Calcineurin
| protein phosphatase 3, catalytic subunit, alpha isozyme | |
|---|---|
| Identifiers | |
| Symbol | PPP3CA |
| Alt. symbols | CALN, CALNA |
| Entrez | 5530 |
| HUGO | 9314 |
| OMIM | 114105 |
| RefSeq | NM_000944 |
| UniProt | Q08209 |
| Other data | |
| EC number | 3.1.3.16 |
| Locus | Chr. 4 q24 |
| protein phosphatase 3, catalytic subunit, beta isozyme | |
|---|---|
| Identifiers | |
| Symbol | PPP3CB |
| Alt. symbols | CALNB |
| Entrez | 5532 |
| HUGO | 9315 |
| OMIM | 114106 |
| RefSeq | NM_021132 |
| UniProt | P16298 |
| Other data | |
| EC number | 3.1.3.16 |
| Locus | Chr. 10 q22.2 |
| protein phosphatase 3, catalytic subunit, gamma isozyme | |
|---|---|
| Identifiers | |
| Symbol | PPP3CC |
| Entrez | 5533 |
| HUGO | 9316 |
| OMIM | 114107 |
| RefSeq | NM_005605 |
| UniProt | P48454 |
| Other data | |
| EC number | 3.1.3.16 |
| Locus | Chr. 8 p21.3 |
| protein phosphatase 3, regulatory subunit B, alpha | |
|---|---|
| Identifiers | |
| Symbol | PPP3R1 |
| Entrez | 5534 |
| HUGO | 9317 |
| OMIM | 601302 |
| RefSeq | NM_000945 |
| UniProt | P63098 |
| Other data | |
| EC number | 3.1.3.16 |
| Locus | Chr. 2 p14 |
| protein phosphatase 3, regulatory subunit B, beta | |
|---|---|
| Identifiers | |
| Symbol | PPP3R2 |
| Entrez | 5535 |
| HUGO | 9318 |
| OMIM | 613821 |
| RefSeq | NM_147180 |
| UniProt | Q96LZ3 |
| Other data | |
| EC number | 3.1.3.16 |
| Locus | Chr. 9 q31 |
Calcineurin (CaN) is a calcium and calmodulin dependent serine/threonine protein phosphatase (also known as protein phosphatase 3, and calcium-dependent serine-threonine phosphatase). It activates the T cells of the immune system and can be blocked by drugs. Calcineurin activates nuclear factor of activated T cell, cytoplasmic (NFATc), a transcription factor, by dephosphorylating it. The activated NFATc is then translocated into the nucleus, where it upregulates the expression of interleukin 2 (IL-2), which, in turn, stimulates the growth and differentiation of T cell response. Calcineurin is the target of a class of drugs called calcineurin inhibitors, which includes cyclosporin, pimecrolimus and tacrolimus.
Calcineurin is a heterodimer of a 61-kD calmodulin-binding catalytic subunit, calcineurin A and a 19-kD Ca2+-binding regulatory subunit, calcineurin B. There are three isozymes of the catalytic subunit, each encoded by a separate gene (PPP3CA, PPP3CB, and PPP3CC) and two isoforms of the regulatory, also encoded by separate genes (PPP3R1, PPP3R2).
When an antigen-presenting cell interacts with a T cell receptor on T cells, there is an increase in the cytoplasmic level of calcium, which activates calcineurin, by binding a regulatory subunit and activating calmodulin binding. Calcineurin induces different transcription factors (NFATs) that are important in the transcription of IL-2 genes. IL-2 activates T-helper lymphocytes and induces the production of other cytokines. In this way, it governs the action of cytotoxic lymphocytes. The amount of IL-2 being produced by the T-helper cells is believed to influence the extent of the immune response significantly.
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