======= SPPL3 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: SPPL3
  * **<color #00a2e8>Official Name</color>**: signal peptide peptidase like 3
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=121665|121665]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q8TCT6|Q8TCT6]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=SPPL3&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20SPPL3|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/608240|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**: N/A
  * **<color #00a2e8>UniProt Summary</color>**:  Intramembrane-cleaving aspartic protease (I-CLiP) that cleaves type II membrane protein substrates in or close to their luminal transmembrane domain boundaries (PubMed:16873890, PubMed:25354954, PubMed:25827571). 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 (PubMed:25354954, PubMed:25827571). 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 (PubMed:23132852). May also have the ability to serve as a shedding protease for subsequent intramembrane proteolysis by SPPL2A and SPPL2B of the envelope glycoprotein gp130 (PubMed:23132852). Plays a role in the regulation of cellular glycosylation processes (PubMed:25354954). 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 (PubMed:25384971). {ECO:0000269|PubMed:16873890, ECO:0000269|PubMed:23132852, ECO:0000269|PubMed:25354954, ECO:0000269|PubMed:25384971, ECO:0000269|PubMed:25827571}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|Peptidase A22B|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|integral component of cytoplasmic side of endoplasmic reticulum membrane|
|aspartic endopeptidase activity, intramembrane cleaving|
|signal peptide processing|
|positive regulation of calcineurin-mediated signaling|
|positive regulation of calcineurin-NFAT signaling cascade|
|Golgi-associated vesicle membrane|
|membrane protein ectodomain proteolysis|
|integral component of lumenal side of endoplasmic reticulum membrane|
|regulation of calcineurin-mediated signaling|
|regulation of calcineurin-NFAT signaling cascade|
|membrane protein proteolysis|
|positive regulation of calcium-mediated signaling|
|positive regulation of protein dephosphorylation|
|positive regulation of dephosphorylation|
|rough endoplasmic reticulum|
|endoplasmic reticulum-Golgi intermediate compartment membrane|
|positive regulation of protein binding|
|regulation of calcium-mediated signaling|
|regulation of protein dephosphorylation|
|protein processing|
|T cell receptor signaling pathway|
|positive regulation of binding|
|regulation of dephosphorylation|
|regulation of protein binding|
|protein maturation|
|positive regulation of cytosolic calcium ion concentration|
|antigen receptor-mediated signaling pathway|
|regulation of cytosolic calcium ion concentration|
|regulation of binding|
|cellular calcium ion homeostasis|
|calcium ion homeostasis|
|immune response-activating cell surface receptor signaling pathway|
|cellular divalent inorganic cation homeostasis|
|immune response-regulating cell surface receptor signaling pathway|
|divalent inorganic cation homeostasis|
|peptide metabolic process|
|cellular metal ion homeostasis|
|immune response-activating signal transduction|
|immune response-regulating signaling pathway|
|metal ion homeostasis|
|activation of immune response|
|cellular cation homeostasis|
|cellular ion homeostasis|
|intracellular membrane-bounded organelle|
|cation homeostasis|
|inorganic ion homeostasis|
|cellular chemical homeostasis|
|ion homeostasis|
|cellular amide metabolic process|
|positive regulation of immune response|
|protein homodimerization activity|
|cellular homeostasis|
|Golgi apparatus|
|positive regulation of intracellular signal transduction|
|chemical homeostasis|
|positive regulation of phosphate metabolic process|
|positive regulation of phosphorus metabolic process|
|regulation of immune response|
|positive regulation of immune system process|
|positive regulation of protein modification process|
|proteolysis|
|positive regulation of cellular protein metabolic process|
|homeostatic process|
|regulation of immune system process|
|positive regulation of signal transduction|
|positive regulation of protein metabolic process|
|positive regulation of molecular function|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|regulation of protein modification process|
|membrane|
|gene expression|
</modal>
\\

 === CRISPR Data ===
<button type='default' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
No hits were found.
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:p:prim1|PRIM1]]|0.559|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 16531
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 5.7 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='SPPL3 Expression in NALM6 Cells: 5.7'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>