Details for: LDB1

Gene ID: 8861

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: LDB1

Ensembl ID: ENSG00000198728

Description: LIM domain binding 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • erythroblast CL0000765
    CSI 6.05
    rCSI 16.05%
    PRS 94.28
  • mucosal invariant T cell CL0000940
    CSI 4.03
    rCSI 3.26%
    PRS 97.26
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 3.25
    rCSI 2.51%
    PRS 96.49
  • melanocyte CL0000148
    CSI 3.2
    rCSI 2.37%
    PRS 92.14
  • keratinocyte CL0000312
    CSI 2.92
    rCSI 2.45%
    PRS 93.94
  • bronchus fibroblast of lung CL2000093
    CSI 2.91
    rCSI 2.37%
    PRS 94.02
  • hepatic stellate cell CL0000632
    CSI 2.87
    rCSI 10.75%
    PRS 91.7
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.5
    rCSI 3.11%
    PRS 83.2
  • common myeloid progenitor CL0000049
    CSI 2.47
    rCSI 2%
    PRS 95.03
  • epithelial cell CL0000066
    CSI 2.42
    rCSI 3.72%
    PRS 83.91
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.34
    rCSI 2.11%
    PRS 93.48
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 2.2
    rCSI 3.89%
    PRS 84.75
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 2.16
    rCSI 2.77%
    PRS 91.2
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.97
    rCSI 3.31%
    PRS 85.43
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.84
    rCSI 2.38%
    PRS 86.25
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.78
    rCSI 3.99%
    PRS 85.52
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.65
    rCSI 4.18%
    PRS 90.57
  • glutamatergic neuron CL0000679
    CSI 1.55
    rCSI 3.18%
    PRS 84.95
  • cardiac muscle cell CL0000746
    CSI 1.32
    rCSI 1.9%
    PRS 88.1
  • stromal cell CL0000499
    CSI 1.3
    rCSI 3.65%
    PRS 91.49
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.99
    rCSI 2.41%
    PRS 83.38
  • endothelial cell of vascular tree CL0002139
    CSI 0.89
    rCSI 4.88%
    PRS 91.01
  • primitive red blood cell CL0002355
    CSI 0.83
    rCSI 4.46%
    PRS 94.72
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.76
    rCSI 2.37%
    PRS 86.28
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.73
    rCSI 2.78%
    PRS 85.47
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.64
    rCSI 2.29%
    PRS 83.65
  • erythroid progenitor cell CL0000038
    CSI 0.5
    rCSI 2.86%
    PRS 95.19

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)

