The pancreas-specific proteome

The pancreas is a composite organ with both exocrine and endocrine functions. The exocrine compartment includes glandular cells that secrete enzymes to the gastrointestinal tract for digestion of food intake. The endocrine function of pancreas is based on the diffusely spread islets of Langerhans, which include endocrine cell types that secrete insulin and other hormones. The transcriptome analysis shows that 49% of all human proteins (n=19628) are expressed in the pancreas and 71 of these genes show an elevated expression in pancreas compared to other tissue types. An analysis of the genes with elevated expression in pancreas reveals that the corresponding proteins are expressed in the various cell types present in pancreas.

  • 35 pancreas enriched genes
  • Most group enriched genes share expression with salivary gland
  • 71 genes defined as elevated in the pancreas
  • Most elevated genes encode secreted proteins

Figure 1. The distribution of all genes across the five categories based on transcript abundance in pancreas as well as in all other tissues.

71 genes show some level of elevated expression in the pancreas compared to other tissues. The three categories of genes with elevated expression in pancreas compared to other organs are shown in Table 1.

Table 1. The genes with elevated expression in pancreas


Number of genes


Tissue enriched 35 At least five-fold higher mRNA levels in a particular tissue as compared to all other tissues
Group enriched 21 At least five-fold higher mRNA levels in a group of 2-7 tissues
Tissue enhanced 15 At least five-fold higher mRNA levels in a particular tissue as compared to average levels in all tissues
Total 71 Total number of elevated genes in pancreas

Table 2. The 12 genes with the highest level of enriched expression in pancreas. "Predicted localization" shows the classification of each gene into three main classes: Secreted, Membrane, and Intracellular, where the latter consists of genes without any predicted membrane and secreted features. "mRNA (tissue)" shows the transcript level asáTPM values,áTS-score (Tissue Specificity score) corresponds to the score calculated as the fold change to the second highest tissue.



Predicted localization

mRNA (tissue)


SYCN syncollin Secreted 6058.1 400
CTRB2 chymotrypsinogen B2 Intracellular,Secreted 29051.6 391
CTRB1 chymotrypsinogen B1 Intracellular,Secreted 48914.0 375
PNLIPRP1 pancreatic lipase-related protein 1 Secreted 2294.5 371
CELA2A chymotrypsin-like elastase family, member 2A Secreted 34325.6 370
CPA1 carboxypeptidase A1 (pancreatic) Intracellular,Secreted 48833.8 366
CTRC chymotrypsin C (caldecrin) Secreted 18181.6 360
CELA3A chymotrypsin-like elastase family, member 3A Intracellular,Secreted 56974.1 351
PNLIP pancreatic lipase Secreted 93652.7 324
PRSS1 protease, serine, 1 (trypsin 1) Intracellular,Secreted 81582.7 316
AMY2A amylase, alpha 2A (pancreatic) Secreted 31311.3 313
CPB1 carboxypeptidase B1 (tissue) Secreted 47265.6 311

Some of the proteins predicted to be membrane-spanning are intracellular, e.g. in the Golgi or mitochondrial membranes, and some of the proteins predicted to be secreted can potentially be retained in a compartment belonging to the secretory pathway, such as the ER, or remain attached to the outer face of the cell membrane by a GPI anchor.

The pancreas transcriptome

An analysis of the expression levels of each gene makes it possible to calculate the relative mRNA pool for each of the categories. The analysis shows that as much as 84% of the mRNA molecules in the pancreas correspond to genes categorized to be either pancreas enriched, group enriched or, pancreas enhanced. Thus, most of the transcriptional activity in the pancreas relates to proteins with presumed pancreas-specific functions, rendering pancreas (and the salivary gland) significantly different compared to all other tissue types in the human body, which are dominated by mRNA molecules encoding housekeeping genes.

Protein expression of genes elevated in pancreas

Gene Ontology-based analysis of all the 71 genes elevated in pancreas indicates a clear overrepresentation of proteins associated with metabolic processes, proteolysis and digestion. A majority of the 71 genes encode secreted proteins.

In-depth analysis of the elevated genes in pancreas using antibody-based protein profiling allowed us to create a map of where these proteins are expressed within the pancreas.

Proteins specifically expressed in islet cells of pancreas

The islet cells constitute 2% of the pancreas, and are responsible for maintaining a steady blood glucose level by secreting hormones regulating uptake and release of glucose. Examples of proteins expressed in islet cells include INS, which is secreted following elevated blood glucose levels, and GCG, which acts in the opposite direct raising blood glucose levels. Another important protein is the transcription factor NKX6-1, essential for development of beta cells.

