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Entry version 248 (23 Feb 2022)
Sequence version 5 (01 May 2007)
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Protein

Histone-lysine N-methyltransferase 2A

Gene

KMT2A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Histone methyltransferase that plays an essential role in early development and hematopoiesis (PubMed:15960975, PubMed:12453419, PubMed:15960975, PubMed:19556245, PubMed:19187761, PubMed:20677832, PubMed:21220120, PubMed:26886794).

Catalytic subunit of the MLL1/MLL complex, a multiprotein complex that mediates both methylation of 'Lys-4' of histone H3 (H3K4me) complex and acetylation of 'Lys-16' of histone H4 (H4K16ac) (PubMed:15960975, PubMed:12453419, PubMed:15960975, PubMed:19556245, PubMed:24235145, PubMed:19187761, PubMed:20677832, PubMed:21220120, PubMed:26886794).

Catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) via a non-processive mechanism. Part of chromatin remodeling machinery predominantly forms H3K4me1 and H3K4me2 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:25561738, PubMed:15960975, PubMed:12453419, PubMed:15960975, PubMed:19556245, PubMed:19187761, PubMed:20677832, PubMed:21220120, PubMed:26886794).

Has weak methyltransferase activity by itself, and requires other component of the MLL1/MLL complex to obtain full methyltransferase activity (PubMed:19187761, PubMed:26886794).

Has no activity toward histone H3 phosphorylated on 'Thr-3', less activity toward H3 dimethylated on 'Arg-8' or 'Lys-9', while it has higher activity toward H3 acetylated on 'Lys-9' (PubMed:19187761).

Binds to unmethylated CpG elements in the promoter of target genes and helps maintain them in the nonmethylated state (PubMed:20010842).

Required for transcriptional activation of HOXA9 (PubMed:12453419, PubMed:20677832, PubMed:20010842).

Promotes PPP1R15A-induced apoptosis (PubMed:10490642).

Plays a critical role in the control of circadian gene expression and is essential for the transcriptional activation mediated by the CLOCK-ARNTL/BMAL1 heterodimer (By similarity).

Establishes a permissive chromatin state for circadian transcription by mediating a rhythmic methylation of 'Lys-4' of histone H3 (H3K4me) and this histone modification directs the circadian acetylation at H3K9 and H3K14 allowing the recruitment of CLOCK-ARNTL/BMAL1 to chromatin (By similarity).

Also has auto-methylation activity on Cys-3882 in absence of histone H3 substrate (PubMed:24235145).

By similarity1 Publication9 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the 'Function' section describes biophysical and chemical properties, such as maximal absorption, kinetic parameters, pH dependence, redox potentials and temperature dependence.<p><a href='/help/biophysicochemical_properties' target='_top'>More...</a></p>Kineticsi

  1. KM=10.4 µM for S-adenosyl-L-methionine (for histone-lysine N-methyltransferase activity)1 Publication
  2. KM=6.5 µM for S-adenosyl-L-methionine (for protein-cysteine methyltransferase)1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the 'Description' field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi1155Zinc 1PROSITE-ProRule annotationCombined sources1 Publication1
Metal bindingi1158Zinc 1PROSITE-ProRule annotationCombined sources1 Publication1
Metal bindingi1161Zinc 1PROSITE-ProRule annotationCombined sources1 Publication1
Metal bindingi1167Zinc 2PROSITE-ProRule annotationCombined sources1 Publication1
Metal bindingi1170Zinc 2PROSITE-ProRule annotationCombined sources1 Publication1
Metal bindingi1173Zinc 2PROSITE-ProRule annotationCombined sources1 Publication1
Metal bindingi1189Zinc 2PROSITE-ProRule annotationCombined sources1 Publication1
Metal bindingi1194Zinc 1PROSITE-ProRule annotationCombined sources1 Publication1
<p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections ('Function', 'PTM / Processing', 'Pathology and Biotech') according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei3765Important for WDR5-recognition and binding1 Publication1
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei3839S-adenosyl-L-methioninePROSITE-ProRule annotationCombined sources2 Publications1
Binding sitei3841S-adenosyl-L-methioninePROSITE-ProRule annotationCombined sources2 Publications1
Binding sitei3883S-adenosyl-L-methioninePROSITE-ProRule annotationCombined sources2 Publications1
Metal bindingi3909ZincCombined sources2 Publications1
Metal bindingi3957ZincCombined sources2 Publications1
Binding sitei3958S-adenosyl-L-methioninePROSITE-ProRule annotationCombined sources2 Publications1
Metal bindingi3959ZincCombined sources2 Publications1
Metal bindingi3964ZincCombined sources2 Publications1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section specifies the position and type of each DNA-binding domain present within the protein.<p><a href='/help/dna_bind' target='_top'>More...</a></p>DNA bindingi169 – 180A.T hook 1Add BLAST12
DNA bindingi217 – 227A.T hook 2Add BLAST11
DNA bindingi301 – 309A.T hook 39
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section specifies the position(s) and type(s) of zinc fingers within the protein.<p><a href='/help/zn_fing' target='_top'>More...</a></p>Zinc fingeri1147 – 1195CXXC-typePROSITE-ProRule annotation1 PublicationAdd BLAST49
Zinc fingeri1431 – 1482PHD-type 1PROSITE-ProRule annotationAdd BLAST52
Zinc fingeri1479 – 1533PHD-type 2PROSITE-ProRule annotationAdd BLAST55
Zinc fingeri1566 – 1627PHD-type 3PROSITE-ProRule annotationAdd BLAST62
Zinc fingeri1870 – 1910C2HC pre-PHD-typePROSITE-ProRule annotationAdd BLAST41
Zinc fingeri1931 – 1978PHD-type 4PROSITE-ProRule annotationAdd BLAST48

