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Aliases for SPPL3 Gene

Aliases for SPPL3 Gene

  • Signal Peptide Peptidase Like 3 2 3 5
  • 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
  • Signal Peptide Peptidase-Like 3 3
  • EC 3.4.23.- 4
  • MDHV1887 3
  • PRO4332 3
  • IMP-2 4

External Ids for SPPL3 Gene

Previous GeneCards Identifiers for SPPL3 Gene

  • GC12P119943
  • GC12M120799
  • GC12M120983
  • GC12M119612
  • GC12M119663
  • GC12M121201
  • GC12M118210
  • GC12M121202
  • GC12M121210
  • GC12M121231
  • GC12M121252
  • GC12M120801

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

Enhancers for SPPL3 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH12F120901 1.1 ENCODE 18.5 +0.8 811 3.6 HDGF PKNOX1 MLX WRNIP1 ARID4B SIN3A DMAP1 YY1 FOS KLF13 ACADS GCN1 SPPL3 C12orf43 PSMD9 SETD1B NME2P1 LINC01089 ARF1P2
GH12F120821 0.6 Ensembl 28 +83.1 83071 0.2 MTA2 MAFG CHD1 ZNF316 IKZF1 NBN MLLT1 MAFK EMSY SPPL3 ACADS ENSG00000256569 PIR38395 ENSG00000255946
GH12F120958 1.4 Ensembl ENCODE 11.4 -56.7 -56703 5.5 HDGF PKNOX1 ARNT MLX CREB3L1 ARID4B SIN3A DMAP1 ZNF2 YY1 ACADS C12orf43 SPPL3 OASL ENSG00000256569 ENSG00000255946 MIR4700 UNC119B MLEC ENSG00000256364
GH12F120533 1.5 FANTOM5 ENCODE 10.3 +367.1 367079 7.1 PKNOX1 ARNT MLX ARID4B SIN3A FEZF1 DMAP1 ZNF2 YY1 SLC30A9 COQ5 GATC C12orf43 MIR4700 POP5 RPL31P52 TRIAP1 ENSG00000111780 DYNLL1 NME2P1
GH12F120792 0.9 Ensembl 16.8 +111.9 111871 0.6 HDGF KLF17 GLI4 YBX1 ZNF2 RAD21 ZNF48 ZEB1 ZNF335 GLIS2 SPPL3 ACADS MLEC ENSG00000256569 ENSG00000255946 MIR4700 UNC119B C12orf43 PIR38395
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around SPPL3 on UCSC Golden Path with GeneCards custom track

Promoters for SPPL3 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000438219 771 2801 HDGF PKNOX1 MLX WRNIP1 ARID4B SIN3A DMAP1 YY1 FOS KLF13

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

Genes around SPPL3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SPPL3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
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

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:0005515 protein binding IPI 2313285
GO:0008233 peptidase activity IEA --
GO:0016787 hydrolase activity IEA --
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

  • Taconic Biosciences Mouse Models for SPPL3

miRNA for SPPL3 Gene

miRTarBase miRNAs that target SPPL3

Inhibitory RNA Products

Clone Products

Flow Cytometry Products

No data available for Human Phenotype Ontology , 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
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for SPPL3 gene
Compartment Confidence
plasma membrane 5
endoplasmic reticulum 5
golgi apparatus 5
lysosome 4
endosome 1

Gene Ontology (GO) - Cellular Components for SPPL3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005765 lysosomal membrane IBA --
GO:0005783 endoplasmic reticulum IEA --
GO:0005789 endoplasmic reticulum membrane IEA --
GO:0005791 rough endoplasmic reticulum IDA 15998642
GO:0005794 Golgi apparatus IEA --
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:0006465 signal peptide processing IBA --
GO:0006508 proteolysis IEA --
GO:0006509 NOT membrane protein ectodomain proteolysis IMP 16829952
GO:0007204 positive regulation of cytosolic calcium ion concentration IEA,ISS --
GO:0032092 positive regulation of protein binding IEA,ISS --
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

Transcripts for SPPL3 Gene

mRNA/cDNA for SPPL3 Gene

(2) 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

Clone Products

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 from GTEx, Illumina, BioGPS, and SAGE for SPPL3 Gene

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



NURSA nuclear receptor signaling pathways regulating expression of SPPL3 Gene:

SPPL3

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

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
chimpanzee
(Pan troglodytes)
Mammalia SPPL3 34 35
  • 99.65 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia SPPL3 35
  • 99 (a)
OneToOne
cow
(Bos Taurus)
Mammalia SPPL3 34 35
  • 94.18 (n)
dog
(Canis familiaris)
Mammalia SPPL3 34 35
  • 93.84 (n)
mouse
(Mus musculus)
Mammalia Sppl3 34 16 35
  • 91.23 (n)
rat
(Rattus norvegicus)
Mammalia Sppl3 34
  • 90.45 (n)
oppossum
(Monodelphis domestica)
Mammalia SPPL3 35
  • 87 (a)
OneToOne
chicken
(Gallus gallus)
Aves SPPL3 34 35
  • 84.29 (n)
lizard
(Anolis carolinensis)
Reptilia SPPL3 35
  • 97 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia sppl3 34
  • 79.82 (n)
MGC75937 34
African clawed frog
(Xenopus laevis)
Amphibia MGC52975 34
zebrafish
(Danio rerio)
Actinopterygii sppl3 34 35
  • 77.87 (n)
fruit fly
(Drosophila melanogaster)
Insecta CG17370 36
  • 65 (a)
SppL 34
  • 62.31 (n)
Sppl 35
  • 58 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP003207 34
  • 61.61 (n)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes -- 35
  • 14 (a)
OneToMany
thale cress
(Arabidopsis thaliana)
eudicotyledons SPPL1 34
  • 45.28 (n)
rice
(Oryza sativa)
Liliopsida Os10g0393100 34
  • 47.53 (n)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.3487 35
  • 59 (a)
OneToOne
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.10348 34
Species where no ortholog for SPPL3 was found in the sources mined by GeneCards:
  • 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
rs10160872 -- 120,895,283(+) TTAGC(C/T)GCGTG intron-variant
rs1027556 -- 120,837,546(-) AAAGC(A/G)TTATA intron-variant
rs1039302 -- 120,798,455(+) CCTGC(C/T)AACGC intron-variant
rs10431373 -- 120,881,816(+) agaaa(A/C)aaaat intron-variant
rs10431387 -- 120,843,036(+) AAACT(A/G)GTAGA intron-variant

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

Variant ID Type Subtype PubMed ID
dgv2915n54 CNV gain 21841781
dgv2916n54 CNV loss 21841781
dgv2917n54 CNV gain 21841781
dgv2918n54 CNV loss 21841781
esv1190904 CNV deletion 17803354
esv1624453 CNV insertion 17803354
esv23186 CNV loss 19812545
esv2591284 CNV deletion 19546169
esv2672947 CNV deletion 23128226
esv2746478 CNV deletion 23290073
esv2763007 CNV loss 21179565
esv3630932 CNV loss 21293372
nsv1045178 CNV gain 25217958
nsv1070133 CNV deletion 25765185
nsv1144659 CNV deletion 24896259
nsv521928 CNV gain 19592680
nsv560438 CNV gain 21841781
nsv560439 CNV loss 21841781
nsv560440 CNV loss 21841781
nsv560442 CNV loss 21841781
nsv560450 CNV gain+loss 21841781
nsv908 CNV insertion 18451855
nsv957924 CNV deletion 24416366

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

SNPedia medical, phenotypic, and genealogical associations of SNPs for
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

No disorders were found for SPPL3 Gene.

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

Publications for SPPL3 Gene

  1. 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) 3 4 22 64
  2. 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) 3 4 22 64
  3. Novel class of polytopic proteins with domains associated with putative protease activity. (PMID: 12139484) Grigorenko A.P. … Rogaev E.I. (Biokhimiia 2002) 2 3 4 64
  4. A protease-independent function for SPPL3 in NFAT activation. (PMID: 25384971) Makowski S.L. … Pomerantz J.L. (Mol. Cell. Biol. 2015) 3 4 64
  5. Secretome analysis identifies novel signal peptide peptidase-like 3 (SPPL3) substrates and reveals a role of SPPL3 in multiple Golgi glycosylation pathways. (PMID: 25827571) Kuhn P.H. … Fluhrer R. (Mol. Cell Proteomics 2015) 3 4 64

Products for SPPL3 Gene

Sources for SPPL3 Gene

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