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Q92585 (MAML1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Mastermind-like protein 1

Short name=Mam-1
Gene names
Name:MAML1
Synonyms:KIAA0200
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1016 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Acts as a transcriptional coactivator for NOTCH proteins. Has been shown to amplify NOTCH-induced transcription of HES1. Enhances phosphorylation and proteolytic turnover of the NOTCH intracellular domain in the nucleus through interaction with CDK8. Binds to CREBBP/CBP which promotes nucleosome acetylation at NOTCH enhancers and activates transcription. Induces phosphorylation and localization of CREBBP to nuclear foci. Plays a role in hematopoietic development by regulating NOTCH-mediated lymphoid cell fate decisions. Ref.2 Ref.3 Ref.4 Ref.5 Ref.6

Subunit structure

Interacts (via N-terminus) with NOTCH1, NOTCH2, NOTCH3 and NOTCH4 (via ankyrin repeat region). Interacts (via N-terminus) with p53 (via DNA-binding region). Forms a DNA-binding complex with Notch proteins and RBPSUH/RBP-J kappa/CBF1. Also binds CREBBP/CBP and CDK8. Ref.2 Ref.3 Ref.4 Ref.5 Ref.6

Subcellular location

Nucleus speckle. Note: Nuclear, in a punctate manner. Ref.2

Tissue specificity

Widely expressed with highest levels in heart, pancreas, peripheral blood leukocytes and spleen. Ref.2

Domain

The C-terminal region is required for transcriptional activation. Ref.2

Sequence similarities

Belongs to the mastermind family.

Sequence caution

The sequence BAA12114.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processNotch signaling pathway
Transcription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityPolymorphism
   Molecular functionActivator
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processNotch signaling pathway

Inferred from direct assay Ref.2. Source: UniProtKB

atrioventricular node cell development

Inferred from sequence or structural similarity. Source: BHF-UCL

atrioventricular node development

Inferred from sequence or structural similarity. Source: BHF-UCL

gene expression

Traceable author statement. Source: Reactome

myoblast differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of myotube differentiation

Inferred from genetic interaction PubMed 16510869. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.2PubMed 16510869. Source: UniProtKB

protein phosphorylation

Inferred from direct assay PubMed 16510869. Source: UniProtKB

transcription initiation from RNA polymerase II promoter

Traceable author statement. Source: Reactome

   Cellular_componentMAML1-RBP-Jkappa- ICN1 complex

Inferred from direct assay PubMed 16510869. Source: UniProtKB

intracellular membrane-bounded organelle

Inferred from direct assay. Source: HPA

nuclear speck

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.2PubMed 16510869PubMed 9874765. Source: UniProtKB

   Molecular_functionpeptide antigen binding

Inferred from physical interaction Ref.6. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.2Ref.3PubMed 16510869Ref.9. Source: UniProtKB

protein kinase binding

Inferred from physical interaction Ref.5. Source: UniProtKB

transcription coactivator activity

Inferred from direct assay Ref.2. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10161016Mastermind-like protein 1
PRO_0000129493

Regions

Region1 – 123123Required for interaction with NOTCH proteins Ref.2
Compositional bias642 – 6454Poly-Gln

Amino acid modifications

Modified residue1201Phosphoserine By similarity
Modified residue3141Phosphoserine Ref.7
Modified residue3601Phosphoserine Ref.7
Modified residue8221N6-acetyllysine Ref.8
Modified residue10151Phosphoserine By similarity

Natural variations

Natural variant5831S → N.
Corresponds to variant rs41285557 [ dbSNP | Ensembl ].
VAR_061335
Natural variant10071S → N. Ref.2
Corresponds to variant rs6895902 [ dbSNP | Ensembl ].
VAR_029010

Secondary structure

... 1016
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q92585 [UniParc].

