U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

SPPL2B signal peptide peptidase like 2B [ Homo sapiens (human) ]

Gene ID: 56928, updated on 11-Apr-2024

Summary

Go to the top of the page Help
Official Symbol
SPPL2Bprovided by HGNC
Official Full Name
signal peptide peptidase like 2Bprovided by HGNC
Primary source
HGNC:HGNC:30627
See related
Ensembl:ENSG00000005206 MIM:608239; AllianceGenome:HGNC:30627
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
IMP4; PSH4; PSL1; IMP-4
Summary
This gene encodes a member of the GXGD family of aspartic proteases. The GXGD proteases are transmembrane proteins with two conserved catalytic motifs localized within the membrane-spanning regions. This enzyme localizes to endosomes, lysosomes, and the plasma membrane. It cleaves the transmembrane domain of tumor necrosis factor alpha to release the intracellular domain, which triggers cytokine expression in the innate and adaptive immunity pathways. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in testis (RPKM 13.2), duodenum (RPKM 10.9) and 25 other tissues See more
Orthologs
mouse all
NEW
Try the new Gene table
Try the new Transcript table

Genomic context

Go to the top of the page Help
Location:
19p13.3
Exon count:
15
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (2328684..2355095)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (2302357..2328755)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (2328683..2355093)

Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene leucine rich repeat and Ig domain containing 3 Neighboring gene uncharacterized LOC101928572 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9785 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13676 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13677 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13678 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13679 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9786 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13680 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:2328300-2328954 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13683 Neighboring gene LSM7 homolog, U6 small nuclear RNA and mRNA degradation associated Neighboring gene ReSE screen-validated silencer GRCh37_chr19:2358582-2358793 Neighboring gene transmembrane serine protease 9 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:2376438-2376950 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13684 Neighboring gene uncharacterized LOC124904612 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:2426331-2427074 Neighboring gene origin of replication adjacent to lamin B2 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:2427075-2427820 Neighboring gene translocase of inner mitochondrial membrane 13

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help
  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

Go to the top of the pageHelp

Related articles in PubMed

  1. Intramembrane proteolysis of GXGD-type aspartyl proteases is slowed by a familial Alzheimer disease-like mutation. Fluhrer R, et al. J Biol Chem, 2008 Oct 31. PMID 18768471, Free PMC Article
  2. Atherogenic LOX-1 signaling is controlled by SPPL2-mediated intramembrane proteolysis. Mentrup T, et al. J Exp Med, 2019 Apr 1. PMID 30819724, Free PMC Article
  3. The transferrin receptor-1 membrane stub undergoes intramembrane proteolysis by signal peptide peptidase-like 2b. Zahn C, et al. FEBS J, 2013 Apr. PMID 23384347
  4. The α-helical content of the transmembrane domain of the British dementia protein-2 (Bri2) determines its processing by signal peptide peptidase-like 2b (SPPL2b). Fluhrer R, et al. J Biol Chem, 2012 Feb 10. PMID 22194595, Free PMC Article
  5. A gamma-secretase-like intramembrane cleavage of TNFalpha by the GxGD aspartyl protease SPPL2b. Fluhrer R, et al. Nat Cell Biol, 2006 Aug. PMID 16829951

See all (29) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. SPPL2a/b negatively regulates LOX-1 signaling and atherosclerosis.
    Title: Atherogenic LOX-1 signaling is controlled by SPPL2-mediated intramembrane proteolysis.
  2. TfR1 N-terminal fragment is a substrate for intramembrane proteolysis by SPPL2b.
    Title: The transferrin receptor-1 membrane stub undergoes intramembrane proteolysis by signal peptide peptidase-like 2b.
  3. The alpha-helical content of the transmembrane domain of the British dementia protein-2 (Bri2) determines its processing by signal peptide peptidase-like 2b (SPPL2b).
    Title: The α-helical content of the transmembrane domain of the British dementia protein-2 (Bri2) determines its processing by signal peptide peptidase-like 2b (SPPL2b).
  4. Alzheimer disease-like mutant SPPL2b slowed intramembrane proteolysis of tumor necrosis factor alpha and caused a relative increase of longer intracellular cleavage products.
    Title: Intramembrane proteolysis of GXGD-type aspartyl proteases is slowed by a familial Alzheimer disease-like mutation.
  5. 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.
  6. SPPL2b is targeted through the secretory pathway to endosomes/lysosomes, whereas SPP and SPPL3 are restricted to the ER.
    Title: Differential localization and identification of a critical aspartate suggest non-redundant proteolytic functions of the presenilin homologues SPPL2b and SPPL3.
  7. 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.
  8. Results demonstrate that SPPL2b utilizes multiple intramembrane cleavages to liberate the intracellular domain of tumor necrosis factor alpha into the cytosol.
    Title: A gamma-secretase-like intramembrane cleavage of TNFalpha by the GxGD aspartyl protease SPPL2b.
Submit: New GeneRIF Correction

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease.
EBI GWAS Catalog

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Interactions

Go to the top of the page Help
Products Interactant Other Gene Complex Source Pubs Description

