ID   MAML1_HUMAN             Reviewed;        1016 AA.
AC   Q92585; Q9NZ12;
DT   05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2005, sequence version 3.
DT   27-MAR-2024, entry version 180.
DE   RecName: Full=Mastermind-like protein 1;
DE            Short=Mam-1;
GN   Name=MAML1 {ECO:0000312|HGNC:HGNC:13632};
GN   Synonyms=KIAA0200 {ECO:0000312|EMBL:BAA12114.2};
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:0000312|EMBL:BAA12114.2}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Bone marrow {ECO:0000269|PubMed:8724849};
RX   PubMed=8724849; DOI=10.1093/dnares/3.1.17;
RA   Nagase T., Seki N., Ishikawa K., Tanaka A., Nomura N.;
RT   "Prediction of the coding sequences of unidentified human genes. V. The
RT   coding sequences of 40 new genes (KIAA0161-KIAA0200) deduced by analysis of
RT   cDNA clones from human cell line KG-1.";
RL   DNA Res. 3:17-24(1996).
RN   [2] {ECO:0000305, ECO:0000312|EMBL:AAF34658.1}
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 124-1016, FUNCTION, SUBCELLULAR LOCATION,
RP   TISSUE SPECIFICITY, INTERACTION WITH NOTCH1; NOTCH2; NOTCH3 AND NOTCH4, AND
RP   VARIANT ASN-1007.
RC   TISSUE=Cervix carcinoma;
RX   PubMed=11101851; DOI=10.1038/82644;
RA   Wu L., Aster J.C., Blacklow S.C., Lake R., Artavanis-Tsakonas S.,
RA   Griffin J.D.;
RT   "MAML1, a human homologue of Drosophila mastermind, is a transcriptional
RT   co-activator for NOTCH receptors.";
RL   Nat. Genet. 26:484-489(2000).
RN   [3]
RP   FUNCTION, AND INTERACTION WITH NOTCH1.
RX   PubMed=11390662; DOI=10.1128/mcb.21.13.4337-4346.2001;
RA   Kitagawa M., Oyama T., Kawashima T., Yedvobnick B., Kumar A., Matsuno K.,
RA   Harigaya K.;
RT   "A human protein with sequence similarity to Drosophila mastermind
RT   coordinates the nuclear form of Notch and a CSL protein to build a
RT   transcriptional activator complex on target promoters.";
RL   Mol. Cell. Biol. 21:4337-4346(2001).
RN   [4]
RP   FUNCTION, AND INTERACTION WITH CREBBP.
RX   PubMed=12050117; DOI=10.1101/gad.991602;
RA   Fryer C.J., Lamar E., Turbachova I., Kintner C., Jones K.A.;
RT   "Mastermind mediates chromatin-specific transcription and turnover of the
RT   Notch enhancer complex.";
RL   Genes Dev. 16:1397-1411(2002).
RN   [5]
RP   FUNCTION, AND INTERACTION WITH CDK8.
RX   PubMed=15546612; DOI=10.1016/j.molcel.2004.10.014;
RA   Fryer C.J., White J.B., Jones K.A.;
RT   "Mastermind recruits CycC:CDK8 to phosphorylate the Notch ICD and
RT   coordinate activation with turnover.";
RL   Mol. Cell 16:509-520(2004).
RN   [6]
RP   FUNCTION, AND INTERACTION WITH TP53.
RX   PubMed=17317671; DOI=10.1074/jbc.m608974200;
RA   Zhao Y., Katzman R.B., Delmolino L.M., Bhat I., Zhang Y., Gurumurthy C.B.,
RA   Germaniuk-Kurowska A., Reddi H.V., Solomon A., Zeng M.S., Kung A., Ma H.,
RA   Gao Q., Dimri G., Stanculescu A., Miele L., Wu L., Griffin J.D.,
RA   Wazer D.E., Band H., Band V.;
RT   "The notch regulator MAML1 interacts with p53 and functions as a
RT   coactivator.";
RL   J. Biol. Chem. 282:11969-11981(2007).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-314 AND SER-360, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Leukemic T-cell;
RX   PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA   Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA   Rodionov V., Han D.K.;
RT   "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT   reveals system-wide modulation of protein-protein interactions.";
RL   Sci. Signal. 2:RA46-RA46(2009).
RN   [8]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-822, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19608861; DOI=10.1126/science.1175371;
RA   Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA   Olsen J.V., Mann M.;
RT   "Lysine acetylation targets protein complexes and co-regulates major
RT   cellular functions.";
RL   Science 325:834-840(2009).
RN   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-45; SER-314 AND SER-360, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma, and 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).
RN   [10]
RP   X-RAY CRYSTALLOGRAPHY (3.25 ANGSTROMS) OF 13-74 IN COMPLEX WITH RBPSUH AND
RP   NOTCH1.
