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    SPPL2A signal peptide peptidase like 2A [ Homo sapiens (human) ]

    Gene ID: 84888, updated on 14-May-2013
    Official Symbol
    SPPL2Aprovided by HGNC
    Official Full Name
    signal peptide peptidase like 2Aprovided by HGNC
    Primary source
    HGNC:30227
    Locus tag
    PSEC0147
    See related
    Ensembl:ENSG00000138600; HPRD:09742; MIM:608238; Vega:OTTHUMG00000131647
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    IMP3; PSL2
    Summary
    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]
    Location :
    15q21.2
    Sequence :
    Chromosome: 15; NC_000015.9 (50999730..51057910, complement)
    See SPPL2A in Epigenomics, MapViewer

    Chromosome 15 - NC_000015.9Genomic Context describing neighboring genes Neighboring gene ubiquitin specific peptidase 8 Neighboring gene ubiquitin specific peptidase 50 Neighboring gene transient receptor potential cation channel, subfamily M, member 7 Neighboring gene ribosomal protein L32 pseudogene 30 Neighboring gene adaptor-related protein complex 4, epsilon 1 subunit Neighboring gene DDB1 and CUL4 associated factor 13 pseudogene 3

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details

    Related articles in PubMed

    1. Toward an understanding of the protein interaction network of the human liver. Wang J, et al. Mol Syst Biol, 2011 Oct 11. PMID 21988832.
    2. Signal-peptide-peptidase-like 2a (SPPL2a) is targeted to lysosomes/late endosomes by a tyrosine motif in its C-terminal tail. Behnke J, et al. FEBS Lett, 2011 Oct 3. PMID 21896273.
    3. Regulated intramembrane proteolysis of Bri2 (Itm2b) by ADAM10 and SPPL2a/SPPL2b. Martin L, et al. J Biol Chem, 2008 Jan 18. PMID 17965014.
    4. The Fas ligand intracellular domain is released by ADAM10 and SPPL2a cleavage in T-cells. Kirkin V, et al. Cell Death Differ, 2007 Sep. PMID 17557115.
    5. SPPL2a and SPPL2b promote intramembrane proteolysis of TNFalpha in activated dendritic cells to trigger IL-12 production. Friedmann E, et al. Nat Cell Biol, 2006 Aug. PMID 16829952.

    See all (15) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. Data show that endogenous SPPL2a - in agreement with overexpression studies - is localised in membranes of lysosomes/late endosomes.
      Title: Signal-peptide-peptidase-like 2a (SPPL2a) is targeted to lysosomes/late endosomes by a tyrosine motif in its C-terminal tail.
    2. SPPL2a and SPPL2b mediate the intramembrane cleavage, whereas neither SPP nor SPPL3 is capable of processing the Bri2 N-terminal fragment.
      Title: Regulated intramembrane proteolysis of Bri2 (Itm2b) by ADAM10 and SPPL2a/SPPL2b.
    3. ADAM10 and SPPL2a were identified as two proteases implicated in FasL processing and release of the FasL intracellular domain, which has been shown to be important for retrograde FasL signaling
      Title: The Fas ligand intracellular domain is released by ADAM10 and SPPL2a cleavage in T-cells.
    4. SPP, SPPL2a, -2b, -2c, and -3 probably cleave type II-oriented substrate peptides as shown by consensus analysis
      Title: Consensus analysis of signal peptide peptidase and homologous human aspartic proteases reveals opposite topology of catalytic domains compared with presenilins.
    Submit: New GeneRIF Correction

    Review eQTL and phenotype association data in this region using PheGenI

    Products Interactant Other Gene Complex Source Pubs Description
    Q8TCT8 O43765 SGTA    HPRD  PubMed  
    BioGRID:124328 BioGRID:110857 NFKB1    BioGRID  PubMed Two-hybrid 
    BioGRID:124328 BioGRID:112347 SGTA    BioGRID  PubMed Two-hybrid 

    Markers

    Genotypes

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    aspartic-type endopeptidase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    protein homodimerization activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    membrane protein ectodomain proteolysis IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    membrane protein intracellular domain proteolysis IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    membrane protein intracellular domain proteolysis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    regulation of immune response IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    Golgi-associated vesicle membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    integral to cytosolic side of endoplasmic reticulum membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    integral to lumenal side of endoplasmic reticulum membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    late endosome membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    lysosomal membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    Preferred Names
    signal peptide peptidase-like 2A
    Names
    signal peptide peptidase-like 2A
    IMP-3
    SPP-like 2A
    intramembrane protease 3
    presenilin-like protein 2
    intramembrane cleaving protease
    NP_116191.2

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_032802.3 → NP_116191.2  signal peptide peptidase-like 2A precursor

