THE HUMAN TISSUE PROTEOMES

The housekeeping proteome


A large number of proteins are needed in all cells throughout the human body. These proteins are sometimes called housekeeping proteins, suggesting that their expression is crucial for the maintenance of basic functionality of all normally functioning cells. 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 7367 protein-coding genes detected in all analyzed tissues.

Table 1. The genes with expression in all tissues.

Category

Description

Number of genes

Expressed in all Detected in all tissues (TPM>=1) 7367

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
"expressed in all"

Ribosomal proteins 149 144
RNA polymerase related proteins 31 25
Citric acid cycle related proteins 30 26


Gene expression


An easily understood class of housekeeping proteins are those involved in the genetic machinery of gene expression, eg 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 take place in the cell nucleus, as illustrated in the images below, the protein is distinctly present 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), 25 are found to be expressed in all tissues.

Figure 1. Immunohistochemical staining showing the nuclear localization of the polymerase protein POLR2A


Ribosomal proteins


The ribosomal proteins make up the ribosome complex together with the ribosomal RNA (rRNA). The role of the ribosome is to translate the genetic code of the mRNA molecules to proteins, by reading the three base codons of the mRNA and forming a 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 149 ribosomal proteins, 144 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 which converts organic matter from carbohydrates, proteins and fats into chemical energy though a series of chemical reactions. The enzymes that catalyze these reactions are good examples of housekeeping proteins, since all cells require energy to sustain. Out of the 30 genes involved in the citric acid cycle (KEGG PATHWAY: hsa00020) 26 are found to be expressed in all tissues. For the exceptions there are always two variants of the gene, with one of them expressed only in some tissues, as exemplified by the pyruvate dehydrogenase complex subunits PDHA1 (ubiquitously expressed) and PDHA2 (expressed exclusively in testis).

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 semiautonomous, 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 to cell survival, most proteins involved in its function and structure are considered as housekeeping.

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 obviously 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


UhlÚn M et al, 2015. Tissue-based map of the human proteome. Science
PubMed: 25613900 DOI: 10.1126/science.1260419