RX   PubMed=16530044; DOI=10.1016/j.cell.2005.12.037;
RA   Nam Y., Sliz P., Song L., Aster J.C., Blacklow S.C.;
RT   "Structural basis for cooperativity in recruitment of MAML coactivators to
RT   Notch transcription complexes.";
RL   Cell 124:973-983(2006).
CC   -!- FUNCTION: Acts as a transcriptional coactivator for NOTCH proteins. Has
CC       been shown to amplify NOTCH-induced transcription of HES1. Enhances
CC       phosphorylation and proteolytic turnover of the NOTCH intracellular
CC       domain in the nucleus through interaction with CDK8. Binds to
CC       CREBBP/CBP which promotes nucleosome acetylation at NOTCH enhancers and
CC       activates transcription. Induces phosphorylation and localization of
CC       CREBBP to nuclear foci. Plays a role in hematopoietic development by
CC       regulating NOTCH-mediated lymphoid cell fate decisions.
CC       {ECO:0000269|PubMed:11101851, ECO:0000269|PubMed:11390662,
CC       ECO:0000269|PubMed:12050117, ECO:0000269|PubMed:15546612,
CC       ECO:0000269|PubMed:17317671}.
CC   -!- SUBUNIT: Interacts (via N-terminus) with NOTCH1, NOTCH2, NOTCH3 and
CC       NOTCH4 (via ankyrin repeat region). Interacts (via N-terminus) with p53
CC       (via DNA-binding region). Forms a DNA-binding complex with Notch
CC       proteins and RBPSUH/RBP-J kappa/CBF1. Also binds CREBBP/CBP and
CC       CDK8.Forms a complex with PRAG1, NOTCH1 and MAML1, in a MAML1-dependent
CC       manner (By similarity). {ECO:0000250|UniProtKB:Q6T264,
CC       ECO:0000269|PubMed:11101851, ECO:0000269|PubMed:11390662,
CC       ECO:0000269|PubMed:12050117, ECO:0000269|PubMed:15546612,
CC       ECO:0000269|PubMed:16530044, ECO:0000269|PubMed:17317671}.
CC   -!- INTERACTION:
CC       Q92585; P46531: NOTCH1; NbExp=15; IntAct=EBI-908250, EBI-636374;
CC   -!- SUBCELLULAR LOCATION: Nucleus speckle {ECO:0000269|PubMed:11101851}.
CC       Note=Nuclear, in a punctate manner.
CC   -!- TISSUE SPECIFICITY: Widely expressed with highest levels in heart,
CC       pancreas, peripheral blood leukocytes and spleen.
CC       {ECO:0000269|PubMed:11101851}.
CC   -!- DOMAIN: The C-terminal region is required for transcriptional
CC       activation. {ECO:0000269|PubMed:11101851}.
CC   -!- SIMILARITY: Belongs to the mastermind family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAA12114.2; Type=Erroneous initiation; Evidence={ECO:0000305};
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; D83785; BAA12114.2; ALT_INIT; mRNA.
DR   EMBL; AF221759; AAF34658.1; -; mRNA.
DR   CCDS; CCDS34315.1; -.
DR   RefSeq; NP_055572.1; NM_014757.4.
DR   PDB; 2F8X; X-ray; 3.25 A; M=13-74.
DR   PDB; 3NBN; X-ray; 3.45 A; C/F=13-74.
DR   PDB; 3V79; X-ray; 3.85 A; M=13-74.
DR   PDB; 6SMV; X-ray; 2.14 A; A=1003-1016.
DR   PDBsum; 2F8X; -.
DR   PDBsum; 3NBN; -.
DR   PDBsum; 3V79; -.
DR   PDBsum; 6SMV; -.
DR   AlphaFoldDB; Q92585; -.
DR   SMR; Q92585; -.
DR   BioGRID; 115138; 70.
DR   ComplexPortal; CPX-937; CSL-NOTCH1-MAML transcriptional activation complex.
DR   CORUM; Q92585; -.
DR   DIP; DIP-29920N; -.
DR   IntAct; Q92585; 35.
DR   MINT; Q92585; -.
DR   STRING; 9606.ENSP00000292599; -.
DR   GlyCosmos; Q92585; 1 site, 1 glycan.
DR   GlyGen; Q92585; 10 sites, 1 O-linked glycan (10 sites).
DR   iPTMnet; Q92585; -.
DR   PhosphoSitePlus; Q92585; -.
DR   BioMuta; MAML1; -.
DR   DMDM; 68565602; -.
DR   EPD; Q92585; -.
DR   jPOST; Q92585; -.
DR   MassIVE; Q92585; -.
DR   MaxQB; Q92585; -.
DR   PaxDb; 9606-ENSP00000292599; -.
