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SPPL2C Gene

protein-coding   GIFtS: 43
GCID: GC17P043923

Signal Peptide Peptidase Like 2C

  See SPPL2C-related disease
at  

(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 2C1 2     SPP-Like 2C2 3
Intramembrane Protease 51 2 3     Signal Peptide Peptidase-Like 2C2
IMP52 3 5     EC 3.4.23.-3
IMP-52 3     SPPL2c3

External Ids:    HGNC: 289021   Entrez Gene: 1625402   Ensembl: ENSG000001852947   OMIM: 6082845   UniProtKB: Q8IUH83   

Export aliases for SPPL2C gene to outside databases


(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 SPPL2C Gene:
SPPL2C (signal peptide peptidase like 2C) is a protein-coding gene. Diseases associated with SPPL2C include progressive supranuclear palsy. GO annotations related to this gene include aspartic-type endopeptidase activity and protein homodimerization activity. An important paralog of this gene is HM13.

UniProtKB/Swiss-Prot: SPP2C_HUMAN, Q8IUH8
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 (By similarity)




(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_000017.10  NC_018928.2  NT_010783.16  NT_167251.2  NT_187663.1  
Regulatory elements:
   Search for regulatory transcription factor binding sites for SPPL2C
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidSPPL2C promoter sequence
   Search Chromatin IP Primers for SPPL2C

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat SPPL2C


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

Entrez Gene cytogenetic band: 17q21.31   Ensembl cytogenetic band:  17q21.31   HGNC cytogenetic band: 17q21.31

SPPL2C Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
SPPL2C gene location

GeneLoc information about chromosome 17         GeneLoc Exon Structure

GeneLoc location for GC17P043923:  view genomic region     (about GC identifiers)

Start:
43,922,256 bp from pter      End:
43,924,438 bp from pter
Size:
2,183 bases      Orientation:
plus strand

1 alternative location:
Chr17-,NT_167251 943,213-945,278     

(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., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: SPP2C_HUMAN, Q8IUH8 (See protein sequence)
Recommended Name: Signal peptide peptidase-like 2C precursor  
Size: 684 amino acids; 74503 Da
Secondary accessions: Q8TC67 Q8WVZ6

Explore the universe of human proteins at neXtProt for SPPL2C: NX_Q8IUH8

Explore proteomics data for SPPL2C at MOPED

Post-translational modifications: 

  • Glycosylated1
  • Glycosylation2 at Asn100

  • See SPPL2C Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_787078.2  
    ENSEMBL proteins: 
     ENSP00000332488  

    SPPL2C Human Recombinant Protein Products:

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    Browse Proteins at Cloud-Clone Corp.

     
    Search eBioscience for Proteins for SPPL2C 

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    LSBio Antibodies in human, mouse, rat for SPPL2C

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    Search eBioscience for ELISAs for SPPL2C 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    3 InterPro protein domains:
     IPR006639 Preselin/SPP
     IPR003137 Protease-assoc_domain
     IPR007369 Peptidase_A22B_SPP

    Graphical View of Domain Structure for InterPro Entry Q8IUH8

    ProtoNet protein and cluster: Q8IUH8

    UniProtKB/Swiss-Prot: SPP2C_HUMAN, Q8IUH8
    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
    Similarity: Belongs to the peptidase A22B family
    Similarity: Contains 1 PA (protease associated) domain


    Find genes that share domains with SPPL2C           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, 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: SPP2C_HUMAN, Q8IUH8
    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 (By similarity)

         Enzyme Number (IUBMB): EC 3.4.23.-1

         Gene Ontology (GO): 2 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004190aspartic-type endopeptidase activity IEA--
    GO:0042803protein homodimerization activity IDA15385547
         
    Find genes that share ontologies with SPPL2C           About GenesLikeMe


    Animal Models:
       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for SPPL2C
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    miRNA
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    miRTarBase miRNAs that target SPPL2C:
    hsa-mir-335-5p (MIRT017486)

