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

Summary

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
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Genomic context

Location:: 19p13.3

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (2328684..2355095)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (2302357..2328755)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (2328683..2355093)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Signal peptide peptidase-like 2b modulates the amyloidogenic pathway and exhibits an Abeta-dependent expression in Alzheimer's disease.
Title: Signal peptide peptidase-like 2b modulates the amyloidogenic pathway and exhibits an Aβ-dependent expression in Alzheimer's disease.
SPPL2a/b negatively regulates LOX-1 signaling and atherosclerosis.
Title: Atherogenic LOX-1 signaling is controlled by SPPL2-mediated intramembrane proteolysis.
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.
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).
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.
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.
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.
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.
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.

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Phenotypes

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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 EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH39163 (e-PCR)
- UniSTS:89388

RH92744 (e-PCR)
- UniSTS:85885

WI-21761 (e-PCR)
- UniSTS:38071

WI-14369 (e-PCR)
- UniSTS:58821

STS-R61296 (e-PCR)
- UniSTS:9727

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
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

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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

EC 3.4.23.-

NP_694533.1

EC 3.4.23.-

XP_011526440.2

EC 3.4.23.-

XP_011526441.1

EC 3.4.23.-

XP_011526442.1

EC 3.4.23.-

XP_016882507.1

EC 3.4.23.-

XP_054177479.1

EC 3.4.23.-

XP_054177480.1

EC 3.4.23.-

XP_054177481.1

EC 3.4.23.-

XP_054177482.1

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.

Genomic

NG_032984.1 RefSeqGene

Range

5055..31466

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000019.10 Reference GRCh38.p14 Primary Assembly

Range

2328684..2355095

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011528138.3 → XP_011526440.2 signal peptide peptidase-like 2B isoform X1
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
XM_017027018.3 → XP_016882507.1 signal peptide peptidase-like 2B isoform X3
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