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionChromatin regulator, DNA-binding, Methyltransferase, Transferase
Biological processApoptosis, Biological rhythms, Transcription, Transcription regulation
LigandMetal-binding, S-adenosyl-L-methionine, Zinc

Enzyme and pathway databases

Pathway Commons web resource for biological pathway data

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PathwayCommonsi
Q03164

Reactome - a knowledgebase of biological pathways and processes

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Reactomei
R-HSA-3214841, PKMTs methylate histone lysines
R-HSA-8936459, RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function
R-HSA-8939236, RUNX1 regulates transcription of genes involved in differentiation of HSCs
R-HSA-9616222, Transcriptional regulation of granulopoiesis

SignaLink: a signaling pathway resource with multi-layered regulatory networks

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SignaLinki
Q03164

SIGNOR Signaling Network Open Resource

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SIGNORi
Q03164

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Histone-lysine N-methyltransferase 2A (EC:2.1.1.3646 Publications)
Short name:
Lysine N-methyltransferase 2A
Alternative name(s):
ALL-11 Publication
CXXC-type zinc finger protein 7
Cysteine methyltransferase KMT2ACurated (EC:2.1.1.-1 Publication)
Myeloid/lymphoid or mixed-lineage leukemia
Myeloid/lymphoid or mixed-lineage leukemia protein 1
Trithorax-like protein
Zinc finger protein HRX
Cleaved into the following 2 chains:
Alternative name(s):
N-terminal cleavage product of 320 kDa
Short name:
p320
Alternative name(s):
C-terminal cleavage product of 180 kDa
Short name:
p180
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:KMT2A
Synonyms:ALL1, CXXC7, HRX, HTRX, MLL, MLL1, TRX1
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 11

Organism-specific databases

Human Gene Nomenclature Database

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HGNCi
HGNC:7132, KMT2A

Online Mendelian Inheritance in Man (OMIM)

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MIMi
159555, gene+phenotype

neXtProt; the human protein knowledge platform

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neXtProti
NX_Q03164

Eukaryotic Pathogen, Vector and Host Database Resources

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VEuPathDBi
HostDB:ENSG00000118058

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Keywords - Cellular componenti

