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Aliases for SPPL3 Gene

Aliases for SPPL3 Gene

  • Signal Peptide Peptidase Like 3 2 3
  • Presenilin-Like Protein 4 2 3 4
  • Intramembrane Protease 2 2 3 4
  • Presenilin Homologous Protein 1 3 4
  • SPP-Like 3 3 4
  • IMP2 3 4
  • PSH1 3 4
  • PSL4 3 4
  • EC 3.4.23.- 4
  • MDHV1887 3
  • PRO4332 3
  • IMP-2 4

External Ids for SPPL3 Gene

Previous GeneCards Identifiers for SPPL3 Gene

  • GC12P119943
  • GC12M120983
  • GC12M119612
  • GC12M119663
  • GC12M121201
  • GC12M118210
  • GC12M121202
  • GC12M121210
  • GC12M121231
  • GC12M121252

Summaries for SPPL3 Gene

GeneCards Summary for SPPL3 Gene

SPPL3 (Signal Peptide Peptidase Like 3) is a Protein Coding gene. GO annotations related to this gene include protein homodimerization activity and aspartic endopeptidase activity, intramembrane cleaving. An important paralog of this gene is SPPL2C.

UniProtKB/Swiss-Prot for SPPL3 Gene

  • 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).

Gene Wiki entry for SPPL3 Gene

No data available for Entrez Gene Summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for SPPL3 Gene

Genomics for SPPL3 Gene

Regulatory Elements for SPPL3 Gene

Epigenetics Products

  • DNA Methylation CpG Assay Predesigned for Pyrosequencing in human,mouse,rat

Genomic Location for SPPL3 Gene

Chromosome:
12
Start:
120,762,510 bp from pter
End:
120,904,371 bp from pter
Size:
141,862 bases
Orientation:
Minus strand

Genomic View for SPPL3 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for SPPL3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SPPL3 Gene

Proteins for SPPL3 Gene

  • Protein details for SPPL3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8TCT6-SPPL3_HUMAN
    Recommended name:
    Signal peptide peptidase-like 3
    Protein Accession:
    Q8TCT6
    Secondary Accessions:
    • Q3MJ04
    • Q8TAU4
    • Q96DD9

    Protein attributes for SPPL3 Gene

    Size:
    385 amino acids
    Molecular mass:
    42563 Da
    Quaternary structure:
    • Monomer (PubMed:15385547, PubMed:15998642, PubMed:16873890). Homodimer (PubMed:15385547, PubMed:15998642, PubMed:16873890). Interacts with STIM1 (via the transmembrane region and the SOAR/CAD domain); the interaction promotes the binding of STIM1 to ORAI1 (PubMed:25384971). Interacts with the simian foamy virus envelope glycoprotein gp130 and its processed leader peptide gp18LP; preferentially interacts with the envelope glycoprotein gp130 (PubMed:23132852).
    SequenceCaution:
    • Sequence=BAC11290.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};

    Alternative splice isoforms for SPPL3 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for SPPL3 Gene

Proteomics data for SPPL3 Gene at MOPED

Post-translational modifications for SPPL3 Gene

Other Protein References for SPPL3 Gene

No data available for DME Specific Peptides for SPPL3 Gene

Domains & Families for SPPL3 Gene

Protein Domains for SPPL3 Gene

Suggested Antigen Peptide Sequences for SPPL3 Gene

Graphical View of Domain Structure for InterPro Entry

Q8TCT6

UniProtKB/Swiss-Prot:

SPPL3_HUMAN :
  • The first transmembrane domain may act as a type I signal anchor (PubMed:15385547). The catalytic loops is exposed toward the lumen (PubMed:15385547). The PAL motif is required for normal active site conformation. The catalytic domains embedded in the membrane are in the opposite orientation to that of the presenilin protein family (By similarity).
  • Belongs to the peptidase A22B family.
Domain:
  • The first transmembrane domain may act as a type I signal anchor (PubMed:15385547). The catalytic loops is exposed toward the lumen (PubMed:15385547). The PAL motif is required for normal active site conformation. The catalytic domains embedded in the membrane are in the opposite orientation to that of the presenilin protein family (By similarity).
Family:
  • Belongs to the peptidase A22B family.
genes like me logo Genes that share domains with SPPL3: view

No data available for Gene Families for SPPL3 Gene

Function for SPPL3 Gene

Molecular function for SPPL3 Gene

UniProtKB/Swiss-Prot EnzymeRegulation:
Its proteolytic activity is blocked by a signal peptide peptidase (SPP) inhibitor, (ZLL)2-ketone (ZLL) or a gamma-secretase inhibitor, LY411,575 (PubMed:16873890). However, is not inhibited by ZLL and LY411,575 for activity on simian foamy virus envelope glycoprotein gp130 (PubMed:23132852).
UniProtKB/Swiss-Prot Function:
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).

