Aliases for SPPL2C Gene

Aliases for SPPL2C Gene

  • Signal Peptide Peptidase Like 2C 2 3 5
  • Intramembrane Protease 5 2 3 4
  • IMP5 2 3 4
  • Signal Peptide Peptidase-Like 2C 3 4
  • SPP-Like 2C 3 4
  • IMP-5 3 4
  • EC 3.4.23.- 4
  • SPPL2C 5
  • SPPL2c 4

External Ids for SPPL2C Gene

Previous GeneCards Identifiers for SPPL2C Gene

  • GC17P043923

Summaries for SPPL2C Gene

GeneCards Summary for SPPL2C Gene

SPPL2C (Signal Peptide Peptidase Like 2C) is a Protein Coding gene. Diseases associated with SPPL2C include Chromosome 17Q21.31 Duplication Syndrome and Caplan's Syndrome. 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 Summary for SPPL2C Gene

  • Intramembrane-cleaving aspartic protease (I-CLiP) that may be able to cleave type II membrane signal peptides in the hydrophobic plane of the membrane.

No data available for Entrez Gene Summary , CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SPPL2C Gene

Genomics for SPPL2C Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for SPPL2C Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SPPL2C on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for SPPL2C

Genomic Locations for SPPL2C Gene

Latest Assembly
chr17:45,844,881-45,847,067
(GRCh38/hg38)
Size:
2,187 bases
Orientation:
Plus strand

Previous Assembly
chr17:43,922,247-43,924,433
(GRCh37/hg19 by Entrez Gene)
Size:
2,187 bases
Orientation:
Plus strand

chr17:43,922,256-43,924,438
(GRCh37/hg19 by Ensembl)
Size:
2,183 bases
Orientation:
Plus strand

Alternative Locations (GRCh38/hg38)

  • chr17(ALT_REF_LOCI_1):941,114-943,300 (-)
  • chr17(ALT_REF_LOCI_2):547,002-549,188 (+)

Genomic View for SPPL2C Gene

Genes around SPPL2C on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SPPL2C Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SPPL2C Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SPPL2C Gene

Proteins for SPPL2C Gene

  • Protein details for SPPL2C Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8IUH8-SPP2C_HUMAN
    Recommended name:
    Signal peptide peptidase-like 2C
    Protein Accession:
    Q8IUH8
    Secondary Accessions:
    • Q8TC67
    • Q8WVZ6

    Protein attributes for SPPL2C Gene

    Size:
    684 amino acids
    Molecular mass:
    74503 Da
    Quaternary structure:
    No Data Available

neXtProt entry for SPPL2C Gene

Post-translational modifications for SPPL2C Gene

Other Protein References for SPPL2C Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for SPPL2C Gene

Domains & Families for SPPL2C Gene

Gene Families for SPPL2C Gene

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

Protein Domains for SPPL2C Gene

Suggested Antigen Peptide Sequences for SPPL2C Gene

GenScript: Design optimal peptide antigens:
  • Intramembrane protease 5 (IMP5_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q8IUH8

UniProtKB/Swiss-Prot:

SPP2C_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.
  • 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.
Family:
  • Belongs to the peptidase A22B family.
genes like me logo Genes that share domains with SPPL2C: view

Function for SPPL2C Gene

Molecular function for SPPL2C Gene

UniProtKB/Swiss-Prot Function:
Intramembrane-cleaving aspartic protease (I-CLiP) that may be able to cleave type II membrane signal peptides in the hydrophobic plane of the membrane.