Nucleus

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Wiedemann-Steiner syndrome (WDSTS)1 Publication
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA syndrome characterized by hairy elbows (hypertrichosis cubiti), intellectual disability, a distinctive facial appearance, and short stature. Facial characteristics include long eyelashes, thick or arched eyebrows with a lateral flare, and downslanting and vertically narrow palpebral fissures.
Related information in OMIM
Chromosomal aberrations involving KMT2A are a cause of acute leukemias. Translocation t(1;11)(q21;q23) with MLLT11/AF1Q; translocation t(3;11)(p21;q23) with NCKIPSD/AF3p21; translocation t(3,11)(q25,q23) with GMPS; translocation t(4;11)(q21;q23) with AFF1/MLLT2/AF4; insertion ins(5;11)(q31;q13q23) with AFF4/AF5Q31; translocation t(5;11)(q12;q23) with AF5-alpha/CENPK; translocation t(6;11)(q27;q23) with AFDN; translocation t(9;11)(p22;q23) with MLLT3/AF9; translocation t(10;11)(p11.2;q23) with ABI1; translocation t(10;11)(p12;q23) with MLLT10/AF10; t(11;15)(q23;q14) with KNL1 and ZFYVE19; translocation t(11;17)(q23;q21) with MLLT6/AF17; translocation t(11;19)(q23;p13.3) with ELL; translocation t(11;19)(q23;p13.3) with MLLT1/ENL; translocation t(11;19)(q23;p23) with GAS7; translocation t(X;11)(q13;q23) with FOXO4/AFX1. Translocation t(3;11)(q28;q23) with LPP. Translocation t(10;11)(q22;q23) with TET1. Translocation t(9;11)(q34;q23) with DAB2IP. Translocation t(4;11)(p12;q23) with FRYL. Fusion proteins KMT2A-MLLT1, KMT2A-MLLT3 and KMT2A-ELL interact with PPP1R15A and, on the contrary to unfused KMT2A, inhibit PPP1R15A-induced apoptosis. Fusion protein KMT2A-MLLT3 interacts with MEN1 and PSIP1 (PubMed:22936661, PubMed:25305204).3 Publications
A chromosomal aberration involving KMT2A may be a cause of chronic neutrophilic leukemia. Translocation t(4;11)(q21;q23) with SEPT11.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi6R → A: Reduced interaction with MEN1. 1 Publication1
Mutagenesisi7W → A: Reduced interaction with MEN1. 1 Publication1
Mutagenesisi8R → A: Reduced interaction with MEN1. 1 Publication1
Mutagenesisi9F → A: Loss of interaction with MEN1. 1 Publication1
Mutagenesisi9F → H or Y: Reduced interaction with MEN1. 1 Publication1
Mutagenesisi10P → A: Reduced interaction with MEN1. 1 Publication1
Mutagenesisi11A → R: Reduced interaction with MEN1. 1 Publication1
Mutagenesisi12R → A: Reduced interaction with MEN1. 1 Publication1
Mutagenesisi13P → A: Reduced interaction with MEN1. 1 Publication1
Mutagenesisi24R → E: Reduced interaction with MEN1; when associated with E-25. 1 Publication1
Mutagenesisi25R → E: Reduced interaction with MEN1; when associated with E-24. 1 Publication1
Mutagenesisi129F → A: Weakly affects interaction with PSIP1 whereas significantly decreases interaction of KMT2A-MEN1 complex with PSIP1. Reduced interaction with PSIP1; when associated with A-133. 2 Publications1
Mutagenesisi132V → A: Reduced interaction with PSIP1; when associated with A-133. 1 Publication1
Mutagenesisi133F → A: Reduced interaction with PSIP1; when associated with A-129 or A-132. 2 Publications1
Mutagenesisi136S → D: Phosphomimetic mutant. Significant increase in interaction with PSIP1; when associated with D-142. 1 Publication1
Mutagenesisi142S → D: Phosphomimetic mutant. Significant increase in interaction with PSIP1; when associated with D-136. 1 Publication1
Mutagenesisi144E → Q: Loss of interaction with PSIP1; when associated with Q-146 and A-148. 1 Publication1
Mutagenesisi146E → Q: Loss of interaction with PSIP1; when associated with Q-144 and A-148. 1 Publication1
Mutagenesisi148F → A: Reduced interaction with PSIP1. Loss of interaction with PSIP1; when associated with A-149 or Q-144 and Q-146. 2 Publications1
Mutagenesisi149L → A: Loss of interaction with PSIP1; when associated with A-148. 1 Publication1
Mutagenesisi151F → A: Reduced interaction with PSIP1. 1 Publication1
Mutagenesisi1150R → A: Impairs DNA-binding. 1 Publication1
Mutagenesisi1151R → A: Impairs DNA-binding. 1 Publication1
Mutagenesisi1153R → A: No effect on stability or DNA-binding. 1 Publication1
Mutagenesisi1154R → A: Impairs DNA-binding. 2 Publications1
Mutagenesisi1155C → A: Abolishes zinc-binding and stability of the CXXC-type zinc finger and causes loss of DNA-binding. 1 Publication1
Mutagenesisi1158C → A: Abolishes zinc-binding and stability of the CXXC-type zinc finger and causes loss of DNA-binding. 1 Publication1
Mutagenesisi1161C → A: Abolishes zinc-binding and stability of the CXXC-type zinc finger and causes loss of DNA-binding. 1 Publication1
Mutagenesisi1162Q → A: No effect on stability or DNA-binding. 1 Publication1
Mutagenesisi1166D → A: Abolishes zinc-binding and stability of the CXXC-type zinc finger and causes loss of DNA-binding. 1 Publication1
Mutagenesisi1167C → A: Abolishes zinc-binding and stability of the CXXC-type zinc finger and causes loss of DNA-binding. 1 Publication1
Mutagenesisi1170C → A: Abolishes zinc-binding and stability of the CXXC-type zinc finger and causes loss of DNA-binding. 1 Publication1
Mutagenesisi1172N → A: No effect on stability or DNA-binding. 1 Publication1
Mutagenesisi1173C → A: Abolishes zinc-binding and stability of the CXXC-type zinc finger and causes loss of DNA-binding. 1 Publication1
