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Aliases for SPPL2A Gene

Aliases for SPPL2A Gene

  • Signal Peptide Peptidase Like 2A 2 3 5
  • Presenilin-Like Protein 2 2 3 4
  • Intramembrane Protease 3 2 3 4
  • SPP-Like 2A 3 4
  • IMP-3 3 4
  • IMP3 3 4
  • PSL2 3 4
  • Signal Peptide Peptidase-Like 2A 3
  • Intramembrane Cleaving Protease 3
  • EC 3.4.23.- 4
  • SPPL2a 4

External Ids for SPPL2A Gene

Previous GeneCards Identifiers for SPPL2A Gene

  • GC15M046557
  • GC15M044045
  • GC15M048578
  • GC15M048715
  • GC15M048787
  • GC15M050999
  • GC15M027830

Summaries for SPPL2A Gene

Entrez Gene Summary for SPPL2A Gene

  • This gene encodes a member of the GXGD family of aspartic proteases, which are transmembrane proteins with two conserved catalytic motifs localized within the membrane-spanning regions, as well as a member of the signal peptide peptidase-like protease (SPPL) family. This protein is expressed in all major adult human tissues and localizes to late endosomal compartments and lysosomal membranes. A pseudogene of this gene also lies on chromosome 15. [provided by RefSeq, Feb 2012]

GeneCards Summary for SPPL2A Gene

SPPL2A (Signal Peptide Peptidase Like 2A) is a Protein Coding gene. Among its related pathways are Signaling by GPCR and TNF signaling (REACTOME). Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and aspartic-type endopeptidase activity. An important paralog of this gene is SPPL2B.

UniProtKB/Swiss-Prot for SPPL2A Gene

  • Intramembrane-cleaving aspartic protease (I-CLiP) that cleaves type II membrane signal peptides in the hydrophobic plane of the membrane. Functions in FASLG, ITM2B and TNF processing (PubMed:16829952, PubMed:16829951, PubMed:17557115, PubMed:17965014). Catalyzes the intramembrane cleavage of the anchored fragment of shed TNF-alpha (TNF), which promotes the release of the intracellular domain (ICD) for signaling to the nucleus (PubMed:16829952). Also responsible for the intramembrane cleavage of Fas antigen ligand FASLG, which promotes the release of the intracellular FasL domain (FasL ICD) (PubMed:17557115). May play a role in the regulation of innate and adaptive immunity (PubMed:16829952). Catalyzes the intramembrane cleavage of the simian foamy virus envelope glycoprotein gp130 independently of prior ectodomain shedding by furin or furin-like proprotein convertase (PC)-mediated cleavage proteolysis (PubMed:23132852).

Gene Wiki entry for SPPL2A Gene

Additional gene information for SPPL2A Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for SPPL2A Gene

Genomics for SPPL2A Gene

GeneHancer (GH) Regulatory Elements for SPPL2A Gene

Promoters and enhancers for SPPL2A Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH15I050763 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE dbSUPER 567.1 +0.9 948 3.3 HDGF PKNOX1 CLOCK FOXA2 SMAD1 ARNT ARID4B NEUROD1 SIN3A FEZF1 SPPL2A GABPB1-IT1 USP8 RPS20P34 ENSG00000259298 TRPM7 ENSG00000259618 AP4E1 RPL32P30 ENSG00000259773
GH15I050766 Enhancer 0.8 ENCODE dbSUPER 550.8 -1.2 -1236 0.9 SCRT1 ELF3 SOX5 FOXA2 TEAD1 HLF HMG20A KMT2B FOXA1 KLF16 SPPL2A GC15P050737 RPL32P30 GC15P050730 GC15P050634
GH15I050883 Enhancer 1.7 FANTOM5 Ensembl ENCODE dbSUPER 16.4 -118.8 -118828 2.8 HDGF FOXA2 PKNOX1 ARID4B SIN3A YBX1 DMAP1 IRF4 YY1 CBX5 GC15P050883 GC15P050885 SPPL2A AP4E1 ENSG00000259306 USP8 ENSG00000259715 TRPM7 ENSG00000273674 GC15P050737
GH15I050685 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE 11.8 +79.5 79482 2.6 HDGF FOXA2 PKNOX1 SMAD1 MLX ARNT ARID4B SIN3A DMAP1 ZNF2 TRPM7 GABPB1-IT1 USP8 ENSG00000259618 ENSG00000259298 ENSG00000259715 SPPL2A DCAF13P3 RPS20P34 GABPB1-AS1
GH15I050906 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE dbSUPER 9.3 -143.1 -143121 6.2 PKNOX1 FOXA2 SMAD1 MLX ARNT ZFP64 ARID4B SIN3A DMAP1 ZBTB7B AP4E1 ENSG00000273674 GABPB1-AS1 DCAF13P3 ENSG00000259715 SPPL2A ENSG00000259306 GC15P050921
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around SPPL2A on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the SPPL2A gene promoter:

