Details for: HELB

Gene ID: 92797

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: HELB

Ensembl ID: ENSG00000127311

Description: DNA helicase B

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • vascular associated smooth muscle cell CL0000359
    CSI 7.55
    rCSI 24.48%
    PRS 82.62
  • CD4-positive, CD25-positive, alpha-beta regulatory T cell CL0000792
    CSI 6.62
    rCSI 6.5%
    PRS 94.94
  • enteroglial cell CL4040002
    CSI 6.1
    rCSI 32.05%
    PRS 85.24
  • CD4-positive, alpha-beta thymocyte CL0000810
    CSI 4.45
    rCSI 3.57%
    PRS 93.82
  • effector CD8-positive, alpha-beta T cell CL0001050
    CSI 3.97
    rCSI 3.02%
    PRS 94.81
  • double negative thymocyte CL0002489
    CSI 3.41
    rCSI 2.37%
    PRS 94.01
  • central memory CD4-positive, alpha-beta T cell CL0000904
    CSI 3.35
    rCSI 1.98%
    PRS 96.32
  • naive T cell CL0000898
    CSI 3.28
    rCSI 2.28%
    PRS 95.22
  • mature T cell CL0002419
    CSI 3.02
    rCSI 2.35%
    PRS 95.03
  • CD8-positive, alpha-beta cytotoxic T cell CL0000794
    CSI 2.96
    rCSI 3.54%
    PRS 95.79
  • CD4-positive, alpha-beta memory T cell CL0000897
    CSI 2.95
    rCSI 2.12%
    PRS 94.74
  • activated CD4-positive, alpha-beta T cell CL0000896
    CSI 2.78
    rCSI 2.57%
    PRS 95.56
  • central memory CD8-positive, alpha-beta T cell CL0000907
    CSI 2.61
    rCSI 1.76%
    PRS 94.84
  • Kupffer cell CL0000091
    CSI 2.56
    rCSI 5.85%
    PRS 85.45
  • bronchus fibroblast of lung CL2000093
    CSI 2.53
    rCSI 2.05%
    PRS 83.88
  • blood vessel endothelial cell CL0000071
    CSI 2.45
    rCSI 5.08%
    PRS 81.65
  • CD4-positive helper T cell CL0000492
    CSI 2.37
    rCSI 1.79%
    PRS 94.36
  • alpha-beta T cell CL0000789
    CSI 2.23
    rCSI 2.61%
    PRS 94.92
  • Mueller cell CL0000636
    CSI 2.2
    rCSI 5.03%
    PRS 76.7
  • promyelocyte CL0000836
    CSI 2.18
    rCSI 3.14%
    PRS 88.87
  • activated type II NK T cell CL0000931
    CSI 2.14
    rCSI 2.41%
    PRS 94.48
  • T follicular helper cell CL0002038
    CSI 2.09
    rCSI 1.56%
    PRS 94.32
  • activated CD8-positive, alpha-beta T cell CL0000906
    CSI 2.09
    rCSI 2.05%
    PRS 94.69
  • effector memory CD8-positive, alpha-beta T cell CL0000913
    CSI 2.06
    rCSI 1.87%
    PRS 94.02
  • myofibroblast cell CL0000186
    CSI 2.03
    rCSI 2.81%