Enzyme Numbers (IUBMB) for SPPL3 Gene

Gene Ontology (GO) - Molecular Function for SPPL3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004190 aspartic-type endopeptidase activity --
GO:0005515 protein binding IPI 2313285
GO:0042500 aspartic endopeptidase activity, intramembrane cleaving IMP 16873890
GO:0042803 protein homodimerization activity IDA 15385547
genes like me logo Genes that share ontologies with SPPL3: view
genes like me logo Genes that share phenotypes with SPPL3: view

Animal Model Products

miRNA for SPPL3 Gene

miRTarBase miRNAs that target SPPL3

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for SPPL3

In Situ Assay Products

Flow Cytometry Products

No data available for Animal Models , Transcription Factor Targets and HOMER Transcription for SPPL3 Gene

Localization for SPPL3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SPPL3 Gene

Endoplasmic reticulum membrane; Multi-pass membrane protein. Golgi apparatus. Membrane; Multi-pass membrane protein; Lumenal side.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for SPPL3 Gene COMPARTMENTS Subcellular localization image for SPPL3 gene
Compartment Confidence
endoplasmic reticulum 5
golgi apparatus 5
cytosol 3
endosome 1
lysosome 1
plasma membrane 1
vacuole 1

Gene Ontology (GO) - Cellular Components for SPPL3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005791 rough endoplasmic reticulum IDA 15998642
GO:0005829 cytosol IEA --
GO:0016020 membrane IDA 2313285
GO:0016021 integral component of membrane --
GO:0030660 Golgi-associated vesicle membrane IDA 16829952
genes like me logo Genes that share ontologies with SPPL3: view

Pathways & Interactions for SPPL3 Gene

SuperPathways for SPPL3 Gene

No Data Available

Interacting Proteins for SPPL3 Gene

Gene Ontology (GO) - Biological Process for SPPL3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006508 proteolysis --
GO:0006509 NOT membrane protein ectodomain proteolysis IMP 16829952
GO:0007204 positive regulation of cytosolic calcium ion concentration ISS --
GO:0032092 positive regulation of protein binding ISS --
GO:0033619 membrane protein proteolysis IDA 2313285
genes like me logo Genes that share ontologies with SPPL3: view

No data available for Pathways by source and SIGNOR curated interactions for SPPL3 Gene

Drugs & Compounds for SPPL3 Gene

No Compound Related Data Available

Transcripts for SPPL3 Gene

mRNA/cDNA for SPPL3 Gene

(3) REFSEQ mRNAs :
(16) Additional mRNA sequences :
(4) Selected AceView cDNA sequences:
(9) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for SPPL3 Gene

Signal peptide peptidase like 3:
Representative Sequences:

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for SPPL3

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for SPPL3 Gene

No ASD Table

Relevant External Links for SPPL3 Gene

GeneLoc Exon Structure for
SPPL3
ECgene alternative splicing isoforms for
SPPL3

Expression for SPPL3 Gene

mRNA expression in normal human tissues for SPPL3 Gene

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for SPPL3 Gene



SOURCE GeneReport for Unigene cluster for SPPL3 Gene Hs.507087

mRNA Expression by UniProt/SwissProt for SPPL3 Gene

Q8TCT6-SPPL3_HUMAN
Tissue specificity: Widely expressed (PubMed:15385547). Expressed in the brain (PubMed:11978763).
genes like me logo Genes that share expression patterns with SPPL3: view

Primer Products

  • QuantiTect SYBR Green Assays in human,mouse,rat
  • Pre-validated RT² qPCR Primer Assay in human,mouse,rat
  • QuantiFast Probe-based Assays in human,mouse,rat

In Situ Assay Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , Protein differential expression in normal tissues and Protein tissue co-expression partners for SPPL3 Gene

