MAML1_HUMAN
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 03-AUG-2022, entry version 171.
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};
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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; 56.
DR CORUM; Q92585; -.
DR DIP; DIP-29920N; -.
DR IntAct; Q92585; 36.
DR MINT; Q92585; -.
DR STRING; 9606.ENSP00000292599; -.
DR GlyGen; Q92585; 1 site, 1 O-linked glycan (1 site).
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; Q92585; -.
DR PeptideAtlas; Q92585; -.
DR PRIDE; Q92585; -.
DR ProteomicsDB; 75342; -.
DR Antibodypedia; 29514; 243 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 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; KEMSSAH; -.
DR OrthoDB; 177202at2759; -.
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 SignaLink; Q92585; -.
DR SIGNOR; Q92585; -.
DR BioGRID-ORCS; 9794; 29 hits in 1084 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 136 other tissues.
DR Genevisible; Q92585; HS.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
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; IDA:HPA.
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; IPR046370; MAML_N_sf.
DR InterPro; IPR019082; Mastermind-like_N.
DR PANTHER; PTHR15692; PTHR15692; 1.
DR Pfam; PF09596; MamL-1; 1.
DR SMART; SM01275; MamL-1; 1.
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