    PRS 81.08
  • fibroblast of lung CL0002553
    CSI 2
    rCSI 1.86%
    PRS 85.42
  • T-helper 17 cell CL0000899
    CSI 1.99
    rCSI 1.58%
    PRS 96.82
  • retinal blood vessel endothelial cell CL0002585
    CSI 1.99
    rCSI 3.18%
    PRS 87.62
  • cerebral cortex endothelial cell CL1001602
    CSI 1.89
    rCSI 3.27%
    PRS 77.02
  • common myeloid progenitor CL0000049
    CSI 1.87
    rCSI 1.51%
    PRS 86.64
  • hepatic stellate cell CL0000632
    CSI 1.81
    rCSI 6.78%
    PRS 77.92
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.77
    rCSI 4.49%
    PRS 76.18
  • ependymal cell CL0000065
    CSI 1.76
    rCSI 3.57%
    PRS 64.55
  • lung secretory cell CL1000272
    CSI 1.68
    rCSI 4.17%
    PRS 84.84
  • activated CD8-positive, alpha-beta T cell, human CL0001049
    CSI 1.57
    rCSI 2.68%
    PRS 94.04
  • helper T cell CL0000912
    CSI 1.56
    rCSI 2.2%
    PRS 82.38
  • lung resident memory CD8-positive, alpha-beta T cell CL4033039
    CSI 1.5
    rCSI 3.89%
    PRS 96.07
  • basal cell CL0000646
    CSI 1.49
    rCSI 2%
    PRS 82.45
  • memory T cell CL0000813
    CSI 1.4
    rCSI 2.7%
    PRS 96.76
  • natural T-regulatory cell CL0000903
    CSI 1.39
    rCSI 2.63%
    PRS 97.33
  • IgG plasma cell CL0000985
    CSI 1.37
    rCSI 1.64%
    PRS 91.78
  • blood vessel smooth muscle cell CL0019018
    CSI 1.17
    rCSI 9.53%
    PRS 79.7
  • myeloid dendritic cell CL0000782
    CSI 1.17
    rCSI 1.69%
    PRS 94.58
  • parietal epithelial cell CL1000452
    CSI 1.16
    rCSI 3.11%
    PRS 77.31
  • effector CD4-positive, alpha-beta T cell CL0001044
    CSI 1.15
    rCSI 3.31%
    PRS 96.82
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 1.12
    rCSI 3.03%
    PRS 88.14
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 1.11
    rCSI 1.34%
    PRS 65.06
  • mature alpha-beta T cell CL0000791
    CSI 1.07
    rCSI 3.86%
    PRS 96.4
  • cytotoxic T cell CL0000910
    CSI 0.75
    rCSI 4.27%
    PRS 86.33
  • retinal ganglion cell CL0000740
    CSI 0.66
    rCSI 1.47%
    PRS 71.56
  • P/D1 enteroendocrine cell CL0002268
    CSI 0.51
    rCSI 2.8%
    PRS 89.97
  • group 2 innate lymphoid cell CL0001069
    CSI 0.4
    rCSI 2.15%
    PRS 96.37
  • effector memory CD8-positive, alpha-beta T cell, terminally differentiated CL0001062
    CSI 0.37
    rCSI 1.85%
    PRS 94

