Q92585 (MAML1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Mastermind-like protein 1
Short name=Mam-1

Gene names

Name:	MAML1
Synonyms:	KIAA0200

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1016 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Notch signaling pathway Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Molecular function	Activator
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Notch signaling pathway Inferred from direct assay Ref.2. Source: UniProtKB atrioventricular node cell development Inferred from sequence or structural similarity. Source: BHF-UCL myoblast differentiation Inferred from electronic annotation. Source: Compara 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_component	MAML1-RBP-Jkappa- ICN1 complex Inferred from direct assay PubMed 16510869. Source: UniProtKB nuclear speck Inferred from electronic annotation. Source: UniProtKB-SubCell nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	peptide antigen binding Inferred from physical interaction Ref.6. Source: UniProtKB transcription coactivator activity Inferred from direct assay Ref.2. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1016

1016

Mastermind-like protein 1

PRO_0000129493

Regions

Region

1 – 123

123

Required for interaction with NOTCH proteins Ref.2

Compositional bias

642 – 645

4

Poly-Gln

Amino acid modifications

Modified residue

120

1

Phosphoserine By similarity

Modified residue

314

1

Phosphoserine Ref.7

Modified residue

360

1

Phosphoserine Ref.7

Modified residue

822

1

N6-acetyllysine Ref.8

Modified residue

1015

1

Phosphoserine By similarity

Natural variations

Natural variant

583

1

S → N.
Corresponds to variant rs41285557 [ dbSNP | Ensembl ].

VAR_061335

Natural variant

1007

1

S → N. Ref.2
Corresponds to variant rs6895902 [ dbSNP | Ensembl ].

VAR_029010

Secondary structure

1

.

.

.

1016

Helix Strand Turn

Details...

Helix

17 – 69

53

Sequences

	Sequence		Length	Mass (Da)
	Q92585 [UniParc]. Last modified July 5, 2005. Version 3. Checksum: C683CB81B73A2A61	FASTA	1,016	108,054
	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

References

	« Hide 'large scale' referencesShow '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. , 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY.
[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.

IPI

IPI00006108.

RefSeq

NP_055572.1. NM_014757.4.

UniGene

Hs.631951.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2F8X	X-ray	3.25	M	13-74	[»]
3NBN	X-ray	3.45	C/F	13-74	[»]
3V79	X-ray	3.85	M	13-74	[»]

ProteinModelPortal

Q92585.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29920N.

IntAct

Q92585. 2 interactions.

STRING

9606.ENSP00000292599.

PTM databases

PhosphoSite

Q92585.

Polymorphism databases

DMDM

68565602.

Proteomic databases

PaxDb

Q92585.

PRIDE

Q92585.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000292599; ENSP00000292599; ENSG00000161021.

GeneID

9794.

KEGG

hsa:9794.

UCSC

uc003mkm.3. human.

Organism-specific databases

CTD

9794.

GeneCards

GC05P179159.

HGNC

HGNC:13632. MAML1.

HPA

HPA037687.

MIM

605424. gene.

neXtProt

NX_Q92585.

PharmGKB

PA30569.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG68229.

HOGENOM

HOG000113473.

HOVERGEN

HBG058017.

InParanoid

Q92585.

KO

K06061.

OMA

SWQHQGM.

OrthoDB

EOG4KSPJ3.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.
REACT_2155. NICD traffics to nucleus.
REACT_71. Gene Expression.

Gene expression databases

Bgee

Q92585.

CleanEx

HS_MAML1.

Genevestigator

Q92585.

GermOnline

ENSG00000161021. Homo sapiens.

Family and domain databases

InterPro

IPR019082. Neuroggenic_mastermind-like_N.
[Graphical view]

Pfam

PF09596. MamL-1. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

MAML1. human.

EvolutionaryTrace

Q92585.

GenomeRNAi

9794.

NextBio

36884.

SOURCE

Search...

Entry information

Entry name

MAML1_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 101 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.