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SPPL3 Gene

protein-coding   GIFtS: 46
GCID: GC12M121252

Signal Peptide Peptidase Like 3

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(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Signal Peptide Peptidase Like 31 2     SPP-Like 32 3
Intramembrane Protease 21 2 3     MDHV18872
Presenilin-Like Protein 41 2 3     PRO43322
IMP22 3 5     Signal Peptide Peptidase-Like 32
Presenilin Homologous Protein 12 3     EC 3.4.23.-3
PSH12 3     IMP-23
PSL42 3     

External Ids:    HGNC: 304241   Entrez Gene: 1216652   Ensembl: ENSG000001578377   OMIM: 6082405   UniProtKB: Q8TCT63   

Export aliases for SPPL3 gene to outside databases

Previous GC identifers: GC12P119943 GC12M120799 GC12M120983 GC12M119612 GC12M119663 GC12M121201 GC12M118210 GC12M121202 GC12M121210 GC12M121231


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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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 HM13.

UniProtKB/Swiss-Prot: SPPL3_HUMAN, Q8TCT6
Function: Intramembrane-cleaving aspartic protease (I-CLiP) that cleaves type II membrane signal peptides in the
hydrophobic plane of the membrane

Gene Wiki entry for SPPL3 (UNQ1887) Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000012.11  NT_029419.13  NC_018923.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the SPPL3 gene promoter:
         STAT1   p53   STAT1beta   CUTL1   STAT1alpha   POU2F1   POU2F1a   FOXO4   AP-2beta   ZID   
         Other transcription factors

Browse SwitchGear Promoter luciferase reporter plasmids
   Search Chromatin IP Primers for SPPL3

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat SPPL3


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 12q24.31   Ensembl cytogenetic band:  12q24.31   HGNC cytogenetic band: 12q24.31

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

GeneLoc information about chromosome 12         GeneLoc Exon Structure

GeneLoc location for GC12M121252:  view genomic region     (about GC identifiers)

Start:
121,200,313 bp from pter      End:
121,342,174 bp from pter
Size:
141,862 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: SPPL3_HUMAN, Q8TCT6 (See protein sequence)
Recommended Name: Signal peptide peptidase-like 3  
Size: 385 amino acids; 42563 Da
Subunit: Monomer. Homodimer
Sequence caution: Sequence=BAC11290.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
Secondary accessions: Q3MJ04 Q8TAU4 Q96DD9
Alternative splicing: 3 isoforms:  Q8TCT6-1   Q8TCT6-2   Q8TCT6-3   

Explore the universe of human proteins at neXtProt for SPPL3: NX_Q8TCT6

Explore proteomics data for SPPL3 at MOPED

Post-translational modifications: 

  • Not glycosylated1
  • Modification sites at neXtProt

  • See SPPL3 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_620584.2  
    ENSEMBL proteins: 
     ENSP00000288680   ENSP00000442484   ENSP00000437603   ENSP00000439390   ENSP00000446088  
     ENSP00000444821  

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    Browse Proteins at Cloud-Clone Corp.

     
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    antibodies-online peptides for SPPL3

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    antibodies-online antibodies for SPPL3 (13 products) 

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    antibodies-online kits for SPPL3 (2 products) 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    2 InterPro protein domains:
     IPR006639 Preselin/SPP
     IPR007369 Peptidase_A22B_SPP

    Graphical View of Domain Structure for InterPro Entry Q8TCT6

    ProtoNet protein and cluster: Q8TCT6

    1 Blocks protein domain: IPB006639 Presenilin signal peptide peptidase

    UniProtKB/Swiss-Prot: SPPL3_HUMAN, Q8TCT6
    Domain: The PAL motif is required for normal active site conformation (By similarity). 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
    Domain: The first transmembrane domain may act as a type I signal anchor
    Similarity: Belongs to the peptidase A22B family


    Find genes that share domains with SPPL3           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: SPPL3_HUMAN, Q8TCT6
    Function: Intramembrane-cleaving aspartic protease (I-CLiP) that cleaves type II membrane signal peptides in the
    hydrophobic plane of the membrane
    Enzyme regulation: Its proteolytic activity is blocked by signal peptide peptidase (SPP) inhibitors

         Enzyme Number (IUBMB): EC 3.4.23.-1

         Gene Ontology (GO): 3 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004190aspartic-type endopeptidase activity ----
    GO:0042500aspartic endopeptidase activity, intramembrane cleaving IMP16873890
    GO:0042803protein homodimerization activity IDA15385547
         
    Find genes that share ontologies with SPPL3           About GenesLikeMe


    Phenotypes:
         3 MGI mutant phenotypes (inferred from 1 allele(MGI details for Sppl3):
     behavior/neurological  growth/size/body  reproductive system 

    Find genes that share phenotypes with SPPL3           About GenesLikeMe

    Animal Models:
       genOway: Develop your customized and physiologically relevant rodent model for SPPL3

