Tchem SPPL2B Signal peptide peptidase-like 2B

Protein Summary

Description

Intramembrane-cleaving aspartic protease (I-CLiP) that cleaves type II membrane signal peptides in the hydrophobic plane of the membrane. Functions in ITM2B and TNF processing (PubMed:16829952, PubMed:16829951, PubMed:17965014, PubMed:19114711, PubMed:22194595). Catalyzes the intramembrane cleavage of the anchored fragment of shed TNF-alpha (TNF), which promotes the release of the intracellular domain (ICD) for signaling to the nucleus (PubMed:16829952, PubMed:16829951). May play a role in the regulation of innate and adaptive immunity (PubMed:16829952). Catalyzes the intramembrane cleavage of the simian foamy virus processed leader peptide gp18 of the envelope glycoprotein gp130 dependently of prior ectodomain shedding by furin or furin-like proprotein convertase (PC)-mediated cleavage proteolysis (PubMed:23132852). 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]

Uniprot Accession IDs

• Q8TCT7
• D6W609
• O60365
• Q567S3
• Q8IUH9
• Q9BUY6
• Q9H3M4
• Q9NPN2
• Q9P1Z6
• SPP-like 2B

Gene Name

• SPPL2B

Ensembl ID

• ENST00000610743
• ENSP00000478510
• ENSG00000005206
• ENST00000613503
• ENSP00000478298
• ENST00000618220
• ENSP00000480813

Symbol

• IMP4
• KIAA1532
• PSL1
• IMP4
• PSH4
• PSL1
• IMP-4

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
cellular component	0.85
histone modification site profile	0.76
tissue	0.67
kinase perturbation	0.66
transcription factor binding site profile	0.64

Protein Classes

PANTHER Classes

Protein / ... / Aspartic Protease / Signal Peptide Peptidase-like 2b

DTO Classes

Protein / Enzyme / Protease / Aspartic Protease / Signal Peptide Peptidase-like 2b

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 35.92   (req: < 5)

Gene RIFs: 7   (req: <= 3)

Antibodies: 65   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 35.92   (req: >= 5)

Gene RIFs: 7   (req: > 3)

Antibodies: 65   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 7

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 1

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Expression Data (0 Tissues)

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No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (4)

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (1)

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1 – 1 of 1

CHEMBL4069936

SPPL2BTchem Enzyme

pIC50 : 7.11

Protein-Protein Interactions (121)

Explore Interacting Targets

1 – 10 of 121

• See Interactions on String-DB

SLC30A5

Tbio

Family:  Transporter

Novelty:  0.02432633

p_int:  0.999995648

p_ni:  0.000004352

Data Source:  BioPlex

PIGN

Tbio

Family:  Enzyme

Novelty:  0.02210783

p_int:  0.999963416

p_ni:  0.000036429

p_wrong:  1.54e-7

Data Source:  BioPlex

KTN1

Tbio

Novelty:  0.01436672

p_int:  0.999947902

p_ni:  0.000052098

Data Source:  BioPlex

SLC30A6

Tbio

Family:  Transporter

Novelty:  0.06083299

p_int:  0.999940761

p_ni:  0.000059202

p_wrong:  3.6e-8

Data Source:  BioPlex

SLC35G2

Tdark

Family:  Transporter

Novelty:  0.57896683

p_int:  0.999915549

p_ni:  0.000075975

p_wrong:  0.000008475

Data Source:  BioPlex

IGSF3

Tbio

Novelty:  0.07528465

p_int:  0.999914058

p_ni:  0.000085941

p_wrong:  1e-9

Data Source:  BioPlex

P2RX4

Tchem

Family:  IC

Novelty:  0.00242958

p_int:  0.999903309

p_ni:  0.000096569

p_wrong:  1.22e-7

Data Source:  BioPlex

TMEM8A

Tdark

Novelty:  0.15724279

p_int:  0.999838688

p_ni:  0.000075478

p_wrong:  0.000085834

Data Source:  BioPlex

PIGW

Tbio

Novelty:  0.0245774

p_int:  0.999771188

p_ni:  0.000228812

Data Source:  BioPlex

MTCH1

Tbio

Novelty:  0.12469914

p_int:  0.999714193

p_ni:  0.000285807

Score:  0.315

Data Source:  BioPlex,STRINGDB

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (4)

Reactome (4)

Death Receptor Signalling (R-HSA-73887)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Death Receptor Signalling	141 targets	R-HSA-73887
Reactome	Regulation of TNFR1 signaling	33 targets	R-HSA-5357905
Reactome	Signal Transduction	2704 targets	R-HSA-162582
Reactome	TNF signaling	43 targets	R-HSA-75893

Name	Explore in Pharos	Explore in Source
Death Receptor Signalling	141 targets	R-HSA-73887
Regulation of TNFR1 signaling	33 targets	R-HSA-5357905
Signal Transduction	2704 targets	R-HSA-162582
TNF signaling	43 targets	R-HSA-75893

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (18)

Functions (2)

Components (11)

Processes (5)

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GO Term	Evidence	Assigned by
aspartic endopeptidase activity, intramembrane cleaving	Inferred from Direct Assay (IDA)	UniProtKB
protein homodimerization activity	Inferred from Direct Assay (IDA)	UniProtKB

Disease Associations (null)

No disease associations found

GWAS Traits (8)

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1 – 5 of 8

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
body mass index	EFO_0004340	2	2	2		72.8
pulse pressure measurement	EFO_0005763	1	1	1		64
self reported educational attainment	EFO_0004784	1	1	1		44.2
body height	EFO_0004339	1	1	1		35
age-related hearing impairment	EFO_0005782	1	1	0	5.9	30.2

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 8

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
body mass index	EFO_0004340	2		72.8
pulse pressure measurement	EFO_0005763	1		64
self reported educational attainment	EFO_0004784	1		44.2
body height	EFO_0004339	1		35
age-related hearing impairment	EFO_0005782	0	5.9	30.2

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UniProt Keyword Find Similar Targets

No Header	No Header
Alternative splicing
Cell membrane
Complete proteome
Endosome
Glycoprotein
Golgi apparatus
Hydrolase
Lysosome
Membrane
Polymorphism

GWAS Trait Find Similar Targets

No Header	No Header
age-related hearing impairment
body height
body mass index
electrocardiography
mathematical ability
pulse pressure measurement
self reported educational attainment
waist-hip ratio

IDG Resources

No IDG generated resources found

Orthologs (8)

1 – 5 of 8

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	signal peptide peptidase like 2B	VGNC:13515	750100
Mouse	signal peptide peptidase like 2B	MGI:1920468	73218
Rat	signal peptide peptidase-like 2B	RGD:1308556	362828
Dog	signal peptide peptidase like 2B	VGNC:46759	485071
Cow	signal peptide peptidase like 2B	VGNC:35235	504285

Species	Name	OMA	EggNOG	Inparanoid
Chimp	signal peptide peptidase like 2B
Mouse	signal peptide peptidase like 2B
Rat	signal peptide peptidase-like 2B
Dog	signal peptide peptidase like 2B
Cow	signal peptide peptidase like 2B

Publication Statistics

PubMed Score 35.92

PubMed score by year

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PubTator Score 18.24

PubTator score by year

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Related Publications

Text Mined References (21)

GeneRif Annotations (7)

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PMID	Year	Title