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 [HELB](/details-gene/92797), or DNA helicase B, is a protein-coding gene located on chromosome 12q14.3. It functions as a 5'-3' DNA helicase, playing a critical role in fundamental cellular processes including [Dna replication](/details-go/GO:0006260), [Dna repair](/details-go/GO:0006281), and the [Dna damage response](/details-go/GO:0006974). Its function is particularly important for maintaining genomic integrity during replication stress and for regulating DNA double-strand break repair. Expression data indicates that **Overall**, [HELB](/details-gene/92797) is most significant in cell types characterized by high proliferative capacity or the need for stringent genomic maintenance, such as [vascular associated smooth muscle cell](/details-cell/CL0000359) and a wide array of T lymphocyte populations, including [CD4-positive, CD25-positive, alpha-beta regulatory T cell](/details-cell/CL0000792). ## Cellular Roles and Expression Landscape The expression profile of [HELB](/details-gene/92797) underscores its importance in cells with demanding DNA metabolism. **Overall**, it shows the highest significance in [vascular associated smooth muscle cell](/details-cell/CL0000359) (CSI: 7.55), a cell type known for its ability to proliferate and switch phenotypes in response to physiological cues. A prominent role for [HELB](/details-gene/92797) is evident within the immune system, specifically within the T cell lineage. It is highly significant across multiple stages of T cell development and differentiation, including in [CD4-positive, CD25-positive, alpha-beta regulatory T cell](/details-cell/CL0000792) (CSI: 6.62), [CD4-positive, alpha-beta thymocyte](/details-cell/CL0000810) (CSI: 4.45), [effector CD8-positive, alpha-beta T cell](/details-cell/CL0001050) (CSI: 3.97), and various memory T cell subsets. This pattern suggests a crucial function in maintaining genomic stability during thymic selection, clonal expansion, and the long-term survival of memory populations. The gene is also significant in other cell types, such as [enteroglial cell](/details-cell/CL4040002) (CSI: 6.10) and [Kupffer cell](/details-cell/CL0000091) (CSI: 2.56), indicating a broad requirement for its DNA maintenance functions across diverse tissues. ## Pathways and Molecular Function The molecular functions of [HELB](/details-gene/92797) are centered on its enzymatic activity and its role in DNA metabolism. As annotated by the Gene Ontology, its primary molecular functions include [5'-3' dna helicase activity](/details-go/GO:0043139), [Atp binding](/details-go/GO:0005524), and [Atp hydrolysis activity](/details-go/GO:0016887), which are essential for unwinding DNA structures. These activities support its involvement in several key biological processes. [HELB](/details-gene/92797) is a core component of the [Dna damage response](/details-go/GO:0006974), localized to the [site of double-strand break](/details-go/GO:0035861). Research has shown that it functions as a feedback inhibitor of DNA end resection, consistent with its annotated role in the [Negative regulation of double-strand break repair via homologous recombination](/details-go/GO:2000042) ([Link](https://doi.org/10.1016/j.molcel.2015.12.013)). Furthermore, [HELB](/details-gene/92797) is integral to DNA replication, where it has been found to interact with replication protein A (RPA) to facilitate recovery from replication stress ([Link](https://doi.org/10.1074/jbc.m111.324582)) and with Cdc45 to promote its binding to chromatin for replication initiation ([Link](https://doi.org/10.1016/j.yexcr.2015.04.014)). This is consistent with its localization within the [Dna replication factor a complex](/details-go/GO:0005662). ## Research Directions The widespread significance of [HELB](/details-gene/92797) in cellular proliferation and DNA repair highlights its potential importance in both normal physiology and disease pathology. **Proposed Hypotheses:** 1. Given its high significance in [CD4-positive, CD25-positive, alpha-beta regulatory T cell](/details-cell/CL0000792), [HELB](/details-gene/92797) may be indispensable for maintaining the lineage stability and suppressive function of regulatory T cells (Tregs). Loss of [HELB](/details-gene/92797) function could lead to genomic instability and impaired proliferation, compromising their ability to control autoimmune responses. 2. The top-ranking significance of [HELB](/details-gene/92797) in [vascular associated smooth muscle cell](/details-cell/CL0000359) suggests it is a key regulator of vascular wall homeostasis. Its role in DNA replication and repair may be critical for preventing senescence or apoptosis during the proliferative response to vascular injury, a process central to conditions like atherosclerosis and restenosis. **Suggested Experimental Approach:** To test the hypothesis regarding the role of [HELB](/details-gene/92797) in Treg function, a conditional knockout mouse model could be generated (e.g., *Helbfl/fl;Foxp3YFP-Cre*). The development, homeostasis, and stability of the Treg population could be assessed via flow cytometry. Functional consequences could be evaluated using in vitro suppression assays and by challenging the mice in an in vivo model of autoimmunity, such as experimental autoimmune encephalomyelitis (EAE), to determine if loss of [HELB](/details-gene/92797) in Tregs exacerbates disease. **Therapeutic Potential:** As a DNA helicase essential for DNA replication and repair, [HELB](/details-gene/92797) represents a potential therapeutic target in oncology. Many cancer cells exhibit high levels of replication stress and are heavily dependent on DNA repair pathways for survival. Therefore, inhibition of [HELB](/details-gene/92797) could selectively induce synthetic lethality in cancer cells or act as a sensitizer to DNA-damaging chemotherapeutics or radiation therapy. The development of small molecule inhibitors targeting its ATPase/helicase activity would be a primary strategy for therapeutic intervention.