Mutagenesisi1175D → A: Impairs DNA-binding. 1 Publication1
Mutagenesisi1176K → A: Impairs DNA-binding. 1 Publication1
Mutagenesisi1178 – 1181KFGG → AAAA: Abolishes zinc-binding and stability of the CXXC-type zinc finger and causes loss of DNA-binding. 1 Publication4
Mutagenesisi1178K → A: Impairs DNA-binding. 1 Publication1
Mutagenesisi1179F → A: Impairs DNA-binding. 1 Publication1
Mutagenesisi1183N → A: Impairs DNA-binding. 1 Publication1
Mutagenesisi1185K → A: Impairs DNA-binding. 2 Publications1
Mutagenesisi1186K → A: Impairs DNA-binding. 1 Publication1
Mutagenesisi1187Q → A: Impairs DNA-binding. 2 Publications1
Mutagenesisi1188C → A: No effect on stability or DNA-binding. 2 Publications1
Mutagenesisi1188C → D: Abolishes DNA-binding and increases CpG methylation of the HOXA9 promoter region. Does not lead to the development of leukemia when overexpressed in mice as gene fusion with MLLT3. 1 Publication1
Mutagenesisi1189C → A: Abolishes zinc-binding and stability of the CXXC-type zinc finger and causes loss of DNA-binding. 1 Publication1
Mutagenesisi1192R → A: Abolishes zinc-binding and stability of the CXXC-type zinc finger and causes loss of DNA-binding. 1 Publication1
Mutagenesisi1193K → A: Impairs DNA-binding. 2 Publications1
Mutagenesisi1194C → A: Impairs zinc-binding and stability of the CXXC-type zinc finger and causes loss of DNA-binding. 1 Publication1
Mutagenesisi1195Q → A: No effect on stability or DNA-binding. 1 Publication1
Mutagenesisi1196N → A: No effect on stability or DNA-binding. 1 Publication1
Mutagenesisi1197L → A: Mildly decreases DNA-binding. 1 Publication1
Mutagenesisi1200M → A: No effect on DNA-binding. 1 Publication1
Mutagenesisi1581Y → A: Decreases affinity for histone H3K4me3. 1 Publication1
Mutagenesisi1587Q → A: Decreases affinity for histone H3K4me3. 1 Publication1
Mutagenesisi1594W → A: Abolishes interaction with histone H3K4me3. 1 Publication1
Mutagenesisi1594W → E: Decreases affinity for histone H3K4me3. 1 Publication1
Mutagenesisi1617V → A: Decreases binding affinity for PPIE. 1 Publication1
Mutagenesisi1619Y → A: May perturb protein folding and thereby decrease binding affinity for PPIE. 1 Publication1
Mutagenesisi2666 – 2667DG → AA: Reduces cleavage without abolishing it. Abolishes cleavage by TASP1; when associated with 2718-A--A-2720. 1 Publication2
Mutagenesisi2718 – 2720DGV → AAA: Abolishes cleavage by TASP1; when associated with 2666-A-A-2667. 2 Publications3
Mutagenesisi3763S → A: Increased interaction with WDR5. 1 Publication1
Mutagenesisi3765R → A: Loss of interaction with the WRAD complex and WDR5. 2 Publications1
Mutagenesisi3769H → A or F: Slight decrease in interaction with WDR5. 1 Publication1
Mutagenesisi3769H → Y: Increased interaction with WDR5. 1 Publication1
Mutagenesisi3858Y → A: Impairs methyltransferase activity toward unmodified or monomethylated H3K4me. 1 Publication1
Mutagenesisi3858Y → F: Slightly affects methyltransferase activity toward unmodified or monomethylated H3K4me. 1 Publication1
Mutagenesisi3861N → I: Leads to stable interaction with ASH2L and RBBP5 in the absence of WDR5; when associated with L-3867. 1 Publication1
Mutagenesisi3861N → T: Leads to stable interaction with ASH2L and RBBP5 in the absence of WDR5; when associated with V-3867. 1 Publication1
Mutagenesisi3864R → A: Disrupts interaction with ASH2L and RBBP5 and nearly abolishes histone methyltransferase activity. 1 Publication1
Mutagenesisi3867Q → A: Slightly affects methyltransferase activity of the enzyme alone, while it impairs methyltransferase activity in complex; when associated with A-3871. 1 Publication1
Mutagenesisi3867Q → L: Leads to stable interaction with ASH2L and RBBP5 in the absence of WDR5; when associated with I-3861. 1 Publication1
Mutagenesisi3867Q → V: Leads to stable interaction with ASH2L and RBBP5 in the absence of WDR5; when associated with T-3861. 1 Publication1
Mutagenesisi3869D → A: Does not affect methyltransferase activity of the enzyme alone or in complex; when associated with A-3872. 1 Publication1
Mutagenesisi3871R → A: Slightly affects methyltransferase activity of the enzyme alone, while it impairs methyltransferase activity in complex; when associated with A-3867. 1 Publication1
Mutagenesisi3872E → A: Does not affect methyltransferase activity of the enzyme alone or in complex; when associated with A-3869. 1 Publication1
Mutagenesisi3874Y → A: Affects methyltransferase activity of the enzyme alone, while it does not affect methyltransferase activity in complex; when associated with A-3878. 1 Publication1
Mutagenesisi3878K → A: Affects methyltransferase activity of the enzyme alone, while it does not affect methyltransferase activity in complex; when associated with A-3874. 1 Publication1
Mutagenesisi3882C → A or S: Abolished auto-methylation. 1 Publication1
Mutagenesisi3906N → A: Loss of the histone H3 methyltransferase activity. Abolishes interaction with S-adenosyl-L-methionine. 2 Publications1
Mutagenesisi3942Y → A or F: Impairs methyltransferase activity toward unmodified or monomethylated H3K4me. 2 Publications1
Mutagenesisi3942Y → F: Shifts from a specific monomethyltransferase to a di- and trimethyltransferase activity. 2 Publications1

