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FLASH GENE
Symbol SPPL2A contributors: npt/mct - updated : 17-09-2014
HGNC name signal peptide peptidase like 2A
HGNC id 30227
Location 15q21.2      Physical location : 50.999.738 - 51.057.910
Genatlas name putative intramembrane cleaving protease
Synonym name
  • presenilin-like protein 2
  • signal peptide peptidase-like 2A
  • Synonym symbol(s) IMP3, PSL2, FLJ14540, PSEC0147
    EC.number 3.4.23.-
    DNA
    TYPE functioning gene
    STRUCTURE 58.18 kb     15 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    DUT 15q21.1 dUTP pyrophosphatase FBN1 15q21.1 fibrillin 1 (Marfan syndrome) LOC388119 15 similar to Oxr1 protein KIAA0912 15q15.3 KIAA0912 protein CRI1 15q21.1-q21.2 CREBBP/EP300 inhibitory protein 1 LOC390582 15 similar to keratin 8; cytokeratin 8; keratin, type II cytoskeletal 8 KIAA0256 15q15.3 KIAA0256 gene product TRIP15 15q21.2 KIAA0256 gene product LOC390583 15 similar to Protein C6orf66 (HSPC125) (My013 protein) GALK2 15q21.1 galactokinase 2 FLJ32800 15q15.3 hypothetical protein FLJ32800 LOC390584 15 similar to putative intramembrane cleaving protease; presenilin-like protein 2; intramembrane protease 3 FGF7 15q15-q21.1 fibroblast growth factor 7 (keratinocyte growth factor) MDS009 15q15.3 x 009 protein LOC388120 15 hypothetical gene supported by BC013357; NM_016120 ATP8B4 15q15.3 ATPase, Class I, type 8B, member 4 SLC27A2 15q21.2 solute carrier family 27 (fatty acid transporter), member 2 HDC 15q15-q21 histidine decarboxylase GABPB2 15q15.2 GA binding protein transcription factor, beta subunit 2, 47kDa FLJ10038 15q15.3 hypothetical protein FLJ10038 USP8 6p21.3 ubiquitin specific protease 8 TRPM7 15q21 transient receptor potential cation channel, subfamily M, member 7 SPPL2A 15q15.3 putative intramembrane cleaving protease AP4E1 15q15.2 adaptor-related protein complex 4, epsilon 1 subunit LOC388121 15 similar to TNF-induced protein CYP19A1 15q21.1 cytochrome P450, family 19, subfamily A, polypeptide 1 FLJ11181 15q15.3 hypothetical protein FLJ11181 CRG-L2 15q15.3 likely ortholog of mouse cancer related gene - liver 2 RC3 15q15.3 rabconnectin-3 SCG3 15q21 secretogranin III MGC35274 15q21.1 hypothetical protein MGC35274 TMOD2 15q21.1-q21.2 tropomodulin 2 (neuronal) TMOD3 15q21.1-q21.2 tropomodulin 3 (ubiquitous) LOC123169 15q21.1 senescence downregulated leo1-like MAPK6 15q21 mitogen-activated protein kinase 6 BCL2L10 15q21 BCL2-like 10 (apoptosis facilitator) GNB5 15q21 guanine nucleotide binding protein (G protein), beta 5 MYO5C 15q21 myosin VC MYO5A 15q21.1 myosin VA (heavy polypeptide 12, myoxin) EEF1B1 15q15.1-q15.3 eukaryotic translation elongation factor 1 beta 1 ARPP-19 15q15.3 eukaryotic translation elongation factor 1 beta 1 FLJ10980 15q21.1 hypothetical protein FLJ10980 ONECUT1 15q21.1-q21.2 one cut domain, family member 1 LOC388122 15 similar to Laminin receptor 1 LOC390585 15 similar to Elongation factor 1-alpha 1 (EF-1-alpha-1) (Elongation factor 1 A-1) (eEF1A-1) (Elongation factor Tu) (EF-Tu)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    15 - 2010 58 520 - Martin (2008)
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivemouthtoothenamel   Homo sapiensFetal
    Endocrineadrenal gland   highly
     parathyroid   highly
    Hearing/Equilibriumear   highly
    Visualeyeuveachoroid  
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier/liningretinal pigment epithelium (RPE)  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticleukocyte
    Digestiveameloblast Homo sapiensFetal
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    HOMOLOGY
    Homologene
    FAMILY
  • presenilin-like protein 2 family (I-Clip family)
  • peptidase A22B family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,organelle,lysosome
    basic FUNCTION
  • may be involved in proteolysis and peptidolysis
  • with SPPL2B mediate the intramembrane cleavage, whereas neither SPP nor SPPL3 is capable of processing the ITM2B N-terminal fragment
  • important role for the final step in the CD74-MHC II pathway and a new target for protease inhibitor treatment of B cell diseases
  • enzyme controlling turnover and functions of the invariant chain (CD74) of the MHCII complex, with critical importance of this process for B cell development
  • presenilin-homologue residing in lysosomes/late endosomes, cleaving type II-oriented transmembrane proteins
  • is critical for formation of dental enamel, and intramembrane proteolysis by SPPL2A is essential for maintaining cellular homeostasis of ameloblasts
  • distinct functions of SPPL2A and SPPL2B and, high abundance of SPPL2B in brain suggests a physiological role of this protease in the central nervous system
  • SPPL2A and SPPL2B have been implicated in regulated intramembrane proteolysis (RIP) of type II transmembrane proteins
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with ADAM10
  • SPPL2A and SPPL2B mediate the intramembrane cleavage, whereas neither SPP nor SPPL3 is capable of processing the ITM2B N-terminal fragment (pMID: 17965014)
  • aspartyl intramembrane protease, implicated in the proteolysis of TNF, FASLG and ITM2B
  • regulation of CD74-NTF levels by SPPL2A is indispensable for B cell development and function by maintaining trafficking and integrity of MHCII-containing endosomes, highlighting SPPL2a as a promising pharmacological target for depleting and/or modulating B cells
  • SPPL2A, and mainly SPPL2B are responsible for the intramembrane proteolysis of TFRC-N-terminal fragment
  • TMEM106B undergoes regulated intramembrane proteolysis through SPPL2A
  • SPPL2A-mediated processing of CD74 N-terminal fragment (NTF) is indispensable to maintain appropriate levels of tonic BCR signaling to promote B cell maturation
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    ANIMAL & CELL MODELS