Overview
| Uniprot ID | Q9HCI7 |
|---|
| Protein Name | E3 ubiquitin-protein ligase MSL2 |
|---|
| Gene Name | MSL2 |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 399 |
GTTPKISKTVLLSTK |
Function
Non-catalytic component of the MSL histone acetyltransferase complex, a multiprotein complex that mediates the majority of histone H4 acetylation at 'Lys-16' (H4K16ac), an epigenetic mark that prevents chromatin compaction (PubMed:16543150, PubMed:33837287). The MSL complex is required for chromosome stability and genome integrity by maintaining homeostatic levels of H4K16ac (PubMed:33837287). The MSL complex is also involved in gene dosage by promoting up-regulation of genes expressed by the X chromosome (By similarity). X up-regulation is required to compensate for autosomal biallelic expression (By similarity). The MSL complex also participates in gene dosage compensation by promoting expression of Tsix non-coding RNA (By similarity). MSL2 plays a key role in gene dosage by ensuring biallelic expression of a subset of dosage-sensitive genes, including many haploinsufficient genes (By similarity). Acts by promoting promoter-enhancer contacts, thereby preventing DNA methylation of one allele and creating a methylation-free environment for methylation-sensitive transcription factors such as SP1, KANSL1 and KANSL3 (By similarity). Also acts as an E3 ubiquitin ligase that promotes monoubiquitination of histone H2B at 'Lys-35' (H2BK34Ub), but not that of H2A (PubMed:21726816, PubMed:30930284). This activity is greatly enhanced by heterodimerization with MSL1 (PubMed:21726816, PubMed:30930284). H2B ubiquitination in turn stimulates histone H3 methylation at 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) and leads to gene activation, including that of HOXA9 and MEIS1 (PubMed:21726816). Also involved in the DNA damage response by mediating ubiquitination of TP53/p53 and TP53BP1 (PubMed:19033443, PubMed:23874665)
Protein Sequence
10
MNPVNATALY
20
ISASRLVLNY
30
DPGDPKAFTE
40
INRLLPYFRQ
50
SLSCCVCGHL
60
LQDPIAPTNS
70
TCQHYVCKTC
80
KGKKMMMKPS
90
CSWCKDYEQF
100
EENKQLSILV
110
NCYKKLCEYI
120
TQTTLARDII
130
EAVDCSSDIL
140
ALLNDGSLFC
150
EETEKPSDSS
160
FTLCLTHSPL
170
PSTSEPTTDP
180
QASLSPMSES
190
TLSIAIGSSV
200
INGLPTYNGL
210
SIDRFGINIP
220
SPEHSNTIDV
230
CNTVDIKTED
240
LSDSLPPVCD
250
TVATDLCSTG
260
IDICSFSEDI
270
KPGDSLLLSV
280
EEVLRSLETV
290
SNTEVCCPNL
300
QPNLEATVSN
310
GPFLQLSSQS
320
LSHNVFMSTS
330
PALHGLSCTA
340
ATPKIAKLNR
350
KRSRSESDSE
360
KVQPLPISTI
370
IRGPTLGASA
380
PVTVKRESKI
390
SLQPIATVPN
400
GGTTPKISKT
410
VLLSTKSMKK
420
SHEHGSKKSH
430
SKTKPGILKK
440
DKAVKEKIPS
450
HHFMPGSPTK
460
TVYKKPQEKK
470
GCKCGRATQN
480
PSVLTCRGQR
490
CPCYSNRKAC
500
LDCICRGCQN
510
SYMANGEKKL
520
EAFAVPEKAL
530
EQTRLTLGIN
540
VTSIAVRNAS
550
TSTSVINVTG
560
SPVTTFLAAS
570
THDDKSLDEA
IDMRFDC
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0000785 |
chromatin |
| Cellular Component |
GO:0072487 |
MSL complex |
| Cellular Component |
GO:0005654 |
nucleoplasm |
| Cellular Component |
GO:0005634 |
nucleus |
| Molecular Function |
GO:0141054 |
histone H2B ubiquitin ligase activity |
| Molecular Function |
GO:0140585 |
promoter-enhancer loop anchoring activity |
| Molecular Function |
GO:0061630 |
ubiquitin protein ligase activity |
| Molecular Function |
GO:0008270 |
zinc ion binding |
| Biological Process |
GO:0006974 |
DNA damage response |
| Biological Process |
GO:0040029 |
epigenetic regulation of gene expression |
| Biological Process |
GO:0045893 |
positive regulation of DNA-templated transcription |
| Biological Process |
GO:0006513 |
protein monoubiquitination |
| Biological Process |
GO:0016567 |
protein ubiquitination |
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.