Genular Protein ID: 3760647696

Symbol: HELB_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q8NG08 A8K4C9 Q4G0T2 Q9H7L5

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 2 CTD 1 ChEBI 5 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EC 1 EMBL 3 Ensembl 3 ExpressionAtlas 1 GO 18 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 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 1 PDBsum 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 RefSeq 2 Rhea 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 12181327

Title: A dominant-negative mutant of human DNA helicase B blocks the onset of chromosomal DNA replication.

PubMed ID: 12181327

DOI: 10.1074/jbc.m208067200

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15146062

Title: Cell cycle-dependent regulation of a human DNA helicase that localizes in DNA damage foci.

PubMed ID: 15146062

DOI: 10.1091/mbc.e04-03-0227

PubMed ID: 17525332

Title: ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage.

PubMed ID: 17525332

DOI: 10.1126/science.1140321

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: 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: 22194613

Title: Human DNA helicase B (HDHB) binds to replication protein A and facilitates cellular recovery from replication stress.

PubMed ID: 22194613

DOI: 10.1074/jbc.m111.324582

PubMed ID: 23186163

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

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 25933514

Title: Human DNA helicase B interacts with the replication initiation protein Cdc45 and facilitates Cdc45 binding onto chromatin.

PubMed ID: 25933514

DOI: 10.1016/j.yexcr.2015.04.014

PubMed ID: 25617833

Title: Human DNA helicase B functions in cellular homologous recombination and stimulates Rad51-mediated 5'-3' heteroduplex extension in vitro.

PubMed ID: 25617833

DOI: 10.1371/journal.pone.0116852

PubMed ID: 26774285

Title: HELB is a feedback inhibitor of DNA end resection.

PubMed ID: 26774285

DOI: 10.1016/j.molcel.2015.12.013

Sequence Information:

  • Length: 1087
  • Mass: 123252
  • Checksum: 05220F3186CE722B
  • Sequence:
    • MARSSPYLRQ LQGPLLPPRD LVEEDDDYLN DDVEEDEESV FIDAEELCSG GVKAGSLPGC 
LRVSICDENT QETCKVFGRF PITGAWWRVK VQVKPVVGSR SYQYQVQGFP SYFLQSDMSP 
PNQKHICALF LKECEVSSDD VNKFLTWVKE VSNYKNLNFE NLRETLRTFH KETGRKDQKQ 
PTQNGQEELF LDNEMSLPLE NTIPFRNVMT ALQFPKIMEF LPVLLPRHFK WIIGSGSKEM 
LKEIEEILGT HPWKLGFSKI TYREWKLLRC EASWIAFCQC ESLLQLMTDL EKNALIMYSR 
LKQICREDGH TYVEVNDLTL TLSNHMSFHA ASESLKFLKD IGVVTYEKSC VFPYDLYHAE 
RAIAFSICDL MKKPPWHLCV DVEKVLASIH TTKPENSSDD ALNESKPDEV RLENPVDVVD 
TQDNGDHIWT NGENEINAEI SEVQLDQDQV EVPLDRDQVA ALEMICSNPV TVISGKGGCG 
KTTIVSRLFK HIEQLEEREV KKACEDFEQD QNASEEWITF TEQSQLEADK AIEVLLTAPT 
GKAAGLLRQK TGLHAYTLCQ VNYSFYSWTQ TMMTTNKPWK FSSVRVLVVD EGSLVSVGIF 
KSVLNLLCEH SKLSKLIILG DIRQLPSIEP GNLLKDLFET LKSRNCAIEL KTNHRAESQL 
IVDNATRISR RQFPKFDAEL NISDNPTLPI SIQDKTFIFV RLPEEDASSQ SSKTNHHSCL 
YSAVKTLLQE NNLQNAKTSQ FIAFRRQDCD LINDCCCKHY TGHLTKDHQS RLVFGIGDKI 
CCTRNAYLSD LLPENISGSQ QNNDLDASSE DFSGTLPDFA KNKRDFESNV RLCNGEIFFI 
TNDVTDVTFG KRRSLTINNM AGLEVTVDFK KLMKYCRIKH AWARTIHTFQ GSEEQTVVYV 
VGKAGRQHWQ HVYTAVTRGR CRVYVIAEES QLRNAIMKNS FPRKTRLKHF LQSKLSSSGA 
PPADFPSPRK SSGDSGGPST PSASPLPVVT DHAMTNDVTW SEASSPDERT LTFAERWQLS 
SPDGVDTDDD LPKSRASKRT CGVNDDESPS KIFMVGESPQ VSSRLQNLRL NNLIPRQLFK 
PTDNQET