Orthologs for SPPL3 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for SPPL3 Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia SPPL3 35
  • 94.18 (n)
  • 99.74 (a)
SPPL3 36
  • 97 (a)
OneToOne
dog
(Canis familiaris)
Mammalia SPPL3 35
  • 93.84 (n)
  • 98.96 (a)
SPPL3 36
  • 89 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Sppl3 35
  • 91.23 (n)
  • 100 (a)
Sppl3 16
Sppl3 36
  • 100 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia SPPL3 35
  • 99.65 (n)
  • 100 (a)
SPPL3 36
  • 100 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Sppl3 35
  • 90.45 (n)
  • 98.96 (a)
oppossum
(Monodelphis domestica)
Mammalia SPPL3 36
  • 87 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia SPPL3 36
  • 99 (a)
OneToOne
chicken
(Gallus gallus)
Aves SPPL3 35
  • 84.29 (n)
  • 98.18 (a)
SPPL3 36
  • 97 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia SPPL3 36
  • 97 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia MGC75937 35
sppl3 35
  • 79.82 (n)
  • 95.79 (a)
African clawed frog
(Xenopus laevis)
Amphibia MGC52975 35
zebrafish
(Danio rerio)
Actinopterygii sppl3 35
  • 77.87 (n)
  • 94.75 (a)
sppl3 36
  • 95 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta CG17370 37
  • 65 (a)
SppL 35
  • 62.31 (n)
  • 67.85 (a)
Sppl 36
  • 58 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP003207 35
  • 61.61 (n)
  • 69.41 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes -- 36
  • 14 (a)
OneToMany
thale cress
(Arabidopsis thaliana)
eudicotyledons SPPL1 35
  • 45.28 (n)
  • 37.95 (a)
rice
(Oryza sativa)
Liliopsida Os10g0393100 35
  • 47.53 (n)
  • 40.97 (a)
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.10348 35
sea squirt
(Ciona savignyi)
Ascidiacea CSA.3487 36
  • 59 (a)
OneToOne
Species with no ortholog for SPPL3:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for SPPL3 Gene

ENSEMBL:
Gene Tree for SPPL3 (if available)
TreeFam:
Gene Tree for SPPL3 (if available)

Paralogs for SPPL3 Gene

Paralogs for SPPL3 Gene

Pseudogenes.org Pseudogenes for SPPL3 Gene

genes like me logo Genes that share paralogs with SPPL3: view

Variants for SPPL3 Gene

Sequence variations from dbSNP and Humsavar for SPPL3 Gene

SNP ID Clin Chr 12 pos Sequence Context AA Info Type MAF
rs3126 -- 120,847,710(+) acagg(C/T)gtgag intron-variant
rs6553 -- 120,764,559(+) TCCCC(C/T)ATAGG utr-variant-3-prime
rs9431 -- 120,764,861(+) CCTTT(A/C)AATGC utr-variant-3-prime
rs11923 -- 120,764,657(+) AAGAC(C/T)CCTCG utr-variant-3-prime
rs13746 -- 120,763,364(+) GAGCT(C/T)GATCC utr-variant-3-prime, downstream-variant-500B

Structural Variations from Database of Genomic Variants (DGV) for SPPL3 Gene

Variant ID Type Subtype PubMed ID
nsv521928 CNV Gain 19592680
esv2746478 CNV Deletion 23290073
esv1190904 CNV Deletion 17803354
esv1624453 CNV Insertion 17803354
esv2672947 CNV Deletion 23128226
esv2591284 CNV Deletion 19546169
nsv899559 CNV Gain 21882294
nsv908 CNV Insertion 18451855
esv23186 CNV Loss 19812545

Variation tolerance for SPPL3 Gene

Residual Variation Intolerance Score: 30.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.15; 3.35% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for SPPL3 Gene

HapMap Linkage Disequilibrium report
SPPL3

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SPPL3 Gene

Disorders for SPPL3 Gene

Relevant External Links for SPPL3

Genetic Association Database (GAD)
SPPL3
Human Genome Epidemiology (HuGE) Navigator
SPPL3
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
SPPL3
genes like me logo Genes that share disorders with SPPL3: view

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for SPPL3 Gene

Publications for SPPL3 Gene

  1. Regulated intramembrane proteolysis of Bri2 (Itm2b) by ADAM10 and SPPL2a/SPPL2b. (PMID: 17965014) Martin L. … Haass C. (J. Biol. Chem. 2008) 23 67
  2. Intramembrane proteolytic cleavage by human signal peptide peptidase like 3 and malaria signal peptide peptidase. (PMID: 16873890) Nyborg A.C. … Golde T.E. (FASEB J. 2006) 23 67
  3. Consensus analysis of signal peptide peptidase and homologous human aspartic proteases reveals opposite topology of catalytic domains compared with presenilins. (PMID: 15385547) Friedmann E. … Martoglio B. (J. Biol. Chem. 2004) 23 67
  4. Novel class of polytopic proteins with domains associated with putative protease activity. (PMID: 12139484) Grigorenko A.P. … Rogaev E.I. (Biokhimiia 2002) 2 67
  5. A protease-independent function for SPPL3 in NFAT activation. (PMID: 25384971) Makowski S.L. … Pomerantz J.L. (Mol. Cell. Biol. 2015) 67

Products for SPPL3 Gene

Sources for SPPL3 Gene

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