The Signal Peptide Peptidase (SPP) is an intramembrane

Intramembrane protease

Intramembrane proteases are enzymes that have the property of cleaving transmembrane domains of integral membrane proteins. All known intramembrane proteases are themselves integral membrane proteins with multiple transmembrane domains, and they have their active sites buried within the lipid...

 aspartyl protease with the conserved active site motifs 'YD' and 'GxGD' in in adjacent transmembrane domains (TMDs). Its sequences is highly conserved in different vertebrate species. Its substrates are signal peptides, which upon cleavage by Signal Peptidase

Signal peptidase

Signal peptidases are enzymes that convert secretory and some membrane proteins to their mature form by cleaving off their N-terminal targeting signals....

 span the ER membrane similar to a type II transmembrane protein

Transmembrane protein

A transmembrane protein is a protein that goes from one side of a membrane through to the other side of the membrane. Many TPs function as gateways or "loading docks" to deny or permit the transport of specific substances across the biological membrane, to get into the cell, or out of the cell as...

.

Physiologically SPP processes signal peptides of classical MHC class I

MHC class I

MHC class I molecules are one of two primary classes of major histocompatibility complex molecules and are found on every nucleated cell of the body...

 preproteins. A nine amino acid-long cleavage fragment is then presented on HLA-E receptors and modulates the activity of natural killer cells.

SPP also plays a pathophysiological role; it cleaves the structural nucleocapsid protein (also known as core protein) of the Hepatitis C

Hepatitis C

Hepatitis C is an infectious disease primarily affecting the liver, caused by the hepatitis C virus . The infection is often asymptomatic, but chronic infection can lead to scarring of the liver and ultimately to cirrhosis, which is generally apparent after many years...

 virus and thus influences viral reproduction rate.

In mice, a nonamer peptide originating from the SPP protein serves as minor histocompatibility antigen HM13

HM13

Minor histocompatibility antigen H13 is a protein that in humans is encoded by the HM13 gene.- Function :The minor histocompatibility antigen 13 is a nonamer peptide that originates from a protein encoded by the H13 gene...

 that plays a role in transplant rejection

Transplant rejection

Transplant rejection occurs when transplanted tissue is rejected by the recipient's immune system, which destroys the transplanted tissue. Transplant rejection can be lessened by determining the molecular similitude between donor and recipient and by use of immunosuppressant drugs after...

The homologous proteases SPPL2A

SPPL2A

Signal peptide peptidase-like 2A, also known as SPPL2A, is a human gene.- Function :This gene is a member of the signal peptide peptidase-like protease family and encodes an endosomal membrane protein with the conserved active site motifs 'YD' and 'GxGD' in in adjacent transmembrane domains...

 and SPPL2B

SPPL2B

Signal peptide peptidase-like 2B, also known as SPPL2B, is a human gene.-Further reading:...

 promote the intramembrane cleavage of TNFα in activated dendritic cells and might play an immunomodulator

Immunomodulator

An immunomodulator, also known as an immunotherapy is a substance which has an effect on the immune system.- Immunosuppressants :Inhibits immune response in organ transplantation and autoimmune diseases.- Immunostimulants :...

y role. For SPPL2c and SPPL3 no substrates are known.

External links

• The MEROPS
  Merops
  Merops may refer to:* Merops , a genus of bee-eaters.* MEROPS, an on-line database for peptidases.It may also refer to several figures from Greek mythology:* King of Ethiopia, husband of Clymene, who lay with Helios and bore Phaethon...
  
  online database for peptidases and their inhibitors: SPP:A22.003, SPPL2a: A22.007, SPPL2b:A22.004, SPPL2c:A22.006, SPPL3:A22.005 - Calculated spatial position of type 1 signal peptidase in membrane