Last modified July 5, 2005. Version 3.
Checksum: C683CB81B73A2A61

FASTA1,016108,054
        10         20         30         40         50         60 
MVLPTCPMAE FALPRHSAVM ERLRRRIELC RRHHSTCEAR YEAVSPERLE LERQHTFALH 

        70         80         90        100        110        120 
QRCIQAKAKR AGKHRQPPAA TAPAPAAPAP RLDAADGPEH GRPATHLHDT VKRNLDSATS 

       130        140        150        160        170        180 
PQNGDQQNGY GDLFPGHKKT RREAPLGVAI SSNGLPPASP LGQSDKPSGA DALQSSGKHS 

       190        200        210        220        230        240 
LGLDSLNKKR LADSSLHLNG GSNPSESFPL SLNKELKQEP VEDLPCMITG TVGSISQSNL 

       250        260        270        280        290        300 
MPDLNLNEQE WKELIEELNR SVPDEDMKDL FNEDFEEKKD PESSGSATQT PLAQDINIKT 

       310        320        330        340        350        360 
EFSPAAFEQE QLGSPQVRAG SAGQTFLGPS SAPVSTDSPS LGGSQTLFHT SGQPRADNPS 

       370        380        390        400        410        420 
PNLMPASAQA QNAQRALAGV VLPSQGPGGA SELSSAHQLQ QIAAKQKREQ MLQNPQQATP 

       430        440        450        460        470        480 
APAPGQMSTW QQTGPSHSSL DVPYPMEKPA SPSSYKQDFT NSKLLMMPSV NKSSPRPGGP 

       490        500        510        520        530        540 
YLQPSHVNLL SHQPPSNLNQ NSANNQGSVL DYGNTKPLSH YKADCGQGSP GSGQSKPALM 

       550        560        570        580        590        600 
AYLPQQLSHI SHEQNSLFLM KPKPGNMPFR SLVPPGQEQN PSSVPVQAQA TSVGTQPPAV 

       610        620        630        640        650        660 
SVASSHNSSP YLSSQQQAAV MKQHQLLLDQ QKQREQQQKH LQQQQFLQRQ QHLLAEQEKQ 

       670        680        690        700        710        720 
QFQRHLTRPP PQYQDPTQGS FPQQVGQFTG SSAAVPGMNT LGPSNSSCPR VFPQAGNLMP 

       730        740        750        760        770        780 
MGPGHASVSS LPTNSGQQDR GVAQFPGSQN MPQSSLYGMA SGITQIVAQP PPQATNGHAH 

       790        800        810        820        830        840 
IPRQTNVGQN TSVSAAYGQN SLGSSGLSQQ HNKGTLNPGL TKPPVPRVSP AMGGQNSSWQ 

       850        860        870        880        890        900 
HQGMPNLSGQ TPGNSNVSPF TAASSFHMQQ QAHLKMSSPQ FSQAVPNRPM APMSSAAAVG 

       910        920        930        940        950        960 
SLLPPVSAQQ RTSAPAPAPP PTAPQQGLPG LSPAGPELGA FSQSPASQMG GRAGLHCTQA 