      Status: REVIEWED

      Source sequence(s)
      AA988423, AK027446, AY169314, DA023801
      Consensus CDS
      CCDS10138.1
      UniProtKB/Swiss-Prot
      Q8TCT8
      Related
      ENSP00000261854, OTTHUMP00000162418, ENST00000261854, OTTHUMT00000254543
      Conserved Domains (2) summary
      cd02129
      Location:41 – 160
      Blast Score: 479
      PA_hSPPL_like; PA_hSPPL_like: Protease-associated domain containing human signal peptide peptidase-like (hSPPL)-like. This group contains various PA domain-containing proteins similar to hSPPL2a and 2b. These SPPLs are GxGD aspartic proteases. SPPL2a is sorted to the ...
      pfam04258
      Location:209 – 491
      Blast Score: 732
      Peptidase_A22B; Signal peptide peptidase

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh37.p10 Primary Assembly

    Genomic

    1. NC_000015.9 Reference GRCh37.p10 Primary Assembly

      Range
      50999730..51057910, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000147.1 Alternate HuRef

      Range
      27830092..27887195, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate CHM1_1.0

    Genomic

    1. NC_018926.1 Alternate CHM1_1.0

      Range
      31066111..31124285, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    genomic ABBA01039104.1 (5473..32015) None
    genomic ABBA01039105.1 None
    genomic AC012100.7 (51836..109935) None
    genomic AMYH01006639.1 (169423..227597) None
    genomic CH471082.1 EAW77410.1
    mRNA AA988423.1 None
    mRNA AJ345028.1 CAC87789.1
    mRNA AJ420896.1 CAD13133.1
    mRNA AK027446.1 BAB55117.1
    mRNA AK075454.1 BAC11630.1
    mRNA AK315651.1 BAG38017.1
    mRNA AY169314.1 AAO12539.1
    mRNA BC025740.1 AAH25740.1
    mRNA DA023801.1 None
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8TCT8.2 GenPept UniProtKB/Swiss-Prot:Q8TCT8

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Molecular Biology Databases
    Research Materials
    Tools
    Miscellaneous

      Supplemental Content

      Table of contents

      Related information

      • Order cDNA clone
        Order cDNA clone
      • BioAssay
        Related PubChem BioAssays
      • BioAssays, RNAi Target,Active
        BioAssays, RNAi Target,Active
      • BioProjects
        BioProjects related to a gene
      • CCDS
        Links from Gene to CCDS are established if a gene encodes a protein sequence that is a member of a Consensus CDS (CCDS).
      • Conserved Domains
        Conserved Domain Database Links between Entrez Gene and Conserved Domain Database (CDD) are calculated from the domains annotated by the CDD group on Reference Sequence proteins.
      • dbVar
        Link from Gene to dbVar
      • EST
        Link to related EST entry
      • Full text in PMC
        PMC links
      • Full text in PMC_nucleotide
        Full text in PubMedCentral identified from shared sequence links
      • Genome
        Genome records having the gene annotated on corresponding genomic reference sequence.
      • GEO Profiles
        Related GEO
      • HomoloGene
        Links between HomoloGene and Gene are provided by the HomoloGene group when a gene is included in a HomoloGene record.
      • Map Viewer
        These links are maintained by the Map Viewer group and are provided when a GeneID is annotated on a map for the same species.
      • Nucleotide
        Link to related Nucleotide entry
      • OMIM
        Links between OMIM and Gene are calculated by Gene based on MIM numbers included in the summary and phenotype sections of the Gene record.
      • Probe
        Related Probe entry
      • Protein
        Link to related protein entry
      • PubChem Compound
        PubChem Compounds
      • PubChem Substance
        PubChem Substances
      • PubMed
        Links between Gene and PubMed are the result of the following: 1. Manual curation within NCBI. Part of the process of generating a REVIEWED RefSeq is an analysis of the current literature. Papers that are seminal in defining the gene, its sequence, and its function are added to the record at that time. Alert users point out gaps or errors in papers associated with a Gene record. These messages are reviewed and implemented as required. 2. Integration of information from other public databases. Gene integrates gene-citation from resources external to NCBI such as model organism-specific databases, Gene Ontology (GO), groups curating interactions, and sequence databases. The assumption in using these source is that they report citations specific to a gene in a known species. Gene does not process citations from OMIM automatically, because many of citations in OMIM refer to studies of genes in species other than human.
      • PubMed (GeneRIF)
        GeneRIF -- Gene Reference Into Function Staff of the Index Section in the National Library of Medicine review the current literature. When they find articles focused on the structure and function of a gene, they write a brief summary of the impact of the paper and make the connection between the citation (PubMed) and Gene. An interface exists for interested users to submit such data as well. http://www.ncbi.nlm.nih.gov/projects/GeneRIF/GeneRIFhelp.html
      • PubMed (OMIM)
        Links are provided when Gene has a link to a record in OMIM, and OMIM explicitly cites these publications in PubMed.
      • PubMed(nucleotide/PMC)
        Citations in PubMed identified from shared sequence and PMC links.
      • RefSeq Proteins
        Link to Protein RefSeqs
      • RefSeq RNAs
        Link to Nucleotide RefSeq RNAs
      • SNP
        Related SNP records
      • SNP: GeneView
        SNPs linked from GeneView
      • SNP: Genotype
        Gene Genotype Report
      • Taxonomy
        Link to related taxonomy entry
      • UniGene
        Links are provided between Gene and UniGene when both databases calculate links to the same mRNA record (gi).
      • UniSTS
        Related UniSTS records

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