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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
    SPP2C_HUMAN, Q8IUH8: Membrane; Multi-pass membrane protein (Probable). Endoplasmic reticulum membrane; Multi-pass
    membrane protein
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    endoplasmic reticulum5
    plasma membrane3
    mitochondrion2

    Gene Ontology (GO): 4 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005789endoplasmic reticulum membrane IDA16829952
    GO:0016021integral component of membrane ----
    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 SPPL2C           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 SPPL2C
    Interactions:

        Search GeneGlobe Interaction Network for SPPL2C

    STRING Interaction Network Preview (showing 4 interactants - click image to see more details)

    4 Interacting proteins for SPPL2C (ENSP000003324884) via UniProtKB, MINT, STRING, and/or I2D
    InteractantInteraction Details
    GeneCardExternal ID(s)
    BAP1ENSP000004171324STRING: ENSP00000417132
    TAF1DENSP000003149714STRING: ENSP00000314971
    DTNBP1ENSP000003416804STRING: ENSP00000341680
    --ENSP000003953934STRING: ENSP00000395393
    About this table

    Gene Ontology (GO): 2 biological process terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006509NOT membrane protein ectodomain proteolysis IMP17965014
    GO:0031293NOT membrane protein intracellular domain proteolysis IMP16829952

    Find genes that share ontologies with SPPL2C           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 SPPL2C (SPP2C)



    (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 SPPL2C gene: 
    NM_175882.2  

    Unigene Cluster for SPPL2C:

    Signal peptide peptidase like 2C
    Hs.144491  [show with all ESTs]
    Unigene Representative Sequence: BC022041
    1 Ensembl transcript including schematic representation, and UCSC links where relevant:
    ENST00000329196(uc010wka.2)
    miRNA
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    OriGene qPCR primer pairs and template standards for SPPL2C
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      QuantiTect SYBR Green Assays in human, mouse, rat SPPL2C
      QuantiFast Probe-based Assays in human, mouse, rat SPPL2C

    Additional mRNA sequence: 

    BC022041.1 BC025401.1 

    3 DOTS entries:

    DT.92042901  DT.424946  DT.95152351 

    23 AceView cDNA sequences:

    NM_175882 AI825668 AI207001 BI830418 AI971700 BC025401 CD171865 AW196531 
    AI214733 AI381573 AI653035 AW182232 AI017554 AI657114 BI460639 BC022041 
    BG721091 AA351014 BI821684 BG723713 BI461717 BI459203 BF510785 

    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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    SPPL2C expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: GCAACAAGAA
    SPPL2C Expression
    About this image

    SPPL2C Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    SPPL2C Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.144491

    UniProtKB/Swiss-Prot: SPP2C_HUMAN, Q8IUH8
    Tissue specificity: Ubiquitous

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    In Situ
    Assay Products:
     

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for SPPL2C

    (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 animals and fungi.

    Orthologs for SPPL2C gene from Selected species (see all 13)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Sppl2c1 , 5 RIKEN cDNA 4933407P14 gene5
    signal peptide peptidase 2C1
    76.05(n)1
    69.78(a)1
      11 (67.79 cM)5
    2379581  NM_199019.21  NP_950184.21 
     1041863275 
    chicken
    (Gallus gallus)
    Aves SPPL2B6
    Gallus gallus signal peptide peptidase like 2B (SP...
    46(a)
    1 ↔ 1
    28(564384-599425)
    lizard
    (Anolis carolinensis)
    Reptilia --
    Uncharacterized protein
    30(a)
    many ↔ many
    GL343218.1(349055-351019)
    zebrafish
    (Danio rerio)
    Actinopterygii sppl26
    signal peptide peptidase-like 2
    47(a)
    1 ↔ 1
    2(37201502-37223842) ENSDARG00000030448
    worm
    (Caenorhabditis elegans)
    Secernentea imp-16
    Protein IMP-1, isoform c (imp-1) mRNA, complete cd...
    22(a)
    1 → many
    I(8752236-8755678) WBGene00007979
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes --
    Putative protein of unknown function with similari...
    16(a)
    1 → many
    XI(253697-255460) YKL100C


