Overview
| Uniprot ID | P42568 |
|---|
| Protein Name | Protein AF-9 |
|---|
| Gene Name | MLLT3 |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 219 |
REHKSAFKEPSRDHN |
| 283 |
QDKKAPSKRPPISDS |
| 324 |
ILTCSADKKQIKDKS |
| 325 |
LTCSADKKQIKDKSH |
| 339 |
HVKMGKVKIESETSE |
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)
Protein Sequence
10
MASSCAVQVK
20
LELGHRAQVR
30
KKPTVEGFTH
40
DWMVFVRGPE
50
HSNIQHFVEK
60
VVFHLHESFP
70
RPKRVCKDPP
80
YKVEESGYAG
90
FILPIEVYFK
100
NKEEPRKVRF
110
DYDLFLHLEG
120
HPPVNHLRCE
130
KLTFNNPTED
140
FRRKLLKAGG
150
DPNRSIHTSS
160
SSSSSSSSSS
170
SSSSSSSSSS
180
SSSSSSSSSS
190
SSSSSSSSSS
200
TSFSKPHKLM
210
KEHKEKPSKD
220
SREHKSAFKE
230
PSRDHNKSSK
240
ESSKKPKENK
250
PLKEEKIVPK
260
MAFKEPKPMS
270
KEPKPDSNLL
280
TITSGQDKKA
290
PSKRPPISDS
300
EELSAKKRKK
310
SSSEALFKSF
320
SSAPPLILTC
330
SADKKQIKDK
340
SHVKMGKVKI
350
ESETSEKKKS
360
TLPPFDDIVD
370
PNDSDVEENI
380
SSKSDSEQPS
390
PASSSSSSSS
400
SFTPSQTRQQ
410
GPLRSIMKDL
420
HSDDNEEESD
430
EVEDNDNDSE
440
MERPVNRGGS
450
RSRRVSLSDG
460
SDSESSSASS
470
PLHHEPPPPL
480
LKTNNNQILE
490
VKSPIKQSKS
500
DKQIKNGECD
510
KAYLDELVEL
520
HRRLMTLRER
530
HILQQIVNLI
540
EETGHFHITN
550
TTFDFDLCSL
560
DKTTVRKLQS
YLETSGTS
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005694 |
chromosome |
| Cellular Component |
GO:0070062 |
extracellular exosome |
| Cellular Component |
GO:0005654 |
nucleoplasm |
| Cellular Component |
GO:0005634 |
nucleus |
| Cellular Component |
GO:0008023 |
transcription elongation factor complex |
| Molecular Function |
GO:0003682 |
chromatin binding |
| Molecular Function |
GO:0003677 |
DNA binding |
| Molecular Function |
GO:0042393 |
histone binding |
| Molecular Function |
GO:0140044 |
histone H3K18ac reader activity |
| Molecular Function |
GO:0140119 |
histone H3K27ac reader activity |
| Molecular Function |
GO:0140072 |
histone H3K9ac reader activity |
| Molecular Function |
GO:0140030 |
modification-dependent protein binding |
| Molecular Function |
GO:0060090 |
molecular adaptor activity |
| Biological Process |
GO:0006351 |
DNA-templated transcription |
| Biological Process |
GO:0060218 |
hematopoietic stem cell differentiation |
| Biological Process |
GO:0090090 |
negative regulation of canonical Wnt signaling pathway |
| Biological Process |
GO:0045893 |
positive regulation of DNA-templated transcription |
| Biological Process |
GO:2000096 |
positive regulation of Wnt signaling pathway, planar cell polarity pathway |
| Biological Process |
GO:1902275 |
regulation of chromatin organization |
| Biological Process |
GO:2000035 |
regulation of stem cell division |
Reference
[1] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.