.1};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5] {ECO:0000305}
RP FUNCTION, DNA-BINDING, INTERACTION WITH MLX, AND SUBCELLULAR LOCATION.
RX PubMed=12446771; DOI=10.1128/mcb.22.24.8514-8526.2002;
RA Eilers A.L., Sundwall E., Lin M., Sullivan A.A., Ayer D.E.;
RT "A novel heterodimerization domain, CRM1, and 14-3-3 control subcellular
RT localization of the MondoA-Mlx heterocomplex.";
RL Mol. Cell. Biol. 22:8514-8526(2002).
RN [6] {ECO:0000305}
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=16782875; DOI=10.1128/mcb.00657-05;
RA Sans C.L., Satterwhite D.J., Stoltzman C.A., Breen K.T., Ayer D.E.;
RT "MondoA-Mlx heterodimers are candidate sensors of cellular energy status:
RT mitochondrial localization and direct regulation of glycolysis.";
RL Mol. Cell. Biol. 26:4863-4871(2006).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27 AND SER-33, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-9 AND SER-669, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
CC -!- FUNCTION: Binds DNA as a heterodimer with MLX and activates
CC transcription. Binds to the canonical E box sequence 5'-CACGTG-3'.
CC Plays a role in transcriptional activation of glycolytic target genes.
CC Involved in glucose-responsive gene regulation.
CC {ECO:0000250|UniProtKB:Q2VPU4, ECO:0000269|PubMed:12446771,
CC ECO:0000269|PubMed:16782875}.
CC -!- SUBUNIT: Efficient DNA binding requires dimerization with another bHLH
CC protein. Binds DNA as a homodimer or a heterodimer with MLX.
CC {ECO:0000250|UniProtKB:Q2VPU4, ECO:0000269|PubMed:12446771}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12446771,
CC ECO:0000269|PubMed:16782875}. Nucleus {ECO:0000255|PROSITE-
CC ProRule:PRU00981, ECO:0000269|PubMed:12446771,
CC ECO:0000269|PubMed:16782875}. Mitochondrion outer membrane
CC {ECO:0000269|PubMed:12446771, ECO:0000269|PubMed:16782875}.
CC Note=Predominantly cytoplasmic but shuttles between cytoplasm and
CC nucleus when associated with MLX. Also associates with the outer
CC mitochondrial membrane and may shuttle between the outer mitochondrial
CC membrane and the nucleus. {ECO:0000250|UniProtKB:Q2VPU4,
CC ECO:0000269|PubMed:12446771, ECO:0000269|PubMed:16782875}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1 {ECO:0000269|PubMed:11073985};
CC IsoId=Q9HAP2-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|Ref.2};
CC IsoId=Q9HAP2-2; Sequence=VSP_052499;
CC Name=3 {ECO:0000269|PubMed:15489334};
CC IsoId=Q9HAP2-3; Sequence=VSP_052501, VSP_052502;
CC Name=4 {ECO:0000269|Ref.2};
CC IsoId=Q9HAP2-4; Sequence=VSP_052499, VSP_052503, VSP_052504;
CC Name=5 {ECO:0000269|PubMed:15489334};
CC IsoId=Q9HAP2-5; Sequence=VSP_052499, VSP_052500, VSP_052501,
CC VSP_052502;
CC -!- TISSUE SPECIFICITY: Widely expressed in adult tissues. Most abundant in
CC skeletal muscle. {ECO:0000269|PubMed:11073985}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA74890.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF312918; AAG34121.1; -; mRNA.
DR EMBL; AF245480; AAL55689.1; -; mRNA.
DR EMBL; AF245481; AAL55690.1; -; mRNA.
DR EMBL; AB020674; BAA74890.2; ALT_INIT; mRNA.
DR EMBL; BC017656; AAH17656.1; -; mRNA.
DR EMBL; BC028309; AAH28309.1; -; mRNA.
DR EMBL; BC039704; AAH39704.1; -; mRNA.
DR EMBL; BC151841; AAI51842.1; -; mRNA.
DR CCDS; CCDS73540.1; -. [Q9HAP2-1]
DR RefSeq; NP_055753.3; NM_014938.5. [Q9HAP2-1]
DR AlphaFoldDB; Q9HAP2; -.
DR SMR; Q9HAP2; -.
