MLLT3
entrez
4300
canonical
uniprot
P42568
canonical
ensembl
ENSG00000171843
resolver
ensp
ENSP00000369695
resolver
ensp
ENSP00000485996
resolver
genesymbol
MLLT3
resolver
genesymbol_syn
AF9
resolver
genesymbol_syn
YEATS3
resolver
hgnc
HGNC:7136
resolver
uniprot
A0A0S2Z448
resolver
uniprot
B1AMQ2
resolver
uniprot
B2R7B3
resolver
uniprot
B7Z755
resolver
uniprot
D3DRJ8
resolver
uniprot
Q8IVB0
resolver
uniprot_entry
A0A0S2Z448_HUMAN
resolver
uniprot_entry
AF9_HUMAN
resolver
uniprot_sec
B1AMQ2
resolver
uniprot_sec
B2R7B3
resolver
uniprot_sec
B7Z755
resolver
uniprot_sec
D3DRJ8
resolver
uniprot_sec
Q8IVB0
resolver
activity_regulation
ACTIVITY REGULATION: Crotonylated lysine binding is strongly inhibited by the peptide XL-07i, carrying a 2-furancarbonyl side chain and capped with a hydrophobic carboxybenzyl group (PubMed:30374167). XL-07i targets the unique pi-pi-pi stacking interaction at the crotonylation recognition site (PubMed:30374167). {ECO:0000269|PubMed:30374167}.
uniprot
proteins
amino_acid_sequence
MASSCAVQVKLELGHRAQVRKKPTVEGFTHDWMVFVRGPEHSNIQHFVEKVVFHLHESFPRPKRVCKDPPYKVEESGYAGFILPIEVYFKNKEEPRKVRFDYDLFLHLEGHPPVNHLRCEKLTFNNPTEDFRRKLLKAGGDPNRSIHTSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSTSFSKPHKLMKEHKEKPSKDSREHKSAFKEPSRDHNKSSKESSKKPKENKPLKEEKIVPKMAFKEPKPMSKEPKPDSNLLTITSGQDKKAPSKRPPISDSEELSAKKRKKSSSEALFKSFSSAPPLILTCSADKKQIKDKSHVKMGKVKIESETSEKKKSTLPPFDDIVDPNDSDVEENISSKSDSEQPSPASSSSSSSSSFTPSQTRQQGPLRSIMKDLHSDDNEEESDEVEDNDNDSEMERPVNRGGSRSRRVSLSDGSDSESSSASSPLHHEPPPPLLKTNNNQILEVKSPIKQSKSDKQIKNGECDKAYLDELVELHRRLMTLRERHILQQIVNLIEETGHFHITNTTFDFDLCSLDKTTVRKLQSYLETSGTS
uniprot
proteins
disease_involvement
DISEASE: Note=A chromosomal aberration involving MLLT3 is associated with acute leukemias. Translocation t(9;11)(p22;q23) with KMT2A/MLL1. The result is a rogue activator protein. Fusion protein KMT2A-MLLT3 interacts with MEN1 and PSIP1 (PubMed:22936661, PubMed:25305204). {ECO:0000269|PubMed:10861294, ECO:0000269|PubMed:22936661, ECO:0000269|PubMed:25305204, ECO:0000269|PubMed:8506309}.; DISEASE: Note=A chromosomal aberration involving MLLT3 was observed in a patient with neuromotor development delay, cerebellar ataxia and epilepsy. Translocation t(4;9)(q35;p22). {ECO:0000269|PubMed:16001262}.
uniprot
proteins
function
FUNCTION: Chromatin reader component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA (PubMed:20159561, PubMed:20471948, PubMed:25417107, PubMed:27105114, PubMed:27545619). Specifically recognizes and binds acylated histone H3, with a preference for histone H3 that is crotonylated (PubMed:25417107, PubMed:27105114, PubMed:27545619, PubMed:30374167, PubMed:30385749). Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors (PubMed:25417107, PubMed:27105114, PubMed:27545619). Recognizes and binds histone H3 crotonylated at 'Lys-9' (H3K9cr), and with slightly lower affinity histone H3 crotonylated at 'Lys-18' (H3K18cr) (PubMed:27105114). Also recognizes and binds histone H3 acetylated and butyrylated at 'Lys-9' (H3K9ac and H3K9bu, respectively), but with lower affinity than crotonylated histone H3 (PubMed:25417107, PubMed:27105114, PubMed:30385749). In the SEC complex, MLLT3 is required to recruit the complex to crotonylated histones (PubMed:27105114, PubMed:27545619). Recruitment of the SEC complex to crotonylated histones promotes recruitment of DOT1L on active chromatin to deposit histone H3 'Lys-79' methylation (H3K79me) (PubMed:25417107). Plays a key role in hematopoietic stem cell (HSC) maintenance by preserving, rather than conferring, HSC stemness (PubMed:31776511). Acts by binding to the transcription start site of active genes in HSCs and sustaining level of H3K79me2, probably by recruiting DOT1L (PubMed:31776511). Required for DOT1L-mediated H3K79 hypermethylation at the SCNN1A promoter, resulting in transcriptional repression (By similarity). May play a role in leukemogenic gene transcription (PubMed:39794553). {ECO:0000250|UniProtKB:A2AM29, ECO:0000269|PubMed:20159561, ECO:0000269|PubMed:20471948, ECO:0000269|PubMed:25417107, ECO:0000269|PubMed:27105114, ECO:0000269|PubMed:27545619, ECO:0000269|PubMed:30374167, ECO:0000269|PubMed:30385749, ECO:0000269|PubMed:31776511, ECO:0000269|PubMed:39794553}.