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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 [LDB1](/details-gene/8861) (LIM domain binding 1) encodes a nuclear protein that functions as a critical transcriptional cofactor. It does not bind DNA directly but acts as a molecular scaffold, assembling and stabilizing multi-protein transcription factor complexes through its LIM-interaction domain [Link](https://doi.org/10.1007/s003359900899). Its widespread but distinct expression pattern underscores its fundamental role in cell fate determination across multiple lineages. **Overall**, [LDB1](/details-gene/8861) shows the highest significance in hematopoietic precursors, particularly [erythroblast](/details-cell/CL0000765)s, suggesting a pivotal role in erythropoiesis. It is also significantly expressed in various immune cells, developing neurons, and epithelial cells, consistent with its involvement in developmental processes, including nervous system development and epithelial maintenance. ## Cellular Roles and Expression Landscape The expression profile of [LDB1](/details-gene/8861) indicates its function as a broadly important, yet cell-type specific, transcriptional regulator. Its roles can be categorized into several key biological systems: * **Hematopoiesis and Erythropoiesis:** The most prominent expression is observed in the hematopoietic system. [LDB1](/details-gene/8861) is a top marker in [erythroblast](/details-cell/CL0000765)s (CSI: 6.05), with significant expression also found in their progenitors, including [common myeloid progenitor](/details-cell/CL0000049)s and [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050)s. This expression pattern is strongly consistent with its annotated role in pathways such as '[Runx1 regulates transcription of genes involved in differentiation of hscs](/details-pathway/R-HSA-8939236)' and biological processes like '[Negative regulation of erythrocyte differentiation](/details-cell/GO:0045647)'. It is known to form a complex with other key hematopoietic factors, such as LMO2, to regulate gene expression during blood cell development [Link](https://doi.org/10.1182/blood-2010-07-293357). * **Immune System:** Beyond hematopoiesis, [LDB1](/details-gene/8861) is significantly expressed in specific immune cell subsets, including [mucosal invariant T cell](/details-cell/CL0000940)s and [CD14-low, CD16-positive monocyte](/details-cell/CL0002396)s. This suggests a role in the function or development of these specialized innate and adaptive immune cells. * **Neural Development:** [LDB1](/details-gene/8861) demonstrates a significant role in the developing nervous system, with notable expression in [neuroblast (sensu Vertebrata)](/details-cell/CL0000031)s and several distinct subtypes of cortical interneurons, such as [pvalb GABAergic cortical interneuron](/details-cell/CL4023018), [lamp5 GABAergic cortical interneuron](/details-cell/CL4023011), and [sst GABAergic cortical interneuron](/details-cell/CL4023017). This aligns with its involvement in '[Nervous system development](/details-pathway/R-HSA-9675108)' and '[Axon guidance](/details-pathway/R-HSA-422475)'. * **Epithelial and Structural Tissues:** The gene is also highly significant in several non-hematopoietic cell types, including [melanocyte](/details-cell/CL0000148)s, [keratinocyte](/details-cell/CL0000312)s, and [bronchus fibroblast of lung](/details-cell/CL2000093)s. This expression is consistent with its annotated functions in '[Epithelial structure maintenance](/details-cell/GO:0010669)' and '[Hair follicle development](/details-cell/GO:0001942)'. ## Pathways and Molecular Function Functionally, [LDB1](/details-gene/8861) is a quintessential transcriptional cofactor. Its molecular function is centered on '[Lim domain binding](/details-cell/GO:0030274)', allowing it to bridge LIM-homeodomain transcription factors to other regulatory proteins, forming a stable '[Transcription regulator complex](/details-cell/GO:0005667)' on chromatin. It participates in both transcriptional activation and repression, as highlighted by its annotation in both '[Positive regulation of transcription by rna polymerase ii](/details-cell/GO:0045944)' and '[Negative regulation of dna-templated transcription](/details-cell/GO:0045892)'. Key Reactome pathways underscore its pleiotropic roles: * **Transcriptional Machinery:** It is a core component of the general transcriptional machinery, as shown by its involvement in '[Generic transcription pathway](/details-pathway/R-HSA-212436)' and '[Gene expression (transcription)](/details-pathway/R-HSA-74160)'. * **Developmental Processes:** Its central role in development is captured by its participation in broad pathways like '[Developmental biology](/details-pathway/R-HSA-1266738)' and more specific ones such as '[Nervous system development](/details-pathway/R-HSA-9675108)' and '[Cardiogenesis](/details-pathway/R-HSA-9733709)'. * **Hematopoietic Regulation:** Its specific function in blood development is highlighted by its role in '[Transcriptional regulation by runx1](/details-pathway/R-HSA-8878171)', a master regulator of hematopoiesis. This pathway provides a direct mechanistic link to its high CSI score in hematopoietic progenitor cells. ## Research Directions The widespread yet specific expression of [LDB1](/details-gene/8861) points to its role as a context-dependent master regulator. Future research should focus on elucidating how it specifies distinct cellular fates by assembling different transcription factor complexes. **Proposed Hypotheses:** 1. Given its paramount significance in [erythroblast](/details-cell/CL0000765)s and its role in '[Positive regulation of hemoglobin biosynthetic process](/details-cell/GO:0046985)', we hypothesize that [LDB1](/details-gene/8861) is essential for the terminal differentiation of red blood cells by mediating long-range chromatin interactions between globin gene promoters and their super-enhancers. 2. Based on its high expression across multiple, distinct cortical interneuron subtypes, we hypothesize that [LDB1](/details-gene/8861) acts as a key determinant of interneuron diversity. By partnering with different sets of LIM-homeodomain factors in progenitor cells, it likely directs lineage commitment towards specific neuronal fates (e.g., PVALB-positive vs. SST-positive neurons). **Experimental Approach:** To test the first hypothesis regarding erythropoiesis, a compelling experiment would be to use a CRISPR-Cas9 based system to specifically deplete [LDB1](/details-gene/8861) in primary human CD34+ hematopoietic stem and progenitor cells. These modified cells would then be cultured in vitro under conditions that promote erythroid differentiation. The impact of [LDB1](/details-gene/8861) loss would be assessed using a multi-omics approach: single-cell RNA-sequencing (scRNA-seq) to determine if differentiation is stalled or misdirected, and techniques like Hi-C or Capture-C to directly measure changes in 3D chromatin architecture at the globin loci. **Therapeutic Potential:** As a ubiquitous and essential nuclear protein, direct targeting of [LDB1](/details-gene/8861) itself is likely to be highly toxic. However, its function relies on specific protein-protein interactions. In pathologies where these interactions are dysregulated, such as certain forms of T-cell acute lymphoblastic leukemia driven by aberrant expression of transcription factors like LMO2, targeting the specific interface between [LDB1](/details-gene/8861) and its oncogenic binding partners presents a promising therapeutic strategy. Therefore, developing small molecule inhibitors that disrupt the LDB1-LMO2 complex, rather than inhibiting [LDB1](/details-gene/8861) globally, could offer a targeted **inhibition** approach with a potentially wider therapeutic window.