DR BioGRID; 116544; 15.
DR IntAct; Q9HAP2; 10.
DR STRING; 9606.ENSP00000312834; -.
DR GlyGen; Q9HAP2; 8 sites, 2 O-linked glycans (8 sites).
DR iPTMnet; Q9HAP2; -.
DR PhosphoSitePlus; Q9HAP2; -.
DR BioMuta; MLXIP; -.
DR DMDM; 156632588; -.
DR EPD; Q9HAP2; -.
DR jPOST; Q9HAP2; -.
DR MassIVE; Q9HAP2; -.
DR MaxQB; Q9HAP2; -.
DR PaxDb; Q9HAP2; -.
DR PeptideAtlas; Q9HAP2; -.
DR PRIDE; Q9HAP2; -.
DR ProteomicsDB; 81411; -. [Q9HAP2-1]
DR ProteomicsDB; 81412; -. [Q9HAP2-2]
DR ProteomicsDB; 81413; -. [Q9HAP2-3]
DR ProteomicsDB; 81414; -. [Q9HAP2-4]
DR ProteomicsDB; 81415; -. [Q9HAP2-5]
DR Antibodypedia; 9815; 156 antibodies from 24 providers.
DR DNASU; 22877; -.
DR Ensembl; ENST00000319080.12; ENSP00000312834.6; ENSG00000175727.14. [Q9HAP2-1]
DR Ensembl; ENST00000377037.3; ENSP00000366236.3; ENSG00000175727.14. [Q9HAP2-5]
DR Ensembl; ENST00000538698.5; ENSP00000440769.1; ENSG00000175727.14. [Q9HAP2-2]
DR Ensembl; ENST00000625732.3; ENSP00000486569.2; ENSG00000281178.4. [Q9HAP2-1]
DR Ensembl; ENST00000629738.4; ENSP00000487003.1; ENSG00000281178.4. [Q9HAP2-1]
DR GeneID; 22877; -.
DR KEGG; hsa:22877; -.
DR MANE-Select; ENST00000319080.12; ENSP00000312834.6; NM_014938.6; NP_055753.3.
DR UCSC; uc001ubq.4; human. [Q9HAP2-1]
DR CTD; 22877; -.
DR DisGeNET; 22877; -.
DR GeneCards; MLXIP; -.
DR HGNC; HGNC:17055; MLXIP.
DR HPA; ENSG00000175727; Tissue enhanced (skeletal).
DR MIM; 608090; gene.
DR neXtProt; NX_Q9HAP2; -.
DR OpenTargets; ENSG00000175727; -.
DR PharmGKB; PA128394590; -.
DR VEuPathDB; HostDB:ENSG00000175727; -.
DR eggNOG; KOG3582; Eukaryota.
DR GeneTree; ENSGT00940000158691; -.
DR HOGENOM; CLU_007471_1_0_1; -.
DR InParanoid; Q9HAP2; -.
DR OMA; QTCQTYQ; -.
DR OrthoDB; 388166at2759; -.
DR PhylomeDB; Q9HAP2; -.
DR TreeFam; TF324749; -.
DR PathwayCommons; Q9HAP2; -.
DR SignaLink; Q9HAP2; -.
DR BioGRID-ORCS; 22877; 28 hits in 343 CRISPR screens.
DR ChiTaRS; MLXIP; human.
DR GenomeRNAi; 22877; -.
DR Pharos; Q9HAP2; Tbio.
DR PRO; PR:Q9HAP2; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q9HAP2; protein.
DR Bgee; ENSG00000175727; Expressed in ileal mucosa and 173 other tissues.
DR ExpressionAtlas; Q9HAP2; baseline and differential.
DR Genevisible; Q9HAP2; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR InterPro; IPR032648; MLXIP.
DR PANTHER; PTHR15741:SF23; PTHR15741:SF23; 1.
DR Pfam; PF00010; HLH; 1.
DR SMART; SM00353; HLH; 1.
DR SUPFAM; SSF47459; SSF47459; 1.
DR PROSITE; PS50888; BHLH; 1.
