cpz (Carboxypeptidase Z) – Responsible for 4 diseases, Interesting facts

What is cpz (Carboxypeptidase Z)

cpz is located on the chromosome 4p16.1

cpz is a newly reported member of the CPE, which is the subfamily of metallocarboxypeptidases.

Carboxypeptidase Z was discovered during a search for novel carboxypeptidases which can compensate for defective carboxypeptidase E in Cpe  mice.

Members of this metallocarboxypeptidases constitutes a 350 to 400 amino acid carboxypeptidase domain flanked by unique extensions. These are commonly involved in processing reactions which are quite selective.

Carboxypeptidase Z commonly exists in the Regulated Secretory Pathway and Extracellular Matrix in Cultured Cells as well as in Human Tissues.

Synonyms

  1. Metallocarboxypeptidase Z
  2. Carboxypeptidase Z

What diseases are involved with cpz

  1. A human adenocarcinoma of the colon shows expression of CPZ in the extracellular matrix adjacent to the cancerous cells.
  2. A study identified the expressions of cpz, cpd, cpe immunoreactivity in 48 pituatory adenomas.
  3. cpz immunostaining was described in the luteinizing and follicle stimulating hormones secreting gonadotrophs adenomas.
  4. Endogenous cpz, is also found in rat pheochromocytoma cell line.

Characteristics of this gene

CPZ constitutes a N-terminal domain which has amino acid sequence similarity to Wnt-binding proteins.

A fraction of the secreted Carboxypeptidase Z remains associated with the extracellular matrix.

Carboxypeptidase Z is also present in human placenta which are lying within invasive trophoblasts as well as in the surrounding extracellular space. This points to an association with extracellular matrix.

Carboxypeptidase Z removes arginine residues from proteins. Arginine residues are a type of carboxyl-terminal basic amino acid residues.

This is even present in amnion cells, although not readily apparent in the extracellular matrix of this cell type. 

What are the functions of Carboxypeptidase Z

  • Carboxypeptidase Z is responsible for many functions, which are ranging from the digestion of food to the selective processing of certain hormones in the body such as neurotransmitters and neuroendocrine peptide hormones.
  • Overall, there are 12 members of the metallocarboxypeptidase gene family. These are further divided into 2 subgroups which are based on the similarities in the amino acid sequence.
  • Each Member of each subgroup share approximately 30–60% amino acid sequence identity with other members of the same group, but approximately only 15–25% amino acid sequence identity with members of the other subgroup.
  • The two groups also differ in their general function; members of the carboxypeptidase A/B subgroup are typically digestive enzymes. Members of the subgroup containing carboxypeptidase E are referred to as “regulatory” enzymes.
  • Other members of the carboxypeptidase E subgroup include carboxypeptidases M, N, D, and Z, and proteins designated CPX-1, CPX-2, and AEBP-1.
  • Except for the latter three proteins, which are not active toward standard carboxypeptidase substrates and have been hypothesized to function as binding proteins, all of the other members of this subfamily cleave C-terminal Arg from small synthetic peptides.

Studies on cpz

Carboxypeptidase Z Links Thyroid Hormone and Wnt Signaling Pathways in Rat Growth Plate Chondrocytes

Research identified that CPZ as an important enzyme which removes the C-terminal arginine from Wnt-4 in growth plate chondrocytes.

This process of removal not only increases Wnt-4 activity, but even further promotes terminal chondrocyte differentiation.

From these findings. it is evident that the potent and positive thyroid hormone effect on skeletal maturation may result in part from CPZ-mediated activation of Wnt signaling in the growth plate.

The expression of this gene overlaps with the expression pattern of several Wnt genes and persists in cartilage condensations throughout mouse gestation.

Wnt signaling has recently been recognized as an important signal transduction pathway in regulating chondrocyte proliferation and differentiation during limb development. There is evidence from the past research studies that thyroid hormone regulates terminal differentiation of growth plate chondrocytes through activation of Wnt-4 expression and Wnt/β-catenin signaling.

As Wnt-4 contains a C-terminal arginine, that Carboxypeptidase Z binds to Wnt-4 through its CRD, and that CPZ enhances the Wnt-4 dependent induction of the homeobox gene Cdx1, it is reasonable to postulate that Carboxypeptidase Z may enhance Wnt-4 activity through enzymatic removal of its terminal arginine.

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