Genomic Locations for SPPL2A Gene

Genomic Locations for SPPL2A Gene
chr15:50,702,266-50,766,158
(GRCh38/hg38)
Size:
63,893 bases
Orientation:
Minus strand
chr15:50,999,506-51,058,005
(GRCh37/hg19)

Genomic View for SPPL2A Gene

Genes around SPPL2A on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SPPL2A Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SPPL2A Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SPPL2A Gene

Proteins for SPPL2A Gene

  • Protein details for SPPL2A Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8TCT8-SPP2A_HUMAN
    Recommended name:
    Signal peptide peptidase-like 2A
    Protein Accession:
    Q8TCT8
    Secondary Accessions:
    • B2RDS0
    • Q8TAW1
    • Q96SZ8

    Protein attributes for SPPL2A Gene

    Size:
    520 amino acids
    Molecular mass:
    58143 Da
    Quaternary structure:
    • Interacts with ITM2B (PubMed:17965014).
    SequenceCaution:
    • Sequence=BAB55117.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=CAD13133.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};

neXtProt entry for SPPL2A Gene

Post-translational modifications for SPPL2A Gene

  • Glycosylated.
  • Glycosylation at posLast=5858, isoforms=66, posLast=7474, isoforms=116, isoforms=126, posLast=149149, and isoforms=155

Other Protein References for SPPL2A Gene

No data available for DME Specific Peptides for SPPL2A Gene

Domains & Families for SPPL2A Gene

Gene Families for SPPL2A Gene

Human Protein Atlas (HPA):
  • Enzymes
  • Plasma proteins
  • Predicted membrane proteins
  • Transporters

Protein Domains for SPPL2A Gene

Suggested Antigen Peptide Sequences for SPPL2A Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q8TCT8

UniProtKB/Swiss-Prot:

SPP2A_HUMAN :
  • 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; therefore, it is predicted to cleave type II-oriented substrate peptides like the prototypic protease SPP. The C-terminal tail is necessary for lysosomal transport.
  • Belongs to the peptidase A22B family.
Domain:
  • 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; therefore, it is predicted to cleave type II-oriented substrate peptides like the prototypic protease SPP. The C-terminal tail is necessary for lysosomal transport.
Family:
  • Belongs to the peptidase A22B family.
genes like me logo Genes that share domains with SPPL2A: view

Function for SPPL2A Gene

Molecular function for SPPL2A Gene

UniProtKB/Swiss-Prot Function:
Intramembrane-cleaving aspartic protease (I-CLiP) that cleaves type II membrane signal peptides in the hydrophobic plane of the membrane. Functions in FASLG, ITM2B and TNF processing (PubMed:16829952, PubMed:16829951, PubMed:17557115, PubMed:17965014). Catalyzes the intramembrane cleavage of the anchored fragment of shed TNF-alpha (TNF), which promotes the release of the intracellular domain (ICD) for signaling to the nucleus (PubMed:16829952). Also responsible for the intramembrane cleavage of Fas antigen ligand FASLG, which promotes the release of the intracellular FasL domain (FasL ICD) (PubMed:17557115). May play a role in the regulation of innate and adaptive immunity (PubMed:16829952). Catalyzes the intramembrane cleavage of the simian foamy virus envelope glycoprotein gp130 independently of prior ectodomain shedding by furin or furin-like proprotein convertase (PC)-mediated cleavage proteolysis (PubMed:23132852).

