The housekeeping proteome

A large number of proteins are essential for all cells throughout the human body. These proteins are sometimes called housekeeping proteins, suggesting that their expression is crucial for the maintenance of basic cellular function. There are a number of definitions of housekeeping proteins, with different stringency. However, the key assumption of any definition of housekeeping genes is that they are expected to be expressed in every cell type in the organism. A transcriptomics analysis of samples representing all major organs and tissues in the body identified 8839 protein-coding genes detected in all analyzed tissues.

Table 1. The genes with expression in all tissues.

Category Description Number of genes
Detected in all Detected in all tissues (TPM>=1) 8839

Housekeeping proteins exist in all classes of proteins, but some classes are clearly overrepresented. The table below gives some examples of well-known housekeeping proteins.

Table 2. Examples of housekeeping protein classes

Protein class Number of genes Number of genes
"detected in all"
Ribosomal proteins 178 174
Citric acid cycle related proteins 30 27
RNA polymerase related proteins 31 28

Gene expression

An easily understood class of housekeeping proteins are those involved in the genetic machinery of gene expression, e.g. RNA polymerases and ribosomal proteins, essential for transcribing and translating the DNA into proteins. It is intuitive that without these genes the cell and organism cannot function at all.

RNA Polymerases

The RNA polymerases are enzymes responsible for synthesizing RNA copies from a DNA template by the process of transcription. In eukaryotic cells, transcription takes place in the cell nucleus, illustrated in the images below showing distinct staining of RNA polymerase II subunit A (POLR2E) in the nucleus of every cell. Some of these RNA transcripts are further processed into messenger RNAs (mRNA), the direct templates for any protein, which are exported to the cytoplasm where translation takes place. Out of the 31 polymerase proteins (KEGG PATHWAY: hsa03020), 28 are found to be expressed in all tissues.

Figure 1. Immunohistochemical staining showing the nuclear localization of the polymerase protein POLR2E.

Ribosomal proteins

The ribosomal proteins form the ribosome complex together with ribosomal RNA (rRNA). The role of the ribosome complex is to translate the genetic code of the mRNA molecules into proteins. Translation is facilitated through a reading of the combination of three base codons of the mRNA, each codon coding for an amino acid, and the formation of a resulting peptide chain, which when done, will be post-processed to be turned into a functional protein. Translation occurs in the cytosol, isolated from transcription, as seen in figure 2. Out of all 178 ribosomal proteins, 174 are found to be expressed in all studied tissues.

Figure 2. Immunohistochemical staining of ribosomal protein RPL17 in liver, showing the cytosolic localization of the protein.

Metabolism

Apart from being able to translate DNA into functional proteins, a cell also needs to extract energy from organic matter and to utilize the energy to construct necessary components. These diverse and essential processes are together referred to as metabolism.

Citric acid cycle

The citric acid cycle is a central part of the metabolic pathway that converts organic matter from carbohydrates, proteins and fats into chemical energy through a series of chemical reactions. The enzymes that catalyze these reactions are apt examples of housekeeping proteins, since all cells require energy to survive and function. Out of the 30 genes involved in the citric acid cycle (KEGG PATHWAY: hsa00020) 27 are expressed in all tissues. Genes that are exceptions always have variants that are expressed in all tissues, as exemplified by the pyruvate dehydrogenase complex subunits PDHA2 (expressed exclusively in testis) and PDHA1 (ubiquitously expressed).

Figure 3. The citric acid cycle takes place in the matrix of the mitochondria, illustrated here by the immunohistochemical staining of SDHB.

Mitochondrial proteins

The main location for energy production in the cell is the mitochondria where, among other pathways, the citric acid cycle takes place. The mitochondrion is an unusual organelle, since it is semi-autonomous, in that it contains its own genome, and has a separate machinery for protein synthesis, while, however, the majority of its genes have been transferred to the nuclear genome. Since the mitochondrion, with its central part in energy production, is crucial for cell survival, most proteins involved in its function and structure are considered to be housekeeping proteins.

Structural proteins

Many proteins involved in the basic structure of the cell are expressed ubiquitously in all cell types, since all cells naturally need certain structures and scaffolds to function. Structural proteins can have numerous functions, but one crucial and obvious housekeeping function is providing rigidity to the cell and to maintain its shape.

Cytoskeleton

The cytoskeleton is a scaffold present in the cytoplasm of all cells, consisting of different types of filaments. The cytoskeleton is also highly involved in the movement of cellular components. Since many specialized uses of the cytoskeleton are present in various cells, far from all genes associated with the cytoskeleton are expressed everywhere. For instance the myosin heavy chains are involved in muscle contraction, and are thus exclusively expressed in muscle tissues. However many of the components are necessary for basic cell functionality and expressed everywhere.

Relevant links and publications

UhlĂ©n M et al., Tissue-based map of the human proteome. Science (2015)
PubMed: 25613900 DOI: 10.1126/science.1260419