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei1334 – 1335Breakpoint for translocation to form KMT2A-ZFYVE19 oncogene2
Sitei1362 – 1363Breakpoint for translocation to form KMT2A-AF3P21 and KMT2A-KNL1 oncogenes2
Sitei1362 – 1363Breakpoint for translocation to form KMT2A-CENPK oncogene2
Sitei1362Breakpoint for translocation to form KMT2A-FRYL fusion protein1
Sitei1406 – 1407Breakpoint for translocation to form KMT2A-AFF4 fusion protein2
Sitei1444 – 1445Breakpoint for translocation to form KMT2A-GAS7 oncogene2
Sitei1444 – 1445Breakpoint for translocation to form KMT2A-LPP2

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

DisGeNET

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DisGeNETi
4297

MalaCards human disease database

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MalaCardsi
KMT2A
MIMi159555, gene+phenotype
605130, phenotype

Open Targets

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OpenTargetsi
ENSG00000118058

Orphanet; a database dedicated to information on rare diseases and orphan drugs

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Orphaneti
98831, Acute myeloid leukemia with 11q23 abnormalities
402017, Acute myeloid leukemia with t(9;11)(p22;q23)
98835, Acute undifferentiated leukemia
530995, Mixed phenotype acute leukemia
99860, Precursor B-cell acute lymphoblastic leukemia
319182, Wiedemann-Steiner syndrome

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA241

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

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Pharosi
Q03164, Tchem

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

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ChEMBLi
CHEMBL1293299

Genetic variation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
KMT2A

Domain mapping of disease mutations (DMDM)

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DMDMi
146345435

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00001248761 – 3969Histone-lysine N-methyltransferase 2AAdd BLAST3969
ChainiPRO_00003909491 – 2718MLL cleavage product N3202 PublicationsAdd BLAST2718
ChainiPRO_00003909502719 – 3969MLL cleavage product C1802 PublicationsAdd BLAST1251