Enzyme Numbers (IUBMB) for SPPL2C Gene

Phenotypes From GWAS Catalog for SPPL2C Gene

Gene Ontology (GO) - Molecular Function for SPPL2C Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004190 aspartic-type endopeptidase activity IEA --
GO:0005515 protein binding IPI 32296183
GO:0008233 peptidase activity IEA --
GO:0016787 hydrolase activity IEA --
GO:0042500 aspartic endopeptidase activity, intramembrane cleaving IBA 21873635
genes like me logo Genes that share ontologies with SPPL2C: view
genes like me logo Genes that share phenotypes with SPPL2C: view

Animal Models for SPPL2C Gene

MGI Knock Outs for SPPL2C:
  • Sppl2c Sppl2c<tm1.1(KOMP)Vlcg>

Animal Models for research

  • Taconic Biosciences Mouse Models for SPPL2C

miRNA for SPPL2C Gene

miRTarBase miRNAs that target SPPL2C

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SPPL2C

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for SPPL2C Gene

Localization for SPPL2C Gene

Subcellular locations from UniProtKB/Swiss-Prot for SPPL2C Gene

Endoplasmic reticulum membrane. Multi-pass membrane protein. 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 SPPL2C gene
Compartment Confidence
plasma membrane 3
lysosome 3
extracellular 1
cytoskeleton 1
endoplasmic reticulum 1
endosome 1

Gene Ontology (GO) - Cellular Components for SPPL2C Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005765 lysosomal membrane IBA 21873635
GO:0005783 endoplasmic reticulum IEA --
GO:0005789 endoplasmic reticulum membrane IEA,IDA 16829952
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with SPPL2C: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for SPPL2C Gene

Pathways & Interactions for SPPL2C Gene

PathCards logo

SuperPathways for SPPL2C Gene

No Data Available

Interacting Proteins for SPPL2C Gene

Gene Ontology (GO) - Biological Process for SPPL2C Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006508 proteolysis IEA --
GO:0006509 NOT membrane protein ectodomain proteolysis IMP 17965014
GO:0031293 NOT membrane protein intracellular domain proteolysis IMP 16829952
GO:0033619 membrane protein proteolysis IBA 21873635
genes like me logo Genes that share ontologies with SPPL2C: view

No data available for Pathways by source and SIGNOR curated interactions for SPPL2C Gene

Drugs & Compounds for SPPL2C Gene

No Compound Related Data Available

Transcripts for SPPL2C Gene

mRNA/cDNA for SPPL2C Gene

1 REFSEQ mRNAs :
2 NCBI additional mRNA sequence :
1 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SPPL2C

Alternative Splicing Database (ASD) splice patterns (SP) for SPPL2C Gene

No ASD Table

Relevant External Links for SPPL2C Gene

GeneLoc Exon Structure for
SPPL2C

Expression for SPPL2C Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for SPPL2C Gene

mRNA differential expression in normal tissues according to GTEx for SPPL2C Gene

This gene is overexpressed in Testis (x44.3).

Protein differential expression in normal tissues from HIPED for SPPL2C Gene

This gene is overexpressed in Testis (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for SPPL2C Gene



Protein tissue co-expression partners for SPPL2C Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for SPPL2C

SOURCE GeneReport for Unigene cluster for SPPL2C Gene:

Hs.144491

mRNA Expression by UniProt/SwissProt for SPPL2C Gene:

Q8IUH8-SPP2C_HUMAN
Tissue specificity: Ubiquitous.
genes like me logo Genes that share expression patterns with SPPL2C: view

Primer products for research

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , Evidence on tissue expression from TISSUES and Phenotype-based relationships between genes and organs from Gene ORGANizer for SPPL2C Gene

Orthologs for SPPL2C Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for SPPL2C Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia SPPL2C 29 30
  • 98.93 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia SPPL2C 29 30
  • 81.33 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia SPPL2C 29 30
  • 79.48 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Sppl2c 29
  • 76.88 (n)
Mouse
(Mus musculus)
Mammalia Sppl2c 29 16 30
  • 76.05 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia SPPL2C 30
  • 69 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia SPPL2C 30
  • 38 (a)
OneToOne
Chicken
(Gallus gallus)
Aves SPPL2B 30
  • 46 (a)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia -- 30
  • 30 (a)
ManyToMany
Zebrafish
(Danio rerio)
Actinopterygii sppl2 30
  • 47 (a)
OneToOne
Worm
(Caenorhabditis elegans)
Secernentea imp-1 30
  • 22 (a)
OneToMany
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes -- 30
  • 16 (a)
OneToMany
Species where no ortholog for SPPL2C was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium 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 (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (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)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)

