SPPL3 - Signal peptide peptidase-like 3 - human protein (Function)
 
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SPPL3 »  Signal peptide peptidase-like 3   [ EC 3.4.23.- ]  (SPP-like 3)
 
Protein also known as:  Presenilin homologous protein 1 (PSH1).
Gene name:  SPPL3
Family name: Peptidase A22B
Entry whose protein(s) existence is based on evidence at protein level
extend overview
1 28 3
GENE REF ISO

Function

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Overview 
Intramembrane-cleaving aspartic protease (I-CLiP) that cleaves type II membrane protein substrates in or close to their luminal transmembrane domain boundaries (PubMed16873890, PubMed25354954, PubMed25827571). Acts like a sheddase by mediating the proteolytic release and secretion of active site-containing ectodomains of glycan-modifiying glycosidase and glycosyltransferase enzymes such as MGAT5, B4GAT1 and B4GALT1 (PubMed25354954, PubMed25827571). Catalyzes the intramembrane cleavage of the envelope glycoprotein gp130 and/or the leader peptide gp18LP of the simian foamy virus independent of prior ectodomain shedding by furin or furin-like proprotein convertase (PC)-mediated cleavage proteolysis (PubMed23132852). May also have the ability to serve as a shedding protease for subsequent intramembrane proteolysis by SPPL2A and SPPL2B of the envelope glycoprotein gp130 (PubMed23132852). Plays a role in the regulation of cellular glycosylation processes (PubMed25354954). Required to link T-cell antigen receptor (TCR) and calcineurin-NFAT signaling cascades in lymphocytes by promoting the association of STIM1 and ORAI1 during store-operated calcium entry (SOCE) in a protease-independent manner (PubMed25384971).  
6
  • UniProtKB
GO molecular function 
Aspartic endopeptidase activity, intramembrane cleavingdefinition[GO:0042500]  
2
  • UniProtKB
Protein bindingdefinition[GO:0005515]  
1
  • UniProtKB
Protein homodimerization activitydefinition[GO:0042803]  
3
  • UniProtKB
GO biological process 
Not  Membrane protein ectodomain proteolysisdefinition[GO:0006509]  
2
  • UniProtKB
Membrane protein proteolysisdefinition[GO:0033619]  
1
  • UniProtKB
Positive regulation of calcineurin-NFAT signaling cascadedefinition[GO:0070886]  
1
  • UniProtKB
Positive regulation of cytosolic calcium ion concentrationdefinition[GO:0007204]  
1
  • Ortholog Curator
Positive regulation of NFAT protein import into nucleusdefinition[GO:0051533]  
2
  • UniProtKB
  • Ortholog Curator
Positive regulation of protein bindingdefinition[GO:0032092]  
1
  • Ortholog Curator
Positive regulation of protein dephosphorylationdefinition[GO:0035307]  
1
  • UniProtKB
T cell receptor signaling pathwaydefinition[GO:0050852]  
2
  • UniProtKB
  • Ortholog Curator
Enzymatic activity 
It is regulated in the following manner
Its proteolytic activity is blocked by a signal peptide peptidase (SPP) inhibitor, (ZLL)2-ketone (ZLL) or a gamma-secretase inhibitor, LY411,575 (PubMed16873890). However, is not inhibited by ZLL and LY411,575 for activity on simian foamy virus envelope glycoprotein gp130 (PubMed23132852).  
3
  • UniProtKB
 
More information is available from:
 

Keywords

Molecular function 
Hydrolase  definition   [KW-0378]
Protease  definition   [KW-0645]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

GeneWiki: UNQ1887
GenomeRNAi: 121665
PRO: PR:Q8TCT6