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei136Phosphoserine; by CK21 Publication1
Modified residuei142Phosphoserine; by CK21 Publication1
Modified residuei153PhosphoserineCombined sources1 Publication1
Modified residuei197PhosphoserineCombined sources1
Modified residuei239N6-acetyllysineBy similarity1
Modified residuei373N6-acetyllysineBy similarity1
Modified residuei518PhosphoserineCombined sources1
Modified residuei636N6-acetyllysineCombined sources1
Modified residuei680PhosphoserineCombined sources1
Modified residuei840PhosphothreonineCombined sources1
Modified residuei926PhosphoserineCombined sources1
Modified residuei1056PhosphoserineCombined sources1
Modified residuei1130N6-acetyllysineCombined sources1
Modified residuei1235N6-acetyllysineCombined sources1
Modified residuei1837PhosphoserineCombined sources1
Modified residuei1845PhosphothreonineCombined sources1
Modified residuei1858PhosphoserineCombined sources1
Modified residuei2098PhosphoserineCombined sources1
Modified residuei2147PhosphothreonineCombined sources1
Modified residuei2151PhosphoserineCombined sources1
Modified residuei2201PhosphoserineCombined sources1
Modified residuei2525PhosphothreonineCombined sources1
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section describes <strong>covalent linkages</strong> of various types formed <strong>between two proteins (interchain cross-links)</strong> or <strong>between two parts of the same protein (intrachain cross-links)</strong>, except the disulfide bonds that are annotated in the <a href="http://www.uniprot.org/manual/disulfid">'Disulfide bond'</a> subsection.<p><a href='/help/crosslnk' target='_top'>More...</a></p>Cross-linki2528Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei2611PhosphoserineCombined sources1
Modified residuei2796PhosphoserineCombined sources1
Modified residuei2955PhosphoserineCombined sources1
Modified residuei2958N6-acetyllysineBy similarity1
Modified residuei3036PhosphoserineCombined sources1
Modified residuei3372PhosphothreonineCombined sources1
Modified residuei3462N6-acetyllysineBy similarity1
Modified residuei3511PhosphoserineCombined sources1
Modified residuei3515PhosphoserineCombined sources1
Modified residuei3527PhosphoserineCombined sources1
Modified residuei3882S-methylcysteine; by autocatalysis1 Publication1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Proteolytic cleavage by TASP1 generates MLL cleavage product N320 and MLL cleavage product C180, which reassemble through a non-covalent association. 2 cleavage sites exist, cleavage site 1 (CS1) and cleavage site 2 (CS2), to generate MLL cleavage products N320 and C180. CS2 is the major site.2 Publications
Phosphorylation increases its interaction with PSIP1.1 Publication
Auto-methylated at Cys-3882: auto-methylation is inhibited by the WRAD complex and unmodified histone H3.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei2666 – 2667Cleavage; by TASP1, site 11 Publication2
Sitei2718 – 2719Cleavage; by TASP1, site 21 Publication2

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
Q03164

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
Q03164

MassIVE - Mass Spectrometry Interactive Virtual Environment

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MassIVEi
Q03164

MaxQB - The MaxQuant DataBase

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MaxQBi
Q03164

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
Q03164

PeptideAtlas

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PeptideAtlasi
Q03164

PRoteomics IDEntifications database

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PRIDEi
Q03164

ProteomicsDB: a multi-organism proteome resource

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ProteomicsDBi
23014
58195 [Q03164-1]
58196 [Q03164-2]

PTM databases

CarbonylDB database of protein carbonylation sites

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CarbonylDBi
Q03164

GlyConnect protein glycosylation platform

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GlyConnecti
2046, 1 N-Linked glycan (1 site)

GlyGen: Computational and Informatics Resources for Glycoscience

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GlyGeni
Q03164, 17 sites, 2 N-linked glycans (1 site), 2 O-linked glycans (16 sites)

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
Q03164

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

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PhosphoSitePlusi
Q03164

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Heart, lung, brain and T- and B-lymphocytes.

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000118058, Expressed in forebrain and 256 other tissues

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
Q03164, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
Q03164, HS

Organism-specific databases

Human Protein Atlas

More...
HPAi
ENSG00000118058, Low tissue specificity

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

MLL cleavage product N320 heterodimerizes with MLL cleavage product C180 (via SET and FYRC domains).

Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, HCFC2, WDR5, DPY30 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MEN1, MGA, KAT8/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10 (PubMed:15199122, PubMed:15960975, PubMed:17500065, PubMed:19556245, PubMed:23508102, PubMed:19187761, PubMed:26886794).

Forms a core complex with the evolutionary conserved subcomplex WRAD composed of WDR5, RBBP5, ASH2L/ASH2 and DPY30 subunits; WRAD differentially stimulates the methyltransferase activity (PubMed:25561738).

Interacts (via WIN motif) with WDR5; the interaction is direct (PubMed:19556245, PubMed:18829459, PubMed:22665483, PubMed:18840606). Interaction with WDR5 is required for stable interaction with ASH2L and RBBP5, and thereby also for optimal histone methyltransferase activity (PubMed:26886794).

Interacts with KAT8/MOF; the interaction is direct (PubMed:15960975).

Interacts with SBF1 and PPP1R15A (PubMed:9537414, PubMed:10490642).

Interacts with ZNF335 (PubMed:23178126).

Interacts with CLOCK and ARNTL/BMAL1 in a circadian manner (By similarity).

Interacts with PPIE; this results in decreased histone H3 methyltransferase activity (PubMed:20677832, PubMed:20541251).

Interacts with CREBBP (PubMed:16253272).

Interacts with the WRAD complex composed of WDR5, RBBP5, ASH2L and DPY30 (PubMed:22665483).

Interacts (via MBM motif) with MEN1 (PubMed:22936661, PubMed:22327296, PubMed:25305204).

Interacts (via IBM motifs) with PSIP1 (via IBD domain) with moderate affinity whereas the KMT2A-MEN1 complex interacts with a greater affinity; MEN1 enhances interaction of KMT2A with PSIP1 (PubMed:22327296, PubMed:25305204, PubMed:25082813, PubMed:29997176). Phosphorylation increases its affinity for PSIP1 (PubMed:29997176).

Forms a complex with CREBBP and CREB1 (PubMed:23651431).

By similarity25 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

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GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

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BioGRIDi
110443, 197 interactors

ComplexPortal: manually curated resource of macromolecular complexes

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ComplexPortali
CPX-5850, Histone-lysine N-methyltransferase complex, KMT2A variant

CORUM comprehensive resource of mammalian protein complexes

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CORUMi
Q03164

Database of interacting proteins

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DIPi
DIP-29221N

The Eukaryotic Linear Motif resource for Functional Sites in Proteins

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ELMi
Q03164

Protein interaction database and analysis system

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IntActi
Q03164, 64 interactors

Molecular INTeraction database

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MINTi
Q03164

STRING: functional protein association networks

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STRINGi
9606.ENSP00000436786

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
Q03164

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

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RNActi
Q03164, protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

13969
Legend: HelixTurnBeta strandPDB Structure known for this area
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3D structure databases

Biological Magnetic Resonance Data Bank

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BMRBi
Q03164

Small Angle Scattering Biological Data Bank

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SASBDBi
Q03164

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
Q03164

Database of comparative protein structure models

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ModBasei
Search...

Protein Data Bank in Europe - Knowledge Base

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PDBe-KBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

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EvolutionaryTracei
Q03164

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family%5Fand%5Fdomains%5Fsection">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini1703 – 1748Bromo; divergentPROSITE-ProRule annotationAdd BLAST46
Domaini2018 – 2074FYR N-terminalPROSITE-ProRule annotationAdd BLAST57
Domaini3666 – 3747FYR C-terminalPROSITE-ProRule annotationAdd BLAST82
Domaini3829 – 3945SETPROSITE-ProRule annotationAdd BLAST117
Domaini3953 – 3969Post-SETPROSITE-ProRule annotationAdd BLAST17

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni1 – 108DisorderedSequence analysisAdd BLAST108
Regioni132 – 253DisorderedSequence analysisAdd BLAST122
Regioni301 – 352DisorderedSequence analysisAdd BLAST52
Regioni445 – 585DisorderedSequence analysisAdd BLAST141
Regioni713 – 780DisorderedSequence analysisAdd BLAST68
Regioni798 – 949DisorderedSequence analysisAdd BLAST152
Regioni1038 – 1066DisorderedSequence analysisAdd BLAST29
Regioni1106 – 1166DisorderedSequence analysisAdd BLAST61
Regioni1200 – 1375DisorderedSequence analysisAdd BLAST176
Regioni1584 – 1600Interaction with histone H3K4me31 PublicationAdd BLAST17
Regioni1663 – 1713DisorderedSequence analysisAdd BLAST51
Regioni1806 – 1869DisorderedSequence analysisAdd BLAST64
Regioni2081 – 2133DisorderedSequence analysisAdd BLAST53
Regioni2145 – 2232DisorderedSequence analysisAdd BLAST88
Regioni2275 – 2333DisorderedSequence analysisAdd BLAST59
Regioni2373 – 2460DisorderedSequence analysisAdd BLAST88
Regioni2475 – 2618DisorderedSequence analysisAdd BLAST144
Regioni2647 – 2675DisorderedSequence analysisAdd BLAST29
Regioni2713 – 2821DisorderedSequence analysisAdd BLAST109
Regioni2961 – 3064DisorderedSequence analysisAdd BLAST104
Regioni3166 – 3244DisorderedSequence analysisAdd BLAST79
Regioni3464 – 3608DisorderedSequence analysisAdd BLAST145
Regioni3620 – 3643DisorderedSequence analysisAdd BLAST24
Regioni3785 – 3808DisorderedSequence analysisAdd BLAST24
Regioni3906 – 3907S-adenosyl-L-methionine bindingCombined sources2 Publications2

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi6 – 25Menin-binding motif (MBM)1 PublicationAdd BLAST20
Motifi123 – 134Integrase domain-binding motif 1 (IBM1)1 PublicationAdd BLAST12
Motifi147 – 152Integrase domain-binding motif 2 (IBM2)1 Publication6
Motifi2847 – 28559aaTAD1 Publication9
Motifi3762 – 3767WDR5 interaction motif (WIN)2 Publications6

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes the position of regions of compositional bias within the protein and the particular type of amino acids that are over-represented within those regions.<p><a href='/help/compbias' target='_top'>More...</a></p>Compositional biasi37 – 58Pro residuesSequence analysisAdd BLAST22
Compositional biasi81 – 103Polar residuesSequence analysisAdd BLAST23
Compositional biasi184 – 203Polar residuesSequence analysisAdd BLAST20
Compositional biasi204 – 226Basic and acidic residuesSequence analysisAdd BLAST23
Compositional biasi236 – 253Basic and acidic residuesSequence analysisAdd BLAST18
Compositional biasi325 – 351Basic and acidic residuesSequence analysisAdd BLAST27
Compositional biasi445 – 495Polar residuesSequence analysisAdd BLAST51
Compositional biasi535 – 556Polar residuesSequence analysisAdd BLAST22
Compositional biasi557 – 576Pro residuesSequence analysisAdd BLAST20
Compositional biasi713 – 731Polar residuesSequence analysisAdd BLAST19
Compositional biasi747 – 780Polar residuesSequence analysisAdd BLAST34
Compositional biasi798 – 845Polar residuesSequence analysisAdd BLAST48
Compositional biasi846 – 898Basic and acidic residuesSequence analysisAdd BLAST53
Compositional biasi1046 – 1061Polar residuesSequence analysisAdd BLAST16
Compositional biasi1249 – 1272Basic and acidic residuesSequence analysisAdd BLAST24
Compositional biasi1278 – 1302Polar residuesSequence analysisAdd BLAST25
Compositional biasi1303 – 1317Pro residuesSequence analysisAdd BLAST15
Compositional biasi1822 – 1847Pro residuesSequence analysisAdd BLAST26
Compositional biasi2096 – 2118Polar residuesSequence analysisAdd BLAST23
Compositional biasi2146 – 2174Polar residuesSequence analysisAdd BLAST29
Compositional biasi2189 – 2232Polar residuesSequence analysisAdd BLAST44
Compositional biasi2275 – 2320Polar residuesSequence analysisAdd BLAST46
Compositional biasi2402 – 2418Polar residuesSequence analysisAdd BLAST17
Compositional biasi2419 – 2445Basic and acidic residuesSequence analysisAdd BLAST27
Compositional biasi2526 – 2594Polar residuesSequence analysisAdd BLAST69
Compositional biasi2721 – 2746Polar residuesSequence analysisAdd BLAST26
Compositional biasi2747 – 2784Basic and acidic residuesSequence analysisAdd BLAST38
Compositional biasi2785 – 2821Polar residuesSequence analysisAdd BLAST37
Compositional biasi3011 – 3064Polar residuesSequence analysisAdd BLAST54
Compositional biasi3166 – 3183Polar residuesSequence analysisAdd BLAST18
Compositional biasi3195 – 3222Polar residuesSequence analysisAdd BLAST28
Compositional biasi3230 – 3244Polar residuesSequence analysisAdd BLAST15
Compositional biasi3464 – 3530Polar residuesSequence analysisAdd BLAST67
Compositional biasi3563 – 3606Polar residuesSequence analysisAdd BLAST44

<p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.1 Publication