uniprot
proteins
mass_dalton
63351
uniprot
proteins
mutagenesis
MUTAGEN 28; /note="F->A: Decreased binding to crotonylated histone H3. Decreased binding to acetylated histone H3."; /evidence="ECO:0000269|PubMed:25417107, ECO:0000269|PubMed:27105114"; MUTAGEN 56; /note="H->A: Decreased binding to crotonylated histone H3. Decreased binding to acetylated histone H3."; /evidence="ECO:0000269|PubMed:25417107, ECO:0000269|PubMed:27105114"; MUTAGEN 58; /note="S->A: Decreased binding to crotonylated histone H3. Decreased binding to acetylated histone H3."; /evidence="ECO:0000269|PubMed:25417107, ECO:0000269|PubMed:27105114"; MUTAGEN 59; /note="F->A: Strongly decreased binding to crotonylated histone H3. Decreased binding to acetylated histone H3."; /evidence="ECO:0000269|PubMed:25417107, ECO:0000269|PubMed:27105114, ECO:0000269|PubMed:27545619"; MUTAGEN 61..67; /note="RPKRVCK->EPERVCE: Decreased DNA-binding."; /evidence="ECO:0000269|PubMed:30385749"; MUTAGEN 77; /note="G->A: Decreased binding to crotonylated histone H3. Decreased binding to acetylated histone H3."; /evidence="ECO:0000269|PubMed:25417107, ECO:0000269|PubMed:27105114"; MUTAGEN 78..79; /note="YA->WG: Binds equally well acetylated and crotonylated histone H3."; /evidence="ECO:0000269|PubMed:30385749"; MUTAGEN 78; /note="Y->A: Strongly decreased binding to crotonylated histone H3. Decreased binding to acetylated histone H3."; /evidence="ECO:0000269|PubMed:25417107, ECO:0000269|PubMed:27105114, ECO:0000269|PubMed:27545619"; MUTAGEN 78; /note="Y->W: Does not affect ability to discriminate between acetylated and crotonylated histone H3."; /evidence="ECO:0000269|PubMed:30385749"; MUTAGEN 81; /note="F->A: Decreased binding to acetylated histone H3."; /evidence="ECO:0000269|PubMed:25417107"; MUTAGEN 103; /note="D->A: Decreased binding to acetylated histone H3."; /evidence="ECO:0000269|PubMed:25417107
uniprot
proteins
pubmed
10861294
uniprot
proteins
pubmed
10898795
uniprot
proteins
pubmed
11313972
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15164053
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16001262
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20159561
uniprot
proteins
pubmed
20471948
uniprot
proteins
pubmed
22195968
uniprot
proteins
pubmed
22895430
uniprot
proteins
pubmed
22936661
uniprot
proteins
pubmed
23145062
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23260655
uniprot
proteins
pubmed
25218447
uniprot
proteins
pubmed
25305204
uniprot
proteins
pubmed
25417107
uniprot
proteins
pubmed
27105114
uniprot
proteins
pubmed
27545619
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
30134174
uniprot
proteins
pubmed
30374167
uniprot
proteins
pubmed
30385749
uniprot
proteins
pubmed
31776511
uniprot
proteins
pubmed
39794553
uniprot
proteins
pubmed
8506309
uniprot
proteins
sequence_length
568
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00376, ECO:0000269|PubMed:27105114}. Chromosome {ECO:0000269|PubMed:25417107, ECO:0000269|PubMed:27105114}. Note=Colocalizes with acylated histone H3 (PubMed:25417107, PubMed:27105114). Colocalizes with histone H3 crotonylated at 'Lys-18' (H3K18cr) (PubMed:27105114). {ECO:0000269|PubMed:25417107, ECO:0000269|PubMed:27105114}.
uniprot
proteins