Enzyme Numbers (IUBMB) for SPPL2A Gene

Phenotypes From GWAS Catalog for SPPL2A Gene

Gene Ontology (GO) - Molecular Function for SPPL2A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 16189514
GO:0008233 peptidase activity IEA --
GO:0016787 hydrolase activity IEA --
GO:0042500 aspartic endopeptidase activity, intramembrane cleaving TAS,IEA --
GO:0042803 protein homodimerization activity IDA 15385547
genes like me logo Genes that share ontologies with SPPL2A: view
genes like me logo Genes that share phenotypes with SPPL2A: view

Animal Models for SPPL2A Gene

MGI Knock Outs for SPPL2A:

Animal Model Products

miRNA for SPPL2A Gene

miRTarBase miRNAs that target SPPL2A

Clone Products

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for SPPL2A Gene

Localization for SPPL2A Gene

Subcellular locations from UniProtKB/Swiss-Prot for SPPL2A Gene

Late endosome membrane; Multi-pass membrane protein. Lysosome membrane; Multi-pass membrane protein. Membrane; Multi-pass membrane protein; Lumenal side. Note=Colocalizes with palmitoylated and myristoylated proteins at the plasma membrane.

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 SPPL2A gene
Compartment Confidence
plasma membrane 5
extracellular 5
endoplasmic reticulum 5
lysosome 5
golgi apparatus 5
endosome 5

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for SPPL2A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005764 lysosome IEA --
GO:0005765 lysosomal membrane IEA,HDA 17897319
GO:0005768 endosome IEA --
GO:0005770 late endosome IDA 16829952
GO:0005886 plasma membrane IDA,TAS --
genes like me logo Genes that share ontologies with SPPL2A: view

Pathways & Interactions for SPPL2A Gene

genes like me logo Genes that share pathways with SPPL2A: view

Pathways by source for SPPL2A Gene

Gene Ontology (GO) - Biological Process for SPPL2A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006508 proteolysis IEA --
GO:0006509 membrane protein ectodomain proteolysis IDA 16829951
GO:0010803 regulation of tumor necrosis factor-mediated signaling pathway TAS --
GO:0031293 membrane protein intracellular domain proteolysis IEA,IMP 16829952
GO:0033619 membrane protein proteolysis IDA 2313285
genes like me logo Genes that share ontologies with SPPL2A: view

No data available for SIGNOR curated interactions for SPPL2A Gene

Drugs & Compounds for SPPL2A Gene

No Compound Related Data Available

Transcripts for SPPL2A Gene

Unigene Clusters for SPPL2A Gene

Signal peptide peptidase like 2A:
Representative Sequences:

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for SPPL2A Gene

ExUns: 1 ^ 2 ^ 3 ^ 4a · 4b ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13a · 13b · 13c ^ 14 ^ 15a · 15b ^ 16 ^ 17
SP1: - - - -
SP2:
SP3:
SP4:

Relevant External Links for SPPL2A Gene

GeneLoc Exon Structure for
SPPL2A
ECgene alternative splicing isoforms for
SPPL2A

Expression for SPPL2A Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for SPPL2A Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for SPPL2A Gene

This gene is overexpressed in Muscle - Skeletal (x4.8).

Protein differential expression in normal tissues from HIPED for SPPL2A Gene

This gene is overexpressed in Nasal epithelium (42.6), Serum (8.8), and Monocytes (7.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for SPPL2A Gene



NURSA nuclear receptor signaling pathways regulating expression of SPPL2A Gene:

SPPL2A

SOURCE GeneReport for Unigene cluster for SPPL2A Gene:

Hs.401537

mRNA Expression by UniProt/SwissProt for SPPL2A Gene:

Q8TCT8-SPP2A_HUMAN
Tissue specificity: Ubiquitous.

Evidence on tissue expression from TISSUES for SPPL2A Gene

  • Blood(4.3)
  • Pancreas(4.3)
  • Lymph node(2.3)
  • Spleen(2.3)
genes like me logo Genes that share expression patterns with SPPL2A: view

No data available for Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for SPPL2A Gene