       970        980        990       1000       1010 
YPVRTAGQEL PFAYSGQPGG SGLSSVAGHT DLIDSLLKNR TSEEWMSDLD DLLGSQ 

« Hide

References

« Hide 'large scale' references
[1]"Prediction of the coding sequences of unidentified human genes. V. The coding sequences of 40 new genes (KIAA0161-KIAA0200) deduced by analysis of cDNA clones from human cell line KG-1."
Nagase T., Seki N., Ishikawa K., Tanaka A., Nomura N.
DNA Res. 3:17-24(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Bone marrow.
[2]"MAML1, a human homologue of Drosophila mastermind, is a transcriptional co-activator for NOTCH receptors."
Wu L., Aster J.C., Blacklow S.C., Lake R., Artavanis-Tsakonas S., Griffin J.D.
Nat. Genet. 26:484-489(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 124-1016, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH NOTCH1; NOTCH2; NOTCH3 AND NOTCH4, VARIANT ASN-1007.
Tissue: Cervix carcinoma.
[3]"A human protein with sequence similarity to Drosophila mastermind coordinates the nuclear form of Notch and a CSL protein to build a transcriptional activator complex on target promoters."
Kitagawa M., Oyama T., Kawashima T., Yedvobnick B., Kumar A., Matsuno K., Harigaya K.
Mol. Cell. Biol. 21:4337-4346(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH NOTCH1.
[4]"Mastermind mediates chromatin-specific transcription and turnover of the Notch enhancer complex."
Fryer C.J., Lamar E., Turbachova I., Kintner C., Jones K.A.
Genes Dev. 16:1397-1411(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CREBBP.
[5]"Mastermind recruits CycC:CDK8 to phosphorylate the Notch ICD and coordinate activation with turnover."
Fryer C.J., White J.B., Jones K.A.
Mol. Cell 16:509-520(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CDK8.
[6]"The notch regulator MAML1 interacts with p53 and functions as a coactivator."
Zhao Y., Katzman R.B., Delmolino L.M., Bhat I., Zhang Y., Gurumurthy C.B., Germaniuk-Kurowska A., Reddi H.V., Solomon A., Zeng M.S., Kung A., Ma H., Gao Q., Dimri G., Stanculescu A., Miele L., Wu L., Griffin J.D. expand/collapse author list , Wazer D.E., Band H., Band V.
J. Biol. Chem. 282:11969-11981(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH TP53.
[7]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-314 AND SER-360, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[8]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-822, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"Structural basis for cooperativity in recruitment of MAML coactivators to Notch transcription complexes."
Nam Y., Sliz P., Song L., Aster J.C., Blacklow S.C.
Cell 124:973-983(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.25 ANGSTROMS) OF 13-74 IN COMPLEX WITH RBPSUH AND NOTCH1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D83785 mRNA. Translation: BAA12114.2. Different initiation.
AF221759 mRNA. Translation: AAF34658.1.
CCDSCCDS34315.1.
RefSeqNP_055572.1. NM_014757.4.
UniGeneHs.631951.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2F8XX-ray3.25M13-74[»]
3NBNX-ray3.45C/F13-74[»]
3V79X-ray3.85M13-74[»]
ProteinModelPortalQ92585.
SMRQ92585. Positions 16-70.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115138. 15 interactions.
DIPDIP-29920N.
IntActQ92585. 2 interactions.
MINTMINT-8176809.
STRING9606.ENSP00000292599.

PTM databases

PhosphoSiteQ92585.

Polymorphism databases

DMDM68565602.

Proteomic databases

MaxQBQ92585.
PaxDbQ92585.
PRIDEQ92585.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000292599; ENSP00000292599; ENSG00000161021.
GeneID9794.
KEGGhsa:9794.
UCSCuc003mkm.3. human.

Organism-specific databases

CTD9794.
GeneCardsGC05P179159.
HGNCHGNC:13632. MAML1.
HPAHPA037687.
MIM605424. gene.
neXtProtNX_Q92585.
PharmGKBPA30569.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG68229.
HOGENOMHOG000113473.
HOVERGENHBG058017.
InParanoidQ92585.
KOK06061.
OMASWQHQGM.
OrthoDBEOG793B7M.
PhylomeDBQ92585.
TreeFamTF332922.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_2155. NICD traffics to nucleus.
REACT_71. Gene Expression.

Gene expression databases

BgeeQ92585.
CleanExHS_MAML1.
GenevestigatorQ92585.

Family and domain databases

InterProIPR019082. Neuroggenic_mastermind-like_N.
[Graphical view]
PfamPF09596. MamL-1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSMAML1. human.
EvolutionaryTraceQ92585.
GeneWikiMAML1.
GenomeRNAi9794.
NextBio36884.
PROQ92585.
SOURCESearch...

Entry information

Entry nameMAML1_HUMAN
AccessionPrimary (citable) accession number: Q92585
Secondary accession number(s): Q9NZ12
Entry history
Integrated into UniProtKB/Swiss-Prot: July 5, 2005
Last sequence update: July 5, 2005
Last modified: July 9, 2014
This is version 113 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM