Details for: MLLT1

Gene ID: 4298

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: MLLT1

Ensembl ID: ENSG00000130382

Description: MLLT1 super elongation complex subunit

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • placental villous trophoblast CL2000060
    CSI 29.67
    rCSI 45.84%
    PRS 86.99
  • ciliated epithelial cell CL0000067
    CSI 8.66
    rCSI 7.62%
    PRS 79.34
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 6.7
    rCSI 11.84%
    PRS 73.55
  • renal interstitial pericyte CL1001318
    CSI 6.62
    rCSI 18.24%
    PRS 85.1
  • hepatic stellate cell CL0000632
    CSI 6.58
    rCSI 24.66%
    PRS 83.09
  • syncytiotrophoblast cell CL0000525
    CSI 6.57
    rCSI 18.93%
    PRS 90.65
  • kidney connecting tubule epithelial cell CL1000768
    CSI 6.09
    rCSI 15.44%
    PRS 81.29
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 5.97
    rCSI 7.23%
    PRS 69
  • VIP GABAergic cortical interneuron CL4023016
    CSI 4.92
    rCSI 5.87%
    PRS 74.15
  • basal cell of epidermis CL0002187
    CSI 4.79
    rCSI 8.49%
    PRS 58.87
  • melanocyte CL0000148
    CSI 4.38
    rCSI 3.25%
    PRS 84.02
  • fibroblast of lung CL0002553
    CSI 4.35
    rCSI 4.05%
    PRS 89.45
  • interneuron CL0000099
    CSI 3.99
    rCSI 8.01%
    PRS 81.54
  • sst GABAergic cortical interneuron CL4023017
    CSI 3.83
    rCSI 4.94%
    PRS 75.18
  • suprabasal keratinocyte CL4033013
    CSI 3.69
    rCSI 6.03%
    PRS 58.25
  • ionocyte CL0005006
    CSI 3.45
    rCSI 3.69%
    PRS 90.09
  • astrocyte of the cerebral cortex CL0002605
    CSI 3.43
    rCSI 7.69%
    PRS 74.66
  • Kupffer cell CL0000091
    CSI 3.35
    rCSI 7.66%
    PRS 89.31
  • midzonal region hepatocyte CL0019028
    CSI 3.34
    rCSI 7.84%
    PRS 86.61
  • interstitial cell of Cajal CL0002088
    CSI 3.25
    rCSI 4.14%
    PRS 92.41
  • multi-ciliated epithelial cell CL0005012
    CSI 3.23
    rCSI 3.23%
    PRS 82.77
  • neural crest cell CL0011012
    CSI 2.77
    rCSI 2.19%
    PRS 80.38
  • perivascular cell CL4033054
    CSI 2.77
    rCSI 3.79%
    PRS 91.68
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 2.57
    rCSI 3.64%
    PRS 85.79
  • pulmonary capillary endothelial cell CL4028001
    CSI 2.53
    rCSI 4.82%
    PRS 94.48
  • hepatocyte CL0000182
    CSI 2.44
    rCSI 4.36%
    PRS 87.39
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 2.42
    rCSI 4.4%
    PRS 81.51
  • lung ciliated cell CL1000271
    CSI 2.29
    rCSI 2.65%
    PRS 82.46
  • skin fibroblast CL0002620
    CSI 2.28
    rCSI 1.97%
    PRS 88.03
  • vascular leptomeningeal cell CL4023051
    CSI 2.22
    rCSI 3.89%
    PRS 84.3
  • chondrocyte CL0000138
    CSI 2.2
    rCSI 3.5%
    PRS 83.28
  • cerebral cortex endothelial cell CL1001602
    CSI 2.12
    rCSI 3.68%
    PRS 82.31
  • respiratory suprabasal cell CL4033048
    CSI 2.11
    rCSI 2.71%
    PRS 90.37
  • choroid plexus epithelial cell CL0000706
    CSI 2.02
    rCSI 3.31%
    PRS 80.41
  • glioblast CL0000030
    CSI 2
    rCSI 3.19%
    PRS 80.62
  • retinal bipolar neuron CL0000748
    CSI 1.99
    rCSI 3.73%
    PRS 79.03
  • common myeloid progenitor CL0000049
    CSI 1.94
    rCSI 1.57%
    PRS 90.13
  • periportal region hepatocyte CL0019026
    CSI 1.93
    rCSI 7.52%
    PRS 85.92
  • retinal blood vessel endothelial cell CL0002585
    CSI 1.91
    rCSI 3.05%
    PRS 91.16
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 1.78
    rCSI 1.37%
    PRS 91.5
  • centrilobular region hepatocyte CL0019029
    CSI 1.75
    rCSI 4.56%
    PRS 84.88
  • extravillous trophoblast CL0008036
    CSI 1.67
    rCSI 2.07%
    PRS 86.97
  • pulmonary artery endothelial cell CL1001568
    CSI 1.63
    rCSI 2.21%
    PRS 93.43
  • retinal cone cell CL0000573
    CSI 1.57
    rCSI 2.53%
    PRS 80.14
  • melanocyte of skin CL1000458
    CSI 1.35
    rCSI 1.84%
    PRS 58.01
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.28
    rCSI 2.06%
    PRS 75.18
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.09
    rCSI 1.83%
    PRS 74.01
  • neural progenitor cell CL0011020
    CSI 1.06
    rCSI 4.66%
    PRS 77.49
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.03
    rCSI 2.51%
    PRS 71.76
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.89
    rCSI 3.35%
    PRS 74.31
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 0.78
    rCSI 1.77%
    PRS 81.56
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.65
    rCSI 2.03%
    PRS 75.44
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 0.64
    rCSI 1.99%
    PRS 77.39
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.49
    rCSI 1.75%
    PRS 71.99

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

Loading network (please wait)...

Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [MLLT1](/details-gene/4298), also known as ENL, is a protein-coding gene located on chromosome 19p13.3. It encodes a subunit of the Super Elongation Complex (SEC), a critical regulator of transcriptional elongation. Functionally, [MLLT1](/details-gene/4298) is involved in [positive regulation of dna-templated transcription](/details-go/GO0045893) through its ability to bind chromatin, specifically recognizing acetylated histones. Its role is integral to the formation and activity of the RNA Polymerase II elongation complex. While expressed across a diverse range of cell types, its significance is exceptionally high in [placental villous trophoblast](/details-cell/CL2000060). Clinically, [MLLT1](/details-gene/4298) is well-documented for its involvement in chromosomal translocations, particularly with the KMT2A (MLL) gene, which are drivers of acute leukemias ([159556](https://omim.org/entry/159556)) ([Link](https://pubmed.ncbi.nlm.nih.gov/1423624/)). ## Cellular Roles and Expression Landscape The expression profile of [MLLT1](/details-gene/4298) highlights its fundamental role in transcription across multiple lineages, with specific cellular contexts showing particularly high significance. **Overall**, the most striking feature is the exceptionally high significance of [MLLT1](/details-gene/4298) in [placental villous trophoblast](/details-cell/CL2000060) (CSI: 29.67), suggesting it is a crucial workhorse for the extensive transcriptional programs required for placental development and function. It is also highly significant in other trophoblast-lineage cells like the [syncytiotrophoblast cell](/details-cell/CL0000525). Beyond the placenta, [MLLT1](/details-gene/4298) shows elevated significance in a variety of other cell types, indicating a broad but contextually important role: * **Epithelial and Epidermal Cells:** High significance in [ciliated epithelial cell](/details-cell/CL0000067), [kidney connecting tubule epithelial cell](/details-cell/CL1000768), [basal cell of epidermis](/details-cell/CL0002187), and [suprabasal keratinocyte](/details-cell/CL4033013) points to a key role in maintaining transcriptional activity in tissues with high turnover and specialized functions. * **Neural Cells:** The gene is a significant marker in several types of interneurons, including [caudal ganglionic eminence derived cortical interneuron](/details-cell/CL4023064), [VIP GABAergic cortical interneuron](/details-cell/CL4023016), and [sst GABAergic cortical interneuron](/details-cell/CL4023017), suggesting its importance in establishing or maintaining the complex transcriptional identities of these neuronal subtypes. * **Mesenchymal and Stromal Cells:** Its notable presence in [renal interstitial pericyte](/details-cell/CL1001318), [hepatic stellate cell](/details-cell/CL0000632), and [fibroblast of lung](/details-cell/CL0002553) is consistent with a general role in regulating gene expression in supportive tissue cells. * **Immune System:** While not a pan-immune marker, its significance in [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203) suggests a potential role in the transcriptional programs that maintain the memory T cell state. This is consistent with early studies showing its transcriptional activation potential in lymphoid cells ([Link](https://pubmed.ncbi.nlm.nih.gov/8080983/)). ## Pathways and Molecular Function [MLLT1](/details-gene/4298) is fundamentally a transcriptional regulator. Its annotated functions converge on the process of controlling gene expression at the level of transcriptional elongation. * **Molecular Function:** At the molecular level, it functions as a [chromatin binding](/details-go/GO0003682) protein, with a specific affinity for [lysine-acetylated histone binding](/details-go/GO0070577). This allows it to "read" epigenetic marks associated with active transcription. It also participates in broader [protein binding](/details-go/GO0005515) interactions, which is essential for its role within multi-protein complexes. * **Cellular