    ENSEMBL Gene Tree for SPPL2C (if available)
    TreeFam Gene Tree for SPPL2C (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for SPPL2C gene
    HM132  SPPL2A2  SPPL32  
    2 SIMAP similar genes for SPPL2C using alignment to 1 protein entry:     SPP2C_HUMAN:
    SPPL2A    SPPL2B

    Find genes that share paralogs with SPPL2C           About GenesLikeMe



    (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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    10 SNPs for SPPL2C    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 17 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1436883551,2
    --39584042(+) AGTGAC/TTGGCC 1 -- us2k10--------
    rs123731231,2,4
    ----see VAR_0380522 mis40--------
    VAR_0605904
    ----see VAR_0605902 M V mis40--------
    rs169406941,2,4
    ----see VAR_0571472 mis40--------
    rs121852681,2,4
    ----see VAR_0380512 mis40--------
    rs177636581,2,4
    ----see VAR_0380482 mis40--------
    rs123731391,2,4
    ----see VAR_0380532 mis40--------
    rs121852331,2,4
    ----see VAR_0380502 mis40--------
    rs2429441,2,4
    ----see VAR_0380492 mis40--------
    rs123731421,2,4
    ----see VAR_0380542 mis40--------

    HapMap Linkage Disequilibrium report for SPPL2C (43922256 - 43924438 bp)

    Structural Variations
          Database of Genomic Variants (DGV) variations for SPPL2C: --
    Human Gene Mutation Database (HGMD): SPPL2C
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing SPPL2C
    DNA2.0 Custom Variant and Variant Library Synthesis for SPPL2C

    (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: 608284    OMIM disorders: --

    1 disease for SPPL2C:    
    About MalaCards
    progressive supranuclear palsy


    Find genes that share disorders with SPPL2C           About GenesLikeMe


    Export disorders for SPPL2C 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 SPPL2C gene, integrated from 10 sources (see all 11):
    (articles sorted by number of sources associating them with SPPL2C)
        Utopia: connect your pdf to the dynamic
    world of online information

    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. 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)
    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 Friedmann E.... Martoglio B. (J. Biol. Chem. 2004)
    4. Regulated intramembrane proteolysis of Bri2 (Itm2b) by ADAM10 and SPPL2a/SPPL2b. (PubMed id 17965014)1, 9 Martin L.... Haass C. (J. Biol. Chem. 2008)
    5. Six novel susceptibility Loci for early-onset androgenetic alopecia and their unexpected association with common diseases. (PubMed id 22693459)1 Li R....Richards J.B. (PLoS Genet. 2012)
    6. Web-based genome-wide association study identifies two novel loci and a substantial genetic component for Parkinson's disease. (PubMed id 21738487)1 Do C.B....Eriksson N. (PLoS Genet. 2011)
    7. DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage. (PubMed id 16625196)2 Zody M.C.... Nusbaum C. (Nature 2006)
    8. High throughput SNP and expression analyses of candidate genes for non-syndromic oral clefts. (PubMed id 16415175)1 Park J.W....Beaty T.H. (J. Med. Genet. 2006)
    9. Novel haplotypes in 17q21 are associated with progressive supranuclear palsy. (PubMed id 15293277)1 Pastor P....Goate A.M. (Ann. Neurol. 2004)
    10. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)2 Gerhard D.S.... Malek J. (Genome Res. 2004)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 162540 HGNC: 28902 AceView: IMP5 Ensembl:ENSG00000185294 euGenes: HUgn162540
    ECgene: SPPL2C H-InvDB: SPPL2C

    (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 SPPL2C Pharmacogenomics, SNPs, Pathways

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for SPPL2C gene:
    Search GeneIP for patents involving SPPL2C

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    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, eBioscience, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
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