Histone H4 (HIST4H4)
The protein contains 103 amino acids for an estimated molecular weight of 11367 Da.
Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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| Variant | Description |
|---|---|
| a breast cancer sample |
Biological Process
Amyloid fibril formation
Beta-catenin-TCF complex assembly
Cellular protein metabolic process
CENP-A containing nucleosome assembly
Chromatin organization
Depurination
DNA methylation on cytosine
DNA replication-dependent nucleosome assembly
DNA replication-independent nucleosome assembly
DNA-templated transcription, initiation
Double-strand break repair
Double-strand break repair via nonhomologous end joining
Gene expression
Histone H4-K20 demethylation
Mitotic cell cycle
Mitotic chromosome condensation
Negative regulation of DNA recombination at telomere
Negative regulation of gene expression, epigenetic
Negative regulation of megakaryocyte differentiation
Nucleosome assembly
Positive regulation of gene expression, epigenetic
Positive regulation of histone exchange
Protein heterotetramerization
RDNA heterochromatin assembly
Regulation of androgen receptor signaling pathway
Regulation of gene expression, epigenetic
Regulation of gene silencing by miRNA
Regulation of hematopoietic stem cell differentiation
Regulation of megakaryocyte differentiation
Telomere capping
Telomere maintenance
Telomere organization
Viral life cycle
The reference OMIM entry for this protein is 142750
Histone gene cluster 2, h4 histone family, member a; hist2h4a
Histone gene cluster 2, h4a
Hist2 cluster, h4a
Hist2h4
H4 histone family, member n; h4fn
H4 histone, family 2; h4f2
For background information on histones, histone gene clusters, and the H4 histone family, see HIST1H4A (602822).
CLONING
By restriction endonuclease digestion of a genomic clone, Sierra et al. (1983) isolated DNA (pF0108) with the capacity to code for a typical H4 histone protein, H4FN. Sequence analysis predicted a 103-amino acid protein. Autoradiographic analysis of an in vitro transcribed pF0108 allowed visualization of a 2.9-kb transcript. By genomic sequence analysis, Marzluff et al. (2002) identified the mouse and human HIST2H4A genes. All mouse and human H4 genes, including HIST2H4A, encode the same protein.GENE STRUCTURE
Sierra et al. (1983) found that H4FN has a 5-prime promoter containing regulatory sequences typically used by RNA polymerase II. The H4FN gene contains no intervening sequences. Sierra et al. (1983) predicted the termination of the mRNA at the ACCA motif just downstream from the hyphenated dyad symmetry characteristic of other histone genes. Pauli et al. (1987) identified 2 regions of DNA with 4 potential protein-binding domains in the 5-prime promoter region of H4FN that are protected from reaction with dimethyl sulfate in cells and from digestion with DNase I in nuclei.MAPPING
By genomic sequence analysis, Marzluff et al. (2002) determined that the histone gene cluster on chromosome 1q21, which they called histone gene cluster-2 (HIST2), contains 6 histone genes, including HIST2H4A.GENE FUNCTION
See HIST1H4A (602822) for functional information on H4 histones. ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for HIST4H4
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 142750 was added.