Proteins specifically expressed in exocrine glandular cells of pancreas

The exocrine part of the pancreas is mainly composed of exocrine glandular cells and ductal cells. The main function of the exocrine glandular cells is to produce digestive enzymes and chloride-rich fluid for transportation of enzymes. Examples of proteins expressed in exocrine glandular cells include AMY2A and CELA3A, both involved in enzymatic digestion of proteins and lipids.

Proteins specifically expressed in ductal cells of pancreas

The enzymes secreted by exocrine glandular cells are transported through the pancreatic ductal system into the main pancreatic duct that ends in the duodenum. The ductal epithelium secretes bicarbonate-rich fluid for regulation of the pH. One example of a protein expressed in ductal cells is the secretin receptor (SCTR), which is involved in regulating bicarbonate and electrolyte secretion by the pancreas.

Genes shared between pancreas and other tissues

There are 21 group enriched genes expressed in the pancreas. Group enriched genes are defined as genes showing a 5-fold higher average level of mRNA expression in a group of 2-7 tissues, including pancreas, compared to all other tissues.

In order to illustrate the relation of pancreas tissue to other tissue types, a network plot was generated, displaying the number of commonly expressed genes between different tissue types.

Figure 2. An interactive network plot of theápancreasáenriched and group enriched genes connected to their respective enriched tissues (grey circles).áRedánodes represent the number ofápancreas enriched genes andáorangeánodes represent the number of genes that are group enriched. The sizes of the red and orange nodes are related to the number of genes displayed within the node. Each node is clickable and results in a list of all enriched genes connected to the highlighted edges. The network is limited to group enriched genes in combinations of up toá3átissues, but the resulting lists show the complete set of group enriched genes in the particular tissue.

Pancreas shares two genes with salivary gland, an organ with an exocrine function highly correlated with the exocrine pancreas. One example of a group enriched gene shared between pancreas and salivary gland is BHLHA15, a transcription factor regulating acinar cell function and stability.

BHLHA15 - pancreas
BHLHA15 - salivary gland

The Lithostathine-1-alpha (REG1A), also known as Regenerating islet-derived protein 1-alpha, is expressed throughout the exocrine pancreas, and is believed to be important for islet cell regeneration. REG1A is group enriched in pancreas, small intestine and duodenum.

REG1A - pancreas
REG1A - small intestine
REG1A - duodenum

Pancreas function

The pancreas is a mixed exocrine/endocrine gland with dual functions essential for maintaining physiological levels of blood glucose and for digestion of food intake. The underlying cell types that execute these diverse functions are exocrine cells, responsible for storing enzymes, and cells in islets of Langerhans, synthesizing different hormones.

Pancreas histology

The exocrine component is composed of lobular units of acini, which discharge their secretions into progressively larger ducts that finally merge into the main pancreatic duct, which ends in duodenum. The pyramidal-shaped acinar cells are filled by eosinophilic zymogen granules.

The islets of Langerhans, which constitute 1-2% of the cell mass in the adult pancreas, represent the endocrine component of the pancreas. The islets are round, compact structures that are highly vascularized with sparse connective tissue. The main cell types in the islets are beta cells - responsible for insulin production, alpha cells - responsible for glucagon secretion, delta cells - responsible for somatostatin secretion and PP cells - the pancreatic polypeptide secreting cells.

The histology of human pancreas including detailed images and information about the different cell types can be viewed in the Protein Atlas Histology Dictionary.


Here, the protein-coding genes expressed in the pancreas are described and characterized, together with examples of immunohistochemically stained tissue sections that visualize protein expression patterns of proteins that correspond to genes with elevated expression in the pancreas.

Transcript profiling and RNA-data analyses based on normal human tissues have been described previously (Fagerberg et al., 2013). Analyses of mRNA expression including over 99% of all human protein-coding genes was performed using deep RNA sequencing of 172 individual samples corresponding to 37 different human normal tissue types. RNA sequencing results of 2 fresh frozen tissues representing normal pancreas was compared to 170 other tissue samples corresponding to 36 tissue types, in order to determine genes with elevated expression in pancreas. A tissue-specific score, defined as the ratio between mRNA levels in pancreas compared to the mRNA levels in all other tissues, was used to divide the genes into different categories of expression. These categories include: genes with elevated expression in pancreas, genes expressed in all tissues, genes with a mixed expression pattern, genes not expressed in pancreas, and genes not expressed in any tissue. Genes with elevated expression in pancreas were further sub-categorized as i) genes with enriched expression in pancreas, ii) genes with group enriched expression including pancreas and iii) genes with enhanced expression in pancreas.

Human tissue samples used for protein and mRNA expression analyses were collected and handled in accordance with Swedish laws and regulation and obtained from the Department of Pathology, Uppsala University Hospital, Uppsala, Sweden as part of the sample collection governed by the Uppsala Biobank. All human tissue samples used in the present study were anonymized in accordance with approval and advisory report from the Uppsala Ethical Review Board.

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Histology dictionary - pancreas