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   27-MAR-2024, entry version 160.
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 Placenta
RC   {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; 19.
DR   ComplexPortal; CPX-2525; MLXIP-MLX transcription factor complex.
DR   IntAct; Q9HAP2; 16.
DR   STRING; 9606.ENSP00000312834; -.
DR   GlyCosmos; Q9HAP2; 8 sites, 2 glycans.
DR   GlyGen; Q9HAP2; 10 sites, 2 O-linked glycans (10 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; 9606-ENSP00000312834; -.
DR   PeptideAtlas; 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   Pumba; Q9HAP2; -.
DR   Antibodypedia; 9815; 170 antibodies from 25 providers.
DR   DNASU; 22877; -.
DR   Ensembl; ENST00000319080.12; ENSP00000312834.6; ENSG00000175727.15. [Q9HAP2-1]
DR   Ensembl; ENST00000538698.5; ENSP00000440769.1; ENSG00000175727.15. [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   AGR; HGNC:17055; -.
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; TEFHSSI; -.
DR   OrthoDB; 2963550at2759; -.
DR   PhylomeDB; Q9HAP2; -.
DR   TreeFam; TF324749; -.
DR   PathwayCommons; Q9HAP2; -.
DR   SignaLink; Q9HAP2; -.
DR   BioGRID-ORCS; 22877; 29 hits in 417 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 175 other cell types or tissues.
DR   ExpressionAtlas; Q9HAP2; baseline and differential.
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   CDD; cd19688; bHLHzip_MLXIP; 1.
DR   CDD; cd21772; NES2-NLS_MLXIP; 1.
DR   Gene3D; 4.10.280.10; Helix-loop-helix DNA-binding domain; 1.
DR   InterPro; IPR011598; bHLH_dom.
DR   InterPro; IPR036638; HLH_DNA-bd_sf.
DR   PANTHER; PTHR10328:SF14; MLX-INTERACTING PROTEIN; 1.
DR   PANTHER; PTHR10328; PROTEIN MAX MYC-ASSOCIATED FACTOR X; 1.
DR   Pfam; PF00010; HLH; 1.
DR   SMART; SM00353; HLH; 1.
DR   SUPFAM; SSF47459; HLH, helix-loop-helix DNA-binding domain; 1.
DR   PROSITE; PS50888; BHLH; 1.
DR   Genevisible; Q9HAP2; HS.
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
//