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    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    SPPL3_HUMAN, Q8TCT6: Membrane; Multi-pass membrane protein. Endoplasmic reticulum membrane; Multi-pass membrane
    protein. Note=Restricted to the early secretory compartment
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    endoplasmic reticulum5
    golgi apparatus5
    plasma membrane3

    Gene Ontology (GO): 5 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005791rough endoplasmic reticulum IDA15998642
    GO:0016021integral component of membrane ----
    GO:0030660Golgi-associated vesicle membrane IDA16829952
    GO:0071458integral component of cytoplasmic side of endoplasmic reticulum membrane IDA15385547
    GO:0071556integral component of lumenal side of endoplasmic reticulum membrane IDA15385547

    Find genes that share ontologies with SPPL3           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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        Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for SPPL3
    Interactions:

        Search GeneGlobe Interaction Network for SPPL3

    STRING Interaction Network Preview (showing 3 interactants - click image to see more details)

    3 Interacting proteins for SPPL3 (ENSP000002886804) via UniProtKB, MINT, STRING, and/or I2D
    InteractantInteraction Details
    GeneCardExternal ID(s)
    ELAVL1ENSP000003852694STRING: ENSP00000385269
    PSMD3ENSP000002646394STRING: ENSP00000264639
    LAMP2ENSP000004084114STRING: ENSP00000408411
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    Gene Ontology (GO): 1 biological process term:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006509NOT membrane protein ectodomain proteolysis IMP16829952

    Find genes that share ontologies with SPPL3           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for SPPL3



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for SPPL3 gene: 
    NM_139015.4  

    Unigene Cluster for SPPL3:

    Signal peptide peptidase like 3
    Hs.507087  [show with all ESTs]
    Unigene Representative Sequence: NM_139015
    9 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000353487(uc001tzc.3 uc001tzd.3) ENST00000392495 ENST00000545209
    ENST00000536996 ENST00000543608 ENST00000543854 ENST00000543181 ENST00000534966
    ENST00000540091
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    Additional mRNA sequence: 

    AB252457.1 AF086117.1 AJ345030.1 AJ420898.1 AK074916.1 AK223590.1 AK291161.1 AL110147.1 
    AY169313.1 AY358767.1 BC009551.1 BC025781.1 BC073910.1 BC101625.1 BC101627.1 BX640849.1 

    12 DOTS entries:

    DT.451557  DT.100680256  DT.121175215  DT.100796289  DT.91751925  DT.100665379  DT.100796290  DT.100796294 
    DT.91702594  DT.95098244  DT.97845833  DT.91945092 

    4 AceView cDNA sequences:

    AK097149 BG260754 BC011943 BG339618 

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    SPPL3 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: TCCACCCAGA
    SPPL3 Expression
    About this image

    SPPL3 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    SPPL3 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.507087

    UniProtKB/Swiss-Prot: SPPL3_HUMAN, Q8TCT6
    Tissue specificity: Ubiquitous

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    In Situ
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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of eukaryotes.

    Orthologs for SPPL3 gene from Selected species (see all 19)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Sppl31 , 5 signal peptide peptidase 31, 5 91.23(n)1
    100(a)1
      5 (55.99 cM)5
    745851  NM_029012.21  NP_083288.21 
     1150111375 
    chicken
    (Gallus gallus)
    Aves SPPL31 signal peptide peptidase like 3 84.29(n)
    98.18(a)
      416968  XM_004934378.1  XP_004934435.1 
    lizard
    (Anolis carolinensis)
    Reptilia SPPL36
    signal peptide peptidase like 3
    97(a)
    1 ↔ 1
    GL343338.1(203364-228851)
    African clawed frog
    (Xenopus laevis)
    Amphibia MGC529752 similar to presenilin-like protein 4 79.81(n)    BC045217.1 
    zebrafish
    (Danio rerio)
    Actinopterygii sppl31 signal peptide peptidase 3 77.87(n)
    94.75(a)
      548609  NM_001015068.1  NP_001015068.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta CG173703
    SppL1
    Signal peptide peptidase-like1 65(a)3
    62.31(n)1
    67.85(a)1
      96F63
    431281  NM_143180.11  NP_651437.11 
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes --
    Putative protein of unknown function with similari...
    14(a)
    1 → many
    XI(253697-255460) YKL100C
    thale cress
    (Arabidopsis thaliana)
    eudicotyledons SPPL11 SPPL1 45.28(n)
    37.95(a)
      829478  NM_119495.2  NP_567918.1 
    rice
    (Oryza sativa)
    Liliopsida Os10g03931001 Os10g0393100 47.53(n)
    40.97(a)
      4348538  NM_001071053.1  NP_001064518.1 


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

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for SPPL3 gene
    HM132  SPPL2C2  SPPL2A2  