DR   PeptideAtlas; Q92585; -.
DR   ProteomicsDB; 75342; -.
DR   Pumba; Q92585; -.
DR   Antibodypedia; 29514; 259 antibodies from 35 providers.
DR   DNASU; 9794; -.
DR   Ensembl; ENST00000292599.4; ENSP00000292599.3; ENSG00000161021.13.
DR   Ensembl; ENST00000638220.2; ENSP00000491444.1; ENSG00000283780.3.
DR   GeneID; 9794; -.
DR   KEGG; hsa:9794; -.
DR   MANE-Select; ENST00000292599.4; ENSP00000292599.3; NM_014757.5; NP_055572.1.
DR   UCSC; uc003mkm.3; human.
DR   AGR; HGNC:13632; -.
DR   CTD; 9794; -.
DR   DisGeNET; 9794; -.
DR   GeneCards; MAML1; -.
DR   HGNC; HGNC:13632; MAML1.
DR   HPA; ENSG00000161021; Low tissue specificity.
DR   MIM; 605424; gene.
DR   neXtProt; NX_Q92585; -.
DR   OpenTargets; ENSG00000161021; -.
DR   PharmGKB; PA30569; -.
DR   VEuPathDB; HostDB:ENSG00000161021; -.
DR   eggNOG; ENOG502QSU1; Eukaryota.
DR   GeneTree; ENSGT00950000183201; -.
DR   HOGENOM; CLU_008569_1_0_1; -.
DR   InParanoid; Q92585; -.
DR   OMA; DLPCMIT; -.
DR   OrthoDB; 4273441at2759; -.
DR   PhylomeDB; Q92585; -.
DR   TreeFam; TF332922; -.
DR   PathwayCommons; Q92585; -.
DR   Reactome; R-HSA-1912408; Pre-NOTCH Transcription and Translation.
DR   Reactome; R-HSA-210744; Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells.
DR   Reactome; R-HSA-2122947; NOTCH1 Intracellular Domain Regulates Transcription.
DR   Reactome; R-HSA-2197563; NOTCH2 intracellular domain regulates transcription.
DR   Reactome; R-HSA-2644606; Constitutive Signaling by NOTCH1 PEST Domain Mutants.
DR   Reactome; R-HSA-2894862; Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
DR   Reactome; R-HSA-350054; Notch-HLH transcription pathway.
DR   Reactome; R-HSA-8941856; RUNX3 regulates NOTCH signaling.
DR   Reactome; R-HSA-9013508; NOTCH3 Intracellular Domain Regulates Transcription.
DR   Reactome; R-HSA-9013695; NOTCH4 Intracellular Domain Regulates Transcription.
DR   Reactome; R-HSA-9793380; Formation of paraxial mesoderm.
DR   SignaLink; Q92585; -.
DR   SIGNOR; Q92585; -.
DR   BioGRID-ORCS; 9794; 31 hits in 1165 CRISPR screens.
DR   ChiTaRS; MAML1; human.
DR   EvolutionaryTrace; Q92585; -.
DR   GeneWiki; MAML1; -.
DR   GenomeRNAi; 9794; -.
DR   Pharos; Q92585; Tbio.
DR   PRO; PR:Q92585; -.
DR   Proteomes; UP000005640; Chromosome 5.
DR   RNAct; Q92585; Protein.
DR   Bgee; ENSG00000161021; Expressed in sural nerve and 138 other cell types or tissues.
DR   GO; GO:0002193; C:MAML1-RBP-Jkappa- ICN1 complex; IDA:UniProtKB.
DR   GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR   GO; GO:0005654; C:nucleoplasm; IBA:GO_Central.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0042605; F:peptide antigen binding; IPI:UniProtKB.
DR   GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR   GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB.
DR   GO; GO:0060928; P:atrioventricular node cell development; ISS:BHF-UCL.
DR   GO; GO:0003162; P:atrioventricular node development; ISS:BHF-UCL.
DR   GO; GO:0045445; P:myoblast differentiation; IEA:Ensembl.
DR   GO; GO:0007219; P:Notch signaling pathway; IDA:UniProtKB.
DR   GO; GO:0010831; P:positive regulation of myotube differentiation; IGI:UniProtKB.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR   GO; GO:0007221; P:positive regulation of transcription of Notch receptor target; IBA:GO_Central.
DR   GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR   Gene3D; 6.10.250.970; -; 1.
DR   IDEAL; IID00220; -.
DR   InterPro; IPR046369; MAML1-3.
DR   InterPro; IPR048456; MAML1_3_TAD1.
DR   InterPro; IPR048455; MAML1_3_TAD2.
DR   InterPro; IPR046370; MAML_N_sf.
DR   InterPro; IPR019082; Mastermind-like_N.