General gene information

Go to the top of the page Help

Markers

Homology

Clone Names

  • FLJ99014, KIAA1532, MGC111084

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables aspartic endopeptidase activity, intramembrane cleaving IBA
Inferred from Biological aspect of Ancestor
more info
  
enables aspartic endopeptidase activity, intramembrane cleaving IDA
Inferred from Direct Assay
more info
 PubMed 
NOT enables aspartic endopeptidase activity, intramembrane cleaving IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables aspartic endopeptidase activity, intramembrane cleaving IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables aspartic endopeptidase activity, intramembrane cleaving TAS
Traceable Author Statement
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein homodimerization activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in membrane protein ectodomain proteolysis IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in membrane protein intracellular domain proteolysis IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in membrane protein intracellular domain proteolysis IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in membrane protein proteolysis IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in membrane protein proteolysis IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of immune response IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of tumor necrosis factor-mediated signaling pathway TAS
Traceable Author Statement
more info
  
Component Evidence Code Pubs
located_in Golgi membrane IEA
Inferred from Electronic Annotation
more info
  
is_active_in Golgi-associated vesicle membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in Golgi-associated vesicle membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in actin cytoskeleton IDA
Inferred from Direct Assay
more info
  
located_in centrosome IDA
Inferred from Direct Assay
more info
  
is_active_in cytoplasmic side of endoplasmic reticulum membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytoplasmic side of endoplasmic reticulum membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in endosome membrane IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in lumenal side of endoplasmic reticulum membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in lumenal side of endoplasmic reticulum membrane IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in lysosomal membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in lysosomal membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane TAS
Traceable Author Statement
more info
  

General protein information

Go to the top of the page Help
Preferred Names
signal peptide peptidase-like 2B
Names
SPP-like 2B
intramembrane protease 4
presenilin homologous protein 4
presenilin-like protein 1
NP_001070706.1
NP_694533.1
XP_011526440.2
XP_011526441.1
XP_011526442.1
XP_016882507.1
XP_054177479.1
XP_054177480.1
XP_054177481.1
XP_054177482.1

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

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.

Genomic

  1. NG_032984.1 RefSeqGene

    Range
    5055..31466
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001077238.2 → NP_001070706.1  signal peptide peptidase-like 2B isoform 3 precursor

    See identical proteins and their annotated locations for NP_001070706.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) uses an alternate splice site in the 3' coding region, compared to variant 2, resulting in an early stop codon. The encoded isoform (3) is shorter and has a distinct C-terminus compared to isoform 2.
    Source sequence(s)
    AB040965, BC028391, BC093046, BU733058
    Consensus CDS
    CCDS74253.1
    UniProtKB/Swiss-Prot
    Q8TCT7
    Related
    ENSP00000478510.1, ENST00000610743.4
    Conserved Domains (2) summary
    cd02129
    Location:44 → 163
    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:213 → 505
    Peptidase_A22B; Signal peptide peptidase

  2. NM_152988.3 → NP_694533.1  signal peptide peptidase-like 2B isoform 2 precursor

    See identical proteins and their annotated locations for NP_694533.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) represents the shorter transcript but encodes the longer isoform (2).
    Source sequence(s)
    AB040965, BC093046, BU733058
    Consensus CDS
    CCDS74252.1
    UniProtKB/Swiss-Prot
    D6W609, O60365, Q567S3, Q8IUH9, Q8TCT7, Q9BUY6, Q9H3M4, Q9NPN2, Q9P1Z6
    Related
    ENSP00000478298.1, ENST00000613503.5
    Conserved Domains (3) summary
    cd02129
    Location:44 → 163
    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:213 → 505
    Peptidase_A22B; Signal peptide peptidase
    cl25865
    Location:519 → 591
    Trypan_PARP; Procyclic acidic repetitive protein (PARP)

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

    Range
    2328684..2355095
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011528138.3 → XP_011526440.2  signal peptide peptidase-like 2B isoform X1

  2. XM_011528139.3 → XP_011526441.1  signal peptide peptidase-like 2B isoform X2

    Conserved Domains (1) summary
    pfam04258
    Location:82 → 374
    Peptidase_A22B; Signal peptide peptidase

  3. XM_017027018.3 → XP_016882507.1  signal peptide peptidase-like 2B isoform X3

  4. XM_011528140.2 → XP_011526442.1  signal peptide peptidase-like 2B isoform X4

    Conserved Domains (1) summary
    pfam04258
    Location:11 → 303
    Peptidase_A22B; Signal peptide peptidase

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060943.1 Alternate T2T-CHM13v2.0

    Range
    2302357..2328755
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054321504.1 → XP_054177479.1  signal peptide peptidase-like 2B isoform X1

  2. XM_054321505.1 → XP_054177480.1  signal peptide peptidase-like 2B isoform X2

  3. XM_054321506.1 → XP_054177481.1  signal peptide peptidase-like 2B isoform X3

  4. XM_054321507.1 → XP_054177482.1  signal peptide peptidase-like 2B isoform X4

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q8TCT7.2 GenPept UniProtKB/Swiss-Prot:Q8TCT7

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
Miscellaneous