Component:** Consistent with its function, [MLLT1](/details-gene/4298) is localized to the sites of transcription, including the [nucleoplasm](/details-go/GO0005654) and the [fibrillar center](/details-go/GO0001650) of the nucleolus. It is a core component of the [transcription elongation factor complex](/details-go/GO0008023). * **Biological Process:** These molecular activities culminate in the [positive regulation of dna-templated transcription](/details-go/GO0045893). This is primarily achieved through its participation in Reactome pathways such as [Formation of rna pol ii elongation complex](/details-go/R-HSA-112382) and [Rna polymerase ii transcription elongation](/details-go/R-HSA-75955). Its involvement in these pathways confirms its role as part of the machinery that ensures efficient transcription of protein-coding genes ([Link](https://doi.org/10.1016/j.molcel.2010.01.026)). ## Research Directions The widespread expression of [MLLT1](/details-gene/4298) underscores its fundamental biological role, while its association with leukemia provides a compelling avenue for translational research. **Proposed Hypotheses:** 1. Given its exceptionally high significance in [placental villous trophoblast](/details-cell/CL2000060), [MLLT1](/details-gene/4298) is likely a master regulator of placental gene expression, essential for driving the transcriptional programs that control trophoblast invasion, differentiation, and endocrine function. 2. In the context of t(11;19) leukemias, the MLL-MLLT1 fusion protein ectopically recruits the Super Elongation Complex to MLL target genes (e.g., *HOX* genes), leading to their aberrant and sustained expression, which in turn blocks hematopoietic differentiation and drives leukemogenesis. **Key Experimental Approach:** To test the second hypothesis, a multi-omics approach in a relevant leukemia cell line (e.g., KOPN-8, which harbors the MLL-MLLT1 fusion) would be powerful. One could perform CUT&RUN or ChIP-seq using antibodies against the MLL N-terminus to map the genome-wide binding sites of the fusion protein. Parallel RNA-seq and ATAC-seq experiments would reveal the corresponding changes in gene expression and chromatin accessibility at these target sites. This would identify the direct downstream gene network dysregulated by the MLL-MLLT1 oncoprotein, providing a mechanistic link between the translocation and the leukemia phenotype. **Therapeutic Potential:** [MLLT1](/details-gene/4298) itself represents a challenging therapeutic target due to its essential role in transcription in healthy tissues. Direct inhibition of the wild-type protein would likely lead to significant toxicity. However, the MLL-MLLT1 fusion protein in leukemia presents a more attractive, cancer-specific target. The therapeutic strategy would focus on **inhibition** of the fusion protein's function. This could be achieved by developing small molecules or proteolysis-targeting chimeras (PROTACs) that specifically disrupt the protein-protein interactions unique to the MLL-MLLT1 neocomplex or that selectively target the fusion protein for degradation. Such an approach would aim to disable the oncogenic driver while sparing the function of wild-type MLLT1 in healthy cells.

Genular Protein ID: 3440031313

Symbol: ENL_HUMAN

Name: Protein ENL

UniProtKB Accession Codes:

Q03111 Q14768

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CORUM 1 CTD 1 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 2 Ensembl 1 GO 7 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 24 PDBsum 24 PIR 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 3 RefSeq 1 SIGNOR 1 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 1423624

Title: Involvement of a homolog of Drosophila trithorax by 11q23 chromosomal translocations in acute leukemias.

PubMed ID: 1423624

DOI: 10.1016/0092-8674(92)90602-9

PubMed ID: 8378076

Title: Two distinct portions of LTG19/ENL at 19p13 are involved in t(11;19) leukemia.

PubMed ID: 8378076

PubMed ID: 8080983

Title: ENL, the gene fused with HRX in t(11;19) leukemias, encodes a nuclear protein with transcriptional activation potential in lymphoid and myeloid cells.