Genular Protein ID: 361765569

Symbol: LDB1_HUMAN

Name: LIM domain-binding protein 1

UniProtKB Accession Codes:

Q86U70 B4DUC4 O75479 O96010 Q1EQX1 Q9UGM4

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CORUM 1 CTD 1 ChiTaRS 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 10 Ensembl 2 EvolutionaryTrace 1 ExpressionAtlas 1 GO 38 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 IDEAL 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 8 PDBsum 8 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 Pumba 1 RNAct 1 Reactome 4 RefSeq 2 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: 9799849

Title: Cloning and chromosomal localization of two novel human genes encoding LIM-domain binding factors CLIM1 and CLIM2/LDB1/NLI.

PubMed ID: 9799849

DOI: 10.1007/s003359900899

PubMed ID: 10640831

Title: Genomic structure, alternative transcripts and chromosome location of the human LIM domain binding protein gene LDB1.

PubMed ID: 10640831

DOI: 10.1159/000015377

PubMed ID: 10083735

Title: Isolation and chromosomal assignment of human genes encoding cofactor of LIM homeodomain proteins, CLIM1 and CLIM2.

PubMed ID: 10083735

DOI: 10.1007/s100380050120

PubMed ID: 16815859

Title: Spliced isoforms of LIM-domain-binding protein (CLIM/NLI/Ldb) lacking the LIM-interaction domain.

PubMed ID: 16815859

DOI: 10.1093/jb/mvj134

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15164054

Title: The DNA sequence and comparative analysis of human chromosome 10.

PubMed ID: 15164054

DOI: 10.1038/nature02462

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 16959763

Title: Transgenic mouse proteomics identifies new 14-3-3-associated proteins involved in cytoskeletal rearrangements and cell signaling.

PubMed ID: 16959763

DOI: 10.1074/mcp.m600147-mcp200

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: 19117995

Title: Regulation of estrogen-dependent transcription by the LIM cofactors CLIM and RLIM in breast cancer.

PubMed ID: 19117995

DOI: 10.1158/0008-5472.can-08-1630

PubMed ID: 19690332

Title: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.

PubMed ID: 19690332

DOI: 10.1126/scisignal.2000007

PubMed ID: 21406692

Title: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.