PE 1: Evidence at protein level;
KW Acetylation; Activator; Alternative splicing; Cytoplasm; DNA-binding;
KW Membrane; Mitochondrion; Mitochondrion outer membrane; Nucleus;
KW Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CHAIN 2..919
FT /note="MLX-interacting protein"
FT /id="PRO_0000298763"
FT DOMAIN 719..769
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 1..72
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 73..327
FT /note="Required for cytoplasmic localization"
FT /evidence="ECO:0000269|PubMed:12446771"
FT REGION 322..445
FT /note="Transactivation domain"
FT /evidence="ECO:0000269|PubMed:12446771"
FT REGION 542..562
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 633..712
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 769..790
FT /note="Leucine-zipper"
FT REGION 832..881
FT /note="Mediates heterotypic interactions between MLXIP and
FT MLX and is required for cytoplasmic localization"
FT /evidence="ECO:0000269|PubMed:12446771"
FT COMPBIAS 668..710
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 9
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 27
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 33
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 39
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q2VPU4"
FT MOD_RES 669
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..393
FT /note="Missing (in isoform 2, isoform 4 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:10048485,
FT ECO:0000303|PubMed:15489334, ECO:0000303|Ref.2"
FT /id="VSP_052499"
FT VAR_SEQ 426..443
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_052500"
FT VAR_SEQ 578..628
FT /note="AAFSGQPQAVIMTSGPLKREGMLASTVSQSNVVIAPAAIARAPGVPEFHSS
FT -> GEPGGETQCGAPPDPEGCFPIPKAFKLVTTTTTLVCTCMRTHIHLNETKVS (in
FT isoform 3 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_052501"
FT VAR_SEQ 629..919
FT /note="Missing (in isoform 3 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_052502"
FT VAR_SEQ 770..772
FT /note="QQE -> LLS (in isoform 4)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_052503"
FT VAR_SEQ 773..919
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_052504"
FT VARIANT 396
FT /note="E -> G (in dbSNP:rs7978353)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.2"
FT /id="VAR_059344"
FT VARIANT 539
FT /note="V -> L (in dbSNP:rs34702867)"
FT /id="VAR_059345"
SQ SEQUENCE 919 AA; 101185 MW; 47375FCC4333E0C2 CRC64;
MAADVFMCSP RRPRSRGRQV LLKPQVSEDD DDSDTDEPSP PPASGAATPA RAHASAAPPP
PRAGPGREEP PRRQQIIHSG HFMVSSPHRE HPPKKGYDFD TVNKQTCQTY SFGKTSSCHL
SIDASLTKLF ECMTLAYSGK LVSPKWKNFK GLKLQWRDKI RLNNAIWRAW YMQYLEKRKN
PVCHFVTPLD GSVDVDEHRR PEAITTEGKY WKSRIEIVIR EYHKWRTYFK KRLQQHKDED
LSSLVQDDDM LYWHKHGDGW KTPVPMEEDP LLDTDMLMSE FSDTLFSTLS SHQPVAWPNP
REIAHLGNAD MIQPGLIPLQ PNLDFMDTFE PFQDLFSSSR SIFGSMLPAS ASAPVPDPNN
PPAQESILPT TALPTVSLPD SLIAPPTAPS LAHMDEQGCE HTSRTEDPFI QPTDFGPSEP
PLSVPQPFLP VFTMPLLSPS PAPPPISPVL PLVPPPATAL NPPAPPTFHQ PQKFAGVNKA
PSVITHTASA TLTHDAPATT FSQSQGLVIT THHPAPSAAP CGLALSPVTR PPQPRLTFVH
PKPVSLTGGR PKQPHKIVPA PKPEPVSLVL KNARIAPAAF SGQPQAVIMT SGPLKREGML
ASTVSQSNVV IAPAAIARAP GVPEFHSSIL VTDLGHGTSS PPAPVSRLFP STAQDPLGKG
EQVPLHGGSP QVTVTGPSRD CPNSGQASPC ASEQSPSPQS PQNNCSGKSD PKNVAALKNR
QMKHISAEQK RRFNIKMCFD MLNSLISNNS KLTSHAITLQ KTVEYITKLQ QERGQMQEEA
RRLREEIEEL NATIISCQQL LPATGVPVTR RQFDHMKDMF DEYVKTRTLQ NWKFWIFSII
IKPLFESFKG MVSTSSLEEL HRTALSWLDQ HCSLPILRPM VLSTLRQLST STSILTDPAQ
LPEQASKAVT RIGKRLGES