Evolution for SPPL2C Gene

ENSEMBL:
Gene Tree for SPPL2C (if available)
TreeFam:
Gene Tree for SPPL2C (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SPPL2C: view image
Alliance of Genome Resources:
Additional Orthologs for SPPL2C

Paralogs for SPPL2C Gene

Paralogs for SPPL2C Gene

(2) SIMAP similar genes for SPPL2C Gene using alignment to 1 proteins:

  • SPP2C_HUMAN
genes like me logo Genes that share paralogs with SPPL2C: view

Variants for SPPL2C Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for SPPL2C Gene

SNP ID Clinical significance and condition Chr 17 pos Variation AA Info Type
rs112690750 Benign: not provided 45,845,434(+) C/T
NM_175882.3(SPPL2C):c.528C>T (p.Tyr176=)
SYNONYMOUS
rs112870186 Likely Benign: not provided 45,845,545(+) A/G
NM_175882.3(SPPL2C):c.639A>G (p.Leu213=)
SYNONYMOUS
rs113793057 Benign: not provided 45,845,422(+) C/T
NM_175882.3(SPPL2C):c.516C>T (p.Arg172=)
SYNONYMOUS
rs114607012 Benign: not provided 45,846,888(+) T/G
NM_175882.3(SPPL2C):c.1982T>G (p.Leu661Arg)
MISSENSE
rs116482551 Benign: not provided 45,845,169(+) C/T
NM_175882.3(SPPL2C):c.263C>T (p.Pro88Leu)
MISSENSE

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for SPPL2C Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for SPPL2C Gene

Variant ID Type Subtype PubMed ID
esv2762433 CNV gain+loss 21179565
nsv1146669 OTHER inversion 26484159
nsv522515 CNV loss 19592680
nsv575141 CNV loss 21841781
nsv833460 CNV loss 17160897
nsv953909 CNV deletion 24416366

Variation tolerance for SPPL2C Gene

Residual Variation Intolerance Score: 99.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 7.29; 81.35% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SPPL2C Gene

Human Gene Mutation Database (HGMD)
SPPL2C
SNPedia medical, phenotypic, and genealogical associations of SNPs for
SPPL2C
Leiden Open Variation Database (LOVD)
SPPL2C

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SPPL2C Gene

Disorders for SPPL2C Gene

MalaCards: The human disease database

(7) MalaCards diseases for SPPL2C Gene - From: COP

Disorder Aliases PubMed IDs
chromosome 17q21.31 duplication syndrome
  • 17q21.31 microduplication syndrome
caplan's syndrome
  • caplan syndrome
koolen-de vries syndrome
  • kdvs
interstitial pneumonitis, desquamative, familial
  • dip
bird fancier's lung
  • avian hypersensitivity pneumonitis
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for SPPL2C

genes like me logo Genes that share disorders with SPPL2C: view

No data available for UniProtKB/Swiss-Prot and Genatlas for SPPL2C Gene

Publications for SPPL2C Gene

  1. Novel class of polytopic proteins with domains associated with putative protease activity. (PMID: 12139484) Grigorenko AP … Rogaev EI (Biochemistry. Biokhimiia 2002) 2 3 4
  2. Regulated intramembrane proteolysis of Bri2 (Itm2b) by ADAM10 and SPPL2a/SPPL2b. (PMID: 17965014) Martin L … Haass C (The Journal of biological chemistry 2008) 3 22
  3. SPPL2a and SPPL2b promote intramembrane proteolysis of TNFalpha in activated dendritic cells to trigger IL-12 production. (PMID: 16829952) Friedmann E … Martoglio B (Nature cell biology 2006) 3 4
  4. 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
  5. A reference map of the human binary protein interactome. (PMID: 32296183) Luck K … Calderwood MA (Nature 2020) 3

Products for SPPL2C Gene

Sources for SPPL2C Gene