PubMed ID: 21406692

DOI: 10.1126/scisignal.2001570

PubMed ID: 23186163

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

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 32417234

Title: LDB1 and the SWI/SNF complex participate in both transcriptional activation and repression by Caenorhabditis elegans BLIMP1/PRDM1.

PubMed ID: 32417234

DOI: 10.1016/j.bbagrm.2020.194577

PubMed ID: 21076045

Title: Structure of the leukemia oncogene LMO2: implications for the assembly of a hematopoietic transcription factor complex.

PubMed ID: 21076045

DOI: 10.1182/blood-2010-07-293357

PubMed ID: 16959974

Title: The consensus coding sequences of human breast and colorectal cancers.

PubMed ID: 16959974

DOI: 10.1126/science.1133427

Sequence Information:

  • Length: 411
  • Mass: 46533
  • Checksum: 5BB5348A36044580
  • Sequence:
    • MSVGCACPGC SSKSFKLYSP KEPPNGNAFP PFHPGTMLDR DVGPTPMYPP TYLEPGIGRH 
TPYGNQTDYR IFELNKRLQN WTEECDNLWW DAFTTEFFED DAMLTITFCL EDGPKRYTIG 
RTLIPRYFRS IFEGGATELY YVLKHPKEAF HSNFVSLDCD QGSMVTQHGK PMFTQVCVEG 
RLYLEFMFDD MMRIKTWHFS IRQHRELIPR SILAMHAQDP QMLDQLSKNI TRCGLSNSTL 
NYLRLCVILE PMQELMSRHK TYSLSPRDCL KTCLFQKWQR MVAPPAEPTR QQPSKRRKRK 
MSGGSTMSSG GGNTNNSNSK KKSPASTFAL SSQVPDVMVV GEPTLMGGEF GDEDERLITR 
LENTQFDAAN GIDDEDSFNN SPALGANSPW NSKPPSSQES KSENPTSQAS Q

Genular Protein ID: 2719115391

Symbol: A0A6E1WJ75_HUMAN

Name: N/A

UniProtKB Accession Codes:

A0A6E1WJ75

Database IDs:

ARBA 2 Antibodypedia 1 Bgee 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 3 Ensembl 2 GO 2 Gene3D 1 GeneTree 1 HGNC 1 InterPro 2 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 2 PROSITE-ProRule 1 PeptideAtlas 1 Pfam 2 Proteomes 2 ProteomicsDB 1 RefSeq 1 SAM 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 11181995

Title: The sequence of the human genome.

PubMed ID: 11181995

DOI: 10.1126/science.1058040

PubMed ID: 15164054

Title: The DNA sequence and comparative analysis of human chromosome 10.

PubMed ID: 15164054

DOI: 10.1038/nature02462

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

Sequence Information:

  • Length: 409
  • Mass: 46336
  • Checksum: B95EDBA28E536931
  • Sequence:
    • MSVGCACPGC SSKSFKLYSP KEPPNGNAFP PFHPGTMLDR DVGPTPMYPP TYLEPGIGRH 
TPYGNQTDYR IFELNKRLQN WTEECDNLWW DAFTTEFFED DAMLTITFCL EDGPKRYTIG 
RTLIPRYFRS IFEGGATELY YVLKHPKEAF HSNFVSLDCD QGSMVTQHGK PMFTQVCVEG 
RLYLEFMFDD MMRIKTWHFS IRQHRELIPR SILAMHAQDP QMLDQLSKNI TRCGLSNSTL 
NYLRLCVILE PMQELMSRHK TYSLSPRDCL KTCLFQKWQR MVAPPAEPTR QQPSKRRKRK 
MSGGSTMSSG GGNTNNSNSK KKSPASTFAL SSQDVMVVGE PTLMGGEFGD EDERLITRLE 
NTQFDAANGI DDEDSFNNSP ALGANSPWNS KPPSSQESKS ENPTSQASQ