DR   PANTHER; PTHR15692; MASTERMIND-LIKE; 1.
DR   PANTHER; PTHR15692:SF19; MASTERMIND-LIKE PROTEIN 1; 1.
DR   Pfam; PF09596; MamL-1; 1.
DR   Pfam; PF20802; MAML1_3_TAD1; 1.
DR   Pfam; PF20801; MAML1_3_TAD2; 1.
DR   SMART; SM01275; MamL-1; 1.
DR   Genevisible; Q92585; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Activator; Notch signaling pathway; Nucleus;
KW   Phosphoprotein; Reference proteome; Transcription;
KW   Transcription regulation.
FT   CHAIN           1..1016
FT                   /note="Mastermind-like protein 1"
FT                   /id="PRO_0000129493"
FT   REGION          1..123
FT                   /note="Required for interaction with NOTCH proteins"
FT                   /evidence="ECO:0000269|PubMed:11101851"
FT   REGION          65..184
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          263..487
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          561..617
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          658..681
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          796..953
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        95..113
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        114..129
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        168..182
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        263..283
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        307..374
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        388..439
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        453..469
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        573..617
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        664..681
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        796..817
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        831..889
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         45
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         120
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q6T264"
FT   MOD_RES         303
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q6T264"
FT   MOD_RES         314
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19690332,
FT                   ECO:0007744|PubMed:23186163"
FT   MOD_RES         360
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19690332,
FT                   ECO:0007744|PubMed:23186163"
FT   MOD_RES         822
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:19608861"
FT   MOD_RES         1015
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q6T264"
FT   VARIANT         583
FT                   /note="S -> N (in dbSNP:rs41285557)"
FT                   /id="VAR_061335"
FT   VARIANT         1007
FT                   /note="S -> N (in dbSNP:rs6895902)"
FT                   /evidence="ECO:0000269|PubMed:11101851"
FT                   /id="VAR_029010"
FT   HELIX           17..69
FT                   /evidence="ECO:0007829|PDB:2F8X"
FT   HELIX           1003..1013
FT                   /evidence="ECO:0007829|PDB:6SMV"
SQ   SEQUENCE   1016 AA;  108054 MW;  C683CB81B73A2A61 CRC64;
     MVLPTCPMAE FALPRHSAVM ERLRRRIELC RRHHSTCEAR YEAVSPERLE LERQHTFALH
     QRCIQAKAKR AGKHRQPPAA TAPAPAAPAP RLDAADGPEH GRPATHLHDT VKRNLDSATS
     PQNGDQQNGY GDLFPGHKKT RREAPLGVAI SSNGLPPASP LGQSDKPSGA DALQSSGKHS
     LGLDSLNKKR LADSSLHLNG GSNPSESFPL SLNKELKQEP VEDLPCMITG TVGSISQSNL
     MPDLNLNEQE WKELIEELNR SVPDEDMKDL FNEDFEEKKD PESSGSATQT PLAQDINIKT
     EFSPAAFEQE QLGSPQVRAG SAGQTFLGPS SAPVSTDSPS LGGSQTLFHT SGQPRADNPS
     PNLMPASAQA QNAQRALAGV VLPSQGPGGA SELSSAHQLQ QIAAKQKREQ MLQNPQQATP
     APAPGQMSTW QQTGPSHSSL DVPYPMEKPA SPSSYKQDFT NSKLLMMPSV NKSSPRPGGP
     YLQPSHVNLL SHQPPSNLNQ NSANNQGSVL DYGNTKPLSH YKADCGQGSP GSGQSKPALM
     AYLPQQLSHI SHEQNSLFLM KPKPGNMPFR SLVPPGQEQN PSSVPVQAQA TSVGTQPPAV
     SVASSHNSSP YLSSQQQAAV MKQHQLLLDQ QKQREQQQKH LQQQQFLQRQ QHLLAEQEKQ
     QFQRHLTRPP PQYQDPTQGS FPQQVGQFTG SSAAVPGMNT LGPSNSSCPR VFPQAGNLMP
     MGPGHASVSS LPTNSGQQDR GVAQFPGSQN MPQSSLYGMA SGITQIVAQP PPQATNGHAH
     IPRQTNVGQN TSVSAAYGQN SLGSSGLSQQ HNKGTLNPGL TKPPVPRVSP AMGGQNSSWQ
     HQGMPNLSGQ TPGNSNVSPF TAASSFHMQQ QAHLKMSSPQ FSQAVPNRPM APMSSAAAVG
     SLLPPVSAQQ RTSAPAPAPP PTAPQQGLPG LSPAGPELGA FSQSPASQMG GRAGLHCTQA
     YPVRTAGQEL PFAYSGQPGG SGLSSVAGHT DLIDSLLKNR TSEEWMSDLD DLLGSQ
//