Sppl2a signal peptide peptidase like 2A [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Sppl2aprovided by MGI
Official Full Name: signal peptide peptidase like 2Aprovided by MGI
Primary source: MGI:MGI:1913802
See related: Ensembl:ENSMUSG00000027366 AllianceGenome:MGI:1913802
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: 2010106G01Rik; C130089K23Rik
Summary: Predicted to enable aspartic endopeptidase activity, intramembrane cleaving and protein homodimerization activity. Predicted to be involved in membrane protein ectodomain proteolysis; membrane protein intracellular domain proteolysis; and regulation of immune response. Predicted to act upstream of or within proteolysis. Located in late endosome membrane and lysosomal membrane. Is expressed in genitourinary system; skeleton; and thymus primordium. Human ortholog(s) of this gene implicated in primary immunodeficiency disease. Orthologous to human SPPL2A (signal peptide peptidase like 2A). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Ubiquitous expression in bladder adult (RPKM 13.9), liver E18 (RPKM 10.3) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 2 F1; 2 61.76 cM

Exon count:: 19

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	2	NC_000068.8 (126732311..126775706, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	2	NC_000068.7 (126890391..126933791, complement)

Chromosome 2 - NC_000068.8 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The intramembrane proteases SPPL2a and SPPL2b regulate the homeostasis of selected SNARE proteins.
Title: The intramembrane proteases SPPL2a and SPPL2b regulate the homeostasis of selected SNARE proteins.
Deficiency of the Intramembrane Protease SPPL2a Alters Antimycobacterial Cytokine Responses of Dendritic Cells.
Title: Deficiency of the Intramembrane Protease SPPL2a Alters Antimycobacterial Cytokine Responses of Dendritic Cells.
SPPL2a/b negatively regulates LOX-1 signaling and atherosclerosis.
Title: Atherogenic LOX-1 signaling is controlled by SPPL2-mediated intramembrane proteolysis.
Sppl2a-/- mice lack conventional dendritic cells, have CD4+ T cells that produce small amounts of IFN-gamma after BCG infection, and are highly susceptible to infection with BCG or Mycobacterium tuberculosis
Title: Disruption of an antimycobacterial circuit between dendritic and helper T cells in human SPPL2a deficiency.
Study propose that elements within the transmembrane segment and the luminal juxtamembrane domain facilitate intramembrane proteolysis of CD74 by SPPL2a.
Title: Substrate determinants of signal peptide peptidase-like 2a (SPPL2a)-mediated intramembrane proteolysis of the invariant chain CD74.
SPPL2a-mediated processing of CD74 NTF is indispensable to maintain appropriate levels of tonic BCR signaling to promote B cell maturation.
Title: Processing of CD74 by the Intramembrane Protease SPPL2a Is Critical for B Cell Receptor Signaling in Transitional B Cells.
Regulated intramembrane proteolysis of the frontotemporal lobar degeneration risk factor, TMEM106B, by signal peptide peptidase-like 2a (SPPL2a).
Title: Regulated intramembrane proteolysis of the frontotemporal lobar degeneration risk factor, TMEM106B, by signal peptide peptidase-like 2a (SPPL2a).
in vivo SPPL2a, but not SPPL2b, exhibit a physiologically relevant contribution to CD74 proteolysis in B and dendritic cells
Title: The intramembrane proteases signal Peptide peptidase-like 2a and 2b have distinct functions in vivo.
intramembrane proteolysis by SPPL2A is essential for maintaining cellular homeostasis of ameloblasts.
Title: The intramembrane protease SPPL2A is critical for tooth enamel formation.
B cell survival and dendritic cells function requires SPPL2A.
Title: B cell survival, surface BCR and BAFFR expression, CD74 metabolism, and CD8- dendritic cells require the intramembrane endopeptidase SPPL2A.