PubMed ID: 8080983

PubMed ID: 12665591

Title: Novel SWI/SNF chromatin-remodeling complexes contain a mixed-lineage leukemia chromosomal translocation partner.

PubMed ID: 12665591

DOI: 10.1128/mcb.23.8.2942-2952.2003

PubMed ID: 17081983

Title: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.

PubMed ID: 17081983

DOI: 10.1016/j.cell.2006.09.026

PubMed ID: 18691976

Title: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.

PubMed ID: 18691976

DOI: 10.1016/j.molcel.2008.07.007

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 19413330

Title: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.

PubMed ID: 19413330

DOI: 10.1021/ac9004309

PubMed ID: 19369195

Title: Large-scale proteomics analysis of the human kinome.

PubMed ID: 19369195

DOI: 10.1074/mcp.m800588-mcp200

PubMed ID: 20159561

Title: AFF4, a component of the ELL/P-TEFb elongation complex and a shared subunit of MLL chimeras, can link transcription elongation to leukemia.

PubMed ID: 20159561

DOI: 10.1016/j.molcel.2010.01.026

PubMed ID: 20471948

Title: HIV-1 Tat and host AFF4 recruit two transcription elongation factors into a bifunctional complex for coordinated activation of HIV-1 transcription.

PubMed ID: 20471948

DOI: 10.1016/j.molcel.2010.04.013

PubMed ID: 20068231

Title: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

PubMed ID: 22195968

Title: The little elongation complex regulates small nuclear RNA transcription.

PubMed ID: 22195968

DOI: 10.1016/j.molcel.2011.12.008

PubMed ID: 23145062

Title: Human ALKBH4 interacts with proteins associated with transcription.

PubMed ID: 23145062

DOI: 10.1371/journal.pone.0049045

PubMed ID: 22814378

Title: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.

PubMed ID: 22814378

DOI: 10.1073/pnas.1210303109

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 27105114

Title: Molecular coupling of histone crotonylation and active transcription by AF9 YEATS domain.

PubMed ID: 27105114

DOI: 10.1016/j.molcel.2016.03.028

PubMed ID: 28241139

Title: Transcription control by the ENL YEATS domain in acute leukaemia.

PubMed ID: 28241139

DOI: 10.1038/nature21688

PubMed ID: 28112733

Title: Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation.

PubMed ID: 28112733

DOI: 10.1038/nsmb.3366

PubMed ID: 30374167

Title: Structure-guided development of YEATS domain inhibitors by targeting pi-pi-pi stacking.

PubMed ID: 30374167

DOI: 10.1038/s41589-018-0144-y

PubMed ID: 28241141

Title: ENL links histone acetylation to oncogenic gene expression in acute myeloid leukaemia.

PubMed ID: 28241141

DOI: 10.1038/nature21687

Sequence Information:

  • Length: 559
  • Mass: 62056
  • Checksum: A8480BA0F8742173
  • Sequence:
    • MDNQCTVQVR LELGHRAQLR KKPTTEGFTH DWMVFVRGPE QCDIQHFVEK VVFWLHDSFP 
KPRRVCKEPP YKVEESGYAG FIMPIEVHFK NKEEPRKVCF TYDLFLNLEG NPPVNHLRCE 
KLTFNNPTTE FRYKLLRAGG VMVMPEGADT VSRPSPDYPM LPTIPLSAFS DPKKTKPSHG 
SKDANKESSK TSKPHKVTKE HRERPRKDSE SKSSSKELER EQAKSSKDTS RKLGEGRLPK 
EEKAPPPKAA FKEPKMALKE TKLESTSPKG GPPPPPPPPP RASSKRPATA DSPKPSAKKQ 
KKSSSKGSRS APGTSPRTSS SSSFSDKKPA KDKSSTRGEK VKAESEPREA KKALEVEESN 
SEDEASFKSE SAQSSPSNSS SSSDSSSDSD FEPSQNHSQG PLRSMVEDLQ SEESDEDDSS 
SGEEAAGKTN PGRDSRLSFS DSESDNSADS SLPSREPPPP QKPPPPNSKV SGRRSPESCS 
KPEKILKKGT YDKAYTDELV ELHRRLMALR ERNVLQQIVN LIEETGHFNV TNTTFDFDLF 
SLDETTVRKL QSCLEAVAT