    Find genes that share paralogs with SPPL3           About GenesLikeMe


    1 Pseudogenes.org Pseudogene for SPPL3
    PGOHUM00000235097


    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for SPPL3 (see all 3225)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 12 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1862559791,2
    Cuntested1121247974(+) GAGACA/GGGGTC 1 -- int10--------
    rs1131083101,2
    C--118301219(+) CACAT-/ACACAC
            
    ACACA
    1 -- int11Minor allele frequency- ACACAC:0.50CSA 2
    rs5800761,2
    C,F,H--121199842(+) CACACT/CAGGCT 1 -- int112Minor allele frequency- C:0.06MN NS EA NA WA 1496
    rs1900699051,2
    --121199872(+) ATATCG/TTCATT 1 -- int10--------
    rs5802401,2
    C,F,A,H--121199903(+) GTTATG/TAAAAA 1 -- int120Minor allele frequency- N:0.00EA NA MN WA CSA 823
    rs775938621,2
    C--121199934(+) CAGTCT/GCTTTG 1 -- int11Minor allele frequency- G:0.01EA 120
    rs1927084341,2
    --121199975(+) AGGAAA/TCTGCT 1 -- int10--------
    rs1472295931,2
    --121200065(+) TAAGAA/GGCGGA 1 -- int10--------
    rs1143545471,2
    C,F--121200067(+) AGAGGC/GGGACC 1 -- int11Minor allele frequency- G:0.04WA 118
    rs1389252051,2
    --121200069(+) AGGCGC/GACCTA 1 -- int10--------

    HapMap Linkage Disequilibrium report for SPPL3 (121200313 - 121342174 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 9 variations for SPPL3:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2591284CNV Deletion19546169
    esv2672947CNV Deletion23128226
    esv1190904CNV Deletion17803354
    esv2746478CNV Deletion23290073
    esv1624453CNV Insertion17803354
    nsv908CNV Insertion18451855
    esv23186CNV Loss19812545
    nsv521928CNV Gain19592680
    nsv899559CNV Gain21882294

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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 608240    OMIM disorders: --


    Find genes that share disorders with SPPL3           About GenesLikeMe

    Genetic Association Database (GAD): SPPL3
    Human Genome Epidemiology (HuGE) Navigator: SPPL3 (3 documents)

    Export disorders for SPPL3 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for SPPL3 gene, integrated from 10 sources (see all 19):
    (articles sorted by number of sources associating them with SPPL3)
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    1. Novel class of polytopic proteins with domains associated with putative protease activity. (PubMed id 12139484)1, 2, 3 Grigorenko A.P.... Rogaev E.I. (Biokhimiia 2002)
    2. Intramembrane proteolytic cleavage by human signal peptide peptidase like 3 and malaria signal peptide peptidase. (PubMed id 16873890)1, 2, 9 Nyborg A.C.... Golde T.E. (FASEB J. 2006)
    3. Consensus analysis of signal peptide peptidase and homologous human aspartic proteases reveals opposite topology of catalytic domains compared with presenilins. (PubMed id 15385547)1, 2, 9 Friedmann E.... Martoglio B. (J. Biol. Chem. 2004)
    4. Genome-wide association studies in an isolated founder population from the Pacific Island of Kosrae. (PubMed id 19197348)1, 4 Lowe J.K....Friedman J.M. (PLoS Genet. 2009)
    5. SPPL2a and SPPL2b promote intramembrane proteolysis of TNFalpha in activated dendritic cells to trigger IL-12 production. (PubMed id 16829952)1, 2 Friedmann E.... Martoglio B. (Nat. Cell Biol. 2006)
    6. Differential localization and identification of a critical aspartate suggest non-redundant proteolytic functions of the presenilin homologues SPPL2b and SPPL3. (PubMed id 15998642)1, 2 Krawitz P.... Haass C. (J. Biol. Chem. 2005)
    7. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)1, 2 Gerhard D.S.... Malek J. (Genome Res. 2004)
    8. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PubMed id 14702039)1, 2 Ota T.... Sugano S. (Nat. Genet. 2004)
    9. Identification of signal peptide peptidase, a presenilin-type aspartic protease. (PubMed id 12077416)1, 2 Weihofen A.... Martoglio B. (Science 2002)
    10. Regulated intramembrane proteolysis of Bri2 (Itm2b) by ADAM10 and SPPL2a/SPPL2b. (PubMed id 17965014)1, 9 Martin L.... Haass C. (J. Biol. Chem. 2008)

    (in PubMed, OMIM, and NCBI Bookshelf)
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    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 121665 HGNC: 30424 AceView: SPPL3.1 Ensembl:ENSG00000157837 euGenes: HUgn121665
    ECgene: SPPL3 H-InvDB: SPPL3

    (According to HUGE)
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    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for SPPL3 Pharmacogenomics, SNPs, Pathways

    (Patent information from GeneIP,
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    IP news from LifeMap Sciences, Inc.)
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    Patent Information for SPPL3 gene:
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    GeneCards and IP:
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