ID   MAD4_HUMAN              Reviewed;         209 AA.
AC   Q14582; A2A335; Q5TZX4;
DT   15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT   15-JUL-1999, sequence version 2.
DT   24-JAN-2024, entry version 173.
DE   RecName: Full=Max dimerization protein 4;
DE            Short=Max dimerizer 4;
DE   AltName: Full=Class C basic helix-loop-helix protein 12;
DE            Short=bHLHc12;
DE   AltName: Full=Max-associated protein 4;
DE   AltName: Full=Max-interacting transcriptional repressor MAD4;
GN   Name=MXD4; Synonyms=BHLHC12, MAD4;
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]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Pribill I., Barnes G.T., Chen J., Church D., Buckler A., Baxendale S.,
RA   Bates G.P., Lehrach H., Gusella M.J., Duyao M.P., Ambrose C.M.,
RA   Macdonald M.E., Gusella J.F.;
RL   Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Qian J.-F., Wang X.-L., Wang E.;
RT   "Cloning and sequencing a novel human Max-associated protein, hMad4 and
RT   characterizing its transcriptional up-regulation in quiescent and senescent
RT   human fibroblasts.";
RL   Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA   Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA   Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA   Phelan M., Farmer A.;
RT   "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15815621; DOI=10.1038/nature03466;
RA   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA   Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA   Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA   Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA   Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA   Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA   Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA   Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA   McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA   Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA   Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA   Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA   Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA   Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA   Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA   Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA   Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA   Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA   Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA   Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT   4.";
RL   Nature 434:724-731(2005).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Lung;
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).
CC   -!- FUNCTION: Transcriptional repressor. Binds with MAX to form a sequence-
CC       specific DNA-binding protein complex which recognizes the core sequence
CC       5'-CAC[GA]TG-3'. Antagonizes MYC transcriptional activity by competing
CC       for MAX and suppresses MYC dependent cell transformation (By
CC       similarity). {ECO:0000250}.
CC   -!- SUBUNIT: Efficient DNA binding requires dimerization with another bHLH
CC       protein. Binds DNA as a heterodimer with MAX. Interacts with SIN3A AND
CC       SIN3B. Interacts with RNF17 (By similarity). {ECO:0000250}.
CC   -!- INTERACTION:
CC       Q14582; Q8TDR4: TCP10L; NbExp=6; IntAct=EBI-3943670, EBI-3923210;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00981}.
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DR   EMBL; AF040963; AAB97009.1; -; mRNA.
DR   EMBL; AF082740; AAF98553.1; -; mRNA.
DR   EMBL; BT019969; AAV38772.1; -; mRNA.
DR   EMBL; BT019970; AAV38773.1; -; mRNA.
DR   EMBL; Z49250; CAA89217.1; -; Genomic_DNA.
DR   EMBL; AL158068; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC068060; AAH68060.1; -; mRNA.
DR   CCDS; CCDS3361.1; -.
DR   RefSeq; NP_006445.1; NM_006454.2.
DR   AlphaFoldDB; Q14582; -.
DR   SMR; Q14582; -.
DR   BioGRID; 115854; 13.
DR   ComplexPortal; CPX-2520; MXD4-MLX transcriptional repressor complex.
DR   ComplexPortal; CPX-7601; MXD4-MAX transcriptional repressor complex.
DR   ELM; Q14582; -.
DR   IntAct; Q14582; 4.
DR   MINT; Q14582; -.
DR   STRING; 9606.ENSP00000337889; -.
DR   iPTMnet; Q14582; -.
DR   PhosphoSitePlus; Q14582; -.
DR   BioMuta; MXD4; -.
DR   DMDM; 6016524; -.
DR   MassIVE; Q14582; -.
DR   PaxDb; 9606-ENSP00000337889; -.
DR   PeptideAtlas; Q14582; -.
DR   ProteomicsDB; 60056; -.
DR   TopDownProteomics; Q14582; -.
DR   Antibodypedia; 8823; 222 antibodies from 30 providers.
DR   DNASU; 10608; -.
DR   Ensembl; ENST00000337190.7; ENSP00000337889.2; ENSG00000123933.17.
DR   GeneID; 10608; -.
DR   KEGG; hsa:10608; -.
DR   MANE-Select; ENST00000337190.7; ENSP00000337889.2; NM_006454.3; NP_006445.1.
DR   UCSC; uc003geu.2; human.
DR   AGR; HGNC:13906; -.
DR   CTD; 10608; -.
DR   DisGeNET; 10608; -.
DR   GeneCards; MXD4; -.
DR   HGNC; HGNC:13906; MXD4.
DR   HPA; ENSG00000123933; Low tissue specificity.
DR   MIM; 620016; gene.
DR   neXtProt; NX_Q14582; -.
DR   OpenTargets; ENSG00000123933; -.
DR   PharmGKB; PA134914966; -.
DR   VEuPathDB; HostDB:ENSG00000123933; -.
DR   eggNOG; KOG2483; Eukaryota.
DR   GeneTree; ENSGT00940000160120; -.
DR   HOGENOM; CLU_082604_2_0_1; -.
DR   InParanoid; Q14582; -.
DR   OMA; GPHCRRP; -.
DR   OrthoDB; 5402993at2759; -.
DR   PhylomeDB; Q14582; -.
DR   TreeFam; TF315654; -.
DR   PathwayCommons; Q14582; -.
DR   Reactome; R-HSA-1251985; Nuclear signaling by ERBB4.
DR   SignaLink; Q14582; -.
DR   SIGNOR; Q14582; -.
DR   BioGRID-ORCS; 10608; 10 hits in 1175 CRISPR screens.
DR   ChiTaRS; MXD4; human.
DR   GeneWiki; MXD4; -.
DR   GenomeRNAi; 10608; -.
DR   Pharos; Q14582; Tbio.
DR   PRO; PR:Q14582; -.
DR   Proteomes; UP000005640; Chromosome 4.
DR   RNAct; Q14582; Protein.
DR   Bgee; ENSG00000123933; Expressed in right hemisphere of cerebellum and 170 other cell types or tissues.
DR   ExpressionAtlas; Q14582; baseline and differential.
DR   GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR   GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
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:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:ARUK-UCL.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   CDD; cd18929; bHLHzip_Mad4; 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; PTHR11969:SF4; MAX DIMERIZATION PROTEIN 4; 1.
DR   PANTHER; PTHR11969; MAX DIMERIZATION, MAD; 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; Q14582; HS.
PE   1: Evidence at protein level;
KW   DNA-binding; Nucleus; Reference proteome; Repressor; Transcription;
KW   Transcription regulation.
FT   CHAIN           1..209
FT                   /note="Max dimerization protein 4"
FT                   /id="PRO_0000127266"
FT   DOMAIN          53..105
FT                   /note="bHLH"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT   REGION          6..23
FT                   /note="Interaction with SIN3A and SIN3B"
FT                   /evidence="ECO:0000250"
FT   REGION          140..209
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        140..154
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        178..192
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   209 AA;  23528 MW;  ACFAFB44EB0FE7A2 CRC64;
     MELNSLLILL EAAEYLERRD REAEHGYASV LPFDGDFARE KTKAAGLVRK APNNRSSHNE
     LEKHRRAKLR LYLEQLKQLV PLGPDSTRHT TLSLLKRAKV HIKKLEEQDR RALSIKEQLQ
     QEHRFLKRRL EQLSVQSVER VRTDSTGSAV STDDSEQEVD IEGMEFGPGE LDSVGSSSDA
     DDHYSLQSGT GGDSGFGPHC RRLGRPALS
//