Details for: H3 5

Gene ID: 440093

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: H3 5

Ensembl ID: ENSG00000188375

Description: H3.5 histone

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • granulocyte CL0000094
    CSI 2.71
    rCSI 4.15%
    PRS 99.65
  • basal cell of epidermis CL0002187
    CSI 1.85
    rCSI 3.29%
    PRS 93.13

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

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  • Node Color (Target Cell CSI, relative to current network):
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  • Node Size: Proportional to Target Cell CSI magnitude
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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 [H3 5](/details-gene/440093) is a protein-coding gene located on chromosome 12 that encodes H3.5, a hominid-specific histone H3 variant. Functionally, it is a core structural component of chromatin, participating in the formation of the nucleosome, the fundamental repeating unit of eukaryotic DNA packaging. Its involvement is noted in '[nucleosomal dna binding](/details-go/GO:0031492)' and the '[positive regulation of cell growth](/details-go/GO:0030307)'. **Overall**, expression data indicates that [H3 5](/details-gene/440093) is a significant gene in [granulocyte](/details-cell/CL0000094)s and [basal cell of epidermis](/details-cell/CL0002187)s. Notably, research has highlighted its highly specific expression in the seminiferous tubules of human testes, suggesting a specialized role in germline biology ([Link](https://doi.org/10.1007/s00412-011-0310-4)). ## Cellular Roles and Expression Landscape The expression profile of [H3 5](/details-gene/440093) points to roles in both somatic and germline cells. In a broad **Overall** context, the gene shows its highest significance in [granulocyte](/details-cell/CL0000094)s (CSI: 2.71), which are terminally differentiated immune cells, and in [basal cell of epidermis](/details-cell/CL0002187)s (CSI: 1.85), a highly proliferative population responsible for skin regeneration. This expression pattern in distinct cell types suggests that the H3.5 variant may be important for maintaining chromatin structure in cells with very different fates and proliferative capacities. Adding a critical layer of specificity, studies have demonstrated that [H3 5](/details-gene/440093) is not broadly expressed but is instead highly restricted to the seminiferous tubules in the testes ([Link](https://doi.org/10.1007/s00412-011-0310-4)). This suggests a specialized function in the male germline, potentially related to the unique chromatin remodeling events that occur during spermatogenesis. The high expression observed in somatic cells like [granulocyte](/details-cell/CL0000094)s in general datasets may reflect specific biological states or contexts not fully captured by tissue-level analysis. ## Pathways and Molecular Function The function of [H3 5](/details-gene/440093) is intrinsically linked to chromatin organization and dynamics. As a histone variant, its primary role is as a '[structural constituent of chromatin](/details-go/GO:0030527)', where it localizes to the '[nucleus](/details-go/GO:0005634)' and is incorporated into the '[nucleosome](/details-go/GO:0000786)'. Its presence within '[euchromatin](/details-go/GO:0000791)' suggests a role in regulating the structure of transcriptionally active genomic regions. The molecular functions of the H3.5 protein include '[nucleosomal dna binding](/details-go/GO:0031492)' and '[protein heterodimerization activity](/details-go/GO:0046982)', reflecting its interaction with DNA and other core histones (e.g., H2A, H2B, and H4) to form the nucleosome core particle. Its annotation under the biological process '[positive regulation of cell growth](/details-go/GO:0030307)' is consistent with its expression in rapidly dividing [basal cell of epidermis](/details-cell/CL0002187)s, where proper chromatin replication and segregation are essential. ## Research Directions Given the unique, hominid-specific nature of [H3 5](/details-gene/440093) and its restricted expression, it presents several compelling avenues for future research. **Proposed Hypotheses:** 1. Given its specific expression in seminiferous tubules ([Link](https://doi.org/10.1007/s00412-011-0310-4)), [H3 5](/details-gene/440093) is essential for proper chromatin compaction and epigenetic programming during human spermatogenesis. Its absence could lead to male infertility by disrupting the histone-to-protamine transition or by failing to establish correct paternal imprints. 2. The expression of [H3 5](/details-gene/440093) in proliferative [basal cell of epidermis](/details-cell/CL0002187)s suggests that this histone variant may facilitate rapid cell division by establishing a more open or plastic chromatin state, allowing for efficient DNA replication and transcription of growth-related genes. **Key Experimental Approach:** To test the role of [H3 5](/details-gene/440093) in human spermatogenesis (Hypothesis 1), an *in vitro* differentiation model using human pluripotent stem cells (hPSCs) to generate male germ cells could be employed. CRISPRi (interference) could be used to specifically repress [H3 5](/details-gene/440093) expression in hPSCs before initiating differentiation. The developmental progression of these modified cells could then be compared to control cells using single-cell RNA-sequencing to identify developmental arrest points and ChIP-seq for H3.5 to confirm its incorporation into specific genomic regions during key stages of germ cell development. **Therapeutic Potential:** Due to its highly restricted expression in the testes, [H3 5](/details-gene/440093) presents a compelling and highly specific target for non-hormonal male contraception. An inhibitor of H3.5 incorporation into chromatin could disrupt spermatogenesis without affecting somatic cells, potentially offering a reversible and safe contraceptive method. Inhibition, rather than activation, would be the therapeutic strategy. Furthermore, its specificity makes it a potential biomarker for certain testicular germ cell tumors.

Genular Protein ID: 2284412822

Symbol: H3C_HUMAN

Name: Histone H3.3C

UniProtKB Accession Codes:

Q6NXT2 E9P281

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 3 EMDB 1 Ensembl 1 EvolutionaryTrace 1 GO 8 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 22 PDBsum 22 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 RefSeq 1 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TopDownProteomics 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 21274551

Title: H3.5 is a novel hominid-specific histone H3 variant that is specifically expressed in the seminiferous tubules of human testes.

PubMed ID: 21274551

DOI: 10.1007/s00412-011-0310-4

PubMed ID: 16541075

Title: The finished DNA sequence of human chromosome 12.

PubMed ID: 16541075

DOI: 10.1038/nature04569

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: 20850016

Title: Quantitative interaction proteomics and genome-wide profiling of epigenetic histone marks and their readers.

PubMed ID: 20850016

DOI: 10.1016/j.cell.2010.08.020

Sequence Information:

  • Length: 135
  • Mass: 15214
  • Checksum: F2941F8A9BC61BB5
  • Sequence:
    • MARTKQTARK STGGKAPRKQ LATKAARKST PSTCGVKPHR YRPGTVALRE IRRYQKSTEL 
LIRKLPFQRL VREIAQDFNT DLRFQSAAVG ALQEASEAYL VGLLEDTNLC AIHAKRVTIM 
PKDIQLARRI RGERA