Submit: New GeneRIF Correction See all GeneRIFs (13)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Targeted (3) 1 citation
Chemically induced (ENU) (4) 1 citation
Endonuclease-mediated (2)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:234518

RH118253 (e-PCR)
- UniSTS:159019

Gene Ontology Provided by MGI

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	ISO Inferred from Sequence Orthology more info
enables hydrolase activity	IEA Inferred from Electronic Annotation more info
enables peptidase activity	IEA Inferred from Electronic Annotation more info
enables protein homodimerization activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in membrane protein ectodomain proteolysis	ISO Inferred from Sequence Orthology more info
involved_in membrane protein intracellular domain proteolysis	ISO Inferred from Sequence Orthology more info
involved_in membrane protein proteolysis	IBA Inferred from Biological aspect of Ancestor more info
involved_in membrane protein proteolysis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in membrane protein proteolysis	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within proteolysis	IEA Inferred from Electronic Annotation more info
involved_in regulation of immune response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of immune response	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
is_active_in Golgi-associated vesicle membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in Golgi-associated vesicle membrane	ISO Inferred from Sequence Orthology 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	ISO Inferred from Sequence Orthology more info
located_in endosome	IEA Inferred from Electronic Annotation more info
located_in intracellular membrane-bounded organelle	ISO Inferred from Sequence Orthology more info
located_in late endosome	ISO Inferred from Sequence Orthology more info
located_in late 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	ISO Inferred from Sequence Orthology more info
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 lysosome	IEA Inferred from Electronic Annotation more info
located_in membrane	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: signal peptide peptidase-like 2A

Names: IMP-3; SPP-like 2A protein; intramembrane protease 3; presenilin-like protein 2; protein SPPL2a

NP_075709.2

EC 3.4.23.-

XP_036018348.1

EC 3.4.23.-

XP_036018349.1

EC 3.4.23.-

XP_036018350.1

EC 3.4.23.-

NCBI Reference Sequences (RefSeq)

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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)

NM_023220.2 → NP_075709.2 signal peptide peptidase-like 2A precursor

See identical proteins and their annotated locations for NP_075709.2

Status: VALIDATED

Source sequence(s)

AB041547, AI853709, AL732330

Consensus CDS

CCDS16690.1

UniProtKB/Swiss-Prot

A2AI51, Q8R354, Q9JJF9

Related

ENSMUSP00000028844.5, ENSMUST00000028844.11

Conserved Domains (2) summary

pfam04258
Location:214 → 499

Peptidase_A22B; Signal peptide peptidase

cl28883
Location:44 → 163

PA; Protease-associated (PA) domain. The PA domain is an insert domain in a diverse fraction of proteases. The significance of the PA domain to many of the proteins in which it is inserted is undetermined. It may be a protein-protein interaction domain. At ...

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

NC_000068.8 Reference GRCm39 C57BL/6J

Range

126732311..126775706 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_036162455.1 → XP_036018348.1 signal peptide peptidase-like 2A isoform X1

Conserved Domains (2) summary

pfam04258
Location:214 → 517

Peptidase_A22B; Signal peptide peptidase

cl28883
Location:44 → 163

PA; Protease-associated (PA) domain. The PA domain is an insert domain in a diverse fraction of proteases. The significance of the PA domain to many of the proteins in which it is inserted is undetermined. It may be a protein-protein interaction domain. At ...
XM_036162456.1 → XP_036018349.1 signal peptide peptidase-like 2A isoform X2

Conserved Domains (2) summary

pfam04258
Location:206 → 491

Peptidase_A22B; Signal peptide peptidase

cl28883
Location:36 → 155

PA; Protease-associated (PA) domain. The PA domain is an insert domain in a diverse fraction of proteases. The significance of the PA domain to many of the proteins in which it is inserted is undetermined. It may be a protein-protein interaction domain. At ...
XM_036162457.1 → XP_036018350.1 signal peptide peptidase-like 2A isoform X2

Conserved Domains (2) summary

pfam04258
Location:206 → 491

Peptidase_A22B; Signal peptide peptidase

cl28883
Location:36 → 155

PA; Protease-associated (PA) domain. The PA domain is an insert domain in a diverse fraction of proteases. The significance of the PA domain to many of the proteins in which it is inserted is undetermined. It may be a protein-protein interaction domain. At ...