Orthologs for SPPL2A Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for SPPL2A Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SPPL2A 34 33
  • 99.74 (n)
OneToOne
cow
(Bos Taurus)
Mammalia SPPL2A 33 34
  • 93.23 (n)
dog
(Canis familiaris)
Mammalia SPPL2A 33 34
  • 92.05 (n)
rat
(Rattus norvegicus)
Mammalia Sppl2a 33
  • 83.94 (n)
mouse
(Mus musculus)
Mammalia Sppl2a 16 34 33
  • 83.75 (n)
oppossum
(Monodelphis domestica)
Mammalia SPPL2A 34
  • 73 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia SPPL2A 34
  • 69 (a)
OneToOne
chicken
(Gallus gallus)
Aves SPPL2A 33 34
  • 74.37 (n)
lizard
(Anolis carolinensis)
Reptilia SPPL2A 34
  • 53 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia sppl2a 33
  • 65.36 (n)
zebrafish
(Danio rerio)
Actinopterygii zgc:123258 33
  • 55.67 (n)
worm
(Caenorhabditis elegans)
Secernentea imp-1 33 34
  • 48.54 (n)
C36B1.12 35
  • 28 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes -- 34
  • 16 (a)
OneToMany
rice
(Oryza sativa)
Liliopsida Os11g0433200 33
  • 48.02 (n)
Species where no ortholog for SPPL2A was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • 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)
  • fruit fly (Drosophila melanogaster)
  • 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 squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for SPPL2A Gene

ENSEMBL:
Gene Tree for SPPL2A (if available)
TreeFam:
Gene Tree for SPPL2A (if available)

Paralogs for SPPL2A Gene

Paralogs for SPPL2A Gene

(2) SIMAP similar genes for SPPL2A Gene using alignment to 3 proteins:

Pseudogenes.org Pseudogenes for SPPL2A Gene

genes like me logo Genes that share paralogs with SPPL2A: view

Variants for SPPL2A Gene

Sequence variations from dbSNP and Humsavar for SPPL2A Gene

SNP ID Clin Chr 15 pos Variation AA Info Type
rs1000051161 -- 50,732,450(-) C/G intron_variant
rs1000081786 -- 50,732,956(-) G/A intron_variant
rs1000099864 -- 50,765,527(-) G/A coding_sequence_variant, missense_variant
rs1000165093 -- 50,734,206(-) C/T intron_variant
rs1000204551 -- 50,729,377(-) T/C intron_variant

Structural Variations from Database of Genomic Variants (DGV) for SPPL2A Gene

Variant ID Type Subtype PubMed ID
nsv569402 CNV loss 21841781
nsv569398 CNV loss 21841781
nsv471242 CNV gain 18288195
nsv457137 CNV loss 19166990
nsv1051400 CNV gain 25217958
nsv1047443 CNV gain 25217958
nsv1044320 CNV loss 25217958
nsv1043273 CNV loss 25217958
esv3636449 CNV loss 21293372
esv2659888 CNV deletion 23128226
esv2609237 CNV deletion 19546169
dgv4526n54 CNV gain 21841781
dgv4525n54 CNV gain 21841781
dgv317n27 CNV gain 19166990
dgv2594n100 CNV gain 25217958

Variation tolerance for SPPL2A Gene

Residual Variation Intolerance Score: 76% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.01; 60.26% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SPPL2A Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
SPPL2A

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SPPL2A Gene

Disorders for SPPL2A Gene

Additional Disease Information for SPPL2A

No disorders were found for SPPL2A Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for SPPL2A Gene

Publications for SPPL2A Gene

  1. Regulated intramembrane proteolysis of Bri2 (Itm2b) by ADAM10 and SPPL2a/SPPL2b. (PMID: 17965014) Martin L … Haass C (The Journal of biological chemistry 2008) 3 4 22 58
  2. The Fas ligand intracellular domain is released by ADAM10 and SPPL2a cleavage in T-cells. (PMID: 17557115) Kirkin V … Zörnig M (Cell death and differentiation 2007) 3 4 22 58
  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 (The Journal of biological chemistry 2004) 3 4 22 58
  4. Novel class of polytopic proteins with domains associated with putative protease activity. (PMID: 12139484) Grigorenko AP … Rogaev EI (Biochemistry. Biokhimiia 2002) 2 3 4 58
  5. Identification of signal peptide peptidase, a presenilin-type aspartic protease. (PMID: 12077416) Weihofen A … Martoglio B (Science (New York, N.Y.) 2002) 2 3 4 58

Products for SPPL2A Gene

Sources for SPPL2A Gene

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